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Sample records for long-lasting intrinsic plasticity

  1. Calcium permeable AMPA receptor-dependent long lasting plasticity of intrinsic excitability in fast spiking interneurons of the dentate gyrus decreases inhibition in the granule cell layer.

    PubMed

    Dasgupta, Debanjan; Sikdar, Sujit Kumar

    2015-03-01

    The local fast-spiking interneurons (FSINs) are considered to be crucial for the generation, maintenance, and modulation of neuronal network oscillations especially in the gamma frequency band. Gamma frequency oscillations have been associated with different aspects of behavior. But the prolonged effects of gamma frequency synaptic activity on the FSINs remain elusive. Using whole cell current clamp patch recordings, we observed a sustained decrease of intrinsic excitability in the FSINs of the dentate gyrus (DG) following repetitive stimulations of the mossy fibers at 30 Hz (gamma bursts). Surprisingly, the granule cells (GCs) did not express intrinsic plastic changes upon similar synaptic excitation of their apical dendritic inputs. Interestingly, pairing the gamma bursts with membrane hyperpolarization accentuated the plasticity in FSINs following the induction protocol, while the plasticity attenuated following gamma bursts paired with membrane depolarization. Paired pulse ratio measurement of the synaptic responses did not show significant changes during the experiments. However, the induction protocols were accompanied with postsynaptic calcium rise in FSINs. Interestingly, the maximum and the minimum increase occurred during gamma bursts with membrane hyperpolarization and depolarization respectively. Including a selective blocker of calcium-permeable AMPA receptors (CP-AMPARs) in the bath; significantly attenuated the calcium rise and blocked the membrane potential dependence of the calcium rise in the FSINs, suggesting their involvement in the observed phenomenon. Chelation of intracellular calcium, blocking HCN channel conductance or blocking CP-AMPARs during the experiment forbade the long lasting expression of the plasticity. Simultaneous dual patch recordings from FSINs and synaptically connected putative GCs confirmed the decreased inhibition in the GCs accompanying the decreased intrinsic excitability in the FSINs. Experimentally constrained network

  2. M1 muscarinic activation induces long-lasting increase in intrinsic excitability of striatal projection neurons.

    PubMed

    Lv, Xiaohui; Dickerson, Jonathan W; Rook, Jerri M; Lindsley, Craig W; Conn, P Jeffrey; Xiang, Zixiu

    2017-03-20

    The dorsolateral striatum is critically involved in movement control and motor learning. Striatal function is regulated by a variety of neuromodulators including acetylcholine. Previous studies have shown that cholinergic activation excites striatal principal projection neurons, medium spiny neurons (MSNs), and this action is mediated by muscarinic acetylcholine subtype 1 receptors (M1) through modulating multiple potassium channels. In the present study, we used electrophysiology techniques in conjunction with optogenetic and pharmacological tools to determine the long-term effects of striatal cholinergic activation on MSN intrinsic excitability. A transient increase in acetylcholine release in the striatum by optogenetic stimulation resulted in a long-lasting increase in excitability of MSNs, which was associated with hyperpolarizing shift of action potential threshold and decrease in afterhyperpolarization (AHP) amplitude, leading to an increase in probability of EPSP-action potential coupling. The M1 selective antagonist VU0255035 prevented, while the M1 selective positive allosteric modulator (PAM) VU0453595 potentiated the cholinergic activation-induced persistent increase in MSN intrinsic excitability, suggesting that M1 receptors are critically involved in the induction of this long-lasting response. This M1 receptor-dependent long-lasting change in MSN intrinsic excitability could have significant impact on striatal processing and might provide a novel mechanism underlying cholinergic regulation of the striatum-dependent motor learning and cognitive function. Consistent with this, behavioral studies indicate that potentiation of M1 receptor signaling by VU0453595 enhanced performance of mice in cue-dependent water-based T-maze, a dorsolateral striatum-dependent learning task.

  3. Translating innate response into long-lasting antibody response by the intrinsic antigen-adjuvant properties of papaya mosaic virus.

    PubMed

    Acosta-Ramírez, Elizabeth; Pérez-Flores, Rebeca; Majeau, Nathalie; Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Ramírez-Saldaña, Maricela; Manjarrez-Orduño, Nataly; Cervantes-Barragán, Luisa; Santos-Argumedo, Leopoldo; Flores-Romo, Leopoldo; Becker, Ingeborg; Isibasi, Armando; Leclerc, Denis; López-Macías, Constantino

    2008-06-01

    Identifying the properties of a molecule involved in the efficient activation of the innate and adaptive immune responses that lead to long-lasting immunity is crucial for vaccine and adjuvant development. Here we show that the papaya mosaic virus (PapMV) is recognized by the immune system as a pathogen-associated molecular pattern (PAMP) and as an antigen in mice (Pamptigen). A single immunization of PapMV without added adjuvant efficiently induced both cellular and specific long-lasting antibody responses. PapMV also efficiently activated innate immune responses, as shown by the induction of lipid raft aggregation, secretion of pro-inflammatory cytokines, up-regulation of co-stimulatory molecules on dendritic cells and macrophages, and long-lasting adjuvant effects upon the specific antibody responses to model antigens. PapMV mixed with Salmonella enterica serovar Typhi (S. typhi) outer membrane protein C increased its protective capacity against challenge with S. typhi, revealing the intrinsic adjuvant properties of PapMV in the induction of immunity. Antigen-presenting cells loaded with PapMV efficiently induced antibody responses in vivo, which may link the innate and adaptive responses observed. PapMV recognition as a Pamptigen might be translated into long-lasting antibody responses and protection observed. These properties could be used in the development of new vaccine platforms.

  4. Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO2 responsiveness to overcome dysfunction

    NASA Astrophysics Data System (ADS)

    Mosher, Bryan Patrick

    The ability of the brain to detect (central CO2 chemosensitivity) and respond to (central CO2 chemoresponsiveness) changes in tissue CO2/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilatory CO 2 chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe contributions to central chemosensitivity involving both 5-HT- and gamma-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO2) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO2 responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO2 responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO2 responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO2 responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO2 responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc--induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into

  5. Reliable long-lasting depression interacts with variable short-term facilitation to determine corticostriatal paired-pulse plasticity in young rats

    PubMed Central

    Akopian, G; Walsh, J P

    2007-01-01

    Synaptic plasticity at corticostraital synapses is proposed to fine tune movment and improve motor skills. We found paired-pulse plasticity at corticostriatal synapses reflected variably expressed short-term facilitation blended with a consistent background of longer-lasting depression. Presynaptic modulation via neuotransmitter receptor activation was ruled out as a mechanism for long-lasting paired-pulse depression by examining the effect of selective receptor antagonists. EPSC amplitude and paired-pulse plasticity, however, was influenced by block of D2 dopamine receptors. Block of glutamate transport with l-transdicarboxylic acid (PDC) reduced EPSCs, possibly through a mechanism of AMPA receptor desensitization. Removal of AMPA receptor desensitization with cyclothiazide reduced the paired-pulse depression at long-duration interstimulus intervals (ISIs), indicating that AMPA receptor desensitization participates in corticostriatal paired-pulse plasticity. The low-affinity glutamate receptor antagonist cis-2,3-piperidine dicarboxylic acid (PDA) increased paired-pulse depression, suggesting that a presynaptic component also exists for long-lasting paired-pulse depression. Low Ca2+–high Mg2+ or BAPTA-AM dramatically reduced the amplitude of corticostriatal EPSCs and both manipulations increased the expression of facilitation and, to a lesser extent, they reduced long-lasting paired-pulse depression. EGTA-AM produced a smaller reduction in EPSC amplitude and it did not alter paired-pulse facilitation, but in contrast to low Ca2+ and BAPTA-AM, EGTA-AM increased long-lasting paired-pulse depression. These experiments suggest that facilitation and depression are sensitive to vesicle depletion, which is dependent upon changes in peak Ca2+ (i.e. low Ca2+–high Mg2+ or BAPTA-AM). In addition, the action of EGTA-AM suggests that basal Ca2+ regulates the recovery from long-lasting paired-pulse depression, possibly thourgh a Ca2+-sensitive process of vesicle delivery

  6. TH-9 (a theophylline derivative) induces long-lasting enhancement in excitatory synaptic transmission in the rat hippocampus that is occluded by frequency-dependent plasticity in vitro.

    PubMed

    Nashawi, H; Bartl, T; Bartl, P; Novotny, L; Oriowo, M A; Kombian, S B

    2012-09-18

    Dementia, especially Alzheimer's disease, is a rapidly increasing medical condition that presents with enormous challenge for treatment. It is characterized by impairment in memory and cognitive function often accompanied by changes in synaptic transmission and plasticity in relevant brain regions such as the hippocampus. We recently synthesized TH-9, a conjugate racetam-methylxanthine compound and tested if it had potential for enhancing synaptic function and possibly, plasticity, by examining its effect on hippocampal fast excitatory synaptic transmission and plasticity. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 hippocampal area of naïve juvenile male Sprague-Dawley rats using conventional electrophysiological recording techniques. TH-9 caused a concentration-dependent, long-lasting enhancement in fEPSPs. This effect was blocked by adenosine A1, acetylcholine (muscarinic and nicotinic) and glutamate (N-methyl-d-aspartate) receptor antagonists but not by a γ-aminobutyric acid receptor type B (GABA(B)) receptor antagonist. The TH-9 effect was also blocked by enhancing intracellular cyclic adenosine monophosphate and inhibiting protein kinase A. Pretreatment with TH-9 did not prevent the induction of long-term potentiation (LTP) or long-term depression (LTD). Conversely, induction of LTP or LTD completely occluded the ability of TH-9 to enhance fEPSPs. Thus, TH-9 utilizes cholinergic and adenosinergic mechanisms to cause long-lasting enhancement in fEPSPs which were occluded by LTP and LTD. TH-9 may therefore employ similar or convergent mechanisms with frequency-dependent synaptic plasticities to produce the observed long-lasting enhancement in synaptic transmission and may thus, have potential for use in improving memory.

  7. Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity

    PubMed Central

    Dixon, Luke; Santora, Danielle; Ibrahim, Mohamed M.

    2015-01-01

    Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans. PMID:26108955

  8. Towards long lasting zirconia-based composites for dental implants: Transformation induced plasticity and its consequence on ceramic reliability.

    PubMed

    Reveron, Helen; Fornabaio, Marta; Palmero, Paola; Fürderer, Tobias; Adolfsson, Erik; Lughi, Vanni; Bonifacio, Alois; Sergo, Valter; Montanaro, Laura; Chevalier, Jérôme

    2017-01-15

    Zirconia-based composites were developed through an innovative processing route able to tune compositional and microstructural features very precisely. Fully-dense ceria-stabilized zirconia ceramics (84vol% Ce-TZP) containing equiaxed alumina (8vol%Al2O3) and elongated strontium hexa-aluminate (8vol% SrAl12O19) second phases were obtained by conventional sintering. This work deals with the effect of the zirconia stabilization degree (CeO2 in the range 10.0-11.5mol%) on the transformability and mechanical properties of Ce-TZP-Al2O3-SrAl12O19 materials. Vickers hardness, biaxial flexural strength and Single-edge V-notched beam tests revealed a strong influence of ceria content on the mechanical properties. Composites with 11.0mol% CeO2 or above exhibited the classical behaviour of brittle ceramics, with no apparent plasticity and very low strain to failure. On the contrary, composites with 10.5mol% CeO2 or less showed large transformation-induced plasticity and almost no dispersion in strength data. Materials with 10.5mol% of ceria showed the highest values in terms of biaxial bending strength (up to 1.1GPa) and fracture toughness (>10MPa√m). In these ceramics, as zirconia transformation precedes failure, the Weibull modulus was exceptionally high and reached a value of 60, which is in the range typically reported for metals. The results achieved demonstrate the high potential of using these new strong, tough and stable zirconia-based composites in structural biomedical applications.

  9. Indoor use of plastic sheeting impregnated with carbamate combined with long-lasting insecticidal mosquito nets for the control of pyrethroid-resistant malaria vectors.

    PubMed

    Djènontin, Armel; Chandre, Fabrice; Dabiré, K Roch; Chabi, Joseph; N'guessan, Raphael; Baldet, Thierry; Akogbéto, Martin; Corbel, Vincent

    2010-08-01

    The combined efficacy of a long-lasting insecticidal net (LLIN) and a carbamate-treated plastic sheeting (CTPS) or indoor residual spraying (IRS) for control of insecticide-resistant mosquitoes was evaluated in experimental huts in Burkina Faso. Anopheles gambiae from the area is resistant to pyrethroids and to a lesser extent, carbamates. Relatively low mortality rates were observed with the LLIN (44%), IRS (42%), and CTPS (52%), whereas both combinations killed significantly more mosquitoes (~70% for LLIN + CTPS and LLIN + IRS). Blood feeding by An. gambiae was uninhibited by IRS and CTPS compared with LLIN (43%), LLIN + CTPS (58%), and LLIN + IRS (56%). No evidence for selection of the kdr and ace-1(R) alleles was observed with the combinations, whereas a survival advantage of mosquitoes bearing the ace-1(R) mutation was observed with IRS and CTPS. The results suggest that the combination of the two interventions constitutes a potential tool for vector-resistance management.

  10. Spike-Timing Dependent Plasticity Beyond Synapse – Pre- and Post-Synaptic Plasticity of Intrinsic Neuronal Excitability

    PubMed Central

    Debanne, Dominique; Poo, Mu-Ming

    2010-01-01

    Long-lasting plasticity of synaptic transmission is classically thought to be the cellular substrate for information storage in the brain. Recent data indicate however that it is not the whole story and persistent changes in the intrinsic neuronal excitability have been shown to occur in parallel to the induction of long-term synaptic modifications. This form of plasticity depends on the regulation of voltage-gated ion channels. Here we review the experimental evidence for plasticity of neuronal excitability induced at pre- or postsynaptic sites when long-term plasticity of synaptic transmission is induced with Spike-Timing Dependent Plasticity (STDP) protocols. We describe the induction and expression mechanisms of the induced changes in excitability. Finally, the functional synergy between synaptic and non-synaptic plasticity and their spatial extent are discussed. PMID:21423507

  11. Long lasting decontamination foam

    DOEpatents

    Demmer, Ricky L.; Peterman, Dean R.; Tripp, Julia L.; Cooper, David C.; Wright, Karen E.

    2010-12-07

    Compositions and methods for decontaminating surfaces are disclosed. More specifically, compositions and methods for decontamination using a composition capable of generating a long lasting foam are disclosed. Compositions may include a surfactant and gelatin and have a pH of less than about 6. Such compositions may further include affinity-shifting chemicals. Methods may include decontaminating a contaminated surface with a composition or a foam that may include a surfactant and gelatin and have a pH of less than about 6.

  12. Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity

    NASA Astrophysics Data System (ADS)

    Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2013-11-01

    The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long-term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75NTR pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75NTR pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75NTR-masking conditions, thus supporting the aforementioned hypothesis.

  13. Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex.

    PubMed

    Kamphuis, Patrick J G H; Gardoni, Fabrizio; Kamal, Amer; Croiset, Gerda; Bakker, Joost M; Cattabeni, Flaminio; Gispen, Willem Hendrik; van Bel, Frank; Di Luca, Monica; Wiegant, Victor M

    2003-05-01

    The effects of neonatal dexamethasone (DEX) treatment on spatial learning and hippocampal synaptic plasticity were investigated in adult rats. Spatial learning in reference and working memory versions of the Morris maze was impaired in DEX-treated rats. In hippocampal slices of DEX rats, long-term depression was facilitated and potentiation was impaired. Paired-pulse facilitation was normal, suggesting a postsynaptic defect as cause of the learning and plasticity deficits. Western blot analysis of hippocampal postsynaptic densities (PSD) revealed a reduction in NR2B subunit protein, whereas the abundance of the other major N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A), AMPA receptor subunits (GluR2/3), scaffolding proteins, and Ca2+/calmodulin-dependent protein kinase II (alphaCaMKII) were unaltered. This selective reduction in NR2B likely resulted from altered receptor assembly rather than subunit expression, because the abundance of NR2B in the homogenate and crude synaptosomal fractions was unaltered. In addition, the activity of alphaCaMKII, an NMDA receptor complex associated protein kinase, was increased in PSD of DEX rats. The results indicate that neonatal treatment with DEX causes alterations in composition and function of the hippocampal NMDA receptor complex that persist into adulthood. These alterations likely explain the deficits in hippocampal synaptic plasticity and spatial learning induced by neonatal DEX treatment.

  14. Plastic Deformation Influence on Intrinsic Magnetic Field of Austenitic Biomaterials

    NASA Astrophysics Data System (ADS)

    Smetana, Milan; Čápová, Klára; Chudáčik, Vladimír; Palček, Peter; Oravcová, Monika

    2016-12-01

    This article deals with non-destructive evaluation of austenitic stainless steels, which are used as the biomaterials in medical practice. Intrinsic magnetic field is investigated using the fluxgate sensor, after the applied plastic deformation. The three austenitic steel types are studied under the same conditions, while several values of the deformation are applied, respectively. The obtained results are presented and discussed in the paper.

  15. Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain

    PubMed Central

    Ono, Munenori; Bishop, Deborah C.; Oliver, Douglas L.

    2016-01-01

    Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound. PMID:26867811

  16. Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain.

    PubMed

    Ono, Munenori; Bishop, Deborah C; Oliver, Douglas L

    2016-02-12

    Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound.

  17. Phenotypic plasticity in prostate cancer: role of intrinsically disordered proteins

    PubMed Central

    Mooney, Steven M; Jolly, Mohit Kumar; Levine, Herbert; Kulkarni, Prakash

    2016-01-01

    A striking characteristic of cancer cells is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition (EMT) that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks (PINs) may play a key role in determining phenotypic plasticity in prostate cancer (PCa). Specifically, we point out that the key players driving transitions among different phenotypes (epithelial, mesenchymal, and hybrid epithelial/mesenchymal), including ZEB1, SNAI1, OVOL1, and OVOL2, are intrinsically disordered proteins (IDPs) and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting IDPs implicated in EMT in PCa may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men. PMID:27427552

  18. Phenotypic plasticity in prostate cancer: role of intrinsically disordered proteins.

    PubMed

    Mooney, Steven M; Jolly, Mohit Kumar; Levine, Herbert; Kulkarni, Prakash

    2016-01-01

    A striking characteristic of cancer cells is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition (EMT) that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks (PINs) may play a key role in determining phenotypic plasticity in prostate cancer (PCa). Specifically, we point out that the key players driving transitions among different phenotypes (epithelial, mesenchymal, and hybrid epithelial/mesenchymal), including ZEB1, SNAI1, OVOL1, and OVOL2, are intrinsically disordered proteins (IDPs) and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting IDPs implicated in EMT in PCa may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men.

  19. Plastic-casting intrinsic-surface unique identifier (tag)

    SciTech Connect

    Palm, R.G.; De Volpi, A.

    1995-04-01

    This report describes the development of an authenticated intrinsic-surf ace tagging method for unique- identification of controlled items. Although developed for control of items limited by an arms control treaty, this method has other potential applications to keep track of critical or high-value items. Each tag (unique-identifier) consists of the intrinsic, microscopic surface topography of a small designated area on a controlled item. It is implemented by making a baseline plastic casting of the designated tag area and usually placing a cover (for example, a bar-code label) over this area to protect the surface from environmental alteration. The plastic casting is returned to a laboratory and prepared for high-resolution scanning electron microscope imaging. Several images are digitized and stored for use as a standard for authentication of castings taken during future inspections. Authentication is determined by numerically comparing digital images. Commercially available hardware and software are used for this tag. Tag parameters are optimized, so unique casting images are obtained from original surfaces, and images obtained from attempted duplicate surfaces are detected. This optimization uses the modulation transfer function, a first principle of image analysis, to determine the parameters. Surface duplication experiments confirmed the optimization.

  20. Sensory Deprivation Triggers Synaptic and Intrinsic Plasticity in the Hippocampus.

    PubMed

    Milshtein-Parush, Hila; Frere, Samuel; Regev, Limor; Lahav, Coren; Benbenishty, Amit; Ben-Eliyahu, Shamgar; Goshen, Inbal; Slutsky, Inna

    2017-04-12

    Hippocampus, a temporal lobe structure involved in learning and memory, receives information from all sensory modalities. Despite extensive research on the role of sensory experience in cortical map plasticity, little is known about whether and how sensory experience regulates functioning of the hippocampal circuits. Here, we show that 9 ± 2 days of whisker deprivation during early mouse development depresses activity of CA3 pyramidal neurons by several principal mechanisms: decrease in release probability, increase in the fraction of silent synapses, and reduction in intrinsic excitability. As a result of deprivation-induced presynaptic inhibition, CA3-CA1 synaptic facilitation was augmented at high frequencies, shifting filtering properties of synapses. The changes in the AMPA-mediated synaptic transmission were accompanied by an increase in NR2B-containing NMDA receptors and a reduction in the AMPA/NMDA ratio. The observed reconfiguration of the CA3-CA1 connections may represent a homeostatic adaptation to augmentation in synaptic activity during the initial deprivation phase. In adult mice, tactile disuse diminished intrinsic excitability without altering synaptic facilitation. We suggest that sensory experience regulates computations performed by the hippocampus by tuning its synaptic and intrinsic characteristics.

  1. A Theory of Rate Coding Control by Intrinsic Plasticity Effects

    PubMed Central

    Naudé, J.; Paz, J. T.; Berry, H.; Delord, B.

    2012-01-01

    Intrinsic plasticity (IP) is a ubiquitous activity-dependent process regulating neuronal excitability and a cellular correlate of behavioral learning and neuronal homeostasis. Because IP is induced rapidly and maintained long-term, it likely represents a major determinant of adaptive collective neuronal dynamics. However, assessing the exact impact of IP has remained elusive. Indeed, it is extremely difficult disentangling the complex non-linear interaction between IP effects, by which conductance changes alter neuronal activity, and IP rules, whereby activity modifies conductance via signaling pathways. Moreover, the two major IP effects on firing rate, threshold and gain modulation, remain unknown in their very mechanisms. Here, using extensive simulations and sensitivity analysis of Hodgkin-Huxley models, we show that threshold and gain modulation are accounted for by maximal conductance plasticity of conductance that situate in two separate domains of the parameter space corresponding to sub- and supra-threshold conductance (i.e. activating below or above the spike onset threshold potential). Analyzing equivalent integrate-and-fire models, we provide formal expressions of sensitivities relating to conductance parameters, unraveling unprecedented mechanisms governing IP effects. Our results generalize to the IP of other conductance parameters and allow strong inference for calcium-gated conductance, yielding a general picture that accounts for a large repertoire of experimental observations. The expressions we provide can be combined with IP rules in rate or spiking models, offering a general framework to systematically assess the computational consequences of IP of pharmacologically identified conductance with both fine grain description and mathematical tractability. We provide an example of such IP loop model addressing the important issue of the homeostatic regulation of spontaneous discharge. Because we do not formulate any assumptions on modification rules

  2. Learning to learn - intrinsic plasticity as a metaplasticity mechanism for memory formation.

    PubMed

    Sehgal, Megha; Song, Chenghui; Ehlers, Vanessa L; Moyer, James R

    2013-10-01

    "Use it or lose it" is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity - a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability - this can prevent or provide treatment for cognitive decline not only in patients with clinical disorders but

  3. Long-lasting memory from evanescent networks

    PubMed Central

    Routtenberg, Aryeh

    2010-01-01

    Current models of memory typically require a protein synthetic step leading to a more or less permanent structural change in synapses of the network that represent the stored information. This instructive role of protein synthesis has recently been called into question [Routtenberg, A., Rekart, J.L. 2005. Post-translational modification of synaptic proteins as the substrate for long-lasting memory. Trends Neurosci. 28, 12–19]. In its place a new theory is proposed in which post-translational modifications (PTMs) of proteins already synthesized and present within the synapse calibrate synaptic strength. PTM is thus the only mechanism required to sustain long-lasting memories. Activity-induced, PTM-dependent structural modifications within brain synapses then define network formation which is thus a product of the concatenation of cascaded PTMs. This leads to a formulation different from current protein synthesis models in which neural networks initially formed from these individual synaptic PTM-dependent changes is maintained by regulated positive feedback maintains. One such positive feedback mechanism is ‘cryptic rehearsal’ typically referred to as ‘noise’ or ‘spontaneous’ activity. This activity is in fact not random or spontaneous but determined in a stochastic sense by the past history of activation of the nerve cell. To prevent promiscuous network formation, the regulated positive feedback maintains the altered state given specific decay kinetics for the PTM. The up or down state of individual synapses actually exists in an infinite number of intermediate states, never fully ‘up’, nor fully ‘down.’ The networks formed from these uncertain synapses are therefore metastable. A particular memory is also multiply represented by a ‘degenerate code’ so that should loss of a subset of representations occur, erasure can be protected against. This mechanism also solves the flexibility–stability problem by positing that the brain eschews

  4. Long-Lasting Effects of Undernutrition

    PubMed Central

    Martins, Vinicius J. B.; Toledo Florêncio, Telma M. M.; Grillo, Luciane P.; Franco, Maria do Carmo P.; Martins, Paula A.; Clemente, Ana Paula G.; Santos, Carla D. L.; Vieira, Maria de Fatima A.; Sawaya, Ana Lydia

    2011-01-01

    Undernutrition is one of the most important public health problems, affecting more than 900 million individuals around the World. It is responsible for the highest mortality rate in children and has long-lasting physiologic effects, including an increased susceptibility to fat accumulation mostly in the central region of the body, lower fat oxidation, lower resting and postprandial energy expenditure, insulin resistance in adulthood, hypertension, dyslipidaemia and a reduced capacity for manual work, among other impairments. Marked changes in the function of the autonomic nervous system have been described in undernourished experimental animals. Some of these effects seem to be epigenetic, passing on to the next generation. Undernutrition in children has been linked to poor mental development and school achievement as well as behavioural abnormalities. However, there is still a debate in the literature regarding whether some of these effects are permanent or reversible. Stunted children who had experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted. Children treated before 6 years of age in day-hospitals and who recovered in weight and height have normal body compositions, bone mineral densities and insulin production and sensitivity. PMID:21776204

  5. Long-lasting desynchronization in rat hippocampal slice induced by coordinated reset stimulation

    NASA Astrophysics Data System (ADS)

    Tass, P. A.; Silchenko, A. N.; Hauptmann, C.; Barnikol, U. B.; Speckmann, E.-J.

    2009-07-01

    In computational models it has been shown that appropriate stimulation protocols may reshape the connectivity pattern of neural or oscillator networks with synaptic plasticity in a way that the network learns or unlearns strong synchronization. The underlying mechanism is that a network is shifted from one attractor to another, so that long-lasting stimulation effects are caused which persist after the cessation of stimulation. Here we study long-lasting effects of multisite electrical stimulation in a rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that desynchronizing coordinated reset stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with a widespread decrease in the amplitude of the epileptiform activity. In contrast, periodic stimulation induces a long-lasting increase in both synchronization and amplitude.

  6. Long-lasting desynchronization in rat hippocampal slice induced by coordinated reset stimulation

    SciTech Connect

    Tass, P. A.; Barnikol, U. B.; Silchenko, A. N.; Hauptmann, C.; Speckmann, E.-J.

    2009-07-15

    In computational models it has been shown that appropriate stimulation protocols may reshape the connectivity pattern of neural or oscillator networks with synaptic plasticity in a way that the network learns or unlearns strong synchronization. The underlying mechanism is that a network is shifted from one attractor to another, so that long-lasting stimulation effects are caused which persist after the cessation of stimulation. Here we study long-lasting effects of multisite electrical stimulation in a rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that desynchronizing coordinated reset stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with a widespread decrease in the amplitude of the epileptiform activity. In contrast, periodic stimulation induces a long-lasting increase in both synchronization and amplitude.

  7. Revealing extraordinary intrinsic tensile plasticity in gradient nano-grained copper.

    PubMed

    Fang, T H; Li, W L; Tao, N R; Lu, K

    2011-03-25

    Nano-grained (NG) metals are believed to be strong but intrinsically brittle: Free-standing NG metals usually exhibit a tensile uniform elongation of a few percent. When a NG copper film is confined by a coarse-grained (CG) copper substrate with a gradient grain-size transition, tensile plasticity can be achieved in the NG film where strain localization is suppressed. The gradient NG film exhibits a 10 times higher yield strength and a tensile plasticity comparable to that of the CG substrate and can sustain a tensile true strain exceeding 100% without cracking. A mechanically driven grain boundary migration process with a substantial concomitant grain growth dominates plastic deformation of the gradient NG structure. The extraordinary intrinsic plasticity of gradient NG structures offers their potential for use as advanced coatings of bulk materials.

  8. Intrinsic Plasticity for Natural Competition in Koniocortex-Like Neural Networks.

    PubMed

    Peláez, Francisco Javier Ropero; Aguiar-Furucho, Mariana Antonia; Andina, Diego

    2016-08-01

    In this paper, we use the neural property known as intrinsic plasticity to develop neural network models that resemble the koniocortex, the fourth layer of sensory cortices. These models evolved from a very basic two-layered neural network to a complex associative koniocortex network. In the initial network, intrinsic and synaptic plasticity govern the shifting of the activation function, and the modification of synaptic weights, respectively. In this first version, competition is forced, so that the most activated neuron is arbitrarily set to one and the others to zero, while in the second, competition occurs naturally due to inhibition between second layer neurons. In the third version of the network, whose architecture is similar to the koniocortex, competition also occurs naturally owing to the interplay between inhibitory interneurons and synaptic and intrinsic plasticity. A more complex associative neural network was developed based on this basic koniocortex-like neural network, capable of dealing with incomplete patterns and ideally suited to operating similarly to a learning vector quantization network. We also discuss the biological plausibility of the networks and their role in a more complex thalamocortical model.

  9. Spike-Dependent Intrinsic Plasticity Increases Firing Probability in Rat Striatal Neurons In Vivo

    PubMed Central

    Mahon, Séverine; Casassus, Guillaume; Mulle, Christophe; Charpier, Stéphane

    2003-01-01

    The collision of pre- and postynaptic activity is known to provide a trigger for controlling the gain of synaptic transmission between neurons. Here, using in vivo intracellular recordings of rat striatal output neurons, we analyse the effect of a single action potential, generated by ongoing synaptic activity, on subsequent excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cerebral cortex. This pairing induced a short-term increase in the probability that cortically evoked EPSPs caused striatal cells to fire. This enhanced EPSP-spike coupling was associated with a decrease in the voltage firing threshold with no apparent change in the synaptic strength itself. Antidromic action potentials in striatal cells were also able to induce the facilitation while subthreshold EPSPs were ineffective, indicating that the postsynaptic spike was necessary and sufficient for the induction of the plasticity. A prior spontaneous action potential also enhanced the probability with which directly applied current pulses elicited firing, suggesting that the facilitation originated from changes in the intrinsic electrical properties of the postsynaptic cell. Using whole-cell recordings in cortico-striatal slices, we found that the increase in membrane excitability as well as in EPSP-spike coupling was abolished by low concentration of 4-aminopyridine. This suggests that the intrinsic plasticity results from a time-dependent modulation of a striatal voltage-dependent potassium current available close to the firing threshold. Action potentials thus provide a postsynaptic signal, not only for associative synaptic plasticity but also for activity-dependent intrinsic plasticity, which directly controls the efficacy of coupling between pre- and postsynaptic neurons. PMID:12844508

  10. Colorful Demos with a Long-Lasting Soap Bubble.

    ERIC Educational Resources Information Center

    Behroozi, F.; Olson, D. W.

    1994-01-01

    Describes several demonstrations that feature interaction of light with soap bubbles. Includes directions about how to produce a long-lasting stationary soap bubble with an easily changeable size and describes the interaction of white light with the bubble. (DDR)

  11. Activation of InsP3 receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

    PubMed Central

    Ashhad, Sufyan; Johnston, Daniel

    2014-01-01

    The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP3) receptors (InsP3R) in a form of intrinsic plasticity by asking if InsP3R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of d-myo-InsP3 in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in all these measurements was dependent on InsP3 concentration, emphasizing the graded dependence of such plasticity on InsP3R activation. Mechanistically, we found that this InsP3-induced plasticity depended on hyperpolarization-activated cyclic nucleotide-gated channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP3Rs, the influx of calcium through N-methyl-d-aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. Our results delineate a causal role for InsP3Rs in graded adaptation of neuronal response dynamics, revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis. PMID:25552640

  12. Optical imaging of the intrinsic signal as a measure of cortical plasticity in the mouse.

    PubMed

    Cang, Jianhua; Kalatsky, Valery A; Löwel, Siegrid; Stryker, Michael P

    2005-01-01

    The responses of cells in the visual cortex to stimulation of the two eyes changes dramatically following a period of monocular visual deprivation (MD) during a critical period in early life. This phenomenon, referred to as ocular dominance (OD) plasticity, is a widespread model for understanding cortical plasticity. In this study, we designed stimulus patterns and quantification methods to analyze OD in the mouse visual cortex using optical imaging of intrinsic signals. Using periodically drifting bars restricted to the binocular portion of the visual field, we obtained cortical maps for both contralateral (C) and ipsilateral (I) eyes and computed OD maps as (C - I)/(C + I). We defined the OD index (ODI) for individual animals as the mean of the OD map. The ODI obtained from an imaging session of less than 30 min gives reliable measures of OD for both normal and monocularly deprived mice under Nembutal anesthesia. Surprisingly, urethane anesthesia, which yields excellent topographic maps, did not produce consistent OD findings. Normal Nembutal-anesthetized mice have positive ODI (0.22 +/- 0.01), confirming a contralateral bias in the binocular zone. For mice monocularly deprived during the critical period, the ODI of the cortex contralateral to the deprived eye shifted negatively towards the nondeprived, ipsilateral eye (ODI after 2-day MD: 0.12 +/- 0.02, 4-day: 0.03 +/- 0.03, and 6- to 7-day MD: -0.01 +/- 0.04). The ODI shift induced by 4-day MD appeared to be near maximal, consistent with previous findings using single-unit recordings. We have thus established optical imaging of intrinsic signals as a fast and reliable screening method to study OD plasticity in the mouse.

  13. Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations

    PubMed Central

    Tadros, M. A.; Farrell, K. E.; Schofield, P. R.; Brichta, A. M.; Graham, B. A.; Fuglevand, A. J.

    2014-01-01

    Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by “gain” in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ΔI) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot. PMID:24401707

  14. Tactile Stimulation Evokes Long-Lasting Potentiation of Purkinje Cell Discharge In Vivo

    PubMed Central

    Ramakrishnan, K. B.; Voges, Kai; De Propris, Licia; De Zeeuw, Chris I.; D’Angelo, Egidio

    2016-01-01

    In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in Purkinje cell (PC) spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here, we show that facial tactile stimuli organized in theta-patterns can induce stereotyped N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA-A) receptor-dependent changes in PCs and molecular layer interneurons (MLIs) firing: invariably, all PCs showed a long-lasting increase (Spike-Related Potentiation or SR-P) and MLIs a long-lasting decrease (Spike-Related Suppression or SR-S) in baseline activity and spike response probability. These observations suggests that tactile sensory stimulation engages multiple long-term plastic changes that are distributed along the mossy fiber-parallel fiber (MF-PF) pathway and operate synergistically to potentiate spike generation in PCs. In contrast, theta-pattern electrical stimulation (ES) of PFs indistinctly induced SR-P and SR-S both in PCs and MLIs, suggesting that tactile sensory stimulation preordinates plasticity upstream of the PF-PC synapse. All these effects occurred in the absence of complex spike changes, supporting the theoretical prediction that PC activity is potentiated when the MF-PF system is activated in the absence of conjunctive climbing fiber (CF) activity. PMID:26924961

  15. Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms.

    PubMed

    Morikawa, H; Paladini, C A

    2011-12-15

    Although the roles of dopaminergic signaling in learning and behavior are well established, it is not fully understood how the activity of dopaminergic neurons is dynamically regulated under different conditions in a constantly changing environment. Dopamine neurons must integrate sensory, motor, and cognitive information online to inform the organism to pursue outcomes with the highest reward probability. In this article, we provide an overview of recent advances on the intrinsic, extrinsic (i.e., synaptic), and plasticity mechanisms controlling dopamine neuron activity, mostly focusing on mechanistic studies conducted using ex vivo brain slice preparations. We also hope to highlight some unresolved questions regarding information processing that takes place at dopamine neurons, thereby stimulating further investigations at different levels of analysis.

  16. Dynamic Regulation of Midbrain Dopamine Neuron Activity: Intrinsic, Synaptic, and Plasticity Mechanisms

    PubMed Central

    Morikawa, Hitoshi; Paladini, Carlos A.

    2011-01-01

    Although the roles of dopaminergic signaling in learning and behavior are well established, it is not fully understood how the activity of dopaminergic neurons is dynamically regulated under different conditions in a constantly changing environment. Dopamine neurons must integrate sensory, motor, and cognitive information online to inform the organism to pursue outcomes with the highest reward probability. In this article, we provide an overview of recent advances on the intrinsic, extrinsic (i.e., synaptic), and plasticity mechanisms controlling dopamine neuron activity, mostly focusing on mechanistic studies conducted using ex vivo brain slice preparations. We also hope to highlight some unresolved questions regarding information processing that takes place at dopamine neurons, thereby stimulating further investigations at different levels of analysis. PMID:21872647

  17. [Poisoning by chromium and its long lasting detoxication].

    PubMed

    Ryselis, Stanislovas; Abdrachmanovas, Olegas; Vitkuviene, Birute; Naginiene, Rima

    2002-01-01

    Long lasting influence of cumulated Cr provide irreversible damages of vascular walls, organs and their systems. During long lasting treatment most of Cr is removed during the first 20 days through bileric tract and at the same time through the renal tract the Cr amounts decreases because chromium-d-penicilamin complex in hepatocytes induces synthesis of specific chromium-d-penicilamin binding labile protein and they are removed with bile. The levels of essential microelements (Cu and Zn) are maintained at the level of the physiological tolerance during treatment. Cr removes very slowly (about a year) from human body, and after treatment patients health do not improve because Cr-inducted damages of vascullars, organs and their systems are not recovered. The treatment must be evaluated continuously by controlling concentrations' of Cr, Cu, Zn and other microelements in the blood, plasma and urine by electrothermal atomic absorbtion spectrophotometry methods.

  18. The h channel mediates location dependence and plasticity of intrinsic phase response in rat hippocampal neurons.

    PubMed

    Narayanan, Rishikesh; Johnston, Daniel

    2008-05-28

    The presence of phenomenological inductances in neuronal membrane has been known for more than one-half a century. Despite this, the dramatic contributions of such inductive elements to the amplitude and, especially, phase of neuronal impedance, and their roles in modulating temporal dynamics of neuronal responses have surprisingly remained unexplored. In this study, we demonstrate that the h channel contributes a location-dependent and plastic phenomenological inductive component to the input impedance of CA1 pyramidal neurons. Specifically, we show that the h channels introduce an apparent negative delay in the local voltage response of these neurons with respect to the injected current within the theta frequency range. The frequency range and the extent of this lead expand with increases in h current either through hyperpolarization, or with increasing distance of dendritic location from the soma. We also demonstrate that a spatially widespread increase in this inductive phase component accompanies long-term potentiation. Finally, using impedance analysis, we show that both location and activity dependence of intrinsic phase response are attributable not to changes in a capacitive or a leak component, but to changes in h-channel properties. Our results suggest that certain voltage-gated ion channels can differentially regulate internal time delays within neurons, thus providing them with an independent control mechanism in temporal coding of neuronal information. Our analyses and results also establish impedance as a powerful measure of intrinsic dynamics and excitability, given that it quantifies temporal relationships among signals and excitability as functions of input frequency.

  19. Effects of cellular homeostatic intrinsic plasticity on dynamical and computational properties of biological recurrent neural networks.

    PubMed

    Naudé, Jérémie; Cessac, Bruno; Berry, Hugues; Delord, Bruno

    2013-09-18

    Homeostatic intrinsic plasticity (HIP) is a ubiquitous cellular mechanism regulating neuronal activity, cardinal for the proper functioning of nervous systems. In invertebrates, HIP is critical for orchestrating stereotyped activity patterns. The functional impact of HIP remains more obscure in vertebrate networks, where higher order cognitive processes rely on complex neural dynamics. The hypothesis has emerged that HIP might control the complexity of activity dynamics in recurrent networks, with important computational consequences. However, conflicting results about the causal relationships between cellular HIP, network dynamics, and computational performance have arisen from machine-learning studies. Here, we assess how cellular HIP effects translate into collective dynamics and computational properties in biological recurrent networks. We develop a realistic multiscale model including a generic HIP rule regulating the neuronal threshold with actual molecular signaling pathways kinetics, Dale's principle, sparse connectivity, synaptic balance, and Hebbian synaptic plasticity (SP). Dynamic mean-field analysis and simulations unravel that HIP sets a working point at which inputs are transduced by large derivative ranges of the transfer function. This cellular mechanism ensures increased network dynamics complexity, robust balance with SP at the edge of chaos, and improved input separability. Although critically dependent upon balanced excitatory and inhibitory drives, these effects display striking robustness to changes in network architecture, learning rates, and input features. Thus, the mechanism we unveil might represent a ubiquitous cellular basis for complex dynamics in neural networks. Understanding this robustness is an important challenge to unraveling principles underlying self-organization around criticality in biological recurrent neural networks.

  20. Psychostimulant-induced plasticity of intrinsic neuronal excitability in ventral subiculum.

    PubMed

    Cooper, Donald C; Moore, Shannon J; Staff, Nathan P; Spruston, Nelson

    2003-10-29

    Psychostimulant drugs such as amphetamine are prescribed to increase vigilance, suppress appetite, and treat attention disorders, but they powerfully activate the dopamine system and have serious abuse potential. Repeated psychostimulant exposure induces neuronal plasticity within the mesolimbic dopamine system. Here we present evidence that repeated amphetamine exposure results in a suppression of intrinsic neuronal excitability in the ventral subiculum, a hippocampal region that activates dopamine neurotransmission. We used patch-clamp recordings from brain slices obtained at different times after withdrawal from repeated amphetamine exposure to determine the long-term effects of amphetamine on subicular excitability. Using several postsynaptic indices of sodium channel function, our results show that excitability is decreased for days, but not weeks, after repeated amphetamine exposure. The resulting increase in action potential threshold and decrease in postsynaptic amplification of excitatory synaptic input provide the first direct evidence that psychostimulants induce plasticity of hippocampal output and suggest one mechanism by which drug withdrawal may influence limbic dopamine-dependent learning and memory.

  1. Intrinsic Functional Plasticity of the Sensory-Motor Network in Patients with Cervical Spondylotic Myelopathy

    PubMed Central

    Zhou, F. Q.; Tan, Y. M.; Wu, L.; Zhuang, Y.; He, L. C.; Gong, H. H.

    2015-01-01

    Several neuroimaging studies have suggested brain reorganisation in patients with cervical spondylotic myelopathy (CSM); however, the changes in spontaneous neuronal activity that are associated with connectedness remain largely unknown. In this study, functional connectivity strength (FCS), a data-driven degree centrality method based on a theoretical approach, was applied for the first time to investigate changes in the sensory-motor network (SMN) at the voxel level. Comparatively, CSM not only showed significantly decreased FCS in the operculum-integrated regions, which exhibited reduced resting-state functional connectivity (rsFC) around the Rolandic sulcus, but it also showed increased FCS in the premotor, primary somatosensory, and parietal-integrated areas, which primarily showed an enhanced rsFC pattern. Correlation analysis showed that altered FCS (in the left premotor-ventral/precentral-operculum, right operculum-parietale 4, and right S1) was associated with worsening Japanese Orthopaedic Association scores and that the rsFC pattern was influenced by cervical cord micro-structural damage at the C2 level. Together, these findings suggest that during myelopathy, the intrinsic functional plasticity of the SMN responds to the insufficient sensory and motor experience in CSM patients. This knowledge may improve our understanding of the comprehensive functional defects found in CSM patients and may inspire the development of new therapeutic strategies in the future. PMID:25897648

  2. Characterizing Interplanetary Structures of Long-Lasting Ionospheric Storm Events

    NASA Astrophysics Data System (ADS)

    Tandoi, C.; Dong, Y.; Ngwira, C. M.; Damas, M. C.

    2015-12-01

    Geomagnetic storms can result in periods of heightened TEC (Total Electron Content) in Earth's ionosphere. These periods of change in TEC (dTEC) can have adverse impacts on a technological society, such as scintillation of radio signals used by communication and navigation satellites. However, it is unknown which exact properties of a given storm cause dTEC. We are comparing different solar wind properties that result in a significant long-lasting dTEC to see if there are any patterns that remain constant in these storms. These properties, among others, include the interplanetary magnetic field By and Bz components, the proton density, and the flow speed. As a preliminary investigation, we have studied 15 solar storms. Preliminary results will be presented. In the future, we hope to increase our sample size and analyze over 80 different solar storms, which result in significant dTEC.

  3. Is Choice-Induced Preference Change Long Lasting?

    PubMed Central

    Yu, Xiaoyu; Koster, Raphael; Dolan, Raymond J.

    2013-01-01

    The idea that decisions alter preferences has had a considerable influence on the field of psychology and underpins cognitive dissonance theory. Yet it is unknown whether choice-induced changes in preferences are long lasting or are transient manifestations seen in the immediate aftermath of decisions. In the research reported here, we investigated whether these changes in preferences are fleeting or stable. Participants rated vacation destinations immediately after making hypothetical choices between destinations and 2.5 to 3 years later. We found that choices altered preferences both immediately and after the delay. These changes could not be accounted for by participants’ preexisting preferences, and they occurred only when participants made the choices themselves. Our findings provide evidence that making a decision can lead to enduring change in preferences. PMID:22933456

  4. Distributional learning has immediate and long-lasting effects.

    PubMed

    Escudero, Paola; Williams, Daniel

    2014-11-01

    Evidence of distributional learning, a statistical learning mechanism centered on relative frequency of exposure to different tokens, has mainly come from short-term learning and therefore does not ostensibly address the development of important learning processes. The present longitudinal study examines both short- and long-term effects of distributional learning of phonetic categories on non-native sound discrimination over a 12-month period. Two groups of listeners were exposed to a two-minute distribution of auditory stimuli in which the most frequently presented tokens either approximated or exaggerated the natural production of the speech sounds, whereas a control group listened to a piece of classical music for the same length of time. Discrimination by listeners in the two distribution groups improved immediately after the short exposure, replicating previous results. Crucially, this improvement was maintained after six and 12 months, demonstrating that distributional learning has long-lasting effects.

  5. Long lasting blindness, availability of resources, and early aging.

    PubMed

    Bachar, E; Shanan, J

    1997-04-01

    The present paper studied the influence of long lasting blindness on processes of aging. It addressed the broader issue of the effects of familiarity with and earlier experience of stress on the capacity of individuals to deal successfully with similar stressful situations at a later point of development. 75 chronically blind men and women, aged 45 to 65, were compared with 75 sighted individuals (matched by age, sex, and cultural origin) on scores on the Shanan Sentence Completion Technique, an interview designed to assess perception of change in various areas of everyday living, and on scores on the Wechsler-Bellevue Intelligence Test. Blind subjects showed less psychological and less social engagement with the outer world. Availability of resources, education, and assistance considerably reduced differences between the nonsighted and sighted subjects. These findings were interpreted as pointing to a potentially preventable process of premature aging.

  6. Is choice-induced preference change long lasting?

    PubMed

    Sharot, Tali; Fleming, Stephen M; Yu, Xiaoyu; Koster, Raphael; Dolan, Raymond J

    2012-10-01

    The idea that decisions alter preferences has had a considerable influence on the field of psychology and underpins cognitive dissonance theory. Yet it is unknown whether choice-induced changes in preferences are long lasting or are transient manifestations seen in the immediate aftermath of decisions. In the research reported here, we investigated whether these changes in preferences are fleeting or stable. Participants rated vacation destinations before making hypothetical choices between destinations, immediately afterward, and 2.5 to 3 years later. We found that choices altered preferences both immediately after being made and after the delay. These changes could not be accounted for by participants' preexisting preferences, and they occurred only when participants made the choices themselves. Our findings provide evidence that making a decision can lead to enduring change in preferences.

  7. Unusual magnetopause crossings during long-lasting radial IMF conditions

    NASA Astrophysics Data System (ADS)

    Grygorov, Kostiantyn; Safrankova, Jana; Nemecek, Zdenek; Prech, Lubomir; Pi, Gilbert; Shue, Jih-Hong

    2016-04-01

    One of the factors which affect the solar wind-magnetosphere interaction is the orientation of the interplanetary magnetic field (IMF). The very rarely observed radial IMF results in magnetopause locations up to several radii farther away from the Earth than predicted and causes a specific magnetopause shape. We present a case study of magnetopause crossings which were observed by the THEMIS spacecraft and analyze the difference between observed magnetopause positions and those which are predicted by an empirical magnetopause model. We use both the data (if available) from the L1 point and from near-Earth solar wind monitors as a model input. We discuss a role of the long-lasting radial IMF orientation on the magnetopause position and the influences of other parameters such as the dynamic pressure and IMF BZ component at different local times.

  8. Retinal lesions induce fast intrinsic cortical plasticity in adult mouse visual system.

    PubMed

    Smolders, Katrien; Vreysen, Samme; Laramée, Marie-Eve; Cuyvers, Annemie; Hu, Tjing-Tjing; Van Brussel, Leen; Eysel, Ulf T; Nys, Julie; Arckens, Lutgarde

    2016-09-01

    Neuronal activity plays an important role in the development and structural-functional maintenance of the brain as well as in its life-long plastic response to changes in sensory stimulation. We characterized the impact of unilateral 15° laser lesions in the temporal lower visual field of the retina, on visually driven neuronal activity in the afferent visual pathway of adult mice using in situ hybridization for the activity reporter gene zif268. In the first days post-lesion, we detected a discrete zone of reduced zif268 expression in the contralateral hemisphere, spanning the border between the monocular segment of the primary visual cortex (V1) with extrastriate visual area V2M. We could not detect a clear lesion projection zone (LPZ) in areas lateral to V1 whereas medial to V2M, agranular and granular retrosplenial cortex showed decreased zif268 levels over their full extent. All affected areas displayed a return to normal zif268 levels, and this was faster in higher order visual areas than in V1. The lesion did, however, induce a permanent LPZ in the retinorecipient layers of the superior colliculus. We identified a retinotopy-based intrinsic capacity of adult mouse visual cortex to recover from restricted vision loss, with recovery speed reflecting the areal cortical magnification factor. Our observations predict incomplete visual field representations for areas lateral to V1 vs. lack of retinotopic organization for areas medial to V2M. The validation of this mouse model paves the way for future interrogations of cortical region- and cell-type-specific contributions to functional recovery, up to microcircuit level.

  9. Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex

    PubMed Central

    Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

    2016-01-01

    Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats—while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. PMID:27193420

  10. Long-Lasting Effects of GABA Infusion Into the Cerebral Cortex of the Rat

    PubMed Central

    Montiel, Teresa; Almeida, Daniel; Arango, Iván; Calixto, Eduardo; Casasola, César; Brailowsky, Simón

    2000-01-01

    In electrophysiological terms, experimental models of durable information storage in the brain include long-term potentiation (LTP), long-term depression, and kindling. Protein synthesis correlates with these enduring processes. We propose a fourth example of long-lasting information storage in the brain, which we call the GABA-withdrawal syndrome (GWS). In rats, withdrawal of a chronic intracortical infusion of GABA, a ubiquitous inhibitory neurotransmitter, induced epileptogenesis at the infusion site. This overt GWS lasted for days. Anisomycin, a protein synthesis inhibitor, prevented the appearance of GWS in vivo. Hippocampal and neocortical slices showed a similar post-GABA hyperexcitability in vitro and an enhanced susceptibility to LTP induction. One to four months after the epileptic behavior disappeared, systemic administration of a subconvulsant dose of pentylenetetrazol produced the reappearance of paroxysmal activity. The long-lasting effects of tonic GABAA receptor stimulation may be involved in long-term information storage processes at the cortical level, whereas the cessation of GABAA receptor stimulation may be involved in chronic pathological conditions, such as epilepsy. Furthermore, we propose that GWS may represent a common key factor in the addiction to GABAergic agents (for example, barbiturates, benzodiazepines, and ethanol). GWS represents a novel form of neurono-glial plasticity. The mechanisms of this phenomenon remain to be understood. PMID:10709209

  11. Long-lasting efficacy of the cognitive enhancer cytotoxic necrotizing factor 1.

    PubMed

    Borrelli, Sonia; Musilli, Marco; Martino, Assunta; Diana, Giovanni

    2013-01-01

    Rho GTPases are key regulators of the activity-dependent changes of neural circuits. Besides being involved in nervous system development and repair, this neural structural plasticity is believed to constitute the cellular basis of learning and memory. Here we report that concurrent modulation of cerebral Rho GTPases, including Rac, Rho and Cdc42 subfamilies, by Cytotoxic Necrotizing Factor 1 (CNF1, 10 fmol/kg intracerebroventricularly) improves object recognition in both C57BL/6J and CD1 mice. The improvement is long lasting, as it is still observed 90 days post treatment. At this time, the treatment is associated with enhancement of neurotransmission and long-term potentiation. The effects depend on changes in Rho GTPase status, since the recombinant molecule CNF1 C866S, in which the enzymatic activity was abolished through substitution of serine to cysteine at position 866, is ineffective. The study confirms the role of Rho GTPases in learning and suggests that a single administration of CNF1 is effective for a long time after administration. In general, the long-lasting cognition enhancing effect of CNF1 might be beneficial for the treatment of CNS disorders. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  12. A Beautician's Dystonia: Long-Lasting Effect of Botulinum Toxin

    PubMed Central

    Di Martino, Siria; Dalise, Stefania; Lamola, Giuseppe; Venturi, Martina; Rossi, Bruno; Chisari, Carmelo

    2014-01-01

    Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders). Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin) into the extensor digitorum communis (35 U), flexor carpi radialis (35 U), and flexor digitorum superficialis (30 U) muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment). In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients' ability to work and quality of life. PMID:25143844

  13. Red long-lasting phosphorescence based on color conversion process

    NASA Astrophysics Data System (ADS)

    Li, Zhanjun; Zhang, Hongwu; Fu, Haixia

    2013-01-01

    The principle of color conversion process was used to generate red long-lasting phosphorescence (LLP) using SrAl2O4:Eu, Dy (SAO) as primary light source and rhodamine B encapsulated mesoporous silica nanoparticles (MCM-R) as effective color conversion agent. The phosphorescence spectra of MCM-R/SAO hybrid samples show green peaks from 425 nm to 550 nm and red peaks from 550 nm to 700 nm, which can be attributed to the phosphorescence of SAO and the fluorescence of MCM-R, respectively. The phosphorescence color can be adjusted from green to red by changing the mass ratio of MCM-R/SAO. When the mass ratio of MCM-R/SAO increases from 0.05 to 1.5, a blue shift for the green peak and a red shift for the red peak of the phosphorescence spectra can be observed and the intensity of the red emission peak increase relatively towards the green one. The phosphorescence decay curves show that MCM-R and SAO have similar decay dynamics and the MCM-R can inherit the LLP properties of SAO. The phosphorescence decay spectra indicate that the MCM-R/SAO hybrid can retain constant and steady visual phosphorescence color. The red phosphorescence can be seen in the dark with naked eyes for more than 5 h. So, the red LLP can be successfully achieved based on the principle of color conversion process.

  14. Taurine-Induced Long-Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters

    PubMed Central

    Sergeeva, O A; Chepkova, A N; Doreulee, N; Eriksson, K S; Poelchen, W; Mönnighoff, I; Heller-Stilb, B; Warskulat, U; Häussinger, D; Haas, H L

    2003-01-01

    Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy. PMID:12824447

  15. Long-lasting virtual motorcycle-riding trainer effectiveness

    PubMed Central

    Vidotto, Giulio; Tagliabue, Mariaelena; Tira, Michael D.

    2015-01-01

    This work aimed to test the long-lasting effects of learning acquired with a virtual motorcycle-riding trainer as a tool to improve hazard perception. During the simulation, the rider can interact with other road actors and experience the most common potential accident situations in order to learn to modify his or her behavior to anticipate hazards and avoid crashes. We compared performance to the riding simulator of the two groups of participants: the experimental group, which was trained with the same simulator one year prior, and the control group that had not received any type of training with a riding or driving simulator. All of the participants had ridden a moped in the previous 12 months. The experimental group showed greater abilities to avoid accidents and recognize hazards in comparison to their performance observed a year before, whereas the performance of the control group was similar to that of the experimental group 1 year before in the first two sessions, and even better in the third. We interpreted this latter result as a consequence of their prior on-road experience. Also, the fact that the performance of the experimental group at the beginning of the follow-up is better than that recorded at the end of the training—1 year before—is in line with the idea of a transfer from the on-road experience to the simulator. The present data confirm our main expectation that the effectiveness of the riding training simulator on the ability to cope with potentially dangerous situations persists over time and provides additional evidence in favor of the idea that simulators may be considered useful tools for training the ability to detect and react to hazards, leading to an improvement of this higher-order cognitive skill that persists over time. Implications for the reciprocal influence of the training with the simulator and the on-the road experience are discussed as well. PMID:26579036

  16. FIELD TOPOLOGY ANALYSIS OF A LONG-LASTING CORONAL SIGMOID

    SciTech Connect

    Savcheva, A. S.; Van Ballegooijen, A. A.; DeLuca, E. E.

    2012-01-01

    We present the first field topology analysis based on nonlinear force-free field (NLFFF) models of a long-lasting coronal sigmoid observed in 2007 February with the X-Ray Telescope on Hinode. The NLFFF models are built with the flux rope insertion method and give the three-dimensional coronal magnetic field as constrained by observed coronal loop structures and photospheric magnetograms. Based on these models, we have computed horizontal maps of the current and the squashing factor Q for 25 different heights in the corona for all six days of the evolution of the region. We use the squashing factor to quantify the degree of change of the field line linkage and to identify prominent quasi-separatrix layers (QSLs). We discuss the major properties of these QSL maps and devise a way to pick out important QSLs since our calculation cannot reach high values of Q. The complexity in the QSL maps reflects the high degree of fragmentation of the photospheric field. We find main QSLs and current concentrations that outline the flux rope cavity and that become characteristically S-shaped during the evolution of the sigmoid. We note that, although intermittent bald patches exist along the length of the sigmoid during its whole evolution, the flux rope remains stable for several days. However, shortly after the topology of the field exhibits hyperbolic flux tubes (HFT) on February 7 and February 12 the sigmoid loses equilibrium and produces two B-class flares and associated coronal mass ejections (CMEs). The location of the most elevated part of the HFT in our model coincides with the inferred locations of the two flares. Therefore, we suggest that the presence of an HFT in a coronal magnetic configuration may be an indication that the system is ready to erupt. We offer a scenario in which magnetic reconnection at the HFT drives the system toward the marginally stable state. Once this state is reached, loss of equilibrium occurs via the torus instability, producing a CME.

  17. Field Topology Analysis of a Long-lasting Coronal Sigmoid

    NASA Astrophysics Data System (ADS)

    Savcheva, A. S.; van Ballegooijen, A. A.; DeLuca, E. E.

    2012-01-01

    We present the first field topology analysis based on nonlinear force-free field (NLFFF) models of a long-lasting coronal sigmoid observed in 2007 February with the X-Ray Telescope on Hinode. The NLFFF models are built with the flux rope insertion method and give the three-dimensional coronal magnetic field as constrained by observed coronal loop structures and photospheric magnetograms. Based on these models, we have computed horizontal maps of the current and the squashing factor Q for 25 different heights in the corona for all six days of the evolution of the region. We use the squashing factor to quantify the degree of change of the field line linkage and to identify prominent quasi-separatrix layers (QSLs). We discuss the major properties of these QSL maps and devise a way to pick out important QSLs since our calculation cannot reach high values of Q. The complexity in the QSL maps reflects the high degree of fragmentation of the photospheric field. We find main QSLs and current concentrations that outline the flux rope cavity and that become characteristically S-shaped during the evolution of the sigmoid. We note that, although intermittent bald patches exist along the length of the sigmoid during its whole evolution, the flux rope remains stable for several days. However, shortly after the topology of the field exhibits hyperbolic flux tubes (HFT) on February 7 and February 12 the sigmoid loses equilibrium and produces two B-class flares and associated coronal mass ejections (CMEs). The location of the most elevated part of the HFT in our model coincides with the inferred locations of the two flares. Therefore, we suggest that the presence of an HFT in a coronal magnetic configuration may be an indication that the system is ready to erupt. We offer a scenario in which magnetic reconnection at the HFT drives the system toward the marginally stable state. Once this state is reached, loss of equilibrium occurs via the torus instability, producing a CME.

  18. Long-lasting Antifouling Coating from Multi-Armed Polymer

    PubMed Central

    Mizrahi, Boaz; Khoo, Xiaojuan; Chaing, Homer H.; Sher, Katalina J.; Feldman, Rose G.; Lee, Jung-Jae; Irusta, Silvia; Kohane, Daniel S.

    2013-01-01

    We describe a new antifouling surface coating, based on aggregation of a short amphiphilic four-armed PEG-dopamine polymer into particles, and on surface binding by catechol chemistry. An unbroken and smooth polymeric coating layer with an average thickness of approximately 4 microns was formed on top of titanium oxide surfaces by a single step reaction. Coatings conferred excellent resistance to protein adhesion. Cell attachment was completely prevented for at least eight weeks, although the membranes themselves did not appear to be intrinsically cytotoxic. When linear PEG or four-armed PEG of higher molecular weight were used, the resulting coatings were inferior in thickness and in preventing protein adhesion. This coating method has potential applicability for biomedical devices susceptible to fouling after implantation. PMID:23855875

  19. Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network.

    PubMed

    Lane, Brian J; Samarth, Pranit; Ransdell, Joseph L; Nair, Satish S; Schulz, David J

    2016-08-23

    Motor neurons of the crustacean cardiac ganglion generate virtually identical, synchronized output despite the fact that each neuron uses distinct conductance magnitudes. As a result of this variability, manipulations that target ionic conductances have distinct effects on neurons within the same ganglion, disrupting synchronized motor neuron output that is necessary for proper cardiac function. We hypothesized that robustness in network output is accomplished via plasticity that counters such destabilizing influences. By blocking high-threshold K(+) conductances in motor neurons within the ongoing cardiac network, we discovered that compensation both resynchronized the network and helped restore excitability. Using model findings to guide experimentation, we determined that compensatory increases of both GA and electrical coupling restored function in the network. This is one of the first direct demonstrations of the physiological regulation of coupling conductance in a compensatory context, and of synergistic plasticity across cell- and network-level mechanisms in the restoration of output.

  20. Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

    PubMed Central

    Guo, Xiaoli; He, Yongzhi; Lu, Hongyang; Li, Yao; Su, Xin; Jiang, Ying; Tong, Shanbao

    2016-01-01

    The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input. PMID:27144032

  1. Muscarinic Cholinergic Modulation of Long-Lasting Synaptic Plasticity in the Rat Dentate Gyrus

    DTIC Science & Technology

    1990-12-14

    Because of its nonsjmaptic nature , the latency to peak of the antidromic spike was usually less than 2 msec. Analysis of changes in the amplitude...population spike produced by both D(-)APV and CPP, so we performed a series of experiments designed to elucidate the nature of this depression. Fig 8 shows... nature of the voltage-dependent Mg^ block of the NMDA receptor at resting membrane potential, the question arose as to 55 Fig 8. NMDA receptor

  2. Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network

    PubMed Central

    Lane, Brian J; Samarth, Pranit; Ransdell, Joseph L; Nair, Satish S; Schulz, David J

    2016-01-01

    Motor neurons of the crustacean cardiac ganglion generate virtually identical, synchronized output despite the fact that each neuron uses distinct conductance magnitudes. As a result of this variability, manipulations that target ionic conductances have distinct effects on neurons within the same ganglion, disrupting synchronized motor neuron output that is necessary for proper cardiac function. We hypothesized that robustness in network output is accomplished via plasticity that counters such destabilizing influences. By blocking high-threshold K+ conductances in motor neurons within the ongoing cardiac network, we discovered that compensation both resynchronized the network and helped restore excitability. Using model findings to guide experimentation, we determined that compensatory increases of both GA and electrical coupling restored function in the network. This is one of the first direct demonstrations of the physiological regulation of coupling conductance in a compensatory context, and of synergistic plasticity across cell- and network-level mechanisms in the restoration of output. DOI: http://dx.doi.org/10.7554/eLife.16879.001 PMID:27552052

  3. A novel short-term plasticity of intrinsic excitability in the hippocampal CA1 pyramidal cells

    PubMed Central

    Sánchez-Aguilera, A; Sánchez-Alonso, J L; Vicente-Torres, M A; Colino, A

    2014-01-01

    Changes in neuronal activity often trigger compensatory mechanisms aimed at regulating network activity homeostatically. Here we have identified and characterized a novel form of compensatory short-term plasticity of membrane excitability, which develops early after the eye-opening period in rats (P16–19 days) but not before that developmental stage (P9–12 days old). Holding the membrane potential of CA1 neurons right below the firing threshold from 15 s to several minutes induced a potentiation of the repolarizing phase of the action potentials that contributed to a decrease in the firing rate of CA1 pyramidal neurons in vitro. Furthermore, the mechanism for inducing this plasticity required the action of intracellular Ca2+ entering through T-type Ca2+ channels. This increase in Ca2+ subsequently activated the Ca2+ sensor K+ channel interacting protein 3, which led to the increase of an A-type K+ current. These results suggest that Ca2+ modulation of somatic A-current represents a new form of homeostatic regulation that provides CA1 pyramidal neurons with the ability to preserve their firing abilities in response to membrane potential variations on a scale from tens of seconds to several minutes. PMID:24756640

  4. Reduced respiratory neural activity elicits a long-lasting decrease in the CO2 threshold for apnea in anesthetized rats.

