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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. Long-lasting antifog plasma modification of transparent plastics.

    PubMed

    Di Mundo, Rosa; d'Agostino, Riccardo; Palumbo, Fabio

    2014-10-01

    Antifog surfaces are necessary for any application requiring optical efficiency of transparent materials. Surface modification methods aimed toward increasing solid surface energy, even when supposed to be permanent, in fact result in a nondurable effect due to the instability in air of highly hydrophilic surfaces. We propose the strategy of combining a hydrophilic chemistry with a nanotextured topography, to tailor a long-lasting antifog modification on commercial transparent plastics. In particular, we investigated a two-step process consisting of self-masked plasma etching followed by plasma deposition of a silicon-based film. We show that the deposition of the silicon-based coatings on the flat (pristine) substrates allows a continuous variation of wettability from hydrophobic to superhydrophilic, due to a continuous reduction of carbon-containing groups, as assessed by Fourier transform infrared and X-ray photoelectron spectroscopies. By depositing these different coatings on previously nanotextured substrates, the surface wettability behavior is changed consistently, as well as the condensation phenomenon in terms of microdroplets/liquid film appearance. This variation is correlated with advancing and receding water contact angle features of the surfaces. More importantly, in the case of the superhydrophilic coating, though its surface energy decreases with time, when a nanotextured surface underlies it, the wetting behavior is maintained durably superhydrophilic, thus durably antifog. PMID:25251610

  3. Neuropeptide Y Gates a Stress-Induced, Long-Lasting Plasticity in the Sympathetic Nervous System

    PubMed Central

    Wang, Qian; Wang, Manqi

    2013-01-01

    Acute stress evokes the fight-or-flight reflex, which via release of the catecholamine hormones affects the function of every major organ. Although the reflex is transient, it has lasting consequences that produce an exaggerated response when stress is reexperienced. How this change is encoded is not known. We investigated whether the reflex affects the adrenal component of the sympathetic nervous system, a major branch of the stress response. Mice were briefly exposed to the cold-water forced swim test (FST) which evoked an increase in circulating catecholamines. Although this hormonal response was transient, the FST led to a long-lasting increase in the catecholamine secretory capacity measured amperometrically from chromaffin cells and in the expression of tyrosine hydroxylase. A variety of approaches indicate that these changes are regulated postsynaptically by neuropeptide Y (NPY), an adrenal cotransmitter. Using immunohistochemistry, RT-PCR, and NPY(GFP) BAC mice, we find that NPY is synthesized by all chromaffin cells. Stress failed to increase secretory capacity in NPY knock-out mice. Genetic or pharmacological interference with NPY and Y1 (but not Y2 or Y5) receptor signaling attenuated the stress-induced change in tyrosine hydroxylase expression. These results indicate that, under basal conditions, adrenal signaling is tonically inhibited by NPY, but stress overrides this autocrine negative feedback loop. Because acute stress leads to a lasting increase in secretory capacity in vivo but does not alter sympathetic tone, these postsynaptic changes appear to be an adaptive response. We conclude that the sympathetic limb of the stress response exhibits an activity-dependent form of long-lasting plasticity. PMID:23904607

  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. Cell-intrinsic gp130 Signaling on CD4+ T cells Shapes Long-lasting Antiviral Immunity

    PubMed Central

    Harker, James A.; Wong, Kurt A.; Dolgoter, Aleksandr; Zuniga, Elina I.

    2015-01-01

    The interleukin-6 (IL-6) cytokine family utilizes the common signal transduction molecule gp130, which can mediate a diverse range of outcomes. To clarify the role of gp130 signaling in vivo during acute viral infection we infected Cd4-cre Il6stfl/fl mice, in which gp130 is conditionally ablated in T cells, with acute lymphocytic choriomeningitis virus (LCMV). We found that by day 12, but not at day 8, post infection the number of virus specific CD4+ T cells was reduced in the absence of gp130, and this was sustained for up to 2 months post infection. Additionally gp130 deficient TFH had lower expression of Maf, IL-21 and ICOS and this was accompanied by a reduction in the proportion of germinal center B cells and plasmablasts. Remarkably, two months post-infection the proportion of IgG2a/c+ memory B cells and the systemic levels of LCMV-specific IgG2 Abs were dramatically decreased, while there was a corresponding increase in IgG1+ memory B cells and virus-specific IgG1 Abs. In the same animals Gp130 deficient virus specific CD8+ T cells showed a reduced proportion of memory cells, which expressed lower levels of Tcf7, and displayed diminished recall responses on secondary infection. Mixed bone marrow chimeras revealed that the aforementioned gp130 effects on CD4+ T cells were cell-intrinsic. Overall our data show that gp130 signaling in T cells influences the quantity and quality of long lasting CD4+ T cell responses as well as CD8+ T cell and antibody mediated immunity after acute viral infection. PMID:26085685

  6. Plasticity-associated gene Krox24/Zif268 is required for long-lasting behavioral effects of cocaine.

    PubMed

    Valjent, Emmanuel; Aubier, Benjamin; Corbillé, Anne-Gaëlle; Brami-Cherrier, Karen; Caboche, Jocelyne; Topilko, Piotr; Girault, Jean-Antoine; Hervé, Denis

    2006-05-01

    The extracellular signal-regulated kinases (ERKs) 1/2 pathway is stimulated by drugs of abuse in striatal neurons through coincident activation of dopamine D1 and glutamate NMDA receptors and is critical for long-lasting behavioral effects of these drugs. Although regulation of transcription is a major target of ERK, the precise mechanisms by which it contributes to behavioral alterations is not known. We examined the role of Zif268, an immediate-early gene induced by drugs of abuse under the control of ERK, in behavioral responses to cocaine using knock-in mutant mice in which Zif268 was replaced by LacZ. No biochemical or behavioral differences between mutant and wild-type mice were observed in basal conditions or in acute responses to cocaine injection. In contrast, locomotor sensitization to single or repeated cocaine injections was dramatically diminished in both heterozygous and homozygous Zif268 mutant mice. Conditioned place preference in response to cocaine was prevented in Zif268-deficient mice. This effect was not attributable to a general learning deficit because the mutant mice displayed normal conditioned place preference when food was used as reward. Our results provide direct genetic evidence for the requirement of Zif268 for long-lasting association of environmental context with specific behavioral responses after short exposures to cocaine. They also underline the common molecular machinery involved in long-lasting drug-induced behavioral alterations and the formation of other types of memory. PMID:16672671

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

    PubMed

    Knikou, Maria; Dixon, Luke; Santora, Danielle; Ibrahim, Mohamed M

    2015-09-01

    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. Reversibility of developmental heat and cold plasticity is asymmetric and has long-lasting consequences for adult thermal tolerance.

    PubMed

    Slotsbo, Stine; Schou, Mads F; Kristensen, Torsten N; Loeschcke, Volker; Sørensen, Jesper G

    2016-09-01

    The ability of insects to cope with stressful temperatures through adaptive plasticity has allowed them to thrive under a wide range of thermal conditions. Developmental plasticity is generally considered to be a non-reversible phenotypic change, e.g. in morphological traits, while adult acclimation responses are often considered to be reversible physiological responses. However, physiologically mediated thermal acclimation might not follow this general prediction. We investigated the magnitude and rate of reversibility of developmental thermal plasticity responses in heat and cold tolerance of adult flies, using a full factorial design with two developmental and two adult temperatures (15 and 25°C). We show that cold tolerance attained during development is readily adjusted to the prevailing conditions during adult acclimation, with a symmetric rate of decrease or increase. In contrast, heat tolerance is only partly reversible during acclimation and is thus constrained by the temperature during development. The effect of adult acclimation on heat tolerance was asymmetrical, with a general loss of heat tolerance with age. Surprisingly, the decline in adult heat tolerance at 25°C was decelerated in flies developed at low temperatures. This result was supported by correlated responses in two senescence-associated traits and in accordance with a lower rate of ageing after low temperature development, suggesting that physiological age is not reset at eclosion. The results have profound ecological consequences for populations, as optimal developmental temperatures will be dependent on the thermal conditions faced in the adult stage and the age at which they occur. PMID:27353229

  9. An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity.

    PubMed

    Lovelace, Jonathan W; Corches, Alex; Vieira, Philip A; Hiroto, Alex S; Mackie, Ken; Korzus, Edward

    2015-12-01

    Cannabis continues to be the most accessible and popular illicit recreational drug. Whereas current data link adolescence cannabinoid exposure to increased risk for dependence on other drugs, depression, anxiety disorders and psychosis, the mechanism(s) underlying these adverse effects remains controversial. Here we show in a mouse model of female adolescent cannabinoid exposure deficient endocannabinoid (eCB)-mediated signaling and presynaptic forms of long-term depression at adult central glutamatergic synapses in the prefrontal cortex. Increasing endocannabinoid levels by blockade of monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG), with the specific inhibitor JZL 184 ameliorates eCB-LTD deficits. The observed deficit in cortical presynaptic signaling may represent a neural maladaptation underlying network instability and abnormal cognitive functioning. Our study suggests that adolescent cannabinoid exposure may permanently impair brain functions, including the brain's intrinsic ability to appropriately adapt to external influences. PMID:25979486

  10. 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.

  11. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24212565

  13. 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

  14. 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

  15. 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. PMID:27427552

  16. 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.

  17. 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

  18. A theory of rate coding control by intrinsic plasticity effects.

    PubMed

    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

  19. Multiple Pathways to Long-lasting Phrenic Motor Facilitation

    PubMed Central

    Dale-Nagle, Erica A.; Hoffman, Michael S.; MacFarlane, Peter M.; Mitchell, Gordon S.

    2010-01-01

    Plasticity is a hallmark of neural systems, including the neural system controlling breathing (Mitchell and Johnson, 2003). Despite its biological and potential clinical significance, our understanding of mechanisms giving rise to any form of respiratory plasticity remains incomplete. Here we discuss recent advances in our understanding of cellular mechanisms giving rise to phrenic long-term facilitation (pLTF), a long-lasting increase in phrenic motor output induced by acute intermittent hypoxia (AIH). Recently, we have come to realize that multiple, distinct mechanisms are capable of giving rise to long-lasting phrenic motor facilitation (PMF); we use PMF as a general term that includes AIH-induced pLTF. It is important to begin an appreciation and understanding of these diverse pathways. Hence, we introduce a nomenclature based on upstream steps in the signaling cascade leading to PMF. Two pathways are featured here: the “Q” and the “S” pathways, named because they are induced by metabotropic receptors coupled to Gq and Gs proteins, respectively. These pathways appear to interact in complex and interesting ways, thus providing a range of potential responses in the face of changing physiological conditions or the onset of disease. PMID:20217354

  20. Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus

    PubMed Central

    Lopez-Rojas, Jeffrey; Heine, Martin; Kreutz, Michael R.

    2016-01-01

    The dentate gyrus is the main entry gate for cortical input to the hippocampus and one of the few brain areas where adult neurogenesis occurs. Several studies have shown that it is relatively difficult to induce synaptic plasticity in mature but not in newborn dentate granule cells. In the present work we have systematically addressed how classical protocols to induce synaptic plasticity affect action potential firing and intrinsic excitability in mature granule cells. We found that stimulation paradigms considered to be relevant for learning processes consistently modified the probability to generate action potentials in response to a given synaptic input in mature cells, in some paradigms even without any modification of synaptic strength. Collectively the results suggest that plasticity of intrinsic dendritic excitability has a lower induction-threshold than synaptic plasticity in mature granule cells and that this form of plasticity might be an important mechanism by which mature granule cells contribute to hippocampal function. PMID:26857841

  1. Composition effect on intrinsic plasticity or brittleness in metallic glasses.

    PubMed

    Zhao, Yuan-Yun; Inoue, Akihisa; Chang, Chuntao; Liu, Jian; Shen, Baolong; Wang, Xinmin; Li, Run-Wei

    2014-01-01

    The high plasticity of metallic glasses is highly desirable for a wide range of novel engineering applications. However, the physical origin of the ductile/brittle behaviour of metallic glasses with various compositions and thermal histories has not been fully clarified. Here we have found that metallic glasses with compositions at or near intermetallic compounds, in contrast to the ones at or near eutectics, are extremely ductile and also insensitive to annealing-induced embrittlement. We have also proposed a close correlation between the element distribution features and the plasticity of metallic glasses by tracing the evolutions of the element distribution rearrangement and the corresponding potential energy change within the sliding shear band. These novel results provide useful and universal guidelines to search for new ductile metallic glasses at or near the intermetallic compound compositions in a number of glass-forming alloy systems. PMID:25043428

  2. Composition Effect on Intrinsic Plasticity or Brittleness in Metallic Glasses

    PubMed Central

    Zhao, Yuan-Yun; Inoue, Akihisa; Chang, Chuntao; Liu, Jian; Shen, Baolong; Wang, Xinmin; Li, Run-Wei

    2014-01-01

    The high plasticity of metallic glasses is highly desirable for a wide range of novel engineering applications. However, the physical origin of the ductile/brittle behaviour of metallic glasses with various compositions and thermal histories has not been fully clarified. Here we have found that metallic glasses with compositions at or near intermetallic compounds, in contrast to the ones at or near eutectics, are extremely ductile and also insensitive to annealing-induced embrittlement. We have also proposed a close correlation between the element distribution features and the plasticity of metallic glasses by tracing the evolutions of the element distribution rearrangement and the corresponding potential energy change within the sliding shear band. These novel results provide useful and universal guidelines to search for new ductile metallic glasses at or near the intermetallic compound compositions in a number of glass-forming alloy systems. PMID:25043428

  3. 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.

  4. Hebbian and Homeostatic Plasticity Mechanisms in Regular Spiking and Intrinsic Bursting Cells of Cortical Layer 5

    PubMed Central

    Greenhill, Stuart David; Ranson, Adam; Fox, Kevin

    2015-01-01

    Summary Layer 5 contains the major projection neurons of the neocortex and is composed of two major cell types: regular spiking (RS) cells, which have cortico-cortical projections, and intrinsic bursting cells (IB), which have subcortical projections. Little is known about the plasticity processes and specifically the molecular mechanisms by which these two cell classes develop and maintain their unique integrative properties. In this study, we find that RS and IB cells show fundementally different experience-dependent plasticity processes and integrate Hebbian and homeostatic components of plasticity differently. Both RS and IB cells showed TNFα-dependent homeostatic plasticity in response to sensory deprivation, but IB cells were capable of a much faster synaptic depression and homeostatic rebound than RS cells. Only IB cells showed input-specific potentiation that depended on CaMKII autophosphorylation. Our findings demonstrate that plasticity mechanisms are not uniform within the neocortex, even within a cortical layer, but are specialized within subcircuits. PMID:26481037

  5. 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. PMID:27255800

  6. 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)

  7. 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

  8. Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression

    PubMed Central

    Ramiro-Cortés, Yazmín; Israely, Inbal

    2013-01-01

    Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation. PMID:23951097

  9. Intact and long-lasting repetition priming in amnesia.

    PubMed

    Cave, C B; Squire, L R

    1992-05-01

    In 2 experiments, we evaluated the ability of amnesic patients to exhibit long-lasting perceptual priming after a single exposure to pictures. Ss named pictures as quickly as possible on a single occasion, and later named the same pictures mixed with new pictures. In Experiment 1, amnesic patients exhibited fully intact priming effects lasting at least 7 days. In Experiment 2, the priming effect for both groups was shown to depend on both highly specific visual information and on less visual, more conceptual information. In contrast, recognition memory was severely impaired in the patients, as assessed by both accuracy and response time. The results provide the first report of a long-lasting priming effect in amnesic patients, based on a single encounter, which occurs as strongly in the patients as in normal Ss. Together with other recent findings, the results suggest that long-lasting priming and recognition memory depend on separate brain systems. PMID:1534352

  10. 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

  11. 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. PMID:24048833

  12. Plasticity of the Intrinsic Period of the Human Circadian Timing System

    PubMed Central

    Scheer, Frank A.J.L.; Wright, Kenneth P.; Kronauer, Richard E.; Czeisler, Charles A.

    2007-01-01

    Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol), which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light (∼450 lux; ∼1.2 W/m2) for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration. PMID:17684566

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

    PubMed Central

    Ehlers, Cindy L.; Criado, José R.

    2009-01-01

    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. In order 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 vapours, 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 EEG and a reduction in the P3 component of the ERP have been demonstrated in adult rats that were exposed to ethanol vapour 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. PMID:20113872

  14. Normal hearing is required for the emergence of long-lasting inhibitory potentiation in cortex

    PubMed Central

    Xu, Han; Kotak, Vibhakar C.; Sanes, Dan H.

    2010-01-01

    Long-term synaptic plasticity is a putative mechanism for learning in adults. However, there is little understanding of how synaptic plasticity mechanisms develop or whether their maturation depends on experience. Since inhibitory synapses are particularly malleable to sensory stimulation, long-lasting potentiation of inhibitory synapses was characterized in auditory thalamocortical slices. Intracortical high frequency electrical stimulation led to a 67% increase in inhibitory synaptic currents. In the absence of stimulation, inhibitory potentiation was induced by a brief exposure to exogenous BDNF. BDNF exposure occluded any further potentiation by high frequency afferent stimulation, suggesting that BDNF signaling is sufficient to account for inhibitory potentiation. Moreover, inhibitory potentiation was reduced significantly by extracellular application of a BDNF scavenger or by intracellular blockade of BDNF receptor (TrkB) signaling. In contrast, glutamatergic or GABAergic antagonists did not prevent the induction of inhibitory potentiation. Since BDNF and TrkB expression are influenced strongly by activity, we predicted that inhibitory potentiation would be diminished by manipulations that decrease central auditory activity, such as hearing loss. Two forms of hearing loss were examined: conductive hearing loss in which the cochleae are not damaged or sensorineural hearing loss in which both cochleae are removed. Both forms of hearing loss were found to reduce significantly the magnitude of inhibitory potentiation. These data indicate that early experience is necessary for the normal development of BDNF-mediated long-lasting inhibitory potentiation, which may be associated with perceptual deficits at later ages. PMID:20053914

  15. 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.

  16. 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. PMID:25128798

  17. 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

  18. α-Synuclein produces a long-lasting increase in neurotransmitter release

    PubMed Central

    Liu, Shumin; Ninan, Ipe; Antonova, Irina; Battaglia, Fortunato; Trinchese, Fabrizio; Narasanna, Archana; Kolodilov, Nikolai; Dauer, William; Hawkins, Robert D; Arancio, Ottavio

    2004-01-01

    Wild-type α-synuclein, a protein of unknown function, has received much attention because of its involvement in a series of diseases that are known as synucleinopathies. We find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of α-synuclein clusters. Conversely, suppression of α-synuclein expression through antisense nucleotide and knockout techniques blocks the potentiation, as well as the glutamate-induced increase in presynaptic functional bouton number. Consistent with these findings, α-synuclein introduction into the presynaptic neuron of a pair of monosynaptically connected cells causes a rapid and long-lasting enhancement of synaptic transmission, and rescues the block of potentiation in α-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of α-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of α-synuclein clusters. Thus, α-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal. PMID:15510220

  19. 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.

  20. Rapid and long-lasting learning of feature binding.

    PubMed

    Yashar, Amit; Carrasco, Marisa

    2016-09-01

    How are features integrated (bound) into objects and how can this process be facilitated? Here we investigated the role of rapid perceptual learning in feature binding and its long-lasting effects. By isolating thecontributions of individual features from their conjunctionsbetween training and test displays, we demonstrate for the first time that training can rapidly and substantially improve feature binding. Observers trained on a conjunction search task consisting of a rapid display with one target-conjunction, then tested with a new target-conjunction. Features were the same between training and test displays. Learning transferred to the new target when its conjunction was presented as a distractor, but not when only its component features were presented in different conjunction distractors during training. Training improvement lasted for up to 16months, but, in all conditions, it was specific to the trained target. Our findings suggest that with short training observers' ability to bind two specific features into an object is improved, and that this learning effect can last for over a year. Moreover, our findings show that while the short-term learning effect reflects activation of presented items and their binding, long-term consolidation is task specific. PMID:27289484

  1. Immunogenicity of long-lasting recombinant factor VIII products.

    PubMed

    Ing, Mathieu; Gupta, Nimesh; Teyssandier, Maud; Maillère, Bernard; Pallardy, Marc; Delignat, Sandrine; Lacroix-Desmazes, Sébastien

    2016-03-01

    Replacement therapy for patients with hemophilia A using plasma-derived or recombinant factor VIII (FVIII) is complicated by the short half-life of the FVIII products and by the occurrence of neutralizing antibodies in a substantial number of patients. In the recent years, enormous efforts have been invested to develop new generations of coagulation factors with extended half-lives. Presumably, the use of long-lasting FVIII products should reduce the frequency of administration to the patients and drastically improve their quality of life. The question of their immunogenicity remains however unanswered as yet. The present review proposes a summary of the different strategies developed to enhance the half-life of FVIII, including fusion of FVIII to the Fc fragment of the human IgG1 or to human serum albumin, or attachment of polyethylene glycol. Based on the available literature, we hypothesize on the potential benefits or risks associated with each of the latter strategies in terms of immunogenicity of the newly derived hemostatic drugs. PMID:26723503

  2. 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

  3. 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

  4. Long-lasting bradypnea induced by repeated social defeat.

    PubMed

    Brouillard, Charly; Carrive, Pascal; Camus, Françoise; Bénoliel, Jean-Jacques; Similowski, Thomas; Sévoz-Couche, Caroline

    2016-08-01

    Repeated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days. Respiratory rate was recorded under anesthesia 6 days (D+10) or 26 days (D+30) after social defeat. At D+10, defeated (D) rats spent less time in the open arms of the elevated plus maze test, had heavier adrenal glands, and displayed bradypnea, unlike nondefeated animals. At D+30, all signs of anxiety had disappeared. However, one-half of the rats still displayed bradypnea (DL rats, for low respiratory rate indicated by a lower RSA frequency), whereas those with higher respiratory rate (DH rats) had recovered. Acute blockade of the dorsomedial hypothalamus (DMH) or nucleus tractus solitarii (NTS) 5-HT3 receptors reversed bradypnea in all D rats at D+10 and in DL rats at D+30. Respiratory rate was also recorded in conscious animals implanted with radiotelemetric ECG probes. DH rats recovered between D+10 and D+18, whereas DL rats remained bradypneic until D+30. In conclusion, social stress induces sustained chronic bradypnea mediated by DMH neurons and NTS 5-HT3 receptors. These changes are associated with an anxiety-like state that persists until D+10, followed by recovery. However, bradypnea may persist in one-half of the population up until D+30, despite apparent recovery of the anxiety-like state. PMID:27225946

  5. Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

    PubMed Central

    Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

    2015-01-01

    The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations. PMID:26125597

  6. Gradient plasticity used for modeling extrinsic and intrinsic size effects in the torsion of Au microwires

    NASA Astrophysics Data System (ADS)

    Wei, Xiaokun; Konstantinidis, Avraam; Qi, Chengzhi; Aifantis, Elias

    2016-04-01

    The gradient plasticity theory proposed by Aifantis and coworkers has been successfully used to model size effect phenomena at the microscale and nanoscale, by introducing into the formulation an internal length scale associated with the phenomenological coefficients of the gradient plasticity model. In this paper, Aifantis' gradient plasticity theory is applied to model the sample size-dependent torsion of thin wires, with a strain-dependent internal length scale as well as grain size dependence based on the Hall-Petch relationship. This study reveals that internal length scale is related with sample size and grain size, with such a connection determined by the ductility of the material.

  7. 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.

