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Sample records for synapse loss induced

  1. Coding deficits in noise-induced hidden hearing loss may stem from incomplete repair of ribbon synapses in the cochlea

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    Lijuan eShi

    2016-05-01

    Full Text Available Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs and type I afferent auditory nerve fibers (ANFs may occur in the absence of permanent threshold shift (PTS, and that synapses connecting IHCs with low spontaneous rate (SR ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise-induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., hidden hearing loss. However, significant noise-induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval.

  2. Rescue of inhibitory synapse strength following developmental hearing loss.

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    Vibhakar C Kotak

    Full Text Available Inhibitory synapse dysfunction may contribute to many developmental brain disorders, including the secondary consequences of sensory deprivation. In fact, developmental hearing loss leads to a profound reduction in the strength of inhibitory postsynaptic currents (IPSCs in the auditory cortex, and this deficit persists into adulthood. This finding is consistent with the general theory that the emergence of mature synaptic properties requires activity during development. Therefore, we tested the prediction that inhibitory strength can be restored following developmental hearing loss by boosting GABAergic transmission in vivo. Conductive or sensorineural hearing loss was induced surgically in gerbils prior to hearing onset and GABA agonists were then administered for one week. IPSCs were subsequently recorded from pyramidal neurons in a thalamocortical brain slice preparation. Administration of either a GABA(A receptor a1 subunit specific agonist (zolpidem, or a selective GABA reuptake inhibitor (SGRI, rescued IPSC amplitude in hearing loss animals. Furthermore, this restoration persisted in adults, long after drug treatment ended. In contrast, a GABA(B receptor agonist baclofen did not restore inhibitory strength. IPSCs could also be restored when SGRI administration began 3 weeks after sensory deprivation. Together, these results demonstrate long-lasting restoration of cortical inhibitory strength in the absence of normal experience. This suggests that in vivo GABA(A receptor activation is sufficient to promote maturation, and this principle may extend to other developmental disorders associated with diminished inhibitory function.

  3. Chronic sleep restriction promotes brain inflammation and synapse loss, and potentiates memory impairment induced by amyloid-β oligomers in mice.

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    Kincheski, Grasielle C; Valentim, Isabela S; Clarke, Julia R; Cozachenco, Danielle; Castelo-Branco, Morgana T L; Ramos-Lobo, Angela M; Rumjanek, Vivian M B D; Donato, José; De Felice, Fernanda G; Ferreira, Sergio T

    2017-08-01

    It is increasingly recognized that sleep disturbances and Alzheimer's disease (AD) share a bidirectional relationship. AD patients exhibit sleep problems and alterations in the regulation of circadian rhythms; conversely, poor quality of sleep increases the risk of development of AD. The aim of the current study was to determine whether chronic sleep restriction potentiates the brain impact of amyloid-β oligomers (AβOs), toxins that build up in AD brains and are thought to underlie synapse damage and memory impairment. We further investigated whether alterations in levels of pro-inflammatory mediators could play a role in memory impairment in sleep-restricted mice. We found that a single intracerebroventricular (i.c.v.) infusion of AβOs disturbed sleep pattern in mice. Conversely, chronically sleep-restricted mice exhibited higher brain expression of pro-inflammatory mediators, reductions in levels of pre- and post-synaptic marker proteins, and exhibited increased susceptibility to the impact of i.c.v. infusion of a sub-toxic dose of AβOs (1pmol) on performance in the novel object recognition memory task. Sleep-restricted mice further exhibited an increase in brain TNF-α levels in response to AβOs. Interestingly, memory impairment in sleep-restricted AβO-infused mice was prevented by treatment with the TNF-α neutralizing monoclonal antibody, infliximab. Results substantiate the notion of a dual relationship between sleep and AD, whereby AβOs disrupt sleep/wake patterns and chronic sleep restriction increases brain vulnerability to AβOs, and point to a key role of brain inflammation in increased susceptibility to AβOs in sleep-restricted mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys

    OpenAIRE

    Elsworth, John D; Jentsch, James D; Groman, Stephanie M; Roth, Robert H; Redmond, D. Eugene; Leranth, Csaba

    2015-01-01

    Bisphenol-A (BPA) is widely used in the manufacture of plastics, epoxy resins and certain paper products. A majority of the population in the developed world is routinely exposed to BPA from multiple sources and has significant circulating levels of BPA. Although BPA is categorized as an endocrine disruptor with a growing literature on adverse effects, it is uncertain whether cognitive dysfunction is induced in humans by exposure to BPA. The present study examined the impact of BPA in primate...