    PubMed

    Baertsch, N A; Baker, T L

    2017-01-01

    Two critical parameters that influence breathing stability are the levels of arterial pCO2 at which breathing ceases and subsequently resumes - termed the apneic and recruitment thresholds (AT and RT, respectively). Reduced respiratory neural activity elicits a chemoreflex-independent, long-lasting increase in phrenic burst amplitude, a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF). The physiological significance of iPMF is unknown. To determine if iPMF and neural apnea have long-lasting physiological effects on breathing, we tested the hypothesis that patterns of neural apnea that induce iPMF also elicit changes in the AT and RT. Phrenic nerve activity and end-tidal CO2 were recorded in urethane-anesthetized, ventilated rats to quantify phrenic nerve burst amplitude and the AT and RT before and after three patterns of neural apnea that differed in their duration and ability to elicit iPMF: brief intermittent neural apneas, a single brief "massed" neural apnea, or a prolonged neural apnea. Consistent with our hypothesis, we found that patterns of neural apnea that elicited iPMF also resulted in changes in the AT and RT. Specifically, intermittent neural apneas progressively decreased the AT with each subsequent neural apnea, which persisted for at least 60min. Similarly, a prolonged neural apnea elicited a long-lasting decrease in the AT. In both cases, the magnitude of the AT decrease was proportional to iPMF. In contrast, the RT was transiently decreased following prolonged neural apnea, and was not proportional to iPMF. No changes in the AT or RT were observed following a single brief neural apnea. Our results indicate that the AT and RT are differentially altered by neural apnea and suggest that specific patterns of neural apnea that elicit plasticity may stabilize breathing via a decrease in the AT.

  5. Spinal 5-HT7 receptor activation induces long-lasting phrenic motor facilitation.

    PubMed

    Hoffman, M S; Mitchell, G S

    2011-03-15

    Acute intermittent hypoxia elicits a form of serotonin-dependent respiratory plasticity known as phrenic long term facilitation (pLTF). Episodic spinal serotonin-2 (5-HT2) receptor activation on or near phrenic motor neurons is necessary for pLTF. A hallmark of pLTF is the requirement for serotonin-dependent synthesis of brain-derived neurotrophic factor (BDNF), and activation of its high affinity receptor, TrkB. Activation of spinal Gs protein-coupled adenosine 2A receptors (GsPCRs) elicits a unique form of long-lasting phrenic motor facilitation (PMF), but via unique mechanisms (BDNF independent TrkB trans-activation).We hypothesized that other GsPCRs elicit PMF, specifically serotonin-7 (5-HT7) receptors, which are expressed in phrenic motor neurons. Cervical spinal (C4) injections of a selective 5-HT7 receptor agonist, AS-19 (10 μM, 5 μl; 3 × 5 min), in anaesthetized, vagotomized and ventilated male Sprague-Dawley rats elicited long-lasting PMF (>120 min), an effect prevented by pretreatment with a 5-HT7 receptor antagonist (SB 269970; 5mM, 7 μl).GsPCR activation 'trans-activates'TrkB by increasing synthesis of an immature TrkB isoform. Spinal injection of a TrkB inhibitor (k252a) and siRNAs that prevent TrkB (but not BDNF) mRNA translation both blocked 5-HT7 agonist-induced PMF, confirming a requirement for TrkB synthesis and activity. k252a affected late PMF (≥ 90 min) only. Spinal inhibition of the PI3K/AKT pathway blocked 5-HT7 agonist-induced PMF, whereas MEK/ERK inhibition delayed, but did not block, PMF. An understanding of signalling mechanisms giving rise to PMF may guide development of novel therapeutic strategies to treat ventilatory control disorders associated with respiratory insufficiency, such as spinal injury and motor neuron disease.

  6. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    PubMed Central

    Siciliano, Cody A.; Fordahl, Steve C.

    2016-01-01

    Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Here we determined that cocaine self-administration in rats produced tolerance to the dopamine transporter-inhibiting effects of cocaine in the nucleus accumbens core, which was normalized following a 14 or 60 d abstinence period; however, although these rats appeared to be similar to controls, a single self-administered infusion of cocaine at the end of abstinence, even after 60 d, fully reinstated tolerance to cocaine's effects. A single cocaine infusion in a naive rat had no effect on cocaine potency, demonstrating that cocaine self-administration leaves the dopamine transporter in a “primed” state, which allows for cocaine-induced plasticity to be reinstated by a subthreshold cocaine exposure. Further, reinstatement of cocaine tolerance was accompanied by decreased cocaine-induced locomotion and escalated cocaine intake despite extended abstinence from cocaine. These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine. Further, these results provide a potential mechanism for severe cocaine binge episodes, which occur even after sustained abstinence from cocaine, and suggest that treatments aimed at transporter sites may be efficacious in promoting binge termination following relapse. SIGNIFICANCE STATEMENT Tolerance is a DSM-V criterion for substance abuse disorders. Abusers consistently show reduced subjective effects of cocaine concomitant with reduced effects of cocaine at its main site of action

  7. Dopamine regulates intrinsic excitability thereby gating successful induction of spike timing-dependent plasticity in CA1 of the hippocampus

    PubMed Central

    Edelmann, Elke; Lessmann, Volkmar

    2013-01-01

    Long-term potentiation (LTP) and long-term depression (LTD) are generally assumed to be cellular correlates for learning and memory. Different types of LTP induction protocols differing in severity of stimulation can be distinguished in CA1 of the hippocampus. To better understand signaling mechanisms and involvement of neuromodulators such as dopamine (DA) in synaptic plasticity, less severe and more physiological low frequency induction protocols should be used. In the study which is reviewed here, critical determinants of spike timing-dependent plasticity (STDP) at hippocampal CA3-CA1 synapses were investigated. We found that DA via D1 receptor signaling, but not adrenergic signaling activated by the β-adrenergic agonist isoproterenol, is important for successful expression of STDP at CA3-CA1 synapses. The DA effect on STDP is paralleled by changes in spike firing properties, thereby changing intrinsic excitability of postsynaptic CA1 neurons, and gating STDP. Whereas β-adrenergic signaling also leads to a similar (but not identical) regulation of firing pattern, it does not enable STDP. In this focused review we will discuss the current literature on dopaminergic modulation of LTP in CA1, with a special focus on timing dependent (t-)LTP, and we will suggest possible reasons for the selective gating of STDP by DA [but not noradrenaline (NA)] in CA1. PMID:23508132

  8. Intrinsic Functional Plasticity of the Thalamocortical System in Minimally Disabled Patients with Relapsing-Remitting Multiple Sclerosis.

    PubMed

    Zhou, Fuqing; Gong, Honghan; Chen, Qi; Wang, Bo; Peng, Yan; Zhuang, Ying; Zee, Chi-Shing

    2016-01-01

    The thalamus plays a crucial role in sensorimotor, cognitive, and attentional circuit functions. Disruptions in thalamic connectivity are believed to underlie the symptoms of multiple sclerosis (MS). Therefore, assessing thalamocortical structural connectivity (SC) and functional connectivity (FC) may provide new insights into the mechanism of intrinsic functional plasticity in a large-scale neural network. We used resting-state FC measurement and diffusion tensor imaging probabilistic tractography to study the functional and structural integrity of the thalamocortical system in patients with relapsing-remitting MS (RRMS) and matched healthy controls. In the thalamocortical connections of RRMS patients, we found lesion load-related regional FC in the right temporal pole, which reflected compensatory hyperconnectivity related to lesion-related demyelination. We also found significant correlations between increased diffusivity and slowed cognitive processing (PASAT) or the impact of fatigue (MFIS-5), as well as between connective fiber loss and disease duration. Taken together, the evidence from SC and FC analysis of the thalamocortical system suggests that minimally disabled RRMS patients exhibit a dissociated SC-FC pattern and limited regional functional plasticity to compensate for the chronic demyelination-related loss of long-distance SC. These results also provide further evidence supporting the notion that MS is a disorder of anatomical disconnection.

  9. Dopamine regulates intrinsic excitability thereby gating successful induction of spike timing-dependent plasticity in CA1 of the hippocampus.

    PubMed

    Edelmann, Elke; Lessmann, Volkmar

    2013-01-01

    Long-term potentiation (LTP) and long-term depression (LTD) are generally assumed to be cellular correlates for learning and memory. Different types of LTP induction protocols differing in severity of stimulation can be distinguished in CA1 of the hippocampus. To better understand signaling mechanisms and involvement of neuromodulators such as dopamine (DA) in synaptic plasticity, less severe and more physiological low frequency induction protocols should be used. In the study which is reviewed here, critical determinants of spike timing-dependent plasticity (STDP) at hippocampal CA3-CA1 synapses were investigated. We found that DA via D1 receptor signaling, but not adrenergic signaling activated by the β-adrenergic agonist isoproterenol, is important for successful expression of STDP at CA3-CA1 synapses. The DA effect on STDP is paralleled by changes in spike firing properties, thereby changing intrinsic excitability of postsynaptic CA1 neurons, and gating STDP. Whereas β-adrenergic signaling also leads to a similar (but not identical) regulation of firing pattern, it does not enable STDP. In this focused review we will discuss the current literature on dopaminergic modulation of LTP in CA1, with a special focus on timing dependent (t-)LTP, and we will suggest possible reasons for the selective gating of STDP by DA [but not noradrenaline (NA)] in CA1.

  10. Thermoset Shape-Memory Polyurethane with Intrinsic Plasticity Enabled by Transcarbamoylation.

    PubMed

    Zheng, Ning; Fang, Zizheng; Zou, Weike; Zhao, Qian; Xie, Tao

    2016-09-12

    Thermoset polymers are known for their superior thermomechanical properties, but the chemical crosslinking typically leads to intractability. This is reflected in the great differences between thermoset and thermoplastic shape-memory polymers; the former exhibit a robust shape memory but are not capable of redefining the permanent shape. Contrary to current knowledge, we reveal here that a classical thermoset shape-memory polyurethane is readily capable of permanent reshaping (plasticity) after a topological network rearrangement that is induced by transcarbamoylation. By employing the Jianzhi technique (also known as kirigami), unexpected shape-shifting versatility was observed for this otherwise classical material. As the essential carbamate moiety in polyurethanes is one of the most common polymer building units, we anticipate that our finding will have significant benefits beyond shape shifting.

  11. Intrinsic Conformational Plasticity of Native EmrE Provides a Pathway for Multidrug Resistance

    PubMed Central

    2015-01-01

    EmrE is a multidrug resistance efflux pump with specificity to a wide range of antibiotics and antiseptics. To obtain atomic-scale insight into the attributes of the native state that encodes the broad specificity, we used a hybrid of solution and solid-state NMR methods in lipid bilayers and bicelles. Our results indicate that the native EmrE dimer oscillates between inward and outward facing structural conformations at an exchange rate (kex) of ∼300 s–1 at 37 °C (millisecond motions), which is ∼50-fold faster relative to the tetraphenylphosphonium (TPP+) substrate-bound form of the protein. These observables provide quantitative evidence that the rate-limiting step in the TPP+ transport cycle is not the outward–inward conformational change in the absence of drug. In addition, using differential scanning calorimetry, we found that the width of the gel-to-liquid crystalline phase transition was 2 °C broader in the absence of the TPP+ substrate versus its presence, which suggested that changes in transporter dynamics can impact the phase properties of the membrane. Interestingly, experiments with cross-linked EmrE showed that the millisecond inward-open to outward-open dynamics was not the culprit of the broadening. Instead, the calorimetry and NMR data supported the conclusion that faster time scale structural dynamics (nanosecond–microsecond) were the source and therefore impart the conformationally plastic character of native EmrE capable of binding structurally diverse substrates. These findings provide a clear example how differences in membrane protein transporter structural dynamics between drug-free and bound states can have a direct impact on the physical properties of the lipid bilayer in an allosteric fashion. PMID:24856154

  12. Intrinsic conformational plasticity of native EmrE provides a pathway for multidrug resistance.

    PubMed

    Cho, Min-Kyu; Gayen, Anindita; Banigan, James R; Leninger, Maureen; Traaseth, Nathaniel J

    2014-06-04

    EmrE is a multidrug resistance efflux pump with specificity to a wide range of antibiotics and antiseptics. To obtain atomic-scale insight into the attributes of the native state that encodes the broad specificity, we used a hybrid of solution and solid-state NMR methods in lipid bilayers and bicelles. Our results indicate that the native EmrE dimer oscillates between inward and outward facing structural conformations at an exchange rate (k(ex)) of ~300 s(-1) at 37 °C (millisecond motions), which is ~50-fold faster relative to the tetraphenylphosphonium (TPP(+)) substrate-bound form of the protein. These observables provide quantitative evidence that the rate-limiting step in the TPP(+) transport cycle is not the outward-inward conformational change in the absence of drug. In addition, using differential scanning calorimetry, we found that the width of the gel-to-liquid crystalline phase transition was 2 °C broader in the absence of the TPP(+) substrate versus its presence, which suggested that changes in transporter dynamics can impact the phase properties of the membrane. Interestingly, experiments with cross-linked EmrE showed that the millisecond inward-open to outward-open dynamics was not the culprit of the broadening. Instead, the calorimetry and NMR data supported the conclusion that faster time scale structural dynamics (nanosecond-microsecond) were the source and therefore impart the conformationally plastic character of native EmrE capable of binding structurally diverse substrates. These findings provide a clear example how differences in membrane protein transporter structural dynamics between drug-free and bound states can have a direct impact on the physical properties of the lipid bilayer in an allosteric fashion.

  13. Chronic sleep restriction during development can lead to long-lasting behavioral effects.

    PubMed

    Saré, R Michelle; Levine, Merlin; Hildreth, Christine; Picchioni, Dante; Smith, Carolyn Beebe

    2016-03-01

    Sleep abnormalities are highly correlated with neurodevelopmental disorders, and the severity of behavioral abnormalities correlates with the presence of sleep abnormalities. Given the importance of sleep in developmental plasticity, we sought to determine the effects of chronic sleep-restriction during development on subsequent adult behavior. We sleep-restricted developing wild-type mice from P5-P42 for 3h per day by means of gentle handling (n=30) and compared behavioral outputs to controls that were handled 10 min daily (n=33). We assayed activity in the open field, social behavior, repetitive behavior, and anxiety immediately following sleep restriction and after four weeks of recovery. At six weeks of age, immediately following chronic sleep-restriction, mice were less active in an open field arena. Sociability was increased, but repetitive behaviors were unchanged in both males and females. After a 4-week period of recovery, some behavioral abnormalities persisted and some became apparent. Sleep-restricted mice had decreased activity in the beginning of an open field test. Female mice continued to have increased sociability and, in addition, increased preference for social novelty. In contrast, male mice demonstrated decreased sociability with medium effect sizes. Repetitive behavior was decreased in sleep-restricted female mice and increased in males. Measures of anxiety were not affected in the sleep-restricted mice. These results indicate that chronic sleep restriction during development can lead to long-lasting behavioral changes that are modulated by sex. Our study may have implications for a role of disrupted sleep in childhood on the unfolding of neurodevelopmental disorders.

  14. The h channel mediates location-dependence and plasticity of intrinsic phase response in rat hippocampal neurons

    PubMed Central

    Narayanan, Rishikesh; Johnston, Daniel

    2008-01-01

    The presence of phenomenological inductances in neuronal membrane has been known for more than half a century. In spite of this, the dramatic contributions of such inductive elements to the amplitude and, especially, phase of neuronal impedance, and their roles in modulating temporal dynamics of neuronal responses have surprisingly remained unexplored. In this study, we demonstrate that the h channel contributes a location-dependent and plastic phenomenological inductive component to the input impedance of CA1 pyramidal neurons. Specifically, we show that the h channels introduce an apparent negative delay in the local voltage response of these neurons with respect to the injected current within the theta frequency range. The frequency-range and the extent of this lead expand with increases in h current either through hyperpolarization, or with increasing distance of dendritic location from the soma. We also demonstrate that a spatially widespread increase in this inductive phase component accompanies long-term potentiation. Finally, employing impedance analysis, we show that both location- and activity-dependence of intrinsic phase response are not due to changes in a capacitive or a leak component, but due to changes in h channel properties. Our results suggest that certain voltage-gated ion channels can differentially regulate internal time delays within neurons, thus providing them with an independent control mechanism in temporal coding of neuronal information. Our analyses and results also establish impedance as a powerful measure of intrinsic dynamics and excitability, given that it quantifies excitability and temporal relationships among signals as functions of input frequency. PMID:18509046

  15. Ethanol exposure in early adolescence inhibits intrinsic neuronal plasticity via sigma-1 receptor activation in hippocampal CA1 neurons

    PubMed Central

    Sabeti, Jilla

    2011-01-01

    Background We demonstrated previously that rats exposed to chronic intermittent ethanol (CIE) vapors in early adolescence show increased magnitudes of long-term potentiation (LTP) of excitatory transmission when recorded at dendritic synapses in hippocampus. Large amplitude LTP following CIE exposure is mediated by sigma-1 receptors; however, not yet addressed is the role of sigma-1 receptors in modulating the intrinsic properties of neurons to alter their action potential firing during LTP. Methods Activity-induced plasticity of spike firing was investigated using rat hippocampal slice recordings to measure changes in both field excitatory postsynaptic potentials (fEPSPs) and population spikes (pop. spikes) concomitantly at dendritic inputs and soma of CA1 pyramidal neurons, respectively. Results We observed unique modifications in plasticity of action potential firing in hippocampal slices from CIE exposed adolescent rats, where the induction of large amplitude LTP by 100 Hz stimulations was accompanied by reduced CA1 neuronal excitability—reflected as decreased pop. spike efficacy and impaired activity-induced fEPSP-to-spike (E-S) potentiation. By contrast, LTP induction in ethanol-naïve control slices resulted in increased spike efficacy and robust E-S potentiation. E-S potentiation impairments emerged at 24 hr after CIE treatment cessation, but not before the alcohol withdrawal period, and were restored with bath-application of the sigma-1 receptor selective antagonist BD1047, but not the NMDA receptor antagonist D-AP5. Further evidence revealed a significantly shortened somatic fEPSP time course in adolescent CIE-withdrawn hippocampal slices during LTP; however, paired-pulse data show no apparent correspondence between E-S dissociation and altered recurrent feedback inhibition. Conclusions Results here suggest that acute withdrawal from adolescent CIE exposure triggers sigma-1 receptors that act to depress the efficacy of excitatory inputs in triggering

  16. Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior.

    PubMed

    Kamii, Hironori; Kurosawa, Ryo; Taoka, Naofumi; Shinohara, Fumiya; Minami, Masabumi; Kaneda, Katsuyuki

    2015-05-01

    The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors.

  17. Long-Lasting Sparks: Multi-Metastability and Release Competition in the Calcium Release Unit Network

    PubMed Central

    Song, Zhen; Karma, Alain; Weiss, James N.; Qu, Zhilin

    2016-01-01

    Calcium (Ca) sparks are elementary events of biological Ca signaling. A normal Ca spark has a brief duration in the range of 10 to 100 ms, but long-lasting sparks with durations of several hundred milliseconds to seconds are also widely observed. Experiments have shown that the transition from normal to long-lasting sparks can occur when ryanodine receptor (RyR) open probability is either increased or decreased. Here, we demonstrate theoretically and computationally that long-lasting sparks emerge as a collective dynamical behavior of the network of diffusively coupled Ca release units (CRUs). We show that normal sparks occur when the CRU network is monostable and excitable, while long-lasting sparks occur when the network dynamics possesses multiple metastable attractors, each attractor corresponding to a different spatial firing pattern of sparks. We further highlight the mechanisms and conditions that produce long-lasting sparks, demonstrating the existence of an optimal range of RyR open probability favoring long-lasting sparks. We find that when CRU firings are sparse and sarcoplasmic reticulum (SR) Ca load is high, increasing RyR open probability promotes long-lasting sparks by potentiating Ca-induced Ca release (CICR). In contrast, when CICR is already strong enough to produce frequent firings, decreasing RyR open probability counter-intuitively promotes long-lasting sparks by decreasing spark frequency. The decrease in spark frequency promotes intra-SR Ca diffusion from neighboring non-firing CRUs to the firing CRUs, which helps to maintain the local SR Ca concentration of the firing CRUs above a critical level to sustain firing. In this setting, decreasing RyR open probability further suppresses long-lasting sparks by weakening CICR. Since a long-lasting spark terminates via the Kramers’ escape process over a potential barrier, its duration exhibits an exponential distribution determined by the barrier height and noise strength, which is modulated

  18. miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

    NASA Astrophysics Data System (ADS)

    Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

    2014-02-01

    Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

  19. Effect of Spike-Timing-Dependent Plasticity on Intrinsic Coherence Resonance in Newman-Watts Stochastic Hodgkin-Huxley Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Xie, Huijuan; Gong, Yubing; Wang, Qi

    2016-07-01

    In this paper, we numerically study the effect of spike-timing-dependent plasticity (STDP) on coherence resonance (CR) induced by channel noise in adaptive Newman-Watts stochastic Hodgkin-Huxley neuron networks. It is found that STDP can either enhance or suppress the intrinsic CR when the adjusting rate of STDP decreases or increases. STDP can alter the effects of network randomness and network size on the intrinsic CR. Under STDP, for electrical coupling there are optimal network randomness and network size by which the intrinsic CR becomes strongest, however, for chemical coupling the intrinsic CR is always enhanced as network randomness or network size increases, which are different from the results for fixed coupling. These results show that the intrinsic CR of the neuronal networks can be either enhanced or suppressed by STDP, and there are optimal network randomness and network size by which the intrinsic CR becomes strongest. These findings could provide a new insight into the role of STDP for the information processing and transmission in neural systems.

  20. A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A.

    PubMed

    Montoliu, Carmina; Piedrafita, Blanca; Serra, Miguel A; del Olmo, Juan A; Rodrigo, José M; Felipo, Vicente

    2007-01-01

    Hepatic encephalopathy in patients with liver disease is associated with poor prognosis. This could be due to the induction by the transient episode of hepatic encephalopathy of long-lasting alterations making patients more susceptible. We show that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction. The content of the regulatory subunit of the protein kinase dependent on cAMP (PKA-RI) is increased in erythrocytes from cirrhotic patients. This increase is reproduced in rats with portacaval anastomosis and in rats with hyperammonemia without liver failure, suggesting that hyperammonemia is responsible for increased PKA-RI in patients. We analyzed whether there is a correlation between ammonia levels and PKA-RI content in patients. All cirrhotic patients had increased content of PKA-RI. Some of them showed normal ammonia levels but had suffered previous hyperammonemia episodes. This suggested that a single transient episode of hyperammonemia could induce the long-lasting increase in PKA-RI. To assess this, we injected normal rats with ammonia and blood was taken at different times. Ammonia returned to basal levels at 2 h. However, PKA-RI was significantly increased in blood cells from rats injected with ammonia 3 wk after injection. In conclusion, it is shown that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction both in blood and brain. These alterations may contribute to the poor prognosis of patients suffering hepatic encephalopathy.

  1. Effect of 14-MeV neutrons on strontium-aluminate-based long-lasting phosphor

    NASA Astrophysics Data System (ADS)

    Toh, K.; Shikama, T.; Katsui, H.; Nagata, S.; Tsuchiya, B.; Yamauchi, M.; Nishitani, T.

    2009-04-01

    Long-lasting phosphor (LLP) emits photons for a long period of time after the cessation of irradiation without external excitation. LLP exhibits not only a long-lasting emission but also strong fluorescence. The fluorescence and long-lasting emission properties of two types of strontium-aluminate-based LLPs - SrAl 2O 4:Eu 2+, Dy 3+ and Sr 4Al 14O 25:Eu 2+, Dy 3+ - are examined under 14-MeV neutron irradiation. The fluorescent spectra of the LLPs have characteristic peaks due to their dopants and the fluorescent intensity of Sr 4Al 14O 25:Eu 2+, Dy 3+ shows good radiation resistance for the neutrons, with a slight change after increasing the irradiation fluence up to 10 19 n/m 2. Long-lasting emissions are exhibited after neutron irradiation, and the emission spectra have one peak due to Eu 2+. A peak due to Dy 3+ ends immediately when the irradiation is stopped. Further, it is found that there is an optimum neutron fluence at which the longest decay time is obtained.

  2. Selective Maintenance of Motor Performance in Older Adults from Long-Lasting Sport Practice

    ERIC Educational Resources Information Center

    Dascal, Juliana Bayeux; Teixeira, Luis Augusto

    2016-01-01

    Purpose: Decline of motor performance in older individuals affects their quality of life. Understanding the contribution of sport-related training in advanced ages might help to attenuate motor performance decay as one gets older. The purpose of our study was to evaluate the extent to which long-lasting training in running or sport-specific skills…

  3. Long-lasting facilitation of respiratory rhythm by treatment with TRPA1 agonist, cinnamaldehyde.

    PubMed

    Tani, Mariho; Yazawa, Itaru; Ikeda, Keiko; Kawakami, Kiyoshi; Onimaru, Hiroshi

    2015-08-01

    The transient receptor potential (TRP) channels are widely distributed in the central nervous system (CNS) and peripheral nervous system. We examined the effects of TRP ankyrin 1 (TRPA1) agonists (cinnamaldehyde and allyl isothiocyanate) on respiratory rhythm generation in brainstem-spinal cord preparations from newborn rats [postnatal days 0-3 (P0-P3)] and in in situ-perfused preparations from juvenile rats (P11-P13). Preparations were superfused with modified Krebs solution at 25-26°C, and activity of inspiratory C4 ventral root (or phrenic nerve) was monitored. In the newborn rat, an in vitro preparation of cinnamaldehyde (0.5 mM) induced typically biphasic responses in C4 rate: an initial short increase and subsequent decrease, then a gradual recovery of rhythm during 15 min of bath application. After washout, the respiratory rhythm rate further increased, remaining 200% of control for >120 min, indicating long-lasting facilitation. Allyl isothiocyanate induced effects similar to those of cinnamaldehyde. The long-lasting facilitation of respiratory rhythm was partially antagonized by the TRPA1 antagonist HC-030031 (10 μM). We obtained similar long-lasting facilitation in an in situ-perfused reparation from P11-P13 rats. On the basis of results from transection experiments of the rostral medulla and whole-cell recordings from preinspiratory neurons in the parafacial respiratory group (pFRG), we suggest that the rostral medulla, including the pFRG, is important to the induction of long-lasting facilitation. A histochemical analysis demonstrated a wide distribution of TRPA1 channel-positive cells in the reticular formation of the medulla, including the pFRG. Our findings suggest that TRPA1 channel activation could induce long-lasting facilitation of respiratory rhythm and provide grounds for future study on the roles of TRPA1 channels in the CNS.

  4. Long-lasting facilitation of respiratory rhythm by treatment with TRPA1 agonist, cinnamaldehyde

    PubMed Central

    Tani, Mariho; Yazawa, Itaru; Ikeda, Keiko; Kawakami, Kiyoshi

    2015-01-01

    The transient receptor potential (TRP) channels are widely distributed in the central nervous system (CNS) and peripheral nervous system. We examined the effects of TRP ankyrin 1 (TRPA1) agonists (cinnamaldehyde and allyl isothiocyanate) on respiratory rhythm generation in brainstem-spinal cord preparations from newborn rats [postnatal days 0–3 (P0–P3)] and in in situ-perfused preparations from juvenile rats (P11–P13). Preparations were superfused with modified Krebs solution at 25–26°C, and activity of inspiratory C4 ventral root (or phrenic nerve) was monitored. In the newborn rat, an in vitro preparation of cinnamaldehyde (0.5 mM) induced typically biphasic responses in C4 rate: an initial short increase and subsequent decrease, then a gradual recovery of rhythm during 15 min of bath application. After washout, the respiratory rhythm rate further increased, remaining 200% of control for >120 min, indicating long-lasting facilitation. Allyl isothiocyanate induced effects similar to those of cinnamaldehyde. The long-lasting facilitation of respiratory rhythm was partially antagonized by the TRPA1 antagonist HC-030031 (10 μM). We obtained similar long-lasting facilitation in an in situ-perfused reparation from P11–P13 rats. On the basis of results from transection experiments of the rostral medulla and whole-cell recordings from preinspiratory neurons in the parafacial respiratory group (pFRG), we suggest that the rostral medulla, including the pFRG, is important to the induction of long-lasting facilitation. A histochemical analysis demonstrated a wide distribution of TRPA1 channel-positive cells in the reticular formation of the medulla, including the pFRG. Our findings suggest that TRPA1 channel activation could induce long-lasting facilitation of respiratory rhythm and provide grounds for future study on the roles of TRPA1 channels in the CNS. PMID:26108952

  5. Mechanisms of long-lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks.

    PubMed Central

    Contreras, D; Timofeev, I; Steriade, M

    1996-01-01

    1. To explore the nature of the long-lasting hyperpolarizations that characterize slow oscillations in corticothalamic circuits in vivo, intracellular recordings were obtained under ketamine-xylazine anaesthesia from cortical (Cx) cells of the cat precruciate motor cortex, thalamic reticular (RE) cells from the rostrolateral sector, and thalamocortical (TC) cells from the ventrolateral (VL) nucleus. 2. Measurements in the three cell types showed input resistance (Rin) to be highest during the long-lasting hyperpolarizations that correspond to depth-positive waves of the cortical EEG. Rin was lowest during the early phase of high-amplitude depth-negative EEG waves and increased thereafter until the next cycle of the slow oscillation. 3. Spontaneous long-lasting hyperpolarizations were compared with those evoked by dorsal thalamic stimulation. Voltage versus current (V-I) plots showed similar membrane potential (Vm) ranges and slopes for spontaneous and evoked hyperpolarizations in both Cx and RE cells. V-I plots from TC cells had similar slopes, but Vm during evoked hyperpolarizations was displaced towards more negative values. 4. Intracellular injection of constant hyperpolarizing current in Cx cells increased the amplitude of the initial part of the depolarizing plateau of the slow oscillation, but decreased the amplitude of the last part. 5. These results suggest disfacilitation to be the dominant mechanism in the membrane of cortical and thalamic cells during the spontaneous long-lasting hyperpolarizations, which shape and synchronize slow oscillations in corticothalamic networks. In Cx and RE cells, the same mechanism underlies thalamically evoked long-lasting hyperpolarizations. By contrast, evoked responses in TC cells show a strong additional hyperpolarizing factor. We propose that GABAB processes are stronger in TC than in Cx neurones, thus rendering the thalamus an easier target for absence-type epileptic phenomena through potentiation of thalamic rebound

  6. [Surgical treatment of the plexus brachialis injury using long-lasting electrostimulation].

    PubMed

    Tsymbaliuk, V I; Tretiak, I B; Tsymbaliuk, Iu V

    2013-06-01

    The results of surgical treatment were analyzed in 103 patients, suffering consequences of the plexus brachialis injury, using the system for long-lasting electrostimulation, called "Henci 3M". The system of a domestic manufacture is an individual one, permits to perform the direct electrostimulation seances in a home conditions several times a day for a long time. There were positive results noted: an enhancement in volume and strength of movements in upper extremity of various degree, restoration of sensitivity and disappearance or reduction of a pain syndrome intensity in 90.6% of patients. Long-lasting electrostimulation permits more effectively and valuably to restore a plexus brachialis function in its traumatic injury.

  7. Long-Lasting Permethrin-Impregnated Clothing Protects Against Mosquito Bites in Outdoor Workers.

    PubMed

    Londono-Renteria, Berlin; Patel, Jaymin C; Vaughn, Meagan; Funkhauser, Sheana; Ponnusamy, Loganathan; Grippin, Crystal; Jameson, Sam B; Apperson, Charles; Mores, Christopher N; Wesson, Dawn M; Colpitts, Tonya M; Meshnick, Steven R

    2015-10-01

    Outdoor exposure to mosquitoes is a risk factor for many diseases, including malaria and dengue. We have previously shown that long-lasting permethrin-impregnated clothing protects against tick and chigger bites in a double-blind randomized controlled trial in North Carolina outdoor workers. Here, we evaluated whether this clothing is protective against mosquito bites by measuring changes in antibody titers to mosquito salivary gland extracts. On average, there was a 10-fold increase in titer during the spring and summer when mosquito exposure was likely to be the highest. During the first year of the study, the increase in titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of control subjects. This finding suggests that long-lasting permethrin-impregnated clothing provided protection against mosquito bites.

  8. Long-Lasting Permethrin-Impregnated Clothing Protects against Mosquito Bites in Outdoor Workers

    PubMed Central

    Londono-Renteria, Berlin; Patel, Jaymin C.; Vaughn, Meagan; Funkhauser, Sheana; Ponnusamy, Loganathan; Grippin, Crystal; Jameson, Sam B.; Apperson, Charles; Mores, Christopher N.; Wesson, Dawn M.; Colpitts, Tonya M.; Meshnick, Steven R.

    2015-01-01

    Outdoor exposure to mosquitoes is a risk factor for many diseases, including malaria and dengue. We have previously shown that long-lasting permethrin-impregnated clothing protects against tick and chigger bites in a double-blind randomized controlled trial in North Carolina outdoor workers. Here, we evaluated whether this clothing is protective against mosquito bites by measuring changes in antibody titers to mosquito salivary gland extracts. On average, there was a 10-fold increase in titer during the spring and summer when mosquito exposure was likely to be the highest. During the first year of the study, the increase in titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of control subjects. This finding suggests that long-lasting permethrin-impregnated clothing provided protection against mosquito bites. PMID:26195460

  9. Pink light emitting long-lasting phosphorescence in Sm 3+-doped CdSiO 3

    NASA Astrophysics Data System (ADS)

    Lei, Bingfu; Liu, Yingliang; Liu, Jie; Ye, Zeren; Shi, Chunshan

    2004-04-01

    Novel pink light emitting long-lasting afterglow CdSiO 3:Sm 3+ phosphors are prepared by the conventional high-temperature solid-state method and their luminescent properties are investigated. XRD and photoluminescence (PL) spectra are used to characterize the synthesized phosphors. The phosphors are well crystallized by calcinations at 1050°C for 5 h. These phosphors emit pink light and show long-lasting phosphorescence after they are excited with 254 nm ultraviolet light. The phosphorescence lasts for nearly 5 h in the light perception of the dark-adapted human eye (0.32 mcd/m 2). The phosphorescence mechanism is also investigated. All the results indicate that these phosphors have promising potential practical applications.

  10. A short bout of HFD promotes long-lasting hepatic lipid accumulation

    PubMed Central

    Chiazza, Fausto; Challa, Tenagne D; Lucchini, Fabrizio C; Konrad, Daniel; Wueest, Stephan

    2016-01-01

    abstract A short bout of high fat diet (HFD) impairs glucose tolerance and induces hepatic steatosis in mice. Here, we aimed to elaborate on long-lasting effects of short-term high fat feeding. As expected, one week of HFD significantly impaired glucose tolerance. Intriguingly, recovery feeding with a standard rodent diet for 8 weeks did not fully normalize glucose tolerance. In addition, mice exposed to a short bout of HFD revealed significantly increased liver fat accumulation paralleled by elevated portal free fatty acid levels after 8 weeks of recovery feeding compared to exclusively chow-fed littermates. In conclusion, a short bout of HFD has long-lasting effects on hepatic lipid accumulation and glucose tolerance. PMID:27144100

  11. Preventing long-lasting fear recovery using bilateral alternating sensory stimulation: A translational study.

    PubMed

    Wurtz, H; El-Khoury-Malhame, M; Wilhelm, F H; Michael, T; Beetz, E M; Roques, J; Reynaud, E; Courtin, J; Khalfa, S; Herry, C

    2016-05-03

    Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery.

  12. Long-Lasting Neural and Behavioral Effects of Iron Deficiency in Infancy

    PubMed Central

    Lozoff, Betsy; Beard, John; Connor, James; Felt, Barbara; Georgieff, Michael; Schallert, Timothy

    2006-01-01

    Infants are at high risk for iron deficiency and iron-deficiency anemia. This review summarizes evidence of long-term effects of iron deficiency in infancy. Follow-up studies from preschool age to adolescence report poorer cognitive, motor, and social-emotional function, as well as persisting neurophysiologic differences. Research in animal models points to mechanisms for such long-lasting effects. Potential mechanisms relate to effects of iron deficiency during brain development on neurometabolism, myelination, and neurotransmitter function. PMID:16770951

  13. Long-lasting airplane headache in a patient with chronic rhinosinusitis.

    PubMed

    Pfund, Z; Trauninger, A; Szanyi, I; Illes, Z

    2010-04-01

    The authors report long-lasting airplane headache in a patient with non-allergic, chronic rhinosinusitis. Association of mucosal inflammation with compromised sinonasal ventilation and sinus barotrauma created a base for not only the pain but also for the prolongation of symptoms. Effective therapy with antihistamine and nasal decongestant supports the theory that sinonasal barotrauma plays a triggering role in the pathophysiology of airplane headache.

  14. Variability in State-Dependent Plasticity of Intrinsic Properties during Cell-Autonomous Self-Regulation of Calcium Homeostasis in Hippocampal Model Neurons1,2,3

    PubMed Central

    Srikanth, Sunandha

    2015-01-01

    Abstract How do neurons reconcile the maintenance of calcium homeostasis with perpetual switches in patterns of afferent activity? Here, we assessed state-dependent evolution of calcium homeostasis in a population of hippocampal pyramidal neuron models, through an adaptation of a recent study on stomatogastric ganglion neurons. Calcium homeostasis was set to emerge through cell-autonomous updates to 12 ionic conductances, responding to different types of synaptically driven afferent activity. We first assessed the impact of theta-frequency inputs on the evolution of ionic conductances toward maintenance of calcium homeostasis. Although calcium homeostasis emerged efficaciously across all models in the population, disparate changes in ionic conductances that mediated this emergence resulted in variable plasticity to several intrinsic properties, also manifesting as significant differences in firing responses across models. Assessing the sensitivity of this form of plasticity, we noted that intrinsic neuronal properties and the firing response were sensitive to the target calcium concentration and to the strength and frequency of afferent activity. Next, we studied the evolution of calcium homeostasis when afferent activity was switched, in different temporal sequences, between two behaviorally distinct types of activity: theta-frequency inputs and sharp-wave ripples riding on largely silent periods. We found that the conductance values, intrinsic properties, and firing response of neurons exhibited differential robustness to an intervening switch in the type of afferent activity. These results unveil critical dissociations between different forms of homeostasis, and call for a systematic evaluation of the impact of state-dependent switches in afferent activity on neuronal intrinsic properties during neural coding and homeostasis. PMID:26464994

  15. Blue and red long lasting phosphorescence (LLP) in β-Zn3(PO4)2:Mn2+,Zr4+

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Su, Qiang; Wang, Shubin

    2005-07-01

    Multi-color long lasting phosphorescent (LLP) phenomenon in β-Zn3(PO4)2:Mn2+,Zr4+ was systematically investigated. It is found that the red (λEm=616 nm) LLP performance of Mn2+ such as brightness and duration is largely improved, and that the blue (λEm=475 nm) LLP of Zr4+ with lower intensity appears when Zr4+ ions are co-doped into the matrix. The fluorescence, phosphorescence and thermoluminescence (TL) spectra show that Mn2+ ion is solely expected as a luminescent center, while Zr4+ ion not only acts as a luminescent center, but also induces an electron trap (TrapZr) associated with a TL peak at 344 K. The trap depth for TrapZr is 0.25 eV, while that for the intrinsic trap is 0.38 eV, associated with a dominant peak at 385 K for Zn3(PO4)2:Mn2+. The Zr4+-induced trap with suitable depth is responsible for the improvement of the red LLP of Mn2+ ion and the appearance of the blue LLP of Zr4+ ion. The LLP mechanism is also investigated.

  16. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family-crucially involved in the regulation of brain structural plasticity and cognitive processes-can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R.

  17. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

    PubMed Central

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family—crucially involved in the regulation of brain structural plasticity and cognitive processes—can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R. PMID:25926782

  18. Adolescent ethanol exposure: does it produce long-lasting electrophysiological effects?

    PubMed

    Ehlers, Cindy L; Criado, José R

    2010-02-01

    This review discusses evidence for long-lasting neurophysiological changes that may occur following exposure to ethanol during adolescent development in animal models. Adolescence is the time that most individuals first experience ethanol exposure, and binge drinking is not uncommon during adolescence. If alcohol exposure is neurotoxic to the developing brain during adolescence, not unlike it is during fetal development, then understanding how ethanol affects the developing adolescent brain becomes a major public health issue. Adolescence is a critical time period when cognitive, emotional, and social maturation occurs and it is likely that ethanol exposure may affect these complex processes. To study the effects of ethanol on adolescent brain, animal models where the dose and time of exposure can be carefully controlled that closely mimic the human condition are needed. The studies reviewed provide evidence that demonstrates that relatively brief exposure to high levels of ethanol, via ethanol vapors, during a period corresponding to parts of adolescence in the rat is sufficient to cause long-lasting changes in functional brain activity. Disturbances in waking electroencephalogram and a reduction in the P3 component of the event-related potential (ERP) have been demonstrated in adult rats that were exposed to ethanol vapor during adolescence. Adolescent ethanol exposure was also found to produce long-lasting reductions in the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS, a finding consistent with a premature aging of sleep. Further studies are necessary to confirm these findings, in a range of strains, and to link those findings to the neuroanatomical and neurochemical mechanisms potentially underlying the lasting effects of adolescent ethanol exposure.

  19. Long-lasting enhancement of corticostriatal transmission by taurine: role of dopamine and acetylcholine.

    PubMed

    Chepkova, A N; Sergeeva, O A; Haas, H L

    2005-06-01

    1. Taurine applied to mouse brain slices evokes a long-lasting enhancement (LLE) of corticostriatal synaptic transmission, LLE(TAU). 2. The occurrence of LLE(TAU) was significantly decreased in the presence of the specific antagonists at either D1 (SCH23390) or D2 (raclopride) dopamine (DA) receptors. 3. LLE(TAU) was prevented by scopolamine, a muscarinic antagonist, and significantly suppressed by the nicotinic antagonist mecamylamine. 4. Thus, dopaminergic and cholinergic mechanisms, in concert with the taurine transporter and glycine receptors, contribute critically to the induction of corticostriatal LLE(TAU).

  20. The substrate for long-lasting memory: if not protein synthesis, then what?

    PubMed

    Routtenberg, Aryeh

    2008-03-01

    The prevailing textbook view that de novo protein synthesis is required for memory (e.g., [Bear, M. F., Connors, B., & Paradiso, M. 2006. Neuroscience. Lippincott, New York]) is seriously flawed and an alternative hypothesis has been proposed in which post-translational modification (PTM) of proteins already synthesized and already present within the synapse is 'the' substrate for long-lasting memory. Protein synthesis serves a replenishment role. The first part of this review discusses how long-lasting memory can be achieved with 'only' PTM of existing synaptic proteins. The second part critically reviews a recent report published in Neuron 2007 that exemplifies the current view of protein synthesis and memory while also illustrating how these results can be understood within this new PTM framework. A necessary yet unexpected conclusion to emerge from consideration of the consequences of a PTM mechanism as the necessary, sufficient and exclusive substrate for long-lasting memory, is that the central Hebbian dogma that cells that 'fire together, wire together' is an unlikely mechanism for long-lasting memory. Thus, a unique feature of the PTM model is that longevity of information storage is achieved not by stability of the synaptic mechanism, but by impermanent pseudoredundant circuits. This is so because PTM is a reversible process and thus any permanent connection, any 'lasting effect' cannot be in the form of stable synapse formation. We have therefore proposed a solution in which network level processes regulate cellular mechanisms, even as such mechanisms regulate the network. Thus, synapses are 'meta-stabilized' by regulated feedback mediated by the circuit in which the synapse is embedded. For example, spontaneous activity is proposed to be a substrate feedback mechanism we term 'cryptic rehearsal' to sustain for some period of time after learning an approximation to the state initially created by input. Additionally, because the duplication of these traces

  1. Combining Organophosphate Treated Wall Linings and Long-lasting Insecticidal Nets for Improved Control of Pyrethroid Resistant Anopheles gambiae

    PubMed Central

    Ngufor, Corine; Tchicaya, Emile; Koudou, Benjamin; N'Fale, Sagnon; Dabire, Roch; Johnson, Paul; Ranson, Hilary; Rowland, Mark

    2014-01-01

    Background New approaches to delivering insecticides need to be developed to improve malaria vector control. Insecticidal durable wall lining (DL) and net wall hangings (NWH) are novel alternatives to indoor residual spraying which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations. Methods Experimental hut trials were carried out in Valley du Kou, Burkina Faso to evaluate the efficacy of pirimiphos methyl treated DL and NWH either alone or in combination with LLINs against pyrethroid resistant Anopheles gambiae ss. Comparison was made with pyrethroid DL. Mosquitoes were genotyped for kdr and ace-1R resistant genes to investigate the insecticide resistance management potential of the combination. Results The overall kdr and ace-1R allele frequencies were 0.95 and 0.01 respectively. Mortality with p-methyl DL and NWH alone was higher than with pyrethroid DL alone (>95% vs 40%; P<0.001). Combining pyrethroid DL with LLINs did not show improvement in mortality (48%) compared to the LLIN alone (44%) (P>0.1). Combining p-methyl DL or NWH with LLINs reduced biting rates significantly (8–9%) compared to p-methyl DL and NWH alone (>40%) and killed all An gambiae that entered the huts. Mosquitoes bearing the ace-1R gene were more likely to survive in huts with p-methyl DL alone (p<0.03) whereas all resistant and susceptible genotypes were killed by the combination. Conclusion P-methyl DL and NWH outperformed pyrethroid DL. Combining p-methyl DL and NWH with LLINs could provide significant epidemiological benefits against a vector population which is resistant to pyrethroids but susceptible to organophosphates. There was evidence that the single intervention would select kdr and ace-1R resistance genes and the combination intervention might select less strongly. Technology to bind organophosphates to plastic wall

  2. Peculiarities of transformation of adaptation level of the astronaut in conditions of long-lasting flight

    NASA Astrophysics Data System (ADS)

    Padashulya, H.; Prisnyakova, L.; Prisnyakov, V.

    Prognostication of the development of adverse factors of psychological processes in the personality of the astronaut who time and again feels transformation of internal structure of his personality is one of cardinal problems of the long-lasting flight Adaptation to changing conditions of long-lasting flight is of particular importance because it has an effect on the efficiency of discharged functions and mutual relations in the team The fact of standard psychological changes emerging in the personality being in the state of structural transformations is the precondition for the possibility of prognostication Age-specific gender and temperamental differences in the personality enable to standardize these changes Examination of the process of transformation of adaptation level of the personality in the varied environment depending on the type of temperament and constituents age and gender is chief object of the report In the report it is shown that in the process of transformation of adaptation parameters - attitude to guillemotleft work guillemotright guillemotleft family guillemotright guillemotleft environment guillemotright and guillemotleft ego guillemotright - the changes can go in two directions - in the direction of increase and decline of indexes The trend of increase enables to accumulate them and form potentiality to reduce or increase the level of personality adaptation There is a hypothesis that the dynamics of the process of transformation of adaptation parameter is shown up in the orientation of increase of

  3. Glutamine triggers long-lasting increase in striatal network activity in vitro.

    PubMed

    Fleischer, Wiebke; Theiss, Stephan; Schnitzler, Alfons; Sergeeva, Olga

    2017-04-01

    Accumulation of ammonium and glutamine in blood and brain is a key factor in hepatic encephalopathy (HE) - a neuropsychiatric syndrome characterized by various cognitive and motor deficits. MRI imaging identified abnormalities notably in the basal ganglia of HE patients, including its major input station, the striatum. While neurotoxic effects of ammonia have been extensively studied, glutamine is primarily perceived as "detoxified" form of ammonia. We applied ammonium and glutamine to striatal and cortical cells from newborn rats cultured on microelectrode arrays. Glutamine, but not ammonium significantly increased spontaneous spike rate with a long-lasting excitation outlasting washout. This effect was more prominent in striatal than in cortical cultures. Calcium imaging revealed that glutamine application caused a rise in intracellular calcium that depended both on system A amino acid transport and activation of ionotropic glutamate receptors. This pointed to downstream glutamate release that was triggered by intracellular glutamine. Using an enzymatic assay kit we confirmed glutamine-provoked glutamate release from striatal cells. Real-time PCR and immunocytochemistry demonstrated the presence of vesicular glutamate transporters (VGLUT1 and VGLUT2) necessary for synaptic glutamate release in striatal neurons. We conclude that extracellular glutamine is taken up by neurons, triggers synaptic release of glutamate which is then taken up by astrocytes and again converted to glutamine. This feedback-loop causes a sustained long-lasting excitation of network activity. Thus, apart from ammonia also its "detoxified" form glutamine might be responsible for the neuropsychiatric symptoms in HE.

  4. Long-Lasting Suppression of Acoustic Startle Response after Mild Traumatic Brain Injury

    PubMed Central

    Sinha, Swamini; Avcu, Pelin; Roland, Jessica J.; Nadpara, Neil; Pfister, Bryan; Long, Mathew; Santhakumar, Vijayalakshmi; Servatius, Richard J.

    2015-01-01

    Abstract Acoustic startle response (ASR) is a defensive reflex that is largely ignored unless greatly exaggerated. ASR is suppressed after moderate and severe traumatic brain injury (TBI), but the effect of mild TBI (mTBI) on ASR has not been investigated. Because the neural circuitry for ASR resides in the pons in all mammals, ASR may be a good measure of brainstem function after mTBI. The present study assessed ASR in Sprague-Dawley rats after mTBI using lateral fluid percussion and compared these effects to those on spatial working memory. mTBI caused a profound, long-lasting suppression of ASR. Both probability of emitting a startle and startle amplitude were diminished. ASR suppression was observed as soon as 1 day after injury and remained suppressed for the duration of the study (21 days after injury). No indication of recovery was observed. mTBI also impaired spatial working memory. In contrast to the suppression of ASR, working memory impairment was transient; memory was impaired 1 and 7 days after injury, but recovered by 21 days. The long-lasting suppression of ASR suggests long-term dysfunction of brainstem neural circuits at a time when forebrain neural circuits responsible for spatial working memory have recovered. These results have important implications for return-to-activity decisions because recovery of cognitive impairments plays an important role in these decisions. PMID:25412226

  5. Surface electromyographic assessment of patients with long lasting temporomandibular joint disorder pain.

    PubMed

    Tartaglia, Gianluca M; Lodetti, Gianluigi; Paiva, Guiovaldo; De Felicio, Claudia Maria; Sforza, Chiarella

    2011-08-01

    The normalized electromyographic characteristics of masticatory muscles in patients with temporomandibular joint disorders (TMD) and healthy controls were compared. Thirty TMD patients (15 men, 15 women, mean age 23 years) with long lasting pain (more than 6 months), and 20 control subjects matched for sex and age were examined. All patients had arthrogenous TMD according to the Research Diagnostic Criteria for TMD (RDC/TMD). Surface electromyography of masseter and temporal muscles was performed during maximum teeth clenching either on cotton rolls or in intercuspal position. Standardized EMG indices and the median power frequency were obtained, and compared between the two groups and sexes using ANOVAs. During clenching, the TMD patients had larger asymmetry in their temporalis muscles, larger temporalis activity relative to masseter, and reduced mean power frequencies than the control subjects (p<0.05, ANOVA). In both groups, the mean power frequencies of the temporalis muscles were larger than those of the masseter muscles (p<0.001). No sex related differences, and no sex × group interactions were found. In conclusion, young adult patients with long lasting TMD have an increased and more asymmetric standardized activity of their temporalis anterior muscle, and reduced mean power frequencies, relative to healthy controls.

  6. Some interesting phenomena in the study of rare earth long lasting phosphors

    NASA Astrophysics Data System (ADS)

    Su, Qiang; Li, Chengyu; Wang, Jing

    2014-09-01

    Long lasting phosphors (LLPs) are a kind of very important and usable luminescent materials. Many new LLPs were found and some interesting phenomena were observed. Some distinctive questions on LLPs have been found and reviewed in this paper. For example: why most of LLPs of rare earth cannot be excited by sun light even they have nearly the same excitation spectra as SrAl2O4:Eu2+, Dy3+, Sr2MgSi2O7:Eu2+, Dy3+ which can be excited by sun light ? why there is only the emission of the activator Eu2+ in SrAl2O4:Eu2+, Dy3+, but no emission of the codopant (Dy3+) was observed under usual excitation condition? why different co-dopants have different effect on the LLP? various mechanisms about LLP of rare earth are still discussing widely and unsolved, which is the suitable one? there is similarity between the mechanisms of thermo-stimulated luminescence (TSL), photo-stimulated luminescence (PSL) and force-stimulated luminescence (FSL or mechanoluminescence) with the mechanisms for long lasting luminescence. For synthesis of LLP, which is a kind of electron trapping materials, the aliovalence (unequal valence) substitution method plays the key role. By using of this method, defects, vacancies and traps are produced. The properties of LLP strongly depend on the effects of doping and co-doping ions and some applications of LLP are presented in this paper.

  7. Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain.

    PubMed

    Salinas-Abarca, Ana Belen; Avila-Rojas, Sabino Hazael; Barragán-Iglesias, Paulino; Pineda-Farias, Jorge Baruch; Granados-Soto, Vinicio

    2017-02-15

    The purpose of this study was to investigate whether 1%, 2% or 5% formalin injection produce hypersensitivity with characteristics of the neuropathic pain induced by spinal nerve injury. Formalin injection (1%, 2% and 5%) produced concentration-dependent long-lasting (at least 14 days) mechanical allodynia and hyperalgesia in both paws. Likewise, L5/L6 spinal nerve ligation induced allodynia and hyperalgesia in both paws. The intensity of hypersensitivity was greater in the ipsilateral than in the contralateral paw in all models. Systemic gabapentin or morphine completely reduced 1% formalin-induced hypersensitivity. In contrast, both drugs were not able to fully diminish 2-5% formalin- and nerve injury-induced hypersensitivity. Indomethacin produced a significant effect in the chronic 1% formalin test. Conversely, this drug did not modify 2 or 5% formalin- and nerve injury-induced hypersensitivity. Spinal nerve injury and 2-5%, but not 1%, formalin injection enhanced ATF3 protein expression and immunofluorescence in dorsal root ganglia (DRG) in a time-dependent manner. Furthermore, 2-5%, but not 1%, formalin injection or spinal nerve injury also enhanced α2δ-1 subunit protein levels in DRG. Our results suggest that 5% and, at lesser extent, 2% formalin injection produces long-lasting hypersensitivity with a pharmacological and molecular pattern that resembles neuropathic pain induced by spinal nerve ligation.

  8. Long-lasting semantic interference effects in object naming are not necessarily conceptually mediated

    PubMed Central

    Riley, Emma; McMahon, Katie L.; de Zubicaray, Greig

    2015-01-01

    Long-lasting interference effects in picture naming are induced when objects are presented in categorically related contexts in both continuous and blocked cyclic paradigms. Less consistent context effects have been reported when the task is changed to semantic classification. Experiment 1 confirmed the recent finding of cumulative facilitation in the continuous paradigm with living/non-living superordinate categorization. To avoid a potential confound involving participants responding with the identical superordinate category in related contexts in the blocked cyclic paradigm, we devised a novel set of categorically related objects that also varied in terms of relative age – a core semantic type associated with the adjective word class across languages. Experiment 2 demonstrated the typical interference effect with these stimuli in basic level naming. In Experiment 3, using the identical blocked cyclic paradigm, we failed to observe semantic context effects when the same pictures were classified as younger–older. Overall, the results indicate the semantic context effects in the two paradigms do not share a common origin, with the effect in the continuous paradigm arising at the level of conceptual representations or in conceptual-to-lexical connections while the effect in the blocked cyclic paradigm most likely originates at a lexical level of representation. The implications of these findings for current accounts of long-lasting interference effects in spoken word production are discussed. PMID:25999892

  9. Long-lasting suppression of acoustic startle response after mild traumatic brain injury.

    PubMed

    Pang, Kevin C H; Sinha, Swamini; Avcu, Pelin; Roland, Jessica J; Nadpara, Neil; Pfister, Bryan; Long, Mathew; Santhakumar, Vijayalakshmi; Servatius, Richard J

    2015-06-01

    Acoustic startle response (ASR) is a defensive reflex that is largely ignored unless greatly exaggerated. ASR is suppressed after moderate and severe traumatic brain injury (TBI), but the effect of mild TBI (mTBI) on ASR has not been investigated. Because the neural circuitry for ASR resides in the pons in all mammals, ASR may be a good measure of brainstem function after mTBI. The present study assessed ASR in Sprague-Dawley rats after mTBI using lateral fluid percussion and compared these effects to those on spatial working memory. mTBI caused a profound, long-lasting suppression of ASR. Both probability of emitting a startle and startle amplitude were diminished. ASR suppression was observed as soon as 1 day after injury and remained suppressed for the duration of the study (21 days after injury). No indication of recovery was observed. mTBI also impaired spatial working memory. In contrast to the suppression of ASR, working memory impairment was transient; memory was impaired 1 and 7 days after injury, but recovered by 21 days. The long-lasting suppression of ASR suggests long-term dysfunction of brainstem neural circuits at a time when forebrain neural circuits responsible for spatial working memory have recovered. These results have important implications for return-to-activity decisions because recovery of cognitive impairments plays an important role in these decisions.

  10. Long-lasting energetic particle modes in tokamak plasmas with low magnetic shear

    NASA Astrophysics Data System (ADS)

    Zhang, Rui-Bin; Wang, Xian-Qu; Xiao, Chi-Jie; Wang, Xiao-Gang; Liu, Yi; Deng, Wei; Chen, Wei; Ding, Xuan-Tong; Duan, Xu-Ru; the HL-2 A Team

    2014-09-01

    A long-lasting (for hundreds of milliseconds) m/n = 1 energetic particle mode driven by trapped fast ions, other than conventional fishbone bursts, is studied theoretically and in comparison with HL-2A experimental results. The mode can be observed in weak shear tokamak plasmas during neutral beam injection with a mostly steady amplitude envelope of long-lasting magnetic perturbation signals. The dispersion relation and radial structure of the mode are calculated with a weak shear q-profile. Both the m/n = 1/1 component and its higher frequency m/n = 2/2 harmonics are found to be unstable, in good agreement with experimental observations on HL-2A. On the other hand, due to the feature of weak magnetic shear, the mode is also significantly different from bursty fishbones, especially the mode structure, temporal behavior, instability threshold and growth rate dependence on the fast ion gradient. The nonlinear evolution of the mode and the comparison with fishbone bursts are also further investigated.

  11. Evolutionary divergence of intrinsic and trans-regulated nucleosome positioning sequences reveals plastic rules for chromatin organization

    PubMed Central

    Tsankov, Alex; Yanagisawa, Yoshimi; Rhind, Nicholas; Regev, Aviv; Rando, Oliver J.

    2011-01-01

    The packaging of eukaryotic genomes into nuclesomes plays critical roles in chromatin organization and gene regulation. Studies in Saccharomyces cerevisiae indicate that nucleosome occupancy is partially encoded by intrinsic antinucleosomal DNA sequences, such as poly(A) sequences, as well as by binding sites for trans-acting factors that can evict nucleosomes, such as Reb1 and the Rsc3/30 complex. Here, we use genome-wide nucleosome occupancy maps in 13 Ascomycota fungi to discover large-scale evolutionary reprogramming of both intrinsic and trans determinants of chromatin structure. We find that poly(G)s act as intrinsic antinucleosomal sequences, comparable to the known function of poly(A)s, but that the abundance of poly(G)s has diverged greatly between species, obscuring their antinucleosomal effect in low-poly(G) species such as S. cerevisiae. We also develop a computational method that uses nucleosome occupancy maps for discovering trans-acting general regulatory factor (GRF) binding sites. Our approach reveals that the specific sequences bound by GRFs have diverged substantially across evolution, corresponding to a number of major evolutionary transitions in the repertoire of GRFs. We experimentally validate a proposed evolutionary transition from Cbf1 as a major GRF in pre-whole-genome duplication (WGD) yeasts to Reb1 in post-WGD yeasts. We further show that the mating type switch-activating protein Sap1 is a GRF in S. pombe, demonstrating the general applicability of our approach. Our results reveal that the underlying mechanisms that determine in vivo chromatin organization have diverged and that comparative genomics can help discover new determinants of chromatin organization. PMID:21914852

  12. Pregnancy leads to long-lasting changes in human brain structure.

    PubMed

    Hoekzema, Elseline; Barba-Müller, Erika; Pozzobon, Cristina; Picado, Marisol; Lucco, Florencio; García-García, David; Soliva, Juan Carlos; Tobeña, Adolf; Desco, Manuel; Crone, Eveline A; Ballesteros, Agustín; Carmona, Susanna; Vilarroya, Oscar

    2017-02-01

    Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective ('pre'-'post' pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not in-between sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women's babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestive of an adaptive process serving the transition into motherhood. Another follow-up session showed that the GM reductions endured for at least 2 years post-pregnancy. Our data provide the first evidence that pregnancy confers long-lasting changes in a woman's brain.

  13. An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.

    PubMed

    Della Valle, M; Chincarini, G; Panagia, N; Tagliaferri, G; Malesani, D; Testa, V; Fugazza, D; Campana, S; Covino, S; Mangano, V; Antonelli, L A; D'Avanzo, P; Hurley, K; Mirabel, I F; Pellizza, L J; Piranomonte, S; Stella, L

    2006-12-21

    Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from the distant Universe. Long-duration GRBs (those lasting more than approximately 2 s) are believed to originate from the deaths of massive stars, mainly on the basis of a handful of solid associations between GRBs and supernovae. GRB 060614, one of the closest GRBs discovered, consisted of a 5-s hard spike followed by softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here we report deep optical observations of GRB 060614 showing no emerging supernova with absolute visual magnitude brighter than M(V) = -13.7. Any supernova associated with GRB 060614 was therefore at least 100 times fainter, at optical wavelengths, than the other supernovae associated with GRBs. This demonstrates that some long-lasting GRBs can either be associated with a very faint supernova or produced by different phenomena.

  14. Human dignity as a component of a long-lasting and widespread conceptual construct.

    PubMed

    Baertschi, Bernard

    2014-06-01

    For some decades, the concept of human dignity has been widely discussed in bioethical literature. Some authors think that this concept is central to questions of respect for human beings, whereas others are very critical of it. It should be noted that, in these debates, dignity is one component of a long-lasting and widespread conceptual construct used to support a stance on the ethical question of the moral status of an action or being. This construct has been used from Modernity onward to condemn slavery and torture as violations of human dignity. In spelling it out, we can come to a better understanding of what "dignity" means and become aware that there exists a quite useful place for this notion in our ethical thought, albeit a modest one.

  15. Mechanisms of long-lasting enhancement of corticostriatal neurotransmission by taurine.

    PubMed

    Chepkova, Aisa N; Sergeeva, Olga A; Haas, Helmut L

    2006-01-01

    The long-lasting enhancement of corticostriatal neurotransmission by taurine, LLE-TAU represents a complex phenomenon requiring concurrent activation of glycine, DA and Ach receptors as well as taurine uptake. The data on the mechanisms of corticostriatal LLE-TAU can be integrated in the following scheme. Taurine interaction with glycine and GABAA receptors causes depolarization of striatal medium spiny cells (Chepkova et al., 2002) which is enhanced by taurine electrogenic uptake by TauT (Sarkar et al., 2003). This depolarization leads to Ca2+ entry via low voltage gated Ca2+ channels. Muscarinic M1 receptors are expressed in medium spiny neurons (Yan et al., 2001) and regulate their excitability mostly via phospholipase C (PLC)/PKC cascade (Lin et al., 2004). Concurrent activation of M1 and PLC-coupled D1 receptors (O'Sullivan et al., 2004) can amplify Ca2+ signal via IP3- stimulated Ca2+ release from intracellular stores and stimulate PKC.

  16. Trials of Improved Practices (TIPs): A Strategy for Making Long-Lasting Nets Last Longer?

    PubMed Central

    Harvey, Steven A.; Paredes Olórtegui, Maribel; Leontsini, Elli; Ramal Asayag, César; Scott, Kerry; Winch, Peter J.