  8. Intrinsic Bauschinger effect and recoverable plasticity in pentatwinned silver nanowires tested in tension.

    PubMed

    Bernal, Rodrigo A; Aghaei, Amin; Lee, Sangjun; Ryu, Seunghwa; Sohn, Kwonnam; Huang, Jiaxing; Cai, Wei; Espinosa, Horacio

    2015-01-14

    Silver nanowires are promising components of flexible electronics such as interconnects and touch displays. Despite the expected cyclic loading in these applications, characterization of the cyclic mechanical behavior of chemically synthesized high-quality nanowires has not been reported. Here, we combine in situ TEM tensile tests and atomistic simulations to characterize the cyclic stress-strain behavior and plasticity mechanisms of pentatwinned silver nanowires with diameters thinner than 120 nm. The experimental measurements were enabled by a novel system allowing displacement-controlled tensile testing of nanowires, which also affords higher resolution for capturing stress-strain curves. We observe the Bauschinger effect, that is, asymmetric plastic flow, and partial recovery of the plastic deformation upon unloading. TEM observations and atomistic simulations reveal that these processes occur due to the pentatwinned structure and emerge from reversible dislocation activity. While the incipient plastic mechanism through the nucleation of stacking fault decahedrons (SFDs) is fully reversible, plasticity becomes only partially reversible as intersecting SFDs lead to dislocation reactions and entanglements. The observed plastic recovery is expected to have implications to the fatigue life and the application of silver nanowires to flexible electronics. PMID:25279701

  9. 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

  10. 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

  11. 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

  12. Spinal adenosine A2a receptor activation elicits long-lasting phrenic motor facilitation.

    PubMed

    Golder, Francis J; Ranganathan, Lavanya; Satriotomo, Irawan; Hoffman, Michael; Lovett-Barr, Mary Rachael; Watters, Jyoti J; Baker-Herman, Tracy L; Mitchell, Gordon S

    2008-02-27

    Acute intermittent hypoxia elicits a form of spinal, brain-derived neurotrophic factor (BDNF)-dependent respiratory plasticity known as phrenic long-term facilitation. Ligands that activate G(s)-protein-coupled receptors, such as the adenosine 2a receptor, mimic the effects of neurotrophins in vitro by transactivating their high-affinity receptor tyrosine kinases, the Trk receptors. Thus, we hypothesized that A2a receptor agonists would elicit phrenic long-term facilitation by mimicking the effects of BDNF on TrkB receptors. Here we demonstrate that spinal A2a receptor agonists transactivate TrkB receptors in the rat cervical spinal cord near phrenic motoneurons, thus inducing long-lasting (hours) phrenic motor facilitation. A2a receptor activation increased phosphorylation and new synthesis of an immature TrkB protein, induced TrkB signaling through Akt, and strengthened synaptic pathways to phrenic motoneurons. RNA interference targeting TrkB mRNA demonstrated that new TrkB protein synthesis is necessary for A2a-induced phrenic motor facilitation. A2a receptor activation also increased breathing in unanesthetized rats, and improved breathing in rats with cervical spinal injuries. Thus, small, highly permeable drugs (such as adenosine receptor agonists) that transactivate TrkB receptors may provide an effective therapeutic strategy in the treatment of patients with ventilatory control disorders, such as obstructive sleep apnea, or respiratory insufficiency after spinal injury or during neurodegenerative diseases. PMID:18305238

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

    PubMed Central

    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. PMID:26834600

  14. 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

  15. 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. PMID:26712276

  16. Conformational Plasticity in Glycomimetics: Fluorocarbamethyl-L-idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings.

    PubMed

    Unione, Luca; Xu, Bixue; Díaz, Dolores; Martín-Santamaría, Sonsoles; Poveda, Ana; Sardinha, João; Rauter, Amelia Pilar; Blériot, Yves; Zhang, Yongmin; Cañada, F Javier; Sollogoub, Matthieu; Jiménez-Barbero, Jesus

    2015-07-13

    Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L-iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free-energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine-containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose- and glucose-like rings. We have used low-temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose-like rings. Under these conditions, the exchange rate becomes slow in the (19) F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of (19) F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved. PMID:26096911

  17. Eye Study Underscores the Long-Lasting Benefits of Controlling Diabetes

    MedlinePlus

    ... Monday, June 13, 2016 Eye study underscores the long-lasting benefits of controlling diabetes NIH-funded study ... received intensive glycemic therapy in the 10-year-long Diabetes Control and Complications Trial on average had ...

  18. Serotonin 5-HT2 Receptors Induce a Long-Lasting Facilitation of Spinal Reflexes Independent of Ionotropic Receptor Activity

    PubMed Central

    Shay, Barbara L.; Sawchuk, Michael; Machacek, David W.; Hochman, Shawn

    2009-01-01

    Dorsal root-evoked stimulation of sensory afferents in the hemisected in vitro rat spinal cord produces reflex output, recorded on the ventral roots. Transient spinal 5-HT2C receptor activation induces a long-lasting facilitation of these reflexes (LLFR) by largely unknown mechanisms. Two Sprague-Dawley substrains were used to characterize network properties involved in this serotonin (5-HT) receptor-mediated reflex plasticity. Serotonin more easily produced LLFR in one substrain and a long-lasting depression of reflexes (LLDR) in the other. Interestingly, LLFR and LLDR were bidirectionally interconvertible using 5-HT2A/2C and 5-HT1A receptor agonists, respectively, regardless of substrain. LLFR was predominantly Aβ afferent fiber mediated, consistent with prominent 5-HT2C receptor expression in the Aβ fiber projection territories (deeper spinal laminae). Reflex facilitation involved an unmasking of polysynaptic pathways and an increased receptive field size. LLFR emerged even when reflexes were evoked three to five times/h, indicating an activity independent induction. Both the NMDA and AMPA/kainate receptor-mediated components of the reflex could be facilitated, and facilitation was dependent on 5-HT receptor activation alone, not on coincident reflex activation in the presence of 5-HT. Selective blockade of GABAA and/or glycine receptors also did not prevent reflex amplification and so are not required for LLFR. Indeed, a more robust response was seen after blockade of spinal inhibition, indicating that inhibitory processes serve to limit reflex amplification. Overall we demonstrate that the serotonergic system has the capacity to induce long-lasting bidirectional changes in reflex strength in a manner that is nonassociative and independent of evoked activity or activation of ionotropic excitatory and inhibitory receptors. PMID:16033939

  19. 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. PMID:25712572

  20. 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

  1. 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.

  2. Does foreplay matter? Gammarus pulex females may benefit from long-lasting precopulatory mate guarding

    PubMed Central

    Galipaud, Matthias; Dechaume-Moncharmont, François-Xavier; Oughadou, Abderrahim; Bollache, Loïc

    2011-01-01

    Precopulatory mate guarding (PCMG) is generally assumed to be costly for both sexes. However, males may gain by displaying long-lasting mate guarding under strong male–male competition. Surprisingly, the potential for females to benefit from being held by males has been largely overlooked in previous studies. In Gammarus pulex, an amphipod crustacean, PCMG lasts several weeks, yet females are described as bearing only cost from such male mating strategy. We investigated potential female benefits by assessing the effect of mate guarding on her intermoult duration. Unpaired females had longer intermoult duration than paired females. Intermoult duration clearly decreased when paired females engaged in early and long-lasting mate guarding. In addition, short intermoults and long-lasting mate guarding had no effect on egg number. These results highlight a potential benefit associated with PCMG for G. pulex females, suggesting that the strength of an intersexual conflict over its duration may be overestimated. PMID:21068026

  3. Variability in State-Dependent Plasticity of Intrinsic Properties during Cell-Autonomous Self-Regulation of Calcium Homeostasis in Hippocampal Model Neurons(1,2,3).

    PubMed

    Srikanth, Sunandha; Narayanan, Rishikesh

    2015-01-01

    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

  4. 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

  5. Branch-PCR Constructed Stable shRNA Transcription Nanoparticles Have Long-Lasting RNAi Effect.

    PubMed

    Liu, Jianbing; Wang, Runyu; Ma, Dejun; Li, Yanyan; Wei, Chao; Xi, Zhen

    2016-06-01

    RNA interference (RNAi) is a cellular process for gene silencing. Because of poor serum stability, transferring dsRNA directly into the target cells is a challenge. We report a facile and universal strategy to construct short hairpin RNA (shRNA) transcription nanoparticles with multiple shRNA transcription templates by PCR with flexible branched primers (branch-PCR). Compared with conventional linear shRNA transcription templates, these shRNA transcription nanoparticles show excellent stability against digestion by exonuclease III. Importantly, we found that our highly stable shRNA transcription nanoparticles can also be transcribed and thus induce efficient and long-lasting RNAi with picomolar activity in living mammalian cells. These chemically well-defined branch-PCR-generated stable shRNA transcription nanoparticles might facilitate RNAi delivery with a long-lasting RNAi effects. PMID:26972444

  6. 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

  7. 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

    2016-05-01

    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. PMID:26091614

  8. Visual reactions in a case of long-lasting cortical blindness

    PubMed Central

    Braak, J. W. G. Ter; Schenk, V. W. D.; Vliet, A. G. M. Van

    1971-01-01

    A case is described of long-lasting cortical blindness in a 71 year old man showing no other visual reactions than pupillary narrowing to light and (only after some months) optokinetic nystagmus of the `passive' type. Necropsy demonstrated total bilateral destruction of the striate area of the cortex caused by bilateral softening in the territory of the posterior cerebral artery, and nearly total loss of ganglion cells in both lateral geniculate bodies. Images

  9. 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. PMID:19515126

  10. Long-lasting upper D-region ionospheric modifications caused by intense +/- CG lightning discharges

    NASA Astrophysics Data System (ADS)

    Haldoupis, Christos

    2013-04-01

    In a recent Geophysical Research Letter we have presented observations from a single maritime storm showing that intense positive cloud-to-ground (+CG) lightning discharges during nighttime, which trigger both an elve and a sprite, are associated with long-lasting conductivity modifications in the upper D-region ionosphere. The ionospheric disturbances can be observed as perturbations in the amplitude and phase of VLF (very low frequency) signals propagating through or near the disturbed region. They are manifested as LOng Recovery early VLF Events (LOREs) which can last up to 20 - 30 minutes. The same ionospheric modifications may also produce abrupt step-like changes in VLF transmissions which offset signal levels for longer times (>30-60 min). Here we discuss these observations supplementing them with new evidence and some statistics. Among other things, the unpublished results show that very intense (currents > 250-300 kA) CG lightning discharges of either positive or negative polarity are always accompanied mainly by step-like LOREs. The evidence suggests that the electromagnetic pulse (EMP) of a very high peak current CG lightning stroke, which is likely able to produce an elve, produces by electron impact long lasting and spatially extended elevations in electron density at VLF ionospheric reflection heights in the upper D region ionosphere. The results identify a mechanism for the LORE VLF signatures and confirm predictions and postulations that elves may be accompanied by significant and long-lasting electron density perturbations in the upper D- lower E- region ionosphere.

  11. Intrinsic plasticity induced by group II metabotropic glutamate receptors via enhancement of high-threshold KV currents in sound localizing neurons.

    PubMed

    Hamlet, W R; Lu, Y

    2016-06-01

    Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization. We found that activation of mGluR II by synthetic agonists resulted in a selective increase of the high-threshold KV currents. More importantly, synaptically released glutamate (with reuptake blocked) also enhanced the high-threshold KV currents. The enhancement was frequency-coding region dependent, being more pronounced in low-frequency neurons compared to middle- and high-frequency neurons. The intracellular mechanism involved the Gβγ signaling pathway associated with phospholipase C and protein kinase C. The modulation strengthened membrane outward rectification, sharpened action potentials, and improved the ability of NL neurons to follow high-frequency inputs. These data suggest that mGluR II provides a feedforward modulatory mechanism that may regulate temporal processing under the condition of heightened synaptic inputs. PMID:26964678

  12. Antioxidants have a rapid and long-lasting effect on neuritic abnormalities in APP:PS1 mice.

    PubMed

    Garcia-Alloza, Monica; Borrelli, Laura A; Hyman, Bradley T; Bacskai, Brian J

    2010-12-01

    Senile plaques are a major pathological hallmark of Alzheimer's disease (AD). Compelling evidence suggests that senile plaques lead to structural alterations of neuronal processes and that local toxicity may be mediated by increased oxidative stress. Anti-oxidant therapy can alleviate the neuronal abnormalities in APP mice, but the time-course of this beneficial effect is unknown. We used multiphoton microscopy to assess in vivo the characteristics of antioxidant treatment on senile plaques and neurites in AD model mice (APPswe/PS1dE9). We observed that α-phenyl-N-tert-butyl nitrone (PBN), Ginkgo biloba extract (EGb 761) and Trolox had no effect on the size of existing senile plaques. However, all anti-oxidants had a straightening effect on curved neurites. This effect was detected as soon as 4 days after commencing the treatment, and was maintained after 1 month of daily treatment, with no further increase in the effect. The straightening of neurites persisted 15 days after stopping the treatment. These data indicate that neuronal plasticity is fast and still active in adult animals, and suggest that amelioration of the neuritic distortions associated with senile plaques with antioxidants is both rapid and long lasting. PMID:19124175

  13. 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

  14. 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. PMID:25926782

  15. A sustained rat model for studying the long-lasting catabolic state of sepsis.

    PubMed

    Breuille, D; Voisin, L; Contrepois, M; Arnal, M; Rose, F; Obled, C

    1999-03-01

    Most animal models of sepsis induced high mortality or early recovery and do not mimic the long-lasting catabolic state observed in patients. The purpose of this study is to develop a model of sepsis which reproduces these disorders, especially the long-lasting muscle wasting. This report summarizes our observations in a series of seven experiments using this model with rats to study the route of live Escherichia coli administration, dose of bacteria, reproducibility of the model, bacterial count in tissues, comparison of injection of live or dead bacteria, metabolic perturbations linked to infection, and potential role of tumor necrosis factor alpha (TNF-alpha) in muscle wasting. After intravenous infection, animals were anorexic and the catabolic state was long-lasting: body weight loss for 2 to 3 days followed by a chronic wasting state for several days. Liver, spleen, lung protein content, and plasma concentration of alpha2-macroglobulin were increased 2 and 6 days after infection. At 6 days, muscle protein content was substantially (-40%) reduced. The plasma TNF-alpha level measured 1.5 h after infection correlated with body weight loss observed 9 days later. The inhibition of TNF-alpha secretion by administration of pentoxifylline 1 h before infection reduced muscle wasting and activation of proteolysis at day 2 and abolished them at day 6. This septic model mimics in rats the prolonged protein metabolism alterations and muscle atrophy characteristics of infected patients and thus is useful for studying the impact of nutritional support on outcome. PMID:10024546

  16. 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

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

    PubMed Central

    Routtenberg, Aryeh

    2011-01-01

    The prevailing textbook view that de novo protein synthesis is required for memory (e.g., Bear, 2006) is seriously flawed and the 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 (Routtenberg and Rekart, 2005). 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 (Routtenberg and Rekart, 2005), 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

  18. PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine.

    PubMed

    Xue, Wenda; Wang, Wei; Gong, Tong; Zhang, Hailou; Tao, Weiwei; Xue, Lihong; Sun, Yan; Wang, Fushun; Chen, Gang

    2016-01-01

    Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju. One day post Yueju in Kunming but not ICR strain mice, expression of total and phosphorylated CREB, as well as the CREB signaling activator, PKA (protein kinase A) was up-regulated in the hippocampus. Although BDNF gene expression increased at 3 hours in both strains, it remained up-regulated at 1 day only in Kunming mice. Ketamine showed similar strain-dependent behavioral effects. However, blockade of PKA/CREB signaling blunted the antidepressant effects and reversed the up-regulation of BDNF gene expression by Yueju, but not ketamine. Conversely, blockade of mammalian target of rapamycin signaling led to opposite effects. Taken altogether, prolonged transcriptional up-regulation of hippocampal BDNF may account for the stain-dependent enduring antidepressant responses to Yueju and ketamine, but it was mediated via PKA/CREB pathway only for Yueju. PMID:27197752

  19. Long-lasting changes in the cochlear K+ recycling structures after acute energy failure.

    PubMed

    Takiguchi, Yoichiro; Sun, Guang-wei; Ogawa, Kaoru; Matsunaga, Tatsuo

    2013-01-01

    Fibrocytes in the cochlear lateral wall and spiral limbus play an important role in transporting K(+) and have the capacity of self-renewal. We showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3NP) caused hearing loss in a concentration-dependent manner, mainly due to degeneration of cochlear fibrocytes. We produced long-lasting profound cochlear damage in this model by modifying the 3NP administration protocol and observed morphological changes at 16 weeks after the administration. In the spiral ligament, severe degeneration of fibrocytes was observed in the basal turn, and the levels of the Na,K-ATPase alpha and beta1 subunits and of NKCC1 were decreased in these cells, whereas connexin 26 (Cx26) level increased in the type 1 fibrocytes adjacent to the stria vascularis. In the stria vascularis, levels of Kir4.1 and L-PGDS decreased. In the spiral limbus, severe degeneration of fibrocytes was observed in the middle and basal turns, but NKCC1 and Cx26 were still found in the center of the limbus in the middle turn. These results indicate long-lasting changes in the cochlear lateral wall and spiral limbus, which may compensate for damaged K(+) recycling and protect cells from ATP shortage. PMID:23827367

  20. Long-lasting anti-emetic effect of T-2328, a novel NK(1) antagonist.

    PubMed

    Watanabe, Yumi; Okamoto, Masahito; Ishii, Taketoshi; Takatsuka, Satomi; Taniguchi, Hiroyuki; Nagasaki, Masaaki; Saito, Akira

    2008-06-01

    The effect of T-2328 {2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride}, a novel tachykinin NK(1)-receptor antagonist, was examined on cisplatin-induced emesis in ferrets. Cisplatin induced acute emesis in 24 h and delayed emesis during 24 and 72 h, respectively. Ondansetron, a 5-HT(3) antagonist, almost completely blocked the acute emesis and transiently reduced the delayed emesis. In contrast, T-2328 elicited long-lasting anti-emetic effects on both acute and delayed phases by a single intravenous administration. Suppression of delayed emesis was not due to elimination of the acute phase because the delayed emesis was also suppressed by administration after the onset of delayed emesis. Persistent blockade of NK(1) receptors in the brain was demonstrated by inhibition of the NK(1) agonist-induced foot tapping response for over 24 h. An appreciable amount of T-2328 was present in the brain 32 and 72 h after the injection. The NK(1) agonist-induced contractions of isolated ileum in guinea pigs was antagonized with IC(50) values of 1.4 nM in an insurmountable manner. It is likely that T-2328 exerts the long-lasting anti-emetic effect by not only long-term presence in the brain but also its insurmountable inhibition of NK(1) receptors. PMID:18544900

  1. 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

  2. PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine

    PubMed Central

    Xue, Wenda; Wang, Wei; Gong, Tong; Zhang, Hailou; Tao, Weiwei; Xue, Lihong; Sun, Yan; Wang, Fushun; Chen, Gang

    2016-01-01

    Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju. One day post Yueju in Kunming but not ICR strain mice, expression of total and phosphorylated CREB, as well as the CREB signaling activator, PKA (protein kinase A) was up-regulated in the hippocampus. Although BDNF gene expression increased at 3 hours in both strains, it remained up-regulated at 1 day only in Kunming mice. Ketamine showed similar strain-dependent behavioral effects. However, blockade of PKA/CREB signaling blunted the antidepressant effects and reversed the up-regulation of BDNF gene expression by Yueju, but not ketamine. Conversely, blockade of mammalian target of rapamycin signaling led to opposite effects. Taken altogether, prolonged transcriptional up-regulation of hippocampal BDNF may account for the stain-dependent enduring antidepressant responses to Yueju and ketamine, but it was mediated via PKA/CREB pathway only for Yueju. PMID:27197752

  3. Control of Culicoides sonorensis (Diptera: Ceratopogonidae) blood feeding on sheep with long-lasting repellent pesticides.

    PubMed

    Reeves, W K; Lloyd, J E; Stobart, R; Stith, C; Miller, M M; Bennett, K E; Johnson, G

    2010-09-01

    Culicoides sonorensis is the primary vector of bluetongue and epizootic hemorrhagic disease viruses in North America. Bluetongue disease is one of the most economically important arthropod-borne diseases of sheep in North America, because it causes significant morbidity and mortality and can lead to local quarantines and international trade restrictions. Long-lasting repellent pesticides could be applied to sheep as they are moved down from mountain pastures to protect them from biting midges until the 1st frost. We tested long-lasting pesticides on sheep as repellents against C. sonorensis. Both Python ear tags with 10% zeta-cypermethrin (9.8 g/tag) synergized with 20% piperonyl butoxide (PBO) and a 12-ml low-volume spray application of ready-to-use sheep insecticide (Y-TEX) with 2.5% permethrin and 2.5% PBO in an oil-based formulation were repellent to C. sonorensis for at least 3-5 wk after a single application. PMID:21033057

  4. Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage.

    PubMed

    Tomaiuolo, Micol; Katche, Cynthia; Viola, Haydee; Medina, Jorge H

    2015-01-01

    The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. PMID:26380116

  5. Bacterial Urease and its Role in Long-Lasting Human Diseases

    PubMed Central

    Konieczna, Iwona; Żarnowiec, Paulina; Kwinkowski, Marek; Kolesińska, Beata; Frączyk, Justyna; Kamiński, Zbigniew; Kaca, Wiesław

    2012-01-01

    Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. The presence of ureolytic activity is an important marker of a number of bacterial infections. Urease is also an immunogenic protein and is recognized by antibodies present in human sera. The presence of such antibodies is connected with progress of several long-lasting diseases, like rheumatoid arthritis, atherosclerosis or urinary tract infections. In bacterial ureases, motives with a sequence and/or structure similar to human proteins may occur. This phenomenon, known as molecular mimicry, leads to the appearance of autoantibodies, which take part in host molecules destruction. Detection of antibodies-binding motives (epitopes) in bacterial proteins is a complex process. However, organic chemistry tools, such as synthetic peptide libraries, are helpful in both, epitope mapping as well as in serologic investigations. In this review, we present a synthetic report on a molecular organization of bacterial ureases - genetic as well as structural. We characterize methods used in detecting urease and ureolytic activity, including techniques applied in disease diagnostic processes and in chemical synthesis of urease epitopes. The review also provides a summary of knowledge about a toxic effect of bacterial ureases on human body and about occurrence of anti-urease antibodies in long-lasting diseases. PMID:23305365

  6. Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage

    PubMed Central

    Tomaiuolo, Micol; Katche, Cynthia; Viola, Haydee; Medina, Jorge H.