  5. Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.

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    Adel Zeidan

    Full Text Available Neuroligins (Nlgns are postsynaptic, integral membrane cell adhesion molecules that play important roles in the formation, validation, and maturation of synapses in the mammalian central nervous system. Given their prominent roles in the life cycle of synapses, it might be expected that the loss of neuroligin family members would affect the stability of synaptic organization, and ultimately, affect the tenacity and persistence of individual synaptic junctions. Here we examined whether and to what extent the loss of Nlgn-1 affects the dynamics of several key synaptic molecules and the constancy of their contents at individual synapses over time. Fluorescently tagged versions of the postsynaptic scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the presynaptic vesicle molecule SV2A were expressed in primary cortical cultures from Nlgn-1 KO mice and wild-type (WT littermates, and live imaging was used to follow the constancy of their contents at individual synapses over periods of 8-12 hours. We found that the loss of Nlgn-1 was associated with larger fluctuations in the synaptic contents of these molecules and a poorer preservation of their contents at individual synapses. Furthermore, rates of synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice. Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1 knockout mice were negated by suppressing spontaneous network activity. These findings suggest that the loss of Nlgn-1 is associated with some use-dependent destabilization of excitatory synapse organization, and indicate that in the absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat impaired.

  6. Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage

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    Ewan West

    2015-06-01

    Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ and the loss of synapses. Aggregation of the cellular prion protein (PrPC by Aβ oligomers induced synapse damage in cultured neurons. PrPC is attached to membranes via a glycosylphosphatidylinositol (GPI anchor, the composition of which affects protein targeting and cell signaling. Monoacylated PrPC incorporated into neurons bound “natural Aβ”, sequestering Aβ outside lipid rafts and preventing its accumulation at synapses. The presence of monoacylated PrPC reduced the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2 and Aβ-induced synapse damage. This protective effect was stimulus specific, as treated neurons remained sensitive to α-synuclein, a protein associated with synapse damage in Parkinson’s disease. In synaptosomes, the aggregation of PrPC by Aβ oligomers triggered the formation of a signaling complex containing the cPLA2.a process, disrupted by monoacylated PrPC. We propose that monoacylated PrPC acts as a molecular sponge, binding Aβ oligomers at the neuronal perikarya without activating cPLA2 or triggering synapse damage.

  7. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress.

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    Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

    2014-07-01

    The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

  8. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress

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    Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

    2014-01-01

    The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress. PMID:24589888

  9. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

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    Geinisman, Y; de Toledo-Morrell, L; Morrell, F

    1986-01-01

    Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory. Images PMID:3458260

  10. Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy.

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    Katherine J Kopeikina

    Full Text Available Neurofibrillary tangles (NFTs of tau are one of the defining hallmarks of Alzheimer's disease (AD, and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

  11. Anatomically detailed and large-scale simulations studying synapse loss and synchrony using NeuroBox

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    Markus eBreit

    2016-02-01

    Full Text Available The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic or reconstruction to the simulation platform UG 4 (which harbors a neuroscientific portfolio and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g. new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

  12. Anatomically Detailed and Large-Scale Simulations Studying Synapse Loss and Synchrony Using NeuroBox.

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    Breit, Markus; Stepniewski, Martin; Grein, Stephan; Gottmann, Pascal; Reinhardt, Lukas; Queisser, Gillian

    2016-01-01

    The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic, or reconstruction) to the simulation platform UG 4 (which harbors a neuroscientific portfolio) and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g., new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

  13. Changes in Properties of Auditory Nerve Synapses following Conductive Hearing Loss.

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    Zhuang, Xiaowen; Sun, Wei; Xu-Friedman, Matthew A

    2017-01-11

    Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL. Normal hearing is important to everyday life, but abnormal auditory experience during development can lead to processing disorders. For example, otitis media reduces sound to the ear, which can cause long-lasting deficits in language skills and verbal