    2013-01-01

    Long-lasting insecticidal net (LLIN) use is a proven malaria prevention method. Mass distribution has greatly expanded LLIN access in sub-Saharan Africa, but a gap remains between LLIN ownership and use. Furthermore, LLINs wear out more quickly than anticipated. This paper suggests a participatory research strategy—trials of improved practices (TIPs)—that could identify locally appropriate approaches to prolonging net life and increasing effective use. We used TIPs to overcome barriers to optimal net use in the Peruvian Amazon. Working with 15 families in three villages, we tested home treatment of cotton nets, use of an alternative netting fabric, and alternative washing and care instructions. TIPs helped confirm feasibility of these interventions. Although our findings are time- and context-specific, TIPs could help improve consistency and effectiveness of current LLIN use and prolong net lifespan in sub-Saharan Africa and elsewhere. This would help maximize the value of shrinking donor resources for malaria. PMID:23530074

  17. An unusually long-lasting outbreak of community-acquired Legionnaires' disease, 2005-2008, Italy.

    PubMed

    Scaturro, M; Fontana, S; Crippa, S; Caporali, M G; Seyler, T; Veschetti, E; Villa, G; Rota, M C; Ricci, M L

    2015-08-01

    An unusually long-lasting community-acquired outbreak of Legionnaires' disease (LD) occurred in the inhabitants of a town in northern Italy from 2005 to 2008. Overall, 43 cases were diagnosed including five deaths. Hundreds of water samples were collected for Legionella isolation but only two clinical samples were obtained. Clinical strains were ST23 as were environmental isolates detected in most Legionella-positive patients' homes and those from a public fountain. Although no Legionella was found in the municipal water mains, a continuous chlorination was applied in 2008. This action resulted in a halving of cases, although incidence remained tenfold higher than the Italian average incidence until the end of 2013, when it dropped to the expected rate. Retrospective analyses of prevalent wind direction suggested that a hidden cooling tower could have been the main cause of this uncommon outbreak, highlighting the importance of implementation of cooling tower registers in supporting LD investigations.

  18. Laboratory evaluation of rubidium as a long-lasting marker for bloodfeeding sand flies (Diptera: Psychodidae).

    PubMed

    Mascari, T M; Stout, R W; Foil, L D

    2012-01-01

    The objective of this study was to evaluate the use of the trace element rubidium (Rb) as a long-lasting systemic biomarker for bloodfeeding females of the sand fly Phlebotomus papatasi Scopoli. Baits containing Rb chloride were found to be palatable to hamsters in this study. We were able to detect Rb using a portable X-ray fluorescence analyzer in all sand flies that fed on Rb-treated hamsters for at least 14 d postbloodmeal. We also detected Rb in sand flies that took a bloodmeal from hamsters up to 10 d after the hamsters were withdrawn from a Rb-treated diet. Results of this study constitute proof of concept for the incorporation of Rb chloride into rodent baits for marking bloodfeeding sand flies, and suggest that Rb marking could be used as a technique for evaluating rodent-targeted sand fly control methods and in ecological studies on sand flies.

  19. The temperature dependence of luminescence from a long-lasting phosphor exposed to ionizing radiation

    NASA Astrophysics Data System (ADS)

    Kowatari, Munehiko; Koyama, Daisuke; Satoh, Yoshiyuki; Iinuma, Kouichi; Uchida, Shunsuke

    2002-03-01

    The temperature dependence of luminescence from a long-lasting phosphor (LLP), SrAl 2O 4 : Eu 2+,Dy 3+, exposed to ionizing radiation has been measured to understand the LLP luminescence mechanism. Evaluation of the decay constants of the LLP exposed to α-, β- or γ-rays at temperatures from 200 to 390 K showed that the decay constant is divided into four components ranging from 10 -4 to 10 -1 s -1 with activation energies of 0.02-0.35 eV. Total luminous intensity from the LLP with changing irradiation temperature has its maximum value around the room temperature. Irradiation at elevated temperature (390 K) has the total luminescence pattern with monotonous decrease as temperature rises. As a result of evaluating the temperature dependence of luminescence, the luminescence mechanism is considered as follows:

  20. Long-lasting seismic repeaters in the Central Basin of the Main Marmara Fault

    NASA Astrophysics Data System (ADS)

    Schmittbuhl, J.; Karabulut, H.; Lengliné, O.; Bouchon, M.

    2016-09-01

    The Main Marmara Fault which crosses the whole Marmara Sea is a significant seismic gap along the North Anatolian Fault. Here we show that nine long-lasting strike-slip seismic repeaters exist below the Central Basin within the seismogenic zone, in a 10 km region where deep creep was previously suggested from the analysis of the local seismicity. The typical recurrence time was 8 months during the 2008-2015 period. The cumulative slip of the repeating sequence appears to be compatible with the regional geodetic slip rate if they are assumed to be part of a large single asperity (10 km). The repeaters also exhibit short-term crises and are possibly related to bursts of creep.

  1. [Understanding the non-use of long-lasting impregnated nets (LLINs) in Niger].

    PubMed

    Faye, S L

    2012-01-01

    In Niger, malaria is the leading cause of mortality and morbidity among pregnant women and children under 5 years. To decrease these rates, the country initiated a prevention policy of free distribution of long-lasting impregnated nets (LLINs). However, improved physical access to this preventive tool has not led to its regular use in households. A nationally representative quantitative and qualitative survey sought to document the reasons for non-use. The results show that the possession of a LLIN is quite low and confirm the low utilization rate, with significant differences by region. Cultural beliefs are not the main barriers to the use of LLINs in Niger. Knowledge and social, technical, environmental and economic dimensions were all more decisive. These results suggest that while improving awareness and communication is important for changing behavior, it cannot alone remove certain socioeconomic barriers and improve LLIN use.

  2. Long-lasting effect of subliminal processes on cardiovascular responses and performance.

    PubMed

    Capa, Rémi L; Cleeremans, Axel; Bustin, Gaëlle M; Hansenne, Michel

    2011-07-01

    Students were exposed to a priming task in which subliminal representations of the goal of studying were directly paired (priming-positive group) or not (priming group) to positive words. A control group without subliminal prime of the goal was added. Just after the priming task, students performed an easy or a difficult learning task based on their coursework. Participants in the priming-positive group performed better and had a stronger decrease of pulse transit time and pulse wave amplitude reactivity than participants of the two other groups, but only during the difficult condition. Results suggested that subliminal priming induces effortful behavior extending over twenty five minutes but only when the primes had been associated with visible positive words acting as a reward. These findings provide evidence that subliminal priming can have long-lasting effects on behaviors typical of daily life.

  3. A personal view from a long-lasting collaborator on the research strategies of Marshall Nirenberg.

    PubMed

    Higashida, Haruhiro

    2012-11-01

    In this review, I summarized transition in Dr. Marshall Nirenberg's research interests during 1970s, from a view of a long-lasting collaborator. Nirenberg switched his research filed to neurobiology after his success in deciphering genetic code and being honored with the Nobel Prize in Physiology or Medicine in 1968. His targets were to obtain genetically pure population of neurons, i.e. neuroblastoma clones, to make somatic hydrid cells, to culture neuronal and muscle cells, and to produce monoclonal antibodies against whole retinal or neuroblastoma cells. He studied neurotransmitters, receptors, cyclic nucleotides, cell differentiation, secretion, synapse formation, and chemical recognition. Especially he liked his hypothesis for opiate tolerance and dependency as a model of cellular memory. Through these studies, he seemed to devote all his time of about 50 years from 1960s to decoding brain memory processes.

  4. NOVAE WITH LONG-LASTING SUPERSOFT EMISSION THAT DRIVE A HIGH ACCRETION RATE

    SciTech Connect

    Schaefer, Bradley E.; Collazzi, Andrew C.

    2010-05-15

    We identify a new class of novae characterized by the post-eruption quiescent light curve being more than roughly a factor of 10 brighter than the pre-eruption light curve. Eight novae (V723 Cas, V1500 Cyg, V1974 Cyg, GQ Mus, CP Pup, T Pyx, V4633 Sgr, and RW UMi) are separated out as being significantly distinct from other novae. This group shares a suite of uncommon properties, characterized by the post-eruption magnitude being much brighter than before eruption, short orbital periods, long-lasting supersoft emission following the eruption, a highly magnetized white dwarf (WD), and secular declines during the post-eruption quiescence. We present a basic physical picture which shows why all five uncommon properties are causally connected. In general, novae show supersoft emission due to hydrogen burning on the WD in the final portion of the eruption, and this hydrogen burning will be long-lasting if new hydrogen is poured onto the surface at a sufficient rate. Most novae do not have adequate accretion for continuous hydrogen burning, but some can achieve this if the companion star is nearby (with short orbital period) and a magnetic field channels the matter onto a small area on the WD so as to produce a locally high accretion rate. The resultant supersoft flux irradiates the companion star and drives a higher accretion rate (with a brighter post-eruption phase), which serves to keep the hydrogen burning and the supersoft flux going. The feedback loop cannot be perfectly self-sustaining, so the supersoft flux will decline over time, forcing a decline in the accretion rate and the system brightness. We name this new group after the prototype, V1500 Cyg. V1500 Cyg stars are definitely not progenitors of Type Ia supernovae. The V1500 Cyg stars have similar physical mechanisms and appearances as predicted for nova by the hibernation model, but with this group accounting for only 14% of novae.

  5. Long-lasting sensitization of reward-directed behavior by amphetamine.

    PubMed

    Mendez, Ian A; Williams, Matthew T; Bhavsar, Atasi; Lu, Annie P; Bizon, Jennifer L; Setlow, Barry

    2009-07-19

    Exposure to psychostimulant drugs of abuse such as amphetamine can result in long-lasting "sensitization" of reward-directed behavior, such that subjects display enhancements in behavior directed by and toward rewards and reward-predictive cues (i.e. "incentive sensitization"). The purpose of these experiments was to determine the degree to which such sensitization resulting from chronic amphetamine exposure influences both appetitive and consummatory food-motivated behavior. Adult male Long-Evans rats received daily i.p. injections of D-amphetamine (2.0 mg/kg) or saline vehicle for five consecutive days. This amphetamine exposure regimen produced lasting sensitization to the acute locomotor stimulant effect of the drug. One month after drug exposure rats were tested for instrumental responding (lever pressing) for food reward under various response schedules. Two months after drug exposure, rats were tested for food consumption in a discriminative Pavlovian context-potentiated eating task, involving pairings of one context with food and another context with no food. Amphetamine exposed rats showed significantly greater instrumental responding for food reward than saline controls, particularly under conditions of high response ratios. In the potentiated eating task, testing under conditions of food satiation revealed that amphetamine exposed rats ate significantly more than saline controls in the food-paired context. These experiments demonstrate that amphetamine exposure can cause enduring increases in both appetitive and consummatory aspects of natural reward-directed behavior. Such long-lasting incentive sensitization could account in part for the propensity for relapse in drug addiction, as well as for reported enhancements in non-drug reward-related behavior.

  6. Acetylcholine Encodes Long-Lasting Presynaptic Plasticity at Glutamatergic Synapses in the Dorsal Striatum after Repeated Amphetamine Exposure

    PubMed Central

    Wang, Wengang; Darvas, Martin; Storey, Granville P.; Bamford, Ian J.; Gibbs, Jeffrey T.; Palmiter, Richard D.

    2013-01-01

    Locomotion and cue-dependent behaviors are modified through corticostriatal signaling whereby short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders, including Parkinson's disease and drug dependence. We found that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted >50 d in treated mice. An amphetamine challenge reversed CPD via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons. This PPP was correlated with locomotor responses after a drug challenge, suggesting that it may underlie the sensitization process. Experiments in brain slices and in vivo indicated that dopamine regulation of acetylcholine release from tonically active interneurons contributes to CPD, PPP, locomotor sensitization, and cognitive ability. Therefore, a chronic decrease in corticostriatal activity during withdrawal is regulated around a new physiological range by tonically active interneurons and returns to normal upon reexposure to amphetamine, suggesting that this paradoxical return of striatal activity to a more stable, normalized state may represent an additional source of drug motivation during abstinence. PMID:23785153

  7. White-light-emitting long-lasting phosphorescence in Dy{sup 3+}-doped SrSiO{sub 3}

    SciTech Connect

    Kuang Jinyong; Liu Yingliang . E-mail: tliuyl@jnu.edu.cn; Zhang Jianxian

    2006-01-15

    We report on a luminescent phenomenon in Dy{sup 3+}-doped SrSiO{sub 3} long-lasting phosphor. After irradiation by a 254-nm UV lamp for 5min, the Dy{sup 3+}-doped SrSiO{sub 3} phosphor emits white light-emitting long-lasting phosphorescence for more than 1h even after the irradiation source has been removed. Photoluminescence, long-lasting phosphorescence and thermoluminescence (TL) spectra are used to explain this phenomenon. Photoluminescence spectra reveal that the white light-emitting long-lasting phosphorescence originated from the two mixtures of Dy{sup 3+} characteristic luminescence, the 480-nm blue emission ({sup 4}F{sub 9/2}->{sup 6}H{sub 15/2}) and the 572-nm yellow emission ({sup 4}F{sub 9/2}->{sup 6}H{sub 13/2}). TL spectra shows that the introduction of Dy{sup 3+} ions into the SrSiO{sub 3} host produces a highly dense trapping level at 377K (0.59eV), which is responsible for the long-lasting phosphorescence at room temperature. A possible mechanism of the long-lasting phosphorescence based on the experimental results is proposed. It is considered that the long-lasting phosphorescence is due to persistent energy transfer from the electron traps to the Dy{sup 3+} ions, which creates the persistent luminescence of Dy{sup 3+} to produce the white light-emitting long-lasting phosphorescence.

  8. Tonotopic and Field-Specific Representation of Long-Lasting Sustained Activity in Rat Auditory Cortex

    PubMed Central

    Shiramatsu, Tomoyo I.; Noda, Takahiro; Akutsu, Kan; Takahashi, Hirokazu

    2016-01-01

    Cortical information processing of the onset, offset, and continuous plateau of an acoustic stimulus should play an important role in acoustic object perception. To date, transient activities responding to the onset and offset of a sound have been well investigated and cortical subfields and topographic representation in these subfields, such as place code of sound frequency, have been well characterized. However, whether these cortical subfields with tonotopic representation are inherited in the sustained activities that follow transient activities and persist during the presentation of a long-lasting stimulus remains unknown, because sustained activities do not exhibit distinct, reproducible, and time-locked responses in their amplitude to be characterized by grand averaging. To address this gap in understanding, we attempted to decode sound information from densely mapped sustained activities in the rat auditory cortex using a sparse parameter estimation method called sparse logistic regression (SLR), and investigated whether and how these activities represent sound information. A microelectrode array with a grid of 10 × 10 recording sites within an area of 4.0 mm × 4.0 mm was implanted in the fourth layer of the auditory cortex in rats under isoflurane anesthesia. Sustained activities in response to long-lasting constant pure tones were recorded. SLR then was applied to discriminate the sound-induced band-specific power or phase-locking value from those of spontaneous activities. The highest decoding performance was achieved in the high-gamma band, indicating that cortical inhibitory interneurons may contribute to the sparse tonotopic representation in sustained activities by mediating synchronous activities. The estimated parameter in the SLR decoding revealed that the informative recording site had a characteristic frequency close to the test frequency. In addition, decoding of the four test frequencies demonstrated that the decoding performance of the SLR

  9. Did the short PETM trigger long-lasting changes in terrestrial environments?

    NASA Astrophysics Data System (ADS)

    Fricke, H. C.; Clyde, W. C.

    2012-12-01

    The Paleocene Eocene Thermal Maximum (PETM) is a well-documented episode of warming where average temperatures increased 5-8 C in both marine and terrestrial settings before returning to pre-PETM values. As a result the PETM is generally thought of as a transient event that is superimposed on a longer-term trend of global change. Nevertheless not all aspects of the climatic-hydrologic-biologic system experienced a transient response to this event. For example, the well-known dispersal of mammals (Artiodactyls, Perrisopdactyls and Primates = APP taxa) at the beginning of the PETM resulted in fundamentally different terrestrial ecosystems dafter the PETM compared to before it. In this case the PETM can be considered not just a transient event, but a triggering, or threshold, event that resulted in long-term biotic change. Here we consider the possibility that the PETM acted as a threshold event for parts of the climatic and hydrologic system as well as the biologic system. A review of terrestrial/fluvial sections from Laramide basins of western North America (Bighorn, Green River, Huerfano/Raton, Piceance Creek, Powder River, San Juan, Tornillo, Uintah, Washakie, Williston, Wind River), reveals a pronounced difference between rocks of Paleocene and of Eocene age. Common differences include absence of lignites/coal beds in the Eocene, and the occurrence of highly oxidized paleosols and relatively fewer organic-rich mudstones compared to the Paleocene. These suggest drier conditions, either a decrease in mean annual precipitation or enhanced seasonal drying. In sections where the PETM can be identified on the basis of biostratigraphic indicators and carbon isotope excursions (Bighorn, Piceance Creek, Powder River and Williston Basins), and where the PETM can be inferred based on carbon isotope data alone (Huerfano/Raton?, Tornillo, Wind River Basins), it is associated with this transition from one long-lasting lithofacies (environment?) to another. This association

  10. Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

    SciTech Connect

    Lundstedt, Dan; Gustafsson, Magnus; Steineck, Gunnar; Malmstroem, Per; Alsadius, David; Sundberg, Agnetha; Wilderaeng, Ulrica; Holmberg, Erik; Johansson, Karl-Axel; Karlsson, Per

    2012-05-01

    Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting

  11. Long-lasting partnership between insulin resistance and endothelial dysfunction: role of metabolic memory

    PubMed Central

    Tallapragada, Divya Sri Priyanka; Karpe, Pinakin Arun; Tikoo, Kulbhushan

    2015-01-01

    Background and Purpose The persistence of deleterious effects of hyperglycaemia even after glucose normalization is referred to as ‘metabolic memory’. However, similar persistent effects of the metabolic consequences of a high fat diet (HFD) have not been described. Experimental Approach Rats were given a normal pellet diet (NPD) or a HFD for 3 months. The animals from the HFD group were then returned to the NPD to observe the long-term effects of insulin resistance. Endothelial dysfunction was assessed by carbachol-mediated vasorelaxation and eNOS phosphorylation. Key Results As expected, HFD consumption resulted in insulin resistance and endothelial dysfunction. Phosphorylation of eNOS at S1177 was decreased in HFD rats, compared with that in the NPD group. Rats on 3 months of HFD showed glucose intolerance and impaired insulin sensitivity and were then switched back to NPD (REV group). Levels of cholesterol and triglyceride, and adiposity returned to normal in REV rats. However, endothelium-dependent vascular responses to carbachol which were impaired in HFD rats, continued to be impaired in REV rats. Similarly, decreased eNOS phosphorylation after HFD was not improved after 1 or 6 months of REV. Conclusions and Implications Our data indicate that returning to NPD did not improve the insulin sensitivity or the endothelial dysfunction induced by HFD. Although some biochemical parameters responsible for insulin resistance and endothelial dysfunction were normalized, molecular and vascular abnormalities, involving NO, persisted for several months, highlighting the long-lasting effects of metabolic memory. PMID:25825057

  12. Leukocyte CD11a expression and granulocyte activation during experimental myocardial ischemia and long lasting reperfusion

    PubMed Central

    Lantos, János; Grama, László; Orosz, Tamás; Temes, Gyula; Rőth, Elizabeth

    2001-01-01

    BACKGROUND: Myocardial ischemia and reperfusion are accompanied by leukocyte activation and expression of surface adhesion molecules, which induce pathological interactions between endothelial cells and circulating neutrophils, leading to tissue damage. While the dynamics of these processes have been well defined during acute reperfusion, there is very little information regarding long lasting reperfusion. OBJECTIVES: To investigate neutrophil granulocyte (PMN) activation and the CD11a expression of leukocytes during myocardial ischemia and reperfusion for four weeks. ANIMALS AND METHODS: The left anterior descending coronary artery was occluded for 1 h in six dogs, followed by reperfusion for four weeks. Peripheral blood samples were collected before the operation, at the end of ischemia, at 5 and 60 min of reperfusion, and on postoperative days 1, 2, 3, 7, 14, 21 and 28. Sham operation on four dogs served as control. Leukocyte expression of CD11a was measured by flow cytometry. Superoxide radical production of isolated PMNs was determined spectrophotometrically. RESULTS: Granulocyte CD11a expression increased while the superoxide radical-producing capacity decreased significantly by the third postoperative day. Sham operation produced similar alterations in these parameters during the first postoperative week. From the second postoperative week, however, granulocyte radical production and adhesion molecule expression were higher in the ischemic animals. CONCLUSIONS: The exhaustion of PMN radical production and maximal CD11a expression during the first postoperative week are probably due to the surgical trauma caused by thoracotomy, but increased granulocyte function during later reperfusion indicates prolonged healing of injured myocardium. PMID:20428266

  13. Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone

    SciTech Connect

    Pang, P.K.T.; Wang, R.; Shan, J.; Karpinski, E.; Benishin, C.G. )

    1990-01-01

    The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.

  14. Long-Lasting Amelioration of Walking Trajectory in Neglect after Prismatic Adaptation

    PubMed Central

    Rabuffetti, Marco; Folegatti, Alessia; Spinazzola, Lucia; Ricci, Raffaella; Ferrarin, Maurizio; Berti, Anna; Neppi-Modona, Marco

    2013-01-01

    In the present study we explored the effect of prismatic adaptation (PA) applied to the upper right limb on the walking trajectory of a neglect patient with more severe neglect in far than in near space. The patient was asked to bisect a line fixed to the floor by walking across it before and after four sessions of PA distributed over a time frame of 67 days. Gait path was analyzed by means of an optoelectronic motion analysis system. The walking trajectory improved following PA and the result was maintained at follow-up, 15 months after treatment. The improvement was greater for the predicted bisection error (estimated on the basis of the trajectory extrapolated from the first walking step) than for the observed bisection error (measured at line bisection). These results show that PA may act on high level spatial representation of gait trajectory rather than on lower level sensory-motor gait components and suggest that PA may have a long-lasting rehabilitative effect on neglect patients showing a deviated walking trajectory. PMID:23882208

  15. Pharmacokinetics of rifapentine, a new long lasting rifamycin, in the rat, the mouse and the rabbit.

    PubMed

    Assandri, A; Ratti, B; Cristina, T

    1984-09-01

    A study on the pharmacokinetics of rifapentine, a new long-lasting rifamycin, has been carried out in the rat, the mouse and the rabbit. The investigation was made using either radioactive or unlabelled rifapentine and both the total 14C and the unchanged compound were assayed. In the rat, the overall evidence obtained was: the oral absorption of rifapentine into central compartment, due to its poor water solubility, appears to be dose-dependent with a satisfactory oral absorption (84%) after a dose of 3 mg/kg, lower (65%) after 10 mg/kg; the antibiotic undergoes rapid liver uptake while it diffuses into the tissue compartment more slowly, with particular affinity for the adrenals, pancreas and kidneys; concentrations higher than in plasma were also measured in the lungs; elimination of rifapentine from the blood and tissue compartments suggests a non linear capacity-limited kinetics where the terminal elimination phase has monoexponential course. Terminal plasma half-life ranged between 14 and 18 hours; the compound is eliminated mainly via the bile with the feces (92% of dose). In mice rifapentine shows a kinetic profile resembling that obtained in rats, whereas in rabbits is metabolized and/or eliminated much more rapidly with a half-life of only 1.8 hours.

  16. DNA shuffling: induced molecular breeding to produce new generation long-lasting vaccines.

    PubMed

    Marshall, Sergio H

    2002-11-01

    The paradigm for classic vaccines has been to mimic natural infection, and their success relies mostly on the induction of neutralizing antibodies followed by long-lasting immunity. The outcome of aggressive chronic infections such as HIV and HCV, the reappearance of fastidious diseases such as tuberculosis and the progression of cancer growth suggest that natural immune responses are definitely insufficient in many cases. A new paradigm is needed to design and develop a new high-efficiency generation of vaccines ideally able to surpass the capabilities of natural immune responses. In vitro evolution is a new, important laboratory method to evolve molecules with desired properties, which appears as an appealing alternative to achieve this goal. In its battle against disease, the vertebrate immune system triggers a series of well-known molecular events in order to produce protective neutralizing antibodies. This natural in vivo response shares remarkable similarities with the in vitro technique known as molecular breeding or "DNA shuffling." This method exploits the recombination between genes to dramatically accelerate the rate at which genes can be evolved under selection pressure in the laboratory, producing optimized high-efficiency mutant proteins. Since new generation vaccines are aimed to overcome natural selection and environmental pressures to fully inactivate rapidly developing pathogen variants, they could be engineered, developed and selected through the application of directed DNA shuffling procedures. This review highlights the potential of the procedure in the complex context of natural immune responses and the equilibrium and interaction existing in nature between hosts and pathogens.

  17. Auditory cortical field coding long-lasting tonal offsets in mice

    PubMed Central

    Baba, Hironori; Tsukano, Hiroaki; Hishida, Ryuichi; Takahashi, Kuniyuki; Horii, Arata; Takahashi, Sugata; Shibuki, Katsuei

    2016-01-01

    Although temporal information processing is important in auditory perception, the mechanisms for coding tonal offsets are unknown. We investigated cortical responses elicited at the offset of tonal stimuli using flavoprotein fluorescence imaging in mice. Off-responses were clearly observed at the offset of tonal stimuli lasting for 7 s, but not after stimuli lasting for 1 s. Off-responses to the short stimuli appeared in a similar cortical region, when conditioning tonal stimuli lasting for 5–20 s preceded the stimuli. MK-801, an inhibitor of NMDA receptors, suppressed the two types of off-responses, suggesting that disinhibition produced by NMDA receptor-dependent synaptic depression might be involved in the off-responses. The peak off-responses were localized in a small region adjacent to the primary auditory cortex, and no frequency-dependent shift of the response peaks was found. Frequency matching of preceding tonal stimuli with short test stimuli was not required for inducing off-responses to short stimuli. Two-photon calcium imaging demonstrated significantly larger neuronal off-responses to stimuli lasting for 7 s in this field, compared with off-responses to stimuli lasting for 1 s. The present results indicate the presence of an auditory cortical field responding to long-lasting tonal offsets, possibly for temporal information processing. PMID:27687766

  18. Long lasting phosphorescence and photostimulated luminescence in Tb-ion-activated reduced calcium aluminate glasses

    NASA Astrophysics Data System (ADS)

    Kinoshita, Takeru; Yamazaki, Masaaki; Kawazoe, Hiroshi; Hosono, Hideo

    1999-10-01

    Long lasting phosphorescence (LLP) and photostimulated luminescence (PSL) were found in reduced calcium aluminate glasses activated with Tb3+ ions. The LLP from Tb3+ was observed by illuminating the Tb3+ 4f→5d charge transfer band with ultraviolet (UV) 254 nm light, while the PSL was seen by stimulating the UV-illuminated glasses with 633 nm light. The decay curve of the LLP was fitted with a second-order kinetic for the initial period (030 min). An electron paramagnetic resonance (EPR) signal, which is attributed to an F+-like center associated with Ca2+ ions, was induced by illumination with UV light and its intensity decay was fitted with a first-order kinetic similarly to the later stage of the LLP. The appearance of the PSL by illumination is accompanied by a distinct intensity reduction of the EPR signal due to the F+-like center. The thermoluminescence spectra of the specimen illuminated with UV light at 77 K consist of two components peaking at ˜240 and ˜390 K. The low temperature component and the high temperature component were attributed to an F-like center and an F+-like center, respectively. These results lead to a conclusion that electrons of the F-like center and the F+-like center contribute predominantly to the emergence of the LLP and the PSL, respectively.

  19. Long-Lasting Phosphorescence Properties of Pyrochlore La2Ti2O7:Pr3+ Phosphor

    NASA Astrophysics Data System (ADS)

    Chu, Ming-Hui; Jiang, Da-Peng; Zhao, Cheng-Jiu; Li, Bin

    2010-04-01

    The La2Ti2O7:Pr3+, which emits red color luminescence upon UV light excitation, is prepared by the conventional high-temperature solid-state method and its luminescent properties are systematically investigated. X-ray diffraction, photoluminescence, afterglow emission spectra and long-lasting phosphorescence (LLP) decay curves are used to characterize this phosphor. After irradiation by a 290-nm UV light for 3 min, the Pr3+-doped La2Ti2O7 phosphor emits intense red emitting afterglow from the 1 D2 → 3H4 transitions, and its afterglow can be seen with the naked eye in the dark clearly for more than 1 h after removal of the excitation source. The afterglow decay curve of the Pr3+-doped La2Ti2O7 phosphor contains a fast decay component and another slow decay one. The possible mechanism of this red light emitting LLP phosphor is also discussed based on the experimental results.

  20. Correction of long-lasting negative effects of neonatal isolation in white rats using semax.

    PubMed

    Volodina, M A; Sebentsova, E A; Glazova, N Yu; Manchenko, D M; Inozemtseva, L S; Dolotov, O V; Andreeva, L A; Levitskaya, N G; Kamensky, A A; Myasoedov, N F

    2012-01-01

    Adverse experience during the early postnatal period induces negative alterations in physiological and neurobiological functions, resulting in long-term disorder in animal behavior. The aim of the present work was to study the long-lasting effects of chronic neonatal stress in white rats and to estimate the possibility of their correction using Semax, an analogue of ACTH fragment (4-10). Early neonatal isolation was used as a model of early-life stress. Rat pups were separated from their mothers and littermates for 5 h daily during postnatal days 1-14. The pups of the control group were left undisturbed with the dams. Half of the rats subjected to neonatal isolation received an intranasal injection of Semax at a dose of 50 µg/kg daily, from postnatal day 15 until day 28. The other animals received intranasal vehicle injections daily at the same time points. It was shown that neonatal isolation leads to a delay in physical development, metabolic disturbances, and a decrease in the corticosterone stress response in white rats. These changes were observed during the first two months of life. Semax administration weakened the influence of neonatal isolation on the animals, body weight , reduced metabolic dysfunction, and led to an increase in stress-induced corticosterone release to the control values. So the chronic intranasal administration of Semax after termination of the neonatal isolation procedure diminishes the negative effects of neonatal stress.

  1. Correction of Long-Lasting Negative Effects of Neonatal Isolation in White Rats Using Semax

    PubMed Central

    Volodina, M.A.; Sebentsova, E.A.; Glazova, N.Yu.; Manchenko, D.M.; Inozemtseva, L.S.; Dolotov, O.V.; Andreeva, L.A.; Levitskaya, N.G.; Kamensky, A.A.; Myasoedov, N.F.

    2012-01-01

    Adverse experience during the early postnatal period induces negative alterations in physiological and neurobiological functions, resulting in long-term disorder in animal behavior. The aim of the present work was to study the long-lasting effects of chronic neonatal stress in white rats and to estimate the possibility of their correction using Semax, an analogue of ACTH fragment (4–10). Early neonatal isolation was used as a model of early-life stress. Rat pups were separated from their mothers and littermates for 5 h daily during postnatal days 1–14. The pups of the control group were left undisturbed with the dams. Half of the rats subjected to neonatal isolation received an intranasal injection of Semax at a dose of 50 µg/kg daily, from postnatal day 15 until day 28. The other animals received intranasal vehicle injections daily at the same time points. It was shown that neonatal isolation leads to a delay in physical development, metabolic disturbances, and a decrease in the corticosterone stress response in white rats. These changes were observed during the first two months of life. Semax administration weakened the influence of neonatal isolation on the animals, body weight , reduced metabolic dysfunction, and led to an increase in stress-induced corticosterone release to the control values. So the chronic intranasal administration of Semax after termination of the neonatal isolation procedure diminishes the negative effects of neonatal stress. PMID:22708068

  2. Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory

    PubMed Central

    Koster, Raphael; Guitart-Masip, Marc; Dolan, Raymond J.; Düzel, Emrah

    2015-01-01

    The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for. PMID:26420783

  3. Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster.

    PubMed

    Trannoy, Séverine; Penn, Jill; Lucey, Kenia; Popovic, David; Kravitz, Edward A

    2016-04-26

    In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters.

  4. Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice.

    PubMed

    Gracia-Rubio, Irene; Moscoso-Castro, Maria; Pozo, Oscar J; Marcos, Josep; Nadal, Roser; Valverde, Olga

    2016-02-04

    Early life experiences play a key role in brain function and behaviour. Adverse events during childhood are therefore a risk factor for psychiatric disease during adulthood, such as mood disorders. Maternal separation is a validated mouse model for maternal neglect, producing negative early life experiences that result in subsequent emotional alteration. Mood disorders have been found to be associated with neurochemical changes and neurotransmitter deficits such as reduced availability of monoamines in discrete brain areas. Emotional alterations like depression result in reduced serotonin availability and enhanced kynurenine metabolism through the action of indoleamine 2, 3-dioxygenase in response to neuroinflammatory factors. This mechanism involves regulation of the neurotransmitter system by neuroinflammatory agents, linking mood regulation to neuroinmunological reactions. In this context, the aim of this study was to investigate the effects of maternal separation with early weaning on emotional behaviour in mice. We investigated neuroinflammatory responses and the state of the tryptophan-kynurenine metabolic pathway in discrete brain areas following maternal separation. We show that adverse events during early life increase risk of long-lasting emotional alterations during adolescence and adulthood. These emotional alterations are particularly severe in females. Behavioural impairments were associated with microglia activation and disturbed tryptophan-kynurenine metabolism in brain areas related to emotional control. This finding supports the preeminent role of neuroinflammation in emotional disorders.

  5. Lynx reproduction--long-lasting life cycle of corpora lutea in a feline species.

    PubMed

    Jewgenow, Katarina; Painer, Johanna; Amelkina, Olga; Dehnhard, Martin; Goeritz, Frank

    2014-04-01

    A review of lynxes' reproductive biology and comparison between the reproductive cycles of the domestic cat and lynxes is presented. Three of the four lynx species (the bobcat excluded) express quite similar reproductive pattern (age at sexual maturity, estrus and pregnancy length, litter size). Similarly to the domestic cat, the bobcat is polyestric and can have more than one litter per year. Domestic cats and many other felid species are known to express anovulatory, pregnant and pseudo-pregnant reproductive cycles in dependence on ovulation induction and fertilization. The formation of corpora lutea (CLs) occurs after ovulation. In pregnant animals, luteal function ends with parturition, whereas during pseudo-pregnancy a shorter life span and lower hormone secretion are observed. The life cycle of corpora lutea in Eurasian lynxes is different from the pattern described in domestic cats. Lynx CLs produce progestagens in distinctive amounts permanently for at least two years, regardless of their origin (pregnancy or pseudo-pregnancy). It is suggested that long-lasting CLs induce a negative feedback to inactivate folliculogenesis, turning a normally polyestric cycle observed in most felids into a monoestric cycle in lynxes.

  6. Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation

    PubMed Central

    Etiévant, Adeline; Manta, Stella; Latapy, Camille; Magno, Luiz Alexandre V.; Fecteau, Shirley; Beaulieu, Jean-Martin

    2015-01-01

    The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings. PMID:26585834

  7. Early GRB Afterglows from Reverse Shocks in Ultra-relativistic, Long-lasting Winds

    NASA Astrophysics Data System (ADS)

    Lyutikov, Maxim; Camilo Jaramillo, Juan

    2017-02-01

    We develop a model of early Gamma-Ray Burst (GRB) afterglows with dominant X-ray contribution from the reverse shock (RS) propagating in highly relativistic (Lorentz factor γw ∼ 106) magnetized wind of a long-lasting central engine. The model reproduces, in a fairly natural way, the overall trends and yet allows for variations in the temporal and spectral evolution of early optical and X-ray afterglows. The high energy and the optical synchrotron emission from the RS particles occurs in the fast cooling regime; the resulting synchrotron power Ls is a large fraction of the wind luminosity, {L}s≈ {L}w/\\sqrt{1+{σ }w} (Lw and σw are wind power and magnetization). Thus, plateaus—parts of afterglow light curves that show slowly decreasing spectral power—are a natural consequence of the RS emission. Contribution from the forward shock (FS) is negligible in the X-rays, but in the optical both FS and RS contribute similarly: FS optical emission is in the slow cooling regime, producing smooth components, while RS optical emission is in the fast cooling regime, and thus can both produce optical plateaus and account for fast optical variability correlated with the X-rays, e.g., due to changes in the wind properties. We discuss how the RS emission in the X-rays and combined FS and RS emission in the optical can explain many puzzling properties of early GRB afterglows.

  8. Long-lasting effects of briefly flashed words and pseudowords in ultrarapid serial visual presentation.

    PubMed

    Albrecht, Thorsten; Vorberg, Dirk

    2010-09-01

    Our ability to identify even complex scenes in rapid serial visual presentation (RSVP) is astounding, but memory for such items seems lacking. Rather than pictures, we used streams of more than 200 verbal stimuli, rushing by on the screen at a rate of more than 12 items per second while participants had to detect infrequent names (Experiments 1 and 2) or words written in capitals (Experiment 3). By direct and indirect tests, we investigated what is remembered of these masses of task-irrelevant distractor words and pseudowords embedded in an RSVP stream. Lexical decision, the indirect test applied either immediately after each stimulus train or with a delay, revealed strong long-term priming effects. Relative to stimuli not shown before, lexical decisions were faster and more accurate to words but slower to pseudowords. The size of these effects mirrored how often words and pseudowords had occurred in a stream, suggesting that memory traces are strengthened with successive presentations and survive for several minutes at least. Moreover, in a direct test (old-new categorization), words as well as pseudowords benefited from prior occurrence in an RSVP stream if they had occurred more than once. These findings parallel recent physiological and behavioral evidence for memory consolidation of distractor pictures in RSVP and highlight that, despite huge numbers of interfering stimuli, distractor words and pseudowords exhibit long-lasting memory effects. Consolidation seems to progress at higher cognitive levels at the same time that subsequent stimuli are perceptually processed.

  9. Doping and musculoskeletal system: short-term and long-lasting effects of doping agents.

    PubMed

    Nikolopoulos, Dimitrios D; Spiliopoulou, Chara; Theocharis, Stamatios E

    2011-10-01

    Doping is a problem that has plagued the world of competition and sports for ages. Even before the dawn of Olympic history in ancient Greece, competitors have looked for artificial means to improve athletic performance. Since ancient times, athletes have attempted to gain an unfair competitive advantage through the use of doping substances. A Prohibited List of doping substances and methods banned in sports is published yearly by the World Anti-Doping Agency. Among the substances included are steroidal and peptide hormones and their modulators, stimulants, glucocorticosteroids, β₂-agonists, diuretics and masking agents, narcotics, and cannabinoids. Blood doping, tampering, infusions, and gene doping are examples of prohibited methods indicated on the List. Apart from the unethical aspect of doping, as it abrogates fair-play's principle, it is extremely important to consider the hazards it presents to the health and well-being of athletes. The referred negative effects for the athlete's health have to do, on the one hand, by the high doses of the performance-enhancing agents and on the other hand, by the relentless, superhuman strict training that the elite or amateur athletes put their muscles, bones, and joints. The purpose of this article is to highlight the early and the long-lasting consequences of the doping abuse on bone and muscle metabolism.

  10. Long lasting clinical response to chemotherapy for advanced uterine leiomyosarcoma: a case report

    PubMed Central

    2013-01-01

    Introduction Uterine leiomyosarcoma is one of the most frequent uterine sarcomas. In the metastatic setting it is sensitive to doxorubicin, ifosfamide, gemcitabine, docetaxel and a few other drugs, but time to progression is generally short. For this reason prognosis is often poor and there are few reports in the literature of long responders. Case presentation We report a case of a 40-year-old Caucasian woman with metastatic uterine leiomyosarcoma who began treatment six years before the presentation of this case report and for the following six years underwent ten lines of chemotherapy, achieving excellent results and a good quality of life. Among the treatments administered we observed a long response to temolozomide, an unconventional drug for this kind of disease. Conclusion Although there are few chemotherapeutic options for the management of metastatic uterine leiomyosarcoma, a small number of patients have an unexpected long lasting response to treatment. For this reason further research is needed to identify new therapeutic agents and the predictive factors for the achievement of response. PMID:23347560

  11. A non-adjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria1

    PubMed Central

    Abanega Kaba, Stephen; Brando, Clara; Guo, Qin; Mittelholzer, Christian; Raman, Senthilkumar; Tropel, David; Aebi, Ueli; Burkhard, Peter; Ervin Lanar, David

    2015-01-01

    We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)2D of the malaria parasite Plasmodium berghei circumsporozoite protein (CSP). Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long lived protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2b, H-2d and H-2k alleles. Immunized mice produced a CD4+ T cell dependent, high titer, long lasting, high avidity antibody response against the B cell epitope. Mice were protected against an initial challenge of parasites given up to 6 months after the last immunization or for up to 15 months against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal specific B cells. PMID:19915055

  12. Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects

    PubMed Central

    Liu, Chen; Fu, Xuekun; Pan, Haobo; Wan, Peng; Wang, Lei; Tan, Lili; Wang, Kehong; Zhao, Ying; Yang, Ke; Chu, Paul K.

    2016-01-01

    A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications. PMID:27271057

  13. The role of excess Zn 2+ ions in improvement of red long lasting phosphorescence (LLP) performance of β-Zn 3(PO 4) 2:Mn phosphor

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Wang, Shubin; Su, Qiang

    2004-03-01

    Influences of excess Zn 2+ ions and intrinsic defects on red ( λ=616 nm) phosphorescence of β-Zn 3(PO 4) 2:Mn 2+ are systematically investigated. It is clearly observed that red long lasting phosphorescence (LLP) properties of Mn 2+, such as brightness and duration, are largely improved when excess Zn 2+ ions are co-doped into the matrix. Photoluminescence (PL), LLP and thermoluminescence (TL) spectra indicate that Mn 2+ ion acts as luminescent center whereas oxygen vacancy associated to Zn 2+ ion plays a significant role in electron trap. The TL peak for oxygen vacancy is centered at 343 K, the depth of which is suitable for improvement in LLP performance of Mn 2+ at room temperature. The possible mechanism for this phenomenon of red LLP of Mn 2+ in β-Zn 3(PO 4) 2:Mn 2+ with excess of Zn 2+ is explained by means of a competitively trapping model.

  14. Effects of submaximal and maximal long-lasting contractions on the compliance of vastus lateralis tendon and aponeurosis in vivo.

    PubMed

    Ullrich, Anne Charlotte; Mademli, Lida; Arampatzis, Adamantios

    2009-06-01

    The present study investigated the effects of submaximal sustained and maximal repetitive contractions on the compliance of human vastus lateralis (VL) tendon and aponeurosis in vivo using two different fatiguing protocols. Twelve male subjects performed three maximum voluntary isometric contractions (MVC) of the knee extensors before and after two fatiguing protocols on a dynamometer. The first fatiguing protocol consisted of a long-lasting sustained isometric knee extension contraction at 25% MVC until failure (inability to hold the defined load). The second fatiguing protocol included long-lasting isokinetic (90 degrees/s) knee extension contractions, where maximum moment was exerted and failure was proclaimed when this value fell below 70% of unfatigued maximum isokinetic moment. Ultrasonography was used to determine the elongation and strain of the VL tendon and aponeurosis. Muscle fatigue was indicated by a significant decrease in maximum resultant knee extension moment (p<0.05) observed during the MVCs after both long-lasting contractions. No significant (p>0.05) differences in elongation and strain of the VL tendon and aponeurosis were found, when compared every 300 N (tendon force) before and after the fatiguing protocols. The present data indicate, that the VL tendon and aponeurosis in vivo do not suffer from changes in the compliance neither after long-lasting static mechanical loading (strain approximately 3.2%) nor after long-lasting cyclic mechanical loading (strain 6.2-5.5%).

  15. Repeated maximal eccentric actions causes long-lasting disturbances in movement control.

    PubMed

    Bottas, Reijo; Linnamo, Vesa; Nicol, Caroline; Komi, Paavo V

    2005-05-01

    This study examined acute and long-lasting effects of fatigue and muscle damage on fast and accurate elbow flexion and extension target movements (TM) with eight male students. An isokinetic machine was used to perform 100 maximal eccentric and concentric elbow flexions at 4-week intervals. Movement range was 40-170 degrees in eccentric exercise (ECCE) and 170-40 degrees in concentric exercise (CONE), with an angular velocity of 2 rad s(-1). TM was performed in sitting position with the right forearm fixed to lever arm above protractor. Subjects performed TM in horizontal plane (amplitude 60 degrees ) by visual feedback of movement from a television monitor. Surface EMG was recorded from the biceps brachii and triceps brachii muscles. TM measurements and serum creatine kinase (CK) determinations were conducted before, after, 0.5 h, 2 days, and 7 days after both exercises. Blood lactate was taken before, after, and 0.5 h after the exercises. Both ECCE and CONE led to a large decline in maximal voluntary contractions, but the recovery was slower after ECCE when it remained incomplete even until day 7 post-exercise. Lactate increased (P < 0.001) similarly after both exercises. Delayed-onset muscle soreness peaked on day 2 and CK peaked on day 7 after ECCE. Exhaustive eccentric exercise of agonistic muscles impaired the flexion TM performance, and had a long-duration modulation effect on the triphasic EMG activity pattern of flexion and extension TM. In the acute phase, the observed changes in performance and in the EMG patterns are suggested to be related to metabolic changes via III and IV muscle afferents. The delayed recovery, on the other hand, may be related to problems in the proprioceptive feedback caused by muscle damage.

  16. NONLINEAR FORCE-FREE MODELING OF A LONG-LASTING CORONAL SIGMOID

    SciTech Connect

    Savcheva, Antonia; Van Ballegooijen, Adriaan

    2009-10-01

    A study of the magnetic configuration and evolution of a long-lasting quiescent coronal sigmoid is presented. The sigmoid was observed by Hinode/XRT and Transition Region and Coronal Explorer (TRACE) between 2007 February 6 and 12 when it finally erupted. We construct nonlinear force-free field models for several observations during this period, using the flux-rope insertion method. The high spatial and temporal resolution of the X-Ray Telescope (XRT) allows us to finely select best-fit models that match the observations. The modeling shows that a highly sheared field, consisting of a weakly twisted flux rope embedded in a potential field, very well describes the structure of the X-ray sigmoid. The flux rope reaches a stable equilibrium, but its axial flux is close to the stability limit of about 5 x 10{sup 20} Mx. The relative magnetic helicity increases with time from February 8 until just prior to the eruption on February 12. We study the spatial distribution of the torsion parameter alpha in the vicinity of the flux rope, and find that it has a hollow-core distribution, i.e., electric currents are concentrated in a current layer at the boundary between the flux rope and its surroundings. The current layer is located near the bald patch separatrix surface (BPSS) of the magnetic configuration, and the X-ray emission appears to come from this current layer/BPSS, consistent with the Titov and Demoulin model. We find that the twist angle PHI of the magnetic field increases with time to about 2pi just prior to the eruption, but never reaches the value necessary for the kink instability.

  17. Long-Lasting Effects of Maternal Condition in Free-Ranging Cervids

    PubMed Central

    Freeman, Eric D.; Larsen, Randy T.; Clegg, Ken; McMillan, Brock R.

    2013-01-01

    Causes of phenotypic variation are fundamental to evolutionary ecology because they influence the traits acted upon by natural selection. One such cause of phenotypic variation is a maternal effect, which is the influence of the environment experienced by a female (and her corresponding phenotype) on the phenotype of her offspring (independent of the offspring’s genotype). While maternal effects are well documented, the longevity and fitness impact of these effects remains unclear because it is difficult to follow free-living individuals through their reproductive lifetimes. For long-lived species, it has been suggested that maternal effects are masked by environmental variables acting on offspring in years following the period of dependence. Our objective was to use indirect measures of maternal condition to determine if maternal effects have long-lasting influences on male offspring in two species of cervid. Because antlers are sexually selected, we used measures of antler size at time of death, 1.5–21.5 years after gestation to investigate maternal effects. We quantified antler size of 11,000 male elk and mule deer born throughout the intermountain western US (6 states) over nearly 30 years. Maternal condition during development was estimated indirectly using a suite of abiotic variables known to influence condition of cervids (i.e., winter severity, spring and summer temperature, and spring and summer precipitation). Antler size of male cervids was significantly associated with our indirect measure of maternal condition during gestation and lactation. Assuming the correctness of our indirect measure, our findings demonstrate that antler size is a sexually selected trait that is influenced–into adulthood–by maternal condition. This link emphasizes the importance of considering inherited environmental effects when interpreting population dynamics or examining reproductive success of long-lived organisms. PMID:23472189

  18. Long-lasting effects of maternal condition in free-ranging cervids.

    PubMed

    Freeman, Eric D; Larsen, Randy T; Clegg, Ken; McMillan, Brock R

    2013-01-01

    Causes of phenotypic variation are fundamental to evolutionary ecology because they influence the traits acted upon by natural selection. One such cause of phenotypic variation is a maternal effect, which is the influence of the environment experienced by a female (and her corresponding phenotype) on the phenotype of her offspring (independent of the offspring's genotype). While maternal effects are well documented, the longevity and fitness impact of these effects remains unclear because it is difficult to follow free-living individuals through their reproductive lifetimes. For long-lived species, it has been suggested that maternal effects are masked by environmental variables acting on offspring in years following the period of dependence. Our objective was to use indirect measures of maternal condition to determine if maternal effects have long-lasting influences on male offspring in two species of cervid. Because antlers are sexually selected, we used measures of antler size at time of death, 1.5-21.5 years after gestation to investigate maternal effects. We quantified antler size of 11,000 male elk and mule deer born throughout the intermountain western US (6 states) over nearly 30 years. Maternal condition during development was estimated indirectly using a suite of abiotic variables known to influence condition of cervids (i.e., winter severity, spring and summer temperature, and spring and summer precipitation). Antler size of male cervids was significantly associated with our indirect measure of maternal condition during gestation and lactation. Assuming the correctness of our indirect measure, our findings demonstrate that antler size is a sexually selected trait that is influenced-into adulthood-by maternal condition. This link emphasizes the importance of considering inherited environmental effects when interpreting population dynamics or examining reproductive success of long-lived organisms.

  19. Evaluation of Interceptor long-lasting insecticidal nets in eight communities in Liberia

    PubMed Central

    2010-01-01

    Background By 2008, the WHO Pesticide Evaluation Scheme (WHOPES) recommended five long-lasting insecticidal nets (LLINs) for the prevention of malaria: Olyset®, PermaNet 2.0®, Netprotect®, Duranet® and Interceptor®. Field information is available for both Olyset® and PermaNet®, with limited data on the newer LLINs. To address this gap, a field evaluation was carried out to determine the acceptability and durability of Interceptor® LLINs. Methods A one-year prospective field study was conducted in eight rural returnee villages in Liberia. Households were randomized to receive Interceptor® LLINs or conventionally treated nets (CTNs). Primary outcomes were levels of residual alpha-cypermethrin measured by HPLC and participant utilization/acceptability of the ITNs. Results A total of 398 nets were analysed for residual alpha-cypermethrin. The median baseline concentrations of insecticide were 175.5 mg/m2 for the Interceptor® LLIN and 21.8 mg/m2 for the CTN. Chemical residue loss after a one year follow-up period was 22% and 93% respectively. Retention and utilization of nets remained high (94%) after one year, irrespective of type, while parasitaemia prevalence decreased from 29.7% at baseline to 13.6% during the follow up survey (p = < 0.001). Interview and survey data show perceived effectiveness of ITNs was just as important as other physical attributes in influencing net utilization. Conclusion Interceptor® LLINs are effective and desirable in rural communities in Liberia. Consideration for end user preferences should be incorporated into product development of all LLINs in the future, in order to achieve optimum retention and utilization. PMID:20334677

  20. Long-lasting memory T cell responses following self-limited acute hepatitis B.

    PubMed Central

    Penna, A; Artini, M; Cavalli, A; Levrero, M; Bertoletti, A; Pilli, M; Chisari, F V; Rehermann, B; Del Prete, G; Fiaccadori, F; Ferrari, C

    1996-01-01

    The molecular and cellular basis of long-term T cell memory against viral antigens is still largely undefined. To characterize anti-viral protection by memory T cells against non-cytopathic viruses able to cause acute self-limited and chronic infections, such as the hepatitis B virus (HBV), we studied HLA class II restricted responses against HBV structural antigens in 17 patients with acute hepatitis B, during the acute stage of infection and 2.2 to 13 yr after clinical resolution of disease. Results indicate that: (a) significant T cell proliferative responses to HBV nucleocapsid antigens were detectable in all patients during the acute phase of infection and in 14/17 also 2-13 yr after clinical resolution of disease; b) long-lasting T cell responses were sustained by CD45RO+T cells, predominantly expressing the phenotype of recently activated cells; c) limiting dilution analysis showed that in some patients the frequency of HBV-specific T cells was comparable to that observed in the acute stage of infection and, usually, higher than in patients with chronic HBV infection; d) the same amino acid sequences were recognized by T cells in the acute and recovery phases of infection; and e) HBV-DNA was detectable by nested-PCR in approximately half of the subjects. to conclusion, our results show that vigorous anti-viral T cell responses are detectable in vitro several years after clinical recovery from acute hepatitis B. Detection of minute amounts of virus in some recovered subjects suggests that long-term maintenance of an active anti-viral T cell response could be important not only for protection against reinfection but also for keeping the persisting virus under tight control. PMID:8787682

  1. Anabolic steroids have long-lasting effects on male social behaviors.

    PubMed

    Salas-Ramirez, Kaliris Y; Montalto, Pamela R; Sisk, Cheryl L

    2010-04-02

    Anabolic androgenic steroids (AAS) use by adolescents is steadily increasing. Adolescence involves remodeling of steroid-sensitive neural circuits that mediate social behaviors, and previous studies using animal models document effects of AAS on male social behaviors. The present experiments tested whether AAS have persistent and more pronounced behavioral consequences when drug exposure occurs during adolescence as compared to exposure in adulthood. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or adulthood (63-77 days of age). As adults, subjects were tested two or four weeks after the last injection for either sexual behavior with a receptive female or male-male agonistic behavior in a resident-intruder test. Compared with vehicle-treated males, AAS-treated males, regardless of age of treatment, displayed fewer long intromissions and a significant increase in latency to the first long intromission, indicative of reduced potential to reach sexual satiety. Increased aggression was observed in males exposed to AAS compared with males treated with vehicle, independently of age of AAS treatment. However, unlike hamsters exposed to AAS in adulthood, hamsters exposed to AAS during adolescence did not display any submissive or risk-assessment behaviors up to 4 weeks after discontinuation of AAS treatment. Thus, AAS have long-lasting effects on male sexual and agonistic behaviors, with AAS exposure during adolescence resulting in a more pronounced reduction in submissive behavior compared to AAS exposure in adulthood.

  2. Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.

    PubMed

    Fowler, Joanna S; Volkow, Nora D; Logan, Jean; Alexoff, David; Telang, Frank; Wang, Gene-Jack; Wong, Christopher; Ma, Yeming; Kriplani, Aarti; Pradhan, Kith; Schlyer, David; Jayne, Millard; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog, Karen

    2008-12-01

    Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.

  3. Long-Lasting Consequences of Neonatal Maternal Separation on Social Behaviors in Ovariectomized Female Mice

    PubMed Central

    Tsuda, Mumeko C.; Ogawa, Sonoko

    2012-01-01

    Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to

  4. Role of manganese in red long-lasting phosphorescence of manganese-doped diopside for in vivo imaging

    SciTech Connect

    Lecointre, A.; Bessière, A.; Priolkar, K.R.; Gourier, D.; Wallez, G.; Viana, B.

    2013-05-15

    Highlights: ► Long-lasting phosphorescence of CaMgSi{sub 2}O{sub 6}:Mn is studied for bioimaging application. ► CaMgSi{sub 2}O{sub 6}:Mn yields orange and red luminescence of Mn{sup II}{sub Ca} and Mn{sup II}{sub Mg}, respectively. ► Red Mn{sup II}{sub Mg} emission dominates long-lasting phosphorescence spectra. ► Mn mainly substitutes Mg. ► Mn{sup II}{sub Mg} plays the role of hole trap in the persistent luminescence mechanism. - Abstract: Materials with red long-lasting phosphorescence, such as Mn{sup II}-doped diopsides, can be used for small animal in vivo imaging. CaMgSi{sub 2}O{sub 6}:Mn powders with various amounts of Mn were prepared by sol–gel to investigate their long-lasting phosphorescence mechanism. X-ray diffraction, X-ray absorption fine and near-edge structure and electron paramagnetic resonance showed that manganese is quantitatively introduced in the structure as Mn{sup II}. Most of the Mn doping ions substitute Mg and possess a highly elongated octahedral environment. While photoluminescence and X-ray excited optical luminescence spectra show both orange (585 nm) and red (685 nm) {sup 4}T{sub 1} ({sup 4}G) → {sup 6}A{sub 1} ({sup 6}S) emission of Mn{sup II}{sub Ca} and Mn{sup II}{sub Mg}, respectively, Mn{sup II}{sub Mg} red emission dominates long-lasting phosphorescence and thermally stimulated luminescence spectra. These results point to Mn{sup II}{sub Mg} as the preferential hole trap and recombination center in the long-lasting phosphorescence mechanism. An intense persistent red emission suitable for in vivo imaging probes is obtained for the highest nominal Mn content (7.5%)

  5. Africa's largest long-lasting insecticide-treated net producer: lessons from A to Z Textiles

    PubMed Central

    2010-01-01

    Background Field trials have demonstrated the efficacy of insecticide-treated nets, and the WHO has recently endorsed a shift toward Long-Lasting Insecticide Treated nets (LLINs) due to factors such as reduced distribution costs. However, the need for LLINs poses several challenges. Is it possible to manufacture LLINs in large quantities in the African continent, where malaria is most endemic? When production is located in low-income countries, what role is played by local funding and employment, scaling up manufacturing, and partnerships? What factors influence availability and pricing? Discussion A case study of A to Z Textiles was undertaken to answer the question of how large-scale production of LLINs can occur in a low income setting. One of the largest sources of bed nets for Africa, A to Z Textiles is Africa-based, and its Tanzanian operations have a production capacity of 30 million LLINs per year, along with full WHO recommendation for its nets. Our analysis is based on semi-structured interviews with key informants familiar with A to Z, site visits in Tanzania, and literature reviews. This paper discusses the history and current status of A to Z Textiles, identifies the factors that led to its success, and suggests policy considerations that could support similar initiatives in the future. Local funding, scaling up manufacturing, technology transfer, and partnerships all played important roles in A to Z’s ascent, as did perceived benefits of local employment and capacity-building. Regulatory issues and procurement rules acted as barriers. A to Z cost-effectively manufactures high-quality LLINs where malaria is most endemic. Summary With a production capacity of 30 million LLINs per year, and full WHOPES (WHO Pesticide Evaluation Scheme) certification, A to Z Textiles demonstrates how key health goods can be successfully produced in the low-income countries that use them. Its example may be instructive and of high interest to readers in the malaria

  6. Long-Lasting Visuo-Vestibular Mismatch in Freely-Behaving Mice Reduces the Vestibulo-Ocular Reflex and Leads to Neural Changes in the Direct Vestibular Pathway

    PubMed Central

    Carcaud, Julie; França de Barros, Filipa; Eugène, Daniel; Reveret, Lionel; Moore, Lee E.; Vidal, Pierre-Paul

    2017-01-01

    Abstract Calibration of the vestibulo-ocular reflex (VOR) depends on the presence of visual feedback. However, the cellular mechanisms associated with VOR modifications at the level of the brainstem remain largely unknown. A new protocol was designed to expose freely behaving mice to a visuo-vestibular mismatch during a 2-week period. This protocol induced a 50% reduction of the VOR. In vivo pharmacological experiments demonstrated that the VOR reduction depends on changes located outside the flocculus/paraflocculus complex. The cellular mechanisms associated with the VOR reduction were then studied in vitro on brainstem slices through a combination of vestibular afferent stimulation and patch-clamp recordings of central vestibular neurons. The evoked synaptic activity demonstrated that the efficacy of the synapses between vestibular afferents and central vestibular neurons was decreased. In addition, a long-term depression protocol failed to further decrease the synapse efficacy, suggesting that the VOR reduction might have occurred through depression-like mechanisms. Analysis of the intrinsic membrane properties of central vestibular neurons revealed that the synaptic changes were supplemented by a decrease in the spontaneous discharge and excitability of a subpopulation of neurons. Our results provide evidence that a long-lasting visuo-vestibular mismatch leads to changes in synaptic transmission and intrinsic properties of central vestibular neurons in the direct VOR pathway. Overall, these results open new avenues for future studies on visual and vestibular interactions conducted in vivo and in vitro. PMID:28303261

  7. Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus

    PubMed Central

    Clarkson, Cheryl; Antunes, Flora M.

    2016-01-01

    Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. SIGNIFICANCE STATEMENT Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of

  8. The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus

    PubMed Central

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Weiss, Craig; Gross, Amanda; Boikess, Steven R.; Kroes, Roger A.; Khan, M. Amin; Burch, Ronald M.; Rex, Christopher S.; Disterhoft, John F.; Stanton, Patric K.; Moskal, Joseph R.

    2016-01-01

    Rapastinel (GLYX-13) is an N-methyl-D-aspartate receptor (NMDAR) modulator that has characteristics of a glycine site partial agonist. Rapastinel is a robust cognitive enhancer and facilitates hippocampal long-term potentiation (LTP) of synaptic transmission in slices. In human clinical trials, rapastinel has been shown to produce marked antidepressant properties that last for at least one week following a single dose. The long-lasting antidepressant effect of a single dose of rapastinel (3 mg/kg IV) was assessed in rats using the Porsolt, open field and ultrasonic vocalization assays. Cognitive enhancement was examined using the Morris water maze, positive emotional learning, and contextual fear extinction tests. LTP was assessed in hippocampal slices. Dendritic spine morphology was measured in the dentate gyrus and the medial prefrontal cortex. Significant antidepressant-like or cognitive enhancing effects were observed that lasted for at least one week in each model. Rapastinel facilitated LTP 1 day – 2 weeks but not 4 weeks post-dosing. Biweekly dosing with rapastinel sustained this effect for at least 8 weeks. A single dose of rapastinel increased the proportion of whole-cell NMDAR current contributed by NR2B-containing NMDARs in the hippocampus 1 week post-dosing, that returned to baseline by 4 weeks postdosing. The NMDAR antagonist CPP blocked the antidepressant-like effect of rapastinel 1 week post dosing. A single injection of rapastinel also increased mature spine density in both brain regions 24 hrs post-dosing. These data demonstrate that rapastinel produces its long-lasting antidepressant effects via triggering NMDAR-dependent processes that lead to increased sensitivity to LTP that persist for up to two weeks. The data also suggest that these processes led to the alterations in dendritic spine morphologies associated with the maintenance of long-term changes in synaptic plasticity associated with learning and memory. PMID:26343295

  9. Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor–dependent synaptic and intrinsic plasticity

    PubMed Central

    Tidball, Patrick; Burn, Hannah V.; Teh, Kai Lun; Volianskis, Arturas; Collingridge, Graham L.; Fitzjohn, Stephen M.

    2017-01-01

    Background The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role. Methods In this study, we have used extracellular field potential recordings to compare basal input/output function and group I metabotropic glutamate receptor-dependent forms of synaptic and intrinsic plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the adult rat hippocampus. Results Using two extracellular electrodes to simultaneously record field EPSPs and population spikes, we show that dorsal and ventral hippocampal slices differ in their basal levels of excitatory synaptic transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore, we show that slices taken from the ventral hippocampus have a greater ability than their dorsal counterparts to exhibit long-term depression of synaptic transmission and EPSP-to-Spike potentiation induced by transient application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine. Conclusions Together, our results provide further evidence that the information processing properties of local hippocampal circuits differ in the dorsal and ventral hippocampal sectors, and that these differences may in turn contribute to the functional differentiation that exists along the hippocampal longitudinal axis.

  10. Long-lasting solid lubrication by CNT-coated patterned surfaces

    PubMed Central

    Reinert, L.; Lasserre, F.; Gachot, C.; Grützmacher, P.; MacLucas, T.; Souza, N.; Mücklich, F.; Suarez, S.

    2017-01-01

    The use of lubricants (solid or liquid) is a well-known and suitable approach to reduce friction and wear of moving machine components. Another possibility to influence the tribological behaviour is the formation of well-defined surface topographies such as dimples, bumps or lattice-like pattern geometries by laser surface texturing. However, both methods are limited in their effect: surface textures may be gradually destroyed by plastic deformation and lubricants may be removed from the contact area, therefore no longer properly protecting the contacting surfaces. The present study focuses on the combination of both methods as an integral solution, overcoming individual limitations of each method. Multiwall carbon nanotubes (MWCNT), a known solid lubricant, are deposited onto laser surface textured samples by electrophoretic deposition. The frictional behaviour is recorded by a tribometer and resulting wear tracks are analysed by scanning electron microscopy and Raman spectroscopy in order to reveal the acting tribological mechanisms. The combined approach shows an extended, minimum fivefold longevity of the lubrication and a significantly reduced degradation of the laser textures. Raman spectroscopy proves decelerated MWCNT degradation and oxide formation in the contact. Finally, a lubricant entrapping model based on surface texturing is proposed and demonstrated. PMID:28211468

  11. Long-lasting solid lubrication by CNT-coated patterned surfaces

    NASA Astrophysics Data System (ADS)

    Reinert, L.; Lasserre, F.; Gachot, C.; Grützmacher, P.; MacLucas, T.; Souza, N.; Mücklich, F.; Suarez, S.