    2015-01-01

    The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. PMID:26380116

  7. 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

  8. Two long-lasting central respiratory responses following acute hypoxia in glomectomized cats.

    PubMed

    Gallman, E A; Millhorn, D E

    1988-01-01

    1. Central respiratory response to acute (10 min) hypoxia, as measured by phrenic nerve activity, was determined in peripheral chemo-denervated cats. 2. Hypoxia was induced by ventilating cats for 10 min at reduced inspired oxygen levels (inspired O2 fraction, FI,O2 = 0.06-0.15). The degree of hypoxaemia was determined from an arterial blood sample and ranged from 'severe' (arterial O2 pressure, Pa,O2 less than 26 Torr) to 'mild' (Pa,O2 greater than 35 Torr). The respiratory response was monitored for 1 h following return to ventilation with 100% oxygen. 3. The results confirmed the finding of prolonged (greater than 60 min) inhibition of respiration upon return to hyperoxic conditions following severe hypoxia, as reported previously (Millhorn, Eldridge, Kiley & Waldrop, 1984). A new finding was a long-lasting (greater than 60 min) facilitation of respiration following exposure to less severe (Pa,O2 greater than 35 Torr) hypoxia. 4. Medullary extracellular fluid pH was measured in six cats. Changes in pH could not explain either the prolonged inhibition following severe hypoxia or the long-lasting facilitation observed following mild hypoxia. 5. Ablation studies were performed in order to determine the locations of the neuronal substrates for the inhibitory and facilitatory mechanisms. The results of this series of experiments indicate that the mesencephalon is necessary for activation of the inhibitory mechanism, while the facilitatory mechanism requires the presence of higher brain structures, notably the diencephalon. 6. Following removal of the diencephalon, the inhibitory response was seen following even mild hypoxic insults, i.e. those shown to produce facilitation in animals with intact brains. In the absence of the mesencephalon, neither prolonged inhibition nor prolonged facilitation could be produced following hypoxia. 7. It is proposed that there are two centrally mediated long-lasting responses to acute hypoxia. Facilitation is seen following mild

  9. 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. PMID:17183317

  10. Ephemeral disturbances have long-lasting impacts on forest invasion dynamics.

    PubMed

    Eschtruth, Anne K; Battles, John J

    2014-07-01

    Ephemeral disturbances are common in many systems. Often, these brief events are assumed to be a nuisance with little long-term ecological impact. We quantified the impact of the ephemeral forest disturbance caused by gypsy moth canopy defoliation on exotic plant invasion in eight hardwood forests in the Delaware Water Gap National Recreation Area, USA. Six years following the gypsy moth disturbance, we were able to predict 59% of the increase in Alliaria petiolata abundance and 42% of the increase in Microstegium vimineum abundance with models incorporating an interaction between disturbance severity and propagule pressure. In addition, we found that the disturbance timing had substantial impacts on the invasion dynamics of Alliaria petiolata. Our results suggest that ephemeral disturbances can have important and long-lasting impacts on plant communities, and highlight the need to account for variations in disturbance characteristics and the role of propagule pressure in determining the disturbance-invasion relationship. PMID:25163111

  11. Energetic ion excited long-lasting ``sword'' modes in tokamak plasmas with low magnetic shear

    NASA Astrophysics Data System (ADS)

    Wang, Xiaogang; Zhang, Ruibin; Deng, Wei; Liu, Yi

    2013-10-01

    An m/ n = 1 mode driven by trapped fast ions with a sword-shape envelope of long-lasting (for hundreds of milliseconds) magnetic perturbation signals, other than conventional fishbones, is studied in this paper. The mode is usually observed in low shear plasmas. Frequency and growth rate of the mode and its harmonics are calculated and in good agreements with observations. The radial mode structure is also obtained and compared with that of fishbones. It is found that due to fast ion driven the mode differs from magnetohydrodynamic long lived modes (LLMs) observed in MAST and NSTX. On the other hand, due to the feature of weak magnetic shear, the mode is also significantly different from fishbones. The nonlinear evolution of the mode and its comparison with fishbones are further investigated to analyze the effect of the mode on energetic particle transport and confinement.

  12. Prenatal exposure to LPS leads to long-lasting physiological consequences in male offspring.

    PubMed

    Asiaei, Masoud; Solati, Jalal; Salari, Ali-Akbar

    2011-12-01

    Growing evidence suggests that early life events are critical determinants for disorders later in life. According to a comprehensive number of epidemiological/animal studies, exposure to lipopolysaccharide, causes alteration in pro-inflammatory cytokine levels, hypothalamic-pituitary-adrenal functioning and the hormonal system which may contribute to behavioral and neurological injuries. In this study we investigated the effects of lipopolysaccharide administration on physiological parameters in pregnant dams and their male offspring aged 9 weeks. In gestational Day 10, pregnant mice were injected intrapritoneally with Salmonella enterica lipopolysaccharide to model prenatal exposure to infection. The following results were obtained for offspring from dams stressed during pregnancy: (a) reduced anxiety-related behavior in the elevated plus maze; (b) reduced food and water intake; (c) reduced body weight from birth up to postnatal Day 40. The observed data provide experimental evidence showing that prenatal stress can have complex and long-lasting physiological/behavioral consequences in offspring. PMID:21630247

  13. Long-lasting Localized Pemphigus Vulgaris without Detectable Serum Autoantibodies Against Desmoglein 3 and Desmoglein 1

    PubMed Central

    Yoshifuku, Asuka; Fujii, Kazuyasu; Kawahira, Hisao; Katsue, Hiromi; Baba, Atsunori; Higashi, Yuko; Aoyama, Yumi; Kanekura, Takuro

    2016-01-01

    Pemphigus vulgaris (PV) is an autoimmune blistering disease elicited by anti-desmoglein (DsG) 3 antibody. Although skin lesions tend to be distributed over the entire body, in some patients, they are confined to a restricted area. We report two patients who presented with long-lasting localized PV without detectable anti-DsG antibodies after suffering antibody-positive systemic PV. Initial treatment with prednisolone (PSL) was successful in both patients, but a local relapse occurred on the cheek or lower lip after a reduction in the PSL dose. Biopsy of the localized lesions showed suprabasal acantholysis; no serum DsG antibodies were found. Local immunosuppression therapy was effective in both patients. Based on our findings, we suggest that localized PV without detectable antibodies can develop after systemic PV. PMID:27512189

  14. 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. PMID:25427871

  15. 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. PMID:24752523

  16. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant.

    PubMed

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  17. Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation

    PubMed Central

    Toprani, Sheela; Durand, Dominique M

    2013-01-01

    Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease. Deep brain electrical stimulation (DBS) of grey matter has been used for MTLE with limited success. However, stimulation of a white matter tract connecting the hippocampi, the ventral hippocampal commissure (VHC), with low frequencies that simulate interictal discharges has shown promising results, with seizure reduction greater than 98% in bilateral hippocampi during stimulation and greater than 50% seizure reduction in bilateral hippocampi after treatment. A major hurdle to the implementation and optimization of this treatment is that the mechanisms of seizure reduction by low frequency electrical stimulation (LFS) are not known. The goal of this study is to understand how commissural fibre tract stimulation reduces bilateral hippocampal epileptic activity in an in vitro slice preparation containing bilateral hippocampi connected by the VHC. It is our hypothesis that electrical stimuli induce hyperpolarization lasting hundreds of milliseconds following each pulse which reduces spontaneous epileptic activity during each inter-stimulus interval (ISI). Stimulus-induced long-lasting-hyperpolarization (LLH) can be mediated by GABAB inhibitory post-synaptic potentials (IPSPs) or slow after-hyperpolarization (sAHP). To test the role of LLH in effective bilateral seizure reduction by fibre tract stimulation, we measured stimulus-induced hyperpolarization during LFS of the VHC using electrophysiology techniques. Antagonism of the GABAB IPSP and/or sAHP diminished stimulus-induced hyperpolarization concurrently with LFS efficacy (greater than 50% reduction). Blocking both the GABAB IPSP and sAHP simultaneously eliminated the effect of electrical stimulation on seizure reduction entirely. These data show that LFS of the VHC is an effective protocol for bilateral hippocampal seizure reduction and that its efficacy relies on the induction of long-lasting hyperpolarization mediated

  18. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant

    PubMed Central

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  19. Long-Lasting Reduction of Blood Pressure by Electroacupuncture in Patients with Hypertension: Randomized Controlled Trial

    PubMed Central

    Li, Peng; Cheng, Ling; Liu, Dongmei; Painovich, Jeannette; Vinjamury, Sivarama; Longhurst, John C.

    2015-01-01

    Abstract Background: Acupuncture at specific acupoints has experimentally been found to reduce chronically elevated blood pressure. Objective: To examine effectiveness of electroacupuncture (EA) at select acupoints to reduce systolic blood pressure (SBP) and diastolic blood pressures (DBP) in hypertensive patients. Design: Two-arm parallel study. Patients: Sixty-five hypertensive patients not receiving medication were assigned randomly to one of the two acupuncture intervention (33 versus 32 patients). Intervention: Patients were assessed with 24-hour ambulatory blood pressure monitoring. They were treated with 30-minutes of EA at PC 5-6+ST 36-37 or LI 6-7+GB 37-39 once weekly for 8 weeks. Four acupuncturists provided single-blinded treatment. Main outcome measures: Primary outcomes measuring effectiveness of EA were peak and average SBP and DBP. Secondary outcomes examined underlying mechanisms of acupuncture with plasma norepinephrine, renin, and aldosterone before and after 8 weeks of treatment. Outcomes were obtained by double-blinded evaluation. Results: After 8 weeks, 33 patients treated with EA at PC 5-6+ST 36-37 had decreased peak and average SBP and DBP, compared with 32 patients treated with EA at LI 6-7+GB 37-39 control acupoints. Changes in blood pressures significantly differed between the two patient groups. In 14 patients, a long-lasting blood pressure–lowering acupuncture effect was observed for an additional 4 weeks of EA at PC 5-6+ST 36-37. After treatment, the plasma concentration of norepinephrine, which was initially elevated, was decreased by 41%; likewise, renin was decreased by 67% and aldosterone by 22%. Conclusions: EA at select acupoints reduces blood pressure. Sympathetic and renin-aldosterone systems were likely related to the long-lasting EA actions. PMID:26392838

  20. 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.

  1. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors.

    PubMed

    Bales, K L; Plotsky, P M; Young, L J; Lim, M M; Grotte, N; Ferrer, E; Carter, C S

    2007-01-01

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations. PMID:17055176

  2. Short stressor induced long-lasting increases of vasopressin stores in hypothalamic corticotropin-releasing hormone (CRH) neurons in adult rats.

    PubMed

    Schmidt, E D; Binnekade, R; Janszen, A W; Tilders, F J

    1996-09-01

    Recently, we demonstrated that single administration of interleukin-1 beta (IL-1) to adult rats induces a long-lasting (weeks) increase of vasopressin (AVP) stores in terminals of CRH neurons in the external zone of the median eminence (ZEME). This is accompanied by hypersecretion of AVP into the pituitary portal circulation and long-lasting hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis to stressors. Here, we determine whether this form of plasticity of hypothalamic CRH neurons is specific for IL-1 or represents a general response to a stressor. Single exposure of rats to lipopolysaccharide (LPS), IL-1, brain surgery or electric footshocks increases the AVP stores in the ZEME 7 and 11 days later. Exposure to insulin or ether does not affect the AVP stores. The stressors have little or no effect on the CRH stores in the ZEME. The amplitude of the increase in AVP as measured 7-11 days after stimulation correlates with the overall ACTH response to the stressor (area under curve, r = 0.89, P < 0.0001), with the peak ACTH levels (r = 0.52, P < 0.05), but not with the duration of the ACTH response nor with any parameter of the corticosterone response. Administration of ACTH or corticosterone at doses that mimic stress-induced plasma levels does not increase AVP stores 7 days later. We conclude that long-lasting increases of AVP stores in CRH terminals in the ZEME can be induced by various stressors and postulate that the amplitude of such increases depends on the degree of activation of the CRH neurons by the stressor. (NWO grant: 900-543-101.) PMID:8877819

  3. 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.

  4. 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

  5. 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

  6. 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

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

    PubMed

    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

  8. 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. PMID:24856466

  9. 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

  10. 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. PMID:27071097

  11. Nongassing long-lasting electro-osmotic pump with polyaniline-wrapped aminated graphene electrodes.

    PubMed

    Kumar, Rudra; Jahan, Kousar; Nagarale, Rajaram K; Sharma, Ashutosh

    2015-01-14

    An efficient nongassing electro-osmotic pump (EOP) with long-lasting electrodes and exceptionally stable operation is developed by using novel flow-through polyaniline (PANI)-wrapped aminated graphene (NH2-G) electrodes. The NH2-G/PANI electrode combines the excellent oxidation/reduction capacity of PANI with the exceptional conductivity and inertness of NH2-G. The flow rate varies linearly with voltage but is highly dependent on the electrode composition. The flow rates at a potential of 5 V for pristine NH2-G and PANI electrodes are 71 and 100 μL min(-1) cm(-2), respectively, which increase substantially by the use of NH2-G/PANI electrode. It increased from 125 to 182 μL min(-1) cm(-2) as the fraction of aniline increased from 66.63 to 90.90%. The maximum flux obtained is 40 μL min(-1) V(-1) cm(-2) with NH2-G/PANI-90.9 electrodes. The assembled EOP remained exceptionally stable until the electrode columbic capacity was fully utilized. The prototype shown here delivered 8.0 μL/min at a constant applied voltage of 2 V for over 7 h of continuous operation. The best EOP produces a maximum stall pressure of 3.5 kPa at 3 V. These characteristics make it suitable for a variety of microfluidic/device applications. PMID:25478894

  12. 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.

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

    PubMed

    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

  14. Long-Lasting Gene Conversion Shapes the Convergent Evolution of the Critical Methanogenesis Genes

    PubMed Central

    Wang, Sishuo; Chen, Youhua; Cao, Qinhong; Lou, Huiqiang

    2015-01-01

    Methanogenesis and its key small-molecule methyltransferase Mtr complex are poorly understood despite their pivotal role in Earth’s global carbon cycle. Mtr complex is encoded by a conserved mtrEDCBAFGH operon in most methanogens. Here we report that two discrete lineages, Methanococcales and Methanomicrobiales, have a noncanonical mtr operon carrying two copies of mtrA resulting from an ancient duplication. Compared to mtrA-1, mtrA-2 acquires a distinct transmembrane domain through domain shuffling and gene fusion. However, the nontransmembrane domains (MtrA domain) of mtrA-1 and mtrA-2 are homogenized by gene conversion events lasting throughout the long history of these extant methanogens (over 2410 million years). Furthermore, we identified a possible recruitment of ancient nonmethanogenic methyltransferase genes to establish the methanogenesis pathway. These results not only provide novel evolutionary insight into the methanogenesis pathway and methyltransferase superfamily but also suggest an unanticipated long-lasting effect of gene conversion on gene evolution in a convergent pattern. PMID:26384370

  15. Multisatellite Observations of Long-lasting Poloidal Pc 4 Pulsations in the Dayside Magnetosphere.

    NASA Astrophysics Data System (ADS)

    Sibeck, D. G.; Korotova, G. I.; Engebretson, M. J.; Wygant, J. R.; Thaller, S. A.

    2015-12-01

    We use magnetic field, plasma and particles observations from Van Allen Probes and THEMIS spacecraft to study the characteristics of long-lasting poloidal Pc4 pulsations in the dayside magnetosphere. They were observed after the main phase of a strong storm during low geomagnetic activity. The Pc 4 pulsations exhibited periods of 40-50 s and amplitudes of 4-6 nT in the dominant radial component. They had a packet-like structure and lasted more than 3 hours. The FFT spectra show that the main spectral power corresponds to frequencies of ~ 20-22 mHz, which argues against a source for the pulsations in the solar wind. The frequencies of the central power peak in the radial component decrease with radial distance from the Earth. The most striking feature of the Pc 4 pulsations was their occurrence at similar locations on three of four successive orbits of Van Allen Probes nine hours apart. We determined that the pulsations were second harmonic mode waves. We test various possible mechanisms for their generation.

  16. Electronic signatures for long-lasting storage purposes in electronic archives.

    PubMed

    Pharow, Peter; Blobel, Bernd

    2005-03-01

    Communication and co-operation in healthcare and welfare require a certain set of trusted third party (TTP) services describing both status and relation of communicating principals as well as their corresponding keys and attributes. Additional TTP services are needed to provide trustworthy information about dynamic issues of communication and co-operation such as time and location of processes, workflow relations, and system behaviour. Legal and ethical requirements demand securely stored patient information and well-defined access rights. Among others, electronic signatures based on asymmetric cryptography are important means for securing the integrity of a message or file as well as for accountability purposes including non-repudiation of both origin and receipt. Electronic signatures along with certified time stamps or time signatures are especially important for electronic archives in general, electronic health records (EHR) in particular, and especially for typical purposes of long-lasting storage. Apart from technical storage problems (e.g. lifetime of the storage devices, interoperability of retrieval and presentation software), this paper identifies mechanisms of e.g. re-signing and re-stamping of data items, files, messages, sets of archived items or documents, archive structures, and even whole archives. PMID:15694634

  17. Neural representation of navigational relevance is rapidly induced and long lasting.

    PubMed

    Janzen, Gabriele; Wagensveld, Barbara; van Turennout, Miranda

    2007-04-01

    Successful navigation is facilitated by the presence of landmarks. Previous functional magnetic resonance imaging (fMRI) evidence indicated that the human parahippocampal gyrus automatically distinguishes between landmarks placed at navigationally relevant (decision points) and irrelevant locations (nondecision points). This storage of navigational relevance can provide a neural mechanism underlying successful navigation. However, an efficient wayfinding mechanism requires that important spatial information is learned quickly and maintained over time. The present study investigates whether the representation of navigational relevance is modulated by time and practice. Participants learned 2 film sequences through virtual mazes containing objects at decision and at nondecision points. One maze was shown one time, and the other maze was shown 3 times. Twenty-four hours after study, event-related fMRI data were acquired during recognition of the objects. The results showed that activity in the parahippocampal gyrus was increased for objects previously placed at decision points as compared with objects placed at nondecision points. The decision point effect was not modulated by the number of exposures to the mazes and independent of explicit memory functions. These findings suggest a persistent representation of navigationally relevant information, which is stable after only one exposure to an environment. These rapidly induced and long-lasting changes in object representation provide a basis for successful wayfinding. PMID:16751297

  18. Net Risk: A Risk Assessment of Long-Lasting Insecticide Bed Nets Used for Malaria Management

    PubMed Central

    Peterson, Robert K. D.; Barber, Loren M.; Schleier, Jerome J.

    2011-01-01

    Despite the demonstrated ability of bed nets that have been factory-impregnated with long-lasting insecticides (LLINs) to protect people from malaria and despite the ambitious plans for their widespread use, the health risks from the LLINs themselves have not been adequately investigated and reported in the peer-reviewed science literature. Here, we use a probabilistic risk assessment approach to estimate the risks to Africans from inhalation, dermal, and oral exposures to the newer LLINs with permethrin, α-cypermethrin, or deltamethrin as the insecticide active ingredient. We estimated exposures to LLINs using 17 age groups to incorporate different body weights and sleeping behaviors. Risk quotients (exposure divided by toxic threshold) at the 50th and 90th percentiles for non-cancer risks were < 1.0 for lifetime adjusted risk and all youth and adult age groups. Risk quotients for infants and toddlers (0–3 years) and child groups from 3 to 10 years were ≥ 1.0 for specific bed nets. PMID:21633033

  19. Evaluation of the long-lasting antihypertensive action of 7-O-ethylfangchinoline.

    PubMed

    Kato, T; Noguchi, K; Sakanashi, M

    1994-09-01

    The antihypertensive effect of 7-O-ethylfangchinoline (TJN-220) was analyzed in an experimental model of hypertensive rats under the conscious condition. Single oral administration of TJN-220 (25 and 50 mg/kg) produced a progressive and long-lasting fall of mean blood pressure in spontaneously hypertensive rats (SHRs), deoxycorticosterone acetate (DOCA)-salt hypertensive rats and renal hypertensive rats until 72 hr after the drug administration, but affected neither the heart rate in these hypertensive rats nor the hemodynamic parameters in normotensive rats. In SHRs implanted with a telemetry transmitter, TJN-220 (50 mg/kg, p.o.) produced falls of systolic and diastolic blood pressures and diminished the difference in blood pressure between the dark period and the light period for 3 days, particularly by suppressing the increasing phase of blood pressure during the dark period without influencing heart rate or locomotor activity. On the other hand, nicardipine (10 mg/kg, p.o.) produced a transient fall of blood pressure associated with a tachycardia during the light period on the first day alone. Clonidine (0.3 mg/kg, p.o.) diminished the increasing phases of blood pressure and heart rate during the dark period on the first day alone. Thus, the antihypertensive action of TJN-220 was much longer than those of nicardipine and clonidine. The present results suggest that TJN-220 may have potential for use as a beneficial antihypertensive drug. PMID:7861666

  20. 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

  1. Long-lasting regulation of hippocampal Bdnf gene transcription after contextual fear conditioning.

    PubMed

    Mizuno, K; Dempster, E; Mill, J; Giese, K P

    2012-08-01

    Long-term memory formation requires de novo protein synthesis and gene transcription. During contextual long-term memory formation brain-derived neurotrophic factor (BDNF) gene expression changes in conjunction with alterations of DNA methylation in the Bdnf gene. However, little is known about the molecular mechanisms underlying the maintenance and persistence of contextual long-term memory. Here, we examined the transcription of specific Bdnf exons in the hippocampus for long periods after contextual fear conditioning. We found changes in transcription lasting for at least 24 h after contextual fear conditioning, with some sex-specific effects. In addition, hypomethylation at a CpG site in CpG island 2 located at the end of Bdnf exon III sequence was detected at 0.5 h and maintained for up to 24 h after contextual fear conditioning. The identification of these long-lasting changes in transcription and DNA methylation at the Bdnf gene suggests that BDNF might have a role for storage of contextual long-term memory in the hippocampus. PMID:22574690

  2. Chronic Methamphetamine Exposure Produces a Delayed, Long-Lasting Memory Deficit

    PubMed Central

    North, Ashley; Swant, Jarod; Salvatore, Michael F.; Gamble-George, Joyonna; Prins, Petra; Butler, Brittany; Mittal, Mukul K.; Heltsley, Rebecca; Clark, John T.; Khoshbouei, Habibeh

    2013-01-01

    Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short-term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short-term memory when measured after 14 days of METH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH-exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short-term as well as long-term consequences of methamphetamine exposure. PMID:23280858

  3. Long lasting effects of the conversion from natural forest to poplar plantation on soil microbial communities.

    PubMed

    Vitali, Francesco; Mastromei, Giorgio; Senatore, Giuliana; Caroppo, Cesarea; Casalone, Enrico

    2016-01-01

    In this study, we evaluate the long-lasting effects on soil microbial communities of a change within a single land-use category, specifically the conversion from natural forest to forest plantation. To minimize the effects of impacts other than land-use (i.e., climatic and anthropogenic), we chose three sites within a Natural Park, with homogeneous orographic and soil texture characteristics. We compared microbial diversity in a total of 156 soil samples from two natural mixed forests and a similar forest converted to poplar plantation about thirty years ago. The diversity and structure of bacterial and fungal communities were investigated by terminal restriction fragments length polymorphism (T-RFLP) analysis of the 16S-rRNA gene and the ITS-rDNA regions, respectively. Bacterial and fungal communities from the forest plantation, compared to those from natural forest soils, showed different community structure and lower α-diversity values, consistently with the significantly higher pH values and lower organic matter content of those soils. β-diversity values, the number of measured and estimated dominant OTUs, and their distribution among the three sites showed that microbial communities from the two natural forests were much more similar to each other than they were to communities from the poplar plantation, suggesting an effect of the forest conversion on the composition and diversity of soil microbial communities. α-diversity in cultivated forest soils had narrower temporal fluctuations than in natural forest soils, suggesting higher temporal stability of microbial communities. Overall, we demonstrated that the conversion from natural forest to forest plantation altered soil microbial communities, changing their structure, lowering their diversity, and causing a spatial and temporal homogenization. PMID:26686617

  4. Evidence of man-vector contact in torn long-lasting insecticide-treated nets

    PubMed Central

    2013-01-01

    Background Studies indicate that physical damage to long-lasting insecticide-treated nets (LLINs) occurs at a surprisingly rapid rate following net distribution. To what extent does such damage affect the impact of LLINs? Can vectors pass a compromised LLIN barrier to bite? Do more resistant vectors enter the insecticide-treated nets (ITNs) through holes? Methods The study was carried out in three geo-locations. Two types of LLINs (polyester and polyethylene) with ‘standardized’ physical damage were compared with similarly damaged, but non-insecticidal (control) nets. The proportionate Holes Index (pHI) of each net was 276. Mosquitoes were captured inside the nets, identified taxonomically, and subjected to molecular analysis to estimate Knock-down resistance (Kdr) frequency. Results The most commonly observed species was Anopheles gambiae, accounting for approximately 70% (1,076/1,550) of the total mosquitoes collected both in LLINs and non-insecticidal nets. When compared with controls, number of vectors captured in torn LLINs was significantly reduced. Nonetheless in a night, an average of 5 An. gambiae s.l could enter the damaged LLINs to bite. Similar numbers of resistant mosquitoes were collected in both LLINs and non-insecticidal (control) nets (p > 0.05). Conclusions At a pHI of 276, man-vector contact was observed in torn LLINs. The insecticide at the surface of LLINs could only reduce the number of vectors. Resistant mosquitoes have opportunity to enter both non-insecticidal (control) nets and LLINs to bite. PMID:23941585

  5. 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. PMID:14550030

  6. 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. PMID:23472189

  7. The inhibitory neurotransmitter GABA evokes long-lasting Ca(2+) oscillations in cortical astrocytes.

    PubMed

    Mariotti, Letizia; Losi, Gabriele; Sessolo, Michele; Marcon, Iacopo; Carmignoto, Giorgio

    2016-03-01

    Studies over the last decade provided evidence that in a dynamic interaction with neurons glial cell astrocytes contribut to fundamental phenomena in the brain. Most of the knowledge on this derives, however, from studies monitoring the astrocyte Ca(2+) response to glutamate. Whether astrocytes can similarly respond to other neurotransmitters, including the inhibitory neurotransmitter GABA, is relatively unexplored. By using confocal and two photon laser-scanning microscopy the astrocyte response to GABA in the mouse somatosensory and temporal cortex was studied. In slices from developing (P15-20) and adult (P30-60) mice, it was found that in a subpopulation of astrocytes GABA evoked somatic Ca(2+) oscillations. This response was mediated by GABAB receptors and involved both Gi/o protein and inositol 1,4,5-trisphosphate (IP3 ) signalling pathways. In vivo experiments from young adult mice, revealed that also cortical astrocytes in the living brain exibit GABAB receptor-mediated Ca(2+) elevations. At all astrocytic processes tested, local GABA or Baclofen brief applications induced long-lasting Ca(2+) oscillations, suggesting that all astrocytes have the potential to respond to GABA. Finally, in patch-clamp recordings it was found that Ca(2+) oscillations induced by Baclofen evoked astrocytic glutamate release and slow inward currents (SICs) in pyramidal cells from wild type but not IP3 R2(-/-) mice, in which astrocytic GABAB receptor-mediated Ca(2+) elevations are impaired. These data suggest that cortical astrocytes in the mouse brain can sense the activity of GABAergic interneurons and through their specific recruitment contribut to the distinct role played on the cortical network by the different subsets of GABAergic interneurons. PMID:26496414

  8. Nonlinear Force-free Modeling of a Long-lasting Coronal Sigmoid

    NASA Astrophysics Data System (ADS)

    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 × 1020 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 α 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 Démoulin model. We find that the twist angle Φ of the magnetic field increases with time to about 2π just prior to the eruption, but never reaches the value necessary for the kink instability.