  14. Alzheimer's disease: synapses gone cold

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    Hyman Bradley T

    2011-08-01

    Full Text Available Abstract Alzheimer's disease (AD is a progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. Synapse loss is the best pathological correlate of cognitive decline in AD and mounting evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble oligomeric forms of amyloid beta (Aβ, the peptide that aggregates to form senile plaques in the brain of AD patients, have been shown to be toxic to neuronal synapses both in vitro and in vivo. Aβ oligomers inhibit long-term potentiation (LTP and facilitate long-term depression (LTD, electrophysiological correlates of memory formation. Furthermore, oligomeric Aβ has also been shown to induce synapse loss and cognitive impairment in animals. The molecular underpinnings of these observations are now being elucidated, and may provide clear therapeutic targets for effectively treating the disease. Here, we review recent findings concerning AD pathogenesis with a particular focus on how Aβ impacts synapses.

  15. Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

    DEFF Research Database (Denmark)

    Soricelli, A; Postiglione, A; Grivet-Fojaja, M R

    1996-01-01

    indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured Vd in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled......Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends...

  16. Remodelling at the calyx of Held-MNTB synapse in mice developing with unilateral conductive hearing loss.

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    Grande, Giovanbattista; Negandhi, Jaina; Harrison, Robert V; Wang, Lu-Yang

    2014-04-01

    Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity

  17. Noise-Induced Hearing Loss

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    ... Home » Health Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is ... I find additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound ...

  18. Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression.

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    Baka, Judith; Csakvari, Eszter; Huzian, Orsolya; Dobos, Nikoletta; Siklos, Laszlo; Leranth, Csaba; MacLusky, Neil J; Duman, Ronald S; Hajszan, Tibor

    2017-02-20

    Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague-Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals. After 'postpartum' withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during 'postpartum' stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during 'postpartum' stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated 'postpartum' females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging 'synaptogenic hypothesis' of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function

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    Rickmann Michael

    2008-10-01

    Full Text Available Abstract Background The formation of functional synapses is a crucial event in neuronal network formation, and with regard to regulation of breathing it is essential for life. Members of the transforming growth factor-beta (TGF-β superfamily act as intercellular signaling molecules during synaptogenesis of the neuromuscular junction of Drosophila and are involved in synaptic function of sensory neurons of Aplysia. Results Here we show that while TGF-β2 is not crucial for the morphology and function of the neuromuscular junction of the diaphragm muscle of mice, it is essential for proper synaptic function in the pre-Bötzinger complex, a central rhythm organizer located in the brainstem. Genetic deletion of TGF-β2 in mice strongly impaired both GABA/glycinergic and glutamatergic synaptic transmission in the pre-Bötzinger complex area, while numbers and morphology of central synapses of knock-out animals were indistinguishable from their wild-type littermates at embryonic day 18.5. Conclusion The results demonstrate that TGF-β2 influences synaptic function, rather than synaptogenesis, specifically at central synapses. The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-β2 knock-out mice.

  20. Mechanism study of laser cochleostomy-induced early hearing loss in a rat model.

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    Ye, Qing; Geng, Yang; Zhang, Xian-Zeng; Chen, Wen-Lie; Tian, Tian-Jie; Xie, Shu-Sen; Huang, Zheng

    2014-03-01

    Hearing loss following laser-assisted ear surgery has been reported. However, the mechanism responsible for the hearing loss remains largely speculative. The aim of this study was to investigate the correlation between laser-induced hearing loss and changes in the number of hair cell ribbon synapses and ultrastructure in the cochlea. Laser cochleostomy was performed with a superpulsed carbon dioxide (CO2) laser at 2 and 5 W in Sprague-Dawley rats. Auditory brainstem responses (ABRs) were measured preoperatively and 2 days after surgery. The synapse numbers in apical and middle cochlear turns were quantified. Transmission electron microscopy was employed to further examine the subcellular changes in the cochlea. Click and tonal ABR threshold shifts in both 2 and 5-W groups displayed a frequency-dependent loss within the frequency range measured. Laser cochleostomy induced a significant decrease of synapse numbers in the middle turn in both groups (p laser-caused hearing loss even under low-energy laser cochleostomy. The high-energy laser-induced hearing loss was associated with more reduction of synapse number.

  1. Changes in the numbers of ribbon synapses and expression of RIBEYE in salicylate-induced tinnitus.

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    Zhang, Feng-Ying; Xue, Yi-Xue; Liu, Wen-Jing; Yao, Yi-Long; Ma, Jun; Chen, Lin; Shang, Xiu-Li

    2014-01-01

    This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus. C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons. The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7(th) d and decreased on the 9(th) and 10(th) d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days. This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus. © 2014 S. Karger AG, Basel.