    2017-02-01

    The use of lubricants (solid or liquid) is a well-known and suitable approach to reduce friction and wear of moving machine components. Another possibility to influence the tribological behaviour is the formation of well-defined surface topographies such as dimples, bumps or lattice-like pattern geometries by laser surface texturing. However, both methods are limited in their effect: surface textures may be gradually destroyed by plastic deformation and lubricants may be removed from the contact area, therefore no longer properly protecting the contacting surfaces. The present study focuses on the combination of both methods as an integral solution, overcoming individual limitations of each method. Multiwall carbon nanotubes (MWCNT), a known solid lubricant, are deposited onto laser surface textured samples by electrophoretic deposition. The frictional behaviour is recorded by a tribometer and resulting wear tracks are analysed by scanning electron microscopy and Raman spectroscopy in order to reveal the acting tribological mechanisms. The combined approach shows an extended, minimum fivefold longevity of the lubrication and a significantly reduced degradation of the laser textures. Raman spectroscopy proves decelerated MWCNT degradation and oxide formation in the contact. Finally, a lubricant entrapping model based on surface texturing is proposed and demonstrated.

  12. Long lasting paleolandscapes stability of the French Massif Central during the Mesozoic

    NASA Astrophysics Data System (ADS)

    Ricordel-Prognon, C.; Thiry, M.; Theveniaut, H.; Lagroix, F.

    2009-04-01

    , and more importantly no Jurassic cover was preserved (if such a cover was even deposited?) on the massif. Consequently, the Massif Central probably never did support an important (more than 500 m) sedimentary cover during the Mesozoic. These paleosurface ages provide important constraints to crustal dynamics modeling. Identification and dating of the successive continental unconformities are evidence for long lasting continental evolution and landscape stability of large areas of the Massif Central during the Mesozoic. The alternative hypothesis was that the Massif Central was subsidizing during Mesozoic time and covered with a 2,000 m thick sedimentary series, which was fairly quickly eroded during early Tertiary (Barbarand et al., 2001). In the future, making substantial progress in paleoweathering profiles dating, especially in the scope of improving time resolution, will allow attempting efficient correlation between the continental records and the diverse processes involved in their development (eustatism, climate, global and regional tectonics). Moreover, progress in dating paleoweathering features and continental azoic deposits, will allow to develop a "continental stratigraphy" of climatic and geomorphological events and to establish a mass balances between weathering/erosion weathering/erosion on land and deposition in basins. References Barbarand J., Lucazeau F., Pagel M., Séranne M., 2001, Burial and exhumation history of the south-eastern Massif Central (France) constrained by apatite fission track thermochronology. Tectonophysics, 335, 3-4, p. 275-290. Besse, J., Courtillot, V., 2003. Apparent true polar wander and the geometry of the geomagnetic field over the last 200 Myr: Correction: Journal of Geophysical Research, 108, p. 2300. Cogné, J.P., 2003. PaleoMac: a MacintoshTM application for treating paleomagnetic data and making plate reconstructions. Geochemistry Geophysics Geosystems, 4 (1), 1007. Edel J.B., Duringer P., 1997, The apparent polar

  13. Characterization of the complex morphinan derivative BU72 as a high efficacy, long-lasting mu-opioid receptor agonist.

    PubMed

    Neilan, Claire L; Husbands, Stephen M; Breeden, Simon; Ko, M C Holden; Aceto, Mario D; Lewis, John W; Woods, James H; Traynor, John R

    2004-09-19

    The development of buprenorphine as a treatment for opiate abuse and dependence has drawn attention to opioid ligands that have agonist actions followed by long-lasting antagonist actions. In a search for alternatives to buprenorphine, we discovered a bridged pyrrolidinomorphinan (BU72). In vitro, BU72 displayed high affinity and efficacy for mu-opioid receptors, but was also a partial delta-opioid receptor agonist and a full kappa-opioid receptor agonist. BU72 was a highly potent and long-lasting antinociceptive agent against both thermal and chemical nociception in the mouse and against thermal nociception in the monkey. These effects were prevented by mu-, but not kappa- or delta-, opioid receptor antagonists. Once the agonist effects of BU72 had subsided, the compound acted to attenuate the antinociceptive action of morphine. BU72 is too efficacious for human use but manipulation to reduce efficacy could provide a lead to the development of a treatment for opioid dependence.

  14. Luminescent Properties of ZnxCa1-xTiO3:yPr3+ Long-Lasting Phosphors

    NASA Astrophysics Data System (ADS)

    Meng, Yanzhi; Wang, Xiaomin; Shen, Yi; Wei, Xiaoli; Han, Liying; Li, Fengfeng; Hou, Luyao

    2016-10-01

    The red long-lasting phosphors (LLPs) ZnxCa1-xTiO3:yPr3+ (ZCTP) were successfully prepared via the sol-gel method. The effects of Zn2+ content and Pr3+ molar concentration on the luminescent properties of ZCTP LLPs were characterized by X-ray diffraction, excitation and emission spectra, long-lasting decay curves and thermoluminescence (TL) curves. In this study, the results indicated that luminescent properties of Zn0.2Ca0.8TiO3:0.2 %Pr3+ phosphor was the best. In addition, when Pr3+ molar concentration reached 0.8 mol %, concentration quenching effect was obvious.

  15. Long-lasting luminescence in ZnGa2O4: Cr3+ through persistent energy transfer

    NASA Astrophysics Data System (ADS)

    Li, Lei; Wang, Yinhai; Huang, Haiju; Li, Hong; Zhao, Hui

    2016-01-01

    Cr3+-doped zinc gallate (ZnGa2O4) near-infrared (NIR) phosphors were synthesized via a high temperature solid state method. The luminescence properties of the phosphors were studied systematically. A significant spectra overlap between the emission of ZnGa2O4 and the absorption of Cr3+ was observed and 300 nm excitation exhibited the most excellent long-lasting luminescence properties among the three main excitation bands. Luminescence intensity was changed with the ratio of Ga3+/Cr3+ and the blue host emission of ZnGa2O4 was suppressed when doping Cr3+ into ZnGa2O4. The fluorescence decay curves of blue emission of ZnGa2O4 with different Cr3+ doping concentrations indicated that the lifetime of ZnGa2O4 at 505 nm become shorter with the increase of the Cr3+ concentration. Herein, a possible mechanism of long-lasting luminescence in ZnGa2O4: Cr3+ was proposed that the NIR long-lasting luminescence in ZnGa2O4: Cr3+ comes from the persistent energy transfer from ZnGa2O4 to Cr3+.

  16. IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats

    PubMed Central

    Pang, Yi; Bhatt, Abhay J.; Fan, Lir-Wan

    2015-01-01

    We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an antiinflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist. PMID:25665855

  17. IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats.

    PubMed

    Lan, Kuo-Mao; Tien, Lu-Tai; Pang, Yi; Bhatt, Abhay J; Fan, Lir-Wan

    2015-04-02

    We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist.

  18. Modulatory effect of insulin on T cell receptor mediated calcium signaling is blunted in long lasting type 1 diabetes mellitus.

    PubMed

    Demkow, Urszula; Winklewski, Paweł; Ciepiela, Olga; Popko, Katarzyna; Lipińska, Anna; Kucharska, Anna; Michalska, Beata; Wąsik, Maria

    2012-01-01

    Insulin significantly influences Ca(2+) signals evoked by various stimulants. In type 1 recent onset diabetes mellitus the proliferative response of T cells is significantly decreased. The number of clinical trials exploring the role of anti-CD3 monoclonal antibodies (mAb) as a therapeutic agent in recent onset diabetes mellitus type 1 is increasing last years. Therefore, a better understanding of the interplay between T cell receptor (TCR) dependent Ca(2+) increase, and insulin is of vital clinical significance. The aim of the study was to assess the effect of insulin on TCR evoked Ca(2+) responses in T lymphocytes obtained from healthy volunteers and patients suffering from long lasting diabetes mellitus type 1. Analysis was performed with use of the flow cytometer. We demonstrated that T cells ability to mobilize Ca(2+) was significantly reduced in long lasting diabetes mellitus type 1. Ca(2+) decrease achieved by the long term incubation with anti-CD3 mAb in T cells from healthy volunteers was restored by insulin. Strong interrelationship between baseline Ca(2+) level and plateau phase response to TCR stimulation was observed in the cytoplasm of cells pre-incubated with insulin from both healthy subjects and diabetic patients (r = 0.95, p < 0.0001 and r = 0.94, p < 0.0001, respectively). We postulate the existence of the interplay between TCR mediated activation and insulin. The TCR-insulin interplay is blunted in long lasting diabetes mellitus type 1. These observations may have an important implication for future therapeutic options in diabetes.

  19. Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

    PubMed

    Ueda, S; Sakakibara, S; Yoshimoto, K

    2005-01-01

    The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

  20. Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid.

    PubMed Central

    Ben-Ari, Y; Gho, M

    1988-01-01

    1. The action of a short bath application of kainic acid (KA, 200-250 nM, 3-5 min) on the CA3 region of rat hippocampal slices has been studied with intracellular and extracellular recording techniques. 2. KA evoked bursts which persisted for 10-15 min. In addition, after KA, electrical stimulation of various inputs to CA3 which elicited an EPSP-IPSP sequence in control conditions evoked an EPSP followed by a burst. This evoked response persisted for several hours after removal of KA suggesting the occurrence of a long-lasting modification of the synaptic properties of CA3 neurones. 3. Intracellular recordings showed the spontaneous and evoked bursts to consist of five to ten action potentials riding on a depolarizing shift 10-25 mV in amplitude and 40-100 ms in duration. Both spontaneous and evoked bursts were followed by a long-lasting hyperpolarization 15-25 mV in amplitude and 1-1.5 s in duration. 4. We propose that both spontaneous and evoked synchronized bursts are generated by a polysynaptic network since: (a) intracellularly recorded bursts were synchronized with the bursts in extracellular field recording; (b) bursts disappeared when synaptic transmission or Na+ action potential were blocked by cobalt (1 mM) or TTX (1 microM) respectively; (c) bursts were suppressed by elevated divalent cation concentration; (d) burst occurrence was independent of the membrane potential of the cell; (e) the depolarization shift that underlies the bursts was a linear function of the membrane potential and reversed in polarity at 0 mV. In addition, the evoked bursts were all-or-none events with a variable latency. 5. Laminar profile analysis of the spontaneous and evoked bursts suggests that they were generated by synapses located on the distal apical segments of the dendrites of CA3 pyramidal cells. 7. The persistence of the evoked bursts was neither due to a persistent change in cell excitability nor to a long-lasting reduction in GABAergic synaptic inhibition. 8. Bath

  1. Tennessee and Florida: Continuity and Change in Long-Lasting State Performance Funding Systems for Higher Education. CCRC Brief. Number 43

    ERIC Educational Resources Information Center

    Dougherty, Kevin J.; Natow, Rebecca S.

    2010-01-01

    This study analyzes changes over time in long-lasting state performance funding systems for higher education. It addresses two research questions: First, in what ways have long-lasting systems changed over time in funding levels, indicators used to allocate funds, and measures used for those indicators? Second, what political actors, actions, and…

  2. Simultaneous and long-lasting hydrophilization of inner and outer wall surfaces of polytetrafluoroethylene tubes by transferring atmospheric pressure plasmas

    NASA Astrophysics Data System (ADS)

    Chen, Faze; Song, Jinlong; Huang, Shuai; Xu, Sihao; Xia, Guangqing; Yang, Dezheng; Xu, Wenji; Sun, Jing; Liu, Xin

    2016-09-01

    Plasma hydrophilization is a general method to increase the surface free energy of materials. However, only a few works about plasma modification focus on the hydrophilization of tube inner and outer walls. In this paper, we realize simultaneous and long-lasting plasma hydrophilization on the inner and outer walls of polytetrafluoroethylene (PTFE) tubes by atmospheric pressure plasmas (APPs). Specifically, an Ar atmospheric pressure plasma jet (APPJ) is used to modify the PTFE tube’s outer wall and meanwhile to induce transferred He APP inside the PTFE tube to modify its inner wall surface. The optical emission spectrum (OES) shows that the plasmas contain many chemically active species, which are known as enablers for various applications. Water contact angle (WCA) measurements, x-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) are used to characterize the plasma hydrophilization. Results demonstrate that the wettability of the tube walls are well improved due to the replacement of the surface fluorine by oxygen and the change of surface roughness. The obtained hydrophilicity decreases slowly during more than 180 d aging, indicating a long-lasting hydrophilization. The results presented here clearly demonstrate the great potential of transferring APPs for surface modification of the tube’s inner and outer walls simultaneously.

  3. A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.

    PubMed

    Silva, Carlos D; Neves, Ana F; Dias, Ana I; Freitas, Hugo J; Mendes, Sheena M; Pita, Inês; Viana, Sofia D; de Oliveira, Paulo A; Cunha, Rodrigo A; Fontes Ribeiro, Carlos A; Prediger, Rui D; Pereira, Frederico C

    2014-04-01

    Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis.

  4. Radio Observations Of GRB 100418a: Test Of An Energy Injection Model Explaining Long-Lasting GRB Afterglows

    NASA Astrophysics Data System (ADS)

    Moin, Aquib; Chandra, P.; Miller-Jones, J.; Tingay, S.; Taylor, G. B.; Frail, D. A.; Wang, Z.; Reynolds, C.; Phillips, C.

    2014-01-01

    I will highlight the results of our radio observational campaign on GRB 100418a, for which the Australia Telescope Compact Array (ATCA), Very Large Array (VLA) and the Very Long Baseline Array (VLBA) were used. GRB 100418a was a peculiar GRB with unusual X-ray and optical afterglow profiles featuring a plateau phase with a very shallow rise. This observed plateau phase was believed to be due to a continued energy injection mechanism, which powered the forward shock, giving rise to an unusual and long-lasting afterglow. The radio afterglow of GRB 100418a was detectable several weeks after the prompt emission. We conducted long-term monitoring observations of the afterglow and attempted to test the energy injection model advocating that the continuous energy injection is due to shells of material moving at a wide range of Lorentz factors. We obtained an upper limit of γ < 7 for the expansion rate of the GRB 100418a radio afterglow, indicating that the range-of-Lorentz factor model could only be applicable for relatively slow moving ejecta. A preferred explanation could be that continued activity of the central engine may have powered the long-lasting afterglow.

  5. Radio observations of GRB 100418a: Test of an energy injection model explaining long-lasting GRB afterglows

    SciTech Connect

    Moin, A.; Wang, Z.; Chandra, P.; Miller-Jones, J. C. A.; Tingay, S. J.; Reynolds, C.; Taylor, G. B.; Frail, D. A.; Phillips, C. J.

    2013-12-20

    We present the results of our radio observational campaign of gamma-ray burst (GRB) 100418a, for which we used the Australia Telescope Compact Array, the Very Large Array, and the Very Long Baseline Array. GRB 100418a was a peculiar GRB with unusual X-ray and optical afterglow profiles featuring a plateau phase with a very shallow rise. This observed plateau phase was believed to be due to a continued energy injection mechanism that powered the forward shock, giving rise to an unusual and long-lasting afterglow. The radio afterglow of GRB 100418a was detectable several weeks after the prompt emission. We conducted long-term monitoring observations of the afterglow and attempted to test the energy injection model advocating that the continuous energy injection is due to shells of material moving at a wide range of Lorentz factors. We obtained an upper limit of γ < 7 for the expansion rate of the GRB 100418a radio afterglow, indicating that the range-of-Lorentz factor model could only be applicable for relatively slow-moving ejecta. A preferred explanation could be that continued activity of the central engine may have powered the long-lasting afterglow.

  6. Enzymatic turnover of macromolecules generates long-lasting protein–water-coupled motions beyond reaction steady state

    PubMed Central

    Dielmann-Gessner, Jessica; Grossman, Moran; Conti Nibali, Valeria; Born, Benjamin; Solomonov, Inna; Fields, Gregg B.; Havenith, Martina; Sagi, Irit

    2014-01-01

    The main focus of enzymology is on the enzyme rates, substrate structures, and reactivity, whereas the role of solvent dynamics in mediating the biological reaction is often left aside owing to its complex molecular behavior. We used integrated X-ray– and terahertz- based time-resolved spectroscopic tools to study protein–water dynamics during proteolysis of collagen-like substrates by a matrix metalloproteinase. We show equilibration of structural kinetic transitions in the millisecond timescale during degradation of the two model substrates collagen and gelatin, which have different supersecondary structure and flexibility. Unexpectedly, the detected changes in collective enzyme–substrate–water-coupled motions persisted well beyond steady state for both substrates while displaying substrate-specific behaviors. Molecular dynamics simulations further showed that a hydration funnel (i.e., a gradient in retardation of hydrogen bond (HB) dynamics toward the active site) is substrate-dependent, exhibiting a steeper gradient for the more complex enzyme–collagen system. The long-lasting changes in protein–water dynamics reflect a collection of local energetic equilibrium states specifically formed during substrate conversion. Thus, the observed long-lasting water dynamics contribute to the net enzyme reactivity, impacting substrate binding, positional catalysis, and product release. PMID:25425663

  7. Hyperperfusion counteracted by transient rapid vasoconstriction followed by long-lasting oligemia induced by cortical spreading depression in anesthetized mice

    PubMed Central

    Unekawa, Miyuki; Tomita, Yutaka; Toriumi, Haruki; Osada, Takashi; Masamoto, Kazuto; Kawaguchi, Hiroshi; Itoh, Yoshiaki; Kanno, Iwao; Suzuki, Norihiro

    2015-01-01

    Cortical spreading depression (CSD) involves mass depolarization of neurons and glial cells accompanied with changes in regional cerebral blood flow (rCBF) and energy metabolism. To further understand the mechanisms of CBF response, we examined the temporal diametric changes in pial arteries, pial veins, and cortical capillaries. In urethane-anesthetized mice, the diameters of these vessels were measured while simultaneously recording rCBF with a laser Doppler flowmeter. We observed a considerable increase in rCBF during depolarization in CSD induced by application of KCl, accompanied by a transient dip of rCBF with marked vasoconstriction of pial arteries, which resembled the response to pin-prick-induced CSD. Arterial constriction diminished or disappeared during the second and third passages of CSD, whereas the rCBF increase was maintained without a transient dip. Long-lasting oligemia with a decrease in the reciprocal of mean transit time of injected dye and mild constriction of pial arteries was observed after several passages of the CSD wave. These results indicate that CSD-induced rCBF changes consist of initial hyperemia with a transient dip and followed by a long-lasting oligemia, partially corresponding to the diametric changes of pial arteries, and further suggest that vessels other than pial arteries, such as intracortical vessels, are involved. PMID:25586145

  8. At Long Last

    ERIC Educational Resources Information Center

    Cooper, Kenneth J.

    2012-01-01

    Since 1980, Tufts has offered a minor called Africa in the New World, but for reasons lost to time, the private university north of Boston did not join other schools in the 1960s and 1970s in creating a major in what was usually called Black studies. A faculty-student committee's recommendation in 1972 to do so went unimplemented. African-American…

  9. Luminescence properties of a new bluish green long-lasting phosphorescence phosphor Ca9Bi(PO4)7:Eu2+,Dy3+

    NASA Astrophysics Data System (ADS)

    Jia, Yonglei; Li, Haifeng; Zhao, Ran; Sun, Wenzhi; Su, Qiang; Pang, Ran; Li, Chengyu

    2014-09-01

    A new long-lasting phosphorescence phosphor Ca9Bi(PO4)7:Eu2+,Dy3+ was synthesized by solid state reaction and its long-lasting phosphorescence properties were investigated for the first time. The X-ray powder diffraction, photoluminescence, long-lasting phosphorescence spectra, decay curves and thermoluminescence curves were measured. The Ca9Bi(PO4)7:Eu2+,Dy3+ phosphor exhibits an asymmetric emission centered at 475 nm, which can be ascribed to the 4f65d1-4f7 electronic transition of Eu2+. For the optimized sample, the bright bluish green long-lasting phosphorescence could be observed for 5 h by naked eyes after the excitation source was removed. The long-lasting phosphorescence spectra show that the co-doping of Dy3+ ions greatly enhance the intensity of the long-lasting phosphorescence. Meanwhile, the long-lasting phosphorescence mechanism of this phosphor was discussed. Based on our study, Dy3+ ions are suggested to increase the density of electron or hole traps so as to improve the performance of the bluish green phosphorescence of Eu2+, including the intensity and persistent time.

  10. Long-lasting phosphorescence in Sn2+-Cu2+ codoped silicate glass and its high-pressure treatment effect

    NASA Astrophysics Data System (ADS)

    Qiu, Jianbei; Miyauchi, Koichi; Kawamoto, Yoji; Kitamura, Naoyuki; Qiu, Jianrong; Hirao, Kazuyuki

    2002-07-01

    Long-lasting phosphorescence was observed at 510 nm in a Sn2+-Cu2+ codoped Na2O-CaO-SiO2 glass at room temperature under UV illumination of 254 nm. When the glass was compressed under 3, 6, and 9 GPa, the phosphorescence shifted to 465 nm and its decay rate became shorter. The optical absorption spectra of the samples changed after compression, showing that the cupric ions were reduced to the cuprous ions. The high-pressure treatment also resulted in a lower-energy shift in the absorption edge. It was suggested that Sn2+ ions act as hole trapping centers, while oxygen vacancies surrounding by Ca2+ ions as well as active sites in the glass matrix, i.e., as electron trapping centers.

  11. [Long-lasting behavioral effects of chronic neonatal treatment with ACTH (4-10) analogue semax in white rat pups].

    PubMed

    Sebentsova, E A; Denisenko, A V; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F

    2005-01-01

    It is well known that ACTH/MSH-like peptides (melanocortins) have neurotrophic and neuroprotective effects on the central and peripheral nervous systems in the early postnatal life. The aim of present work was to study consequences of the ACTH (4-10) analogue Semax influence on the developing brain. The work was carried out in white rat pups. The peptide (0.05 mg/kg, i/p) was injected daily on the 8th-21st postnatal days. Delayed long-lasting effects of such treatment on animal behavior were revealed. At the age of four to eight weeks, Semax-treated rats displayed elevated exploratory activity, decreased anxiety level and improved passive avoidance conditioning. The results suggest that neonatal Semax administration modulates the development of the central nervous system.

  12. Activation of spinal microglia in a murine model of peripheral inflammation-induced, long-lasting contralateral allodynia

    PubMed Central

    Schreiber, Kristin L.; Beitz, Alvin J.; Wilcox, George L.

    2008-01-01

    Increased sensitivity contralateral to an injury has been described in humans and in various models of neuropathic pain in rats. The mechanism underlying contralateral hypersensitivity is as yet unclear, although previous studies have implicated involvement of both spinal neurons and glia. We describe the development of a temporally delayed, robust and long-lasting contralateral allodynia in mice after hindpaw injection with 4% carrageenan. Both ipsilateral and contralateral allodynia could be inhibited temporarily by intrathecally administered morphine, clonidine, or neostigmine. The delayed development of contralateral allodynia correlated with an increase in OX-42, but not GFAP immunoreactivity in the contralateral dorsal horn. Furthermore, intrathecal treatment with minocycline inhibited the development of contralateral allodynia, suggesting that microglial activation plays a key role in contralateralization, and may be a potential target for clinical intervention after injury or inflammation has occurred, to eliminate the subsequent development of extraterritorial pain. PMID:18541374

  13. Functional magnetic resonance connectivity studies in infants born preterm: suggestions of proximate and long-lasting changes in language organization.

    PubMed

    Kwon, Soo Hyun; Scheinost, Dustin; Vohr, Betty; Lacadie, Cheryl; Schneider, Karen; Dai, Feng; Sze, Gordon; Constable, R Todd; Ment, Laura R

    2016-03-01

    Sophisticated neuroimaging strategies demonstrate alterations in functional connectivity at school age, adolescence, and young adulthood in individuals born preterm. Recent data suggest these alterations are present in the postnatal period prior to term-equivalent age in neonates born preterm. Likewise, functional organization increases across development, but the influence of preterm birth on this fundamental infrastructure is immediate and unchanging. This article briefly reviews the current methods of measuring functional connectivity throughout development in those born preterm, and the association of functional connectivity with language disorders. Taken together, these data suggest that the effects of preterm birth on the functional organization of language in the developing brain are both proximate and long-lasting.

  14. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain

    PubMed Central

    WEISSHAUPT, ANGELA; WEDEKIND, FRANZISKA; KROLL, TINA; MCCARLEY, ROBERT W.

    2015-01-01

    SUMMARY Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day–1 for 5 consecutive days (SR1–SR5), followed by 3 unrestricted recovery sleep days (R1–R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26–31% from SR1 to R1). A decrease in b-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. PMID:25900125

  15. GABA-A receptor modulators alter emotionality and hippocampal theta rhythm in an animal model of long-lasting anxiety.

    PubMed

    Hoeller, Alexandre Ademar; Duzzioni, Marcelo; Duarte, Filipe Silveira; Leme, Leandro Rinaldi; Costa, Ana Paula Ramos; Santos, Evelyn Cristina da Silva; de Pieri, Claudini Honório; dos Santos, Alessandra Antunes; Naime, Aline Aita; Farina, Marcelo; de Lima, Thereza Christina Monteiro

    2013-09-26

    The cholinergic system is implicated in emotional regulation. The injection of non-convulsant doses of the muscarinic receptor agonist pilocarpine (PILO) induces long-lasting anxiogenic responses in rats evaluated at different time-points (24h to 3 months). To investigate the underlying mechanisms, rats treated with PILO (150mg/kg) were injected 24h or 1 month later with an anxiolytic (diazepam, 1mg/kg, DZP) or anxiogenic (pentylenetetrazole, 15mg/kg, PTZ) drug and evaluated in the elevated plus-maze (EPM). Prefrontal cortex (PFC) and hippocampal (HIP) electroencephalographic recordings and acetylcolinesterase (AChE) activity were also analyzed after PILO treatment. Anxiogenic responses observed in the EPM 24h or 1 month after PILO treatment (e.g., decreased time spent and number of entries into the open arms of the maze) were blocked by DZP but not affected by PTZ. No epileptiform events were registered in the HIP or PFC at 24h or 1 month after PILO injection, but enhanced theta activity was observed in the HIP. DZP decreased hippocampal theta of PILO-treated rats in contrast with PTZ, which increased this parameter in saline- and PILO-treated rats. The HIP and PFC AChE activity did not change after PILO treatment. Our findings demonstrate that the long-term effects on the emotionality of rats induced by PILO are associated with electrophysiological changes in the HIP and sensitive to pharmacological manipulation of the GABAergic system. The present work may support this new research model of long-lasting anxiety, while also highlighting the muscarinic system as a potential target involved in anxiety disorders.

  16. A comparison study between two long-lasting synoptic-scale wave trains and associated tropical cyclogeneses

    NASA Astrophysics Data System (ADS)

    Feng, Tao; Huang, Ronghui; Yang, Xiuqun; Wu, Liang; Zhou, Wen

    2016-04-01

    Tropical cyclogenesis is closely related to the activity of convectively coupled equatorial waves over the western North Pacific. Previous studies usually focused on the role of single cyclonic disturbance on tropical cyclogenesis. From a view of continuously propagating wave train, this study compared two long-lasting synoptic-scale wave trains with distinct tropical cyclone activities in 2004 and 2006 for investigating the essential factors affecting low-level perturbations and tropical cyclone activities. By employing CFSR reanalysis data, JTWC best track, TRMM precipitation rate and ERSST sea surface temperature, analyses show that the long-lasting wave train during 2004 mainly occurs over the region from 130°E to 160°E, featuring enhanced synoptic perturbations in association with enhanced tropical cyclone activity. In contrast, during 2006, the wave train maintains over the region from 120°E to 150°E with more poleward propagation, and the tropical cyclone activity is relatively inactive. Furthermore, the substantial differences between these two wave trains are that the primary propagation occurring at mid-lower-troposphere with a nearly equivalent barotropic structure during 2004, but at upper- and lower- troposphere with significant westward tilt during 2006. This is essentially attributed to effects of different vertical wind shears. In 2004, affected by weak easterly shear, the synoptic-scale waves are confined at mid-low-level. However, in 2006, waves are usually trapped at upper-troposphere by weak westerly shear. Thus, different patterns of vertical wind shears fundamentally affect the structures of synoptic-scale waves and associated tropical cyclogeneses.

  17. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons

    PubMed Central

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-01-01

    The CB1 cannabinoid receptor, the main target of Δ9-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling. PMID:26460022

  18. Short-term stress experienced at time of immunization induces a long-lasting increase in immunologic memory.

    PubMed

    Dhabhar, Firdaus S; Viswanathan, Kavitha

    2005-09-01

    It would be extremely beneficial if one could harness natural, endogenous, health-promoting defense mechanisms to fight disease and restore health. The psychophysiological stress response is the most underappreciated of nature's survival mechanisms. We show that acute stress experienced before primary immunization induces a long-lasting increase in immunity. Compared with controls, mice restrained for 2.5 h before primary immunization with keyhole limpet hemocyanin (KLH) show a significantly enhanced immune response when reexposed to KLH 9 mo later. This immunoenhancement is mediated by an increase in numbers of memory and effector helper T cells in sentinel lymph nodes at the time of primary immunization. Further analyses show that the early stress-induced increase in T cell memory may stimulate the robust increase in infiltrating lymphocyte and macrophage numbers observed months later at a novel site of antigen reexposure. Enhanced leukocyte infiltration may be driven by increased levels of the type 1 cytokines, IL-2 and IFN-gamma, and TNF-alpha, observed at the site of antigen reexposure in animals that had been stressed at the time of primary immunization. In contrast, no differences were observed in type 2 cytokines, IL-4 or IL-5. Given the importance of inducing long-lasting increases in immunologic memory during vaccination, we suggest that the neuroendocrine stress response is nature's adjuvant that could be psychologically and/or pharmacologically manipulated to safely increase vaccine efficacy. These studies introduce the novel concept that a psychophysiological stress response is nature's fundamental survival mechanism that could be therapeutically harnessed to augment immune function during vaccination, wound healing, or infection.

  19. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

    PubMed

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-11-03

    The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

  20. Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety.

    PubMed

    Muñoz-Abellán, Cristina; Daviu, Nuria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

    2009-10-01

    A single exposure to a cat or cat odors has been reported by some groups to induce contextual and auditory fear conditioning and long-lasting changes in anxiety-like behaviour, but there is no evidence for parallel changes in biological stress markers. In the present study we demonstrated in male rats that exposure to a novel environment containing a cloth impregnated with cat fur odor resulted in avoidance of the odor, lower levels of activity and higher pituitary-adrenal (PA) response as compared to those exposed to the novel environment containing a clean cloth, suggesting increased levels of stress in the former animals. When re-exposed 9 days later to the same environment with a clean cloth, previously cat fur exposed rats again showed avoidance of the cloth area and lower levels of activity, suggesting development of contextual fear conditioning, which again was associated with a higher PA activation. In contrast, unaltered both anxiety-like behaviour and PA responsiveness to an elevated plus-maze were found 7 days after cat odor exposure. It is concluded that: (i) PA activation is able to reflect both the stressful properties of cat fur odor and odor-induced contextual fear conditioning; (ii) development of cat odor-induced contextual fear conditioning is independent of the induction of long-lasting changes in anxiety-like behaviour; and (iii) greater PA activation during exposure to the odor context is not explained by non-specific sensitization of the PA axis caused by previous exposure to cat fur odor.

  1. Co-encapsulation of amyloglucosidase with starch and Saccharomyces cerevisiae as basis for a long-lasting CO2 release.

    PubMed

    Humbert, Pascal; Vemmer, Marina; Giampà, Marco; Bednarz, Hanna; Niehaus, Karsten; Patel, Anant V

    2017-04-01

    CO2 is known as a major attractant for many arthropod pests which can be exploited for pest control within novel attract-and-kill strategies. This study reports on the development of a slow-release system for CO2 based on calcium alginate beads containing granular corn starch, amyloglucosidase and Saccharomyces cerevisiae. Our aim was to evaluate the conditions which influence the CO2 release and to clarify the biochemical reactions taking place within the beads. The amyloglucosidase was immobilized with a high encapsulation efficiency of 87% in Ca-alginate beads supplemented with corn starch and S. cerevisiae biomass. The CO2 release from the beads was shown to be significantly affected by the concentration of amyloglucosidase and corn starch within the beads as well as by the incubation temperature. Beads prepared with 0.1 amyloglucosidase units/g matrix solution led to a long-lasting CO2 emission at temperatures between 6 and 25 °C. Starch degradation data correlated well with the CO2 release from beads during incubation and scanning electron microscopy micrographs visualized the degradation of corn starch granules by the co-encapsulated amyloglucosidase. By implementing MALDI-ToF mass spectrometry imaging for the analysis of Ca-alginate beads, we verified that the encapsulated amyloglucosidase converts starch into glucose which is immediately consumed by S. cerevisiae cells. When applied into the soil, the beads increased the CO2 concentration in soil significantly. Finally, we demonstrated that dried beads showed a CO2 production in soil comparable to the moist beads. The long-lasting CO2-releasing beads will pave the way towards novel attract-and-kill strategies in pest control.

  2. Reductions in frontocortical cytokine levels are associated with long-lasting alterations in reward valuation after methamphetamine.

    PubMed

    Stolyarova, Alexandra; Thompson, Andrew B; Barrientos, Ruth M; Izquierdo, Alicia

    2015-03-13

    Alterations in reward valuation are thought to have a central role at all stages of the addiction process. We previously reported work aversion in an effortful T-maze task following a binge exposure to methamphetamine, and no such changes in effort following escalating doses. Limitations of the T-maze task include its two available options, with an effort requirement, in the form of increasing barrier height, varying incrementally as a function of time, and reward magnitudes held constant. Reward preferences and choices, however, are likely affected by the number of options available and the manner in which alternatives are presented. In the present experiment, we investigated the long-lasting, off-drug effects of methamphetamine on reward choices in a novel effortful maze task with three possible courses of action, each associated with different effort requirements and reward magnitudes. Neuroinflammatory responses associated with drug exposure, proposed as one of the mechanisms contributing to suboptimal choices on effort-based tasks, were also examined. We investigated region-specific changes in pro- and anti-inflammatory markers in the mesocorticolimbic pathway after methamphetamine, and their relationship with animals' reward choices. We observed long-lasting, increased sensitivity to differences in reward magnitude in the methamphetamine group: animals were more likely to overcome greater effort costs to obtain larger rewards on our novel effortful maze task. These behavioral changes were strongly predicted by pronounced decreases in frontocortical cytokines, but not amygdalar or striatal markers. The present results provide the first evidence that neuroinflammatory processes are associated with alterations in reward valuation during protracted drug withdrawal.

  3. Phase-Dependent Modulation of Oscillatory Phase and Synchrony by Long-Lasting Depolarizing Inputs in Central Neurons

    PubMed Central

    2016-01-01

    Oscillatory neural activities have been implicated in various types of information processing in the CNS. The procerebral (PC) lobe of the land mollusk Limax valentianus shows an ongoing oscillatory local field potential (LFP). Olfactory input increases both the frequency and spatial synchrony of the LFP oscillation by a nitric oxide (NO)-mediated mechanism, but how NO modulates the activity in a specific manner has been unclear. In the present study, we used electrical stimulation and NO uncaging to systematically analyze the response of the LFP oscillation and found phase-dependent effects on phase shifting and synchrony. The neurons that presumably release NO in the PC lobe preferentially fired at phases in which NO has a synchronizing effect, suggesting that the timing of NO release is regulated to induce a stereotyped response to natural sensory stimuli. The phase–response curve (PRC) describes the timing dependence of responses of an oscillatory system to external input. PRCs are usually constructed by recording the temporal shifts of the neural activity in response to brief electrical pulses. However, NO evokes a long-lasting depolarization persisting for several cycles of oscillation. The phase–response relationship obtained by NO stimulation was approximately the integral of the PRC. A similar relationship was also shown for regular firing of mouse cerebellar Purkinje cells receiving step depolarization, suggesting the generality of the results to oscillatory neural systems with highly distinct properties. These results indicate novel dynamic effects of long-lasting inputs on network oscillation and synchrony, which are based on simple and ubiquitous mechanisms. PMID:27785464

  4. The physical and chemical characteristics of long-lasting trans-boundary mixed pollutants over East Asia

    NASA Astrophysics Data System (ADS)

    Hara, Y.; Uno, I.; Kobayashi, H.; Itahashi, S.; PAN, X.; Nishizawa, T.; Shimizu, A.; Matsui, I.; Sugimoto, N.

    2014-12-01

    Trans-boundary air pollution lasted about 1 week over East Asia from late May to early June 2014. Daily averaged PM2.5 and PM10 exceeded respectively 35μg/m3 and 100μg/m3 during this episode at Fukuoka, southeastern city of Japan. The continuous aerosol plumes were constructed by Asian dust and anthropogenic pollutants, and observed by many aerosol measurements, such as ground-based lidar, space-born lidar, Aerosol Chemical Speciation Analyzer (ACSA) and Polarization Optical Particle Counter (POPC). Regional chemical transport model was used to clarify the meteorological condition forming long-lasting aerosol plumes and the 3D structure. The continuous aerosol plume was made by 2 sequential low pressure systems passing over desert area, and subsequently generated blocking high pressure system over Japan. The averaged aerosol depolarization ratio derived by ground-based lidar and POPC at around 0.5μm during this episode were 0.11 and 0.146, these values were very low for dust case. ACSA data at Fukuoka also showed that coarse model nitrate and fine mode sulfate concentration was very high (3~6μg/m3 for coarse mode nitrate, 5-15 μg/m3 for fine mode sulfate) during this episode. These results suggested that transport of anthropogenic aerosols were occurred during this event together with dust plume. Coarse mode nitrate might be made by internal mixing between dust particles and nitrate. Numerical chemical transport model could not reproduced high concentration of coarse mode nitrate because model did not consider the process of internal mixing between dust particles and nitrate. Further vertical structure and mixing state during long-lasting trans-boundary pollution are clarified.

  5. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain.

    PubMed

    Kim, Youngsoo; Elmenhorst, David; Weisshaupt, Angela; Wedekind, Franziska; Kroll, Tina; Mccarley, Robert W; Strecker, Robert E; Bauer, Andreas

    2015-10-01

    Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in β-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction.

  6. Long-lasting effects of performance-contingent unconscious and conscious reward incentives during cued task-switching.

    PubMed

    Capa, Rémi L; Bouquet, Cédric A; Dreher, Jean-Claude; Dufour, André

    2013-01-01

    Motivation is often thought to interact consciously with executive control, although recent studies have indicated that motivation can also be unconscious. To date, however, the effects of unconscious motivation on high-order executive control functions have not been explored. Only a few studies using subliminal stimuli (i.e., those not related to motivation, such as an arrow to prime a response) have reported short-lived effects on high-order executive control functions. Here, building on research on unconscious motivation, in which a behavior of perseverance is induced to attain a goal, we hypothesized that subliminal motivation can have long-lasting effects on executive control processes. We investigated the impact of unconscious/conscious monetary reward incentives on evoked potentials and neural activity dynamics during cued task-switching performance. Participants performed long runs of task-switching. At the beginning of each run, a reward (50 cents or 1 cent) was displayed, either subliminally or supraliminally. Participants earned the reward contingent upon their correct responses to each trial of the run. A higher percentage of runs was achieved with higher (conscious and unconscious) than lower rewards, indicating that unconscious high rewards have long-lasting behavioral effects. Event-related potential (ERP) results indicated that unconscious and conscious rewards influenced preparatory effort in task preparation, as suggested by a greater fronto-central contingent negative variation (CNV) starting at cue-onset. However, a greater parietal P3 associated with better reaction times (RTs) was observed only under conditions of conscious high reward, suggesting a larger amount of working memory invested during task performance. Together, these results indicate that unconscious and conscious motivations are similar at early stages of task-switching preparation but differ during task performance.

  7. A four year (2007-2010) analysis of long-lasting deep convective systems in the Mediterranean basin

    NASA Astrophysics Data System (ADS)

    Melani, S.; Pasi, F.; Gozzini, B.; Ortolani, A.

    2013-04-01

    Long-lasting, deep convective systems (DCS) occurring in the Mediterranean basin have been investigated for the 2007-2010 years using geostationary Meteosat Second Generation (MSG) satellite data, supported by the European Centre for Medium-Range Weather Forecasts (ECMWF) analyses and severe weather reports recorded by the European Severe Weather Database (ESWD). The spatial and seasonal variability of DCS occurrence have been investigated, as well as the most favourable synoptic precursors for their initiation. The analysis has shown the existence of some preferential areas of DCS genesis, mainly located in the western (i.e., around Balearic Islands) and central (i.e., Ionic and Tyrrhenian seas) Mediterranean, where these systems develop and grow preferentially in fall (i.e., September and October). The analysis of a selected set of Synoptic Precursors (SPs) has shown how the totality of the identified cases has occurred downstream a mid-tropospheric (500 hPa) disturbance (trough or cut-off) within a southerly flow, with high values of θe (at 850 hPa) and precipitable water. Moreover, the approaching of an upper level tropopause dynamical anomaly coupled with a local maximum of upper and low level horizontal wind speed, seems to play a very important role in triggering convection. Finally, a careful crosscheck of the detected cases with the ESWD reports has allowed to investigate the severity of these systems, as they often affect population and produce significant damages. This study has to be considered a necessary step towards the development of a larger climatologic database of long-lasting, deep convective events occurring in the Mediterranean sea, as well as the definition of a specific conceptual model based on synoptic precursors, having the long-term issue of setting up an objective procedure to support regional meteorological services in early decisions and accurate nowcasting.

  8. Synaptic plasticity by antidromic firing during hippocampal network oscillations.

    PubMed

    Bukalo, Olena; Campanac, Emilie; Hoffman, Dax A; Fields, R Douglas

    2013-03-26

    Learning and other cognitive tasks require integrating new experiences into context. In contrast to sensory-evoked synaptic plasticity, comparatively little is known of how synaptic plasticity may be regulated by intrinsic activity in the brain, much of which can involve nonclassical modes of neuronal firing and integration. Coherent high-frequency oscillations of electrical activity in CA1 hippocampal neurons [sharp-wave ripple complexes (SPW-Rs)] functionally couple neurons into transient ensembles. These oscillations occur during slow-wave sleep or at rest. Neurons that participate in SPW-Rs are distinguished from adjacent nonparticipating neurons by firing action potentials that are initiated ectopically in the distal region of axons and propagate antidromically to the cell body. This activity is facilitated by GABA(A)-mediated depolarization of axons and electrotonic coupling. The possible effects of antidromic firing on synaptic strength are unknown. We find that facilitation of spontaneous SPW-Rs in hippocampal slices by increasing gap-junction coupling or by GABA(A)-mediated axon depolarization resulted in a reduction of synaptic strength, and electrical stimulation of axons evoked a widespread, long-lasting synaptic depression. Unlike other forms of synaptic plasticity, this synaptic depression is not dependent upon synaptic input or glutamate receptor activation, but rather requires L-type calcium channel activation and functional gap junctions. Synaptic stimulation delivered after antidromic firing, which was otherwise too weak to induce synaptic potentiation, triggered a long-lasting increase in synaptic strength. Rescaling synaptic weights in subsets of neurons firing antidromically during SPW-Rs might contribute to memory consolidation by sharpening specificity of subsequent synaptic input and promoting incorporation of novel information.

  9. Long-Lasting Cortical Reorganization as the Result of Motor Imagery of Throwing a Ball in a Virtual Tennis Court

    PubMed Central

    Cebolla, Ana M.; Petieau, Mathieu; Cevallos, Carlos; Leroy, Axelle; Dan, Bernard; Cheron, Guy

    2015-01-01

    In order to characterize the neural signature of a motor imagery (MI) task, the present study investigates for the first time the oscillation characteristics including both of the time-frequency measurements, event related spectral perturbation and intertrial coherence (ITC) underlying the variations in the temporal measurements (event related potentials, ERP) directly related to a MI task. We hypothesize that significant variations in both of the time-frequency measurements underlie the specific changes in the ERP directly related to MI. For the MI task, we chose a simple everyday task (throwing a tennis ball), that does not require any particular motor expertise, set within the controlled virtual reality scenario of a tennis court. When compared to the rest condition a consistent, long-lasting negative fronto-central ERP wave was accompanied by significant changes in both time frequency measurements suggesting long-lasting cortical activity reorganization. The ERP wave was characterized by two peaks at about 300 ms (N300) and 1000 ms (N1000). The N300 component was centrally localized on the scalp and was accompanied by significant phase consistency in the delta brain rhythms in the contralateral central scalp areas. The N1000 component spread wider centrally and was accompanied by a significant power decrease (or event related desynchronization) in low beta brain rhythms localized in fronto-precentral and parieto-occipital scalp areas and also by a significant power increase (or event related synchronization) in theta brain rhythms spreading fronto-centrally. During the transition from N300 to N1000, a contralateral alpha (mu) as well as post-central and parieto-theta rhythms occurred. The visual representation of movement formed in the minds of participants might underlie a top-down process from the fronto-central areas which is reflected by the amplitude changes observed in the fronto-central ERPs and by the significant phase synchrony in contralateral fronto

  10. Laboratory and experimental hut evaluation of a long-lasting insecticide treated blanket for protection against mosquitoes

    PubMed Central

    2014-01-01

    Background Long-lasting insecticide treated blankets (LLIBs) may provide additional protection against malaria where use of long lasting insecticidal nets (LLIN) is low or impractical such as in disaster or emergency situations. Methods Initial efficacy testing of a new candidate LLIB was carried out at LSHTM and KCMUCo, before and after washing, in cone and ball bioassays and arm-in-cage tests against pyrethroid susceptible Anopheles gambiae. A small scale field trial was conducted using veranda-trap experimental huts in northern Tanzania against wild An. arabiensis and Culex quinquefasciatus mosquitoes. Treatments included unwashed and 5 times washed permethrin treated LLIB and blankets hand-treated with permethrin (ITB), untreated blankets, and a holed unwashed Olyset net. Results Cone test mortality was 75% for LLIB when unwashed, but decreased to 32% after 5 washes and <10% after 10 washes. In arm-in-cage tests protection against biting was 100% for LLIBs regardless of the number of washes while reduction in landings was 79% when unwashed, 75% after 5 washes, but declined to 41% after 10 and 33% after 20 washes. In ball bioassays using pyrethroid resistant An. arabiensis, mortality was low in all treatments (<35%) and there was no significant difference in mortality between Olyset net, LLIB or ITB (p > 0.05). Percentage mortality of An. arabiensis in huts with LLIB unwashed (26%) was not statistically different to Olyset net (31%, p = 0.5). The 5 times washed LLIB reduced blood-feeding by 49% which was equivalent to Olyset net (p > 0.086). There was no significant difference in percentage blood-feeding between LLIB and ITB unwashed or 5 times washed (p = 0.147 and p = 0.346 respectively). The 5 times washed LLIB reduced blood-feeding of Culex quinquefasciatus by 40%, although the Olyset provided the greatest protection with 85% inhibition. ELISA analysis of a sub-sample of blood fed mosquitoes showed that not all had fed on humans in the

  11. Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses

    PubMed Central

    Low, Lucie A.; Bauer, Lucy C.; Pitcher, Mark H.; Bushnell, M. Catherine

    2016-01-01

    Abstract With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the “nociceptive” central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli. PMID:27058679

  12. The Plasma Structure of a Long-lasting Sigmoid as Revealed by Hinode and Magnetic Field Modeling

    NASA Astrophysics Data System (ADS)

    Stefanova Savcheva, Antonia

    2015-04-01

    We present multi-thermal observations from Hinode/XRT and EIS plasma diagnostics over a large part of the lifetime of a long-lasting sigmoid observed between Dec 05 and Dec 07, 2007. This region is the best observationally covered sigmoidal region by XRT and EIS simultaneously. We analyze EIS/XRT thermal maps as well EIS Doppler velocity, density and non-thermal width (NTW) maps in conjunction with non-linear force-free field (NLFFF) models constrained by the XRT data. We show that material accumulates in the dips oftwisted flux rope field lines, the temperature is enhanced at the locations of strong current concentrations in the model, and NTWs are enhanced at the outskirts of the region coinciding with large-scale QSLs that envelope the region. We follow the evolution of these plasma parameters and the filed lines from the best-fit NLFFF models in time and space leading to the flare on Dec 07, 2007.

  13. Hinode Observation of the Magnetic Fields in a Sunspot Light Bridge Accompanied by Long-Lasting Chromospheric Plasma Ejections

    NASA Astrophysics Data System (ADS)

    Shimizu, Toshifumi; Katsukawa, Yukio; Kubo, Masahito; Lites, Bruce W.; Ichimoto, Kiyoshi; Suematsu, Yoshinori; Tsuneta, Saku; Nagata, Shin'ichi; Shine, Richard A.; Tarbell, Theodore D.

    2009-05-01

    We present high-resolution magnetic field measurements of a sunspot light bridge (LB) that produced chromospheric plasma ejections intermittently and recurrently for more than 1 day. The observations were carried out with the Hinode Solar Optical Telescope on 2007 April 29 and 30. The spectro-polarimeter reveals obliquely oriented magnetic fields with vertical electric current density higher than 100 mA m-2 along the LB. The observations suggest that current-carrying highly twisted magnetic flux tubes are trapped below a cusp-shaped magnetic structure along the LB. The presence of trapped current-carrying flux tubes is essential for causing long-lasting chromospheric plasma ejections at the interface with pre-existing vertically oriented umbral fields. A bidirectional jet was clearly detected, suggesting magnetic reconnections occurring at very low altitudes, slightly above the height where the vector magnetic fields are measured. Moreover, we found another strong vertical electric current on the interface between the current-carrying flux tube and pre-existing umbral field, which might be a direct detection of the currents flowing in the current sheet formed at the magnetic reconnection sites.

  14. Long-Lasting WNT-TCF Response Blocking and Epigenetic Modifying Activities of Withanolide F in Human Cancer Cells

    PubMed Central

    Seth, Chandan; Mas, Christophe; Conod, Arwen; Mueller, Jens; Siems, Karsten; Kuciak, Monika; Borges, Isabel; Ruiz i Altaba, Ariel

    2016-01-01

    The WNT-TCF signaling pathway participates in adult tissue homeostasis and repair, and is hyperactive in a number of human diseases including cancers of the colon. Whereas to date there are no antagonists approved for patient use, a potential problem for their sustained use is the blockade of WNT signaling in healthy tissues, thus provoking potentially serious co-lateral damage. Here we have screened a library of plant and microorganism small molecules for novel WNT signaling antagonists and describe withanolide F as a potent WNT-TCF response blocker. This steroidal lactone inhibits TCF-dependent colon cancer xenograft growth and mimics the effects of genetic blockade of TCF and of ivermectin, a previously reported WNT-TCF blocker. However, withanolide F is unique in that it imposes a long-lasting repression of tumor growth, WNT-TCF targets and cancer stem cell clonogenicity after drug treatment. These findings are paralleled by its modulation of chromatin regulators and its alteration of overall H3K4me1 levels. Our results open up the possibility to permanently repress essential signaling responses in cancer cells through limited treatments with small molecules. PMID:27973612

  15. Long-lasting effects of prenatal dietary choline availability on object recognition memory ability in adult rats.

    PubMed

    Moreno, Hayarelis C; de Brugada, Isabel; Carias, Diamela; Gallo, Milagros

    2013-11-01

    Choline is an essential nutrient required for early development. Previous studies have shown that prenatal choline availability influences adult memory abilities depending on the medial temporal lobe integrity. The relevance of prenatal choline availability on object recognition memory was assessed in adult Wistar rats. Three groups of pregnant Wistar rats were fed from E12 to E18 with choline-deficient (0 g/kg choline chloride), standard (1.1 g/kg choline chloride), or choline-supplemented (5 g/kg choline chloride) diets. The offspring was cross-fostered to rat dams fed a standard diet during pregnancy and tested at the age of 3 months in an object recognition memory task applying retention tests 24 and 48 hours after acquisition. Although no significant differences have been found in the performance of the three groups during the first retention test, the supplemented group exhibited improved memory compared with both the standard and the deficient group in the second retention test, 48 hours after acquisition. In addition, at the second retention test the deficient group did not differ from chance. Taken together, the results support the notion of a long-lasting beneficial effect of prenatal choline supplementation on object recognition memory which is evident when the rats reach adulthood. The results are discussed in terms of their relevance for improving the understanding of the cholinergic involvement in object recognition memory and the implications of the importance of maternal diet for lifelong cognitive abilities.

  16. Genetic Immunization With In Vivo Dendritic Cell-targeting Liposomal DNA Vaccine Carrier Induces Long-lasting Antitumor Immune Response

    PubMed Central

    Garu, Arup; Moku, Gopikrishna; Gulla, Suresh Kumar; Chaudhuri, Arabinda

    2016-01-01

    A major limiting factor retarding the clinical success of dendritic cell (DC)-based genetic immunizations (DNA vaccination) is the scarcity of biologically safe and effective carrier systems for targeting the antigen-encoded DNA vaccines to DCs under in vivo settings. Herein, we report on a potent, mannose receptor selective in vivo DC-targeting liposomes of a novel cationic amphiphile with mannose-mimicking shikimoyl head-group. Flow cytometric experiments with cells isolated from draining lymph nodes of mice s.c. immunized with lipoplexes of pGFP plasmid (model DNA vaccine) using anti-CD11c antibody-labeled magnetic beads revealed in vivo DC-targeting properties of the presently described liposomal DNA vaccine carrier. Importantly, s.c. immunizations of mice with electrostatic complex of the in vivo DC-targeting liposome and melanoma antigen-encoded DNA vaccine (p-CMV-MART1) induced long-lasting antimelanoma immune response (100 days post melanoma tumor challenge) with remarkable memory response (more than 6 months after the second tumor challenge). The presently described direct in vivo DC-targeting liposomal DNA vaccine carrier is expected to find future exploitations toward designing effective vaccines for various infectious diseases and cancers. PMID:26666450

  17. Twelve-week physical exercise does not have a long-lasting effect on kynurenines in plasma of depressed patients

    PubMed Central

    Millischer, Vincent; Erhardt, Sophie; Ekblom, Örjan; Forsell, Yvonne; Lavebratt, Catharina

    2017-01-01

    Background Physical exercise has well-characterized positive effects on depressive symptoms. The underlying biologic mechanisms are, however, far from established. A recently discovered mechanism has linked the enhanced conversion of kynurenine to kynurenic acid (KYNA) to an increased resilience toward stress-induced depression in mice. The aim of this study was to translate these findings to humans. Materials and methods Kynurenine and KYNA levels were measured by high-performance liquid chromatography in plasma samples from 117 patients affected by mild-to-moderate depression before and within a week after a 12-week training period at three different intensities. The patients were part of the Regassa study. Results No differences in plasma levels of kynurenine and KYNA or in their ratio could be detected between before and after training. No effect of the intensity group could be observed. No correlation with the improvement in cardiovascular fitness (Åstrand score) or the improvement in mood (Montgomery Åsberg Depression Rating Scale score) could be observed. Limitations As the Regassa study is based on an intention-to-treat protocol, the exact time and the exact intensity of the physical exercise are not known. Analyses of pulse data as well as personal interviews, however, were used to control the exercise protocols. Furthermore, the observations reflect chronic changes. Conclusion Physical exercise positively affects mood and cardiovascular fitness, but does not lead to long-lasting changes in plasma levels of kynurenine and KYNA in patients affected by mild-to-moderate depression.

  18. Treating seeds with activators of plant defence generates long-lasting priming of resistance to pests and pathogens.

    PubMed

    Worrall, Dawn; Holroyd, Geoff H; Moore, Jason P; Glowacz, Marcin; Croft, Patricia; Taylor, Jane E; Paul, Nigel D; Roberts, Michael R

    2012-02-01

    • Priming of defence is a strategy employed by plants exposed to stress to enhance resistance against future stress episodes with minimal associated costs on growth. Here, we test the hypothesis that application of priming agents to seeds can result in plants with primed defences. • We measured resistance to arthropod herbivores and disease in tomato (Solanum lycopersicum) plants grown from seed treated with jasmonic acid (JA) and/or β-aminobutryric acid (BABA). • Plants grown from JA-treated seed showed increased resistance against herbivory by spider mites, caterpillars and aphids, and against the necrotrophic fungal pathogen, Botrytis cinerea. BABA seed treatment provided primed defence against powdery mildew disease caused by the biotrophic fungal pathogen, Oidium neolycopersici. Priming responses were long-lasting, with significant increases in resistance sustained in plants grown from treated seed for at least 8 wk, and were associated with enhanced defence gene expression during pathogen attack. There was no significant antagonism between different forms of defence in plants grown from seeds treated with a combination of JA and BABA. • Long-term defence priming by seed treatments was not accompanied by reductions in growth, and may therefore be suitable for commercial exploitation.

  19. The BCR-ABL/NF-κB signal transduction network: a long lasting relationship in Philadelphia positive Leukemias

    PubMed Central

    Carrà, Giovanna; Torti, Davide; Crivellaro, Sabrina; Panuzzo, Cristina; Taulli, Riccardo; Cilloni, Daniela; Guerrasio, Angelo; Saglio, Giuseppe; Morotti, Alessandro

    2016-01-01

    The Nuclear Factor-kappa B (NF-κB) family of transcription factors plays a key role in cancer pathogenesis due to the ability to promote cellular proliferation and survival, to induce resistance to chemotherapy and to mediate invasion and metastasis. NF-κB is recruited through different mechanisms involving either canonical (RelA/p50) or non-canonical pathways (RelB/p50 or RelB/p52), which transduce the signals originated from growth-factors, cytokines, oncogenic stress and DNA damage, bacterial and viral products or other stimuli. The pharmacological inhibition of the NF-κB pathway has clearly been associated with significant clinical activity in different cancers. Almost 20 years ago, NF-κB was described as an essential modulator of BCR-ABL signaling in Chronic Myeloid Leukemia and Philadelphia-positive Acute Lymphoblastic Leukemia. This review summarizes the role of NF-κB in BCR-ABL-mediated leukemogenesis and provides new insights on the long lasting BCR-ABL/NF-κB connection. PMID:27563822

  20. Operational Assessment of Long-Lasting Insecticidal Nets by Using an Anopheles Salivary Biomarker of Human-Vector Contact.

    PubMed

    Noukpo, Mahoutin H; Damien, Georgia B; Elanga-N'Dille, Emmanuel; Sagna, André B; Drame, Papa M; Chaffa, Evelyne; Boussari, Olayidé; Corbel, Vincent; Akogbéto, Martin; Remoue, Franck

    2016-12-07

    The widespread implementation of long-lasting insecticidal nets (LLINs) is a major intervention method for malaria control. Although the LLINs coverage increases, information available on the physical integrity (PI) of implemented LLINs is incomplete. This study aimed to validate human IgG antibody (Ab) response to Anopheles gSG6-P1 salivary peptide antigen, previously demonstrated as a pertinent biomarker of human exposure to Anopheles bites, for evaluating the PI of LLINs in field conditions. We analyzed data from 262 randomly selected children (< 5 years of age) in health districts of Benin. Anti-gSG6-P1 IgG responses were assessed and compared with the PI of LLINs that these same children slept under, and evaluated by the hole index (HI). Specific IgG levels were positively correlated to LLINs HI (r = 0.342; P < 0.0001). According to antipeptide IgG level (i.e., intensity of vector exposure), two categories of LLINs PI were defined: 1) group "HI: [0, 100]" corresponding to LLINs with "good" PI and 2) "HI > 100" corresponding to LLINs with "bad" PI. These results suggest that human Ab response to salivary peptide could be a complementary tool to help defining a standardized threshold of efficacy for LLINs under field use.

  1. Human Exposure to Early Morning Anopheles funestus Biting Behavior and Personal Protection Provided by Long-Lasting Insecticidal Nets

    PubMed Central

    Moiroux, Nicolas; Damien, Georgia B.; Egrot, Marc; Djenontin, Armel; Chandre, Fabrice; Corbel, Vincent; Killeen, Gerry F.; Pennetier, Cédric

    2014-01-01

    A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply. PMID:25115830

  2. Single-dose microparticle delivery of a malaria transmission-blocking vaccine elicits a long-lasting functional antibody response.

    PubMed

    Dinglasan, R R; Armistead, J S; Nyland, J F; Jiang, X; Mao, H Q

    2013-05-01

    Malaria sexual stage and mosquito transmission-blocking vaccines (SSM-TBV) have recently gained prominence as a necessary tool for malaria eradication. SSM-TBVs are unique in that, with the exception of parasite gametocyte antigens, they primarily target parasite or mosquito midgut surface antigens expressed only inside the mosquito. As such, the primary perceived limitation of SSM-TBVs is that the absence of natural boosting following immunization will limit its efficacy, since the antigens are never presented to the human immune system. An ideal, safe SSM-TBV formulation must overcome this limitation. We provide a focused evaluation of relevant nano-/microparticle technologies that can be applied toward the development of leading SSM-TBV candidates, and data from a proof-of-concept study demonstrating that a single inoculation and controlled release of antigen in mice, can elicit long-lasting protective antibody titers. We conclude by identifying the remaining critical gaps in knowledge and opportunities for moving SSM-TBVs to the field.

  3. TRANSIENT EARLY-LIFE FOREBRAIN CRH ELEVATION CAUSES LONG LASTING ANXIOGENIC AND DESPAIR-LIKE CHANGES IN MICE

    PubMed Central

    Kolber, Benedict J.; Boyle, Maureen P.; Wieczorek, Lindsay; Kelley, Crystal L.; Onwuzurike, Chiamaka C.; Nettles, Sabin; Vogt, Sherri K.; Muglia, Louis J.

    2010-01-01

    During development, early-life stress, such as abuse or trauma, induces long-lasting changes that are linked to adult anxiety and depressive behavior. It has been postulated that altered expression of corticotropin-releasing hormone (CRH) can at least partially account for the various effects of stress on behavior. In accord with this hypothesis, evidence from pharmacological and genetic studies has indicated the capacity of differing levels of CRH activity in different brain areas to produce behavioral changes. Furthermore, stress during early life or adulthood causes an increase in CRH release in a variety of neural sites. To evaluate the temporal and spatial specificity of the effect of early-life CRH exposure on adult behavior, the tetracycline-off system was used to produce mice with forebrain-restricted inducible expression of CRH (FBCRHOE). After transient elevation of CRH during development only, behavioral testing in adult mice revealed a persistent anxiogenic and despair-like phenotype. These behavioral changes were not associated with alterations in adult circadian or stress-induced corticosterone release but were associated with changes in CRH receptor type 1 expression. Furthermore, the despair-like changes were normalized with antidepressant treatment. Overall, these studies suggest that forebrain-restricted CRH signaling during development can permanently alter stress adaptation leading to increases in maladaptive behavior in adulthood. PMID:20164342

  4. Activation of Exchange Protein Activated by Cyclic-AMP Enhances Long-Lasting Synaptic Potentiation in the Hippocampus

    ERIC Educational Resources Information Center

    Gelinas, Jennifer N.; Banko, Jessica L.; Peters, Melinda M.; Klann, Eric; Weeber, Edwin J.; Nguyen, Peter V.

    2008-01-01

    cAMP is a critical second messenger implicated in synaptic plasticity and memory in the mammalian brain. Substantial evidence links increases in intracellular cAMP to activation of cAMP-dependent protein kinase (PKA) and subsequent phosphorylation of downstream effectors (transcription factors, receptors, protein kinases) necessary for long-term…

  5. Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats.

    PubMed

    Wang, Zhiqiang; Fan, Jin; Wang, Jian; Li, Yuxia; Duan, Dan; Du, Guo; Wang, Qingsong

    2016-03-15

    Synaptic dysfunction underlies cognitive deficits induced by chronic cerebral hypoperfusion (CCH). There are silent synapses in neural circuits, but the effect of CCH on silent synapses is unknown. The present study was designed to explore learning and memory deficits and dynamic changes in silent synapses by direct visualization in a rat model of CCH. Adult male Sprague-Dawley rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) to reproduce CCH. Learning and memory effects were examined at 1, 4, 12, and 24 weeks after BCCAO. In addition, immunofluorescent confocal microscopy was used to detect AMPA and N-methyl-d-aspartate receptors colocalized with synaptophysin, and Golgi-Cox staining was used to observe dendritic spine density. We found that BCCAO rats exhibited recognition memory deficits from 4 weeks; spatial learning and memory, as well as working memory impairment began at 1 week and persistent to 24 weeks after surgery. Following BCCAO, the percentage of silent synapses increased by 29.81-55.08% compared with the controls at different time points (P<0.001). Compared with control groups, dendritic spine density in the CA1 region of BCCAO groups significantly decreased (P<0.001). Thus, the present study suggests that CCH can induce long-lasting cognitive deficits and long-term increase in the number of silent synapses. Furthermore, the decrease in dendritic spine density was correlated with the decrease in the number of functional synapses. The results suggest a potential mechanism by which CCH can induce learning and memory deficits.

  6. Weaning induces both transient and long-lasting modifications of absorptive, secretory, and barrier properties of piglet intestine.