  9. 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%)

  10. Planning long lasting insecticide treated net campaigns: should households’ existing nets be taken into account?

    PubMed Central

    2013-01-01

    Background Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. Methods A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net ‘decay’ parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered

  11. 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

  12. System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania

    PubMed Central

    2010-01-01

    Background Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. Methods Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. Results The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). Conclusions Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain

  13. Long-Lasting and Transgenerational Effects of an Environmental Enrichment on Memory Formation

    PubMed Central

    Arai, Junko A.; Feig, Larry A.

    2010-01-01

    It has long been believed that genetically-determined, but not environmentally-acquired, phenotypes can be inherited. However, a large number of recent studies have reported that phenotypes acquired from an animal’s environment can be transmitted to the next generation. Moreover, epidemiology studies have hinted that a similar phenomenon occurs in humans. This type of inheritance does not involve gene mutations that change DNA sequence. Instead, it is thought that epigenetic changes in chromatin, such as DNA methylation and histone modification, occur. In this review, we will focus on one exciting new example of this phenomenon, transfer across generations of enhanced synaptic plasticity and memory formation induced by exposure to an “enriched” environment. PMID:21078373

  14. Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats.

    PubMed

    Burgos, H; Cofré, C; Hernández, A; Sáez-Briones, P; Agurto, R; Castillo, A; Morales, B; Zeise, M L

    2015-09-15

    Methylphenidate (MPH) is widely used as a "nootropic" agent and in the treatment of disorders of attention, and has been shown to modulate synaptic plasticity in vitro. Here we present in vivo evidence that this MPH-induced metaplasticity can last long after the end of treatment. MPH (0, 0.2, 1 and 5mg/kg) was administered daily to male rats from postnatal day 42 for 15 days. The animals were tested daily in a radial maze. Long-term potentiation (LTP), a marker of neural plasticity, was induced in vivo in the prefrontal cortex after 2-3h, 15-18 days or 5 months without treatment. The behavioral performance of the 1mg/kg group improved, while that of animals that had received 5mg/kg deteriorated. In the 1 and 5mg/kg groups LTP induced 2-3h after the last MPH treatment was twice as large as in the controls. Further, 15-18 days after the last MPH administration, in groups receiving 1 and 5mg/kg, LTP was about fourfold higher than in controls. However, 5 months later, LTP in the 1mg/kg group was similar to controls and in the 5mg/kg group LTP could not be induced at all. No significant changes of LTP were seen in the low-dose group of animals (0.2mg/kg). Thus, firstly, doses of MPH that improve learning coincide approximately with those that augment LTP. Secondly, MPH-induced increases in LTP can last for several weeks, but these may disappear over longer periods or deteriorate at high doses. PMID:25997580

  15. 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

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

    PubMed

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

    2012-11-01

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

  17. Long-lasting D-region ionospheric modifications, caused by intense lightning in association with elve and sprite pairs

    NASA Astrophysics Data System (ADS)

    Haldoupis, Christos; Cohen, Morris; Cotts, Benjamin; Arnone, Enrico; Inan, Umran

    2012-08-01

    Observations show that intense +CG lightning discharges which trigger both an elve and a sprite are associated with long-lasting conductivity modifications in the upper D-region ionosphere. They are observed as strong perturbations in VLF signals propagating through the disturbed region, manifested as LOng Recovery Early VLF events (LORE), which can last up to 30 minutes. These same ionospheric modifications are also responsible for step-like changes, seen mostly in off-storm VLF transmissions, which offset signal levels even for longer times. The evidence suggests that when a very intense positive cloud to ground lightning stroke leads to an elve and a high altitude sprite, and possibly a sprite halo as well, there is production of long lasting elevations in electron density at VLF reflection heights that cause LOREs and severe effects on VLF propagation. The present results confirm past predictions and postulations that elves may be accompanied by long-lasting electron density perturbations in the lower ionosphere.

  18. A Long Lasting β1 Adrenergic Receptor Stimulation of cAMP/Protein Kinase A (PKA) Signal in Cardiac Myocytes*

    PubMed Central

    Fu, Qin; Kim, Sungjin; Soto, Dagoberto; De Arcangelis, Vania; DiPilato, Lisa; Liu, Shubai; Xu, Bing; Shi, Qian; Zhang, Jin; Xiang, Yang K.

    2014-01-01

    Small-molecule, ligand-activated G protein-coupled receptors are generally thought to be rapidly desensitized within a period of minutes through receptor phosphorylation and internalization after repeated or prolonged stimulation. This transient G protein-coupled receptor activation remains at odds with many observed long-lasting cellular and physiological responses. Here, using live cell imaging of cAMP with a FRET-based biosensor and myocyte contraction assay, we show that the catecholamine-activated β1 adrenergic receptor (β1AR) continuously stimulates second messenger cAMP synthesis in primary cardiac myocytes and neurons, which lasts for more than 8 h (a decay t½ of 3.9 h) in cardiac myocytes. However, the β1AR-induced cAMP signal is counterbalanced and masked by the receptor-bound phosphodiesterase (PDE) 4D8-dependent cAMP hydrolysis. Inhibition of PDE4 activity recovers the receptor-induced cAMP signal and promotes contractile response in mouse hearts during extended periods of agonist stimulation. β1AR associates with PDE4D8 through the receptor C-terminal PDZ motif-dependent binding to synaptic-associated protein 97 (SAP97). Knockdown of SAP97 or mutation of the β1AR PDZ motif disrupts the complex and promotes sustained agonist-induced cAMP activity, PKA phosphorylation, and cardiac myocyte contraction response. Together, these findings unveil a long lasting adrenergic signal in neurons and myocytes under prolonged stimulation and an underappreciated role of PDE that is essential in classic receptor signaling desensitization and in maintaining a long lasting cAMP equilibrium for ligand-induced physiological response. PMID:24713698

  19. Long-Lasting Insecticidal Nets Are Synergistic with Mass Drug Administration for Interruption of Lymphatic Filariasis Transmission in Nigeria

    PubMed Central

    Eigege, Abel; Miri, Emmanuel; Sallau, Adamu; Umaru, John; Mafuyai, Hayward; Chuwang, Yohanna S.; Danjuma, Goshit; Danboyi, Jacob; Adelamo, Solomon E.; Mancha, Bulus S.; Okoeguale, Bridget; Patterson, Amy E.; Rakers, Lindsay; Richards, Frank O.

    2013-01-01

    In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission. PMID:24205421

  20. 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…

  1. Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract.

    PubMed

    Dai, Jin; Zhang, Tianyuan; Wang, Luying; Shao, Lili; Zhu, Cuiming; Zhang, Yuyang; Failor, Courtney; Schenken, Robert; Baseman, Joel; He, Cheng; Zhong, Guangming

    2016-08-01

    Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarum can spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarum strain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivo imaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of the C. muridarum organisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridarum inoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract. PMID:27271744

  2. An inhibitor of neuronal exocytosis (DD04107) displays long-lasting in vivo activity against chronic inflammatory and neuropathic pain.

    PubMed

    Ponsati, Berta; Carreño, Cristina; Curto-Reyes, Verdad; Valenzuela, Belen; Duart, María José; Van den Nest, Wim; Cauli, Omar; Beltran, Beatriz; Fernandez, Jimena; Borsini, Franco; Caprioli, Antonio; Di Serio, Stefano; Veretchy, Mario; Baamonde, Ana; Menendez, Luis; Barros, Francisco; de la Pena, Pilar; Borges, Ricardo; Felipo, Vicente; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

    2012-06-01

    Small peptides patterned after the N terminus of the synaptosomal protein of 25 kDa, a member of the protein complex implicated in Ca(2+)-dependent neuronal exocytosis, inhibit in vitro the release of neuromodulators involved in pain signaling, suggesting an in vivo analgesic activity. Here, we report that compound DD04107 (palmitoyl-EEMQRR-NH(2)), a 6-mer palmitoylated peptide that blocks the inflammatory recruitment of ion channels to the plasma membrane of nociceptors and the release of calcitonin gene-related peptide from primary sensory neurons, displays potent and long-lasting in vivo antihyperalgesia and antiallodynia in chronic models of inflammatory and neuropathic pain, such as the complete Freund's adjuvant, osteosarcoma, chemotherapy, and diabetic neuropathic models. Subcutaneous administration of the peptide produced a dose-dependent antihyperalgesic and antiallodynic activity that lasted ≥24 h. The compound showed a systemic distribution, characterized by a bicompartmental pharmacokinetic profile. Safety pharmacology studies indicated that the peptide is largely devoid of side effects and substantiated that the in vivo activity is not caused by locomotor impairment. Therefore, DD04107 is a potent and long-lasting antinociceptive compound that displays a safe pharmacological profile. These findings support the notion that neuronal exocytosis of receptors and neuronal algogens pivotally contribute to chronic inflammatory and neuropathic pain and imply a central role of peptidergic nociceptor sensitization to the pathogenesis of pain. PMID:22393248

  3. Long lasting MDM2/Translocator protein modulator: a new strategy for irreversible apoptosis of human glioblastoma cells

    PubMed Central

    Zappelli, Elisa; Marinelli, Luciana; Novellino, Ettore; Da Settimo, Federico; Taliani, Sabrina; Trincavelli, Maria L.; Martini, Claudia

    2016-01-01

    The development of multi-target drugs and irreversible modulators of deregulated signalling proteins is the major challenge for improving glioblastoma multiforme (GBM) treatment. Reversible single-target drugs are not sufficient to sustain a therapeutic effect over time and may favour the activation of alternative signalling pathways and the onset of resistance phenomena. Thus, a multi-target compound that has a long-lasting mechanism of action might have a greater and longer life span of anti-proliferative activity. Recently, a dual-target indol-3ylglyoxyldipeptide derivative, designed to bind to the Translocator Protein (TSPO) and reactivate p53 function via dissociation from its physiological inhibitor, murine double minute 2 (MDM2), has been developed as a potent GBM pro-apoptotic agent. In this study, this derivative was chemically modified to irreversibly bind MDM2 and TSPO. The new compound elicited a TSPO-mediated mitochondrial membrane dissipation and restored p53 activity, triggering a long-lasting apoptosis of GBM cells. These effects were sustained over time, involved a stable activation of extracellular signal regulated kinases and were specifically observed in cancer cells, in which these protein kinases are deregulated. Dual-targeting and irreversible binding properties combined in the same molecule may represent a useful strategy to overcome the time-limited effects elicited by classical chemotherapies. PMID:26761214

  4. Long-lasting deficits in hedonic and nucleus accumbens reactivity to sweet rewards by sugar overconsumption during adolescence.

    PubMed

    Naneix, Fabien; Darlot, Florence; Coutureau, Etienne; Cador, Martine

    2016-03-01

    Adolescence is a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system might constitute an important factor in vulnerability to pathological development. In spite of the dramatic increase in the consumption of sweet palatable foods during adolescence in our modern societies, the long-term consequences of such exposure on brain reward processing remain poorly understood. Here, we investigated in rats the long-lasting effects of sugar overconsumption during their adolescence on their adult reactivity to the hedonic properties of sweet rewards. Adolescent rats with continuous access to 5% sucrose solution (from postnatal day 30-46) showed escalating intake. At adulthood (post-natal day 70), using two-bottle free choice tests, sucrose-exposed rats showed lower intake than non-exposed rats suggesting decreased sensitivity to the rewarding properties of sucrose. In Experiment 1, we tested their hedonic-related orofacial reactions to intraoral infusion of tasty solutions. We showed that sucrose-exposed rats presented less hedonic reactions in response to sweet tastes leaving the reactivity to water or quinine unaltered. Hence, in Experiment 2, we observed that this hedonic deficit is associated with lower c-Fos expression levels in the nucleus accumbens, a brain region known to play a central role in hedonic processing. These findings demonstrate that a history of high sucrose intake during the critical period of adolescence induces long-lasting deficits in hedonic treatment that may contribute to reward-related disorders. PMID:26762310

  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. 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.

  7. 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…

  8. 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.

  9. Community-Wide Distribution of Long-Lasting Insecticidal Nets Can Halt Transmission of Lymphatic Filariasis in Southeastern Nigeria

    PubMed Central

    Richards, Frank O.; Emukah, Emmanuel; Graves, Patricia M.; Nkwocha, Omeni; Nwankwo, Lawrence; Rakers, Lindsay; Mosher, Aryc; Patterson, Amy; Ozaki, Masayo; Nwoke, Bertram E. B.; Ukaga, Chinyere N.; Njoku, Chidiebere; Nwodu, Kenrick; Obasi, Andrew; Miri, Emmanuel S.

    2013-01-01

    Lymphatic filariasis (LF) in rural southeastern Nigeria is transmitted mainly by Anopheles spp. mosquitoes. Potential coinfection with Loa loa in this area has prevented use of ivermectin in the mass drug administration (MDA) strategy for LF elimination because of potential severe adverse L. loa-related reactions. This study determined if long-lasting insecticidal net (LLIN) distribution programs for malaria would interrupt LF transmission in such areas, without need for MDA. Monthly entomologic monitoring was conducted in sentinel villages before and after LLIN distribution to all households and all age groups (full coverage) in two districts, and to pregnant women and children less than five years of age in the other two districts. No change in human LF microfilaremia prevalence was observed, but mosquito studies showed a statistically significant decrease in LF infection and infectivity with full-coverage LLIN distribution. We conclude that LF transmission can be halted in southeastern Nigeria by full-coverage LLIN distribution, without MDA. PMID:23939708

  10. 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. PMID:27027605

  11. Long-lasting seizure-related anxiety in patients with temporal lobe epilepsy and comorbid psychiatric disorders.

    PubMed

    Boulogne, Sebastien; Catenoix, Hélène; Ryvlin, Philippe; Rheims, Sylvain

    2015-09-01

    Ictal anxiety is a frequent epileptic symptom; it is usually brief, associated with objective clinical signs, and is not positively influenced by external factors, in contrast to psychiatric disorders. These criteria can, however, be misleading, especially in patients with psychiatric comorbidities. We report two patients with a history of drug-resistant right temporal lobe epilepsy, who developed long-lasting psychiatric symptoms, suggestive of exacerbation of their comorbid anxiety disorder. However, intracranial EEG data and [(18)F] FDG-PET suggested that these symptoms were related to seizure activity, highlighting the difficulties in differentiating ictal symptoms from psychiatric episodes in some patients with epilepsy and comorbid psychiatric disorders. [Published with video sequence]. PMID:26235301

  12. Community-wide distribution of long-lasting insecticidal nets can halt transmission of lymphatic filariasis in southeastern Nigeria.

    PubMed

    Richards, Frank O; Emukah, Emmanuel; Graves, Patricia M; Nkwocha, Omeni; Nwankwo, Lawrence; Rakers, Lindsay; Mosher, Aryc; Patterson, Amy; Ozaki, Masayo; Nwoke, Bertram E B; Ukaga, Chinyere N; Njoku, Chidiebere; Nwodu, Kenrick; Obasi, Andrew; Miri, Emmanuel S

    2013-09-01

    Lymphatic filariasis (LF) in rural southeastern Nigeria is transmitted mainly by Anopheles spp. mosquitoes. Potential coinfection with Loa loa in this area has prevented use of ivermectin in the mass drug administration (MDA) strategy for LF elimination because of potential severe adverse L. loa-related reactions. This study determined if long-lasting insecticidal net (LLIN) distribution programs for malaria would interrupt LF transmission in such areas, without need for MDA. Monthly entomologic monitoring was conducted in sentinel villages before and after LLIN distribution to all households and all age groups (full coverage) in two districts, and to pregnant women and children less than five years of age in the other two districts. No change in human LF microfilaremia prevalence was observed, but mosquito studies showed a statistically significant decrease in LF infection and infectivity with full-coverage LLIN distribution. We conclude that LF transmission can be halted in southeastern Nigeria by full-coverage LLIN distribution, without MDA. PMID:23939708

  13. Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission

    PubMed Central

    Chauvin, Alain; Moreau, Emmanuelle; Bonnet, Sarah; Plantard, Olivier; Malandrin, Laurence

    2009-01-01

    Babesia, the causal agent of babesiosis, are tick-borne apicomplexan protozoa. True babesiae (Babesia genus sensu stricto) are biologically characterized by direct development in erythrocytes and by transovarial transmission in the tick. A large number of true Babesia species have been described in various vertebrate and tick hosts. This review presents the genus then discusses specific adaptations of Babesia spp. to their hosts to achieve efficient transmission. The main adaptations lead to long-lasting interactions which result in the induction of two reservoirs: in the vertebrate host during low long-term parasitemia and throughout the life cycle of the tick host as a result of transovarial and transstadial transmission. The molecular bases of these adaptations in vertebrate hosts are partially known but few of the tick-host interaction mechanisms have been elucidated. PMID:19379662

  14. The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging.

    PubMed

    Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria

    2016-09-15

    Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. PMID:27185737

  15. 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

  16. 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

    2015-04-01

    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. PMID:25409594

  17. Long-lasting genomic instability following arsenite exposure in mammalian cells: the role of reactive oxygen species.

    PubMed

    Sciandrello, G; Mauro, M; Catanzaro, I; Saverini, M; Caradonna, F; Barbata, G

    2011-08-01

    Previously, we reported that the progeny of mammalian cells, which has been exposed to sodium arsenite for two cell cycles, exhibited chromosomal instability and concurrent DNA hypomethylation, when they were subsequently investigated after two months of subculturing (about 120 cell generations) in arsenite-free medium. In this work, we continued our investigations of the long-lasting arsenite-induced genomic instability by analyzing additional endpoints at several time points during the cell expanded growth. In addition to the progressive increase of aneuploid cells, we also noted micronucleated and multinucleated cells that continued to accumulate up to the 50th cell generation, as well as dicentric chromosomes and/or telomeric associations and other complex chromosome rearrangements that began to appear much later, at the 90th cell generation following arsenite exposure. The increasing genomic instability was further characterized by an increased frequency of spontaneous mutations. Furthermore, the long-lasting genomic instability was related to elevated levels of reactive oxygen species (ROS), which at the 50th cell generation appeared higher than in stable parental cells. To gain additional insight into the continuing genomic instability, we examined several individual clones isolated at different time points from the growing cell population. Chromosomally and morphologically unstable cell clones, the number of which increased with the expanded growth, were also present at early phases of growth without arsenite. All genomically unstable clones exhibited higher ROS levels than untreated cells suggesting that oxidative stress is an important factor for the progression of genomic instability induced by arsenite. PMID:21520292

  18. Long-lasting adverse effects after short-term low-dose treatment with metoclopramide for vomiting.

    PubMed

    Dahl, Eilif; Diskin, Arthur L

    2014-01-01

    Metoclopramide is commonly used to treat vomiting caused by seasickness and acute gastroenteritis on cruise ships and serious adverse effects have not been reported from use at sea. We report severe long-lasting adverse effects in a young female seafarer following short-term, low-dose use of metoclopramide. During rough seas a 25-year-old female musician on a cruise vessel presented with nausea and vomiting. She was given intramuscular metoclopramide 10 mg and diphenhydramine 25 mg. Vomiting stopped after the injections, but she felt tired, confused and dizzy. She then had been taking metoclopramide 5-10 mg a day, but stopped after a total per oral dose of 30 mg as she developed disturbing symptoms that she related to the medication, including dizziness, anxiety, fatigue, depression and involuntary movements (twitches, jerks, ticks, and tremors of the eyelids, tongue, neck, fingers, arms and legs). Neurological examination, blood tests, electrocardiography and magnetic resonance imaging of the brain were all normal. Although gradually reduced in strength and frequency, the adverse effects were very disturbing for about 10 months, but at 13 months she was almost fully recovered. For many years numerous vomiting sea travellers have been successfully treated with a single parenteral 10 mg dose of metoclopramide. There are no obvious reasons why our previously healthy patient experienced such serious and long-lasting side effects after low-dose, short-term metoclopramide administration. Until more is known, metoclopramide should be reserved for debilitating cases - and only be given after other remedies have been tried and found ineffective. PMID:24677122

  19. 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

  20. 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.

  1. 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.