  2. GABA and Endocannabinoids Mediate Depotentiation of Schaffer Collateral Synapses Induced by Stimulation of Temperoammonic Inputs.

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    Izumi, Yukitoshi; Zorumski, Charles F

    2016-01-01

    Long-term potentiation (LTP) of Schaffer collateral (SC) synapses in the hippocampus is thought to play a key role in episodic memory formation. Because the hippocampus is a shorter-term, limited capacity storage system, repeated bouts of learning and synaptic plasticity require that SC synapses reset to baseline at some point following LTP. We previously showed that repeated low frequency activation of temperoammonic (TA) inputs to the CA1 region depotentiates SC LTP without persistently altering basal transmission. This heterosynaptic depotentiation involves adenosine A1 receptors but not N-methyl-D-aspartate receptors, metabotropic glutamate receptors or L-type calcium channels. In the present study, we used rat hippocampal slices to explore other messengers contributing to TA-induced SC depotentiation, and provide evidence for the involvement of cannabinoid-1 and γ-aminobutyric acid (GABA) type-A receptors as more proximal signaling events leading to synaptic resetting, with A1 receptor activation serving as a downstream event. Surprisingly, we found that TA-induced SC depotentiation is independent of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors. We also examined the involvement of mitogen-activated protein kinases (MAPKs), and found a role for extracellular-signal related kinase 1/2 and p38 MAPK, but not c-Jun-N-terminal kinase. These results indicate that low frequency stimulation of TA inputs to CA1 activates a complex signaling network that instructs SC synaptic resetting. The involvement of GABA and endocannabinoids suggest mechanisms that could contribute to cognitive dysfunction associated with substance abuse and neuropsychiatric disorders.

  3. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

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    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  4. Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress

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    Laura eMusazzi

    2015-04-01

    Full Text Available Increasing evidence has shown that the pathophysiology of neuropsychiatric disorders, including mood disorders, is associated with abnormal function and regulation of the glutamatergic system. Consistently, preclinical studies on stress-based animal models of pathology showed that glucocorticoids and stress exert crucial effects on neuronal excitability and function, especially in cortical and limbic areas. In prefrontal and frontal cortex, acute stress was shown to induce enhancement of glutamate release/transmission dependent on activation of corticosterone receptors. Although the mechanisms whereby stress affects glutamate transmission have not yet been fully understood, it was shown that synaptic, non-genomic action of corticosterone is required to increase the readily releasable pool of glutamate vesicles but is not sufficient to enhance transmission in prefrontal and frontal cortex. Slower, partly genomic mechanisms are probably necessary for the enhancement of glutamate transmission induced by stress.Combined evidence has suggested that the changes in glutamate release and transmission are responsible for the dendritic remodeling and morphological changes induced by stress and it has been argued that sustained alterations of glutamate transmission may play a key role in the long-term structural/functional changes associated with mood disorders in patients. Intriguingly, modifications of the glutamatergic system induced by stress in the prefrontal cortex seem to be biphasic. Indeed, while the fast response to stress suggests an enhancement in the number of excitatory synapses, synaptic transmission and working memory, long-term adaptive changes -including those consequent to chronic stress- induce opposite effects. Better knowledge of the cellular effectors involved in this biphasic effect of stress may be useful to understand the pathophysiology of stress-related disorders, and open new paths for the development of therapeutic approaches.

  5. Facial stimulation induces long-term depression at cerebellar molecular layer interneuron–Purkinje cell synapses in vivo in mice

    Directory of Open Access Journals (Sweden)