    PubMed

    Boudry, Gaëlle; Péron, Vincent; Le Huërou-Luron, Isabelle; Lallès, Jean Paul; Sève, Bernard

    2004-09-01

    This study investigated intestinal physiology of piglets at weaning. Piglets (n = 60) weaned at 21 d were food deprived for 2 d and then tube-fed using 2 different diets (a conventional diet vs. a wheat-enriched diet). They were slaughtered at d 0, 2, 5, 8, or 15 postweaning. Jejunum, ileum, and colon were mounted in Ussing chambers. In addition, segments of the proximal jejunum of 4 growing pigs were studied 35 d after weaning. Secretory function was assessed by basal short-circuit current (Isc) and secretagogue-stimulated Isc. Glucose absorption was measured by the increase in Isc after the addition of glucose. Epithelial barrier function was measured by transmucosal resistance (R) and horseradish peroxidase (HRP) fluxes across the epithelium. There were no significant differences between the pigs fed the 2 diets for any of the parameters studied. As already reported, a transient villous atrophy was observed. At the same time, we observed an increased basal Isc in jejunum and colon, increased glucose absorption and a dramatic drop of R in jejunum. These parameters had returned to preweaning values by d 5. Weaning was also followed by long-lasting modifications. In jejunum, responses to the secretagogues and glucose absorption were decreased at wk 2 after weaning and were not different between d 15 and 35. Ileal transmucosal resistance increased on d 5 and was stable thereafter. HRP flux in jejunum declined on d 2 and stayed at this low level throughout the experiment. We conclude that weaning induces transient dramatic changes in intestinal physiology but is also a period of maturation of the intestine.

  7. HIF-1α triggers long-lasting glutamate excitotoxicity via system xc(-) in cerebral ischaemia-reperfusion.

    PubMed

    Hsieh, Chia-Hung; Lin, Yu-Jung; Chen, Wei-Ling; Huang, Yen-Chih; Chang, Chi-Wei; Cheng, Fu-Chou; Liu, Ren-Shyan; Shyu, Woei-Cherng

    2017-02-01

    Hypoxia-inducible factor 1α (HIF-1α) controls many genes involved in physiological and pathological processes. However, its roles in glutamatergic transmission and excitotoxicity are unclear. Here, we proposed that HIF-1α might contribute to glutamate-mediated excitotoxicity during cerebral ischaemia-reperfusion (CIR) and investigated its molecular mechanism. We showed that an HIF-1α conditional knockout mouse displayed an inhibition in CIR-induced elevation of extracellular glutamate and N-methyl-d-aspartate receptor (NMDAR) activation. By gene screening for glutamate transporters in cortical cells, we found that HIF-1α mainly regulates the cystine-glutamate transporter (system xc(-) ) subunit xCT by directly binding to its promoter; xCT and its function are up-regulated in the ischaemic brains of rodents and humans, and the effects lasted for several days. Genetic deletion of xCT in cortical cells of mice inhibits either oxygen glucose deprivation/reoxygenation (OGDR) or CIR-mediated glutamate excitotoxicity in vitro and in vivo. Pharmaceutical inhibition of system xc(-) by a clinically approved anti-cancer drug, sorafenib, improves infarct volume and functional outcome in rodents with CIR and its therapeutic window is at least 3 days. Taken together, these findings reveal that HIF-1α plays a role in CIR-induced glutamate excitotoxicity via the long-lasting activation of system xc(-) -dependent glutamate outflow and suggest that system xc(-) is a promising therapeutic target with an extended therapeutic window in stroke. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Long lasting preventive effects of piperlongumine and a Piper longum extract against stress triggered pathologies in mice

    PubMed Central

    Yadav, Vaishali; Chatterjee, Shyam Sunder; Majeed, Muhammed; Kumar, Vikas

    2015-01-01

    Aim: To compare doxycycline (DOX) such as oral efficacies of piperlongumine (PL) and a Piper longum fruits extract (PLE) as stress resistance inducers. Materials and Methods: Efficacies of oral pretreatments with 5 mg/kg PL or PLE or of 50 mg/kg DOX for 10 consecutive days against stress resistance were compared. Mice in treated groups were subjected to a stress induced hyperthermia on the 1st, 5th, 7th, and 10thday. Treated mice were then subjected to tail suspension test on the 11thday. Alteration in body weights, core temperatures, and gastric ulcers triggered by occasional exposures to foot shocks were determined. Results: DOX like long-lasting protective effects of PL and PLE against gradual alterations in body weights, basal temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed 1 day after the last foot-shock exposures and gastric ulcers and other pathologies quantified 1 day after the test were also suppressed in PL or PLE or DOX pretreated groups. Conclusion: PL and crude PLE are DOX like long-acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of P. longum and other plants of the Piperaceae family, and reveal that PL is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant-derived products enriched in PL or piperine like amide alkaloids in volunteers and patients can be warranted. PMID:26649232

  9. Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting.

    PubMed

    Reibel, S; Vivien-Roels, B; Lê, B T; Larmet, Y; Carnahan, J; Marescaux, C; Depaulis, A

    2000-02-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal neuroplasticity. In particular, BDNF upregulation in the hippocampus by epileptic seizures suggests its involvement in the neuronal rearrangements accompanying epileptogenesis. We have shown previously that chronic infusion of BDNF in the hippocampus induces a long-term delay in hippocampal kindling progression. Although BDNF has been shown to enhance the excitability of this structure upon acute application, long-term transcriptional regulations leading to increased inhibition within the hippocampus may account for its suppressive effects on epileptogenesis. Therefore, the long-term consequences of a 7-day chronic intrahippocampal infusion of BDNF (12 microg/day) were investigated up to 2 weeks after the end of the infusion, on the expression of neurotransmitters contained in inhibitory hippocampal interneurons and which display anti-epileptic properties. Our results show that BDNF does not modify levels of immunostaining for glutamic acid decarboxylase, the rate-limiting enzyme for gamma-aminobutyric acid (GABA) synthesis, and somatostatin. Conversely, BDNF induces a long-lasting increase of neuropeptide Y (NPY) in the hippocampus, measured by immunohistochemistry and radioimmunoassay, outlasting the end of the infusion by at least 7 days. The distribution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pattern observed in animals submitted to hippocampal kindling, with the exception of mossy fibres which only become immunoreactive following seizure activity. The enduring increase of neuropeptide Y expression induced by BDNF in the hippocampus suggests that this neurotrophin can trigger long-term genomic effects, which may contribute to the neuroplasticity of this structure, in particular during epileptogenesis.

  10. Long-lasting alterations of hippocampal GABAergic neurotransmission in adult rats following perinatal Δ(9)-THC exposure.

    PubMed

    Beggiato, Sarah; Borelli, Andrea Celeste; Tomasini, Maria Cristina; Morgano, Lucia; Antonelli, Tiziana; Tanganelli, Sergio; Cuomo, Vincenzo; Ferraro, Luca

    2017-03-01

    The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored. To this purpose, pregnant rats were treated daily with Delta(9)-tetrahydrocannabinol (Δ(9)-THC; 5mg/kg) or its vehicle. Perinatal exposure to Δ(9)-THC induced a significant reduction (p<0.05) in basal and K(+)-evoked [(3)H]-GABA outflow of 90-day-old rat hippocampal slices. These effects were associated with a reduction of hippocampal [(3)H]-GABA uptake compared to vehicle exposed group. Perinatal exposure to Δ(9)-THC induced a significant reduction of CB1 receptor binding (Bmax) in the hippocampus of 90-day-old rats. However, a pharmacological challenge with either Δ(9)-THC (0.1μM) or WIN55,212-2 (2μM), similarly reduced K(+)-evoked [(3)H]-GABA outflow in both experimental groups. These reductions were significantly blocked by adding the selective CB1 receptor antagonist SR141716A. These findings suggest that maternal exposure to cannabinoids induces long-term alterations of hippocampal GABAergic system. Interestingly, previous behavioral studies demonstrated that, under the same experimental conditions as in the present study, perinatal cannabinoids exposure induced cognitive impairments in adult rats, thus resembling some effects observed in humans. Although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of hippocampus aminoacidergic transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of

  11. Long-lasting neonatal inflammation enhances pain responses to subsequent inflammation, but not peripheral nerve injury in adult rats.

    PubMed

    Lim, Eun Jeong; Back, Seung Keun; Kim, Myung Ah; Li, Chengjin; Lee, Jaehee; Jeong, Keun Yeong; Na, Heung Sik

    2009-05-01

    The early postnatal period has been suggested to be the vulnerable time for structural and functional reorganization of sensory systems, and painful stimuli at this time may alter neuronal circuits, thereby leading to changes in an individual's response to pain later in life. In the present study, we examined whether inflammatory experience in the early life can affect pain responses to subsequent noxious insults later in life. The two groups of neonatal rats, treated with an inflammatory irritant and untreated, were subjected to inflammation and peripheral nerve injury in adulthood. Neonatal inflammation was induced by injection of complete Freund's adjuvant (CFA, 25 microl) into the hindpaw or tail of newborn rat pups. Adult rats which had suffered from neonatal paw inflammation at P0 were subjected to re-injection of CFA into the paw neonatally exposed to CFA or L5 spinal nerve ligation. Paw thickness and histology of inflamed paw were examined to assess the neonatal inflammation. Adult animals whose tail had been subjected to CFA injection on P3 received tail-innervating nerve injury. The results showed that the neonatal CFA-treated rats suffered from chronic inflammation, confirmed by persistent increase of paw thickness and histological result of inflamed paw. These animals showed enhanced pain responses to re-inflammatory challenge by injection of CFA (200 microl) into the neonatally inflamed paw 8 weeks after birth compared with the neonatally untreated animals. However, neuropathic pain on the hindpaw and the tail which had been induced by peripheral nerve injury in the neonatal CFA-treated group were not different from those of the untreated group. The present data suggest that early neonatal long-lasting inflammation differentially affects pain responses later in life, depending on the types of subsequent noxious insults.

  12. Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons

    PubMed Central

    Dubois, C. J.; Ramamoorthy, P.; Whim, M. D.

    2012-01-01

    Neuropeptide Y (NPY), a widely distributed neuropeptide in the central nervous system, can transiently suppress inhibitory synaptic transmission and alter membrane excitability via Y2 and Y1 receptors (Y2rs and Y1rs), respectively. Although many GABAergic neurons express Y5rs, the functional role of these receptors in inhibitory neurons is not known. Here, we investigated whether activation of Y5rs can modulate inhibitory transmission in cerebellar slices. Unexpectedly, application of NPY triggered a long-lasting increase in the frequency of miniature inhibitory postsynaptic currents in stellate cells. NPY also induced a sustained increase in spontaneous GABA release in cultured cerebellar neurons. When cerebellar cultures were examined for Y5r immunoreactivity, the staining colocalized with that of VGAT, a presynaptic marker for GABAergic cells, suggesting that Y5rs are located in the presynaptic terminals of inhibitory neurons. RT-PCR experiments confirmed the presence of Y5r mRNA in the cerebellum. The NPY-induced potentiation of GABA release was blocked by Y5r antagonists and mimicked by application of a selective peptide agonist for Y5r. Thus Y5r activation is necessary and sufficient to trigger an increase in GABA release. Finally, the potentiation of inhibitory transmission could not be reversed by a Y5r antagonist once it was initiated, consistent with the development of a long-term potentiation. These results indicate that activation of presynaptic Y5rs induces a sustained increase in spontaneous GABA release from inhibitory neurons in contrast to the transient suppression of inhibitory transmission that is characteristic of Y1r and Y2r activation. Our findings thus reveal a novel role of presynaptic Y5rs in inhibitory interneurons in regulating GABA release and suggest that these receptors could play a role in shaping neuronal network activity in the cerebellum. PMID:22190627

  13. Maternal stress during late gestation has moderate but long-lasting effects on the immune system of the piglets.

    PubMed

    Couret, David; Jamin, Agnès; Kuntz-Simon, Gaëlle; Prunier, Armelle; Merlot, Elodie

    2009-09-15

    Events acting prenatally on developing foetuses are important determinants for disorders later in life. Prenatal stress (PNS) is one of these events. The purpose of this study was to determine the consequences of a repeated social stress applied during late gestation of the pregnant gilt on the immune system and hypothalamo-pituitary-adrenal (HPA) axis activity of the piglets from birth to two months of age. Pregnant gilts were submitted to repeated social stress which was induced by housing unfamiliar gilts in pairs modified twice a week during 4 weeks between days 77 and 105 of gestation (S group, n=18). Control gilts were housed in stable pairs during the same period (C group, n=18). Blood cortisol, haptoglobin and IgG levels, immune cell counts, mitogen-induced whole-blood proliferation and TNF-alpha production were evaluated in piglets at 4 days of age (D4), before and after weaning (D26 and 28) and before and after relocation to a new building (D60 and 62). We found that PNS did not affect growth rate of the progeny. It decreased the relative weight of adrenal glands on D4 (P<0.05) but plasma cortisol levels were similar in both groups at all ages. IgG levels in colostrum and in the serum of piglets were not affected. PNS decreased the total numbers of white blood cells, lymphocytes and granulocytes from D26 to D60 (P<0.05), the CD4(+)/CD8(+) T cell ratio on D4 (P<0.05), and LPS induced-TNF-alpha production on D60 (P<0.05). PNS increased the ConA-induced lymphocyte proliferation on D4 and D60 and the PWM-induced proliferation on D60 (P<0.05). Our results demonstrate that a repeated social stress applied to pregnant sows during late gestation can induce long-lasting effects on several parameters of the immune function of the offspring. These effects are not due to modifications of the HPA axis activity and may impair the abilities of the piglets to efficiently react against infections during the suckling period and around weaning.

  14. Robotic guidance induces long-lasting changes in the movement pattern of a novel sport-specific motor task.

    PubMed

    Kümmel, Jakob; Kramer, Andreas; Gruber, Markus

    2014-12-01

    Facilitating the learning or relearning of motor tasks is one of the main goals of coaches, teachers and therapists. One promising way to achieve this goal is guiding the learner through the correct movement trajectory with the help of a robotic device. The aim of this study was to investigate if haptic guidance can induce long-lasting changes in the movement pattern of a complex sport-specific motor task. For this purpose, 31 subjects were assigned to one of three groups: EA (early angle, n=10), LA (late angle, n=11) and CON (control, n=10). EA and LA successfully completed five training sessions, which consisted of 50 robot-guided golf swings and 10 free swings each, whereas CON had no training. The EA group was guided through the movement with the wrist being bent early during backswing, whereas in the LA group it was bent late. The participants of EA and LA were not told about this difference in the movement patterns. To assess if the robot-guided training was successful in shaping the movement pattern, the timing of the wrist bending during the backswing in free swings was measured before (PRE), one day after (POST), and 7 days after (FUP) the five training sessions. The ANOVA (time×group×angle) showed that during POST and FUP, the participants of the EA group bent their wrist significantly earlier during the backswing than the other groups. Post-hoc analyses revealed that this interaction effect was mainly due to the differences in the wrist angle progression during the first 5° of the backswing. The robot-guided training was successful in shaping the movement pattern, and these changes persisted even after 7 days without further practice. This might have implications for the learning of complex motor tasks in general, as haptic guidance might quickly provide the beginner with an internal model of the correct movement pattern without having to direct the learner's attention towards the key points of the correct movement pattern.

  15. Analysing and recommending options for maintaining universal coverage with long-lasting insecticidal nets: the case of Tanzania in 2011

    PubMed Central

    2013-01-01

    Background Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or “Keep-Up” distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Methods Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. Results LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of $449 million USD and ensure

  16. Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

    PubMed

    Sikiric, P; Jadrijevic, S; Seiwerth, S; Sosa, T; Deskovic, S; Perovic, D; Aralica, G; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Ziger, T; Rotkvic, I; Mise, S; Zoricic, I; Sebecic, B; Patrlj, L; Kocman, B; Sarlija, M; Mikus, D; Separovic, J; Hanzevacki, M; Gjurasin, M; Miklic, P

    1999-12-01

    values, BPC 157-treated groups consistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated groups showed no difference compared with control values. Thus, despite limitations, a generalization supporting a direct importance of a common cytoprotective approach, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions.

  17. De-immunized and Functional Therapeutic (DeFT) versions of a long lasting recombinant alpha interferon for antiviral therapy.

    PubMed

    Mufarrege, Eduardo F; Giorgetti, Sofía; Etcheverrigaray, Marina; Terry, Frances; Martin, William; De Groot, Anne S

    2017-01-10

    Interferon α (IFN-α) exerts potent antiviral, immunomodulatory, and antiproliferative activity and have proven clinical utility in chronic hepatitis B and C virus infections. However, repeated IFN-α administration induces neutralizing antibodies (NAb) against the therapeutic in a significant number of patients. Associations between IFN-α immunogenicity and loss of efficacy have been described. So as to improve the in vivo biological efficacy of IFN-α, a long lasting hyperglycosylated protein (4N-IFN) derived from IFN-α2b wild type (WT-IFN) was developed. However, in silico analysis performed using established in silico methods revealed that 4N-IFN had more T cell epitopes than WT-IFN. In order to develop a safer and more efficient IFN therapy, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of 4N-IFN. Using the OptiMatrix in silico tool in ISPRI, the 4N-IFN sequence was modified to reduce HLA binding potential of specific T cell epitopes. Following verification of predictions by HLA binding assays, eight modifications were selected and integrated in three variants: 4N-IFN(VAR1), (VAR2) and (VAR3). Two of the three variants (VAR1 and VAR3) retained anti-viral function and demonstrated reduced T-cell immunogenicity in terms of T-cell proliferation and Th1 and Th2 cytokine levels, when compared to controls (commercial NG-IFN (non-glycosylated), PEG-IFN, WT-IFN and 4N-IFN). It was previously demonstrated that N-glycosylation improved IFN-α pharmacokinetic properties. Here, we further reduce immunogenicity as measured in vitro using T cell assays and cytokine profiling by modifying the T cell epitope content of a protein (de-immunizing). Taking into consideration the present results and previously reported immunogenicity data for commercial IFN-α2b variants, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be promising candidates for improved IFN-α therapy of HCV and HBV.

  18. Impact of operational effectiveness of long-lasting insecticidal nets (LLINs) on malaria transmission in pyrethroid-resistant areas

    PubMed Central

    2013-01-01

    Background A dynamic study on the transmission of malaria was conducted in two areas (R+ area: Low resistance area; R+++ area: High resistance area) in the department of Plateau in South Eastern Benin, where the population is protected by Long Lasting Insecticidal Nets (LLINs). The aim of this study was to determine if the resistance of malaria vectors to insecticides has an impact on their behavior and on the effectiveness of LLINs in the reduction of malaria transmission. Methods Populations of Anopheles gambiae s.l. were sampled monthly by human landing catch in the two areas to evaluate human biting rates (HBR). Collected mosquitoes were identified morphologically and female Anopheles mosquitoes were tested for the presence of Plasmodium falciparum antigen as assessed using ELISA. The entomological inoculation rate (EIR) was also calculated (EIR = HBR x sporozoitic index [S]). We estimated the parity rate by dissecting the females of An. gambiae. Finally, window catch and spray catch were conducted in order to assess the blood feeding rate and the exophily rate of vectors. Results After 6 months of tracking the mosquito's behavior in contact with the LLINs (Olyset) in R+++ and R+ areas, the entomological indicators of the transmission of malaria (parity rate and sporozoitic index) were similar in the two areas. Also, An. gambiae populations showed the same susceptibility to P. falciparum in both R+ and R+++ areas. The EIR and the exophily rate are higher in R+ area than in R+++ area. But the blood-feeding rate is lower in R+ area comparing to R+++. Conclusion The highest entomological inoculation rate observed in R+ area is mostly due to the strong aggressive density of An. gambiae recorded in one of the study localities. On the other hand, the highest exophily rate and the low blood-feeding rate recorded in R+ area compared to R+++ area are not due to the resistance status of An. gambiae, but due to the differences in distribution and availability of

  19. Evaluation of the 2011 long-lasting, insecticide-treated net distribution for universal coverage in Togo

    PubMed Central

    2013-01-01

    Background Malaria remains a substantial public health problem in Togo. An integrated child health campaign was conducted in Togo in October 2011. This campaign included a component of free distribution of 2,799,800 long-lasting, insecticide-treated nets (LLINs) to households throughout Togo. This distribution marked the first effort in Togo at universal LLIN coverage and was not targeted specifically to children under five years and pregnant women, but to all household members. This study reports the results of the LLIN distribution campaign in terms of bed net possession and utilization. Methods A representative household survey was implemented during the rainy season nine months after the LLIN distribution component of the campaign. Some 6,015 households selected through two stages of probability proportion to size stratified random sampling were interviewed using a brief questionnaire that included a demographic section with questions on the number of household members and sleeping spaces, and a campaign participation section with questions used to evaluate non-LLIN aspects of the campaign. A net roster listed all nets and their characteristics, and a household roster listed all members and visitors with information about bed net use. The questions addressed different aspects of bed net and LLIN possession and utilization. Crude weighted frequencies, percentages, and t- tests of association were calculated using the Stata 12.0 Survey features. Results Possession of at least one bed net and/or LLIN increased from 41.3% to 96.7% (P <0.001). Household possession of at least one campaign LLIN was 93.3%. Report LLIN among pregnant women was 77.5% and 79.3% for children under five. For the general population LLIN use was 68.3%. Conclusions Due to the gap in LLIN possession and use and the significant number of individuals reporting a lack of nets as a reason for non-use, additional national LLIN distribution campaigns with a stronger educational component need to be

  20. Postsynaptic Signaling and Plasticity Mechanisms

    NASA Astrophysics Data System (ADS)

    Sheng, Morgan; Jong Kim, Myung

    2002-10-01

    In excitatory synapses of the brain, specific receptors in the postsynaptic membrane lie ready to respond to the release of the neurotransmitter glutamate from the presynaptic terminal. Upon stimulation, these glutamate receptors activate multiple biochemical pathways that transduce signals into the postsynaptic neuron. Different kinds of synaptic activity elicit different patterns of postsynaptic signals that lead to short- or long-lasting strengthening or weakening of synaptic transmission. The complex molecular mechanisms that underlie postsynaptic signaling and plasticity are beginning to emerge.

  1. Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity

    PubMed Central

    Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt

    2016-01-01

    Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level. PMID:27548330

  2. Intrinsic Geodesy

    DTIC Science & Technology

    1952-03-01

    Variation with the Height of the Principal Radii of Curvature in Somigliana’s Theory"), Bollettino di Geodesia e Scienze Affini, anno VIII, 1950 46...MARUSSI, A., "Principi di Geodesia Intrinseca applicati al campo di Somigliana" ("Principles of Intrinsic Geodesy Applied to Somigliana’s Field...34), Bollettino di Geodesia e Scienze Affini, anno VIII, 1950; and also Atti della XLII Riunione _dela Socie&Ljtsjjganaper il Progresso delle Scienze, Roma

  3. Red long-lasting phosphorescence (LLP) in β-TCP type Ca 9.5Mn(PO 4) 7 compounds

    NASA Astrophysics Data System (ADS)

    Lecointre, A.; Ait Benhamou, R.; Bessiére, A.; Wallez, G.; Elaatmani, M.; Viana, B.

    2011-12-01

    Mn-ion doped calcium phosphates namely Ca 5(PO 4) 3(OH) hydroxyapatite (HAP), β-Ca 3(PO 4) 2 (β-TCP) as well as Ca 9.5Mn(PO 4) 7 whitlockite were synthesized and the optical properties of the Mn 2+ cations were investigated. Annealing under reducing atmosphere enhances the emission of the divalent manganese species. Electron paramagnetic resonance (EPR) and optical spectroscopies confirm that Mn 2+ ions are the active species. Orange and red emissions occur respectively for the Mn:HAP and Mn:TCP. For this latter, long-lasting phosphorescence (LLP) coming from the Mn 2+ emission ( 4T 1 → 6A 1 transition) is observed at 640 nm but it appears that the traps depths are either two shallow or too deep to lead to an efficient long-lasting emission.

  4. Palatable Hyper-Caloric Foods Impact on Neuronal Plasticity

    PubMed Central

    Morin, Jean-Pascal; Rodríguez-Durán, Luis F.; Guzmán-Ramos, Kioko; Perez-Cruz, Claudia; Ferreira, Guillaume; Diaz-Cintra, Sofia; Pacheco-López, Gustavo

    2017-01-01

    Neural plasticity is an intrinsic and essential characteristic of the nervous system that allows animals “self-tuning” to adapt to their environment over their lifetime. Activity-dependent synaptic plasticity in the central nervous system is a form of neural plasticity that underlies learning and memory formation, as well as long-lasting, environmentally-induced maladaptive behaviors, such as drug addiction and overeating of palatable hyper-caloric (PHc) food. In western societies, the abundance of PHc foods has caused a dramatic increase in the incidence of overweight/obesity and related disorders. To this regard, it has been suggested that increased adiposity may be caused at least in part by behavioral changes in the affected individuals that are induced by the chronic consumption of PHc foods; some authors have even drawn attention to the similarity that exists between over-indulgent eating and drug addiction. Long-term misuse of certain dietary components has also been linked to chronic neuroimmune maladaptation that may predispose individuals to neurodegenerative conditions such as Alzheimer’s disease. In this review article, we discuss recent evidence that shows how consumption of PHc food can cause maladaptive neural plasticity that converts short-term ingestive drives into compulsive behaviors. We also discuss the neural mechanisms of how chronic consumption of PHc foods may alter brain function and lead to cognitive impairments, focusing on prenatal, childhood and adolescence as vulnerable neurodevelopmental stages to dietary environmental insults. Finally, we outline a societal agenda for harnessing permissive obesogenic environments. PMID:28261067

  5. Hippocampal Injections of Oligomeric Amyloid β-peptide (1–42) Induce Selective Working Memory Deficits and Long-lasting Alterations of ERK Signaling Pathway

    PubMed Central

    Faucher, Pierre; Mons, Nicole; Micheau, Jacques; Louis, Caroline; Beracochea, Daniel J.

    2016-01-01

    Increasing evidence suggests that abnormal brain accumulation of soluble rather than aggregated amyloid-β1–42 oligomers (Aβo(1–42)) plays a causal role in Alzheimer’s disease (AD). However, as yet, animal’s models of AD based on oligomeric amyloid-β1–42 injections in the brain have not investigated their long-lasting impacts on molecular and cognitive functions. In addition, the injections have been most often performed in ventricles, but not in the hippocampus, in spite of the fact that the hippocampus is importantly involved in memory processes and is strongly and precociously affected during the early stages of AD. Thus, in the present study, we investigated the long-lasting impacts of intra-hippocampal injections of oligomeric forms of Aβo(1–42) on working and spatial memory and on the related activation of ERK1/2. Indeed, the extracellular signal-regulated kinase (ERK) which is involved in memory function had been found to be activated by amyloid peptides. We found that repeated bilateral injections (1injection/day over 4 successive days) of oligomeric forms of Aβo(1–42) into the dorsal hippocampus lead to long-lasting impairments in two working memory tasks, these deficits being observed 7 days after the last injection, while spatial memory remained unaffected. Moreover, the working memory deficits were correlated with sustained impairments of ERK1/2 activation in the medial prefrontal cortex (mPFC) and the septum, two brain areas tightly connected with the hippocampus and involved in working memory. Thus, our study is first to evidence that sub-chronic injections of oligomeric forms of Aβo(1–42) into the dorsal hippocampus produces the main sign of cognitive impairments corresponding to the early stages of AD, via long-lasting alterations of an ERK/MAPK pathway in an interconnected brain networks. PMID:26793098

  6. Aedes aegypti (Diptera: Culicidae): evaluation of natural long-lasting materials containing pyriproxyfen to improve control strategies.

    PubMed

    Seccacini, Emilia; Juan, Laura; Zerba, Eduardo; Licastro, Susana

    2014-09-01

    Natural materials such as beeswax or a paraffin/stearin mixture containing pyriproxyfen and used as a slow release formulation may convert any breeding place into a larvicidal ovitrap for Aedes aegypti (L.) control. Effectiveness and residual activity of beeswax and paraffin/stearin 1:1 discs containing from 10(-5) to 10(-1) % pyriproxyfen and sticked at the bottom of plastic jars were evaluated for adult emergence inhibition (EI) on late 3rd or early 4th instar A. aegypti larvae. At the initial time t = 0, the EI was 100% for vessels containing beeswax or paraffin/stearin 1:1 discs containing up to 10(-4)% pyriproxyfen. For the lowest pyriproxyfen concentration of 10(-5)%, paraffin/stearin mixture gave a higher EI% value than beeswax (100 and 50%, respectively). Jars were kept at room temperature, and water was totally replaced every 15 days. Bioassays for residual activity repeated monthly showed that at 30 days and for pyriproxyfen 10(-5) % and both matrices, the EI values were low and comparable to control values. For pyriproxyfen 10(-4) %, EI remained above 95% for at least 90 days and around 75% up to 180 days. The EI values are always higher for paraffin/stearin mixture than for beeswax. For all other higher concentrations, 100% EI was obtained at least during 300 days. In a semi-field trial, paraffin/stearin/sand O-rings (2:1:2), containing pyriproxyfen 1%, were sunken in 200-l water-storage tanks and held outdoors in a shadow place. After 72 h, a 250-ml aliquot was taken (t = 0) obtaining 100 % EI. Water level was completed to 200 l every 15 days and bioassays repeated monthly as before. Residual activity remains with 100% EI at least for 6 months.

  7. In Vivo and Ex Vivo Imaging Reveals a Long-Lasting Chlamydial Infection in the Mouse Gastrointestinal Tract following Genital Tract Inoculation

    PubMed Central

    Zhang, Qi; Huang, Yumeng; Gong, Siqi; Yang, Zhangsheng; Sun, Xin; Schenken, Robert

    2015-01-01

    Intravaginal infection with Chlamydia muridarum in mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected with C. trachomatis. Here, we utilized in vivo imaging of C. muridarum infection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. Unexpectedly, the C. muridarum-derived signal was still detectable in the abdominal area 100 days after inoculation. Ex vivo imaging of the mouse organs revealed that the long-lasting presence of the chlamydial signal was restricted to the gastrointestinal (GI) tract, which was validated by directly measuring the chlamydial live organisms and genomes in the same organs. The C. muridarum organisms spreading from the genital to the GI tracts were detected in different mouse strains and appeared to be independent of oral or rectal routes. Mice prevented from orally taking up excretions also developed the long-lasting GI tract infection. Inoculation of C. muridarum directly into the upper genital tract, which resulted in a delayed vaginal shedding of live organisms, accelerated the chlamydial spreading to the GI tract. Thus, we have demonstrated that the genital tract chlamydial organisms may use a systemic route to spread to and establish a long-lasting infection in the GI tract. The significance of the chlamydial spreading from the genital to GI tracts is discussed. PMID:26099591

  8. Presence of long-lasting peripheral adaptation in oblique-banded leafroller, Choristoneura rosaceana and absence of such adaptation in redbanded leafroller, Argyrotaenia velutinana.

    PubMed

    Stelinski, Lukasz L; Miller, James R; Gut, Larry J

    2003-02-01

    Pre-exposure of male oblique-banded leafrollers, Choristoneura rosaceana (Harris), to the main component of their pheromone blend and traces of its geometric isomer (Z11-14:Ac and E11-14:Ac, respectively) at 36 +/- 12 ng/ml air for durations of 15 and 60 min in sealed Teflon chambers with continuous air exchange significantly reduced peripheral sensory responses to these compounds as measured by electroantennograms (EAGs). The EAG responses of C. rosaceana to all tested dosages of pheromonal stimuli and blank controls were lowered by 55-58% and made a linear recovery to 70-100% of the pre-exposure amplitude within 12.5 min at a rate of 3-4 %/min. Exposures of 5 min were insufficient to maximally adapt C. rosaceana; however, exposures of 15 and 60 min reduced sensory responsiveness to the same minimum. In contrast, EAG responses of redbanded leafroller, Argyrotaenia velutinana (Walker), after identical pheromone exposure for 5 and 60 min yielded no long-lasting peripheral sensory adaptation as measured by EAGs, even though this species shares the same main pheromone components with C. rosaceana. We postulate that the long-lasting peripheral adaptation observed for C. rosaceana is a mechanism that impedes central nervous system habituation in this species. In contrast, A. velutinana may be more susceptible to central nervous system habituation because it lacks the capacity for minutes-long adaptation. We propose that long-lasting adaptation may be a mechanism explaining some of the variation in efficacy of pheromone-based mating disruption across taxa.

  9. A novel red long lasting phosphorescent (LLP) material {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+}, Sm{sup 3+}

    SciTech Connect

    Wang Jing; Su Qiang . E-mail: cessuq@zsu.edu.cn; Wang Shubin

    2005-04-20

    A novel red long lasting phosphorescent materials {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+},Sm{sup 3+} is firstly synthesized by high-temperature solid-state reaction. The influence of Sm{sup 3+} ions on luminescence and long lasting phosphorescence properties of Mn{sup 2+} in phosphor {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+},Sm{sup 3+} are systematically investigated. It is found that the red phosphorescence ({lambda} = 616 nm) performance of Mn{sup 2+} ion such as brightness and duration is largely improved when Sm{sup 3+} ion is co-doped into the matrix in which Mn{sup 2+} ion acts as luminescent center and Sm{sup 3+} ion plays an important role of electron trap. Thermoluminescence spectrums show that there exists one peak in {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+},Sm{sup 3+}, the depth of which is 0.33 eV, and that there are three peaks in {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+}, among which the depth of the lowest temperature peak in {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+} is 0.37 eV. Such differences in the trap depth result in the improvement of red long lasting phosphorescence of Mn{sup 2+} in present matrix.

  10. On the nature of a compound formed from dinitrosyl-iron complexes with cysteine and responsible for a long-lasting vasorelaxation.

    PubMed

    Mokh, Vladimir P; Poltorakov, Alexander P; Serezhenkov, Vladimir A; Vanin, Anatoly F

    2010-05-15

    The nature of a compound able to induce long-lasting (> or =20 min) relaxation of rat abdominal aorta rings after addition of rapidly (within several minutes) disappeared mono- and binuclear dinitrosyl iron complexes with cysteine (M- and B-DNICs, respectively) (10 micromol) to the Krebs medium has been investigated. It has been found that long-lasting vasorelaxation is not induced either by S-nitrosocysteine formed upon decomposition of DNICs or by accumulation of free nitric oxide molecules or nitrite remaining in the incubation medium. Long-term air bubbling of the Krebs medium initially containing M-DNIC is accompanied by conversion of the complex first into B-DNIC, which represents a Roussin's red salt cysteine ester and then into a more stable diamagnetic compound X, which displays an intense absorption band at 278 nm. Compound X is decomposed after treatment with the strong bivalent iron chelator bathophenanthroline disulfonate (BPDS) and N-methyl-D-glucamine dithiocarbamate (MGD). The MGD-induced decomposition of compound X is concomitant with the formation of EPR-detectable mononitrosyl iron complexes with MGD. Treatment of compound X with cysteine results in its decomposition and the appearance of optical absorption bands characteristic of M- and B-DNICs. Evidently, compound X, has an iron-nitrosyl origin similar to that of M- and B-DNICs and its formation in oxygenated DNIC solutions is determined by the lowering cysteine content in them. It is hypothesized that compound X represents a cysteine ester of nitrosyl iron complexes, namely, a black Roussin's salt cysteine ester responsible for long-lasting vasorelaxation initiated by addition of M- and B-DNICs that are rapidly decomposed to compound X to the incubation medium.

  11. An influence of long-lasting and gradual magnetic flux transport on fate of magnetotail fast plasma flows: An energetic particle injection substorm event study

    NASA Astrophysics Data System (ADS)

    Nowada, Motoharu; Fu, Suiyan; Parks, George K.; Pulkkinen, Tuija I.; Pu, Zuyin

    2014-10-01

    Based on multi-satellite and ground observations, we investigated an influence of long-lasting and gradual enhancements of magnetic flux transport rate on the magnetotail fast flow duration. On March 10th, 2009, THEMIS-B, which was located in the central plasma sheet of middle distant magnetotail (XGSM ~-25.8 RE), observed the fast flows with the velocity exceeding 300 km/s, lasting over 3 h for intense southward Interplanetary Magnetic Field (IMF) period. During long-lasting fast flows, AL index variations were very extensive and their recovery was much slow. Pi 2 waves were observed at the ground observatories around the THEMIS's footpoints and at low-/mid-latitudes. The aspect for these AL variations suggests Steady Magnetospheric Convection (SMC), but clear substorm signatures were also observed. Further magnetic dipolarization was detected by THEMIS-A at XGSM ~-8.2 RE and its nearby THEMIS-E. Only THEMIS-A observed the associated energetic electron flux enhancements. Therefore, the fast flows occurred during substorm with energetic particle injections at “imitative” SMC, which would be driven by prolonged intense southward IMF. The cumulative transport rates of magnetic and Poynting fluxes consecutively and gradually enhanced. On the other hand, THEMIS-C detected much shorter fast flows with the duration of 37 min at XGSM ~-18.1 RE and weak/gradual substorm-associated dipolarization. However, the cumulative magnetic flux transport rate was enhanced only during the fast flow interval and was saturated after the fast flows. From different magnetic transport rate profiles at THEMIS-B and THEMIS-C, the realms of dipolar-configured field lines expanded to near THEMIS-C's position responsible for long-lasting fast flow-associated consecutive and gradual magnetic flux pileup. Because the resultant “high-speed flow braking” region was retreated into a few RE tailward direction, long-lasting fast flows were almost stemmed. These results suggest that the

  12. Synthesis, conformation, and biological characterization of a sugar derivative of morphine that is a potent, long-lasting, and nontolerant antinociceptive.

    PubMed

    Arsequell, Gemma; Salvatella, Mariona; Valencia, Gregorio; Fernández-Mayoralas, Alfonso; Fontanella, Marco; Venturi, Chiara; Jiménez-Barbero, Jesús; Marrón, Ezequiel; Rodríguez, Raquel E

    2009-05-14

    A synthetic mannoside derivative, namely, 6-morphinyl-alpha-D-mannopyranoside, shows a naloxone-reversible antinociception that is 100-fold more potent and twice as long lasting compared to morphine when administered intraperitoneally to rats in paw pressure and tail flick tests. The compound does not produce tolerance and binds to rat mu opioid receptors with twice the affinity of morphine. NMR studies suggest that differences of activity between the derivative and its parent compound M6G might be related to their differing molecular dynamic behavior.

  13. Think twice, it's all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear.

    PubMed

    Björkstrand, Johannes; Agren, Thomas; Åhs, Fredrik; Frick, Andreas; Larsson, Elna-Marie; Hjorth, Olof; Furmark, Tomas; Fredrikson, Mats

    2017-05-01

    Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10min than the 6h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10min than the 6h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

  14. The photoluminescence and thermoluminescence properties of novel green long-lasting phosphorescence materials Ca8Mg(SiO4)4Cl2:Eu2+,Nd3+

    NASA Astrophysics Data System (ADS)

    Wang, J.; Zhang, M.; Zhang, Q.; Ding, W.; Su, Q.

    2007-04-01

    The novel green long-lasting phosphorescence (LLP) material Ca8Mg(SiO4)4Cl2:Eu2+,Nd3+ was systematically investigated by means of photoluminescence (PL) excitation and emission, a thermal quenching process, long-lasting phosphorescent emission, decay curves, chromaticity and thermoluminescence (TL) spectra. It is clearly observed that there exist two distinguishable Eu sites, EuI for 426-nm and EuII for 504-nm emissions, but only the green LLP appears at the EuII site. The emissions for both PL and LLP are due to the 5d→4f transitions. The green phosphorescence with the chromaticity coordination x=0.196, y=0.506 can still be observed in the dark for no less than 5 h by the naked eye. The results of TL show that Nd3+ ions induce the predominating band at 335 K, associated with the charge-trapping centers that are responsible for the appearance of intense green phosphorescence.

  15. Repeated electroconvulsive stimuli have long-lasting effects on hippocampal BDNF and decrease immobility time in the rat forced swim test.

    PubMed

    Li, Bingjin; Suemaru, Katsuya; Cui, Ranji; Araki, Hiroaki

    2007-03-27

    Electroconvulsive therapy is considered an effective treatment for severe depression. However, the mechanisms for its long-lasting antidepressant efficacy are poorly understood. In the present study, we investigated changes of the immobility time in the forced swim test and brain-derived neurotrophic factor (BDNF) protein after withdrawal from 14-day repeated electroconvulsive stimuli (ECS, 50 mA, 0.2 s) in rats. Immobility time in the forced swim test was markedly decreased 6 h after withdrawal following 14-day ECS treatment. Thereafter, prolongation of the withdrawal period gradually diminished the decreasing effect of immobility time, but significant effects persisted for up to 3 days after the withdrawal. Locomotor activity in the open-field test increased 6 h after withdrawal from the ECS treatment, and the enhanced effect persisted for at least 7 days. The BDNF protein level in the hippocampus was markedly increased 6 h after the withdrawal, and remained high for at least 7 days. These findings provide further evidence that repeated ECS has long-lasting effect on increase in BDNF and locomotor activity and decrease in immobility time in the forced swim test.

  16. Lymph node positive head and neck carcinoma after curative radiochemotherapy: a long lasting debate on elective post-therapeutic neck dissections comes to a conclusion.

    PubMed

    Hermann, R M; Christiansen, H; Rödel, R M

    2013-01-01

    There has been a long lasting debate, whether planned neck dissections after curative radio(chemo)therapy for locally advanced head and neck squamous cell carcinomas offer some benefit in tumor control or survival. We did a thorough literature research on that topic. The results of several recently published studies are described, summarized, and reviewed. Patients with residual disease in clinical or radiographic examinations (CT or MRI scans) up to 3 months after completion of radiochemotherapy profit from neck dissections. In patients with an initial or delayed clinical complete remission after completion of radiochemotherapy, a neck dissection can be safely omitted. In conclusion, there is no longer evidence for a benefit of prophylactic post-radiochemotherapy neck dissections, but strong evidence for a therapeutic post-radiochemotherapy neck dissection in this group of patients.

  17. Observation of the simultaneous transport of Asian mineral dust aerosols with anthropogenic pollutants using a POPC during a long-lasting dust event in late spring 2014

    NASA Astrophysics Data System (ADS)

    Pan, Xiaole; Uno, Itsushi; Hara, Yukari; Kuribayashi, Masatoshi; Kobayashi, Hiroshi; Sugimoto, Nobuo; Yamamoto, Shigekazu; Shimohara, Takaaki; Wang, Zifa

    2015-03-01

    We observed a long-lasting dust event from 25 May to 2 June 2014, using a polarization optical particle counter (POPC). The transport of dust plumes over East Asia was verified on the basis of observations of Moderate Resolution Imaging Spectroradiometer, a lidar network, and surface synoptic observation stations. Mixing of dust and anthropogenic pollutants was investigated according to the variation in the depolarization ratio as a function of particle size. The nonsphericity of dust particles varied due to the impact of anthropogenic pollutants on their pathway. In the coarse mode, dust particles always had a clear nonspherical configuration, although large amounts of nitrate were also present. Supermicron particles are occasionally present in a spherical configuration, possibly due to the complex mixing of natural dust and anthropogenic particles. Statistically, ~64% of the total nitrate mass was deemed to be transported from outside of Japan due to a trapping effect in the dust plume.

  18. [Dependence of long-lasting effects of the ACTH(4-10) analogue semax on the time of its neonatal administration].

    PubMed

    Sebentsova, E A; Glazova, N Iu; Levitskaia, N G; Andreeva, L A; Alfeeva, L Iu; Kamenskiĭ, A A; Miasoedov, N F

    2005-02-01

    Long-lasting behavioural effects of chronic administration of synthetic ACT(4-10) analogue Semax (MEHFPGP) during early neonatal life were studied. The peptide was injected daily intraperitoneally in dose 0.05 mg/kg during the first, second or second-third weeks of postnatal development. It was shown that the peptide injections during the first week lead to a decrease and during second or second-third weeks--to an increase of exploratory activity in 4-8-week aged rats. Furthermore, the peptide adminictration at all times diminished anxiety and improved learning ability of adult rats. The data obtained show that Semax neonatal administration during the first three weeks of life modulates development of brain structures involved in regulation of exploration, anxiety and learning.

  19. A LIGHT-CURVE MODEL OF THE SYMBIOTIC NOVA PU Vul (1979): A VERY QUIET EXPLOSION WITH LONG-LASTING FLAT PEAK

    SciTech Connect

    Kato, Mariko; Hachisu, Izumi; Cassatella, Angelo; Gonzalez-Riestra, Rosario

    2011-02-01

    We present a light-curve model of the symbiotic nova PU Vul (Nova Vulpeculae 1979) that shows a long-lasting flat peak with no spectral indication of wind mass loss before decline. Our quasi-evolution models consisting of a series of static solutions explain both the optical flat peak and ultraviolet (UV) light curve simultaneously. The white dwarf mass is estimated to be {approx}0.6 M{sub sun}. We also provide a new determination of the reddening, E(B - V) = 0.43 {+-} 0.05, from UV spectral analysis. Theoretical light-curve fitting of UV 1455 A provides the distance of d = 3.8 {+-} 0.7 kpc.

  20. GRB 120711A: an intense INTEGRAL burst with long-lasting soft γ-ray emission and a powerful optical flash

    NASA Astrophysics Data System (ADS)

    Martin-Carrillo, A.; Hanlon, L.; Topinka, M.; LaCluyzé, A. P.; Savchenko, V.; Kann, D. A.; Trotter, A. S.; Covino, S.; Krühler, T.; Greiner, J.; McGlynn, S.; Murphy, D.; Tisdall, P.; Meehan, S.; Wade, C.; McBreen, B.; Reichart, D. E.; Fugazza, D.; Haislip, J. B.; Rossi, A.; Schady, P.; Elliott, J.; Klose, S.

    2014-07-01

    A long and intense γ-ray burst (GRB) was detected by INTEGRAL on 11 July 2012 with a duration of ~115 s and fluence of 2.8 × 10-4 erg cm-2 in the 20 keV-8 MeV energy range. GRB 120711A was at z ~ 1.405 and produced soft γ-ray emission (>20 keV) for at least ~10 ks after the trigger. The GRB was observed by several ground-based telescopes that detected a powerful optical flash peaking at an R-band brightness of ~11.5 mag at ~126 s after the trigger, or ~9th magnitude when corrected for the host galaxy extinction (AV ~ 0.85). The X-ray afterglow was monitored by the Swift, XMM-Newton, and Chandra observatories from 8 ks to 7 Ms and provides evidence for a jet break at ~0.9 Ms. We present a comprehensive temporal and spectral analysis of the long-lasting soft γ-ray emission detected in the 20-200 keV band with INTEGRAL/IBIS, the Fermi/LAT post-GRB detection above 100 MeV, the soft X-ray afterglow and the optical/near-infrared detections from Watcher, Skynet/PROMPT, GROND, and REM. The prompt emission had a very hard spectrum (Epeak ~ 1 MeV) and yields an Eγ,iso ~ 1054 erg (1 keV-10 MeV rest frame), making GRB 120711A one of the most energetic GRBs detected so far. We modelled the long-lasting soft γ-ray emission using the standard afterglow scenario, which indicates a forward shock origin. The combination of data extending from the near-infrared to GeV energies suggest that the emission is produced by a broken power-law spectrum consistent with synchrotron radiation. The afterglow is well modelled using a stratified wind-like environment with a density profile k ~ 1.2, suggesting a massive star progenitor (i.e. Wolf-Rayet) with a mass-loss rate between ~10-5-10-6 M⊙ yr-1 depending on the value of the radiative efficiency (ηγ = 0.2 or 0.5). The analysis of the reverse and forward shock emission reveals an initial Lorentz factor of ~120-340, a jet half-opening angle of ~2°-5°, and a baryon load of ~10-5 - 10-6 M⊙ consistent with the expectations of the

  1. A long-lasting, single-dose nasal vaccine for Ebola: a practical armament for an outbreak with significant global impact.

    PubMed

    Jonsson-Schmunk, Kristina; Croyle, Maria A

    2015-05-01

    In response to the severity and scale of the 2014 Ebola outbreak, several experimental vaccines were granted fast-track status for clinical testing. Although they may provide long-lasting protection from Ebola, they are, in their current states, far from optimal for populations that need them the most. In this context, nasal immunization addresses the: immune response required at the mucosa where Ebola initiates infection; needs of a population in terms of cost and compliance; and potency of each platform as they contain viruses that naturally infect the respiratory tract. Understanding the attributes of nasal immunization and its application will lead to potent vaccines that can effectively end Ebola and other emerging infectious diseases in developing and industrialized countries.

  2. Acute intrastriatal injection of quinolinic acid provokes long-lasting misregulation of the cytoskeleton in the striatum, cerebral cortex and hippocampus of young rats.

    PubMed

    Pierozan, Paula; Gonçalves Fernandes, Carolina; Ferreira, Fernanda; Pessoa-Pureur, Regina

    2014-08-19

    Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, considered to be involved in aging and some neurodegenerative disorders, including Huntington׳s disease. In the present work we have studied the long-lasting effect of acute intrastriatal injection of QUIN (150 nmol/0.5 µL) in 30 day-old rats on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits (NFL, NFM and NFH) respectively, until 21 days after injection. The acute administration of QUIN altered the homeostasis of IF phosphorylation in a selective manner, progressing from striatum to cerebral cortex and hippocampus. Twenty four hours after QUIN injection, the IFs were hyperphosphorylated in the striatum. This effect progressed to cerebral cortex causing hypophosphorylation at day 14 and appeared in the hippocampus as hyperphosphorylation at day 21 after QUIN infusion. PKA and PKCaMII have been activated in striatum and hippocampus, since Ser55 and Ser57 in NFL head domain were hyperphosphorylated. However, MAPKs (Erk1/2, JNK and p38MAPK) were hyperphosphorylated/activated only in the hippocampus, suggesting different signaling mechanisms in these two brain structures during the first weeks after QUIN infusion. Also, protein phosphatase 1 (PP1) and 2B (PP2B)-mediated hypophosphorylation of the IF proteins in the cerebral cortex 14 after QUIN injection reinforce the selective signaling mechanisms in different brain structures. Increased GFAP immunocontent in the striatum and cerebral cortex 24h and 14 days after QUIN injection respectively, suggests reactive astrocytes in these brain regions. We propose that disruption of cytoskeletal homeostasis in neural cells takes part of the long-lasting molecular mechanisms of QUIN toxicity in adolescent rats, showing selective and progressive misregulation of the signaling mechanisms targeting the IF proteins in the

  3. MHC class II tetramer analyses in AE37-vaccinated prostate cancer patients reveal vaccine-specific polyfunctional and long-lasting CD4(+) T-cells.

    PubMed

    Anastasopoulou, Eleftheria A; Voutsas, Ioannis F; Papamichail, Michael; Baxevanis, Constantin N; Perez, Sonia A

    2016-07-01

    Realizing the basis for generating long-lasting clinical responses in cancer patients after therapeutic vaccinations provides the means to further ameliorate clinical efficacy. Peptide cancer vaccines stimulating CD4(+) T helper cells are often promising for inducing immunological memory and persistent CD8(+) cytotoxic T cell responses. Recent reports from our clinical trial with the AE37 vaccine, which is a HER2 hybrid polypeptide, documented its efficacy to induce CD4(+) T cell immunity, which was associated with clinical improvements preferentially among HLA-DRB1*11(+) prostate cancer patients. Here, we performed in-depth investigation of the CD4(+) T cell response against the AE37 vaccine. We used the DR11/AE37 tetramer in combination with multicolor flow cytometry to identify and characterize AE37-specific CD4(+) T cells regarding memory and Tregs phenotype in HLA-DRB1*11(+) vaccinated patients. To verify vaccine-specific immunological memory in vivo, we also assessed AE37-specific CD4(+) T cells in defined CD4(+) memory subsets by cell sorting. Finally, vaccine-induced AE37-specific CD4(+) T cells were assessed regarding their functional profile. AE37-specific memory CD4(+) T cells could be detected in peptide-stimulated cultures from prostate cancer patients following vaccination even 4 y post-vaccination. The vast majority of vaccine-induced AE37-specific CD4(+) T cells exhibited a multifunctional, mostly Th1 cytokine signature, with the potential of granzyme B production. In contrast, we found relatively low frequencies of Tregs among AE37-specific CD4(+) T cells. This is the first report on the identification of vaccine-induced HER2-specific multifunctional long-lasting CD4(+) T cells in vaccinated prostate cancer patients.

  4. Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

    SciTech Connect

    Axelstad, Marta Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Soren Peter; Hougaard, Karin Sorig; Hass, Ulla

    2008-10-01

    Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T{sub 4}) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T{sub 4} during development. This supports the hypothesis that decreased T{sub 4} may be a relevant predictor for long-lasting developmental neurotoxicity.

  5. Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

    PubMed Central

    Cupertino, Marli C; Costa, Kyvia L C; Santos, Daiane C M; Novaes, Rômulo D; Condessa, Suellen S; Neves, Ana C; Oliveira, Juraci A; Matta, Sérgio L P

    2013-01-01

    Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis. PMID:24020407

  6. Epigenetic Influences on Brain Development and Plasticity

    PubMed Central

    Fagiolini, Michela; Jensen, Catherine L.; Champagne, Frances A.

    2009-01-01

    A fine interplay exists between sensory experience and innate genetic programs leading to the sculpting of neuronal circuits during early brain development. Recent evidence suggests that the dynamic regulation of gene expression through epigenetic mechanisms is at the interface between environmental stimuli and long-lasting molecular, cellular and complex behavioral phenotypes acquired during periods of developmental plasticity. Understanding these mechanisms may give insight into the formation of critical periods and provide new strategies for increasing plasticity and adaptive change in adulthood. PMID:19545993

  7. Long-lasting control of Anopheles arabiensis by a single spray application of micro-encapsulated pirimiphos-methyl (Actellic® 300 CS)

    PubMed Central

    2014-01-01

    performance of p-methyl CS was consistent in bioassays and experimental huts. The CS outperformed the EC in laboratory and hut bioassays but the EC longevity in huts was unexpected. Long-lasting p-methyl CS formulations should be more effective than both p-methyl EC and bendiocarb considering a single spray could be sufficient for annual malaria control. IRS with p-methyl 300 CS is a timely addition to the limited portfolio of long-lasting residual insecticides. PMID:24476070

  8. Over-the-scope-clip closure of long lasting gastrocutaneous fistula after percutaneous endoscopic gastrostomy tube removal in immunocompromised patients: A single center case series.

    PubMed

    Heinrich, Henriette; Gubler, Christoph; Valli, Piero V

    2017-02-16

    Over-the-scope-clips (OTSC(®)) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC(®) treatment have grown in number and also include gastro cutaneous fistula (GCF) after percutaneous endoscopic gastrostomy (PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC(®) closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC(®) closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism (cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5 (21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d (range 144-850 d). The intervention was well tolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC(®) closure of long lasting GCF in five consecutive middle-aged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC(®) was achieved in all

  9. Synthetic sex pheromone in a long-lasting lure attracts the visceral leishmaniasis vector, Lutzomyia longipalpis, for up to 12 weeks in Brazil.

    PubMed

    Bray, Daniel P; Carter, Vicky; Alves, Graziella B; Brazil, Reginaldo P; Bandi, Krishna K; Hamilton, James G C

    2014-03-01

    Current control methodologies have not prevented the spread of visceral leishmaniasis (VL) across Brazil. Here, we describe the development of a new tool for controlling the sand fly vector of the disease: a long-lasting lure, which releases a synthetic male sex pheromone, attractive to both sexes of Lutzomyia longipalpis. This device could be used to improve the effectiveness of residual insecticide spraying as a means of sand fly control, attracting L. longipalpis to insecticide-treated animal houses, where they could be killed in potentially large numbers over a number of weeks. Different lure designs releasing the synthetic pheromone (±)-9-methylgermacrene-B (CAS 183158-38-5) were field-tested in Araçatuba, São Paulo (SP). Experiments compared numbers of sand flies caught overnight in experimental chicken sheds with pheromone lures, to numbers caught in control sheds without pheromone. Prototype lures, designed to last one night, were first used to confirm the attractiveness of the pheromone in SP, and shown to attract significantly more flies to test sheds than controls. Longer-lasting lures were tested when new, and at fortnightly intervals. Lures loaded with 1 mg of pheromone did not attract sand flies for more than two weeks. However, lures loaded with 10 mg of pheromone, with a releasing surface of 15 cm2 or 7.5 cm2, attracted female L. longipalpis for up to ten weeks, and males for up to twelve weeks. Approximately five times more sand flies were caught with 7.5 cm2 10 mg lures when first used than occurred naturally in non-experimental chicken resting sites. These results demonstrate that these lures are suitably long-lasting and attractive for use in sand fly control programmes in SP. To our knowledge, this is the first sex pheromone-based technology targeting an insect vector of a neglected human disease. Further studies should explore the general applicability of this approach for combating other insect-borne diseases.

  10. Over-the-scope-clip closure of long lasting gastrocutaneous fistula after percutaneous endoscopic gastrostomy tube removal in immunocompromised patients: A single center case series

    PubMed Central

    Heinrich, Henriette; Gubler, Christoph; Valli, Piero V

    2017-01-01

    Over-the-scope-clips (OTSC®) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC® treatment have grown in number and also include gastro cutaneous fistula (GCF) after percutaneous endoscopic gastrostomy (PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC® closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC® closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism (cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5 (21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d (range 144-850 d). The intervention was well tolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC® closure of long lasting GCF in five consecutive middle-aged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC® was achieved in all patients

  11. Plastic Surgery

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Plastic Surgery KidsHealth > For Teens > Plastic Surgery Print A ... her forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word " ...

  12. Effectiveness and feasibility of long-lasting insecticide-treated curtains and water container covers for dengue vector control in Colombia: a cluster randomised trial

    PubMed Central

    Quintero, Juliana; García-Betancourt, Tatiana; Cortés, Sebastian; García, Diana; Alcalá, Lucas; González-Uribe, Catalina; Brochero, Helena; Carrasquilla, Gabriel

    2015-01-01

    Background Long-lasting insecticide-treated net (LLIN) window and door curtains alone or in combination with LLIN water container covers were analysed regarding effectiveness in reducing dengue vector density, and feasibility of the intervention. Methods A cluster randomised trial was conducted in an urban area of Colombia comparing 10 randomly selected control and 10 intervention clusters. In control clusters, routine vector control activities were performed. The intervention delivered first, LLIN curtains (from July to August 2013) and secondly, water container covers (from October to March 2014). Cross-sectional entomological surveys were carried out at baseline (February 2013 to June 2013), 9 weeks after the first intervention (August to October 2013), and 4–6 weeks after the second intervention (March to April 2014). Results Curtains were installed in 922 households and water container covers in 303 households. The Breteau index (BI) fell from 14 to 6 in the intervention group and from 8 to 5 in the control group. The additional intervention with LLIN covers for water containers showed a significant reduction in pupae per person index (PPI) (p=0.01). In the intervention group, the PPI index showed a clear decline of 71% compared with 25% in the control group. Costs were high but options for cost savings were identified. Conclusions Short term impact evaluation indicates that the intervention package can reduce dengue vector density but sustained effect will depend on multiple factors. PMID:25604762

  13. Transient early-life forebrain corticotropin-releasing hormone elevation causes long-lasting anxiogenic and despair-like changes in mice.

    PubMed

    Kolber, Benedict J; Boyle, Maureen P; Wieczorek, Lindsay; Kelley, Crystal L; Onwuzurike, Chiamaka C; Nettles, Sabin A; Vogt, Sherri K; Muglia, Louis J

    2010-02-17

    During development, early-life stress, such as abuse or trauma, induces long-lasting changes that are linked to adult anxiety and depressive behavior. It has been postulated that altered expression of corticotropin-releasing hormone (CRH) can at least partially account for the various effects of stress on behavior. In accord with this hypothesis, evidence from pharmacological and genetic studies has indicated the capacity of differing levels of CRH activity in different brain areas to produce behavioral changes. Furthermore, stress during early life or adulthood causes an increase in CRH release in a variety of neural sites. To evaluate the temporal and spatial specificity of the effect of early-life CRH exposure on adult behavior, the tetracycline-off system was used to produce mice with forebrain-restricted inducible expression of CRH. After transient elevation of CRH during development only, behavioral testing in adult mice revealed a persistent anxiogenic and despair-like phenotype. These behavioral changes were not associated with alterations in adult circadian or stress-induced corticosterone release but were associated with changes in CRH receptor type 1 expression. Furthermore, the despair-like changes were normalized with antidepressant treatment. Overall, these studies suggest that forebrain-restricted CRH signaling during development can permanently alter stress adaptation leading to increases in maladaptive behavior in adulthood.

  14. Modeling storm-time electrodynamics of the low-latitude ionosphere thermosphere system: Can long lasting disturbance electric fields be accounted for?

    NASA Astrophysics Data System (ADS)

    Maruyama, Naomi; Sazykin, Stanislav; Spiro, Robert W.; Anderson, David; Anghel, Adela; Wolf, Richard A.; Toffoletto, Frank R.; Fuller-Rowell, Timothy J.; Codrescu, Mihail V.; Richmond, Arthur D.; Millward, George H.

    2007-07-01

    Storm-time ionospheric disturbance electric fields are studied for two large geomagnetic storms, March 31, 2001 and April 17 18, 2002, by comparing low-latitude observations of ionospheric plasma drifts with results from numerical simulations based on a combination of first-principles models. The simulation machinery combines the Rice convection model (RCM), used to calculate inner magnetospheric electric fields, and the coupled thermosphere ionosphere plasmasphere electrodynamics (CTIPe) model, driven, in part, by RCM-computed electric fields. Comparison of model results with measured or estimated low-latitude vertical drift velocities (zonal electric fields) shows that the coupled model is capable of reproducing measurements under a variety of conditions. In particular, our model results suggest, from theoretical grounds, a possibility of long-lasting penetration of magnetospheric electric fields to low latitudes during prolonged periods of enhanced convection associated with southward-directed interplanetary magnetic field, although the model probably overestimates the magnitude and duration of such penetration during extremely disturbed conditions. During periods of moderate disturbance, we found surprisingly good overall agreement between model predictions and data, with penetration electric fields accounting for early main phase changes and oscillations in low-latitude vertical drift, while the disturbance dynamo mechanism becomes increasingly important later in the modeled events. Discrepancies between the model results and the observations indicate some of the difficulties in validating these combined numerical models, and the limitations of the available experimental data.

  15. Interleukin-1 Receptor Antagonist Reduces Neonatal Lipopolysaccharide-Induced Long-Lasting Neurobehavioral Deficits and Dopaminergic Neuronal Injury in Adult Rats

    PubMed Central

    Pang, Yi; Tien, Lu-Tai; Zhu, Hobart; Shen, Juying; Wright, Camilla F.; Jones, Tembra K.; Mamoon, Samir A.; Bhatt, Abhay J.; Cai, Zhengwei; Fan, Lir-Wan

    2015-01-01

    Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure. PMID:25898410

  16. Chondromatosis of the Temporomandibular Joint as a Consequence of Persistent Long-Lasting Joint Dysfunction: Late Diagnosis of a Rare Occurrence.

    PubMed

    Paparo, Francesco; Massarelli, Mauro; Cordeschi, Riccardo; Sciannameo, Vito; Spallaccia, Fabrizio

    2016-10-01

    The authors present a rare patient of right synovial chondromatosis (SC) of the temporomandibular joint in which diagnosis was late and delay led to SC extension to the cranial base. Synovial chondromatosis is a rare benign disorder characterized by multiple cartilaginous free-floating nodules originated from the synovial membrane of large articular joints of the body. Differential diagnosis is with neoplasm and radical surgical removal is essential. The patient came to the authors' observation complaining about long-lasting temporomandibular joint dysfunction. The patient already underwent either functional or medical therapy in times without any improvement. Clinical examination showed limited mouth opening and swelling of the right preauricolar region with no signs of facial nerve palsy and without paresthesia or hearing loss. No history of recent trauma was recorded. Magnetic resonance imaging showed a mucous-like hyperintense mass with small hypointense spots inside. A preoperative computed tomography scan was performed and showed a mass extending from the superior aspect of the temporomandibular joint to the glenoid fossa, which was partially eroded. The patient underwent either open joint surgery or arthroscopy of the superior joint space and a large number of chondrocytes were removed. No complications were recorded postoperatively and the patient completely recovered after 6 months. Histology confirmed the diagnosis of synovial condromatosys of the right temporomandibular joint.