  2. The Novelty-Seeking Phenotype Modulates the Long-Lasting Effects of Intermittent Ethanol Administration during Adolescence

    PubMed Central

    Montagud-Romero, Sandra; Daza-Losada, Manuel; Vidal-Infer, Antonio; Maldonado, Concepción; Aguilar, María A.; Miñarro, Jose; Rodríguez-Arias, Marta

    2014-01-01

    The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels - measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype. PMID:24658541

  3. 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

    2015-11-01

    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. PMID:26460022

  4. The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

    PubMed

    Montagud-Romero, Sandra; Daza-Losada, Manuel; Vidal-Infer, Antonio; Maldonado, Concepción; Aguilar, María A; Miñarro, Jose; Rodríguez-Arias, Marta

    2014-01-01

    The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype. PMID:24658541

  5. Long-lasting hypoglycemic effect of modified FGF-21 analog with polyethylene glycol in type 1 diabetic mice and its systematic toxicity.

    PubMed

    Ye, Xianlong; Qi, Jianying; Wu, Qiang; Yu, Dan; Li, Shujie; Wu, Yunzhou; Li, Deshan

    2016-06-15

    Fibroblast growth factor-21 (FGF-21) is a novel metabolic regulator and has the potential to become a powerful therapy to treat diabetes mellitus. However, we found that the clinical application of wild type FGF-21 was influenced by its low intrinsic bio-stability and poor hypoglycemic potency. In this study, The N-terminus of FGF-21 analog (mFGF-21) was PEGylated in a site-specific manner by 20kD methoxy poly-ethylene glycol-propionaldehyde (mPEG-ALD). PEGylated mFGF-21 was isolated by Capto Q anion exchange chromatography. The properties of PEGylated mFGF-21 including the in vitro bio-stability and biological activity were evaluated. As well as the anti-diabetic effect of PEGylated mFGF-21 were studied in streptozotocin (STZ)-induced type 1 diabetic mice. Results demonstrated that PEGylated mFGF-21 had a similar capacity of stimulating glucose uptake in HepG2 cells with mFGF-21 and PEGylation of mFGF-21 significantly enhanced the anti-protease ability and the long acting anti-diabetic effect in type 1 diabetic mice. Furthermore, the preliminary safety of PEGylated mFGF-21 following subcutaneously injection was assessed using healthy mice by measuring the body weight, histopathology and clinical biochemical parameters, and the results showed no subacute toxicity to major organs or tissues and no significant changes in physiological and biochemical parameters in healthy mice. Taken together, under the premise of remaining the in vitro biological activity of mFGF-21, PEGylation significantly improves the long lasting hypoglycemic effect of mFGF-21 in type 1 diabetic mice. Our valuation shows that PEGylated mFGF-21 is a potential drug for the effective treatment of type 1 diabetes. PMID:27089817

  6. Pattern of nonadrenergic, noncholinergic responses during short- or long-lasting electrical stimulation in guinea-pig ileum.

    PubMed

    Ivancheva, C; Pencheva, N; Radomirov, R

    1997-08-01

    1. The pattern of responses of longitudinally oriented guinea pig ileum organ bath preparations was studied during short- (1-5 sec) or long-lasting (20 sec) electrical field stimulation (EFS, 0.8 msec, 40 V, 1-20 Hz). 2. In the presence of phentolamine (5 microM), propranolol (5 microM), and atropine (3 microM), the EFS elicited nonadrenergic, noncholinergic (NANC), tetrodotoxin (0.3 microM)-sensitive responses. 3. The 1-sec EFS evoked relaxation. The response to 5-sec EFS consisted of relaxation followed by twitch, whereas relaxation, twitch and tonic contraction characterized the NANC response to 20-sec EFS. The maximum relaxation was observed at 10-Hz short- or long-lasting EFS. 4. Both N-G-nitro-L-arginine (L-NNA, 0.1-0.5 mM) and apamin (1-5 microM) concentration dependently inhibited the relaxation of the NANC response to 10-Hz 20-sec EFS. During L-NNA treatment, the twitch and the tonic contractions were increased. The inhibitory effect of L-NNA was reversed by L-arginine (0.1-0.5 mM) but not by D-arginine. Sodium nitroprusside (1-10 microM) was without effect. 5. AP 13.2 ACOH (0.1 microM), a blocker of Substance P receptors, inhibited the twitch and the tonic contractions. The contractions were decreased after desensitization of purinoceptors by ATP and in the presence of the GABA(A) receptor antagonist bicuculline (30 microM). 6. Depending on the EFS duration, a subsequent occurrence of relaxation and contractions characterized the NANC responses. It seems that relaxation is mediated by nitric oxide whereas Substance P and ATP are involved in the maintenance of the twitch and the tonic contractions. Nitric oxide appears to exert an inhibitory effect on the excitatory transmitters, whereas purinergic mechanism(s) could modulate the nitric oxide-dependent relaxation. PMID:9251905

  7. 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

  8. 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

  9. Cost and cost effectiveness of long-lasting insecticide-treated bed nets - a model-based analysis

    PubMed Central

    2012-01-01

    Background The World Health Organization recommends that national malaria programmes universally distribute long-lasting insecticide-treated bed nets (LLINs). LLINs provide effective insecticide protection for at least three years while conventional nets must be retreated every 6-12 months. LLINs may also promise longer physical durability (lifespan), but at a higher unit price. No prospective data currently available is sufficient to calculate the comparative cost effectiveness of different net types. We thus constructed a model to explore the cost effectiveness of LLINs, asking how a longer lifespan affects the relative cost effectiveness of nets, and if, when and why LLINs might be preferred to conventional insecticide-treated nets. An innovation of our model is that we also considered the replenishment need i.e. loss of nets over time. Methods We modelled the choice of net over a 10-year period to facilitate the comparison of nets with different lifespan (and/or price) and replenishment need over time. Our base case represents a large-scale programme which achieves high coverage and usage throughout the population by distributing either LLINs or conventional nets through existing health services, and retreats a large proportion of conventional nets regularly at low cost. We identified the determinants of bed net programme cost effectiveness and parameter values for usage rate, delivery and retreatment cost from the literature. One-way sensitivity analysis was conducted to explicitly compare the differential effect of changing parameters such as price, lifespan, usage and replenishment need. Results If conventional and long-lasting bed nets have the same physical lifespan (3 years), LLINs are more cost effective unless they are priced at more than USD 1.5 above the price of conventional nets. Because a longer lifespan brings delivery cost savings, each one year increase in lifespan can be accompanied by a USD 1 or more increase in price without the cheaper net

  10. Clinical factors increasing radiation doses to patients undergoing long-lasting procedures: Abdominal stent-graft implantation

    PubMed Central

    Majewska, Natalia; Stanisic, Michal G.; Blaszak, Magdalena Aleksandra; Juszkat, Robert; Frankiewicz, Maciej; Krasinski, Zbigniew; Makalowski, Marcin; Majewski, Waclaw

    2011-01-01

    Summary Background An important negative factor of EVAR is the radiation acquired during long-lasting procedures. The aim of the study was to document the radiation doses of EVAR and to discuss potential reasons for prolongation of radiological procedures. Material/Methods Dose-area product (DAP) (Gy cm2) and air kerma (AK) (Gy) obtained during EVAR from 92 patients were analyzed retrospectively in regards to body mass index (BMI), angulations of aneurysm neck, length of aneurysm neck and occurrence of tortuosity of iliac arteries. Results Total AK for fluoroscopy differed significantly between normal BMI (373 mGy) and BMI 25–29.9 (1125 mGy) or BMI >30 (1085 mGy). Iliac artery tortuosities >45° and short aneurysm necks caused higher doses of total AK (1097 mGy and 1228 mGy, respectively) than iliac artery tortuosities <45° and long aneurysm necks (605 mGy and 720 mGy, respectively). Conclusions The main factors contributing to a high radiation dose being acquired by patients during EVAR are: BMI >25, tortuosity of iliac arteries >45° and short aneurysm necks. PMID:22037751

  11. TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria.

    PubMed

    Alba, Martha P; Suarez, Carlos F; Varela, Yahson; Patarroyo, Manuel A; Bermudez, Adriana; Patarroyo, Manuel E

    2016-09-01

    Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche(-) rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche(+) orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory. PMID:27363338

  12. Discontinuation of alpha-interferon treatment in patients with chronic myeloid leukemia in long-lasting complete molecular response.

    PubMed

    Latagliata, Roberto; Romano, Angela; Mancini, Marco; Breccia, Massimo; Carmosino, Ida; Vozella, Federico; Montagna, Chiara; Volpicelli, Paola; De Angelis, Federico; Petrucci, Luigi; Serrao, Alessandra; Molica, Matteo; Salaroli, Adriano; Diverio, Daniela; Alimena, Giuliana

    2016-01-01

    To evaluate follow-up after α-interferon (IFN) discontinuation, 23 patients with chronic myeloid leukemia (CML) in stable complete molecular response (CMolR) with IFN were revisited. After a median IFN treatment of 105.8 months (IR 56.1 - 127.3), all patients discontinued IFN for prolonged CMolR (12), intolerance (8) or planned ABMT (3). After 12.5 months, one patient developed an extramedullar blast crisis. Four patients needed to start imatinib, all achieving again molecular response. Eighteen patients are still off-therapy (median time from IFN discontinuation 125.5 months, IR 86.9-205.3); among these, five are BCR-ABL negative, six present with a sporadic positivity (BCR-ABL ratio < 0.1) and seven show a stable and long-lasting mild positivity (BCR-ABL ratio < 0.5). Patients in prolonged CMolR with IFN have low risk of recurrence after discontinuation; the reappearance of a BCR-ABL positivity < 0.5 did not always precede a relapse, suggesting mechanisms of immunological control induced by IFN. PMID:25997497

  13. DNA Superresolution Structure of Reed-Sternberg Cells Differs Between Long-Lasting Remission Versus Relapsing Hodgkin's Lymphoma Patients.

    PubMed

    Righolt, Christiaan H; Knecht, Hans; Mai, Sabine

    2016-07-01

    Recent developments in microscopy have led to superresolution microscopy images of cells. Structured illumination microscopy was used before to reveal new details in the DNA structure and the structure of the DNA-free space in the DAPI-stained cell nuclei of the Hodgkin's lymphoma HDLM-2 cell line. This study extends this technology to primary pre-treatment classical Hodgkin's lymphoma samples of ten patients. Significant differences in both the DNA structure and the structure of the DNA-free space were detected between lymphocytes and malignant cells. Both types of structures were similar for lymphocytes of different patients. When the patients were un-blinded and grouped based on their clinical outcome, either non-relapsed or relapsed, a significant difference in the DNA structure of their Reed-Sternberg (RS) cells was found. Since, RS cells develop from mono-nucleated Hodgkin (H) cells, these data suggest distinct architectural restructuring of nuclei during RS cell formation in patients going to long-lasting remission versus relapse. J. Cell. Biochem. 117: 1633-1637, 2016. © 2015 Wiley Periodicals, Inc. PMID:26639515

  14. Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line.

    PubMed

    Zanette, Caterina; Pelin, Marco; Crosera, Matteo; Adami, Gianpiero; Bovenzi, Massimo; Larese, Francesca Filon; Florio, Chiara

    2011-08-01

    For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products designed to come in direct contact with the skin. In this study we investigated the effects of Ag NPs on skin using the human-derived keratinocyte HaCaT cell line model. Ag NPs caused a concentration- and time-dependent decrease of cell viability, with IC(50) values of 6.8 ± 1.3 μM (MTT assay) and 12 ± 1.2 μM (SRB assay) after 7 days of contact. A 24h treatment, followed by a 6 day recovery period in Ag NPs-free medium, reduced cell viability with almost the same potency (IC(50)s of 15.3 ± 4.6 and 35 ± 20 μM, MTT and SRB assays, respectively). Under these conditions, no evidence of induction of necrotic events (propidium iodide assay) was found. Apocynin, NADPH-oxidase inhibitor, or N(G)-monomethyl-L-argynine, nitric oxide synthase inhibitor, did not prevent NPs-induced reduction of cell viability. TEM analysis of cells exposed to NPs for 24h revealed alteration of nuclear morphology but only a marginal presence of individual NPs inside the cells. These results demonstrate that on HaCaT keratinocytes a relatively short time of contact with Ag NPs causes a long-lasting inhibition of cell growth, not associated with consistent Ag NPs internalization. PMID:21501681

  15. Initial breakdown and fast leaders in lightning discharges producing long-lasting disturbances of the lower ionosphere

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.; Zhu, Y.; Tran, M. D.; Rakov, V. A.; Pilkey, J. T.; Caicedo, J. A.; Hare, B.; Jordan, D. M.; Uman, M. A.

    2016-06-01

    The recent discovery of long recovery, early VLF scattering events (LOREs) indicates that the electric field changes from lightning discharges are capable of producing long-lasting disturbances (up to tens of minutes) in the upper mesosphere and lower ionosphere. Comparison of lightning mapping array, broadband (up to 10 MHz) electric field, and VLF (˜300 Hz to 42 kHz) magnetic field measurements shows that the field changes produced by initial breakdown (IB) processes and the following leaders in natural, cloud-to-ground lightning discharges are detectable in VLF magnetic field measurements at long distances. IB radiation has been detected in VLF for lightning discharges occurring up to 2630 km away from the VLF observing station. Radio atmospherics associated with 52 LOREs, 51 regular recovery events, and 3098 flashes detected by National Lightning Detection Network and/or GLD360 were examined for IB radiation occurring up to 15 ms before the return stroke. Our analysis reveals that in contrast to regular recovery early VLF events, LOREs are strongly associated with lightning discharges which exhibit an intense IB process and a fast first leader (typical duration <4 ms). These experimental results demonstrate that initial breakdown and leader processes are indicators of discharge properties highly relevant to the total energy transfer between lightning discharges and the middle/upper atmosphere.

  16. Longitudinal frequency variation of long-lasting EMIC Pc1-Pc2 waves localized in the inner magnetosphere

    NASA Astrophysics Data System (ADS)

    Kim, K.-H.; Shiokawa, K.; Mann, I. R.; Park, J.-S.; Kwon, H.-J.; Hyun, K.; Jin, H.; Connors, M.

    2016-02-01

    Long-lasting (> 20 h) electromagnetic ion cyclotron (EMIC) Pc1-Pc2 waves were observed by the Athabasca (L =˜ 4.6) induction magnetometer and Canadian Array for Realtime Investigations of Magnetic Activity (L =˜ 4-6) fluxgate magnetometers on 5 April 2007. These waves showed a systematic frequency change with local time, the minimum frequency near dusk, and the maximum frequency near dawn. Assuming the plasmapause as a potential source region of the waves, we estimated the plasmapause location from localized proton enhancement (LPE) events observed at NOAA-Polar Orbiting Environmental Satellites and METOP-2 satellites. We found that the longitudinal frequency variation of EMIC waves has a clear correlation with the estimated plasmapause location and that the waves are in the frequency band between the equatorial helium and oxygen gyrofrequencies at the estimated plasmapause. With our analysis results we suggest that the LPE events are caused by wave-particle interaction with the helium band EMIC waves generated near the plasmapause.

  17. Postnatal Exposure to Sodium Arsenite (NaAsO2) Induces Long Lasting Effects in Rat Testes

    PubMed Central

    Kaushal, Parul; Dhar, Pushpa; Shivaprasad, Somesh Meludurga; Mehra, Raj D.

    2012-01-01

    Objective: The present study was undertaken to investigate the effects of early postnatal exposure to sodium arsenite (NaAsO2) on rat testis. Materials and Methods: Wistar rat pups were administered aqueous solution of NaAsO2, 1.5 mg/kg body weight (bw) (experimental) and distilled water (control), respectively, by intraperitoneal route (i.p.) from postnatal day (PND) 1 to 14. Testes were collected after 1, 7 and 36 days (at PND 15, 21 and 50) after the treatment period (PND1-14) from the animals and immersion fixed in Bouin's fluid followed by paraffin embedding. Seven micrometer thick serial sections were cut and stained with hematoxylin and eosin for light microscopic observations. At PND 50, morphological features of sperms and their counting was carried out besides processing the perfusion-fixed testes for electron microscopy (EM). Results and Conclusions: The observations revealed an altered morphology of the seminiferous tubules (ST) along with degeneration and dissociation of spermatogenic cells in the experimental animals at PND 15, 21 and 50. Also, increased number of sperms with abnormal morphology and decreased sperm count was noted in the experimental animals. These features together with electron microscopic observations of abnormal mitochondria and apoptotic nuclei of spermatogonia and spermatocytes could be indicative of long-lasting adverse effects on the rat testis induced by exposure to As during early postnatal period. PMID:22778523

  18. Areas of long-lasting anthropopression: Assessment and monitoring of pollution potential to soil and ground water

    SciTech Connect

    Twardowska, I.

    1995-12-31

    Correct identification and assessment of the prevailing source, scope and extent of pollution potential is essential for providing efficient preventive remedial actions and management of already occurring contamination on the least-cost basis. In this paper, the identification/assessment procedure for the areas with several sources of long-lasting nonpoint contamination is illustrated by example of the Wroclaw waterworks area in Poland impacted by emission from ferro-chrome smelter and power plant, as well as by various sources of polycyclic aromatic hydrocarbons. Investigations and studies comprised (1) analysis of physicochemical composition of emitted particulates and deposited wastes their time-dependant transformations and leachability of contaminants as a function of time (2) direct multilevel sampling of dump and vadose zone profiles and examination of pore solutions and matrices; (3) ground-water survey in saturation zone; (4) investigation on infiltration and contaminant migration for radioisotope data; (5) survey of surface water quality; (6) numerical simulation and direct measurements of particulate emission from various sources; (7) analysis and comparison of data on point and nonpoint emission/imission of contaminants with the extent and scope of contamination. In another example, current investigations on the vadose zone screening and monitoring in the area of a high environmental risk in the vicinity of Sendzimir Steelworks near Cracow, Poland, are presented.

  19. 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

  20. Shift in species composition in the Anopheles gambiae complex after implementation of long-lasting insecticidal nets in Dielmo, Senegal.

    PubMed

    Sougoufara, S; Harry, M; Doucouré, S; Sembène, P M; Sokhna, C

    2016-09-01

    Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the cornerstones of malaria vector control. However, the effectiveness of these control tools depends on vector ecology and behaviour, which also largely determine the efficacy of certain Anopheles mosquitoes (Diptera: Culicidae) as vectors. Malaria vectors in sub-Saharan Africa are primarily species of the Anopheles gambiae complex, which present intraspecific differences in behaviour that affect how they respond to vector control tools. The focus of this study is the change in species composition in the An. gambiae complex after the implementation of LLINs in Dielmo, Senegal. The main findings referred to dramatic decreases in the proportions of Anopheles coluzzii and An. gambiae after the introduction of LLINs, and an increase in the proportion of Anopheles arabiensis. Two years after LLINs were first introduced, An. arabiensis remained the most prevalent species and An. gambiae had begun to rebound. This indicated a need to develop additional vector control tools that can target the full range of malaria vectors. PMID:27058993

  1. β3 Integrin Promotes Long-Lasting Activation and Polarization of Vascular Endothelial Growth Factor Receptor 2 by Immobilized Ligand

    PubMed Central

    Ravelli, Cosetta; Grillo, Elisabetta; Corsini, Michela; Coltrini, Daniela

    2015-01-01

    Objective— During neovessel formation, angiogenic growth factors associate with the extracellular matrix. These immobilized factors represent a persistent stimulus for the otherwise quiescent endothelial cells (ECs), driving directional EC migration and proliferation and leading to new blood vessel growth. Vascular endothelial growth factor receptor 2 (VEGFR2) is the main mediator of angiogenesis. Although VEGFR2 signaling has been deeply characterized, little is known about its subcellular localization during neovessel formation. Aim of this study was the characterization and molecular determinants of activated VEGFR2 localization in ECs during neovessel formation in response to matrix-immobilized ligand. Approach and Results— Here we demonstrate that ECs stimulated by extracellular matrix–associated gremlin, a noncanonical VEGFR2 ligand, are polarized and relocate the receptor in close contact with the angiogenic factor–enriched matrix both in vitro and in vivo. GM1 (monosialotetrahexosylganglioside)-positive planar lipid rafts, β3 integrin receptors, and the intracellular signaling transducers focal adhesion kinase and RhoA (Ras homolog gene family, member A) cooperate to promote VEGFR2 long-term polarization and activation. Conclusions— A ligand anchored to the extracellular matrix induces VEGFR2 polarization in ECs. Long-lasting VEGFR2 relocation is closely dependent on lipid raft integrity and activation of β3 integrin pathway. The study of the endothelial responses to immobilized growth factors may offer insights into the angiogenic process in physiological and pathological conditions, including cancer, and for a better engineering of synthetic tissue scaffolds to blend with the host vasculature. PMID:26293466

  2. Long-lasting chemiluminescence of luminol on electrochemically pre-oxidized platinum electrodes in NaOH solution.

    PubMed

    Lin, X Q; Sun, Y G; Cui, H

    2000-01-01

    A long-lasting bright chemiluminescence (CL) of luminol was generated at polycrystalline platinum electrodes with open circuit. The CL can last for several hours with the presence of O(2) in the solution when the electrode was preoxidized at potentials more positive than 1.10 V vs. SCE. The effects of the varieties of solution conditions and surface states of the electrode on the CL intensity and the interfacial potential of the electrode were investigated. It was proposed that PtO was generated at the pre-oxidized potentials and played a role of catalyst of luminol oxidation for generating the CL. The redox couple of PtO/Pt(active) at the electrode surface was maintained in the presence of O(2) and luminol, and generated the interfacial potential more positive than 140 mV. Mathematical treatment of the reaction mechanism was conducted, which led to an approximated expression of a steady CL intensity (I(CL)) as a function of the pre-polarization potential (E( h)) and time (tau( h)) of the electrode. An empirical equation, (I(CL))(4/3) = 3480(-1 + 0.82E( h) + 0.037 ln tau( h)), was estimated from the experimental data. PMID:11038487

  3. Effective insect repellent formulation in both surfactantless and classical microemulsions with a long-lasting protection for human beings.

    PubMed

    Drapeau, Jeremy; Verdier, Marie; Touraud, Didier; Kröckel, Ulla; Geier, Martin; Rose, Andreas; Kunz, Werner

    2009-06-01

    The aim of this work is to develop a new generation of repellent products with a long-lasting protection based on a natural component, para-menthane-3,8-diol (PMD). The active is first rendered soluble in a surfactantless microemulsion (H(2)O/(i)PrOH/PMD) and then in classical microemulsions. The presence of self-associated nanostructures is detected by dynamic light scattering (DLS). A synergetic system of surfactants (Cremophor) RH40 and Texapon N70) is used. Additionally, 2-ethylhexane-1,3-diol and ethyl (-)-(S)-lactate are incorporated. The final product contains, as main components, 46% of H(2)O, 25% of (i)PrOH, 20% of non-H(2)O-soluble PMD, and only 4% of surfactants. Investigations of lasting protection on human volunteers are carried out using a cage test bioassay protocol and Aedes aegypti mosquitoes. A complete protection of 315 min is found on the test persons using the surfactantless microemulsion. An extension is observed with the final formulation to reach a mean of complete protection of 385 min. This study demonstrates that alternative formulations using a natural active instead of synthetic chemicals like N,N-diethyl-m-methylbenzamide (DEET) can be efficient for human protection against mosquitoes. PMID:19551736

  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. TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects.

    PubMed

    Gatto, Gregory J; Bohme, G Andrees; Caldwell, William S; Letchworth, Sharon R; Traina, Vincent M; Obinu, M Carmen; Laville, Michel; Reibaud, Michel; Pradier, Laurent; Dunbar, Geoffrey; Bencherif, Merouane

    2004-01-01

    The development of selective ligands targeting neuronal nicotinic acetylcholine receptors to alleviate symptoms associated with neurodegenerative diseases presents the advantage of affecting multiple deficits that are the hallmarks of these pathologies. TC-1734 is an orally active novel neuronal nicotinic agonist with high selectivity for neuronal nicotinic receptors. Microdialysis studies indicate that TC-1734 enhances the release of acetylcholine from the cortex. TC-1734, by either acute or repeated administration, exhibits memory enhancing properties in rats and mice and is neuroprotective following excitotoxic insult in fetal rat brain in cultures and against alterations of synaptic transmission induced by deprivation of glucose and oxygen in hippocampal slices. At submaximal doses, TC-1734 produced additive cognitive effects when used in combination with tacrine or donepezil. Unlike (-)-nicotine, behavioral sensitization does not develop following repeated administration of TC-1734. Its pharmacokinetic (PK) profile (half-life of 2 h) contrasts with the long lasting improvement in working memory (18 h) demonstrating that cognitive improvement extends beyond the lifetime of the compound. The very low acute toxicity of TC-1734 and its receptor activity profile provides additional mechanistic basis for its suggested potential as a clinical candidate. TC-1734 was very well tolerated in acute and chronic oral toxicity studies in mice, rats and dogs. Phase I clinical trials demonstrated TC-1734's favorable pharmacokinetic and safety profile by acute oral administration at doses ranging from 2 to 320 mg. The bioavailability, pharmacological, pharmacokinetic, and safety profile of TC-1734 provides an example of a safe, potent and efficacious neuronal nicotinic modulator that holds promise for the management of the hallmark symptomatologies observed in dementia. PMID:15179444

  6. Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain

    PubMed Central

    Bonnard, Elisabeth; Poras, Hervé; Nadal, Xavier; Maldonado, Rafael; Fournié-Zaluski, Marie-Claude; Roques, Bernard P

    2015-01-01

    The peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain generation as suggested by the modulation of opioid receptors expression and enkephalins (ENKs) release observed in these painful conditions. Accordingly, an innovative approach in the treatment of these nocifensive events is to increase and maintain high local concentrations of extracellular pain-evoked ENKs, by preventing their physiological enzymatic inactivation by two Zn metallopeptidases, the neutral endopeptidase (NEP, neprilysin, EC 3.4.24.11) and the neutral aminopeptidase (APN, EC 3.4.11.2). With this aim, new orally active dual ENKephalinase inhibitors (DENKIs) were designed as soluble prodrugs by introducing a N-terminal cleavable carbamate in the previously described aminophosphinic inhibitors. This induces long-lasting antinociceptive responses after oral administration, in various rodent models of inflammatory and neuropathic pain. These responses are mediated through stimulation of peripheral opioid receptors by DENKIs-protected ENKs as demonstrated by naloxone methiodide reversion. In all tested models, the most efficient prodrug 2a (PL265) was active, at least during 150–180 min, after single oral administration of 25–50 mg/kg in mice and of 100–200 mg/kg in rats. In models of neuropathic pain, both hyperalgesia and allodynia were markedly reduced. Interestingly, combination of inactive doses of 2a (PL265) and of the anti-epileptic drug gabapentin had synergistic effect on neuropathic pain. Pharmacokinetic studies of 2a (PL265) in rats show that the active drug is the only generated metabolite produced. These encouraging results have made 2a (PL265) a suitable candidate for clinical development. PMID:25692029

  7. Lesions of the basolateral amygdala reverse the long-lasting interference with shuttle box escape produced by uncontrollable stress

    PubMed Central

    Greenwood, Benjamin N.; Strong, Paul V.; Fleshner, Monika

    2010-01-01

    Exposure to an uncontrollable, but not a controllable, stressor produces a constellation of behaviors called learned helplessness. In rodents, uncontrollable stress interferes with the ability to learn to escape from escapable shocks delivered in a shuttle box. The stress-induced shuttle box escape deficit is a common screening tool for potential antidepressant strategies. Inconsistencies in the literature exist regarding the time-course of, and mechanisms underlying, stress-induced escape deficits. When no common cues are shared between the stressor and testing environment, the escape deficit is short lived and independent of conditioned freezing. In contrast, when stress and testing occur in the same or similar environments, the escape deficit is very long-lasting. The current studies address the hypothesis that the long-lived escape deficit produced by uncontrollable stress is dependent upon conditioned fear and the basolateral amygdala (BLA). Rats received bilateral excitotoxic lesions of the BLA 2 wk following uncontrollable foot shocks. One wk after surgery, rats were tested for conditioned freezing and escape behavior in the same shuttle boxes in which prior foot shocks were delivered. Stressed rats with sham lesions displayed robust conditioned freezing and failed to escape during shuttle box testing. Lesions of the BLA eliminated conditioned freezing and completely restored stressed rats' ability to perform the escape contingency. These data indicate that the long-lived stress-induced escape deficit produced under conditions in which the stressor and testing environments share common cues is dependent upon conditioned freezing elicited by the BLA. Results have important implications for the mechanisms underlying learned helplessness phenomena. PMID:20226213

  8. Excitotoxic Insult Results in a Long-Lasting Activation of CaMKIIα and Mitochondrial Damage in Living Hippocampal Neurons

    PubMed Central

    Otmakhov, Nikolai; Gorbacheva, Elena V.; Regmi, Shaurav; Yasuda, Ryohei; Hudmon, Andy; Lisman, John

    2015-01-01

    Over-activation of excitatory NMDA receptors and the resulting Ca2+ overload is the main cause of neuronal toxicity during stroke. CaMKII becomes misregulated during such events. Biochemical studies show either a dramatic loss of CaMKII activity or its persistent autonomous activation after stroke, with both of these processes being implicated in cell toxicity. To complement the biochemical data, we monitored CaMKII activation in living hippocampal neurons in slice cultures using high spatial/temporal resolution two-photon imaging of the CaMKIIα FRET sensor, Camui. CaMKII activation state was estimated by measuring Camui fluorescence lifetime. Short NMDA insult resulted in Camui activation followed by a redistribution of its protein localization: an increase in spines, a decrease in dendritic shafts, and concentration into numerous clusters in the cell soma. Camui activation was either persistent (> 1–3 hours) or transient (~20 min) and, in general, correlated with its protein redistribution. After longer NMDA insult, however, Camui redistribution persisted longer than its activation, suggesting distinct regulation/phases of these processes. Mutational and pharmacological analysis suggested that persistent Camui activation was due to prolonged Ca2+ elevation, with little impact of autonomous states produced by T286 autophosphorylation and/or by C280/M281 oxidation. Cell injury was monitored using expressible mitochondrial marker mito-dsRed. Shortly after Camui activation and clustering, NMDA treatment resulted in mitochondrial swelling, with persistence of the swelling temporarily linked to the persistence of Camui activation. The results suggest that in living neurons excitotoxic insult produces long-lasting Ca2+-dependent active state of CaMKII temporarily linked to cell injury. CaMKII function, however, is to be restricted due to strong clustering. The study provides the first characterization of CaMKII activation dynamics in living neurons during excitotoxic

  9. Long lasting increase in nociceptive threshold induced in mice by forced swimming: involvement of an endorphinergic mechanism.

    PubMed

    Suaudeau, C; Costentin, J

    2000-05-01

    Mice submitted to forced swimming session(s) displayed a long lasting modification in their nociceptive threshold, assessed through their jump latency from a hot plate (55 degrees C). Thus two forced swimming sessions (6 min each, 8h apart), in water at 33 degrees C, increased by about 50% the jump latency when the hot plate test was performed 14 hours, 3 days or 6 days thereafter. The water temperature (16 degrees C vs 33 degrees C) had no critical influence in this respect. To be clearly effective (at 33 degrees C) the swimming session had to be performed twice (when performed only once it was irregularly effective); it apparently culminated for a 6 min duration, since its effectiveness was not significantly increased by extending the swimming time to 12 min or 18 min. Performing 2 forced swimming sessions (6 min each, 8h apart), 5 consecutive days, resulted in a suppression of the increase in jump latency in the hot plate test. The two forced swimming episodes-induced analgesia was prevented by the s.c. administration of diazepam (from 0.125 mg/kg) or morphine (from 5 mg/kg) or scopolamine (1 mg/kg) before each forced swimming episode. Morphine (7.5 mg/kg) was uneffective to prevent the induction of two forced swimming episodes-induced analgesia when it was administered immediately after each forced swimming session. Finally this analgesia was dose dependently reversed by naloxone (ID(50) = 0.14 mg/kg, s.c., 30 min before the hot plate test). It is hypothesized that the handling of mice immediately before the hot plate test induces the remembrance of the stress induced by previous forced swimming episodes, triggering a fear reaction which increases the nociceptive threshold. PMID:10938583

  10. Prostacyclin induces a surprising long-lasting motility in quiescent uterine strips (indomethacin-treated) isolated from ovariectomized rats.

    PubMed

    Gimeno, A L; Chaud, M; Bonacossa, A; Franchi, A M; Gimeno, M F

    1983-10-01

    Dose-response curves for several prostaglandins (PGI2; PGD2; PGF2 and PGE2); BaCl2 or prostaglandin metabolites (15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha; 6-keto-PGF1 alpha and 6-keto PGE1 in quiescent (indomethacin-treated) uterine strips from ovariectomized rats, were constructed. All PGs tested as well as BaCl2, triggered at different concentrations, evident phasic contractions. Within the range of concentrations tested the portion of the curves for the metabolites of PGF2 alpha was shifted to the right of that for PGF2 alpha itself; the curve for 6-keto-PGF1 alpha was displaced to the right of the curve for PGI2 and that for 6-keto-PGE1 to the left. It was also demonstrated that the uterine motility elicited by 10(-5) M PGF2 alpha and its metabolites was long lasting (more than 3 hours) and so it was the activity evoked by PGI2;6-keto-PGF1 alpha and BaCl2, but not the contractions following 6-keto-PGE1, which disappeared much earlier. The contractile tension after PGF2 alpha; 15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha and PGI2, increased as time progressed whilst that evoked by 6-keto-PGF1 alpha or BaCl2 fluctuated during the same period around more constant levels. The surprising sustained and gradually increasing contractile activity after a single dose of an unstable prostaglandin such as PGI2, on the isolated rat uterus rendered quiescent by indomethacin, is discussed in terms of an effect associated to its transformation into more stable metabolites (6-keto-PGF1 alpha, or another not tested) or as a consequence of a factor which might protects prostacyclin from inactivation. PMID:6361911

  11. DISPARATE EVOLUTION OF RIGHT AND LEFT ATRIAL RATE DURING ABLATION OF LONG-LASTING PERSISTENT ATRIAL FIBRILLATION

    PubMed Central

    Hocini, Mélèze; Nault, Isabelle; Wright, Matthew; Veenhuyzen, George; Narayan, Sanjiv M.; Jaïs, Pierre; Lim, Kang-Teng; Knecht, Sébastien; Matsuo, Seiichiro; Forclaz, Andrei; Miyazaki, Shinsuke; Jadidi, Amir; O’Neill, Mark D.; Sacher, Frédéric; Clémenty, Jacques; Haïssaguerre, Michel

    2010-01-01

    Objectives To assess whether additional ablation in the right atrium(RA) improves termination rate in long-lasting persistent atrial fibrillation(PsAF). Background Prolongation of atrial fibrillation(AF) cycle length(CL) measured from the left atrial appendage predicts favorable outcome during catheter ablation of PsAF. However, in some patients despite prolongation of AFCL in the left atrium(LA) with ablation, AF persists. We hypothesized that this is due to RA drivers and these patients may benefit from RA ablation. Methods 148 consecutive patients undergoing catheter ablation of PsAF(duration 25±32 months) were studied. AFCL was monitored in both atria during stepwise ablation commencing in the LA. Ablation was performed in the RA when all LA sources in AF had been ablated and a RA-LA gradient existed. The procedural endpoint was AF termination. Results Two distinct patterns of AFCL change emerged during LA ablation. In 104patients(70%), there was parallel increase of AFCL in LA and RA culminating in AF termination (baseline: LA 153ms[140,170], RA 155ms[143,171]; after ablation: LA 181ms[170,200], RA 186ms[175,202]). In 24 patients(19%), RA AFCL did not prolong, creating a right-to-left frequency gradient, (baseline: LA 142ms[143,153], RA 145 ms[139,162]; after ablation: LA 177 ms[165–185], RA 152ms[147,175]). These patients had a longer AF history (23versus12 months, p=0.001), and larger RA diameter (42versus39mm, p=0.005) and RA ablation terminated AF in 55%. In the remaining 20 patients, biatrial ablation failed to terminate AF. Conclusions A divergent pattern of AFCL prolongation after LA ablation resulting in a right-to-left gradient demonstrating that the right atrium is driving AF in about 20 % of PsAF. PMID:20202517

  12. [Operation to promote use of long-lasting insecticidal nets (LLIN) in French Guiana in 2006: design, implementation and results].

    PubMed

    Mansotte, F; Ravachol, F; Carlisi, R; Caudal, J; Pinchon, S; Maison, D

    2010-06-01

    In 2006, the Regional Health Office (DSDS) in French Guiana undertook a major operation involving importation and distribution of long-lasting insecticide treated nets (LLIN/ITN). In collaboration with the WHO, a Vietnamese manufacturer of LLINs suited to the requirements of French Guiana was sourced. With the help of a dynamic local importer and dealer, a sales network was developed through chemist shops located all over French Guiana. This network provided wide coverage since these outlets can be found in all large communities. The selling price ranged from 15 to 23 euros depending on the model, i.e., hammock or bed size. In addition, LLINs were distributed within the framework of two special programs. First they are given to women giving birth in French Guiana and undergoing medical surveillance as part of the Mother and Child Protection program by public healthcare system. Second they are distributed in case of natural disaster or other events that could lead to an increased risk of vector-borne outbreaks. Thanks to this operation, a total of 13,882 LLINs were delivered in French Guiana from July 2006 to December 2008. This milestone operation in the fight against malaria was made possible thanks to funding granted on a one-time basis after the outbreak of dengue in 2005-2006. The structure of this operation and its survival will depend on the continued goodwill and determination of a small group of local partners who created this successful distribution campaign with no specific guidance or program from the national authorities. PMID:20734592

  13. The effect of long-lasting insecticidal water container covers on field populations of Aedes aegypti (L.) mosquitoes in Cambodia.

    PubMed

    Seng, Chang Moh; Setha, To; Nealon, Joshua; Chantha, Ngan; Socheat, Doung; Nathan, Michael B

    2008-12-01

    Dengue in Cambodia is mainly transmitted by Aedes aegypti (L.) mosquitoes that primarily breed in large, concrete jars (> or =200 liters) used for the storage of water for domestic use. Following a preliminary risk assessment, long-lasting insecticidal netting (LN) treated with deltamethrin was incorporated into the design of the covers for these jars. Their effect on immature and adult female populations of Ae. aegypti in six villages in a peri-urban area of Cambodia were compared with populations in six nearby control villages before and for 22 weeks after distribution of the jar covers. There were significantly fewer pupae per house in intervention villages than in control villages (6.6 and 31.9, respectively, p<0.01). Fewer pupae were recovered from intervention houses than from control houses at every post-intervention assessment. Two weeks after the intervention, the average number of indoor resting female Ae. aegypti per house in the intervention villages had declined approximately three-fold, whereas in the controls there was only a slight reduction (16%). The magnitude of the difference between the two areas diminished over time, which contact bioassays confirmed was likely due to a gradual reduction of insecticidal effect of the jar covers. In the study area, insecticide-treated covers for large concrete water storage jars were efficacious for controlling Ae. aegypti in the protected water jars and with a demonstrable effect on adult densities and survival. Further studies of this targeted container strategy in Cambodia, and elsewhere, are recommended. However, improvements in technology that would extend the duration of insecticidal effectiveness of LN materials may be needed for the development of cost-effective public health applications. PMID:19263854

  14. 7-oxo-PGI2 induced late appearing and long lasting antiischaemic and antiarrhythmic action in dogs.

    PubMed

    Végh, A; Udvary, E; Szekeres, L; Szilvássy, Z

    1988-01-01

    In our earlier experiments administration of the stable PGI2 analogue: 7-oxo-PGI2-ephedrine salt to dogs resulted in a late-appearing and long-lasting protection from coronary ligation induced ischaemia as well as from postocclusion and reperfusion arrhythmias. Objective of the present study was to evaluate the extent and duration of antiischaemic and antiarrhythmic action induced by a single dose 50 ug/kg i.m. 7-oxo-PGI2 in dogs subjected to myocardial ischaemia evoked by left anterior descending coronary artery (LAD) ligation at different intervals (2, 6, 24, 48, 72 hours and 2 weeks) after treatment. After anaesthesia and thoracotomy the electrophysiological parameters - sinus cycle length (SCL), corrected sinus node recovery time (CSNRT), atrial and ventricular functional refractory period (AFRP, VFRP), and atrio-ventricular effective refractory period (A-V ERP) - were determined by means of computer controlled programmed electrical stimulation. Then the animals were subjected to LAD occlusion for 25 minutes and subsequent reperfusion. 7-oxo-PGI2 pretreatment considerably protected against myocardial ischaemia i.e. there was significant reduction in ST-segment elevation, the number of extrasystoles (ES) and the incidence of ventricular fibrillation (VF). The antiischaemic action started 2 or 6 hours after the drug administration, however, the maximal protection - indicated by the diminution of ischaemic epicardial ST-segment elevation - as well as the most striking reduction in postocclusion and reperfusion arrhythmias could be observed 48 hours after the single dose of 7-oxo-PGI2 and in case of two weeks treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3073767

  15. A case study of ionospheric storm effects during long-lasting southward IMF Bz-driven geomagnetic storm

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Liu, Libo; Nakamura, Takuji; Zhao, Biqiang; Ning, Baiqi; Yoshikawa, A.

    2014-09-01

    Multiple instrumental observations including GPS total electron content (TEC), foF2 and hmF2 from ionosondes, vertical ion drift measurements from Communication/Navigation Outage Forecasting System, magnetometer data, and far ultraviolet airglow measured by Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics/Global Ultraviolet Imager (TIMED/GUVI) are used to investigate the profound ionospheric disturbances at midlatitude and low latitude during the 14-17 July 2012 geomagnetic storm event, which was featured by prolonged southward interplanetary geomagnetic field component for about 30 h below -10 nT. In the East Asian/Australian sector, latitudinal profile of TEC variations in the main phase were characterized by three bands of increments and separated by weak depressions in the equatorial ionospheric anomaly (EIA) crest regions, which were caused by the combined effects of disturbance dynamo electric fields (DDEF) and equatorward neutral winds. In the recovery phase, strong inhibition of EIA occurred and the summer crest of EIA disappeared on 16 July due to the combined effects of intrusion of neutral composition disturbance zone as shown by the TIMED/GUVI O/N2 measurements and long-lasting daytime westward DDEF inferred from the equatorial electrojet observations. The transit time of DDEF over the dip equator from westward to eastward is around 2200 LT. In the American longitude, the salient ionospheric disturbances in the summer hemisphere were characterized by daytime periodical intrusion of negative phase for three consecutive days in the recovery phase, preceded by storm-enhanced density plume in the initial phase. In addition, multiple short-lived prompt penetration electric fields appeared during stable southward interplanetary magnetic field (IMF) Bz in the recovery phase and were responsible for enhanced the EIA and equatorial ionospheric uplift around sunset.

  16. A case study of Ionospheric storm effects during long-lasting southward IMF Bz driven geomagnetic storm

    NASA Astrophysics Data System (ADS)

    Liu, J., Sr.

    2014-12-01

    Multiple instrumental observations including GPS TEC, foF2 and hmF2 from ionosondes, vertical ion drift measurements from C/NOFS, magnetometer data and far-ultraviolet airglow measured by TIMED/GUVI are used to investigate the profound ionospheric disturbances at mid- and low-latitudes during the 14-17 July 2012 geomagnetic storm event, which was featured by prolonged southward interplanetary geomagnetic field component for about 30 hours below -10 nT. In the East Asian/Australian sector, latitudinal profile of TEC variations in the main phase were characterized by three bands of increments and separated by weak depressions in the Equatorial Ionospheric Anomaly (EIA) crest regions, which were caused by the combined effects of disturbance dynamo electric fields (DDEF) and equatorward neutral winds. In the recovery phase, strong inhibition of EIA occurred and the summer crest of EIA disappeared on 16 July due to the combined effects of intrusion of neutral composition disturbance zone as shown by the TIME/GUVI O/N2 measurements and long-lasting daytime westward DDEF inferred from the equatorial electric electrojet (EEJ) observations. The transit time of DDEF over the dip equator from westward to eastward is around 2200 LT. In the American longitude, the salient ionospheric disturbances in the summer hemisphere were characterized by daytime periodical intrusion of negative phase for three consecutive days in the recovery phase, preceded by storm enhanced density (SED) plume in the initial phase. In addition, multiple short-lived prompt penetration electric fields (PPEF) appeared during stable southward IMF Bz in the recovery phase and were responsible for enhanced the EIA and equatorial ionospheric uplift around sunset.

  17. Malaria knowledge and long-lasting insecticidal net use in rural communities of central Côte d'Ivoire

    PubMed Central

    2011-01-01

    Background To improve effectiveness of malaria control interventions, it is essential to deepen the knowledge of contextual factors that govern people's practice for preventive and curative measures. The aim of this study was to determine factors that influence the use of long-lasting insecticidal nets (LLINs) in three rural communities of Côte d'Ivoire, two of which benefited from recent interventions. Methods The study was carried out in 957 households in three villages (Bozi, N'Dakonankro and Yoho) located in central Côte d'Ivoire. Indicators of socioeconomic position (SEP), malaria knowledge and practice, placing special emphasis on LLINs, were investigated during a cross-sectional questionnaire survey. Principal component analysis was used to calculate the SEP of households by means of a list of household assets ownership. The concentration index was used to assess the direction of the association between SEP and a given variable. To compare groups or means, Fisher's exact test, χ2 and Kruskal-Wallis test were used, as appropriate. Results Significant differences were found between SEP and reported malaria symptoms, such as fever or hot body, convulsion, anaemia and jaundice (yellow eyes). Individuals from the least poor group cited more often the use of bed nets and insecticide-treated nets (ITNs) compared to poorer groups. The mean number of individuals reporting the use of bed nets and LLINs was different between groups with different educational level. Moreover, the mean number of LLINs in a household was influenced by the presence of children below five years of age. Conclusion The study not only confirmed that education and SEP play important roles in the prevention and control of malaria and promotion of health in general, but pointed at the basic essential knowledge and the key behavioural elements that should guide education and learning processes among the poorer segments of the population. In turn, such knowledge may change behaviour and lead to

  18. The effects of washing and duration of use of long-lasting insecticidal nets (PermaNets) on insecticidal effectiveness.