  17. Long-lasting insecticide-treated house screens and targeted treatment of productive breeding-sites for dengue vector control in Acapulco, Mexico

    PubMed Central

    Che-Mendoza, Azael; Guillermo-May, Guillermo; Herrera-Bojórquez, Josué; Barrera-Pérez, Mario; Dzul-Manzanilla, Felipe; Gutierrez-Castro, Cipriano; Arredondo-Jiménez, Juan I.; Sánchez-Tejeda, Gustavo; Vazquez-Prokopec, Gonzalo; Ranson, Hilary; Lenhart, Audrey; Sommerfeld, Johannes; McCall, Philip J.; Kroeger, Axel; Manrique-Saide, Pablo

    2015-01-01

    Background Long-lasting insecticidal net screens (LLIS) fitted to domestic windows and doors in combination with targeted treatment (TT) of the most productive Aedes aegypti breeding sites were evaluated for their impact on dengue vector indices in a cluster-randomised trial in Mexico between 2011 and 2013. Methods Sequentially over 2 years, LLIS and TT were deployed in 10 treatment clusters (100 houses/cluster) and followed up over 24 months. Cross-sectional surveys quantified infestations of adult mosquitoes, immature stages at baseline (pre-intervention) and in four post-intervention samples at 6-monthly intervals. Identical surveys were carried out in 10 control clusters that received no treatment. Results LLIS clusters had significantly lower infestations compared to control clusters at 5 and 12 months after installation, as measured by adult (male and female) and pupal-based vector indices. After addition of TT to the intervention houses in intervention clusters, indices remained significantly lower in the treated clusters until 18 (immature and adult stage indices) and 24 months (adult indices only) post-intervention. Conclusions These safe, simple affordable vector control tools were well-accepted by study participants and are potentially suitable in many regions at risk from dengue worldwide. PMID:25604761

  18. School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania

    PubMed Central

    Lalji, Shabbir; Ngondi, Jeremiah M; Thawer, Narjis G; Tembo, Autman; Mandike, Renata; Mohamed, Ally; Chacky, Frank; Mwalimu, Charles D; Greer, George; Kaspar, Naomi; Kramer, Karen; Mlay, Bertha; Issa, Kheri; Lweikiza, Jane; Mutafungwa, Anold; Nzowa, Mary; Willilo, Ritha A; Nyoni, Waziri; Dadi, David; Ramsan, Mahdi M; Reithinger, Richard; Magesa, Stephen M

    2016-01-01

    ABSTRACT Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country’s Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania. PMID:27353618

  19. Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

    PubMed Central

    Chauchet, Xavier; Hannani, Dalil; Djebali, Sophia; Laurin, David; Polack, Benoit; Marvel, Jacqueline; Buffat, Laurent; Toussaint, Bertrand; Le Gouëllec, Audrey

    2016-01-01

    Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy. PMID:28035332

  20. CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms

    PubMed Central

    Lee, Hong Kyung; Kim, Hyung Sook; Kim, Ji Sung; Kim, Yong Guk; Park, Ki Hwan; Lee, Jae Hee; Kim, Ki Hun; Chang, In Young; Bae, Sang-Cheol; Kim, Youngsoo; Hong, Jin Tae; Kehrl, John H.; Han, Sang-Bae

    2017-01-01

    Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Faslpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Faslpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Faslpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-γ production by T cells and upon transfer no longer prolonged survival of MRL.Faslpr mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC–T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL.Faslpr mice. PMID:28117437

  1. History of Illicit Stimulant Use Is Not Associated with Long-Lasting Changes in Learning of Fine Motor Skills in Humans

    PubMed Central

    Todd, Gabrielle; Pearson-Dennett, Verity; Flavel, Stanley C.; Haberfield, Miranda; Edwards, Hannah; White, Jason M.

    2016-01-01

    Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent individuals with a history of primarily methamphetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users (n = 21; 27 ± 6 yrs) and two gender-matched control groups comprising nondrug users (n = 16; 22 ± 4 yrs) and cannabis users (n = 16; 23 ± 5 yrs). Motor learning was assessed with a three-minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in individuals with a history of illicit stimulant use. PMID:26819778

  2. Stage-specific inhibition of TrkB activity leads to long-lasting and sexually dimorphic effects on body weight and hypothalamic gene expression.

    PubMed

    Byerly, Mardi S; Swanson, Roy D; Wong, G William; Blackshaw, Seth

    2013-01-01

    During development, prenatal and postnatal factors program homeostatic set points to regulate food intake and body weight in the adult. Combinations of genetic and environmental factors contribute to the development of neural circuitry that regulates whole-body energy homeostasis. Brain-derived neurotrophic factor (Bdnf) and its receptor, Tyrosine kinase receptor B (TrkB), are strong candidates for mediating the reshaping of hypothalamic neural circuitry, given their well-characterized role in the central regulation of feeding and body weight. Here, we employ a chemical-genetic approach using the TrkB(F616A/F616A) knock-in mouse model to define the critical developmental period in which TrkB inhibition contributes to increased adult fat mass. Surprisingly, transient TrkB inhibition in embryos, preweaning pups, and adults all resulted in long-lasting increases in body weight and fat content. Moreover, sex-specific differences in the effects of TrkB inhibition on both body weight and hypothalamic gene expression were observed at multiple developmental stages. Our results highlight both the importance of the Bdnf/TrkB pathway in maintaining normal body weight throughout life and the role of sex-specific differences in the organization of hypothalamic neural circuitry that regulates body weight.

  3. An observational study of material durability of three World Health Organization-recommended long-lasting insecticidal nets in eastern Chad.

    PubMed

    Allan, Richard; O'Reilly, Laura; Gilbos, Valery; Kilian, Albert

    2012-09-01

    A total of 876 nets (229 Interceptor(®), 363 Olyset(®), and 284 PermaNet(®)) were collected 14 months post-distribution of long-lasting insecticidal nets (LLINs) from 811 households of internally displaced and host communities in Dar Sila District in eastern Chad to examine their physical condition. Holes were recorded by using three hole categories (average diameter = 2, 3.5, and 15 cm) and a Proportionate Hole Index (pHI). A total of 69.5% were in poor or very poor condition. There was no significant difference in the performance between the polyester 75 denier LLINs, but they had 4.22 times the odds of having a pHI ≥ 175 (poor or very poor condition) than polyethylene 150 denier LLINs; and 39.2% were unserviceable (pHI ≥ 300) compared with only 7.7% of the polyethylene LLINs. These results provide the first comparative data on LLIN material durability to guide procurement and replacement practice, and to inform urgently needed changes in LLIN international minimum specifications and product standards.

  4. Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses

    PubMed Central

    Mohan, Teena; Berman, Zachary; Luo, Yuan; Wang, Chao; Wang, Shelly; Compans, Richard W.; Wang, Bao-Zhong

    2017-01-01

    Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups. PMID:28067290

  5. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors.

    PubMed

    Mecha, M; Feliú, A; Iñigo, P M; Mestre, L; Carrillo-Salinas, F J; Guaza, C

    2013-11-01

    Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component.

  6. Bio-efficacy, physical integrity, community usage and washing practices of mosquito nets treated with ICON MAXX long-lasting insecticidal treatment in India

    PubMed Central

    Sahu, Sudhansu Sekhar; Gunasekaran, Kasinathan; Vijayakumar, Kilakootil Narayanan; Jambulingam, Purushothaman

    2017-01-01

    BACKGROUND New brands of potential long lasting insecticide nets (LLINs) and LLIN treatment kits require field evaluation before they are used in a vector control programme. OBJECTIVES The aim of this study was to evaluate the bio-efficacy, usage, washing practice and physical integrity of nets treated with LLIN treatment kit, ICON MAXX in a phase III field trial in Odisha state, India. METHODS A total of 300 polyester nets treated with ICON MAXX and 140 polyester nets treated conventionally with lambda-cyhalothrin CS 2.5% ITNs were distributed. The bio-efficacy was evaluated with WHO cone bioassay. The chemical analysis of netting pieces was done at the beginning, after 12 and 36 months of the trial. FINDINGS After one year of distribution of nets, the bioassay showed 100% mortality on both ITNs and ICON MAXX treated nets. At 36 months, the overall pass rate was 58.8% and the mean lambda-cyhalothrin content of LLINs was 34.5 mg ai/m2, showing a loss of 44.4% of the original concentration. CONCLUSION ICON MAXX treated LLIN was found to retain bio-efficacy causing 97% knockdown of Anopheles stephensi up to 30 months and met the WHOPES criteria. However, the desired bio-efficacy was not sustained up to 36 months. PMID:28125134

  7. Luminescent properties of long lasting phosphor Ca{sub 2}MgSi{sub 2}O{sub 7}:Eu{sup 2+}

    SciTech Connect

    Gong Yu; Wang Yuhua; Jiang Ziqiang; Xu Xuhui; Li Yanqin

    2009-09-15

    Long afterglow phosphors (Ca{sub 1-x}Eu{sub x}){sub 2}MgSi{sub 2}O{sub 7} (0.002 {<=} x {<=} 0.02) were prepared by solid-state reactions under a weak reductive atmosphere. X-ray diffraction pattern, photoluminescence spectra, decay curve, afterglow spectra and thermoluminescence curves were investigated. The phosphors showed two emission peaks when they were excited by 343 nm, due to two types of Eu{sup 2+} centers existing in the Ca{sub 2}MgSi{sub 2}O{sub 7} lattice. However, only one emission peak can be found in their afterglow spectra. Energy transfer between Eu{sup 2+} ions in inequivalent sites was found. A possible mechanism was presented and discussed. The afterglow decay time of Ca{sub 1.998}MgSi{sub 2}O{sub 7}:Eu{sub 0.002} was nearly 12.5 h which means it was a good long lasting phosphor.

  8. Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression

    PubMed Central

    Pastori, Claudia; Weiser, Barbara; Barassi, Claudia; Uberti-Foppa, Caterina; Ghezzi, Silvia; Longhi, Renato; Calori, Giliola; Burger, Harold; Kemal, Kimdar; Poli, Guido; Lazzarin, Adriano; Lopalco, Lucia

    2006-01-01

    Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV+ patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs(23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4+ lymphocytes from LTNPs having anti-CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics. PMID:16522810

  9. Biting by Anopheles funestus in broad daylight after use of long-lasting insecticidal nets: a new challenge to malaria elimination

    PubMed Central

    2014-01-01

    Background Malaria control is mainly based on indoor residual spraying and insecticide-treated bed nets. The efficacy of these tools depends on the behaviour of mosquitoes, which varies by species. With resistance to insecticides, mosquitoes adapt their behaviour to ensure their survival and reproduction. The aim of this study was to assess the biting behaviour of Anopheles funestus after the implementation of long-lasting insecticidal nets (LLINs). Methods A study was conducted in Dielmo, a rural Senegalese village, after a second massive deployment of LLINs in July 2011. Adult mosquitoes were collected by human landing catch and by pyrethrum spray catch monthly between July 2011 and April 2013. Anophelines were identified by stereomicroscope and sub-species by PCR. The presence of circumsporozoite protein of Plasmodium falciparum and the blood meal origin were detected by ELISA. Results Anopheles funestus showed a behavioural change in biting activity after introduction of LLINs, remaining anthropophilic and endophilic, while adopting diurnal feeding, essentially on humans. Six times more An. funestus were captured in broad daylight than at night. Only one infected mosquito was found during day capture. The mean of day CSP rate was 1.28% while no positive An. funestus was found in night captures. Conclusion Mosquito behaviour is an essential component for assessing vectorial capacity to transmit malaria. The emergence of new behavioural patterns of mosquitoes may significantly increase the risk for malaria transmission and represents a new challenge for malaria control. Additional vector control strategies are, therefore, necessary. PMID:24678587

  10. Efficacy of Olyset® Plus, a new long-lasting insecticidal net incorporating permethrin and piperonyl-butoxide against multi-resistant malaria vectors [corrected].

    PubMed

    Pennetier, Cédric; Bouraima, Aziz; Chandre, Fabrice; Piameu, Michael; Etang, Josiane; Rossignol, Marie; Sidick, Ibrahim; Zogo, Barnabas; Lacroix, Marie-Noëlle; Yadav, Rajpal; Pigeon, Olivier; Corbel, Vincent

    2013-01-01

    Due to the rapid extension of pyrethroid resistance in malaria vectors worldwide, manufacturers are developing new vector control tools including insecticide mixtures containing at least two active ingredients with different mode of action as part of insecticide resistance management. Olyset® Plus is a new long-lasting insecticidal net (LLIN) incorporating permethrin and a synergist, piperonyl butoxide (PBO), into its fibres in order to counteract metabolic-based pyrethroid resistance of mosquitoes. In this study, we evaluated the efficacy of Olyset® Plus both in laboratory and field against susceptible and multi-resistant malaria vectors and compared with Olyset Net, which is a permethrin incorporated into polyethylene net. In laboratory, Olyset® Plus performed better than Olyset® Net against susceptible Anopheles gambiae strain with a 2-day regeneration time owing to an improved permethrin bleeding rate with the new incorporation technology. It also performed better than Olyset® Net against multiple resistant populations of An. gambiae in experimental hut trials in West Africa. Moreover, the present study showed evidence for a benefit of incorporating a synergist, PBO, with a pyrethroid insecticide into mosquito netting. These results need to be further validated in a large-scale field trial to assess the durability and acceptability of this new tool for malaria vector control.

  11. Evaluation of Polyethylene-Based Long Lasting Treated Bed Net Netprotect on Anopheles Mosquitoes, Malaria Incidence, and Net Longivity in Western Kenya

    PubMed Central

    Odhiambo, M. T. O.; Skovmand, O.; Vulule, J. M.; Kokwaro, E. D.

    2013-01-01

    We studied the effect on malaria incidence, mosquito abundance, net efficacy, net use rate, chemical analysis, and holes of a long lasting insecticide treated bed net (Netprotect) in western Kenya, 2007–2010. Nets were hung in 150 households 6 months before they were hung in a second, 2 km away. Indoor resting densities were monitored by pyrethrum spray catch and malaria cases by passive detection using clinical manifestations and rapid diagnostic test. The probability of finding An. arabiensis in the control area was 2.6 times higher than that in intervention area during the first 6 months. Human blood feeding index of Anopheles funestus declined 17%. After bed nets were hung in the second area, malaria incidence declined 25% down to the level in the first area. Incidence remained at this low level for 2 years. 90% of collected nets were efficacious after 3-year use. Deltamethrin dosage declined from 1.9 to 0.5 g/kg over 3 years. Attrition rate after 3 years was 21%. WHO hole index changed from 333 to 114 to 381 over the three years. This index summarizes the numbers of holes in size categories and multiplies with the mean hole area per category. It is very sensitive to the impact of big holes in a few nets. PMID:24194770

  12. Wash Resistance and Bioefficacy of Alpha-cypermethrin Long Lasting Impregnated Nets (LLIN-Interceptor®) against Anopheles stephensi using Tunnel Test

    PubMed Central

    Vatandoost, Hassan; Mamivandpoor, Hossein; Abai, Mohammad Reza; Shayeghi, Mansoreh; Rafi, Fatemeh; Raeisi, Ahmad; Nikpoor, Fatemeh

    2013-01-01

    Background: The Long-lasing insecticide impregnated nets (LLINs) is considered as an effective tools for malaria vector control. The aim of this study was to evaluate the residual efficacy of alpha-cypermethrin long lasting impregnated nets (LLIN-Interceptor®) against Anopheles stephensi using tunnel test. Methods: The wash-resistance of Interceptor® nets were assessed under laboratory conditions using tunnel test. Females of An. stephensi were released into the tunnel and then they were provided blood meals from guinea pigs. Bed nets were washed according to the standard procedure up to 20 times. The bioefficacy indicators such as inhibition of bloodmeal from experimental animal, knockdown, irritancy rate, survival rate, entry index and mortality were calculated. Results: It induced 90–100% mortalities in the population of An. stephensi up to 15 washes. The KT50 values reduced from 73.47 to 26.30 minutes in unwashed in comparison to one washed, respectively. The mean of mortality rate of blood-feeding inhibition and entry indexes was reached to 91.6%±2.8, 87.0±3.4 and 24.9±2.8 respectively after 20 washing. Conclusion: This net could provide a good personal protection against malaria vectors and could induce relatively high mortality, inhibit the blood-feeding as well as reduce the entry rates of female mosquitoes even after several washes. PMID:23785693

  13. Dexmedetomidine and clonidine induce long-lasting activation of the respiratory rhythm generator of neonatal mice: possible implication for critical care.

    PubMed

    Voituron, Nicolas; Hilaire, Gérard; Quintin, Luc

    2012-01-15

    Dexmedetomidine and clonidine are alpha-2 adrenoceptor agonists increasingly used in the critical care unit as sedative agents for their benzodiazepine-sparing effects and their limited depressing effect on breathing. However adverse effects on breathing have been also reported with alpha-2 adrenoceptor agonists and their central effects on the respiratory rhythm generator are poorly known. We therefore examined the effects of dexmedetomidine, clonidine, the alpha-2 adrenoceptor antagonist yohimbine and the benzodiazepine midazolam on the activity of the isolated respiratory rhythm generator of neonatal mice using medullary preparations where the respiratory rhythm generator continued to function in vitro. For the first time, we showed that 5min bath applications of dexmedetomidine or clonidine activated the respiratory rhythm generator for periods over than 30min. Second, we showed that the long-lasting effect of dexmedetomidine implicated receptors other than alpha-2 adrenoceptors as it persisted after their blockade with yohimbine. Third, we reported that 5min bath applications of the benzodiazepine midazolam significantly depressed the respiratory rhythm generator, and that this depression was prevented by pre-treatment with either dexmedetomidine or clonidine. Although further experiments are still required to identify the mechanisms through which dexmedetomidine and clonidine activate the respiratory rhythm generator, our current in vitro results in neonatal mice support the use of dexmedetomidine and clonidine in the critical care unit.

  14. Long-lasting negative ionospheric storm effects in low and middle latitudes during the recovery phase of the 17 March 2013 geomagnetic storm

    NASA Astrophysics Data System (ADS)

    Yue, Xinan; Wang, Wenbin; Lei, Jiuhou; Burns, Alan; Zhang, Yongliang; Wan, Weixing; Liu, Libo; Hu, Lianhuan; Zhao, Biqiang; Schreiner, William S.

    2016-09-01

    In this paper, an ionospheric electron density reanalysis algorithm was used to generate global optimized electron density during the 17-18 March 2013 geomagnetic storm by assimilating 10 low Earth orbit satellites based and 450 ground global navigation satellite system receiver-based total electron content into a background ionospheric model. The reanalyzed electron density could identify the large-scale ionospheric features quite well during storm time, including the storm-enhanced density, the positive ionospheric storm effect during the initial and main phases, and the negative ionospheric storm effect during the recovery phase. The simulations from the Thermosphere Ionosphere Electrodynamics General Circulation Model can reproduce similar large-scale ionospheric disturbances as seen in the reanalysis results. Both the reanalysis and simulations show long-lasting (>17 h) daytime negative storm effect over the Asia sector as well as hemispheric asymmetry during the recovery phase. Detailed analysis of the Global Ultraviolet Imager-derived O/N2 ratio and model simulations indicate that the polar ward meridional wind disturbance, the downward E × B drift disturbance and O/N2 depletion might be responsible for the negative storm effect. The hemispheric asymmetry is mainly caused by the geomagnetic field line configuration, which could cause hemispheric asymmetry in the O/N2 depletion.

  15. Long-lasting cardiovascular depression induced by acupuncture-like stimulation of the sciatic nerve in unanaesthetized rats. Effects of arousal and type of hypertension.

    PubMed

    Hoffmann, P; Thorén, P

    1986-05-01

    Prolonged low frequency stimulation of the sciatic nerve in conscious spontaneously hypertensive rats (SHR), is reported to induce a naloxone-reversible long-lasting depressor response (Yao et al. 1982a). In the present study this depressor response was compared during daytime and night-time conditions to determine whether different degrees of arousal affect this response. In addition, the effect of sciatic nerve stimulation was examined in one-clip, two-kidney renal hypertensive rats (RHR); a type of secondary hypertension which lacks the central autonomic hyper-reactivity which characterizes the SHR variant of primary hypertension. A maximal fall in blood pressure of 20 mm Hg was observed 1 h after sciatic nerve stimulation in SHR examined in daytime. We also found a significant bradycardia that lasted for 2.5 h. Neither poststimulatory depression nor bradycardia were observed in RHR examined at daytime. A short-lasting, non-significant decrease in blood pressure and heart rate was found following sciatic stimulation in SHR examined at night.

  16. Biochemical mechanisms for translational regulation in synaptic plasticity.

    PubMed

    Klann, Eric; Dever, Thomas E

    2004-12-01

    Changes in gene expression are required for long-lasting synaptic plasticity and long-term memory in both invertebrates and vertebrates. Regulation of local protein synthesis allows synapses to control synaptic strength independently of messenger RNA synthesis in the cell body. Recent reports indicate that several biochemical signalling cascades couple neurotransmitter and neurotrophin receptors to translational regulatory factors in protein synthesis-dependent forms of synaptic plasticity and memory. In this review, we highlight these translational regulatory mechanisms and the signalling pathways that govern the expression of synaptic plasticity in response to specific types of neuronal stimulation.

  17. The efficacy of long-lasting nets with declining physical integrity may be compromised in areas with high levels of pyrethroid resistance

    PubMed Central

    2013-01-01

    Background Long-lasting insecticide-treated mosquito nets (LLINs) are a primary malaria prevention strategy in sub-Saharan Africa. However, emergence of insecticide resistance threatens the effectiveness of LLINs. Methods Cross-sectional surveys of LLINs were conducted in houses of seven and four villages in Gem and Bungoma Districts in western Kenya, respectively. Condition (number and area of holes in the nets), number and species of mosquitoes resting inside them, and insecticidal activity of nets were quantified. Mosquitoes collected inside nets were allowed to lay eggs and progeny tested for susceptibility to deltamethrin and permethrin, pyrethoids commonly deployed in LLINs in western Kenya. Results In Gem, 83.3% of nets were less than three years old and 32.4% had at least one hole of any size; while in Bungoma, 92% were less than three years old and 48% had at least one hole. No anopheline and five Culex spp. mosquitoes were found resting inside nets in Gem regardless of the number and size of holes, while 552 Anopheles gambiae s.l., five Anopheles funestus s.l. and 137 Culex spp. were in nets in Bungoma. The number of mosquitoes resting inside nets increased with hole areas >50 cm in Bungoma. In WHO resistance assays, f1 offspring of samples collected in nets in Bungoma were 94 and 65% resistant to deltamethrin and permethrin, respectively. Nets from Bungoma retained strong activity against a susceptible laboratory strain, but not against f1 offspring of field-collected An. gambiae s.s. All An. gambiae s.s. samples collected in nets were homozygous for the kdr genotype L1014S. Conclusions In areas with pyrethroid resistant vectors, LLINs with modest hole areas permit mosquito entry and feeding, providing little protection against the vectors. LLIN formulations develop large holes within three years of use, diminishing their presupposed lifetime effectiveness. PMID:24156715

  18. Influence of dentin substrates to simplify wet-bonding: a leakage-free and reliable tensile strength interface for long-lasting restorations.

    PubMed

    Piemjai, Morakot; Waleepitackdej, Onusa; Nakabayashi, Nobuo

    2011-11-01

    The wet-bonding procedure can be simplified by eliminating the primer. An aqueous mixture of 1% citric acid and 1% ferric chloride (1-1) was hypothesized as providing an easier dehydratable thinner substrate to which 4-META/MMA-TBB resin can adhere reliably. The 1-1 was applied for 10 s and rinsed off with water for 10 s. Demineralized dentin under four conditions was prepared before bonding to PMMA rod using 4-META/MMA-TBB resin: air-dried 10 s (D-NP); air-dried 10 s, primed 60 s with 5% 4-META in acetone (D-P); blotted dry 10 s (W-NP); blotted dry 10 s, primed 60 s (W-P). The tensile strengths (MPa) using mini-dumbbell specimens were 4.0 ± 2.4 for D-NP, 10.6 ± 5.4 for D-P, 38.3 ± 4.4 for W-NP, and 42.9 ± 3.3 for W-P. There was no significant difference between W-NP and W-P with cohesive failure in the dentin and the cured resin. In the wet groups, the hybridized dentin was stable against both HCl and NaOCl challenges. TEM examination and a leakage tests confirmed a perfect seal with a leakage-free interface of W-NP. These results suggest that this primer-less wet-bonding is promising method to protect the underlying intact dentin and pulp, thus providing long-lasting dental treatment.

  19. A New Long-Lasting Indoor Residual Formulation of the Organophosphate Insecticide Pirimiphos Methyl for Prolonged Control of Pyrethroid-Resistant Mosquitoes: An Experimental Hut Trial in Benin

    PubMed Central

    Rowland, Mark; Boko, Pelagie; Odjo, Abibatou; Asidi, Alex; Akogbeto, Martin; N’Guessan, Raphael

    2013-01-01

    Background Indoor residual spraying (IRS) is widely used for malaria transmission control in sub-Saharan Africa. Resistance to pyrethroids in the mosquito Anopheles gambiae is a growing problem. There is an urgent need to develop long-lasting alternative insecticides to reduce selection pressure for pyrethroid resistance and to provide control with a single IRS application in countries with long transmission seasons. Methods Two capsule suspension formulations (CS) of the organophosphate pirimiphos methyl were evaluated as IRS treatments in experimental huts in an area of Benin where the mosquitoes Anopheles gambiae and Culex quinquefasciatus are resistant to pyrethroids but susceptible to organophosphates. The CS formulations were tested alongside an emulsifiable concentrate (EC) formulation of pirimiphos methyl and a CS formulation of the pyrethroid lambdacyhalothrin. Results The two CS formulations of pirimiphos methyl gave prolonged control of An. gambiae and Cx. quinquefasciatus. In cement huts application rates of 0.5 g/m2 induced high mortality of An. gambiae for almost a year: overall mortality rates 87% (95% CI 82–91%) and 92% (95% CI 88–94%). In mud huts application rates of 1 g/m2 induced high mortality of An. gambiae for 10 months: overall mortality rates 75% (95% CI 69–81%) and 76% (95% CI 68–83%). The EC formulation of pirimiphos methyl failed to control An. gambiae two months after spraying. The pyrethroid lambdacyhalothrin demonstrated prolonged residual activity in bioassay tests but failed to control pyrethroid resistant An. gambiae that entered the huts. Pirimiphos methyl CS was highly active against Culex quinquefasciatus and gave control for 10 months in cement huts and 6 months in mud huts. Conclusion Pirimiphos methyl CS (Actellic 300 CS) applied at 1 g/m2 shows great promise for providing prolonged control of pyrethroid-resistant An gambiae and for delaying pyrethroid resistance. An alternative to DDT, giving year-round transmission

  20. [A Case of Dengue Fever and Subsequent Long-lasting Depression Accompanied by Alopecia in a Japanese Traveler Returning from Bali, Indonesia].

    PubMed

    Hitani, Akihiro; Yamaya, Waka; To, Masako; Kano, Ichino; Honda-Hosono, Natsue; Takasaki, Tomohiko; Haruki, Kosuke

    2015-03-01

    Recovery from dengue fever is generally rapid and uneventful. However, recuperation is often prolonged and may be accompanied by noticeable depression. We present herein on a traveler to Indonesia who developed long-lasting depression after the classic symptoms of dengue fever such as fever, arthralgia, and macropapular rash had resolved. A previously healthy 42-year old japanese woman presented to the Travel Clinic of Seirei Yokohama Hospital with complaints of 4 days of fever, joint aches, bone pain, and a macropapular rash on her torso. She had returned from Bali 5 days previously. During her 1-week stay, one day was spent in rural, mountainous areas where she was exposed to several mosquito bites. The 1st serum sample collected 4 days after the disease onset gave positive result in the rapid dengue IgM antibody test and the rapid dengue NS1 antigen immunechromatographic test. The DENV-1 genome was detected with RT-PCR. Her 13-year old son, who had accompanied her, was also diagnosed as having dengue fever and he recovered without event. The Above-mentioned symptoms resolved within one week. However, the patient suffered from prolonged depression. She also noticed loss of hair 3 months after the disease onset Administration of a Serotonin-Noradrenalin Reuptake Inhibitor and a minor tranquillizer required to allow her requied to lead a normal life. Although she gradually felt better, it took approximately 2 years until she had recovered completely without taking any antidepressant and minor tranquillizer. It is a well-known fact in endemic countries that dengue fever could have an significant impact on the patients' mental well-being. However, it appears that physicians in non-endemic countries are not fully aware of the prolonged depression, which can occur subsequent to the acute illness. Follow-up consultations of returing travelers who have recoverd from dengu fever should be arranged to monitor their mental and emotional states closely.

  1. Long-lasting sensitization induced by repeated risperidone treatment in adolescent Sprague-Dawley rats: A possible D2 receptor mediated phenomenon?

    PubMed Central

    Zhang, Qinglin; Hu, Gang; Li, Ming

    2014-01-01

    Rationale Risperidone use in children and adolescents for the treatment of various neuropsychiatric disorders (e.g. schizophrenia, autism, disruptive behavior, etc.) has increased substantially in recent decades. However, its long-term effect on the brain and behavioral functions is not well understood. Objective The present study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response in adulthood in the conditioned avoidance response and PCP-induced hyperlocomotion tests. Methods Male adolescent Sprague-Dawley rats (postnatal days [P] 40-44 or 43-48) were first treated with risperidone (0.3, 0.5 or 1.0 mg/kg, sc) and tested in the conditioned avoidance or PCP (3.2 mg/kg, sc)-induced hyperlocomotion model daily for 5 consecutive days. After they became adults (~P 76-80), they were challenged with risperidone (0.3 mg/kg, sc) to assess their sensitivity to risperidone re-exposure. A quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test was later conducted to assess the risperidone-induced functional changes in D2 receptor. Results In the risperidone challenge test in adulthood, adult rats previously treated with risperidone in adolescence made significantly fewer avoidance responses and exhibited significantly lower PCP-induced hyperlocomotion than those previously treated with vehicle. They also appeared to be more hyperactive than the vehicle-pretreated ones in the quinpirole-induced hyperlocomotion test. Prepulse inhibition of acoustic startle or fear-induced 22 kHz ultrasonic vocalizations in adulthood was not altered by adolescence risperidone treatment. Conclusions Adolescent risperidone exposure induces a long-term increase in behavioral sensitivity to risperidone that persists into adulthood. This long-lasting change might be due to functional upregulation of D2-mediated neurotransmission. PMID:24363078

  2. Pre- and Postnatal Exposure to Moderate Levels of Ethanol Can Have Long-Lasting Effects on Hippocampal Glutamate Uptake in Adolescent Offspring

    PubMed Central

    de Souza, Daniela F.; Lopes, Fernanda M.; Leite, Marina C.; Gonçalves, Carlos-Alberto

    2015-01-01

    The developing brain is vulnerable to the effects of ethanol. Glutamate is the main mediator of excitatory signals in the brain and is probably involved in most aspects of normal brain function during development. The aim of this study was to investigate vulnerability to and the impact of ethanol toxicity on glutamate uptake signaling in adolescent rats after moderate pre and postnatal ethanol exposure. Pregnant female rats were divided into three groups and treated only with water (control), non-alcoholic beer (vehicle) or 10% (v/v) beer solution (moderate prenatal alcohol exposure—MPAE). Thirty days after birth, adolescent male offspring were submitted to hippocampal acute slice procedure. We assayed glutamate uptake and measured glutathione content and also quantified glial glutamate transporters (EAAT 1 and EAAT 2). The glutamate system vulnerability was tested with different acute ethanol doses in naïve rats and compared with the MPAE group. We also performed a (lipopolysaccharide-challenge (LPS-challenge) with all groups to test the glutamate uptake response after an insult. The MPAE group presented a decrease in glutamate uptake corroborating a decrease in glutathione (GSH) content. The reduction in GSH content suggests oxidative damage after acute ethanol exposure. The glial glutamate transporters were also altered after prenatal ethanol treatment, suggesting a disturbance in glutamate signaling. This study indicates that impairment of glutamate uptake can be dose-dependent and the glutamate system has a higher vulnerability to ethanol toxicity after moderate ethanol exposure In utero. The effects of pre- and postnatal ethanol exposure can have long-lasting impacts on the glutamate system in adolescence and potentially into adulthood. PMID:25978644

  3. Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP

    PubMed Central

    Escoffier, Jessica; Rahban, Rita; Nef, Serge; Paoloni-Giacobino, Ariane

    2017-01-01

    The endocrine disruptor bis(2-ethylhexyl) phthalate (DEHP) has been shown to exert adverse effects on the male animal reproductive system. However, its mode of action is unclear and a systematic analysis of its molecular targets is needed. In the present study, we investigated the effects of prenatal exposure to 300 mg/kg/day DEHP during a critical period for gonads differentiation to testes on male mice offspring reproductive parameters, including the genome-wide RNA expression and associated promoter methylation status in the sperm of the first filial generation. It was observed that adult male offspring displayed symptoms similar to the human testicular dysgenesis syndrome. A combination of sperm transcriptome and methylome data analysis allowed to detect a long-lasting DEHP-induced and robust promoter methylation-associated silencing of almost the entire cluster of the seminal vesicle secretory proteins and antigen genes, which are known to play a fundamental role in sperm physiology. It also resulted in the detection of a DEHP-induced promoter demethylation associated with an up-regulation of three genes apparently not relevant for sperm physiology and partially related to the immune system. As previously reported, DEHP induced an increase in mir-615 microRNA expression and a genome-wide decrease in microRNA promoter methylation. A functional analysis revealed DEHP-induced enrichments in down-regulated gene transcripts coding for peroxisome proliferator-activated receptors and tumor necrosis factor signaling pathways, and in up-regulated gene transcripts coding for calcium binding and numerous myosin proteins. All these enriched pathways and networks have been described to be associated in some way with the reproductive system. This study identifies a large new array of genes dysregulated by DEHP that may play a role in the complex system controlling the development of the male reproductive system. PMID:28085963

  4. Spinal astrocytic activation contributes to both induction and maintenance of pituitary adenylate cyclase-activating polypeptide type 1 receptor-induced long-lasting mechanical allodynia in mice

    PubMed Central

    Yokai, Masafumi; Miyata, Atsuro

    2016-01-01

    Background Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are present in the spinal dorsal horn and dorsal root ganglia, suggesting an important role of PACAP–PACAP receptors signaling system in the modulation of spinal nociceptive transmission. We have previously reported that a single intrathecal injection of PACAP or a PACAP specific (PAC1) receptor selective agonist, maxadilan, in mice induced dose-dependent aversive behaviors, which lasted more than 30 min, and suggested that the maintenance of the nociceptive behaviors was associated with the spinal astrocytic activation. Results We found that a single intrathecal administration of PACAP or maxadilan also produced long-lasting hind paw mechanical allodynia, which persisted at least 84 days without affecting thermal nociceptive threshold. In contrast, intrathecal application of vasoactive intestinal polypeptide did not change mechanical threshold, and substance P, calcitonin gene-related peptide, or N-methyl-D-aspartate induced only transient mechanical allodynia, which disappeared within 21 days. Western blot and immunohistochemical analyses with an astrocytic marker, glial fibrillary acidic protein, revealed that the spinal PAC1 receptor stimulation caused sustained astrocytic activation, which also lasted more than 84 days. Intrathecal co-administration of L-α-aminoadipate, an astroglial toxin, with PACAP or maxadilan almost completely prevented the induction of the mechanical allodynia. Furthermore, intrathecal treatment of L-α-aminoadipate at 84 days after the PAC1 stimulation transiently reversed the mechanical allodynia accompanied by the reduction of glial fibrillary acidic protein expression level. Conclusion Our data suggest that spinal astrocytic activation triggered by the PAC1 receptor stimulation contributes to both induction and maintenance of the long-term mechanical allodynia. PMID:27175011

  5. Genetically modified rabies virus ERA strain is safe and induces long-lasting protective immune response in dogs after oral vaccination.

    PubMed

    Shuai, Lei; Feng, Na; Wang, Xijun; Ge, Jinying; Wen, Zhiyuan; Chen, Weiye; Qin, Lide; Xia, Xianzhu; Bu, Zhigao

    2015-09-01

    Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG333E) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) were generated by reverse genetic. The recombinant virus rERAG333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12months after immunization. Dogs received oral vaccination with rERAG333E induced strong protective RABV VNA response, which lasted for over 3years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs.

  6. Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies.

    PubMed

    Hu, R L; Liu, Y; Zhang, S F; Zhang, F; Fooks, A R

    2007-07-20

    During the past decade, human rabies caused by cats has ranked the second highest in China. Several recombinant rabies vaccines have been developed for dogs. However, seldom have these vaccines been assessed or used in cats. In this trial, we report the experimental immunization of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Delta-RGP, in cats. Thirty cats were inoculated with the recombinant vaccine intramuscularly, orally and intranasally, respectively. Safety and efficacy studies were undertaken using the fluorescent antibody virus neutralization (FAVN) test and evaluated. Results showed that this recombinant vaccine is safe for cats as demonstrated by the three different routes of administration. The vaccine stimulated an efficient humoral response in the vaccinated cats when 10(8.5)PFU/ml of the recombinant vaccine was injected intramuscularly in a single dose. The neutralizing antibody level increased above 0.5IU/ml at 4 weeks after the vaccination. The mean antibody level ranged from 0.96+/-0.26 to 4.47+/-1.57IU/ml among individuals, and the antibody levels were elicited for at least 12 months. After this period, the immunized cats survived the challenge of CVS-24 and an obvious anemnestic and protective immune response was stimulated after the challenge. The immune response occurred later than the inactivated vaccine and the overall antibody level in the vaccinated cats was lower, but it was sufficient to confer protection of cats against infection. This demonstrated that a single, intramuscular dose of CAV-2-E3Delta-RGP stimulated a long-lasting protective immune response in cats and suggested that CAV-2-E3Delta-RGP could be considered as a potential rabies vaccine candidate for cats.

  7. Syn-collisional granitoids in the Qilian Block on the Northern Tibetan Plateau: A long-lasting magmatism since continental collision through slab steepening

    NASA Astrophysics Data System (ADS)

    Huang, Hui; Niu, Yaoling; Mo, Xuanxue

    2016-03-01

    In this paper we present a new model that can explain the large zircon age spectrum of 510 - 420 Ma within a single sample from the Gangcha (Gcha) biotite granodiorite and the Huangyuan (HY) two-mica monzogranite on the northern Tibetan Plateau. The large age spread recorded in zircons is characteristic of granitoid samples from the studied region, which is best explained by the long-lasting magmatism since the onset of continental collision at 500 Ma, followed by slab steepening and the ultimate slab break-off at 450 Ma. These granitoids have a large major and trace element compositional variation, but limited initial Sr (ISr[450] = 0.709 to 0.715), Nd (ԐNd[450] = - 6.5 to - 3.7), Hf (ԐHf[450] = - 4.3 to 1.5) and Pb (206Pb/204Pb[450] = 17.70 to 17.17; 207Pb/204Pb[450] = 15.60 to 15.69; 208Pb/204Pb[450] = 38.04 to 38.73) isotopic variation. The small negative whole rock ԐNd[450] and ԐHf[450] values are most consistent with the granitoid source being dominated by subducted seafloor materials. The inherited zircons with large negative ԐHf[450] values (e.g. - 50) are indicative of input from the lower continental crust and subducted sediments. The correlated variations among major elements, trace elements and radiogenic isotopes are best interpreted as reflecting melting-induced mixing of a compositionally heterogeneous source with superimposed effect of varying extent of fractional crystallization and crustal assimilation. The inherited zircons of Palaeo-Proterozoic age and the Archean crustal model ages signify the involvement of ancient basement rocks.

  8. Stimulation of deep somatic tissue with capsaicin produces long-lasting mechanical allodynia and heat hypoalgesia that depends on early activation of the cAMP pathway.

    PubMed

    Sluka, K A

    2002-07-01

    Pain and hyperalgesia from deep somatic tissue (i.e., muscle and joint) are processed differently from that from skin. This study examined differences between deep and cutaneous tissue allodynia and the role of cAMP in associated behavioral changes. Capsaicin was injected into the plantar aspect of the skin, plantar muscles of the paw, or ankle joint, and responses to mechanical and heat stimuli were assessed until allodynia resolved. Capsaicin injected into skin resulted in a secondary mechanical allodynia and heat hypoalgesia lasting approximately 3 hr. In contrast, capsaicin injection into muscle or joint resulted in a long-lasting bilateral (1-4 weeks) mechanical allodynia with a simultaneous unilateral heat hypoalgesia. The pattern and degree of inflammation were similar when capsaicin was injected into skin, muscle, or joint, with peak increases 24 hr after injection. Heat hypoalgesia that occurs after injection into deep tissue was reversed by spinal blockade of adenylate cyclase or protein kinase A (PKA). Interestingly, mechanical allodynia was reversed if adenylate cyclase or PKA inhibitors were administered spinally 24 hr, but not 1 week, after injection of capsaicin. Spinally administered 8-bromo-cAMP resulted in a similar pattern, with heat hypoalgesia and mechanical allodynia occurring simultaneously. Thus, injection of capsaicin into deep tissues results in a longer-lasting mechanical allodynia and heat hypoalgesia compared with injection of capsaicin into skin. The mechanical allodynia depends on early activation of the cAMP pathway during the first 24 hr but is independent of the cAMP pathway by 1 week after injection of capsaicin.

  9. Luminescence properties of tunable white-light long-lasting phosphor YPO4: Eu3+, Tb3+, Sr2+, Zr4+

    NASA Astrophysics Data System (ADS)

    Tang, Wei; Wang, Mingwen; Meng, Xiangxue; Lin, Wei

    2016-04-01

    A series of novel YPO4: Eu3+, Tb3+, Sr2+, Zr4+ tunable white-light long lasting phosphors were synthesized by conventional solid-state reaction method. The luminescent properties were systematically characterized by X-ray diffraction, photoluminescent excitation and emission spectra, thermoluminescence spectrum and decay curves. The XRD patterns indicated that the samples belonged to tetragonal phase and co-doping Eu3+, Tb3+, Sr2+ and Zr4+ ions have no effect on the basic crystal structure. Under the excitation of 372 nm wavelength, it was first discovered that the specific concentration of Sr2+ can improve the emission intensity of Eu2+. The blue (Eu2+), green (Tb3+) and red (Eu3+) lights were emitted simultaneously and therefore produced white light in the same YPO4 matrix. Tunable color from the white to purple region was achieved not only by increasing the concentration of Zr4+ and Sr2+, but also by increasing the concentration of Eu3+. The CIE chromaticity coordinates of Y0.89PO4: Eu3+0.06, Tb3+0.05, Sr2+0.06, Zr4+0.06 (0.33, 0.31) were the closest to point (0.33, 0.33) which delegates the ideal white and trap depths for the two glow peaks are 0.88 eV and 0.85 eV. The fitting decay constant of τ2 corresponding to the slow exponentially decay components was 101.30 s.

  10. Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

    PubMed

    Fuertes Marraco, Silvia A; Soneson, Charlotte; Cagnon, Laurène; Gannon, Philippe O; Allard, Mathilde; Abed Maillard, Samia; Montandon, Nicole; Rufer, Nathalie; Waldvogel, Sophie; Delorenzi, Mauro; Speiser, Daniel E

    2015-04-08

    Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans.

  11. The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats

    PubMed Central

    Zheng, Qingshan; Yang, Xiaolin; Lv, Rong; Ma, Longxiang; Liu, Jin; Zhu, Tao; Zhang, Wensheng

    2017-01-01

    Objective The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination. Methods QX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10). Rats were inspected for durations of effective sensory and motor nerve blocks, systemic adverse effects, and histological changes of local tissues. Mathematical models were established to reveal drug-interaction, concentration-effect relationships, and the optimal ratio of QX-314 to bupivacaine. Results 0.2~1.5% QX-314 with 0.03~0.5% bupivacaine produced 5.8~23.8 h of effective nerve block; while 0.5% bupivacaine alone was effective for 4 h. No systemic side effects were observed; local tissue reactions were similar to those caused by 0.5% bupivacaine if QX-314 were used < 1.2%. The weighted modification model was successfully established, which revealed that QX-314 was the main active ingredient while bupivacaine was the synergist. The formulation, 0.9% QX-314 plus 0.5% bupivacaine, resulted in 10.1 ± 0.8 h of effective sensory and motor nerve blocks. Conclusion The combination of QX-314 and bupivacaine facilitated prolonged sciatic nerve block in rats with a satisfactory safety profile, maximizing the duration of nerve block without clinically important systemic and local tissue toxicity. It may emerge as an alternative approach to post-operative pain treatment. PMID:28334014

  12. Effects of benidipine, a long-lasting dihydropyridine-Ca2+ channel blocker, on cerebral blood flow autoregulation in spontaneously hypertensive rats.

    PubMed

    Ikeda, Jun-ichi; Yao, Kozo; Matsubara, Masahiro

    2006-11-01

    Chronic hypertension shifts cerebral blood flow (CBF) autoregulation towards higher blood pressure. We examined whether or not benidipine, a long-lasting dihydropyridine calcium channel blocker (CCB), improves the CBF autoregulation in spontaneously hypertensive rats (SHRs). CBF was analyzed by laser-Doppler flowmetry during stepwise hypotension by controlled bleeding. The lower limit of CBF autoregulation was calculated as the mean arterial blood pressure at which CBF decreased by 10% of the baseline. Mean arterial blood pressure and cerebral vascular resistance in SHRs were higher than those in normotensive Wistar rats. Oral administration of benidipine (3 mg/kg) for 8 d lowered the mean arterial blood pressure and cerebral vascular resistance, which were equivalent to the effects of amlodipine (3 mg/kg), another CCB, or candesartan (1 mg/kg), an Angiotensin II type-1 receptor blocker. The lower limit of CBF autoregulation in SHRs (142+/-4 mmHg) was significantly shifted to a higher-pressure level compared with Wistar rats (59+/-2 mmHg). The lower limit of CBF autoregulation was significantly lower in the benidipine-treated group (91+/-4 mmHg) than that in the control SHRs, and similar to that of the amlodipine group (97+/-6 mmHg). Benidipine reduced the lower limit of CBF autoregulation more effectively than candesartan (109+/-4 mmHg). In conclusion, benidipine shifted the limit of CBF autoregulation towards lower blood pressure in SHRs under hypotensive conditions by hemorrhage. These results suggest that benidipine may be useful for the treatment of hypertensive patients with the elderly or cerebrovascular disorders, in whom autoregulation of CBF is impaired.

  13. Enhancement of long-lasting immunoprotective effect against Androctonus australis hector envenomation using safe antigens: Comparative role of MF59 and Alum adjuvants.

    PubMed

    Nouri, Abdelmounaim; Laraba-Djebari, Fatima

    2015-10-26

    Envenomation is a public health problem in many regions of the world. The only available treatment is the serotherapy that has limited efficiency due to the delay of its administration. The goal of this study is to provide a new and more efficient alternative to this treatment. A comparative study of the effects of two adjuvants in their ability to enhance the efficiency of the detoxified and safe antigens to produce a long lasting immunoprotection is undertaken using Aluminum Hydroxide adjuvant (Alum) or the water-in-oil MF59 adjuvant mixed with Androctonus australis hector (Aah) detoxified venom, and compare their effects on the immune system. Immunization schedule was performed with two groups of rabbits, which were injected with attenuated venom and Alum or MF59 adjuvant preparations, once a month during three months. Blood samples were collected each week for cell count, evaluation of myeloperoxidase (MPO) and eosinoperoxydase (EPO) activities and antibody titer. After four months from the last immunization, rabbits were challenged with increased doses of native Aah venom. Results showed that MF59 effect was immediate in the first 24h post-immunization by activating the recruitment of lymphocytes, monocytes and neutrophils, while Alum adjuvant effect seems to be delayed, and appeared in the second week after immunization. An important cell infiltration was observed with Alum preparation, due to its specific local depot effect. However, immunized animals with MF59 preparation challenged with the native venom showed a protective effect against its toxicity until 6 LD50 compared to those immunized with Alum preparation which are only protected at 4 LD50. One week after challenge, only immunized animals with Alum preparation present an increase in cell infiltration, MPO and EPO activities. These results are correlated with the ability of MF59 adjuvant to induce a potent immunoprotective effect against Aah venom compared to Alum adjuvant.

  14. Reconstruction of total grain size distribution of the climactic phase of a long-lasting eruption: the example of the 2008-2013 Chaitén eruption

    NASA Astrophysics Data System (ADS)

    Alfano, Fabrizio; Bonadonna, Costanza; Watt, Sebastian; Connor, Chuck; Volentik, Alain; Pyle, David M.

    2016-07-01

    The 2008-2013 eruption of Chaitén Volcano (Chile) was a long-lasting eruption whose climactic phase (May 6, 2008) produced a sub-Plinian plume, with height ranging between 14 and 20 km that dispersed to the NE, reaching the Atlantic coast of Argentina. The erupted material was mainly of lithic origin (˜77 wt%), resulting in a unimodal total grain size distribution (TGSD) dominated by coarse ash (77 wt%), with Mdϕ of 2.7 and σϕ of 2.4. Lapilli clasts (>2 mm) dominate the proximal deposit within ~20 km of the vent, while coarse (63 μm-2 mm) and fine ash (<63 μm) sedimented as far as 800 km from vent, generating mostly poly-modal grain size distributions across the entire deposit. Given that most of the mass is sedimented in proximal areas, results show that possible contributions of later explosive events to the thickness of the distal deposit where layers are less distinguishable (>400 km) do not significantly affect the determination of the TGSD. In contrast, gaps in data sampling in the medial deposit (in particular the gap between 50 and 350 km from vent that coincides with shifts in sedimentation regimes) have large impacts on estimates of TGSD. Particle number distribution for this deposit is characterized by a high power-law exponent (3.0) following a trend very similar to the vesicle size distribution in the juvenile pyroclasts. Although this could be taken to indicate a bubble-driven fragmentation process, we suggest that fragmentation was more likely the result of a shear-driven process because of the predominance of non-vesicular products (lithics and obsidians) and the large fraction of coarse ash in the TGSD.

  15. Multipoint spacecraft observations of long-lasting poloidal Pc4 pulsations in the dayside magnetosphere on 1-2 May 2014

    NASA Astrophysics Data System (ADS)

    Korotova, Galina; Sibeck, David; Engebretson, Mark; Wygant, John; Thaller, Scott; Spence, Harlan; Kletzing, Craig; Angelopoulos, Vassilis; Redmon, Robert

    2016-11-01

    We use magnetic field and plasma observations from the Van Allen Probes, Time History of Events and Macroscale Interactions during Substorms (THEMIS) and Geostationary Operational Environmental Satellite system (GOES) spacecraft to study the spatial and temporal characteristics of long-lasting poloidal Pc4 pulsations in the dayside magnetosphere. The pulsations were observed after the main phase of a moderate storm during low geomagnetic activity. The pulsations occurred during various interplanetary conditions and the solar wind parameters do not seem to control the occurrence of the pulsations. The most striking feature of the Pc4 magnetic field pulsations was their occurrence at similar locations during three of four successive orbits. We used this information to study the latitudinal nodal structure of the pulsations and demonstrated that the latitudinal extent of the magnetic field pulsations did not exceed 2 Earth radii (RE). A phase shift between the azimuthal and radial components of the electric and magnetic fields was observed from ZSM = 0.30 RE to ZSM = -0.16 RE. We used magnetic and electric field data from Van Allen Probes to determine the structure of ULF waves. We showed that the Pc4 magnetic field pulsations were radially polarized and are the second-mode harmonic waves. We suggest that the spacecraft were near a magnetic field null during the second orbit when they failed to observe the magnetic field pulsations at the local times where pulsations were observed on previous and successive orbits. We investigated the spectral structure of the Pc4 pulsations. Each spacecraft observed a decrease of the dominant period as it moved to a smaller L shell (stronger magnetic field strength). We demonstrated that higher frequencies occurred at times and locations where Alfvén velocities were greater, i.e., on Orbit 1. There is some evidence that the periods of the pulsations increased during the plasmasphere refilling following the storm.

  16. Luminescence properties of long-lasting phosphor SrMg2(PO4)2:Eu2+, Ho3+, Zr4+

    NASA Astrophysics Data System (ADS)

    Tang, Wei; Wang, Mingwen; Lin, Wei; Ye, Yaping; Wu, Xue

    2016-12-01

    Novel long lasting phosphors SrMg2(PO4)2:Eu2+, SrMg2(PO4)2:Eu2+, Zr4+, SrMg2(PO4)2:Eu2+, Ho3+ and SrMg2(PO4)2:Eu2+, Ho3+, Zr4+ were synthesized by conventional solid-state reaction method. The luminescent properties were systematically characterized by X-ray diffraction, photoluminescent excitation and emission spectra, as well as thermoluminescence spectrum and decay curves. The XRD patterns indicated that the samples belonged to monoclinic phase and co-doping Eu2+, Ho3+ and Zr4+ ions had no effect on the basic crystal structure. These phosphors emitting purplish blue light is related to the characteristic emission of Eu2+. The afterglow time of Eu2+ activated SrMg2(PO4)2 can be greatly enhanced by the co-doping of Ho3+, Zr4+. After the 365 nm UV light excitation source switching off, the Sr0.92Mg1.95(PO4)2:Eu2+0.01, Zr4+0.05, Ho3+0.07 phosphorescence can be observed for more than 1013 s in the limit of light perception of dark-adapted human eyes (0.32 mcd/m2). Different kinds of TL peaks at 423, 448 and 473 K have appeared, and traps densities have increased compared with the Eu2+ single doped SrMg2(PO4)2 phosphor. By analyzing the TL curve the depths of traps were calculated to be 0.846, 0.896 and 0.946 eV, respectively, which suggested that the co-doping of Ho3+, Zr4+ improved the electron storage ability of material. Besides, the mechanism was discussed in this report.

  17. Pre- and postnatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal glutamate uptake in adolescent offspring.

    PubMed

    Brolese, Giovana; Lunardi, Paula; de Souza, Daniela F; Lopes, Fernanda M; Leite, Marina C; Gonçalves, Carlos-Alberto

    2015-01-01

    The developing brain is vulnerable to the effects of ethanol. Glutamate is the main mediator of excitatory signals in the brain and is probably involved in most aspects of normal brain function during development. The aim of this study was to investigate vulnerability to and the impact of ethanol toxicity on glutamate uptake signaling in adolescent rats after moderate pre and postnatal ethanol exposure. Pregnant female rats were divided into three groups and treated only with water (control), non-alcoholic beer (vehicle) or 10% (v/v) beer solution (moderate prenatal alcohol exposure-MPAE). Thirty days after birth, adolescent male offspring were submitted to hippocampal acute slice procedure. We assayed glutamate uptake and measured glutathione content and also quantified glial glutamate transporters (EAAT 1 and EAAT 2). The glutamate system vulnerability was tested with different acute ethanol doses in naïve rats and compared with the MPAE group. We also performed a (lipopolysaccharide-challenge (LPS-challenge) with all groups to test the glutamate uptake response after an insult. The MPAE group presented a decrease in glutamate uptake corroborating a decrease in glutathione (GSH) content. The reduction in GSH content suggests oxidative damage after acute ethanol exposure. The glial glutamate transporters were also altered after prenatal ethanol treatment, suggesting a disturbance in glutamate signaling. This study indicates that impairment of glutamate uptake can be dose-dependent and the glutamate system has a higher vulnerability to ethanol toxicity after moderate ethanol exposure In utero. The effects of pre- and postnatal ethanol exposure can have long-lasting impacts on the glutamate system in adolescence and potentially into adulthood.

  18. Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP.

    PubMed

    Stenz, Ludwig; Escoffier, Jessica; Rahban, Rita; Nef, Serge; Paoloni-Giacobino, Ariane

    2017-01-01

    The endocrine disruptor bis(2-ethylhexyl) phthalate (DEHP) has been shown to exert adverse effects on the male animal reproductive system. However, its mode of action is unclear and a systematic analysis of its molecular targets is needed. In the present study, we investigated the effects of prenatal exposure to 300 mg/kg/day DEHP during a critical period for gonads differentiation to testes on male mice offspring reproductive parameters, including the genome-wide RNA expression and associated promoter methylation status in the sperm of the first filial generation. It was observed that adult male offspring displayed symptoms similar to the human testicular dysgenesis syndrome. A combination of sperm transcriptome and methylome data analysis allowed to detect a long-lasting DEHP-induced and robust promoter methylation-associated silencing of almost the entire cluster of the seminal vesicle secretory proteins and antigen genes, which are known to play a fundamental role in sperm physiology. It also resulted in the detection of a DEHP-induced promoter demethylation associated with an up-regulation of three genes apparently not relevant for sperm physiology and partially related to the immune system. As previously reported, DEHP induced an increase in mir-615 microRNA expression and a genome-wide decrease in microRNA promoter methylation. A functional analysis revealed DEHP-induced enrichments in down-regulated gene transcripts coding for peroxisome proliferator-activated receptors and tumor necrosis factor signaling pathways, and in up-regulated gene transcripts coding for calcium binding and numerous myosin proteins. All these enriched pathways and networks have been described to be associated in some way with the reproductive system. This study identifies a large new array of genes dysregulated by DEHP that may play a role in the complex system controlling the development of the male reproductive system.

  19. Long-lasting effects of maternal separation on an animal model of post-traumatic stress disorder: effects on memory and hippocampal oxidative stress.

    PubMed

    Diehl, Luisa A; Alvares, Lucas O; Noschang, Cristie; Engelke, Douglas; Andreazza, Ana C; Gonçalves, Carlos Alberto S; Quillfeldt, Jorge A; Dalmaz, Carla

    2012-04-01

    Adverse early life events, such as periodic maternal separation, may alter the normal pattern of brain development and subsequently the vulnerability to a variety of mental disorders in adulthood. Patients with a history of early adversities show higher frequency of post-traumatic stress disorder (PTSD). This study was undertaken to verify if repeated long-term separation of pups from dams would affect memory and oxidative stress parameters after exposure to an animal model of PTSD. Nests of Wistar rats were divided into intact and subjected to maternal separation (incubator at 32°C, 3 h/day) during post-natal days 1-10. When adults, the animals were subdivided into exposed or not to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. One month after exposure to the shock, the animals were exposed to a memory task (Morris water maze) and another month later animals were sacrificed and DNA breaks and antioxidant enzymes activities were measured in the hippocampus. Rats exposed to shock or maternal separation plus shock showed long-lasting effects on spatial memory, spending more time in the opposite quadrant of the water maze. This effect was higher in animals subjected to both maternal separation and shock. Both shock and maternal separation induced a higher score of DNA breaks in the hippocampus. No differences were observed on antioxidant enzymes activities. In conclusion, periodic maternal separation may increase the susceptibility to the effects of a stressor applied in adulthood on performance in the water maze. Increased DNA breaks in hippocampus was induced by both, maternal separation and exposure to shock.

  20. TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus.

    PubMed

    Yu, Shaoyong; Gao, Guofeng; Peterson, Blaise Z; Ouyang, Ann

    2009-07-01

    Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. Mast cell tryptase via protease-activated receptor 2 (PAR2)-mediated pathways sensitizes sensory nerves and induces hyperalgesia. Transient receptor potential A1 (TRPA1) plays an important role in mechanosensory transduction and nociception. Here we tested the hypothesis that mast cell activation via a PAR2-dependent mechanism sensitizes TRPA1 to induce mechanical hypersensitivity in esophageal vagal C-fibers. The expression profiles of PAR2 and TRPA1 in vagal nodose ganglia were determined by immunostaining, Western blot, and RT-PCR. Extracellular recordings from esophageal nodose neurons were performed in ex vivo guinea pig esophageal-vagal preparations. Action potentials evoked by esophageal distention and chemical perfusion were compared. Both PAR2 and TRPA1 expressions were identified in vagal nodose neurons by immunostaining, Western blot, and RT-PCR. Ninety-one percent of TRPA1-positive neurons were of small and medium diameters, and 80% coexpressed PAR2. Esophageal mast cell activation significantly enhanced the response of nodose C-fibers to esophageal distension (mechanical hypersensitivity). This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activation-induced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus.

  1. Social Determinants of Long Lasting Insecticidal Hammock-Use Among the Ra-Glai Ethnic Minority in Vietnam: Implications for Forest Malaria Control

    PubMed Central

    Muela Ribera, Joan; Ngo Duc, Thang; van Bortel, Wim; Truong Ba, Nhat; Van, Ky Pham; Le Xuan, Hung; D'Alessandro, Umberto; Erhart, Annette

    2012-01-01

    Background Long-lasting insecticidal hammocks (LLIHs) are being evaluated as an additional malaria prevention tool in settings where standard control strategies have a limited impact. This is the case among the Ra-glai ethnic minority communities of Ninh Thuan, one of the forested and mountainous provinces of Central Vietnam where malaria morbidity persist due to the sylvatic nature of the main malaria vector An. dirus and the dependence of the population on the forest for subsistence - as is the case for many impoverished ethnic minorities in Southeast Asia. Methods A social science study was carried out ancillary to a community-based cluster randomized trial on the effectiveness of LLIHs to control forest malaria. The social science research strategy consisted of a mixed methods study triangulating qualitative data from focused ethnography and quantitative data collected during a malariometric cross-sectional survey on a random sample of 2,045 study participants. Results To meet work requirements during the labor intensive malaria transmission and rainy season, Ra-glai slash and burn farmers combine living in government supported villages along the road with a second home at their fields located in the forest. LLIH use was evaluated in both locations. During daytime, LLIH use at village level was reported by 69.3% of all respondents, and in forest fields this was 73.2%. In the evening, 54.1% used the LLIHs in the villages, while at the fields this was 20.7%. At night, LLIH use was minimal, regardless of the location (village 4.4%; forest 6.4%). Discussion Despite the free distribution of insecticide-treated nets (ITNs) and LLIHs, around half the local population remains largely unprotected when sleeping in their forest plot huts. In order to tackle forest malaria more effectively, control policies should explicitly target forest fields where ethnic minority farmers are more vulnerable to malaria. PMID:22253852

  2. Long-lasting distortion of GABA signaling in MS/DB neurons after binge-like ethanol exposure during initial synaptogenesis

    PubMed Central

    Wang, Haiying; DuBois, Dustin W.; Tobery, Angelika N.; Griffith, William H.; Brandt, Paul; Frye, Gerald D.

    2013-01-01

    Using a well-established model of binge-like ethanol treatment of rat pups on postnatal days (PD) 4–9, we found that maturation of GABAA receptor (GABAAR) miniature postsynaptic currents (mPSCs) was substantially blunted for medial septum/diagonal band (MS/DB) neurons in brain slices on PD 11–16. Ethanol reduced mPSC amplitude, frequency, and decay kinetics, while attenuating or exaggerating allosteric actions of zolpidem and allopregnanolone, respectively. The impact of ethanol in vivo was long lasting as most changes in MS/DB GABAAR mPSCs were still observed as late as PD 60–85. Maturing MS/DB neurons in naïve brain slices PD 4–16 showed increasing mPSC frequency, decay kinetics, and zolpidem sensitivity that were nearly identical to our earlier findings in cultured septal neurons [17, 18]. These rapidly developing mPSC parameters continued to mature through the first month of life then stabilized throughout the remainder of the lifespan. Finally, equivalent ethanol-induced alterations in GABAAR mPSC signaling were present in MS/DB neurons from both male and female animals. Previously, we showed ethanol treatment of cultured embryonic day 20 septal neurons distorts the maturation of GABAAR mPSCs predicting that early stages of GABAergic transmission in MS/DB neurons are vulnerable to intoxication injury [17, 18]. Since the overall character, timing, and magnitude of GABAergic mPSC developmental- and ethanol-induced changes in the in vivo model so closely mirror chronologically equivalent adaptations in cultured septal neurons, this suggests that such parallel models of ethanol impairment of GABAergic synaptic development in vivo and in vitro should be useful for translational studies exploring the efficacy and mechanism of action of potential therapeutic interventions from the cellular to whole animal level. PMID:23685190

  3. Review of the partitioning of chemicals into different plastics: Consequences for the risk assessment of marine plastic debris.

    PubMed

    O'Connor, Isabel A; Golsteijn, Laura; Hendriks, A Jan

    2016-12-15

    Marine plastic debris are found worldwide in oceans and coastal areas. They degrade only slowly and contain chemicals added during manufacture or absorbed from the seawater. Therefore, they can pose a long-lasting contaminant source and potentially transfer chemicals to marine organisms when ingested. In order to assess their risk, the contaminant concentration in the plastics needs to be estimated and differences understood. We collected from literature plastic water partition coefficients of various organic chemicals for seven plastic types: polydimethylsiloxane (PDMS), high-density, low-density and ultra-high molecular weight polyethylene (LDPE, HDPE, UHMWPE), polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC). Most data was available for PDMS (1060) and LDPE (220), but much less for the remaining plastics (73). Where possible, regression models were developed and the partitioning was compared between the different plastic types. The partitioning of chemicals follows the order of LDPE≈HDPE≥PP>PVC≈PS. Data describing the impact of weathering are urgently needed.