    PubMed

    Msangi, S; Lyatuu, E; Masenga, C; Kihumo, E

    2008-07-01

    The use of insecticide-treated nets (ITNs) is one of the most feasible weapons available for malaria control in Africa today. One of the important requirements for ITN use is regular re-treatment at an appropriate time. As a response to the low re-treatment rate when the ITN users are expected to purchase insecticide and re-treat their nets, manufacturers have developed long-lasting insecticidal nets (LLIN) that are pre-treated in the factory, and are claimed to require no further treatment during their lifespan. A study was conducted to assess the possible effects of number of washings, frequency of washing and the duration of use on the effectiveness of PermaNets, a LLIN, against mosquitoes. The study was done for 9 months at Chekereni village, Northeastern Tanzania. The LLINs and untreated control nets were distributed to villagers in three groups. Group 1 nets were used without being washed for the whole study period. Group 2 nets received one wash per month, while group 3 received two washes per month. The effectiveness was assessed by contact bioassays using World Health Organization (WHO) bioassay cones. Mosquitoes were exposed to the netting for 3min. The knock down and mortality was scored after 3min and 24h, respectively. Results showed that the number and frequency of washes had no significant effect on the efficacy for up to 18 washes. Similarly, we could not detect a significant effect of duration of use and conditions of use on the efficacy for up to 9 months. PermaNets caused short-lived irritation and sneezing but appear to be well accepted by the community in which the study was conducted. PMID:18502395

  19. Enzymatic mono-pegylation of glucagon-like peptide 1 towards long lasting treatment of type 2 diabetes

    PubMed Central

    Selis, Fabio; Schrepfer, Rodolfo; Sanna, Riccardo; Scaramuzza, Silvia; Tonon, Giancarlo; Dedoni, Simona; Onali, Pierluigi; Orsini, Gaetano; Genovese, Stefano

    2012-01-01

    Human glucagon-like peptide-1 (GLP-1) is a physiological gastrointestinal peptide with glucose-dependent insulinotropic effects which is therefore considered an interesting antidiabetic agent. However, after in vivo administration, exogenous GLP-1 does not exert its physiological action due to the combination of rapid proteolytic degradation by ubiquitous dipeptidyldipeptidase IV (DPP IV) enzyme and renal clearance resulting in an extremely short circulating half-life. In this work we describe the conjugation of GLP-1-(7-36)-amide derivatives with polyethylene glycol (PEG) by enzymatic site-specific transglutamination reaction as an approach to reduce both the proteolysis and the renal clearance rates. The compound GLP-1-(7-36)-amide-Q23-PEG 20 kDa monopegylated on the single glutamine residue naturally present in position 23 maintained the ability to activate the GLP-1 receptor expressed in the rat β-cell line RIN-m5F with nanomolar potency along with an increased in vitro resistance to DDP IV and a circulating half-life of about 12 h after subcutaneous administration in rats. These properties enabled GLP-(7-36)-amide-Q23-PEG 20 kDa to exert a glucose-stabilizing effect for a period as long as 8 h, as demonstrated by a single subcutaneous injection to diabetic mice concomitantly challenged with an oral glucose load. The results reported in this work indicate that GLP-(7-36)-amide-Q23-PEG 20 kDa could be a lead compound for the development of long-lasting anti-diabetic agents useful in the treatment of type 2 diabetes affected patients. PMID:25755995

  20. Challenges for malaria elimination in Zanzibar: pyrethroid resistance in malaria vectors and poor performance of long-lasting insecticide nets

    PubMed Central

    2013-01-01

    Background Long-lasting insecticide treated nets (LLINs) and indoor residual house spraying (IRS) are the main interventions for the control of malaria vectors in Zanzibar. The aim of the present study was to assess the susceptibility status of malaria vectors against the insecticides used for LLINs and IRS and to determine the durability and efficacy of LLINs on the island. Methods Mosquitoes were sampled from Pemba and Unguja islands in 2010–2011 for use in WHO susceptibility tests. One hundred and fifty LLINs were collected from households on Unguja, their physical state was recorded and then tested for efficacy as well as total insecticide content. Results Species identification revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a small number of An. gambiae s.s. and An. merus being present. Susceptibility tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible to all pyrethroids tested. A physical examination of 150 LLINs showed that two thirds were damaged after only three years in use. All used nets had a significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2 compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly against both susceptible An. gambiae s.s. colony mosquitoes and wild-type mosquitoes from Pemba after just six washes (p < 0.001). Conclusion The sustainability of the gains achieved in malaria control in Zanzibar is seriously threatened by the resistance of malaria vectors to pyrethroids and the short-lived efficacy of LLINs. This study has revealed that even in relatively well-resourced and logistically manageable places like Zanzibar, malaria elimination is going to be difficult to achieve with the current control measures. PMID:23537463

  1. 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

  2. RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions.

    PubMed

    Broad, John; Takahashi, Nobuyuki; Tajimi, Masaomi; Sudo, Masaki; Góralczyk, Adam; Parampalli, Umesh; Mannur, Kesava; Yamamoto, Toshinori; Sanger, Gareth J

    2016-02-01

    The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 μM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 μM this activity was usually prolonged. At higher concentrations (3-30 μM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 μM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying. PMID:26685754

  3. Inflammation and neurological adverse drugs reactions: a case of long lasting impaired consciousness after oxatomide administration in a patient with gastroenteritis

    PubMed Central

    2012-01-01

    Oxatomide at therapeutic doses generates occasionally drowsiness in children. When administered at toxic doses, however oxatomide may induce long lasting impaired consciousness. We now report a case of severe long lasting impaired consciousness induced by therapeutic doses of oxatomide occurring in a child affected by acute gastroenteritis. The clinical symptoms, the pharmacogenetic tests of polymorphisms in cytochrome P450 metabolizing enzymes (CYPs) and the clinical and laboratory analyses indicate that the enhanced drug sedative effect is likely due to an acute, yet mild, inflammatory state of the patient. These findings highlight the importance of assessing common, not serious inflammatory states when oxatomide is prescribed in paediatric patients. PMID:22464080

  4. 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. PMID:25238621

  5. 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. PMID:10672991

  6. A tracking tool for long-lasting insecticidal (mosquito) net intervention following a 2011 national distribution in Benin

    PubMed Central

    2014-01-01

    Background Following a mass distribution of long-lasting insecticidal nets (LLINs) in Benin, we used WHO guidelines to develop an assessment tool which is described in this report. It involved assessment of the three WHO indicators: survivorship, integrity and bio-efficacy. Methods To evaluate the assessment tool, we selected four communities, two in the Southern part of the country, and two in the North. One of the two assessment communities in each geographic setting had ready access to water and a higher reported frequency of washing LLINs. It was assumed that nets in communities with greater washing frequencies would show greater loss of durability. If the tool was sensitive enough to detect such differences, the field testing would confirm its suitability for general use in different settings in Benin. While durability indicators of survival and fabric integrity were quantified using standard WHO methodology, bio-efficacy was assessed using a ‘new’ alternative (to the WHO bioassay test), involving gas chromatography. Additionally, data management used current internet technology for ‘real time’ analysis at a central monitoring location. Results While no difference in survivorship was observed between sites with ready access to water for washing, both in the North and the South, there was a significant difference in integrity. In the South and in the North, nets from sites near water (Kessounou and Malanville) showed greater damage to integrity than did the nets from Allada and Kandi (sites far from water). As expected, LLIN integrity was significantly lower when a community was near water (p < 0.01). Bio-efficacy measurements, based on GC, were found to be so variable. Conclusion A rapid decrease of the LLINs fabric integrity was observed in areas near water for washing following the first 6 months post-distribution. Due to the way that the insecticide is incorporated into the LLIN fiber and its migration to the surface, confounding results were

  7. 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

  8. Bio-efficacy of selected long-lasting insecticidal nets against pyrethroid resistant Anopheles arabiensis from South-Western Ethiopia

    PubMed Central

    2012-01-01

    Background The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae s.s. and Anopheles arabiensis may compromise control initiatives based on insecticide-treated nets (ITNs) or indoor residual spraying (IRS), and thus threaten the global malaria elimination strategy. Methods We investigated pyrethroid resistance in four populations of An. arabiensis from south-western Ethiopia and then assessed the bio-efficacy of six World Health Organization recommended long lasting insecticidal nets (LLINs) using these populations. Results For all four populations of An. arabiensis, bottle bioassays indicated low to moderate susceptibility to deltamethrin (mortality at 30 minutes ranged between 43 and 80%) and permethrin (mortality ranged between 16 and 76%). Pre-exposure to the synergist piperonylbutoxide (PBO) significantly increased the susceptibility of all four populations to both deltamethrin (mortality increased between 15.3 and 56.8%) and permethrin (mortality increased between 11.6 and 58.1%), indicating the possible involvement of metabolic resistance in addition to the previously identified kdr mutations. There was reduced susceptibility of all four An. arabiensis populations to the five standard LLINs tested (maximum mortality 81.1%; minimum mortality 13.9%). Bio-efficacy against the four populations varied by net type, with the largest margin of difference observed with the Jimma population (67.2% difference). Moreover, there were differences in the bio-efficacy of each individual standard LLIN against the four mosquito populations; for example there was a difference of 40% in mortality of Yorkool against two populations. Results from standard LLINs indicated reduced susceptibility to new, unused nets that was likely due to observed pyrethroid resistance. The roof of the combination LLIN performed optimally (100% mortality) against all the four populations of An. arabiensis, indicating that observed reductions in

  9. 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

  10. Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

    PubMed Central

    McPherson, Jacob G.; Miller, Robert R.; Perlmutter, Steve I.

    2015-01-01

    Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

  11. Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury.

    PubMed

    McPherson, Jacob G; Miller, Robert R; Perlmutter, Steve I

    2015-09-29

    Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural-computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

  12. Long-Lasting Impact of Neonatal Exposure to Total Body Gamma Radiation on Secondary Lymphoid Organ Structure and Function.

    PubMed

    Rangel-Moreno, Javier; de la Luz Garcia-Hernandez, Maria; Ramos-Payan, Rosalio; Biear, Jamie; Hernady, Eric; Sangster, Mark Y; Randall, Troy D; Johnston, Carl J; Finkelstein, Jacob N; Williams, Jacqueline P

    2015-10-01

    population, and used the induction of adaptive immunity against influenza virus as a functional end point. We demonstrated that, in adult animals irradiated as neonates, high endothelial venule (HEV) expansion, generation of follicular helper T cells (TFH) and formation of splenic germinal centers (GC) were rapidly and, more importantly, persistently impaired in SLO, suggesting that the early-life exposure to sublethal radiation had long-lasting effects on the induction of humoral immunity. Although the neonatal TBI did not affect the overall outcome from influenza infection in the adults at the earlier time points assessed, we believe that they nonetheless contribute significantly to the increased mortality observed at subsequent late time points. Furthermore, we speculate that the detrimental and persistent impact on the induction of CD4 T- and B-cell responses in the mediastinal lymph nodes will decrease the animals' ability to respond to other aerial pathogens. Since many of these pathogens are normally cleared by antibodies, our findings provide an explanation for the susceptibility of survivors of childhood HCT to life-threatening respiratory tract infections. These findings have implications regarding the need for increased monitoring in pediatric hematopoietic cell transplant patients, since they indicate that there are ongoing and cumulative defects in SLO, which, importantly, develop during the immediate and early postirradiation period when patients may appear immunologically competent. The identification of changes in immune-related signals may offer bioindicators of progressive dysfunction, and of potential mechanisms that could be targeted so as to reduce the risk of infection from extracellular pathogens. Furthermore, these results support the potential susceptibility of the pediatric population to infection after sublethal irradiation in the context of a nuclear or radiological event. PMID:26397175

  13. Tonic contraction of canine gastric muscle during long-lasting calcium removal and its dependence on magnesium.

    PubMed

    Filipponi, K; Golenhofen, K; Hofstetter, V; Hohnsbein, J; Lammel, E; Lukanow, J

    1987-12-01

    1. Tonic contractions induced by acetylcholine (ACh) in canine gastric fundus preparations were shown to persist during long-lasting exposure to Ca2+-free solution containing EGTA (1 mmol/l). These EGTA-resistant contractions amounted to up to more than 50% of maximal ACh-control responses in physiological salt solution. They could be evoked repeatedly for more than 20 h without reduction in size, each contraction lasting as long as ACh was present. 2. During prolonged exposure to Ca2+-free solution at normal Mg2+ concentration ([Mg2+]O = 1.2 mmol/l), the preparations exhibited a slowly developing contracture (elevation of the baseline of contraction), which was particularly pronounced in strips taken from the circular layer of the muscular wall (44% of control ACh-maximum after 4 h in Ca2+-free solution). Contracture could be suppressed either by increasing [Mg2+]O to 6-10 mmol/l or by depolarizing the cell membrane (replacement of external Na+ by K+). However, contracture also developed if, at physiological [Na+]O and [K+]O, [Mg2+]O was further increased to 50 mmol/l. 3. The combined effects of [Mg2+]O and membrane potential suggest that contracture is caused by a gain of Mg2+ by the cells. This conclusion is based on the assumption that (a) the cytoplasmic Mg2+ concentration is determined by the transmembrane electrochemical gradient acting on Mg2+, the magnesium permeability of the cell membrane (PMg) and an active extrusion mechanism, and that (b) Ca2+ removal leads to an increase of PMg which is (partly) prevented by an appropriate increase of [Mg2+]O. 4. 45Ca efflux experiments, performed at [Mg2+]O = 10 mmol/l to avoid interference of ACh responses with contracture, showed that the cellular 45Ca content decreased from some 200 mumol/kg wet wt. to less than 10 mumol/kg wet wt. within 10-20 h in Ca2+-free solution. Activations by ACh did not produce any detectable increase in 45Ca efflux. 5. The calcium ionophore A23187 (10(-5) mol/l), applied in order to

  14. 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

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

    PubMed

    Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt; Férézou, Isabelle; Pezet, Sophie

    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

  16. Long-Lasting Effects of Early-Life Antibiotic Treatment and Routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs

    PubMed Central

    Schokker, Dirkjan; Zhang, Jing; Vastenhouw, Stéphanie A.; Heilig, Hans G. H. J.; Smidt, Hauke; Rebel, Johanna M. J.; Smits, Mari A.

    2015-01-01

    Background In intensive pig husbandry systems, antibiotics are frequently administrated during early life stages to prevent respiratory and gastro-intestinal tract infections, often in combination with stressful handlings. The immediate effects of these treatments on microbial colonization and immune development have been described recently. Here we studied whether the early life administration of antibiotics has long-lasting effects on the pig’s intestinal microbial community and on gut functionality. Methodology/Principal Findings To investigate the long-lasting effect of early-life treatment, piglets were divided into three different groups receiving the following treatments: 1) no antibiotics and no stress, 2) antibiotics and no stress, and 3) antibiotics and stress. All treatments were applied at day four after birth. Sampling of jejunal content for community scale microbiota analysis, and jejunal and ileal tissue for genome-wide transcription profiling, was performed at day 55 (~8 weeks) and day 176 (~25 weeks) after birth. Antibiotic treatment in combination with or without exposure to stress was found to have long-lasting effects on host intestinal gene expression involved in a multitude of processes, including immune related processes. Conclusions/Significance The results obtained in this study indicate that early life (day 4 after birth) perturbations have long-lasting effects on the gut system, both in gene expression (day 55) as well as on microbiota composition (day 176). At day 55 high variance was observed in the microbiota data, but no significant differences between treatment groups, which is most probably due to the newly acquired microbiota during and right after weaning (day 28). Based on the observed difference in gene expression at day 55, it is hypothesized that due to the difference in immune programming during early life, the systems respond differently to the post-weaning newly acquired microbiota. As a consequence, the gut systems of

  17. 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

  18. 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. PMID:24974963

  19. Early Fasting Is Long Lasting: Differences in Early Nutritional Conditions Reappear under Stressful Conditions in Adult Female Zebra Finches

    PubMed Central

    Krause, E. Tobias; Honarmand, Mariam; Wetzel, Jennifer; Naguib, Marc

    2009-01-01

    Conditions experienced during early life can have profound effects on individual development and condition in adulthood. Differences in nutritional provisioning in birds during the first month of life can lead to differences in growth, reproductive success and survival. Yet, under natural conditions shorter periods of nutritional stress will be more prevalent. Individuals may respond differently, depending on the period of development during which nutritional stress was experienced. Such differences may surface specifically when poor environmental conditions challenge individuals again as adults. Here, we investigated long term consequences of differences in nutritional conditions experienced during different periods of early development by female zebra finches (Taeniopygia guttata) on measures of management and acquisition of body reserves. As nestlings or fledglings, subjects were raised under different nutritional conditions, a low or high quality diet. After subjects reached sexual maturity, we measured their sensitivity to periods of food restriction, their exploration and foraging behaviour as well as adult resting metabolic rate (RMR). During a short period of food restriction, subjects from the poor nutritional conditions had a higher body mass loss than those raised under qualitatively superior nutritional conditions. Moreover, subjects that were raised under poor nutritional conditions were faster to engage in exploratory and foraging behaviour. But RMR did not differ among treatments. These results reveal that early nutritional conditions affect adult exploratory behaviour, a representative personality trait, foraging and adult's physiological condition. As early nutritional conditions are reflected in adult phenotypic plasticity specifically when stressful situations reappear, the results suggest that costs for poor developmental conditions are paid when environmental conditions deteriorate. PMID:19325706

  20. Molecular changes associated with hippocampal long-lasting depression induced by the serine protease subtilisin-A.

    PubMed

    Forrest, Caroline M; Addae, Jonas I; Murthy, Sahana; Darlington, L Gail; Morris, Brian J; Stone, Trevor W

    2011-10-01

    The serine protease subtilisin-A (SubA) induces a form of long-term depression (LTD) of synaptic transmission in the rat hippocampus, and molecular changes associated with SubA-induced LTD (SubA-LTD) were explored by using recordings of evoked postsynaptic potentials and immunoblotting. SubA-LTD was prevented by a selective inhibitor of SubA proteolysis, but the same inhibitor did not affect LTD induced by electrical stimulation or activation of metabotropic glutamate receptors. SubA-LTD was reduced by the protein kinase inhibitors genistein and lavendustin A, although not by inhibitors of p38 mitogen-activated protein kinase, glycogen synthase kinase-3, or protein phosphatases. It was also reduced by (RS)-α-methyl-4-carboxyphenylglycine, a broad-spectrum antagonist at metabotropic glutamate receptors. Inhibition of the Rho kinase enzyme Rho-associated coiled-coil kinase reduced SubA-LTD, although inhibitors of the RhoGTPase-activating enzymes farnesyl transferase and geranylgeranyl transferase did not. In addition, a late phase of SubA-LTD was dependent on new protein synthesis. There was a small, non-significant difference in SubA-LTD between wild-type and RhoB(-/-) mice. Marked decreases were seen in the levels of Unc-5H3, a protein that is intimately involved in the development and plasticity of glutamatergic synapses. Smaller changes were noted, at higher concentrations of SubA, in Unc-5H1, vesicle-associated membrane protein-1 (synaptobrevin), and actin, with no changes in the levels of synaptophysin, synaptotagmin, RhoA, or RhoB. None of these changes was associated with LTD induced electrically or by the metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine. These results indicate that SubA induces molecular changes that overlap with other forms of LTD, but that the overall molecular profile of SubA-LTD is quite different. PMID:21999580

  1. 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

  2. Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats.

    PubMed

    Visser, Sandra A G; Sällström, Björn; Forsberg, Tomas; Peletier, Lambertus A; Gabrielsson, Johan

    2006-04-01

    The aim of the present investigation was to develop a pharmacokinetic-pharmacodynamic model for the characterization of clomethiazole (CMZ)-induced hypothermia and the rapid development of long-lasting tolerance in rats while taking into account circadian rhythm in baseline and the influence of handling. CMZ-induced hypothermia and tolerance was measured using body temperature telemetry in male Sprague-Dawley rats, which were given s.c. bolus injections of 0, 15, 150, 300, and 600 micromol kg(-1) and 24-h s.c. continuous infusions of 0, 20, and 40 micromol kg(-1) h(-1) using osmotic pumps. The duration of tolerance was studied by repeated injections of 300 micromol kg(-1) at 3- to 32-day intervals. Plasma exposure to CMZ was obtained in satellite groups of catheterized rats. Fitted population concentration-time profiles served as input for the pharmacodynamic analysis. The asymmetric circadian rhythm in baseline body temperature was successfully described by a novel negative feedback model incorporating external light-dark conditions. An empirical function characterized the transient increase in temperature upon handling of the animal. A feedback model for temperature regulation and tolerance development allowed estimation of CMZ potency at 30 +/- 1 microM. The delay in onset of tolerance was estimated via a series of four transit compartments at 7.6 +/- 2 h. The long-lasting tolerance was assumed to be caused by inactivation of a mediator with an estimated turnover time of 46 +/- 3 days. This multicomponent turnover model was able to quantify the CMZ-induced hypothermia, circadian rhythm in baseline, and rapid onset of a long-lasting tolerance to CMZ in rats. PMID:16339393

  3. 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.

  4. Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus.

    PubMed

    Gouveia, Telma Luciana Furtado; Scorza, Fulvio Alexandre; Silva, Michele Juliana Vieira; Bandeira, Tatiane de Aquino; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, Marcelo de Paula; Araujo, Thiago Rodrigues; Frangiotti, Maria Isabel Berzaghi; Amado, Débora; Cavalheiro, Esper Abrão; Silva, José Antonio; Naffah-Mazzacoratti, Maria da Graça

    2011-01-01

    Statins may act on inflammatory responses, decreasing oxidative stress and also reducing temperature after a brain ischemic insult. Previous data have indicated that statins protect neurons from death during long-lasting status epilepticus (SE) and attenuate seizure behaviors in animals treated with kainic acid. In this context, the study described here aimed to investigate the effect of lovastatin on body temperature and on mRNA expression levels of hippocampal cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 and B2 receptors of rats submitted to pilocarpine-induced SE. Quantitative real-time polymerase chain reaction showed a significant decrease in mRNA expression of interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 receptor in animals with SE treated with lovastatin, compared with untreated animals with SE (P<0.001). Lovastatin also reduced SE-induced hyperthermia, indicating that mechanisms related to brain protection are triggered by this drug under conditions associated with acute excitotoxicity or long-lasting SE. PMID:21130693

  5. Inability to evoke a long-lasting protective immune response to respiratory syncytial virus infection in mice correlates with ineffective nasal antibody responses.

    PubMed

    Singleton, Richard; Etchart, Nathalie; Hou, Sam; Hyland, Lisa

    2003-11-01

    Long-lasting protective antibody is not normally generated in children following primary respiratory syncytial virus (RSV) infection, frequently leading to reinfection. We used the BALB/c mouse model to examine the role of the nasal-associated lymphoid tissue and the bone marrow in the generation of RSV-specific long-lasting plasma cells, with a view to further understanding the mechanisms responsible for the poorly sustained RSV antibody levels following primary infection. We show here that substantial numbers of RSV-specific plasma cells were generated in the bone marrow following challenge, which were maintained thereafter. In contrast, in the nasal-associated lymphoid tissue, RSV-specific plasma cell numbers waned quickly both after primary infection and after challenge and were not maintained at a higher level after boosting. These data indicate that the inability to generate a robust local mucosal response in the nasal tissues may contribute substantially to the likelihood of subsequent reinfection and that the presence of serum anti-RSV antibody without local protection is not enough to protect against reinfection. PMID:14557616

  6. Genome-wide RNA profiling of long-lasting stem cell-like memory CD8 T cells induced by Yellow Fever vaccination in humans.

    PubMed

    Fuertes Marraco, Silvia A; Soneson, Charlotte; Delorenzi, Mauro; Speiser, Daniel E

    2015-09-01

    The live-attenuated Yellow Fever (YF) vaccine YF-17D induces a broad and polyfunctional CD8 T cell response in humans. Recently, we identified a population of stem cell-like memory CD8 T cells induced by YF-17D that persists at stable frequency for at least 25 years after vaccination. The YF-17D is thus a model system of human CD8 T cell biology that furthermore allows to track and study long-lasting and antigen-specific human memory CD8 T cells. Here, we describe in detail the sample characteristics and preparation of a microarray dataset acquired for genome-wide gene expression profiling of long-lasting YF-specific stem cell-like memory CD8 T cells, compared to the reference CD8 T cell differentiation subsets from total CD8 T cells. We also describe the quality controls, annotations and exploratory analyses of the dataset. The microarray data is available from the Gene Expression Omnibus (GEO) public repository with accession number GSE65804. PMID:26484272

  7. Characterization of Long-Lasting Oatp Inhibition by Typical Inhibitor Cyclosporine A and In Vitro-In Vivo Discrepancy in Its Drug Interaction Potential in Rats.