  4. Evaluation of the long-lasting insecticidal net Interceptor LN: laboratory and experimental hut studies against anopheline and culicine mosquitoes in northeastern Tanzania

    PubMed Central

    2013-01-01

    Background Long lasting insecticidal nets (LN) are a primary method of malaria prevention. Before new types of LN are approved they need to meet quality and efficacy standards set by the WHO Pesticide Evaluation Scheme. The process of evaluation has three phases. In Phase I the candidate LN must meet threshold bioassay criteria after 20 standardized washes. In Phase II washed and unwashed LNs are evaluated in experimental huts against wild, free flying anopheline mosquitoes. In Phase III the LN are distributed to households in malaria endemic areas, sampled over three years of use and tested for continuing insecticidal efficacy. Interceptor® LN (BASF Corporation, Germany) is made of polyester netting coated with a wash resistant formulation of alpha-cypermethrin. Methods Interceptor LN was subjected to bioassay evaluation and then to experimental hut trial against pyrethroid-susceptible Anopheles gambiae and An. funestus and resistant Culex quinquefasciatus. Mosquito mortality, blood feeding inhibition and personal protection were compared between untreated nets, conventional alpha-cypermethrin treated nets (CTN) washed 20 times and LNs washed 0, 20 and 30 times. Results In Phase I Interceptor LN demonstrated superior wash resistance and efficacy to the CTN. In the Phase II hut trial the LN killed 92% of female An. gambiae when unwashed and 76% when washed 20 times; the CTN washed 20 times killed 44%. The LN out-performed the CTN in personal protection and blood-feeding inhibition. The trend for An. funestus was similar to An. gambiae for all outcomes. Few pyrethroid-resistant Cx. quinquefasciatus were killed and yet the level of personal protection (75-90%) against Culex was similar to that of susceptible An. gambiae (76-80%) even after 20 washes. This protection is relevant because Cx. quinquefasciatus is a vector of lymphatic filariasis in East Africa. After 20 washes and 60 nights’ use the LN retained 27% of its initial insecticide dose. Conclusions

  5. Transmission of malaria in relation to distribution and coverage of long-lasting insecticidal nets in central Côte d’Ivoire

    PubMed Central

    2014-01-01

    Background The use of long-lasting insecticidal nets (LLINs) is an effective malaria control strategy. However, there are challenges to achieve high coverage, such as distribution sustainability, and coverage keep-up. This study assessed the effect of LLINs coverage and contextual factors on entomological indicators of malaria in rural Côte d’Ivoire. Methods The study was carried out between July 2009 and May 2012 in three villages (Bozi, N’Dakonankro and Yoho) of central Côte d’Ivoire. In Bozi and Yoho, LLINs were distributed free of charge by the national malaria control programme in 2008. In Bozi, an additional distribution was carried out in May 2011. No specific interventions were done in N’Dakonankro. Entomological surveys were conducted in July 2009 and July 2010 (baseline), and in August and November 2011 and in February 2012. Frequency of circumsporozoite protein was determined using an enzyme-linked immunosorbent assay. Regression models were employed to assess the impact of LLINs and changing patterns of irrigated rice farming on entomological parameters, and to determine associations with LLINs coverage and other contextual factors. Results In Bozi, high proportion of LLIN usage was observed (95-100%). After six months, 95% of LLINs were washed at least once and 79% were washed up to three times within one year. Anopheles gambiae was the predominant malaria vector (66.6% of all mosquitoes caught). From 2009 to 2012, in N’Dakonankro, the mean annual entomological inoculation rate (EIR) increased significantly from 116.8 infectious bites/human/year (ib/h/y) to 408.8 ib/h/y, while in the intervention villages, the EIR decreased significantly from 514.6 ib/h/y to 62.0 ib/h/y (Bozi) and from 83.9 ib/h/y to 25.5 ib/h/y (Yoho). The risk of an infectious bite over the three-year period was significantly lower in the intervention villages compared to the control village (p <0.001). Conclusion High coverage and sensitization of households to use

  6. Success of Senegal's first nationwide distribution of long-lasting insecticide-treated nets to children under five - contribution toward universal coverage

    PubMed Central

    2011-01-01

    Background In 2009, the first national long-lasting insecticide-treated net (LLIN) distribution campaign in Senegal resulted in the distribution of 2.2 million LLINs in two phases to children aged 6-59 months. Door-to-door teams visited all households to administer vitamin A and mebendazole, and to give a coupon to redeem later for an LLIN. Methods A nationwide community-based two-stage cluster survey was conducted, with clusters selected within regions by probability proportional to size sampling, followed by GPS-assisted mapping, simple random selection of households in each cluster, and administration of a questionnaire using personal digital assistants (PDAs). The questionnaire followed the Malaria Indicator Survey format, with rosters of household members and bed nets, and questions on campaign participation. Results There were 3,280 households in 112 clusters representing 33,993 people. Most (92.1%) guardians of eligible children had heard about the campaign, the primary sources being health workers (33.7%), neighbours (26.2%), and radio (22.0%). Of eligible children, 82.4% received mebendazole, 83.8% received vitamin A, and 75.4% received LLINs. Almost all (91.4%) LLINs received during the campaign remained in the household; of those not remaining, 74.4% had been given away and none were reported sold. At least one insecticide-treated net (ITN) was present in 82.3% of all households, 89.2% of households with a child < 5 years and 57.5% of households without a child < 5 years. Just over half (52.4%) of ITNs had been received during the campaign. Considering possible indicators of universal coverage, 39.8% of households owned at least one ITN per two people, 21.6% owned at least one ITN per sleeping space and 34.7% of the general population slept under an ITN the night before the survey. In addition, 45.6% of children < 5 years, and 49.2% of pregnant women had slept under an ITN. Conclusions The nationwide integrated LLIN distribution campaign allowed

  7. Rapid-rate paired associative stimulation of the median nerve and motor cortex can produce long-lasting changes in motor cortical excitability in humans

    PubMed Central

    Quartarone, Angelo; Rizzo, Vincenzo; Bagnato, Sergio; Morgante, Francesca; Sant'Angelo, Antonino; Girlanda, Paolo; Roman Siebner, Hartwig

    2006-01-01

    Repetitive transcranial magnetic stimulation (rTMS) or repetitive electrical peripheral nerve stimulation (rENS) can induce changes in the excitability of the human motor cortex (M1) that is often short-lasting and variable, and occurs only after prolonged periods of stimulation. In 10 healthy volunteers, we used a new repetitive paired associative stimulation (rPAS) protocol to facilitate and prolong the effects of rENS and rTMS on cortical excitability. Sub-motor threshold 5 Hz rENS of the right median nerve was synchronized with submotor threshold 5 Hz rTMS of the left M1 at a constant interval for 2 min. The interstimulus interval (ISI) between the peripheral stimulus and the transcranial stimulation was set at 10 ms (5 Hz rPAS10ms) or 25 ms (5 Hz rPAS25ms). TMS was given over the hot spot of the right abductor pollicis brevis (APB) muscle. Before and after rPAS, we measured the amplitude of the unconditioned motor evoked potential (MEP), intracortical inhibition (ICI) and facilitation (ICF), short- and long-latency afferent inhibition (SAI and LAI) in the conditioned M1. The 5 Hz rPAS25ms protocol but not the 5 Hz rPAS10ms protocol caused a somatotopically specific increase in mean MEP amplitudes in the relaxed APB muscle. The 5 Hz rPAS25ms protocol also led to a loss of SAI, but there was no correlation between individual changes in SAI and corticospinal excitability. These after-effects were still present 6 h after 5 Hz rPAS25ms. There was no consistent effect on ICI, ICF and LAI. The 5 Hz rENS and 5 Hz rTMS protocols failed to induce any change in corticospinal excitability when given alone. These findings show that 2 min of 5 Hz rPAS25ms produce a long-lasting and somatotopically specific increase in corticospinal excitability, presumably by sensorimotor disinhibition. PMID:16825301

  8. The impact of mass drug administration and long-lasting insecticidal net distribution on Wuchereria bancrofti infection in humans and mosquitoes: an observational study in northern Uganda

    PubMed Central

    2011-01-01

    Background Lymphatic filariasis (LF) in Uganda is caused by Wuchereria bancrofti and transmitted by anopheline mosquitoes. The mainstay of elimination has been annual mass drug administration (MDA) with ivermectin and albendazole, targeted to endemic districts, but has been sporadic and incomplete in coverage. Vector control could potentially contribute to reducing W. bancrofti transmission, speeding up progress towards elimination. To establish whether the use of long-lasting insecticidal nets (LLINs) can contribute towards reducing transmission of W. bancrofti in a setting with ongoing MDA, a study was conducted in an area of Uganda highly endemic for both LF and malaria. Baseline parasitological and entomological assessments were conducted in 2007, followed by high-coverage LLIN distribution. Net use and entomological surveys were carried out after one year, and final parasitological and entomological evaluations were conducted in 2010. Three rounds of MDA had taken place before the study commenced, with a further three rounds completed during the course of the study. Results In 2007, rapid mapping indicated 22.3% of schoolchildren were W. bancrofti antigen positive, and a baseline survey during the same year found age-adjusted microfilaraemia prevalence was 3.7% (95% confidence interval (CI): 2.6-5.3%). In 2010, age-adjusted microfilaraemia prevalence had fallen to 0.4%, while antigenaemia rates were 0.2% in children < 5 years and 6.0% in ≥ 5 years. In 2010, universal coverage of mosquito nets in a household was found to be protective against W. bancrofti antigen (odds ratio = 0.44, 95% CI: 0.22-0.89). Prevalence of W. bancrofti larvae in anopheline mosquitoes had decreased significantly between the 2007 and 2010 surveys, but there was an apparent increase in vector densities. Conclusion A marked reduction in W. bancrofti infection and infectivity in humans was observed in the study area, where both MDA and LLINs were used to reduce transmission. The extent

  9. Japanese encephalitis protein vaccine candidates expressing neutralizing epitope and M.T hsp70 induce virus-specific memory B cells and long-lasting antibodies in swine.

    PubMed

    Fei-fei, Ge; Jian, Wang; Feng, Xu; Li-ping, Sheng; Quan-yun, Sun; Jin-ping, Zhou; Pu-yan, Chen; Pei-hong, Liu

    2008-10-16

    Swine are an important amplifier of Japanese encephalitis (JE) virus in the paradomestic environment. In this study, two JE protein vaccine candidates were evaluated for immunogenicity in swine. Both vaccine plasmids are based on a prokaryotic vector pET-32a(+). One plasmid, designated pET-32a(+)-epitope, encode a cassette consisting of a neutralizing epitope on envelope (E) protein of JE virus, whereas the other plasmid, designated pET-32a(+)-epitope-hsp70, express the fusion protein of the epitope and M.T hsp70. Some differences were detected in the immunogenicity of these two proteins in swine. Swine immunized twice with 2000pmol of the neutralizing epitope or the fusion protein developed neutralizing antibody titers of respectively, 154 and 300, and anti-neutralizing epitope antibody titers of 10(4.25) and 10(6.0) by 3 weeks after the second immunization. In addition, swine immunized with the neutralizing epitope emulsified with adjuvant S206 or with imported mineral oil and Tween-80 induced neutralizing antibody titers of 196 and 244, and anti-neutralizing epitope antibody titers of 10(5.25) or 10(5.6) at the same time point. However, swine administered two doses of a commercial JE vaccine (attenuated virus preparation; JEV SA14-14-2 strain) developed less favorable antibody responses with neutralizing antibody titer 40 and anti-neutralizing epitope antibody titers 10(3.7). The anamnestic response was followed by monitoring titers 1 week after boosting with a viral antigen; swine immunized twice with the fusion protein showed a 177-fold increase in anti-neutralizing epitope titer, indicating a strong recall of the antibody response. The animals maintained detectable levels of anti-neutralizing epitope antibody for at least 105 days after two immunizations, indicating that these four protein antigens are able to stimulate virus-specific memory B cells and long-lasting antibodies at higher levels than is achieved using a current commercial attenuated JEV vaccine

  10. Pilot study on the combination of an organophosphate-based insecticide paint and pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors in Burkina Faso.

    PubMed

    Mosqueira, Beatriz; Soma, Dieudonné D; Namountougou, Moussa; Poda, Serge; Diabaté, Abdoulaye; Ali, Ouari; Fournet, Florence; Baldet, Thierry; Carnevale, Pierre; Dabiré, Roch K; Mas-Coma, Santiago

    2015-08-01

    A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical

  11. Magmatic and metasomatic imprints in a long-lasting subduction zone: Evidence from zircon in rodingite and serpentinite of Kochi, SW Japan

    NASA Astrophysics Data System (ADS)

    Hu, Chao-Nan; Santosh, M.; Yang, Qiong-Yan; Kim, S. W.; Nakagawa, M.; Maruyama, S.

    2017-03-01

    rodingitisation from an isotopically primitive source. Our study provides insights into melt and fluid infiltration processes in a mantle wedge associated with long-lasting subduction along an active convergent margin.

  12. Tumor Mouse Model Confirms MAGE-A3 Cancer Immunotherapeutic As an Efficient Inducer of Long-Lasting Anti-Tumoral Responses

    PubMed Central

    Gérard, Catherine; Baudson, Nathalie; Ory, Thierry; Louahed, Jamila

    2014-01-01

    Purpose MAGE-A3 is a potential target for immunotherapy due to its tumor-specific nature and expression in several tumor types. Clinical data on MAGE-A3 immunotherapy have raised many questions that can only be addressed by using animal models. In the present study, different aspects of the murine anti-tumor immune responses induced by a recombinant MAGE-A3 protein (recMAGE-A3) in combination with different immunostimulants (AS01, AS02, CpG7909 or AS15) were investigated. Experimental Design and Results Based on cytokine profile analyses and protection against challenge with MAGE-A3-expressing tumor, the combination recMAGE-A3+AS15 was selected for further experimental work, in particular to study the mechanisms of anti-tumor responses. By using MHC class I-, MHC class II-, perforin-, B-cell- and IFN-γ- knock-out mice and CD4+ T cell-, CD8+ T cell- and NK cell- depleted mice, we demonstrated that CD4+ T cells and NK cells are the main anti-tumor effectors, and that IFN-γ is a major effector molecule. This mouse tumor model also established the need to repeat recMAGE-A3+AS15 injections to sustain efficient anti-tumor responses. Furthermore, our results indicated that the efficacy of tumor rejection by the elicited anti-MAGE-A3 responses depends on the proportion of tumor cells expressing MAGE-A3. Conclusions The recMAGE-A3+AS15 cancer immunotherapy efficiently induced an antigen-specific, functional and long-lasting immune response able to recognize and eliminate MAGE-A3-expressing tumor cells up to several months after the last immunization in mice. The data highlighted the importance of the immunostimulant to induce a Th1-type immune response, as well as the key role played by IFN-γ, CD4+ T cells and NK cells in the anti-tumoral effect. PMID:24830315

  13. Evaluation of a universal long-lasting insecticidal net (LLIN) distribution campaign in Ghana: cost effectiveness of distribution and hang-up activities

    PubMed Central

    2014-01-01

    Background Between May 2010 and October 2012, approximately 12.5 million long-lasting insecticidal nets (LLINs) were distributed through a national universal mass distribution campaign in Ghana. The campaign included pre-registration of persons and sleeping places, door-to-door distribution of LLINs with ‘hang-up’ activities by volunteers and post-distribution ‘keep-up’ behaviour change communication activities. Hang-up activities were included to encourage high and sustained use. Methods The cost and cost-effectiveness of the LLIN Campaign were evaluated using a before-after design in three regions: Brong Ahafo, Central and Western. The incremental cost effectiveness of the ‘hang-up’ component was estimated using reported variation in the implementation of hang-up activities and LLIN use. Economic costs were estimated from a societal perspective assuming LLINs would be replaced after three years, and included the time of unpaid volunteers and household contributions given to volunteers. Results Across the three regions, 3.6 million campaign LLINs were distributed, and 45.5% of households reported the LLINs received were hung-up by a volunteer. The financial cost of the campaign was USD 6.51 per LLIN delivered. The average annual economic cost was USD 2.90 per LLIN delivered and USD 6,619 per additional child death averted by the campaign. The cost-effectiveness of the campaign was sensitive to the price, lifespan and protective efficacy of LLINs. Hang-up activities constituted 7% of the annual economic cost, though the additional financial cost was modest given the use of volunteers. LLIN use was greater in households in which one or more campaign LLINs were hung by a volunteer (OR = 1.57; 95% CI = 1.09, 2.27; p = 0.02). The additional economic cost of the hang-up activities was USD 0.23 per LLIN delivered, and achieved a net saving per LLIN used and per death averted. Conclusion In this campaign, hang-up activities were estimated to be net

  14. Traditional Nets Interfere with the Uptake of Long-Lasting Insecticidal Nets in the Peruvian Amazon: The Relevance of Net Preference for Achieving High Coverage and Use

    PubMed Central

    Grietens, Koen Peeters; Muela Ribera, Joan; Soto, Veronica; Tenorio, Alex; Hoibak, Sarah; Aguirre, Angel Rosas; Toomer, Elizabeth; Rodriguez, Hugo; Llanos Cuentas, Alejandro; D'Alessandro, Umberto; Gamboa, Dionicia; Erhart, Annette

    2013-01-01

    Background While coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset® LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru. Methods The study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses). Results A total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset® LLINs ultimately did not. The LLINs' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], p<0.001). Conclusion Net preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent

  15. Wash durability and optimal drying regimen of four brands of long-lasting insecticide-treated nets after repeated washing under tropical conditions

    PubMed Central

    2010-01-01

    Background The current study was undertaken to determine the optimal wash-drying regimen and the effects of different washing procedures on the efficacy, and durability of four brands of newly introduced long-lasting insecticide-treated nets (LLINs) under tropical conditions. Methods In the current study, the following four LLINs were tested: Olyset®, PermaNet ®2.0, BASF® and TNT®. Nets were divided into three sets; one set was washed by hand rubbing and air-dried either hanging or spread on the ground in direct sunlight or hanging or spread on the ground under the shade. A second set was washed using the WHO protocol (machine) and the third set was washed by beating the nets on rocks. The biological activities of the nets were assessed by a three-minute bioassay cone test and the residual insecticide contents were determined using high performance liquid chromatography (HPLC) procedure. Results Nets that were dried hanging under the shade retained more insecticide, 62.5% and recorded higher mortality compared to nets which were dried lying on the ground in direct sunlight 58.8%, nets dried under the shade spread on the ground 56.3%, and 57.8% for nets dried hanging in direct sunlight. It was also observed that nets washed by the standard WHO protocol, retained more insecticide and were more effective in killing mosquitoes compared to nets washed by local methods of hand rubbing and beating on rocks. There were significant differences between drying regimens (p < 0.0001) and between washing procedures (p < 0.001) respectively. However, the effect of net type was statistically insignificant. The statistical differences on individual nets were also compared, for PermaNet® and TNT there were no significant differences observed between the four drying regimens (p = 0.7944 and 0.4703) respectively). For BASF and Olyset, the differences were significant (p < 0.001 and p > 0.0001). Conclusion The results of this study suggest that washing and drying regimen influence

  16. Plastic Jellyfish.

    ERIC Educational Resources Information Center

    Moseley, Christine

    2000-01-01

    Presents an environmental science activity designed to enhance students' awareness of the hazards of plastic waste for wildlife in aquatic environments. Discusses how students can take steps to reduce the effects of plastic waste. (WRM)

  17. Lack of Long-Lasting Hydrosalpinx in A/J Mice Correlates with Rapid but Transient Chlamydial Ascension and Neutrophil Recruitment in the Oviduct following Intravaginal Inoculation with Chlamydia muridarum

    PubMed Central

    Zhang, Hongbo; Zhou, Zhou; Chen, Jianlin; Wu, Ganqiu; Yang, Zhangsheng; Zhou, Zhiguang; Baseman, Joel; Zhang, Jin; Reddick, Robert Lee

    2014-01-01

    Lower genital tract infection with Chlamydia trachomatis and C. muridarum can induce long-lasting hydrosalpinx in the upper genital tract of women and female mice, respectively. However, A/J mice were highly resistant to induction of long-lasting hydrosalpinx by C. muridarum. We further compared host inflammatory responses and chlamydial infection courses between the hydrosalpinx-resistant A/J mice and CBA/J mice known to be susceptible to hydrosalpinx induction. Both mouse strains developed robust pyosalpinx during the acute phase followed by hydrosalpinx during the chronic phase. However, the hydrosalpinges disappeared in A/J mice by day 60 after infection, suggesting that some early hydrosalpinges are reversible. Although the overall inflammatory responses were indistinguishable between CBA/J and A/J mice, we found significantly more neutrophils in oviduct lumen of A/J mice on days 7 and 10, which correlated with a rapid but transient oviduct invasion by C. muridarum with a peak infection on day 7. In contrast, CBA/J mice developed a delayed and extensive oviduct infection. These comparisons have revealed an important role of the interactions of oviduct infection with inflammatory responses in chlamydial induction of long-lasting hydrosalpinx, suggesting that a rapid but transient invasion of oviduct by chlamydial organisms can prevent the development of the long-lasting hydrosalpinges. PMID:24711570

  18. Implications of bio-efficacy and persistence of insecticides when indoor residual spraying and long-lasting insecticide nets are combined for malaria prevention

    PubMed Central

    2012-01-01

    Background Bio-efficacy and residual activity of insecticides used for indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs) were assessed against laboratory-reared and wild populations of the malaria vector, Anopheles arabiensis in south eastern Tanzania. Implications of the findings are examined in the context of potential synergies and redundancies where IRS and LLINs are combined. Methods Bioassays were conducted monthly for six months on three LLIN types (Olyset® PermaNet 2.0®,and Icon Life®) and three IRS treatments (2 g/m2 pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m2 lambda-cyhalothrin, sprayed on mud walls and palm ceilings of experimental huts). Tests used susceptible laboratory-reared An. arabiensis exposed in cones (nets and IRS) or wire balls (nets only). Susceptibility of wild populations was assessed using WHO diagnostic concentrations and PCR for knock-down resistance (kdr) genes. Results IRS treatments killed ≥ 85% of mosquitoes exposed on palm ceilings and ≥ 90% of those exposed on mud walls, but up to 50% of this toxicity decayed within 1–3 months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda-cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud walls sprayed with the same insecticides. In wire-ball assays, mortality decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet 2.0®, from 100% to 61.1% on Icon Life® and from 93.2% to 33.3% on Olyset® nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in 6th month on PermaNet 2.0®, from 96.9% to 43.80% on Icon Life® and from 85.6% to 14.6% on Olyset®. Wild An. arabiensis were 100% susceptible to DDT, 95.8% to deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No kdr gene mutations were detected. Conclusions In bioassays where sufficient contact with treated surfaces is

  19. Protein Phosphatase 1-Dependent Transcriptional Programs for Long-Term Memory and Plasticity

    ERIC Educational Resources Information Center

    Graff, Johannes; Koshibu, Kyoko; Jouvenceau, Anne; Dutar, Patrick; Mansuy, Isabelle M.

    2010-01-01

    Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and…

  20. Plastic surgery: understanding abdominoplasty and liposuction.

    PubMed

    Logan, Judith M; Broughton, George

    2008-10-01

    Requests for plastic surgery procedures that alter one's body image are on the rise. To ensure the best possible outcome, patients who request a combined procedure (eg, abdominoplasty and liposuction) must meet certain criteria to be eligible for surgery. It is critically important for patients to understand that these surgeries are not weight-reduction procedures, and they must be prepared to make lifestyle changes to ensure long-lasting results. These procedures are performed in a variety of facilities (eg, surgeons' offices, surgery centers, hospitals). Perioperative nurses must have a basic knowledge and understanding of abdominoplasty and liposuction and the special requirements and potential complications involved with these procedures.

  1. Measures of Malaria Burden after Long-Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study

    PubMed Central

    Katureebe, Agaba; Zinszer, Kate; Arinaitwe, Emmanuel; Charland, Katia; Kigozi, Ruth; Kilama, Maxwell; Nankabirwa, Joaniter; Yeka, Adoke; Mawejje, Henry; Mpimbaza, Arthur; Donnelly, Martin J.; Rosenthal, Philip J.; Lindsay, Steve W.; Staedke, Sarah G.; Smith, David L.; Kamya, Moses R.; Dorsey, Grant

    2016-01-01

    Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites. Methods and Findings Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera). Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera. High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107). The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN. In Walukuba, over the 28-mo post-intervention period

  2. Drug-induced neurobehavioral plasticity: the role of environmental context.

    PubMed

    Badiani, A; Robinson, T E

    2004-09-01

    Repeated administrations of addictive drugs produce long-lasting changes in brain and behavior. However, drug-induced neurobehavioral plasticity is not a mere function of the neuropharmacological actions of drugs, but the result of complex drug-environment interactions. In the present review we summarize results obtained in a series of studies using an animal model of drug-environment interaction, showing that environmental context and past drug history interact to modulate the effects of amphetamine, cocaine and morphine on behavior, gene expression and structural plasticity. These findings may help shed some light on the conditions necessary for addictive drugs to enduringly alter brain and behavior.

  3. Distinctive features of adult ocular dominance plasticity.

    PubMed

    Sato, Masaaki; Stryker, Michael P

    2008-10-08

    Sensory experience profoundly shapes neural circuitry of juvenile brain. Although the visual cortex of adult rodents retains a capacity for plasticity in response to monocular visual deprivation, the nature of this plasticity and the neural circuit changes that accompany it remain enigmatic. Here, we investigate differences between adult and juvenile ocular dominance plasticity using Fourier optical imaging of intrinsic signals in mouse visual cortex. This comparison reveals that adult plasticity takes longer than in the juvenile mouse, is of smaller magnitude, has a greater contribution from the increase in response to the open eye, and has less effect on the hemisphere ipsilateral to the deprived eye. Binocular deprivation also causes different changes in the adult. Adult plasticity is similar to juvenile plasticity in its dependence on signaling through NMDA receptors. We propose that adult ocular dominance plasticity arises from compensatory mechanisms that counterbalance the loss of afferent activity caused by visual deprivation.

  4. Plastics Technology.

    ERIC Educational Resources Information Center

    Barker, Tommy G.

    This curriculum guide is designed to assist junior high schools industrial arts teachers in planning new courses and revising existing courses in plastics technology. Addressed in the individual units of the guide are the following topics: introduction to production technology; history and development of plastics; safety; youth leadership,…

  5. Intrinsic Nilpotent Approximation.

    DTIC Science & Technology

    1985-06-01

    RD-A1II58 265 INTRINSIC NILPOTENT APPROXIMATION(U) MASSACHUSETTS INST 1/2 OF TECH CAMBRIDGE LAB FOR INFORMATION AND, DECISION UMCLRSSI SYSTEMS C...TYPE OF REPORT & PERIOD COVERED Intrinsic Nilpotent Approximation Technical Report 6. PERFORMING ORG. REPORT NUMBER LIDS-R-1482 7. AUTHOR(.) S...certain infinite-dimensional filtered Lie algebras L by (finite-dimensional) graded nilpotent Lie algebras or g . where x E M, (x,,Z) E T*M/O. It

  6. Epigenetic Basis of Neuronal and Synaptic Plasticity.

    PubMed

    Karpova, Nina N; Sales, Amanda J; Joca, Samia R

    2017-01-01

    Neuronal network and plasticity change as a function of experience. Altered neural connectivity leads to distinct transcriptional programs of neuronal plasticity-related genes. The environmental challenges throughout life may promote long-lasting reprogramming of gene expression and the development of brain disorders. The modifications in neuronal epigenome mediate gene-environmental interactions and are required for activity-dependent regulation of neuronal differentiation, maturation and plasticity. Here, we highlight the latest advances in understanding the role of the main players of epigenetic machinery (DNA methylation and demethylation, histone modifications, chromatin-remodeling enzymes, transposons, and non-coding RNAs) in activity-dependent and long- term neural and synaptic plasticity. The review focuses on both the transcriptional and post-transcriptional regulation of gene expression levels, including the processes of promoter activation, alternative splicing, regulation of stability of gene transcripts by natural antisense RNAs, and alternative polyadenylation. Further, we discuss the epigenetic aspects of impaired neuronal plasticity and the pathogenesis of neurodevelopmental (Rett syndrome, Fragile X Syndrome, genomic imprinting disorders, schizophrenia, and others), stressrelated (mood disorders) and neurodegenerative Alzheimer's, Parkinson's and Huntington's disorders. The review also highlights the pharmacological compounds that modulate epigenetic programming of gene expression, the potential treatment strategies of discussed brain disorders, and the questions that should be addressed during the development of effective and safe approaches for the treatment of brain disorders.

  7. Plastic Surgery Statistics

    MedlinePlus

    ... PRS GO PSN PSEN GRAFT Contact Us News Plastic Surgery Statistics Plastic surgery procedural statistics from the ... Plastic Surgery Statistics 2005 Plastic Surgery Statistics 2016 Plastic Surgery Statistics Stats Report 2016 National Clearinghouse of ...

  8. JOINING THE DOTS: FROM CHROMATIN REMODELING TO NEURONAL PLASTICITY

    PubMed Central

    Zocchi, Loredana; Sassone-Corsi, Paolo

    2010-01-01

    SUMMARY In recent years spectacular advances in the field of epigenetics have taken place. Multiple lines of evidence that connect epigenetic regulation to brain functions have been accumulating. Neurons daily convert a variety of external stimuli into rapid or long-lasting changes in gene expression. Control is achieved through several post-translational modifications that occur both on DNA and chromatin. Specific modifications mediate many developmental processes and adult brain functions, such as synaptic plasticity and memory. In this review, we focus on critical chromatin remodeling events that mediate long-lasting neuronal responses. The challenging goal is to reach sufficient understanding of these epigenetic pathways in the brain so that they may be useful for future development of specific pharmacological strategies. PMID:20471240

  9. Report on the first WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Hong Kong SAR, China, 24-26 January 2013.

    PubMed

    Girard, Marc P; Tam, John S; Pervikov, Yuri; Katz, Jacqueline M

    2013-08-20

    On January 24-26, 2013, the World Health Organization convened the first integrated meeting on "The development and clinical trials of vaccines that induce broadly protective and long-lasting immune responses" to review the current status of development and clinical evaluation of novel influenza vaccines as well as strategies to produce and deliver vaccines in novel ways. Special attention was given to the development of possible universal influenza vaccines. Other topics that were addressed included an update on clinical trials of pandemic and seasonal influenza vaccines in high-risk groups and vaccine safety, as well as regulatory issues.

  10. Accumulation and fragmentation of plastic debris in global environments

    PubMed Central

    Barnes, David K. A.; Galgani, Francois; Thompson, Richard C.; Barlaz, Morton

    2009-01-01

    One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences (fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly

  11. Accumulation and fragmentation of plastic debris in global environments.

    PubMed

    Barnes, David K A; Galgani, Francois; Thompson, Richard C; Barlaz, Morton

    2009-07-27

    One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences (fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly

  12. Predicting Intrinsic Motivation

    ERIC Educational Resources Information Center

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the extent to…

  13. [Intrinsic cardiac ganglia].

    PubMed

    Birand, Ahmet

    2008-12-01

    Heart has been considered as the source and the seat of emotions, passion and love. But from the dawn of XIXth century, scientists have emphasized that the heart, though life depends on its ceaseless activity, is merely a electromechanical pump, pumping oxygenated blood. Nowadays, we all know that heart pumps blood commensurate with the needs of the body and this unending toil, and its regulation depends on the intrinsic properties of the myocardium, Frank-Starling Law and neurohumoral contribution. It has been understood, though not clearly enough, that these time-tensions may cause structural or functional cardiac impairments and arrhythmias are related to the autonomic nervous system. Less well known and less taken in account in daily cardiology practice is the fact that heart has an intrinsic cardiac nervous system, or "heart brain" consisting of complex ganglia, intrinsic cardiac ganglia containing afferent (receiving), local circuit (interneurons) and efferent (transmitting) sympathetic and parasympathetic neurons. This review enlightens structural and functional aspects of intrinsic cardiac ganglia as the very first step in the regulation of cardiac function. This issue is important for targets of pharmacological treatment and techniques of cardiac surgery interventions as repair of septal defects, valvular interventions and congenital corrections.

  14. Competition and Intrinsic Motivation.

    ERIC Educational Resources Information Center

    Tripathi, Kailas Nath

    1992-01-01

    Reports on a study of competition, motivation, and performance among 60 adolescents in India. Finds that direct competition with another person led to higher levels of immediate performance. Also finds that indirect competition against a pre-set standard resulted in greater intrinsic motivation. (CFR)

  15. Evaluating Intrinsic Goals.

    ERIC Educational Resources Information Center

    Silberman, Harry F.

    1984-01-01

    A social learning model focusing on intrinsic outcomes of vocational programs is proposed. It would assess technical skills and knowledge, communication skills and literacy, and personal skills and attitudes. Instruments should be devised to measure characteristics of the learning setting, learner involved activities, and nature of consequences of…

  16. Epigenetics of memory and plasticity.

    PubMed

    Woldemichael, Bisrat T; Bohacek, Johannes; Gapp, Katharina; Mansuy, Isabelle M

    2014-01-01

    Although all neurons carry the same genetic information, they vary considerably in morphology and functions and respond differently to environmental conditions. Such variability results mostly from differences in gene expression. Among the processes that regulate gene activity, epigenetic mechanisms play a key role and provide an additional layer of complexity to the genome. They allow the dynamic modulation of gene expression in a locus- and cell-specific manner. These mechanisms primarily involve DNA methylation, posttranslational modifications (PTMs) of histones and noncoding RNAs that together remodel chromatin and facilitate or suppress gene expression. Through these mechanisms, the brain gains high plasticity in response to experience and can integrate and store new information to shape future neuronal and behavioral responses. Dynamic epigenetic footprints underlying the plasticity of brain cells and circuits contribute to the persistent impact of life experiences on an individual's behavior and physiology ranging from the formation of long-term memory to the sequelae of traumatic events or of drug addiction. They also contribute to the way lifestyle, life events, or exposure to environmental toxins can predispose an individual to disease. This chapter describes the most prominent examples of epigenetic marks associated with long-lasting changes in the brain induced by experience. It discusses the role of epigenetic processes in behavioral plasticity triggered by environmental experiences. A particular focus is placed on learning and memory where the importance of epigenetic modifications in brain circuits is best understood. The relevance of epigenetics in memory disorders such as dementia and Alzheimer's disease is also addressed, and promising perspectives for potential epigenetic drug treatment discussed.

  17. Early exposure to ethanol or red wine and long-lasting effects in aged mice. A study on nerve growth factor, brain-derived neurotrophic factor, hepatocyte growth factor, and vascular endothelial growth factor.

    PubMed

    Ceccanti, Mauro; Mancinelli, Rosanna; Tirassa, Paola; Laviola, Giovanni; Rossi, Simona; Romeo, Marina; Fiore, Marco

    2012-02-01

    Prenatal ethanol exposure produces severe changes in brain, liver, and kidney through mechanisms involving growth factors. These molecules regulate survival, differentiation, maintenance, and connectivity of brain, liver, and kidney cells. Despite the abundant available data on the short and mid-lasting effects of ethanol intoxication, only few data show the long-lasting damage induced by early ethanol administration. The aim of this study was to investigate changes in nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in brain areas, liver, and kidney of 18-mo-old male mice exposed perinatally to ethanol at 11% vol or to red wine at the same ethanol concentration. The authors found that ethanol per se elevated NGF, BDNF, HGF, and VEGF measured by ELISA in brain limbic system areas. In the liver, early exposure to ethanol solution and red wine depleted BDNF and VEGF concentrations. In the kidney, red wine exposure only decreased VEGF. In conclusion, the present study shows that, in aged mice, early administration of ethanol solution induced long-lasting damage at growth factor levels in frontal cortex, hippocampus, and liver but not in kidney. Otherwise, in mice exposed to red wine, significant changes were observed in the liver and kidney but not in the hippocampus and frontal cortex. The brain differences in ethanol-induced toxicity when ethanol is administered alone or in red wine may be related to compounds with antioxidant properties present in the red wine.

  18. Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages.

    PubMed

    Moretti, Sarah; Franchi, Silvia; Castelli, Mara; Amodeo, Giada; Somaini, Lorenzo; Panerai, Alberto; Sacerdote, Paola

    2015-06-01

    Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC did not affect brain cytokines in adult mice, but a proinflammatory cytokine decrease was evident in the adolescent brain. A similar effect was present in the hypothalamus and hippocampus after 10 days' THC administration. In contrast, when brain cytokines were measured 47 days after the final THC administration, we observed an inverted effect in adult mice treated as adolescents, i.e., IL-1β and TNF-α increased and IL-10 decreased, indicating a shift toward neuroinflammation. These data suggest that THC exposure in adolescence has long-lasting effects on brain cytokines that parallel those present in the periphery. This modulation may affect vulnerability to immune and behavioural diseases in adulthood.

  19. Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors.

    PubMed

    Mateos, B; Borcel, E; Loriga, R; Luesu, W; Bini, V; Llorente, R; Castelli, M P; Viveros, M-P

    2011-12-01

    We have analysed the long-term effects of adolescent (postnatal day 28-43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB(1) cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB(1) receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB(1) and nicotinic receptors.

  20. Compensatory plasticity: time matters

    PubMed Central

    Lazzouni, Latifa; Lepore, Franco

    2014-01-01

    Plasticity in the human and animal brain is the rule, the base for development, and the way to deal effectively with the environment for making the most efficient use of all the senses. When the brain is deprived of one sensory modality, plasticity becomes compensatory: the exception that invalidates the general loss hypothesis giving the opportunity of effective change. Sensory deprivation comes with massive alterations in brain structure and function, behavioral outcomes, and neural interactions. Blind individuals do as good as the sighted and even more, show superior abilities in auditory, tactile and olfactory processing. This behavioral enhancement is accompanied with changes in occipital cortex function, where visual areas at different levels become responsive to non-visual information. The intact senses are in general used more efficiently in the blind but are also used more exclusively. New findings are disentangling these two aspects of compensatory plasticity. What is due to visual deprivation and what is dependent on the extended use of spared modalities? The latter seems to contribute highly to compensatory changes in the congenitally blind. Short-term deprivation through the use of blindfolds shows that cortical excitability of the visual cortex is likely to show rapid modulatory changes after few minutes of light deprivation and therefore changes are possible in adulthood. However, reorganization remains more pronounced in the congenitally blind. Cortico-cortical pathways between visual areas and the areas of preserved sensory modalities are inhibited in the presence of vision, but are unmasked after loss of vision or blindfolding as a mechanism likely to drive cross-modal information to the deafferented visual cortex. The development of specialized higher order visual pathways independently from early sensory experience is likely to preserve their function and switch to the intact modalities. Plasticity in the blind is also accompanied with

  1. Plastic Bronchitis.

    PubMed

    Rubin, Bruce K

    2016-09-01

    Plastic bronchitis is an uncommon and probably underrecognized disorder, diagnosed by the expectoration or bronchoscopic removal of firm, cohesive, branching casts. It should not be confused with purulent mucous plugging of the airway as seen in patients with cystic fibrosis or bronchiectasis. Few medications have been shown to be effective and some are now recognized as potentially harmful. Current research directions in plastic bronchitis research include understanding the genetics of lymphatic development and maldevelopment, determining how abnormal lymphatic malformations contribute to cast formation, and developing new treatments.

  2. Long lasting dynamic disequilibrium in river basins

    NASA Astrophysics Data System (ADS)

    Goren, Liran; Willett, Sean D.; McCoy, Scott W.; Perron, J. Taylor; Chen, Chia-Yu

    2014-05-01

    The river basins of ancient landscapes such as the southeastern United States exhibit disequilibrium in the form of migrating divides and stream capture. This observation is surprising in light of the relatively short theoretical fluvial response time, which is controlled by the celerity of the erosional wave that propagates upstream the fluvial channels. The response time is believed to determine the time required for fluvial landscapes to adjust to tectonic, climatic, and base-level perturbations, and its global estimations range between 0.1 Myr and 10s Myr. To address this discrepancy, we develop a framework for mapping continuous dynamic reorganization of natural river basins, and demonstrate the longevity of disequilibrium along the river basins in the southeastern United States that are reorganizing in response to escarpment retreat and coastal advance. The mapping of disequilibrium is based on a proxy for steady-state elevation, Ξ, that can be easily calculated from digital elevation models. Disequilibrium is inferred from differences in the value of Ξ across water divides. These differences indicate that with the present day drainage area distribution and river topology the steady-state channels elevation across the divides differs, and therefore divides are expected to migrate in the direction of the higher Ξ value. We further use the landscape evolution model DAC to explore the source of the longevity of disequilibrium in fluvial landscapes. DAC solves accurately for the location of water divides, using a combination of an analytical solution for hillslopes and low-order channels together with a numerical solution for higher order channels. DAC simulations demonstrate topological, geometrical, and topographical adjustments that persist much longer than the theoretical response time, and consequently, extend the time needed to diminish disequilibrium in the landscape and to reach topological and topographical steady-state. This behavior is interpreted as resulting from a positive feedback between divide migration, which causes topological modifications and area change, on the one hand, and channel slope adjustments, which change the erosion rates on opposing sides of water divides and promote their migration, on the other hand. Furthermore, the constantly shifting drainage area and the changing topology of the drainage network are shown to be a possible source for autogenic sediment flux variations.

  3. Plastics Technician.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document contains 16 units to consider for use in a tech prep competency profile for the occupation of plastics technician. All the units listed will not necessarily apply to every situation or tech prep consortium, nor will all the competencies within each unit be appropriate. Several units appear within each specific occupation and would…

  4. Neuronal plasticity and thalamocortical sleep and waking oscillations.

    PubMed

    Timofeev, Igor

    2011-01-01

    Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma.

  5. Neuronal plasticity and thalamocortical sleep and waking oscillations

    PubMed Central

    Timofeev, Igor

    2011-01-01

    Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma. PMID:21854960

  6. Sol–gel synthesis of long-lasting phosphors CdSiO{sub 3}: Mn{sup 2+}, RE{sup 3+} (RE = Tb, Eu, Nd) and luminescence mechanism research

    SciTech Connect

    Qu, Xiaofei; Cao, Lixin; Liu, Wei; Su, Ge; Wang, Pingping; Schultz, Isabel

    2012-06-15

    Highlights: ► New long-lasting CdSiO{sub 3}: Mn{sup 2+}, RE{sup 3+} (RE = Tb, Eu, Nd) phosphors were synthesized by a sol–gel method. ► The afterglow performance of the CdSiO{sub 3}: Mn{sup 2+}, Eu{sup 3+} phosphor was the best. ► The role of RE{sup 3+} co-doped into the CdSiO{sub 3}: Mn{sup 2+} matrix was discussed in this paper. -- Abstract: Mn{sup 2+} and RE{sup 3+} (RE = Tb, Eu, Nd) co-doped CdSiO{sub 3} orange phosphors were prepared at 1050 °C by a sol–gel method. The phase and crystallinity of the synthesized materials were investigated by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The luminescence characteristics were analyzed using photoluminescence (PL) spectra, afterglow decay curves, long-lasting phosphorescence spectra, and thermoluminescence (TL) spectra. Due to the difference in co-doped rare earth ionic radii, it varied greatly in trap density and trap depth caused by the different defects deriving from RE{sup 3+} ions co-doping into the CdSiO{sub 3}: Mn{sup 2+} host. The afterglow intensity and time for these samples increased as follows: CdSiO{sub 3}: Mn{sup 2+}0.2%, Nd{sup 3+}0.8% < CdSiO{sub 3}: Mn{sup 2+}0.4%, Tb{sup 3+}0.8% < CdSiO{sub 3}: Mn{sup 2+}0.4%, Eu{sup 3+}0.3%. CdSiO{sub 3}: Mn{sup 2+}0.4%, Eu{sup 3+}0.3% had the best afterglow properties, which could be due to the proper traps formed by Eu{sup 3+} ions co-doping into the host. The role of RE{sup 3+} co-doped into the CdSiO{sub 3}: Mn{sup 2+} matrix and the possible long-lasting phosphorescence process was also discussed in this paper.

  7. GLASS FIBER REINFORCED PLASTICS,

    DTIC Science & Technology

    Contents: Fibrous glass fillers Binders used in the glass plastic industry Method of manufacturing glass plastics and glass plastic articles Properties of fiberglass Primary areas for use of glass fibre reinforced plastics

  8. Cell-specific synaptic plasticity induced by network oscillations

    PubMed Central

    Zarnadze, Shota; Bäuerle, Peter; Santos-Torres, Julio; Böhm, Claudia; Schmitz, Dietmar; Geiger, Jörg RP

    2016-01-01

    Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner. DOI: http://dx.doi.org/10.7554/eLife.14912.001 PMID:27218453

  9. [Medical visits before return to work, after a long lasting absence, above 60 days, for injuries or common diseases in a public transport company. Analysis and discussions of utility and consequences in term of evaluation of fitness to specific job].

    PubMed

    Verga, A; Bordini, L; Ricci, M G; Di Lucca, P; Todaro, A

    2012-01-01

    The aim of this study is to evaluate the opportunity to do medical visits before return to work, after a long continuous absence, above 60 days, for injuries (occupational and non-occupational) or common diseases. We have examined medical records of 403 workers, in 2010 and 2011, occupied in a public transport company, in order to control the following variables: job, age, clinical conditions related to the absences, classification of the absence as injuries or common disease and conclusions about medical fitness to specific job. Our findings have shown an equal percentage of causes of absences in term of injuries or common diseases. The main cause of absence and of non fit to specific job, after medical evaluation, is depending on orthopaedic post-traumatic diseases. This evidence support the importance to do medical visits after long-lasting absence from work, particularly in case of jobs (bus, tram, subway drivers) at risk for other people.

  10. Removal of S6K1 and S6K2 Leads to Divergent Alterations in Learning, Memory, and Synaptic Plasticity

    ERIC Educational Resources Information Center

    Antion, Marcia D.; Merhav, Maayan; Hoeffer, Charles A.; Reis, Gerald; Kozma, Sara C.; Thomas, George; Schuman Erin M.; Rosenblum, Kobi; Klann, Eric

    2008-01-01

    Protein synthesis is required for the expression of enduring memories and long-lasting synaptic plasticity. During cellular proliferation and growth, S6 kinases (S6Ks) are activated and coordinate the synthesis of de novo proteins. We hypothesized that protein synthesis mediated by S6Ks is critical for the manifestation of learning, memory, and…

  11. Direct and long-lasting effects elicited by repeated drug administration on 50-kHz ultrasonic vocalizations are regulated differently: implications for the study of the affective properties of drugs of abuse.

    PubMed

    Simola, Nicola; Frau, Lucia; Plumitallo, Antonio; Morelli, Micaela

    2014-03-01

    Several studies suggest that 50-kHz ultrasonic vocalizations (USVs) may indicate a positive affective state in rats, and these vocalizations are increasingly being used to investigate the properties of psychoactive drugs. Previous studies, however, have focused on dopaminergic psychostimulants and morphine, whereas little is known about how other drugs modulate 50-kHz USVs. To further elucidate the neuropharmacology of 50-kHz USVs, the present study characterized the direct and long-lasting effects of different drugs of abuse, by measuring the number of 50-kHz USVs and their 'trill' subtype emitted by adult male rats. Rats received repeated administrations of amphetamine (2 mg/kg, i.p.), 3,4-methylenedioxymethamphetamine (MDMA, 7.5 mg/kg, i.p.), morphine (7.5 mg/kg, s.c.), or nicotine (0.4 mg/kg, s.c.), on either consecutive or alternate days (five administrations in total) in a novel environment. Seven days later, rats were re-exposed to the drug-paired environment, subjected to USVs recording, and then challenged with the same drug. Finally, 7 d after the challenge, rats were repeatedly exposed to the drug-paired environment and vocalizations were measured. Amphetamine was the only drug to stimulate 50-kHz USVs and 'trill' subtype emission during administration and challenge. Conversely, all rats emitted 50-kHz USVs when re-exposed to the test cage, and this effect was most marked in morphine-treated rats, and less evident in nicotine-treated rats. This study demonstrates that the direct and long-lasting effects of drugs on 50-kHz USVs are regulated differently, providing a better understanding of the usefulness of these vocalizations in the study of psychoactive drugs.

  12. Plastic bronchitis

    PubMed Central

    Singhi, Anil Kumar; Vinoth, Bharathi; Kuruvilla, Sarah; Sivakumar, Kothandam

    2015-01-01

    Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its current understanding. PMID:26556975

  13. Plasticity of Sensorimotor Networks: Multiple Overlapping Mechanisms.

    PubMed

    Buch, Ethan R; Liew, Sook-Lei; Cohen, Leonardo G

    2016-03-16

    Redundancy is an important feature of the motor system, as abundant degrees of freedom are prominent at every level of organization across the central and peripheral nervous systems, and musculoskeletal system. This basic feature results in a system that is both flexible and robust, and which can be sustainably adapted through plasticity mechanisms in response to intrinsic organismal changes and dynamic environments. While much early work of motor system organization has focused on synaptic-based plasticity processes that are driven via experience, recent investigations of neuron-glia interactions, epigenetic mechanisms and large-scale network dynamics have revealed a plethora of plasticity mechanisms that support motor system organization across multiple, overlapping spatial and temporal scales. Furthermore, an important role of these mechanisms is the regulation of intrinsic variability. Here, we review several of these mechanisms and discuss their potential role in neurorehabilitation.

  14. Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells

    NASA Astrophysics Data System (ADS)

    He, Qionger; Duguid, Ian; Clark, Beverley; Panzanelli, Patrizia; Patel, Bijal; Thomas, Philip; Fritschy, Jean-Marc; Smart, Trevor G.

    2015-07-01

    Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABAA receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABAA receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABAA receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABAA receptors and is abolished by preventing CaMKII phosphorylation of GABAA receptors. Our results reveal a novel GABAA receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum.

  15. Intrinsically Disordered Energy Landscapes

    NASA Astrophysics Data System (ADS)

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-05-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.

  16. Intrinsically Disordered Energy Landscapes

    PubMed Central

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-01-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium. PMID:25999294

  17. Intrinsic Feature Motion Tracking

    SciTech Connect

    Goddard, Jr., James S.

    2013-03-19

    Subject motion during 3D medical scanning can cause blurring and artifacts in the 3D images resulting in either rescans or poor diagnosis. Anesthesia or physical restraints may be used to eliminate motion but are undesirable and can affect results. This software measures the six degree of freedom 3D motion of the subject during the scan under a rigidity assumption using only the intrinsic features present on the subject area being monitored. This movement over time can then be used to correct the scan data removing the blur and artifacts. The software acquires images from external cameras or images stored on disk for processing. The images are from two or three calibrated cameras in a stereo arrangement. Algorithms extract and track the features over time and calculate position and orientation changes relative to an initial position. Output is the 3D position and orientation change measured at each image.

  18. Gaussian Intrinsic Entanglement

    NASA Astrophysics Data System (ADS)

    Mišta, Ladislav; Tatham, Richard

    2016-12-01

    We introduce a cryptographically motivated quantifier of entanglement in bipartite Gaussian systems called Gaussian intrinsic entanglement (GIE). The GIE is defined as the optimized mutual information of a Gaussian distribution of outcomes of measurements on parts of a system, conditioned on the outcomes of a measurement on a purifying subsystem. We show that GIE vanishes only on separable states and exhibits monotonicity under Gaussian local trace-preserving operations and classical communication. In the two-mode case, we compute GIE for all pure states as well as for several important classes of symmetric and asymmetric mixed states. Surprisingly, in all of these cases, GIE is equal to Gaussian Rényi-2 entanglement. As GIE is operationally associated with the secret-key agreement protocol and can be computed for several important classes of states, it offers a compromise between computable and physically meaningful entanglement quantifiers.

  19. Intrinsically variable stars

    NASA Technical Reports Server (NTRS)

    Bohm-Vitense, Erika; Querci, Monique

    1987-01-01

    The characteristics of intrinsically variable stars are examined, reviewing the results of observations obtained with the IUE satellite since its launch in 1978. Selected data on both medium-spectral-class pulsating stars (Delta Cep stars, W Vir stars, and related groups) and late-type variables (M, S, and C giants and supergiants) are presented in spectra, graphs, and tables and described in detail. Topics addressed include the calibration of the the period-luminosity relation, Cepheid distance determination, checking stellar evolution theory by the giant companions of Cepheids, Cepheid masses, the importance of the hydrogen convection zone in Cepheids, temperature and abundance estimates for Population II pulsating stars, mass loss in Population II Cepheids, SWP and LWP images of cold giants and supergiants, temporal variations in the UV lines of cold stars, C-rich cold stars, and cold stars with highly ionized emission lines.

  20. Intrinsic-surface-tag image authentication

    SciTech Connect

    Palm, R.G.; DeVolpi, A.

    1991-12-01

    The objective of this work is to further the development of a unique treaty limited item (TLI) intrinsic surface tag for arms control applications. This tag's unique feature is the ability to capture the sub-micron scale topography of the TLI surface. The surface topography is captured by plastic castings of the surface as digitally imaged by an electron microscope. Tag authentication is accomplished by comparing digital castings images obtained in two different inspections. Surface replication experiments are described, as these experiments from the basis for the authentication algorithm. Both the experiments and the authentication algorithm are analyzed using the modulation transfer function. Recommendations for future improvements in tag authentication are also suggested by the modulation transfer function analysis. 4 refs.

  1. Intrinsic-surface-tag image authentication

    SciTech Connect

    Palm, R.G.; DeVolpi, A.

    1991-12-01

    The objective of this work is to further the development of a unique treaty limited item (TLI) intrinsic surface tag for arms control applications. This tag`s unique feature is the ability to capture the sub-micron scale topography of the TLI surface. The surface topography is captured by plastic castings of the surface as digitally imaged by an electron microscope. Tag authentication is accomplished by comparing digital castings images obtained in two different inspections. Surface replication experiments are described, as these experiments from the basis for the authentication algorithm. Both the experiments and the authentication algorithm are analyzed using the modulation transfer function. Recommendations for future improvements in tag authentication are also suggested by the modulation transfer function analysis. 4 refs.

  2. Qutrit teleportation under intrinsic decoherence

    NASA Astrophysics Data System (ADS)

    Jafarpour, Mojtaba; Naderi, Negar

    2016-08-01

    We study qutrit teleportation and its fidelity in the presence and absence of intrinsic decoherence through a qutrit channel. The channel consists of a Heisenberg chain with xyz interaction model and the intrinsic decoherence is implemented through the Milburn model. It is shown that while the fidelity diminishes due to intrinsic decoherence, it may be enhanced if the channel is initially in an entangled state. It is also observed that, for stronger intrinsic decoherence, the initial entanglement of the channel is more effective in enhancing of fidelity.

  3. Intrinsically Disordered Side of the Zika Virus Proteome

    PubMed Central

    Giri, Rajanish; Kumar, Deepak; Sharma, Nitin; Uversky, Vladimir N.

    2016-01-01

    Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of disorder-based drugs. PMID:27867910

  4. Report on the second WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Geneva, Switzerland, 5-7 May 2014.

    PubMed

    Cox, Nancy J; Hickling, Julian; Jones, Rebecca; Rimmelzwaan, Guus F; Lambert, Linda C; Boslego, John; Rudenko, Larisa; Yeolekar, Leena; Robertson, James S; Hombach, Joachim; Ortiz, Justin R

    2015-11-27

    On 5-7 May 2014, the World Health Organization (WHO) convened the second integrated meeting on "influenza vaccines that induce broadly protective and long-lasting immune responses". Around 100 invited experts from academia, the vaccine industry, research and development funders, and regulatory and public health agencies attended the meeting. Areas covered included mechanisms of protection in natural influenza-virus infection and vaccine-induced immunity, new approaches to influenza-vaccine design and production, and novel routes of vaccine administration. A timely focus was on how this knowledge could be applied to both seasonal influenza and emerging viruses with pandemic potential such as influenza A (H7N9), currently circulating in China. Special attention was given to the development of possible universal influenza vaccines, given that the Global Vaccine Action Plan calls for at least one licensed universal influenza vaccine by 2020. This report highlights some of the topics discussed and provides an update on studies published since the report of the previous meeting.

  5. White long-lasting phosphorescence generation in a CaAl2Si2O8 : Eu2+, Mn2+, Dy3+ system through persistent energy transfer

    NASA Astrophysics Data System (ADS)

    Zhang, Jinsu; Chen, Baojiu; Sun, Jiashi; Li, Xiangping; Cheng, Lihong; Zhong, Haiyang

    2012-08-01

    Based on the persistent energy transfer principle, Mn2+ was introduced into a CaAl2Si2O8 : Eu2+/Dy3+ phosphor to achieve white long-lasting emissions. Eu2+, Mn2+ and Dy3+ tri-doped CaAl2Si2O8 phosphors with various Mn2+ concentrations were prepared via a solid-state reaction, and the crystal structure of the phosphors was identified by the x-ray diffraction technique. The luminescent properties of the Eu2+, Mn2+ and Dy3+ tri-doped CaAl2Si2O8 phosphors were studied. The energy transfer behaviour from Eu2+ to Mn2+ was analysed within the framework of Dexter theory. The physical mechanism of energy transfer was assigned to the electric dipole-quadrupole interaction. It was also demonstrated that the colour coordinates of the phosphors can be tuned from the blue region to the white region in the colour space. Furthermore, the afterglow decay and thermoluminescence curves were measured, indicating excellent phosphorescence properties of the current phosphors.

  6. Long-lasting production of new T and B cells and T-cell repertoire diversity in patients with primary immunodeficiency who had undergone stem cell transplantation: a single-centre experience.

    PubMed

    Valotti, Monica; Sottini, Alessandra; Lanfranchi, Arnalda; Bolda, Federica; Serana, Federico; Bertoli, Diego; Giustini, Viviana; Tessitore, Marion Vaglio; Caimi, Luigi; Imberti, Luisa

    2014-01-01

    Levels of Kappa-deleting recombination excision circles (KRECs), T-cell receptor excision circles (TRECs), and T-cell repertoire diversity were evaluated in 1038 samples of 124 children with primary immunodeficiency, of whom 102 (54 with severe combined immunodeficiency and 48 with other types of immunodeficiency) underwent hematopoietic stem cell transplantation. Twenty-two not transplanted patients with primary immunodeficiency were used as controls. Only data of patients from whom at least five samples were sent to the clinical laboratory for routine monitoring of lymphocyte reconstitutions were included in the analysis. The mean time of the follow-up was 8 years. The long-lasting posttransplantation kinetics of KREC and TREC production occurred similarly in patients with severe combined immunodeficiency and with other types of immunodeficiency and, in both groups, the T-cell reconstitution was more efficient than in nontransplanted children. Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period. However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire. Overall, our data suggest that long-term B- and T-cell reconstitution was equally achieved in children with severe combined immunodeficiency and with other types of primary immunodeficiency.

  7. Intrinsic Friction Microscopy

    NASA Astrophysics Data System (ADS)

    Knorr, Daniel; Overney, Rene

    2008-03-01

    A novel scanning probe methodology based on lateral force microscopy is presented wherein kinetic friction measurements, obtained as a function of velocity for various temperatures, are used to deduce apparent Arrhenius-type activation energies for surface and subsurface molecular mobilities. Depending on the coupling strength (cooperativity) between molecular mobilities involved the dissipation energy can carry a significant entropic energy contribution, accounting for the majority of the apparent Arrhenius activation energy. The intrinsic friction methodology also provides a means of directly separating enthalpic energy contributions from entropic ones by employing absolute rate theory. As such, the degree of cooperativity in the system is readily apparent. This methodology is illustrated with nanoscale tribological experiments on two systems, (1) monodisperse, atactic polystyrene and (2) self assembling molecular glassy chromophores. In polystyrene, dissipation was found to be a discrete function of loading, where the γ-relaxation (phenyl group rotation) was recovered for ultra low loads and the β-relaxation (local backbone translation) for higher loads in the same temperature range, indicating sensitivity to surface and subsurface mobilities. For self assembling glassy chromophores, the degree of intermolecular cooperativity was deduced using the methodology, resulting in an increased understanding of the interactions between self assembling molecules.

  8. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  9. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-12-25

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat. 11 figs.

  10. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. the second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  11. Activity-Regulated Genes as Mediators of Neural Circuit Plasticity

    PubMed Central

    Leslie, Jennifer H.; Nedivi, Elly

    2011-01-01

    Modifications of neuronal circuits allow the brain to adapt and change with experience. This plasticity manifests during development and throughout life, and can be remarkably long lasting. Many electrophysiological and molecular mechanisms are common to the seemingly diverse types of activity-dependent functional adaptation that take place during developmental critical periods, learning and memory, and alterations to sensory map representations in the adult. Experience-dependent plasticity is triggered when neuronal excitation activates cellular signaling pathways from the synapse to the nucleus that initiate new programs of gene expression. The protein products of activity-regulated genes then work via a diverse array of cellular mechanisms to modify neuronal functional properties. They fine-tune brain circuits by strengthening or weakening synaptic connections or by altering synapse numbers. Their effects are further modulated by posttranscriptional regulatory mechanisms, often also dependent on activity, that control activity-regulated gene transcript and protein function. Thus, the cellular response to neuronal activity integrates multiple tightly coordinated mechanisms to precisely orchestrate long-lasting, functional and structural changes in brain circuits. PMID:21601615

  12. Translational regulatory mechanisms in persistent forms of synaptic plasticity.

    PubMed

    Kelleher, Raymond J; Govindarajan, Arvind; Tonegawa, Susumu

    2004-09-30

    Memory and synaptic plasticity exhibit distinct temporal phases, with long-lasting forms distinguished by their dependence on macromolecular synthesis. Prevailing models for the molecular mechanisms underlying long-lasting synaptic plasticity have largely focused on transcriptional regulation. However, a growing body of evidence now supports a crucial role for neuronal activity-dependent mRNA translation, which may occur in dendrites for a subset of neuronal mRNAs. Recent work has begun to define the signaling mechanisms coupling synaptic activation to the protein synthesis machinery. The ERK and mTOR signaling pathways have been shown to regulate the activity of the general translational machinery, while the translation of particular classes of mRNAs is additionally controlled by gene-specific mechanisms. Rapid enhancement of the synthesis of a diverse array of neuronal proteins through such mechanisms provides the components necessary for persistent forms of LTP and LTD. These findings have important implications for the synapse specificity and associativity of protein synthesis-dependent changes in synaptic strength.

  13. Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

    NASA Astrophysics Data System (ADS)

    Toto, Angelo; Camilloni, Carlo; Giri, Rajanish; Brunori, Maurizio; Vendruscolo, Michele; Gianni, Stefano

    2016-02-01

    Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions.

  14. Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

    PubMed Central

    Toto, Angelo; Camilloni, Carlo; Giri, Rajanish; Brunori, Maurizio; Vendruscolo, Michele; Gianni, Stefano

    2016-01-01

    Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions. PMID:26912067

  15. Epilepsies and neuronal plasticity: for better or for worse?

    PubMed

    Ben-Ari, Yehezkel

    2008-01-01

    Extensive experimental investigations have confirmed that "seizures beget seizures." Thus, in adults, limbic seizures lead to cell loss, followed by the formation of novel excitatory synapses that contribute to generating further seizures. The triggering signal is an enhancement of synaptic efficacy, followed by a molecular cascade that triggers axonal sprouting. New synapses are aberrant, since they are formed in regions in which they are not present in controls. They also involve receptors that are not present in controls, and this facilitates the generation of seizures. Therefore, an aberrant form of reactive neuronal plasticity provides a substrate for the long-lasting sequelae of seizures. Since these events take place in brain structures involved in integrative and mnemonic functions, they will have an important impact. Reactive plasticity is documented for other insults and disorders, and may be the basis for the long-term progression of neurodegenerative disorders.

  16. Epilepsies and neuronal plasticity: for better or for worse?

    PubMed Central

    Yehezkel, Ben-Ari

    2008-01-01

    Extensive experimental investigations have confirmed that “seizures beget seizures.” Thus, in adults, limbic seizures lead to cell loss, followed by the formation of novel excitatory synapses that contribute to generating further seizures. The triggering signal is an enhance ment of synaptic efficacy, followed by a molecular cas cade that triggers axonal sprouting. New synapses are aberrant, since they are formed in regions in which they are not present in controls. They also involve receptors that are not present in controls, and this facilitates the generation of seizures. Therefore, an aberrant form of reactive neuronal plasticity provides a sub strate for the long-lasting seguelae of seizures. Since these events take place in brain structures involved in integrative and mnemonic functions, they will have an important impact. Reactive plasticity is documented for other insults and disorders, and may be the basis for the long-term progression of neurodegenerative disorders. PMID:18472481

  17. Intrinsic adaptation in autonomous recurrent neural networks.

    PubMed

    Marković, Dimitrije; Gros, Claudius

    2012-02-01

    A massively recurrent neural network responds on one side to input stimuli and is autonomously active, on the other side, in the absence of sensory inputs. Stimuli and information processing depend crucially on the quality of the autonomous-state dynamics of the ongoing neural activity. This default neural activity may be dynamically structured in time and space, showing regular, synchronized, bursting, or chaotic activity patterns. We study the influence of nonsynaptic plasticity on the default dynamical state of recurrent neural networks. The nonsynaptic adaption considered acts on intrinsic neural parameters, such as the threshold and the gain, and is driven by the optimization of the information entropy. We observe, in the presence of the intrinsic adaptation processes, three distinct and globally attracting dynamical regimes: a regular synchronized, an overall chaotic, and an intermittent bursting regime. The intermittent bursting regime is characterized by intervals of regular flows, which are quite insensitive to external stimuli, interceded by chaotic bursts that respond sensitively to input signals. We discuss these findings in the context of self-organized information processing and critical brain dynamics.