    PubMed

    Taguchi, Takayuki; Masuo, Yusuke; Kogi, Tatsuya; Nakamichi, Noritaka; Kato, Yukio

    2016-07-01

    Quantitative assessment of potential drug-drug interactions (DDIs) is one of the major focuses in drug development. The aim of the present study was to quantitatively evaluate in vitro-in vivo discrepancy of DDI potential for prototypical organic anion transporting polypeptide (Oatp) inhibitor cyclosporine A (CsA) using rats. Plasma concentration of pravastatin, prototypical Oatp substrate, after oral administration was increased by CsA intravenously administered at 1 d before the pravastatin administration. The ratio of the area under the curve of pravastatin to the control was much higher than the R-values calculated using the plasma unbound concentrations of CsA and the inhibition constant (Ki) assessed in isolated hepatocytes, indicating in vitro-in vivo discrepancy. This interaction with pravastatin persisted for 3 d after CsA administration, demonstrating long-lasting inhibition in vivo. The Ki value for unbound CsA in the presence of serum was comparable with that in its absence. M1, the major metabolite of CsA inhibited pravastatin uptake at much higher concentration compared with its plasma unbound concentration. Thus, the DDI potential of CsA-mediated hepatic Oatp inhibition cannot be extrapolated from in vitro data, and this could be due to the long-lasting Oatp inhibition by CsA, but not the effect of plasma protein or metabolites. PMID:27290622

  8. Acute and long-lasting effects of peripheral injection of caerulein and CCK-8 on the central GABAergic system in mice.

    PubMed

    Nagahama, H

    1989-01-01

    Acute and long-lasting effects of peripheral injection of caerulein (CLN) and cholecystokinin octapeptide (CCK-8) on the gamma-aminobutylic acid (GABA) content and the GABA accumulation by aminooxyacetic acid (AOAA) in the discrete brain regions of mice were examined. The content and accumulation of GABA in the striatum, hypothalamus, and frontal cortex was measured with high performance liquid chromatography with electrochemical detection (HPLC-ECD). The GABA content slightly decreased in the striatum 60 min after CLN and CCK-8 were administered, whereas it slightly increased in the hypothalamus and frontal cortex. Moreover, with CLN and CCK-8, the GABA accumulation after AOAA treatment decreased in the striatum and hypothalamus 30 min after injection. Meanwhile, when administering CLN, the GABA content as well as the GABA accumulation after AOAA treatment increased in the striatum and frontal cortex 1 day after injection, and continued to increase the second and third day in the striatum. These results showed that peripheral injection of CLN and CCK-8 had effects on the central GABAergic system with local specific actions, and also the long-lasting and time-dependent biphasic effects of CLN. PMID:2622803

  9. Intrinsic n

    SciTech Connect

    Zhang, S. B.; Wei, S.-H.; Zunger, Alex

    2001-02-15

    ZnO typifies a class of materials that can be doped via native defects in only one way: either n type or p type. We explain this asymmetry in ZnO via a study of its intrinsic defect physics, including Zn{sub O}, Zn{sub i}, V{sub O}, O{sub i}, and V{sub Zn} and n-type impurity dopants, Al and F. We find that ZnO is n type at Zn-rich conditions. This is because (i) the Zn interstitial, Zn{sub i}, is a shallow donor, supplying electrons; (ii) its formation enthalpy is low for both Zn-rich and O-rich conditions, so this defect is abundant; and (iii) the native defects that could compensate the n-type doping effect of Zn{sub i} (interstitial O, O{sub i}, and Zn vacancy, V{sub Zn}), have high formation enthalpies for Zn-rich conditions, so these ''electron killers'' are not abundant. We find that ZnO cannot be doped p type via native defects (O{sub i},V{sub Zn}) despite the fact that they are shallow (i.e., supplying holes at room temperature). This is because at both Zn-rich and O-rich conditions, the defects that could compensate p-type doping (V{sub O},Zn{sub i},Zn{sub O}) have low formation enthalpies so these ''hole killers'' form readily. Furthermore, we identify electron-hole radiative recombination at the V{sub O} center as the source of the green luminescence. In contrast, a large structural relaxation of the same center upon double hole capture leads to slow electron-hole recombination (either radiative or nonradiative) responsible for the slow decay of photoconductivity.

  10. Reduction of epileptiform activity by valproic acid in a mouse model of Alzheimer's disease is not long-lasting after treatment discontinuation.

    PubMed

    Ziyatdinova, Sofya; Viswanathan, Jayashree; Hiltunen, Mikko; Tanila, Heikki; Pitkänen, Asla

    2015-05-01

    Patients with Alzheimer's disease are at increased risk for unprovoked seizures and epilepsy compared with age-matched controls. Experimental evidence suggests that neuronal hyperexcitability and epilepsy can be triggered by amyloid-β (Aβ), the main component of amyloid plaques. Previous studies demonstrated that the administration of an anticonvulsant and histone deacetylase inhibitor, valproic acid, leads to a long-lasting reduction in Aβ levels. Here we used an APdE9 mouse model of Alzheimer's disease with overproduction of Aβ to assess whether treatment with valproic acid initiated immediately after epilepsy onset modifies the occurrence of epileptiform activity. We also analyzed whether the effect is long-lasting and associated with antiamyloidogenesis and histone-modifications. Male APdE9 mice (15 week old) received daily intraperitoneal injections of 30mg/kg valproic acid for 1 week. After a 3-week wash-out, the same animals received injections of a higher dose of valproic acid (300mg/kg) daily for 1 week. Long-term video-electroencephalography monitoring was performed prior to, during, and after the treatments. Aβ and total histone H3 and H4 acetylation levels were measured at 1 month after the final valproic acid treatment. While 30mg/kg valproic acid reduced spontaneous seizures in APdE9 mice (p<0.05, chi-square), epileptiform discharges were not reduced. Administration of 300mg/kg valproic acid, however, reduced epileptiform discharges in APdE9 mice for at least 1 week after treatment discontinuation (p<0.05, Wilcoxon test), but there was no consistent long-term effects on epileptiform activity after treatment withdrawal. Further, we found no long-lasting effect on Aβ levels (p>0.05, Mann-Whitney test), only a meager increase in global acetylation of histone H3 (p<0.05), and no effects on H4 acetylation (p>0.05). In conclusion, valproic acid treatment of APdE9 mice at the stage when amyloid plaques are beginning to develop and epileptiform activity

  11. 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

  12. 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.

  13. 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.

  14. Exposure of mice to secondhand smoke elicits both transient and long-lasting transcriptional changes in cancer-related functional networks.

    PubMed

    Tommasi, Stella; Zheng, Albert; Besaratinia, Ahmad

    2015-05-15

    Secondhand smoke (SHS) has long been linked to lung cancer and other diseases in nonsmokers. Yet, the underlying mechanisms of SHS carcinogenicity in nonsmokers remain to be elucidated. We investigated the immediate and long-lasting effects of SHS exposure on gene expression in mice in vivo. We exposed mice whole body to SHS for 5 h/day, 5 days/week for 4 months in exposure chambers of a microprocessor-controlled smoking machine. Subsequently, we performed microarray gene expression profiling, genome-wide, to construct the pulmonary transcriptome of SHS-exposed mice, immediately after discontinuation of exposure (T0) and following 1-month (T1) and 7-month (T2) recoveries in clean air. Sub-chronic exposure of mice to SHS elicited a robust transcriptomic response, including both reversible and irreversible changes in gene expression. There were 674 differentially expressed transcripts immediately after treatment (T0), of which the majority were involved in xenobiotic metabolism, signaling, and innate immune response. Reduced, yet, substantial numbers of differentially expressed transcripts were detectable in mice after cessation of SHS-exposure (254 transcripts at T1 and 30 transcripts at T2). Top biofunctional networks disrupted in SHS-exposed mice, even after termination of exposure, were implicated in cancer, respiratory disease, and inflammatory disease. Our data show that exposure of mice to SHS induces both transient and long-lasting changes in gene expression, which impact cancer-related functional networks. The pattern of transcriptional changes in SHS-exposed mice may provide clues on the underlying mechanisms of lung tumorigenesis in nonsmokers. Our findings underscore the importance of eliminating SHS from environments where nonsmokers are unavoidably exposed to this carcinogen. PMID:25346222

  15. 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.

  16. Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

    PubMed

    Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; 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(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(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity. PMID:18573268

  17. A qualitative study on the acceptability and preference of three types of long-lasting insecticide-treated bed nets in Solomon Islands: implications for malaria elimination

    PubMed Central

    Atkinson, Jo-An; Bobogare, Albino; Fitzgerald, Lisa; Boaz, Leonard; Appleyard, Bridget; Toaliu, Hilson; Vallely, Andrew

    2009-01-01

    Background In March 2008, the Solomon Islands and Vanuatu governments raised the goal of their National Malaria Programmes from control to elimination. Vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal bed nets (LLINs) are key integral components of this programme. Compliance with these interventions is dependent on their acceptability and on the socio-cultural context of the local population. These factors need to be investigated locally prior to programme implementation. Method Twelve focus group discussions (FGDs) were carried out in Malaita and Temotu Provinces, Solomon Islands in 2008. These discussions explored user perceptions of acceptability and preference for three brands of long-lasting insecticide-treated bed nets (LLINs) and identified a number of barriers to their proper and consistent use. Results Mosquito nuisance and perceived threat of malaria were the main determinants of bed net use. Knowledge of malaria and the means to prevent it were not sufficient to guarantee compliance with LLIN use. Factors such as climate, work and evening social activities impact on the use of bed nets, particularly in men. LLIN acceptability plays a varying role in compliance with their use in villages involved in this study. Participants in areas of reported high and year round mosquito nuisance and perceived threat of malaria reported LLIN use regardless of any reported unfavourable characteristics. Those in areas of low or seasonal mosquito nuisance were more likely to describe the unfavourable characteristics of LLINs as reasons for their intermittent or non-compliance. The main criterion for LLIN brand acceptability was effectiveness in preventing mosquito bites and malaria. Discussions highlighted considerable confusion around LLIN care and washing which may be impacting on their effectiveness and reducing their acceptability in Solomon Islands. Conclusion Providing LLINs that are acceptable will be more important for

  18. 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. PMID:27622033

  19. [Animal experimental evidence of the long-lasting efficacy of etofenamate by prolongation of the half-life after intramuscular application].

    PubMed

    Dell, H D; Brons, J; Fiedler, J; Kamp, R; Pelster, B

    1990-03-01

    Animal Experimental Evidence of Long-lasting Liberation of Etofenamate by Half-life Prolongation after Intramuscular Application. The purpose of this investigation was to show in animal experiments that by i.m. injection of etofenamate (active substance of Rheumon i.m.) in oily solution the following effects could be obtained: a fast onset of action (gain of therapeutically relevant drug levels shortly after injection) a long-lasting efficacy (prolonged liberation from the oil depot) and better tolerability as compared to other intramuscularly applicable antiinflammatory drugs (avoidance of high plasma spikes). Etofenamate in rats is liberated with a half-life of 1.29 days from the place of application (cutaneous half-life 8.5 h). Flufenamic acid in muscles is found only in traces. After i.m. administration of etofenamate to dogs maximum plasma levels of etofenamate and flufenamic acid were reached within 2 and 4 h, resp. The mean half-lives of plasma elimination are 14 h for etofenamate and 23.2 h for flufenamic acid formed esterolytically from etofenamate (flufenamic acid oral half-life 2-4 h). Maximum plasma levels after etofenamate are only 6.5-11.8% of the maximum levels after equivalent amounts of flufenamic acid administered orally. According to these data etofenamate i.m. is a drug formulation with fast increasing plasma levels, prolonged half-life and lower maximum plasma levels as compared to orally administered preparations. The results are confirmed in animals (pharmacodynamics, toxicology and tolerability) and man (kinetics, clinical studies). PMID:2346540

  20. Activation of glial glutamate transporter via MAPK p38 prevents enhanced and long-lasting non-evoked resting pain after surgical incision in rats.

    PubMed

    Reichl, Sylvia; Segelcke, Daniel; Keller, Viktor; Jonas, Robin; Boecker, Armin; Wenk, Manuel; Evers, Dagmar; Zahn, Peter K; Pogatzki-Zahn, Esther M

    2016-06-01

    Pain after surgery has recently become a major issue not only due to lack of treatment success in the acute phase; even more alarming is the large number of patients developing prolonged pain after surgery. Because spinal glutamate as well as spinal glia plays a major role in acute incisional pain, we investigated the role of the spinal glial glutamate transporters (GT), GLAST, GLT-1, for acute and prolonged pain and hyperalgesia caused by an incision. Spinal administration of the GT-inhibitor DL-TBOA increased non-evoked pain but not evoked pain behavior (hyperalgesia) up to 2 weeks after incision. In accordance, spinal GLAST (and to a lesser degree GLT-1) were upregulated after incision for several days. Long-term incision induced GT upregulation was prevented by long-lasting p38-inhibitor administration but not by long-lasting ERK1/2-inhibition after incision. In accordance, daily treatment with the p38-inhibitor (but not the ERK1/2 inhibitor) prolonged non-evoked but not evoked pain behavior after incision. In electrophysiological experiments, spontaneous activity of high threshold (HT) (but not wide dynamic range (WDR)) neurons known to transmit incision induced non-evoked pain was increased after prolonged treatment with the p38-inhibitor. In conclusion, our findings indicate a new spinal pathway by which non-evoked pain behavior after incision is modulated. The pathway is modality (non-evoked pain) and neuron (HT) specific and disturbance contributes to prolonged long-term pain after surgical incision. This may have therapeutic implications for the treatment of acute and - even more relevant - for prevention of chronic pain after surgery in patients. PMID:26920805

  1. 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

  2. Transcutaneous induction of stimulus-timing-dependent plasticity in dorsal cochlear nucleus

    PubMed Central

    Wu, Calvin; Martel, David T.; Shore, Susan E.

    2015-01-01

    The cochlear nucleus (CN) is the first site of multisensory integration in the ascending auditory pathway. The principal output neurons of the dorsal cochlear nucleus (DCN), fusiform cells, receive somatosensory information relayed by the CN granule cells from the trigeminal and dorsal column pathways. Integration of somatosensory and auditory inputs results in long-term enhancement or suppression in a stimulus-timing-dependent manner. Here, we demonstrate that stimulus-timing-dependent plasticity (STDP) can be induced in DCN fusiform cells using paired auditory and transcutaneous electrical stimulation of the face and neck to activate trigeminal and dorsal column pathways to the CN, respectively. Long-lasting changes in fusiform cell firing rates persisted for up to 2 h after this bimodal stimulation, and followed Hebbian or anti-Hebbian rules, depending on tone duration, but not somatosensory stimulation location: 50 ms paired tones evoked predominantly Hebbian, while 10 ms paired tones evoked predominantly anti-Hebbian plasticity. The tone-duration-dependent STDP was strongly correlated with first inter-spike intervals, implicating intrinsic cellular properties as determinants of STDP. This study demonstrates that transcutaneous stimulation with precise auditory–somatosensory timing parameters can non-invasively induce fusiform cell long-term modulation, which could be harnessed in the future to moderate tinnitus-related hyperactivity in DCN. PMID:26321928

  3. Plastic Surgery

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? 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 " ...

  4. Melting the Plastic Ceiling: Overcoming Obstacles to Foster Leadership in Women Plastic Surgeons.

    PubMed

    Silva, Amanda K; Preminger, Aviva; Slezak, Sheri; Phillips, Linda G; Johnson, Debra J

    2016-09-01

    The underrepresentation of women leaders in plastic surgery echoes a phenomenon throughout society. The importance of female leadership is presented, and barriers to gender equality in plastic surgery, both intrinsic and extrinsic, are discussed. Strategies for fostering women in leadership on an individual level and for the specialty of plastic surgery are presented. PMID:27556609

  5. 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

  6. Evidence for a useful life of more than three years for a polyester-based long-lasting insecticidal mosquito net in Western Uganda

    PubMed Central

    2011-01-01

    Background Long-lasting insecticidal nets (LLIN) are now standard for the prevention of malaria. However, only products with recommendation for public use from the World Health Organization should be used and this evaluation includes the assessment of net effectiveness after three years of field use. Results for one of the polyester-based products, Interceptor® is presented. Methods In five villages, 190 LLIN and 90 nets conventionally treated with the insecticide alpha-cypermethrin at 25 mg/m2 were distributed randomly and used by the families. Following a baseline household survey a net survey was carried out every six months to capture use, washing habits and physical condition of the nets. Randomly selected nets were collected after 6, 12, 24, 36 and 42 months and tested for remaining insecticide content and ability to knock-down and kill malaria transmitting mosquitoes. Results During the three and a half years of observation only 16 nets were lost to follow-up resulting in an estimated attrition rate of 12% after three and 20/% after 3.5 years. Nets were used regularly and washed on average 1.5 times per year. After three and a half years 29% of the nets were still in good condition while 13% were seriously torn with no difference between the LLIN and control nets. The conventionally treated nets quickly lost insecticide and after 24 months only 7% of the original dose remained (1.6 mg/m2). Baseline median concentration of alpha-cypermethrin for LLIN was 194.5 mg/m2 or 97% of the target dose with between and within net variation of 11% and 4% respectively (relative standard deviation). On the LLIN 73.8 mg/m2 alpha-cypermethrin remained after three years of use and 56.2 mg/m2 after three and a half and 94% and 81% of the LLIN still had > 15 mg/m2 left respectively. Optimal effectiveness in bio-assays (≥95% 60 minute knock-down or ≥ 80% 24 hour mortality) was found in 83% of the sampled LLIN after three and 71% after three and a half years. Conclusions

  7. The valence of the long-lasting emotional experiences with various handlers modulates discrimination and generalization of individual humans in sheep.

    PubMed

    Destrez, A; Coulon, M; Deiss, V; Delval, E; Boissy, A; Boivin, X

    2013-11-01

    Between-farm variation in animal reactions to humans can reflect different management styles and behavioral tendencies among farmers. Animals are well known to discriminate among humans, but less clear is the key issue of whether they more or less easily generalize their experience from specific humans to others depending on management style. Here, we chose 2 contrasted management styles by known handlers: "gentle" management, that is, long-lasting exposure to positive human interactions (with limited negative interactions), and "aversive" management including long-lasting exposure to various negative human interactions (with only food delivery considered a positive interaction) and aversive events. Over a period of 19 wk, 15 female lambs were exposed to the gentle management treatment ("gently treated" group) and another 15 lambs ("aversively treated" group) were exposed to the aversive management treatment. To facilitate discrimination by animals, experimenters wore white clothes for aversive events and green clothes for farming handling (positive handling and feeding for the gently treated group and only feeding for the aversively treated group). Sheep perception of the human was assessed after the management period by submitting lambs from each group to 2 standardized tests: 1) the presence of a stationary human (familiar human in white vs. familiar human in green vs. unknown human) and 2) the presence of a moving human (familiar human in white vs. familiar human in green vs. unknown human). As expected, during the stationary human test, aversively treated lambs spent less time in the human zone (P<0.0001), showed greater latency to approach the human (P=0.05), and had fewer contacts with the human (P=0.05) than gently treated lambs. During the moving human test, aversively treated lambs also showed a greater escape distance from humans than gently treated lambs (P<0.0001). Aversively treated lambs showed the same fear responses towards familiar and unknown

  8. A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity.

    PubMed Central

    Baker-Zander, S.; Sell, S.

    1980-01-01

    Inoculation of the causative agent of syphilis, Treponema pallidum into the testes of rabbits initiated the following sequence of events: 1) a rapid proliferation of organisms in the interstitial tissues of the testes, reaching a maximum at about 10-11 days after infection; 2) systemic spread of organisms primarily in the lymphoid organs; 3) a prompt immune response manifested by hyperplasia of T cell domains in draining lymph nodes and spleen, blast transformation responses of lymphoid cells to sonicates of T pallidum, the appearance of serum antibody, and the marked infiltration of the infected areas of the testes by T cells; 4) essential clearing of organisms identified by immunofluorescence from the infected site 10-14 days after infection associated with evolution of the inflammatory response from primarily a T cell infiltrate to a larger mononuclear cell type, and the immunofluorescent identification of presumptive T pallidum antigen in macrophages; 5) interstitial fibrosis or resolution 17-21 days after infection so that examination of infected testes from 1 to 24 months later reveals foci of tubular atrophy and fibrosis of varying size, alternating with regenerated tubules, separated by interstitial areas with only minimal fibrosis. During the long period of latency there is no evidence of atrophy or hypoplasia of the lymphoid organs and long-lasting T cell memory with regard to T pallidum sonicates is demonstrable. Reinfection of previously inoculated rabbits indicates partial protection at 25 days after infection followed by essentially complete protection after 55 days. It is concluded that there is a prompt and long-lasting immune response to T pallidum in experimentally infected rabbits. The main mechanism for destruction of infecting organisms appears to be T-cell-initiated macrophage-mediated destruction, but a role for antibody dependent phagocytosis cannot be ruled out. The reason that some organisms may survive in various body organs remains

  9. AMA1-Deficient Toxoplasma gondii Parasites Transiently Colonize Mice and Trigger an Innate Immune Response That Leads to Long-Lasting Protective Immunity

    PubMed Central

    Lagal, Vanessa; Dinis, Márcia; Cannella, Dominique; Bargieri, Daniel; Gonzalez, Virginie; Andenmatten, Nicole; Meissner, Markus

    2015-01-01

    The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until we genetically engineered viable parasites lacking AMA1. The reduction in invasiveness of the Toxoplasma gondii RH-AMA1 knockout (RH-AMA1KO) tachyzoite population, in vitro, raised key questions about the outcome associated with these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1KO tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leukocytes. While the RH-AMA1KO population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts, where immune cells in combination sense parasites and secrete proinflammatory cytokines. This innate response further leads to a long-lasting status immunoprotective against a secondary challenge by high inocula of the homologous type I or a distinct type II T. gondii genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population in vivo. PMID:25847964

  10. Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice.

    PubMed

    Wack, Andreas; Baudner, Barbara C; Hilbert, Anne K; Manini, Ilaria; Nuti, Sandra; Tavarini, Simona; Scheffczik, Hanno; Ugozzoli, Mildred; Singh, Manmohan; Kazzaz, Jina; Montomoli, Emanuele; Del Giudice, Giuseppe; Rappuoli, Rino; O'Hagan, Derek T

    2008-01-24

    Influenza is controlled by protective titres of neutralizing antibodies, induced with the help of CD4 T-cells, and by antiviral T-cell effector function. Adjuvants are essential for the efficient vaccination of a naïve population against avian influenza. We evaluated a range of adjuvants for their ability to enhance, in naïve mice, protective hemagglutination inhibition (HI) titres, which represent the generally accepted correlate of protection, virus-neutralizing titres and T-cell responses to a new generation influenza vaccine produced in cell culture. The selected adjuvants include alum, calcium phosphate (CAP), MF59, the delivery system poly-(lactide co-glycolide) (PLG) and the immune potentiator CpG. MF59 was clearly the most potent single adjuvant and induced significantly enhanced, long-lasting HI and neutralizing titres and T-cell responses in comparison to all alternatives. The combination of alum, MF59, CAP or PLG with CpG generally induced slightly more potent titres. The addition of CpG to MF59 also induced a more potent Th1 cellular immune response, represented by higher IgG2a titres and the induction of a strongly enhanced IFN-gamma response in splenocytes from immunized mice. These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains. PMID:18162266