  18. Intrinsic Angular Momentum of Light.

    ERIC Educational Resources Information Center

    Santarelli, Vincent

    1979-01-01

    Derives a familiar torque-angular momentum theorem for the electromagnetic field, and includes the intrinsic torques exerted by the fields on the polarized medium. This inclusion leads to the expressions for the intrinsic angular momentum carried by the radiation traveling through a charge-free medium. (Author/MA)

  19. The intrinsic resistance of bacteria.

    PubMed

    Gang, Zhang; Jie, Feng

    2016-10-20

    Antibiotic resistance is often considered to be a trait acquired by previously susceptible bacteria, on the basis of which can be attributed to the horizontal acquisition of new genes or the occurrence of spontaneous mutation. In addition to acquired resistance, bacteria have a trait of intrinsic resistance to different classes of antibiotics. An intrinsic resistance gene is involved in intrinsic resistance, and its presence in bacterial strains is independent of previous antibiotic exposure and is not caused by horizontal gene transfer. Recently, interest in intrinsic resistance genes has increased, because these gene products not only may provide attractive therapeutic targets for development of novel drugs that rejuvenate the activity of existing antibiotics, and but also might predict future emergence of resistant pathogens if they become mobilized. In the present review, we summarize the conventional examples of intrinsic resistance, including the impermeability of cellular envelopes, the activity of multidrug efflux pumps or lack of drug targets. We also demonstrate that transferases and enzymes involved in basic bacterial metabolic processes confer intrinsic resistance in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. We present as well information on the cryptic intrinsic resistance genes that do not confer resistance to their native hosts but are capable of conferring resistance when their expression levels are increased and the activation of the cryptic genes. Finally, we discuss that intrinsic genes could be the origin of acquired resistance, especially in the genus Acinetobacter.

  20. Development of intrinsic IPT scintillator

    SciTech Connect

    Bross, A.D.

    1989-07-31

    We report on the development of a new polystyrene based plastic scintillator. Optical absorption, fluorescence and light output measurements are presented. Preliminary results of radiation damage effects are also given and compared to the effects on a commercial plastic scintillator, NE 110. 6 refs., 12 figs.

  1. Novel long-lasting impregnation technique transferred from clothing to bednets: extended efficacy and residual activity of different pyrethroids against Aedes aegypti as shown by EN ISO 6330-standardized machine laundering.

    PubMed

    Faulde, Michael; Albiez, Gunther; Nehring, Oliver

    2012-06-01

    A novel long-lasting insecticide-treated net (LLIN) has been designed by embedding the pyrethroids deltamethrin, cyfluthrin, permethrin, or etofenprox, onto the fibres of bed net cotton fabric by transferring a new polymer-coating technique from clothing to netting material. EN ISO 6330, the more stringent European Norm for domestic washing and drying procedures for textile testing, has been newly employed to monitor and validate more precise wash durability and residual bioactivity of LLINs. Wash durability, residual insecticidal activity and mosquito landing/biting protection has been investigated and compared with four commercially available LLINs. The pyrethroid-embedding impregnation technique allows binding of high concentrations exceeding 8,000 mg permethrin/m(2) within one single-polymer layer. Recovery rates of 95.7 ± 5.8%, 92.4 ± 14.0%, 70.2 ± 9.1%, and 64.2 ± 6.3% for cyfluthrin; 32.4 ± 11.4%, 32.4 ± 12%, 35.1 ± 16.2%, and 35.8 ± 15.7% for deltamethrin; 75.3 ± 12.9%, 57.1 ± 15.8%, 48.5 ± 4.0%, and 35.6 ± 4.7% for etofenprox; and 95.7 ± 5.8%, 80.2 ± 8.6%, 39.1 ± 7.9%, and 34.1 ± 8.8% were measured after 1, 5, 10, and 20 launderings. Laundering resistance was highest with cyfluthrin > deltamethrin ≈ etofenprox ≈ permethrin. After one and five launderings, commercial LLINs revealed percentage pyrethroid recovery rates of 26.3 ± 11.8% and 0.9 ± 1.2% for the Care Plus(®) net; 31.8% and 28.9% for the Permanet(®) 2.0; 61.4% and 45.6% for the Net Protect(®); and 80.4% and 68.3% for the Conmanet(®). Recovery rates reveal that the polymer-coating method resulted in extended wash durability. Dose-dependent 100% knockdown rates were most effective with deltamethrin > cyfluthrin > permethrin ≈ etofenprox. LLINs tested at concentrations up to 8,000 mg permethrin/m(2) did not protect from mosquito bites. Results on long-lasting efficacy and

  2. Large-scale implementation of disease control programmes: a cost-effectiveness analysis of long-lasting insecticide-treated bed net distribution channels in a malaria-endemic area of western Kenya—a study protocol

    PubMed Central

    Gama, Elvis; Were, Vincent; Ouma, Peter; Desai, Meghna; Niessen, Louis; Buff, Ann M; Kariuki, Simon

    2016-01-01

    Introduction Historically, Kenya has used various distribution models for long-lasting insecticide-treated bed nets (LLINs) with variable results in population coverage. The models presently vary widely in scale, target population and strategy. There is limited information to determine the best combination of distribution models, which will lead to sustained high coverage and are operationally efficient and cost-effective. Standardised cost information is needed in combination with programme effectiveness estimates to judge the efficiency of LLIN distribution models and options for improvement in implementing malaria control programmes. The study aims to address the information gap, estimating distribution cost and the effectiveness of different LLIN distribution models, and comparing them in an economic evaluation. Methods and analysis Evaluation of cost and coverage will be determined for 5 different distribution models in Busia County, an area of perennial malaria transmission in western Kenya. Cost data will be collected retrospectively from health facilities, the Ministry of Health, donors and distributors. Programme-effectiveness data, defined as the number of people with access to an LLIN per 1000 population, will be collected through triangulation of data from a nationally representative, cross-sectional malaria survey, a cross-sectional survey administered to a subsample of beneficiaries in Busia County and LLIN distributors’ records. Descriptive statistics and regression analysis will be used for the evaluation. A cost-effectiveness analysis will be performed from a health-systems perspective, and cost-effectiveness ratios will be calculated using bootstrapping techniques. Ethics and dissemination The study has been evaluated and approved by Kenya Medical Research Institute, Scientific and Ethical Review Unit (SERU number 2997). All participants will provide written informed consent. The findings of this economic evaluation will be disseminated through

  3. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

    SciTech Connect

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-12-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 {mu}g/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 {mu}g/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.

  4. Microdistribution of the resistance of malaria vectors to deltamethrin in the region of Plateau (southeastern Benin) in preparation for an assessment of the impact of resistance on the effectiveness of Long Lasting Insecticidal Nets (LLINs)

    PubMed Central

    2014-01-01

    Background This study aims to research two areas, one with a resistant and the other with a susceptible profile of An. gambiae to deltamethrin in the region of Plateau (southern Benin). In each area, eight localities were sought. Both areas were needed for the assessment of the impact of malaria vector resistance to pyrethroids on the effectiveness of Long Lasting Insecticidal Nets (LLINs). The susceptible area of An. gambiae to deltamethrin was used as a control. Methods In total, 119 localities in the region of Plateau were screened by sampling An. gambiae s.l larvae. Female mosquitoes resulting from these larvae were exposed to 0.05% deltamethrin following WHO standards. PCR was used to identify species and molecular forms of the dead and alive mosquitoes. Finally, we identified kdr mutations (1014 F and1014S) using the HOLA technique. Results Fifty-six out of 119 prospected localities tested positive for Anopheles gambae s.l breeding sites. The results showed that An. gambiae was resistant to deltamethrin in 39 localities and susceptible in only 2 localities; resistance to deltamethrin was suspected in 15 localities. The HOLA technique confirmed the presence of kdr 1014 F mutation and the absence of kdr 1014S mutation. The kdr 1014 F mutation was found in both M and S molecular forms at relatively high frequencies therefore confirming the susceptibility tests. Conclusion We were unable to identify the eight susceptible areas due to the overall resistance of An. gambiae to deltamethrin in the region of Plateau. To implement the study, we kept two areas, one with high resistance (R+++) and the other with low resistance (R+) of An. gambiae to deltamethrin. PMID:24564260

  5. Long-lasting changes in morphine-induced locomotor sensitization and tolerance in Long-Evans mother rats as a result of periodic postpartum separation from the litter: a novel model of increased vulnerability to drug abuse?

    PubMed

    Kalinichev, Mikhail; Easterling, Keith W; Holtzman, Stephen G

    2003-02-01

    Daily postpartum separations from the litter produce enduring changes in anxiety and sensitivity to the antinociceptive effects of morphine in Long-Evans dams. We tested whether postpartum experience alters sensitivity to the effects of morphine on locomotor activity. Dams were tested 4-6 weeks after their pups were weaned, and had one of the following backgrounds: daily separation from the litter on postpartum days 2-14 for either 3 h (prolonged separation-LS) or 15 min (brief separation-BS), or no separation (nonhandled control-NH). After 2 consecutive days (B1-2) of baseline activity measurements, subjects were tested daily after s.c. injections of either morphine (10 mg/kg) or saline for 7 days and again on day 10. Beginning 5 days later, saline and 1.0-10 mg/kg of morphine were tested in all dams. On B1, LS and BS dams habituated slower than NH controls, yielding higher horizontal counts. LS dams failed to habituate across baseline days and were more active than other dams on B2. Sensitization, a progressive increase in horizontal activity, was more rapid and robust in LS and BS dams compared to NH animals. LS was the only group that developed tolerance to morphine-induced decreases in vertical activity. In LS dams with the history of morphine treatment, injection of saline resulted in higher horizontal activity and center time compared to saline-treated counterparts, indicative of conditioning. Among animals with a history of saline treatment, LS dams were more sensitive to morphine challenges than BS and NH dams. As a result of the robust and long-lasting increases in the ability of morphine to induce behavioral sensitization in litter-separated dams, periodic postpartum separation may represent a new animal model of increased vulnerability to substance abuse.

  6. Lipo-oxytocin-1, a Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups, Has Long-Lasting Effects on Anxiety-Related Behavior and Social Avoidance in CD157 Knockout Mice.

    PubMed

    Mizuno, Akira; Cherepanov, Stanislav M; Kikuchi, Yusuke; Fakhrul, Azam Akm; Akther, Shirin; Deguchi, Kisaburo; Yoshihara, Toru; Ishihara, Katsuhiko; Shuto, Satoshi; Higashida, Haruhiro

    2015-01-20

    Oxytocin (OT) is a nonapeptide hormone that is secreted into the brain and blood circulation. OT has not only classical neurohormonal roles in uterine contraction and milk ejection during the reproductive phase in females, but has also been shown to have new pivotal neuromodulatory roles in social recognition and interaction in both genders. A single administration of OT through nasal spray increases mutual recognition and trust in healthy subjects and psychiatric patients, suggesting that OT is a potential therapeutic drug for autism spectrum disorders, schizophrenia, and some other psychiatric disorders. Although the mechanism is not well understood, it is likely that OT can be transported into the brain where it activates OT receptors to exert its function in the brain. However, the amount transported into the brain may be low. To ensure equivalent effects, an OT analog with long-lasting and effective blood-brain barrier penetration properties would be beneficial for use as a therapeutic drug. Here, we designed and synthesized a new oxytocin analog, lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated at the amino group of the cysteine9 residue and the phenolic hydroxyl group of the tyrosine8 residue of the OT molecule. To determine whether LOT-1 actually has an effect on the central nervous system, we examined its effects in a CD157 knockout model mouse of the non-motor psychiatric symptoms of Parkinson's disease. Similar to OT, this analog rescued anxiety-like behavior and social avoidance in the open field test with the social target in a central arena 30 min after intraperitoneal injection in CD157 knockout mice. When examined 24 h after injection, the mice treated with LOT-1 displayed more recovery than those given OT. The results suggest that LOT-1 has a functional advantage in recovery of social behavioral impairment, such as those caused by neurodegenerative diseases, autism spectrum disorders, and schizophrenia.

  7. Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region.

    PubMed

    Luo, Pan; Lu, Yun; Li, Changjun; Zhou, Mei; Chen, Cheng; Lu, Qing; Xu, Xulin; He, Zhi; Guo, Lianjun

    2015-09-01

    Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12weeks group, 2VO 4, 8 and 12weeks group. Learning and memory performance were evaluated with Morris water maze (MWM) and long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Expression of NeuN, HCN1 and HCN2 in hippocampal CA1, DG and CA3 areas was quantified by immunohistochemistry and western blotting. Our data showed that CCH induced a remarkable spatial learning and memory deficits in rats of 2VO 4, 8, and 12weeks group although neuronal loss only occurred after 4weeks of 2VO surgery in CA1. In addition, a significant reduction of HCN1 surface expression in CA1 was observed in the group that suffered 4weeks ischemia but neither 8 nor 12weeks. However, HCN2 surface expression in CA1 increased throughout the ischemia time-scales (4, 8 and 12w). Our findings indicate spatial learning and memory deficits in the CCH model are associated with disturbed HCN1 and HCN2 surface expression in hippocampal CA1. The altered patterns of both HCN1 and HCN2 surface expression may be implicated in the early stage (4w) of spatial learning and memory impairments; and the stable and long-lasting impairments of spatial learning and memory may partially attribute to the up-regulated HCN2 surface expression.

  8. Exendin-4-loaded PLGA microspheres relieve cerebral ischemia/reperfusion injury and neurologic deficits through long-lasting bioactivity-mediated phosphorylated Akt/eNOS signaling in rats

    PubMed Central

    Chien, Chiang-Ting; Jou, Ming-Jia; Cheng, Tai-Yu; Yang, Chih-Hui; Yu, Tzu-Ying; Li, Ping-Chia

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) receptor activation in the brain provides neuroprotection. Exendin-4 (Ex-4), a GLP-1 analog, has seen limited clinical usage because of its short half-life. We developed long-lasting Ex-4-loaded poly(D,L-lactide-co-glycolide) microspheres (PEx-4) and explored its neuroprotective potential against cerebral ischemia in diabetic rats. Compared with Ex-4, PEx-4 in the gradually degraded microspheres sustained higher Ex-4 levels in the plasma and cerebrospinal fluid for at least 2 weeks and improved diabetes-induced glycemia after a single subcutaneous administration (20 μg/day). Ten minutes of bilateral carotid artery occlusion (CAO) combined with hemorrhage-induced hypotension (around 30 mm Hg) significantly decreased cerebral blood flow and microcirculation in male Wistar rats subjected to streptozotocin-induced diabetes. CAO increased cortical O2− levels by chemiluminescence amplification and prefrontal cortex edema by T2-weighted magnetic resonance imaging analysis. CAO significantly increased aquaporin 4 and glial fibrillary acidic protein expression and led to cognition deficits. CAO downregulated phosphorylated Akt/endothelial nitric oxide synthase (p-Akt/p-eNOS) signaling and enhanced nuclear factor (NF)-κBp65/intercellular adhesion molecule-1 (ICAM-1) expression, endoplasmic reticulum (ER) stress, and apoptosis in the cerebral cortex. PEx-4 was more effective than Ex-4 to improve CAO-induced oxidative injury and cognitive deficits. The neuroprotection provided by PEx-4 was through p-Akt/p-eNOS pathways, which suppressed CAO-enhanced NF-κB/ICAM-1 signaling, ER stress, and apoptosis. PMID:26058696

  9. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain.

    PubMed

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-12-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 microg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 microg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.

  10. Targeting the genital tract mucosa with a lipopeptide/recombinant adenovirus prime/boost vaccine induces potent and long-lasting CD8+ T cell immunity against herpes: importance of MyD88.

    PubMed

    Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; Benmohamed, Lbachir

    2012-11-01

    Targeting of the mucosal immune system of the genital tract with subunit vaccines has failed to induce potent and durable local CD8(+) T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), which causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8(+) T cell immunity to protect the female genital tract from herpes. The lipopeptide vaccine and the rAdv5 vaccine express the immunodominant HSV-2 CD8(+) T cell epitope (gB(498-505)), and both were delivered intravaginally in the progesterone-induced B6 mouse model of genital herpes. Compared with mice immunized with the homologous lipopeptide/lipopeptide (Lipo/Lipo) vaccine, the Lipo/rAdv5 prime/boost immunized mice 1) developed potent and sustained HSV-specific CD8(+) T cells, detected in both the genital tract draining nodes and in the vaginal mucosa; 2) had significantly lower virus titers; 3) had decreased overt signs of genital herpes disease; and 4) did not succumb to lethal infection (p < 0.005) after intravaginal HSV-2 challenge. Polyfunctional CD8(+) T cells, producing IFN-γ, TNF-α, and IL-2 and exhibiting cytotoxic activity, were associated with protection (p < 0.005). The protective CD8(+) T cell response was significantly compromised in the absence of the adapter MyD88 (p = 0.0001). Taken together, these findings indicate that targeting of the vaginal mucosa with a Lipo/rAdv5 prime/boost vaccine elicits a potent, MyD88-dependent, and long-lasting mucosal CD8(+) T cell protective immunity against sexually transmitted herpes infection and disease.

  11. Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

    PubMed

    Suzukawa, J; Omori, K; Okugawa, G; Fujiseki, Y; Heizmann, C W; Inagaki, C

    1999-07-10

    A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

  12. [Methods for the phase IV evaluation of malaria vector control interventions: a case-control study of the effectiveness of long lasting impregnated bed nets after their deployment in Benin].

    PubMed

    Rogier, C; Henry, M C; Luxemburger, C

    2009-04-01

    Vector-control measures are a component of integrated malaria control strategies. After evaluation in phase III pilot studies, these measures are currently being deployed in many endemic malaria zones. Their effectiveness must be evaluated under actual conditions of use but it is not ethically acceptable to use unexposed individuals for control groups. In a attempt to overcome this problem, a case-control study was undertaken to evaluate the effectiveness of long-lasting insecticide treated mosquito nets (LLITN) against clinical malaria attacks due to Plasmodium falciparum in an endemic area of southern Benin. During a 4-month period (July to October 2008), 35 clinically documented cases of uncomplicated malaria (fever + parasite density > 3000/microL) were diagnosed in children less than 5 years old from 6 villages in the Tori Bossito medical district. The parents of these children were interviewed at the same time as the parents of 181 children randomly selected from the same 6 villages. A total of 115 of the randomly selected children who had not been feverish during study period were used as controls. The proportion of children having consistently slept under LLITN throughout the study period was 46% in the case group and 78% in the control group (OR=0.32, 95%CI: 0.15-0.71). These data show that the LLITN provided a significant level of protection, i.e., 68% (IC95%: 29%-85%). This case-control study shows that vector control measures can be effectively evaluated after deployment in population. The limitations of this methodology are discussed.

  13. Lipo-oxytocin-1, a Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups, Has Long-Lasting Effects on Anxiety-Related Behavior and Social Avoidance in CD157 Knockout Mice

    PubMed Central

    Mizuno, Akira; Cherepanov, Stanislav M.; Kikuchi, Yusuke; Fakhrul, Azam AKM; Akther, Shirin; Deguchi, Kisaburo; Yoshihara, Toru; Ishihara, Katsuhiko; Shuto, Satoshi; Higashida, Haruhiro

    2015-01-01

    Oxytocin (OT) is a nonapeptide hormone that is secreted into the brain and blood circulation. OT has not only classical neurohormonal roles in uterine contraction and milk ejection during the reproductive phase in females, but has also been shown to have new pivotal neuromodulatory roles in social recognition and interaction in both genders. A single administration of OT through nasal spray increases mutual recognition and trust in healthy subjects and psychiatric patients, suggesting that OT is a potential therapeutic drug for autism spectrum disorders, schizophrenia, and some other psychiatric disorders. Although the mechanism is not well understood, it is likely that OT can be transported into the brain where it activates OT receptors to exert its function in the brain. However, the amount transported into the brain may be low. To ensure equivalent effects, an OT analog with long-lasting and effective blood-brain barrier penetration properties would be beneficial for use as a therapeutic drug. Here, we designed and synthesized a new oxytocin analog, lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated at the amino group of the cysteine9 residue and the phenolic hydroxyl group of the tyrosine8 residue of the OT molecule. To determine whether LOT-1 actually has an effect on the central nervous system, we examined its effects in a CD157 knockout model mouse of the non-motor psychiatric symptoms of Parkinson’s disease. Similar to OT, this analog rescued anxiety-like behavior and social avoidance in the open field test with the social target in a central arena 30 min after intraperitoneal injection in CD157 knockout mice. When examined 24 h after injection, the mice treated with LOT-1 displayed more recovery than those given OT. The results suggest that LOT-1 has a functional advantage in recovery of social behavioral impairment, such as those caused by neurodegenerative diseases, autism spectrum disorders, and schizophrenia. PMID:25612002

  14. Endocannabinoids in Synaptic Plasticity and Neuroprotection

    PubMed Central

    Xu, Jian-Yi; Chen, Chu

    2014-01-01

    Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of physiological, pharmacological, and pathological processes. While activation of the eCB system primarily induces inhibitory effects on both GABAergic and glutamatergic synaptic transmission and plasticity through acting on presynaptically-expressed CB1 receptors in the brain, accumulated information suggests that eCB signaling is also capable of facilitating or potentiating excitatory synaptic transmission in the hippocampus. Recent studies show that a long-lasting potentiation of excitatory synaptic transmission at Schaffer collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs, accompanying with a long-term depression of inhibitory synaptic transmission (I-LTD) in hippocampal CA1 pyramidal neurons. This input-timing-dependent long-lasting synaptic potentiation at SC-CA1 synapses is mediated by 2-arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic NMDA receptors, group I metabotropic glutamate receptors (mGluRs), and a concurrent rise in intracellular Ca2+. Emerging evidence now also indicates that 2-AG is an important signaling mediator keeping brain homeostasis by exerting its anti-inflammatory and neuroprotective effects in response to harmful insults through CB1/2 receptor-dependent and/or independent mechanisms. Activation of the nuclear receptor protein peroxisome proliferator-activated receptor-γ (PPARγ) apparently is one of the important mechanisms in resolving neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the information summarized in this review suggests that the role of eCB signaling in maintaining integrity of brain function is greater than what we thought previously. PMID:24571856

  15. Recent progress on intrinsic charm

    NASA Astrophysics Data System (ADS)

    Hobbs, T. J.

    2017-03-01

    Over the past ˜10 years, the topic of the nucleon's nonperturbative or intrinsic charm (IC) content has enjoyed something of a renaissance, largely motivated by theoretical developments involving quark modelers and PDF-fitters. In this talk I will briefly describe the importance of intrinsic charm to various issues in high-energy phenomenology, and survey recent progress in constraining its overall normalization and contribution to the momentum sum rule of the nucleon. I end with the conclusion that progress on the side of calculation has now placed the onus on experiment to unambiguously resolve the proton's intrinsic charm component.

  16. On intrinsic time measure in the modeling of cyclic behavior of a Nitinol cubic block

    NASA Astrophysics Data System (ADS)

    Chiroiu, Veturia; Florinel Ionescu, Marius; Sireteanu, Tudor; Ioan, Rodica; Munteanu, Ligia

    2015-03-01

    In this paper, the cyclic behavior of a superelastic-plastic nitinol cubic block is described by using the Bouc-Wen model coupled to an intrinsic time measure other than clock time, which governs the behavior of the materials. As a consequence, the thermodynamic admissibility of the Bouc-Wen model is provided by the endochronic theory of plasticity. The role of the intrinsic time measure is described by capturing the stiffness and strength degradation and the opposite phenomena. Such behavior is due to the permanent-strain addition of residual martensite and alterations in the properties of the texture during phase transformation.

  17. Providing plastic zone extrusion

    DOEpatents

    Manchiraju, Venkata Kiran; Feng, Zhili; David, Stan A.; Yu, Zhenzhen

    2017-04-11

    Plastic zone extrusion may be provided. First, a compressor may generate frictional heat in stock to place the stock in a plastic zone of the stock. Then, a conveyer may receive the stock in its plastic zone from the compressor and transport the stock in its plastic zone from the compressor. Next, a die may receive the stock in its plastic zone from the conveyer and extrude the stock to form a wire.

  18. The Emerging Neuroscience of Intrinsic Motivation: A New Frontier in Self-Determination Research.

    PubMed

    Di Domenico, Stefano I; Ryan, Richard M

    2017-01-01

    Intrinsic motivation refers to people's spontaneous tendencies to be curious and interested, to seek out challenges and to exercise and develop their skills and knowledge, even in the absence of operationally separable rewards. Over the past four decades, experimental and field research guided by self-determination theory (SDT; Ryan and Deci, 2017) has found intrinsic motivation to predict enhanced learning, performance, creativity, optimal development and psychological wellness. Only recently, however, have studies begun to examine the neurobiological substrates of intrinsic motivation. In the present article, we trace the history of intrinsic motivation research, compare and contrast intrinsic motivation to closely related topics (flow, curiosity, trait plasticity), link intrinsic motivation to key findings in the comparative affective neurosciences, and review burgeoning neuroscience research on intrinsic motivation. We review converging evidence suggesting that intrinsically motivated exploratory and mastery behaviors are phylogenetically ancient tendencies that are subserved by dopaminergic systems. Studies also suggest that intrinsic motivation is associated with patterns of activity across large-scale neural networks, namely, those that support salience detection, attentional control and self-referential cognition. We suggest novel research directions and offer recommendations for the application of neuroscience methods in the study of intrinsic motivation.

  19. The Emerging Neuroscience of Intrinsic Motivation: A New Frontier in Self-Determination Research

    PubMed Central

    Di Domenico, Stefano I.; Ryan, Richard M.

    2017-01-01

    Intrinsic motivation refers to people’s spontaneous tendencies to be curious and interested, to seek out challenges and to exercise and develop their skills and knowledge, even in the absence of operationally separable rewards. Over the past four decades, experimental and field research guided by self-determination theory (SDT; Ryan and Deci, 2017) has found intrinsic motivation to predict enhanced learning, performance, creativity, optimal development and psychological wellness. Only recently, however, have studies begun to examine the neurobiological substrates of intrinsic motivation. In the present article, we trace the history of intrinsic motivation research, compare and contrast intrinsic motivation to closely related topics (flow, curiosity, trait plasticity), link intrinsic motivation to key findings in the comparative affective neurosciences, and review burgeoning neuroscience research on intrinsic motivation. We review converging evidence suggesting that intrinsically motivated exploratory and mastery behaviors are phylogenetically ancient tendencies that are subserved by dopaminergic systems. Studies also suggest that intrinsic motivation is associated with patterns of activity across large-scale neural networks, namely, those that support salience detection, attentional control and self-referential cognition. We suggest novel research directions and offer recommendations for the application of neuroscience methods in the study of intrinsic motivation. PMID:28392765

  20. Intrinsic magnetization of antiferromagnetic textures

    NASA Astrophysics Data System (ADS)

    Tveten, Erlend G.; Müller, Tristan; Linder, Jacob; Brataas, Arne

    2016-03-01

    Antiferromagnets (AFMs) exhibit intrinsic magnetization when the order parameter spatially varies. This intrinsic spin is present even at equilibrium and can be interpreted as a twisting of the homogeneous AFM into a state with a finite spin. Because magnetic moments couple directly to external magnetic fields, the intrinsic magnetization can alter the dynamics of antiferromagnetic textures under such influence. Starting from the discrete Heisenberg model, we derive the continuum limit of the free energy of AFMs in the exchange approximation and explicitly rederive that the spatial variation of the antiferromagnetic order parameter is associated with an intrinsic magnetization density. We calculate the magnetization profile of a domain wall and discuss how the intrinsic magnetization reacts to external forces. We show conclusively, both analytically and numerically, that a spatially inhomogeneous magnetic field can move and control the position of domain walls in AFMs. By comparing our model to a commonly used alternative parametrization procedure for the continuum fields, we show that the physical interpretations of these fields depend critically on the choice of parametrization procedure for the discrete-to-continuous transition. This can explain why a significant amount of recent studies of the dynamics of AFMs, including effective models that describe the motion of antiferromagnetic domain walls, have neglected the intrinsic spin of the textured order parameter.

  1. Evaluation of the efficacy of DDT indoor residual spraying and long-lasting insecticidal nets against insecticide resistant populations of Anopheles arabiensis Patton (Diptera: Culicidae) from Ethiopia using experimental huts

    PubMed Central

    2014-01-01

    Background Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal nets (LLINs) are major malaria vector control tools in Ethiopia. However, recent reports from different parts of the country showed that populations of Anopheles arabiensis, the principal malaria vector, have developed resistance to most families of insecticides recommended for public health use which may compromise the efficacy of both of these key vector control interventions. Thus, this study evaluated the efficacy of DDT IRS and LLINs against resistant populations of An. arabiensis using experimental huts in Asendabo area, southwestern Ethiopia. Methods The susceptibility status of populations of An. arabiensis was assessed using WHO test kits to DDT, deltamethrin, malathion, lambda-cyhalothrin, fenitrothion and bendiocarb. The efficacy of LLIN (PermaNet® 2.0), was evaluated using the WHO cone bioassay. Moreover, the effect of the observed resistance against malaria vector control interventions (DDT IRS and LLINs) were assessed using experimental huts. Results The findings of this study revealed that populations of An. arabiensis were resistant to DDT, deltamethrin, lambda-cyhalothrin and malathion with mortality rates of 1.3%, 18.8%, 36.3% and 72.5%, respectively but susceptible to fenitrothion and bendiocarb with mortality rates of 98.81% and 97.5%, respectively. The bio-efficacy test of LLIN (PermaNet® 2.0) against An. arabiensis revealed that the mosquito population showed moderate knockdown (64%) and mortality (78%). Moreover, mosquito mortalities in DDT sprayed huts and in huts with LLINs were not significantly different (p > 0.05) from their respective controls. Conclusion The evaluation of the efficacy of DDT IRS and LLINs using experimental huts showed that both vector control tools had only low to moderate efficacy against An. arabiensis populations from Ethiopia. Despite DDT being replaced by carbamates for IRS, the low efficacy of LLINs against the resistant population of An

  2. Comparative field evaluation of combinations of long-lasting insecticide treated nets and indoor residual spraying, relative to either method alone, for malaria prevention in an area where the main vector is Anopheles arabiensis

    PubMed Central

    2013-01-01

    Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Methods Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. Results All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Conclusions Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In

  3. A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    PubMed

    Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

    2016-02-01

    Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development.

  4. Mechanisms of action of escapin, a bactericidal agent in the ink secretion of the sea hare Aplysia californica: rapid and long-lasting DNA condensation and involvement of the OxyR-regulated oxidative stress pathway.

    PubMed

    Ko, Ko-Chun; Tai, Phang C; Derby, Charles D

    2012-04-01

    The marine snail Aplysia californica produces escapin, an L-amino acid oxidase, in its defensive ink. Escapin uses L-lysine to produce diverse products called escapin intermediate products of L-lysine (EIP-K), including α-amino-ε-caproic acid, Δ¹-piperidine-2-carboxylic acid, and Δ²-piperidine-2-carboxylic acid. EIP-K and H₂O₂ together, but neither alone, is a powerful bactericide. Here, we report bactericidal mechanisms of escapin products on Escherichia coli. We show that EIP-K and H₂O₂ together cause rapid and long-lasting DNA condensation: 2-min treatment causes significant DNA condensation and killing, and 10-min treatment causes maximal effect, lasting at least 70 h. We isolated two mutants resistant to EIP-K plus H₂O₂, both having a single missense mutation in the oxidation regulatory gene, oxyR. A complementation assay showed that the mutated gene, oxyR(A233V), renders resistance to EIP-K plus H₂O₂, and a gene dosage effect leads to reduction of resistance for strains carrying wild-type oxyR. Temperature stress with EIP-K does not produce the bactericidal effect, suggesting the effect is due to a specific response to oxidative stress. The null mutant for any single DNA-binding protein--Dps, H-NS, Hup, Him, or MukB--was not resistant to EIP-K plus H₂O₂, suggesting that no single DNA-binding protein is necessary to mediate this bactericidal effect, but allowing for the possibility that EIP-K plus H₂O₂ could function through a combination of DNA-binding proteins. The bactericidal effect of EIP-K plus H₂O₂ was eliminated by the ferrous ion chelator 1,10-phenanthroline, and it was reduced by the hydroxyl radical scavenger thiourea, suggesting hydroxyl radicals mediate the effects of EIP-K plus H₂O₂.

  5. Ulnar intrinsic anatomy and dysfunction.

    PubMed

    Dell, Paul C; Sforzo, Christopher R

    2005-01-01

    Normal hand function is a balance between the extrinsic and intrinsic musculature. Although individually the intrinsics are small muscles in diameter, collectively they represent a large muscle that contributes approximately 50% of grip strength. Dysfunction of the intrinsics consequently leads to impaired grip and pinch strength as well recognized deformities. Low ulnar nerve palsy preserves ulnar innervated extrinsics resulting in sensory loss, digital clawing, thumb deformity, abduction of the small finger, and asynchronous finger motion. High ulnar nerve palsy is characterized by the above plus paralysis of the ulnar profundi and the flexor carpi ulnaris. Understanding the normal anatomy allows the clinician to identify the site of the lesion and plan appropriate surgical intervention. This article revisits the classic work of Richard J. Smith on ulnar nerve palsy with contemporary perspective.

  6. Plastic encapsulated parts

    SciTech Connect

    Castillo, T.

    1994-10-01

    Plastic semiconductor packages were characterized as possible alternatives for canned devices, which are susceptible to internal shorts caused by conductive particles. Highly accelerated stress testing (HAST) as well as electrical and mechanical testing were conducted on plastic technology devices.

  7. Plastic casting resin poisoning

    MedlinePlus

    Epoxy poisoning; Resin poisoning ... Epoxy and resin can be poisonous if they are swallowed or their fumes are breathed in. ... Plastic casting resins are found in various plastic casting resin products.

  8. Recovering automotive plastics

    SciTech Connect

    Not Available

    1993-10-01

    This article reports on the results of a study on increasing the recycling of plastics in automobiles. Plastics are being used in increasing amounts in vehicles and new methods of retrieving these plastics for recycling are needed to reduce the amount of automotive shredder residue that is currently being sent to residues. The study concentrated on increasing the ease of disassembly and contaminant removal.

  9. Plastics in Building.

    ERIC Educational Resources Information Center

    Skeist, Irving, Ed.

    The evaluation and use of plastics in the construction industry are explained. The contributors offer extensive, timely, and thoroughly researched data on the chemistry, properties, functions, engineering behavior, and specific applications of plastics to building requirements. The major subjects discussed in depth are--(1) the role of plastics in…

  10. Processing of plastics

    PubMed Central

    Spaak, Albert

    1975-01-01

    An overview is given of the processing of plastic materials from the handling of polymers in the pellet and powder form to manufacturing of a plastic fabricated product. Various types of equipment used and melt processing ranges of various polymer formulations to make the myriad of plastic products that are commercially available are discussed. PMID:1175556

  11. Tomorrow's Plastic World

    ERIC Educational Resources Information Center

    Macdonald, Averil

    2005-01-01

    Far from being just cheap packaging materials, plastics may be the materials of tomorrow. Plastic can conduct electricity, and this opens up a host of high-tech possibilities in the home and in energy generation. These possibilities are discussed here along with how plastic can be recycled and perhaps even grown.

  12. Intrinsic Motivation in Physical Education

    ERIC Educational Resources Information Center

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  13. Individual Patterns in Intrinsic Motivation.

    ERIC Educational Resources Information Center

    Hom, Harry L., Jr.; Maxwell, Frederick R.

    The effects of extrinsic reward on students' intrinsic interest was investigated using a single-subject design in a behavior disorders classroom. Baseline measures of the interest level of five children (ages 9-11 years) were collected for academic and non-academic tasks. Assessment was then made of each subject's response hierarchy or level of…

  14. Biodegradability of Plastics

    PubMed Central

    Tokiwa, Yutaka; Calabia, Buenaventurada P.; Ugwu, Charles U.; Aiba, Seiichi

    2009-01-01

    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed. PMID:19865515

  15. Biodegradability of plastics.

    PubMed

    Tokiwa, Yutaka; Calabia, Buenaventurada P; Ugwu, Charles U; Aiba, Seiichi

    2009-08-26

    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

  16. Plastic Deformation of Accreted Planetesimals

    NASA Astrophysics Data System (ADS)

    Kadish, J.

    2005-08-01

    The early stages of planetesimal growth follow an accretion model (Weidenschilling, Icarus 2000), which influences the intrinsic strength of a body and may control how its shape evolves after growth. In previous work we have determined the stress field of an accreted planetesimal accounting for possible variation in the object's spin as it accretes (Kadish et al., IJSS In Press) At the end of growth, these objects are subject to transport mechanisms that can distribute them throughout the solar system. As they are transported these objects can be spun-up by tidal forces (Scheeres et al, Icarus 2000), YORP (Bottke et al., Asteroids III 2002), and collisions (Binzel et al., Asteroids II 1989). Such an increase of spin will cause perturbations to the initial stress field and may lead to failure. We are able to show analytically that failure is initiated on the object's surface and a plastic zone propagates inward as the object's spin is increased. If we model an accreted body as a conglomeration of rocks similar to a gravel or sand, the deformation in the region of failure is characterized using a Mohr-Coulomb failure criterion with negligible cohesion and zero hardening(e.g. Holsapple, Icarus 2001). Such a response is highly non-linear and must be solved using finite elements and iterative methods (Simo and Hughes, Computational Inelasticity 1998). Using the commercial finite element code ABAQUS, we present the shape deformation resulting from an elasto-plastic analysis of a spinning, self-gravitating accreted sphere that is spun-up after growth is complete. The methodology can be extended to model plastic deformation due to local failure for more complex planetesimal shapes, such as for the asteroid Kleopatra. This work has implications for the evolution of planetesimal shapes, the creation of binary and contact binary asteroids, and for the maximum spin rate of small planetary bodies.

  17. Intrinsic randomness and intrinsic irreversibility in classical dynamical systems

    PubMed Central

    Courbage, M.; Prigogine, I.

    1983-01-01

    We continue our previous work on dynamic “intrinsically random” systems for which we can derive dissipative Markov processes through a one-to-one change of representation. For these systems, the unitary group of evolution can be transformed in this way into two distinct Markov processes leading to equilibrium for either t→ + ∞ or t→ - ∞. To lift the degeneracy, we first formulate the second principle as a selection rule that is meaningful in intrinsically random systems. For these systems, this excludes a set of unrealizable states. As a result of this exclusion, permitted initial conditions correspond to a set of states that is not invariant through velocity inversion. In this way, the time-reversal symmetry of dynamics is broken and these systems acquire a new feature we may call “intrinsic irreversibility.” The set of admitted initial conditions can be characterized by an entropy displaying the amount of information necessary for their preparation. The initial conditions selected by the second law correspond to a finite amount of information, while the initial conditions that are rejected correspond to an infinite amount of information and are therefore “impossible.” We believe that our formulation permits a microscopic formulation of the second law of thermodynamics for well-defined classes of dynamical systems. PMID:16578774

  18. How Plastics Work

    NASA Astrophysics Data System (ADS)

    Bloomfield, Louis

    2013-03-01

    We encounter plastics every day, but despite their widespread use, amazing range of properties, and basic scientific underpinnings, most physicists--like most people--know relatively little about plastics. In contrast to hard crystalline and amorphous solids (e.g., metals, salts, ceramics, and glasses), we take plastics for granted, select them carelessly, and examine them more closely only on a need-to-know basis. By ignoring plastics until we need them, however, we risk not knowing what we don't know and using the wrong ones. To repurpose a familiar advertisement, ``there's a plastic for that.'' This talk will review some of the basic physics and science of plastics. It will examine the roles of temperature, order, intermolecular forces, entanglements, and linkages in plastics, and how those issues affect the properties of a given plastic. We'll stop along the way to recognize a few of the more familiar plastics, natural and synthetic, and explain some of their mechanical, chemical, and optical properties. The talk will conclude by explaining the remarkable properties of a plastic that has been largely misunderstood since its discovery 70 years ago: Silly Putty.

  19. Quasar redshifts: the intrinsic component

    NASA Astrophysics Data System (ADS)

    Hansen, Peter M.

    2016-09-01

    The large observed redshift of quasars has suggested large cosmological distances and a corresponding enormous energy output to explain the brightness or luminosity as seen at earth. Alternative or complementary sources of redshift have not been identified by the astronomical community. This study examines one possible source of additional redshift: an intrinsic component based on the plasma characteristics of high temperature and high electron density which are believed to be present.

  20. Our plastic age.

    PubMed

    Thompson, Richard C; Swan, Shanna H; Moore, Charles J; vom Saal, Frederick S

    2009-07-27

    Within the last few decades, plastics have revolutionized our daily lives. Globally we use in excess of 260 million tonnes of plastic per annum, accounting for approximately 8 per cent of world oil production. In this Theme Issue of Philosophical Transactions of the Royal Society, we describe current and future trends in usage, together with the many benefits that plastics bring to society. At the same time, we examine the environmental consequences resulting from the accumulation of waste plastic, the effects of plastic debris on wildlife and concerns for human health that arise from the production, usage and disposal of plastics. Finally, we consider some possible solutions to these problems together with the research and policy priorities necessary for their implementation.

  1. Intrinsic Patterns of Human Activity

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  2. Plastics and health risks.

    PubMed

    Halden, Rolf U

    2010-01-01

    By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrine-disrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs--i.e., reduce, reuse, recycle, rethink, restrain--for minimizing pre- and postnatal exposures to potentially harmful components of plastics.

  3. Additives in plastics.

    PubMed Central

    Deanin, R D

    1975-01-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products. PMID:1175566

  4. Additives in plastics.

    PubMed

    Deanin, R D

    1975-06-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products.

  5. Aggressive bronchoscopic management of plastic bronchitis.

    PubMed

    Preciado, Diego; Verghese, Susan; Choi, Sukgi

    2010-07-01

    Plastic bronchitis or "Bronchitis Plastica" is a rare disease characterized by the formation of thick, tenacious, arborizing mucofibrinous tracheobronchial casts that result in life-threatening airway obstruction and pulmonary failure. We review three children who developed recurrent plastic bronchitis after undergoing a Fontan procedure for single ventricle physiology. Case series of three patients with plastic bronchitis at a tertiary referral children's hospital. All patients required repeated bronchoscopies, one requiring four separate ones over a week's period, for removal of the rigid casts. Extra-corporal membrane oxygenation (ECMO) was needed in two children because of severe respiratory failure. All were also managed with adjunctive intensive medical support. Pulmonary function returned to normal in all children, but recurred 2 months later in one who subsequently expired due to pulmonary failure. Plastic bronchitis is an unusual condition of unknown cause that occurs in multiple clinical settings, but especially in those children who have undergone a Fontan operation. Management of this distressing situation is difficult and early diagnosis and aggressive measures to remove rigid casts combined with intensive medical care are necessary. The intrinsic cardiopulmonary physiology of children with Fontan procedures, including the risk of arrhythmias, hypo-oxygenation, and pulmonary hypertension make this condition even more complex.

  6. Nuclear Filtering of Intrinsic Charm

    SciTech Connect

    Kopeliovich, B. Z.; Potashnikova, I. K.; Schmidt, Ivan

    2010-11-12

    Nuclei are transparent for a heavy intrinsic charm (IC) component of the beam hadrons, what leads to an enhanced nuclear dependence of open charm production at large Feynman x{sub F}. Indeed, such an effect is supported by data from the SELEX experiment published recently [1]. Our calculations reproduce well the data, providing strong support for the presence of IC in hadrons in amount less than 1%. Moreover, we performed an analysis of nuclear effects in J/{Psi} production and found at large x{sub F} a similar, albeit weaker effect, which does not contradict data.

  7. Detecting plastics in seedcotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To increase global market share and value the US cotton industry needs to supply cotton lint that is free of contamination. Removing plastic contamination first requires developing a means to detect plastics in seedcotton. This study was conducted to validate a custom Ion Mobility Spectrometer (IM...

  8. Detecting plastics in seedcotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The US cotton industry wants to increase market share and value by supplying pure cotton. Removing contamination requires developing a means to detect plastics in seedcotton. This study was conducted to determine if Ion Mobility Spectrometry (IMS) could be used to find small amounts of plastic in ...

  9. Biodegradation of plastics.

    PubMed

    Shimao, M

    2001-06-01

    Widespread studies on the biodegradation of plastics have been carried out in order to overcome the environmental problems associated with synthetic plastic waste. Recent work has included studies of the distribution of synthetic polymer-degrading microorganisms in the environment, the isolation of new microorganisms for biodegradation, the discovery of new degradation enzymes, and the cloning of genes for synthetic polymer-degrading enzymes.

  10. Track recording plastic compositions

    NASA Technical Reports Server (NTRS)

    Tarle, Gregory (Inventor)

    1983-01-01

    Improved nuclear track recording plastic compositions are provided which exhibit greatly decreased surface roughness when etched to produce visible tracks of energetic nuclear particles which have passed into and/or through said plastic. The improved compositions incorporate a small quantity of a phthalic acid ester into the major plastic component which is derived from the polymerization of monomeric di-ethylene glycol bis allyl carbonate. Di-substituted phthalic acid esters are preferred as the added component, with the further perference that the ester substituent has a chain length of 2 or more carbon atoms. The inclusion of the phthalic acid ester to an extent of from about 1-2% by weight of the plastic compositions is sufficient to drastically reduce the surface roughness ordinarily produced when the track recording plastic is contacted by etchants.

  11. Activity- and age-dependent GABAergic synaptic plasticity in the developing rat hippocampus.

    PubMed

    Gubellini, P; Ben-Ari, Y; Gaïarsa, J L

    2001-12-01

    Activity-dependent plasticity of GABAergic synaptic transmission was investigated in rat hippocampal slices obtained between postnatal day (P) 0-15 using the whole-cell patch-clamp recording technique. Spontaneous GABA(A) receptor-mediated postsynaptic currents (sGABA(A)-PSCs) were isolated in the presence of ionotropic glutamate receptor antagonists. A conditioning protocol relevant to the physiological condition, consisting of repetitive depolarizing pulses (DPs) at 0.1 Hz, was able to induce long-lasting changes in both frequency and amplitude of sGABA(A)-PSCs between P0 and P8. Starting from P12, DPs were unable to induce any form of synaptic plasticity. The effects of DPs were tightly keyed to the frequency at which they were delivered. When delivered at a lower (0.05 Hz) or higher (1 Hz) frequency, DPs failed to induce any long-lasting change in the frequency or amplitude of sGABA(A)-PSCs. In two cases, DPs were able to activate sGABA(A)-PSCs in previously synaptically silent cells at P0-1. These results show that long-term changes in GABAergic synaptic activity can be induced during a restricted period of development by a conditioning protocol relevant to the physiological condition. It is suggested that such activity-induced modifications may represent a physiological mechanism for the functional maturation of GABAergic synaptic transmission.

  12. American Society of Plastic Surgeons

    MedlinePlus

    ... that instill confidence. Do Your Homework Patient Safety Plastic Surgery When you choose a doctor who is ... to procedure selector Why Choose A Board Certified Plastic Surgeon Choose a board-certified plastic surgeon and ...

  13. Intrinsically disordered proteins and intrinsically disordered protein regions.

    PubMed

    Oldfield, Christopher J; Dunker, A Keith

    2014-01-01

    Intrinsically disordered proteins (IDPs) and IDP regions fail to form a stable structure, yet they exhibit biological activities. Their mobile flexibility and structural instability are encoded by their amino acid sequences. They recognize proteins, nucleic acids, and other types of partners; they accelerate interactions and chemical reactions between bound partners; and they help accommodate posttranslational modifications, alternative splicing, protein fusions, and insertions or deletions. Overall, IDP-associated biological activities complement those of structured proteins. Recently, there has been an explosion of studies on IDP regions and their functions, yet the discovery and investigation of these proteins have a long, mostly ignored history. Along with recent discoveries, we present several early examples and the mechanisms by which IDPs contribute to function, which we hope will encourage comprehensive discussion of IDPs and IDP regions in biochemistry textbooks. Finally, we propose future directions for IDP research.

  14. Therapeutic opportunities in the intrinsic subtypes of muscle-invasive bladder cancer.

    PubMed

    McConkey, David J; Choi, Woonyoung; Ochoa, Andrea; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin P N

    2015-04-01

    Recent studies revealed that muscle-invasive bladder cancers segregate into intrinsic basal and luminal subtypes that are similar to those described for breast cancer. Each subtype is enriched with potentially clinically actionable genomic alterations and epigenetic signatures; there are associations between tumor subtype and sensitivity to conventional cisplatin-based chemotherapy. The authors review biological and clinical characteristics of the intrinsic subtypes and describe their implications for the development of conventional and targeted agents. The role that tumor plasticity seems to play in basal and luminal bladder cancer biology and its potential effects on the development of therapeutic resistance is also discussed.

  15. Bacterial Community Profiling of Plastic Litter in the Belgian Part of the North Sea.

    PubMed

    De Tender, Caroline A; Devriese, Lisa I; Haegeman, Annelies; Maes, Sara; Ruttink, Tom; Dawyndt, Peter

    2015-08-18

    Bacterial colonization of marine plastic litter (MPL) is known for over four decades. Still, only a few studies on the plastic colonization process and its influencing factors are reported. In this study, seafloor MPL was sampled at different locations across the Belgian part of the North Sea to study bacterial community structure using 16S metabarcoding. These marine plastic bacterial communities were compared with those of sediment and seawater, and resin pellets sampled on the beach, to investigate the origin and uniqueness of plastic bacterial communities. Plastics display great variation of bacterial community composition, while each showed significant differences from those of sediment and seawater, indicating that plastics represent a distinct environmental niche. Various environmental factors correlate with the diversity of MPL bacterial composition across plastics. In addition, intrinsic plastic-related factors such as pigment content may contribute to the differences in bacterial colonization. Furthermore, the differential abundance of known primary and secondary colonizers across the various plastics may indicate different stages of bacterial colonization, and may confound comparisons of free-floating plastics. Our studies provide insights in the factors that shape plastic bacterial colonization and shed light on the possible role of plastic as transport vehicle for bacteria through the aquatic environment.

  16. POLYESTER GLASS PLASTICS FOR SHIPBUILDING,

    DTIC Science & Technology

    POLYESTER PLASTICS , SHIP HULLS), (*SHIP HULLS, POLYESTER PLASTICS ), GLASS TEXTILES, REINFORCING MATERIALS, SHIP STRUCTURAL COMPONENTS, COMPOSITE MATERIALS, PROCESSING, CHEMISTRY, HANDBOOKS, BINDERS, USSR

  17. Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis.

    PubMed

    Lovinger, David M; Kash, Thomas L

    2015-01-01

    Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction.Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder.

  18. Intrinsic optimization using stochastic nanomagnets

    NASA Astrophysics Data System (ADS)

    Sutton, Brian; Camsari, Kerem Yunus; Behin-Aein, Behtash; Datta, Supriyo

    2017-03-01

    This paper draws attention to a hardware system which can be engineered so that its intrinsic physics is described by the generalized Ising model and can encode the solution to many important NP-hard problems as its ground state. The basic constituents are stochastic nanomagnets which switch randomly between the ±1 Ising states and can be monitored continuously with standard electronics. Their mutual interactions can be short or long range, and their strengths can be reconfigured as needed to solve specific problems and to anneal the system at room temperature. The natural laws of statistical mechanics guide the network of stochastic nanomagnets at GHz speeds through the collective states with an emphasis on the low energy states that represent optimal solutions. As proof-of-concept, we present simulation results for standard NP-complete examples including a 16-city traveling salesman problem using experimentally benchmarked models for spin-transfer torque driven stochastic nanomagnets.

  19. Intrinsic optimization using stochastic nanomagnets

    PubMed Central

    Sutton, Brian; Camsari, Kerem Yunus; Behin-Aein, Behtash; Datta, Supriyo

    2017-01-01

    This paper draws attention to a hardware system which can be engineered so that its intrinsic physics is described by the generalized Ising model and can encode the solution to many important NP-hard problems as its ground state. The basic constituents are stochastic nanomagnets which switch randomly between the ±1 Ising states and can be monitored continuously with standard electronics. Their mutual interactions can be short or long range, and their strengths can be reconfigured as needed to solve specific problems and to anneal the system at room temperature. The natural laws of statistical mechanics guide the network of stochastic nanomagnets at GHz speeds through the collective states with an emphasis on the low energy states that represent optimal solutions. As proof-of-concept, we present simulation results for standard NP-complete examples including a 16-city traveling salesman problem using experimentally benchmarked models for spin-transfer torque driven stochastic nanomagnets. PMID:28295053

  20. Profibus features intrinsic safety, interoperability

    SciTech Connect

    Bryant, M.

    1996-11-01

    The newest member of the Profibus (process fieldbus) family of interoperable field-bus protocols is {open_quotes}PA{close_quotes}, an intrinsically safe (IS) standard released more than a year ago. IS and non-IS plants using PA for process chemicals, energy production, and food manufacturing are coming online. PA was developed by vendor and user members of the Profibus standards community to meet the needs of customers in the process industries. PA complies with IEC 1158-2, which, among non-IS capabilities, specifies a low-speed, intrinsically safe fieldbus for automating explosive chemical manufacturing. PA thus provides all H1, or {open_quotes}hunk{close_quotes} 1, IS and non-IS services. Importantly, it also provides all H2, or {open_quotes}hunk{close_quotes} 2, services. As the newest segment of the site-proven system of fieldbus protocols, Profibus-PA defines by example the concepts of interoperability and interchangeability. It is a field instrument network that automatically interoperates with a large installed base of fieldbus nodes. As low-speed networks, PA and its competitor, Foundation fieldbus H1 comply with the same standard. They do the same job; auxiliary power to the application, with a data rate of 31.25 kbit/sec. Similarities include a function-block-based architecture and a device description language (DDL). They use the same physical layer for digital data transfer. A casual observer would find PA and H1 virtually the same. The key differences are in the protocol implementations. Although PA and H1 could be wired together, the messages delivered by one would make no sense to the other. At least not yet. PA protocols are capable of both IS and non-IS operations. This opens the door to a wide range of interoperable process-manufacturing requirements. 1 fig., 1 tab.

  1. MicroRNAs regulate neuronal plasticity and are involved in pain mechanisms.

    PubMed

    Elramah, Sara; Landry, Marc; Favereaux, Alexandre

    2014-01-01

    MicroRNAs (miRNAs) are emerging as master regulators of gene expression in the nervous system where they contribute not only to brain development but also to neuronal network homeostasis and plasticity. Their function is the result of a cascade of events including miRNA biogenesis, target recognition, and translation inhibition. It has been suggested that miRNAs are major switches of the genome owing to their ability to regulate multiple genes at the same time. This regulation is essential for normal neuronal activity and, when affected, can lead to drastic pathological conditions. As an example, we illustrate how deregulation of miRNAs can affect neuronal plasticity leading to chronic pain. The origin of pain and its dual role as a key physiological function and a debilitating disease has been highly debated until now. The incidence of chronic pain is estimated to be 20-25% worldwide, thus making it a public health problem. Chronic pain can be considered as a form of maladaptive plasticity. Long-lasting modifications develop as a result of global changes in gene expression, and are thus likely to be controlled by miRNAs. Here, we review the literature on miRNAs and their targets responsible for maladaptive plasticity in chronic pain conditions. In addition, we conduct a retrospective analysis of miRNA expression data published for different pain models, taking into account recent progress in our understanding of the role of miRNAs in neuronal plasticity.

  2. Spatiotemporal computations of an excitable and plastic brain: neuronal plasticity leads to noise-robust and noise-constructive computations.

    PubMed

    Toutounji, Hazem; Pipa, Gordon

    2014-03-01

    It is a long-established fact that neuronal plasticity occupies the central role in generating neural function and computation. Nevertheless, no unifying account exists of how neurons in a recurrent cortical network learn to compute on temporally and spatially extended stimuli. However, these stimuli constitute the norm, rather than the exception, of the brain's input. Here, we introduce a geometric theory of learning spatiotemporal computations through neuronal plasticity. To that end, we rigorously formulate the problem of neural representations as a relation in space between stimulus-induced neural activity and the asymptotic dynamics of excitable cortical networks. Backed up by computer simulations and numerical analysis, we show that two canonical and widely spread forms of neuronal plasticity, that is, spike-timing-dependent synaptic plasticity and intrinsic plasticity, are both necessary for creating neural representations, such that these computations become realizable. Interestingly, the effects of these forms of plasticity on the emerging neural code relate to properties necessary for both combating and utilizing noise. The neural dynamics also exhibits features of the most likely stimulus in the network's spontaneous activity. These properties of the spatiotemporal neural code resulting from plasticity, having their grounding in nature, further consolidate the biological relevance of our findings.

  3. Spatiotemporal Computations of an Excitable and Plastic Brain: Neuronal Plasticity Leads to Noise-Robust and Noise-Constructive Computations

    PubMed Central

    Toutounji, Hazem; Pipa, Gordon

    2014-01-01

    It is a long-established fact that neuronal plasticity occupies the central role in generating neural function and computation. Nevertheless, no unifying account exists of how neurons in a recurrent cortical network learn to compute on temporally and spatially extended stimuli. However, these stimuli constitute the norm, rather than the exception, of the brain's input. Here, we introduce a geometric theory of learning spatiotemporal computations through neuronal plasticity. To that end, we rigorously formulate the problem of neural representations as a relation in space between stimulus-induced neural activity and the asymptotic dynamics of excitable cortical networks. Backed up by computer simulations and numerical analysis, we show that two canonical and widely spread forms of neuronal plasticity, that is, spike-timing-dependent synaptic plasticity and intrinsic plasticity, are both necessary for creating neural representations, such that these computations become realizable. Interestingly, the effects of these forms of plasticity on the emerging neural code relate to properties necessary for both combating and utilizing noise. The neural dynamics also exhibits features of the most likely stimulus in the network's spontaneous activity. These properties of the spatiotemporal neural code resulting from plasticity, having their grounding in nature, further consolidate the biological relevance of our findings. PMID:24651447

  4. Back to the Definitions Themselves: The Pragmatics of Intrinsic Justification.

    ERIC Educational Resources Information Center

    Bahm, Kenneth

    Such terms as "intrinsic justification,""intrinsicness," and "intrinsicality" are increasingly being heard in academic debate circles. Intrinsic justification consists of an argument which focuses evaluation of a resolutional term on the term's definitional contours. Essential qualities are defining characteristics…

  5. Perceptual learning and sensomotor flexibility: cortical plasticity under attentional control?

    PubMed Central

    Fahle, Manfred

    2008-01-01

    Recent research reveals long-lasting cortical plasticity of early sensory cortices even in adults. Sensory signals could be modified under top-down control if necessary quite early in order to optimize their signal-to-noise ratio, leading to ‘low level’ or ‘early’ perceptual learning (PL). For easy tasks, such elaborate top-down influences are usually not required, and learning is restricted to late selection of the appropriate signals on higher cortical levels, which seems easier and faster to achieve. But to reach the absolute limits of sensory performance, PL seems to optimize the entire chain of sensory processing. Hence, improvement for these extreme perceptual abilities is quite specific for a number of stimulus parameters, such as the position in the visual field and sometimes even the trained eye, reflecting the specificity of receptive fields in early sensory cortices. Early PL may be just one example—even if a very extensive one—of the mechanisms of neuronal plasticity and sensomotor flexibility that are constantly updating our sensomotor representations as a result of experience. As an illustration, this review contains some new experimental results on PL and sensory flexibility in the context of adaptation to multifocal intraocular lenses. PMID:18977730

  6. Mechanical plasticity of cells

    NASA Astrophysics Data System (ADS)

    Bonakdar, Navid; Gerum, Richard; Kuhn, Michael; Spörrer, Marina; Lippert, Anna; Schneider, Werner; Aifantis, Katerina E.; Fabry, Ben

    2016-10-01

    Under mechanical loading, most living cells show a viscoelastic deformation that follows a power law in time. After removal of the mechanical load, the cell shape recovers only incompletely to its original undeformed configuration. Here, we show that incomplete shape recovery is due to an additive plastic deformation that displays the same power-law dynamics as the fully reversible viscoelastic deformation response. Moreover, the plastic deformation is a constant fraction of the total cell deformation and originates from bond ruptures within the cytoskeleton. A simple extension of the prevailing viscoelastic power-law response theory with a plastic element correctly predicts the cell behaviour under cyclic loading. Our findings show that plastic energy dissipation during cell deformation is tightly linked to elastic cytoskeletal stresses, which suggests the existence of an adaptive mechanism that protects the cell against mechanical damage.

  7. Shape-Shifting Plastic

    SciTech Connect

    2015-05-20

    A new plastic developed by ORNL and Washington State University transforms from its original shape through a series of temporary shapes and returns to its initial form. The shape-shifting process is controlled through changes in temperature

  8. A Plastic Menagerie

    ERIC Educational Resources Information Center

    Hadley, Mary Jane

    2010-01-01

    Bobble heads had become quite popular, depicting all sorts of sports figures, animals, and even presidents. In this article, the author describes how her fourth graders made bobble head sculptures out of empty plastic drink bottles. (Contains 1 online resource.)

  9. Strain avalanches in plasticity

    NASA Astrophysics Data System (ADS)

    Argon, A. S.

    2013-09-01

    Plastic deformation at the mechanism level in all solids occurs in the form of discrete thermally activated individual stress relaxation events. While there are clear differences in mechanisms between dislocation mediated events in crystalline solids and by individual shear transformations in amorphous metals and semiconductors, such relaxation events interact strongly to form avalanches of strain bursts. In all cases the attendant distributions of released energy as amplitudes of acoustic emissions, or in serration amplitudes in flow stress, the levels of strain bursts are of fractal character with fractal exponents in the range from -1.5 to -2.0, having the character of phenomena of self-organized criticality, SOC. Here we examine strain avalanches in single crystals of ice, hcp metals, the jerky plastic deformations of nano-pillars of fcc and bcc metals deforming in compression, those in the plastic flow of bulk metallic glasses, all demonstrating the remarkable universality of character of plastic relaxation events.

  10. Dreaming in plastic

    NASA Astrophysics Data System (ADS)

    Korzhov, Marianna; Andelman, David; Shikler, Rafi

    2008-07-01

    Plastic is one of the most versatile materials available. It is cheap, flexible and easy to process, and as a result it is all around us - from our computer keyboards to the soles of our shoes. One of its most common applications is as an insulating coating for electric wires; indeed, plastic is well known for its insulating characteristics. It came as something of a surprise, therefore, when in the late 1970s a new generation of plastics was discovered that displayed exactly the opposite behaviour - the ability to conduct electricity. In fact, plastics can be made with a whole range of conductivities - there are polymer materials that behave like semiconductors and there are those that can conduct as well as metals. This discovery sparked a revolution in the electronics community, and three decades of research effort is now yielding a range of stunning new applications for this ubiquitous material.

  11. Physics in Plastics Technology.

    ERIC Educational Resources Information Center

    Thomas, Ken

    1980-01-01

    Discusses the increasing role of the physicist in plastics technology. Relationships of molecular structure to material behavior, design which is related to the material, and the practical problems of fabricating a material into an article are included. (HM)

  12. Laser cutting plastic materials

    SciTech Connect

    Van Cleave, R.A.

    1980-08-01

    A 1000-watt CO/sub 2/ laser has been demonstrated as a reliable production machine tool for cutting of plastics, high strength reinforced composites, and other nonmetals. More than 40 different plastics have been laser cut, and the results are tabulated. Applications for laser cutting described include fiberglass-reinforced laminates, Kevlar/epoxy composites, fiberglass-reinforced phenolics, nylon/epoxy laminates, ceramics, and disposable tooling made from acrylic.

  13. Buying into conservation: intrinsic versus instrumental value.

    PubMed

    Justus, James; Colyvan, Mark; Regan, Helen; Maguire, Lynn

    2009-04-01

    Many conservation biologists believe the best ethical basis for conserving natural entities is their claimed intrinsic value, not their instrumental value for humans. But there is significant confusion about what intrinsic value is and how it could govern conservation decision making. After examining what intrinsic value is supposed to be, we argue that it cannot guide the decision making conservation requires. An adequate ethical basis for conservation must do this, and instrumental value does it best.

  14. Synaptic and nonsynaptic plasticity approximating probabilistic inference

    PubMed Central

    Tully, Philip J.; Hennig, Matthias H.; Lansner, Anders

    2014-01-01

    Learning and memory operations in neural circuits are believed to involve molecular cascades of synaptic and nonsynaptic changes that lead to a diverse repertoire of dynamical phenomena at higher levels of processing. Hebbian and homeostatic plasticity, neuromodulation, and intrinsic excitability all conspire to form and maintain memories. But it is still unclear how these seemingly redundant mechanisms could jointly orchestrate learning in a more unified system. To this end, a Hebbian learning rule for spiking neurons inspired by Bayesian statistics is proposed. In this model, synaptic weights and intrinsic currents are adapted on-line upon arrival of single spikes, which initiate a cascade of temporally interacting memory traces that locally estimate probabilities associated with relative neuronal activation levels. Trace dynamics enable synaptic learning to readily demonstrate a spike-timing dependence, stably return to a set-point over long time scales, and remain competitive despite this stability. Beyond unsupervised learning, linking the traces with an external plasticity-modulating signal enables spike-based reinforcement learning. At the postsynaptic neuron, the traces are represented by an activity-dependent ion channel that is shown to regulate the input received by a postsynaptic cell and generate intrinsic graded persistent firing levels. We show how spike-based Hebbian-Bayesian learning can be performed in a simulated inference task using integrate-and-fire (IAF) neurons that are Poisson-firing and background-driven, similar to the preferred regime of cortical neurons. Our results support the view that neurons can represent information in the form of probability distributions, and that probabilistic inference could be a functional by-product of coupled synaptic and nonsynaptic mechanisms operating over several timescales. The model provides a biophysical realization of Bayesian computation by reconciling several observed neural phenomena whose