    De-Lai eQiu

    2015-06-01

    Full Text Available Cerebellar long-term synaptic plasticity has been proposed to provide a cellular mechanism for motor learning. Numerous studies have demonstrated the induction and mechanisms of synaptic plasticity at parallel fiber–Purkinje cell (PF–PC, parallel fiber–molecular layer interneurons (PF–MLI and mossy fiber–granule cell (MF–GC synapses, but no study has investigated sensory stimulation-evoked synaptic plasticity at MLI–PC synapses in the cerebellar cortex of living animals. We studied the expression and mechanism of MLI–PC GABAergic synaptic plasticity induced by a train of facial stimulation in urethane-anesthetized mice by cell-attached recordings and pharmacological methods. We found that 1 Hz, but not a 2 Hz or 4 Hz, facial stimulation induced a long-term depression (LTD of GABAergic transmission at MLI–PC synapses, which was accompanied with a decrease in the stimulation-evoked pause of spike firing in PCs, but did not induce a significant change in the properties of the sensory-evoked spike events of MLIs. The MLI–PC GABAergic LTD could be prevented by blocking cannabinoid type 1 (CB1 receptors, and could be pharmacologically induced by a CB1 receptor agonist. Additionally, 1 Hz facial stimulation delivered in the presence of a metabotropic glutamate receptor 1 (mGluR1 antagonist, JNJ16259685, still induced the MLI–PC GABAergic LTD, whereas blocking N-methyl-D-aspartate (NMDA receptors during 1 Hz facial stimulation abolished the expression of MLI–PC GABAergic LTD. These results indicate that sensory stimulation can induce an endocannabinoid (eCB-dependent LTD of GABAergic transmission at MLI–PC synapses via activation of NMDA receptors in cerebellar cortical Crus II in vivo in mice. Our results suggest that the sensory stimulation-evoked MLI–PC GABAergic synaptic plasticity may play a critical role in motor learning in animals.

  6. Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus.

    Science.gov (United States)

    Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

    2016-01-01

    A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission.

  7. Methadone Induced Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Chadi Saifan

    2013-01-01

    Full Text Available Background. Sudden sensorineural hearing loss (SSHL caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiometry exams, he displayed persistent moderately severe sensorineural hearing loss bilaterally. Discussion. This case is notable because unlike all but one previously reported case, the patient—who was restated on methadone—did not make a complete recovery. Conclusion. Methadone overuse in rare cases causes SSHL.

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

    Science.gov (United States)

    Clarkson, Cheryl; Antunes, Flora M; Rubio, Maria E

    2016-09-28

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

  9. Cellular mechanisms of noise-induced hearing loss.

    Science.gov (United States)

    Kurabi, Arwa; Keithley, Elizabeth M; Housley, Gary D; Ryan, Allen F; Wong, Ann C-Y

    2017-06-01

    Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation. Published by Elsevier B.V.

  10. Local and global synchronization transitions induced by time delays in small-world neuronal networks with chemical synapses.

    Science.gov (United States)

    Yu, Haitao; Wang, Jiang; Du, Jiwei; Deng, Bin; Wei, Xile

    2015-02-01

    Effects of time delay on the local and global synchronization in small-world neuronal networks with chemical synapses are investigated in this paper. Numerical results show that, for both excitatory and inhibitory coupling types, the information transmission delay can always induce synchronization transitions of spiking neurons in small-world networks. In particular, regions of in-phase and out-of-phase synchronization of connected neurons emerge intermittently as the synaptic delay increases. For excitatory coupling, all transitions to spiking synchronization occur approximately at integer multiples of the firing period of individual neurons; while for inhibitory coupling, these transitions appear at the odd multiples of the half of the firing period of neurons. More importantly, the local synchronization transition is more profound than the global synchronization transition, depending on the type of coupling synapse. For excitatory synapses, the local in-phase synchronization observed for some values of the delay also occur at a global scale; while for inhibitory ones, this synchronization, observed at the local scale, disappears at a global scale. Furthermore, the small-world structure can also affect the phase synchronization of neuronal networks. It is demonstrated that increasing the rewiring probability can always improve the global synchronization of neuronal activity, but has little effect on the local synchronization of neighboring neurons.

  11. Noise-induced hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Catlin, F.I.

    1986-03-01

    Hearing loss affects 30 million people in the United States; of these, 21 million are over the age of 65 years. This disorder may have several causes: heredity, noise, aging, and disease. Hearing loss from noise has been recognized for centuries but was generally ignored until some time after the Industrial Revolution. Hearing loss from occupational exposure to hazardous noise was identified as a compensable disability by the United States courts in 1948 to 1959. Development of noisy jet engines and supersonic aircraft created additional claims for personal and property damage in the 1950s and 1960s. These conditions led to legislation for noise control in the form of the Occupational Safety and Health Act of 1970 and the Noise Control Act of 1972. Protection of the noise-exposed employee was also an objective of the Hearing Conservation Act of 1971. Subsequent studies have confirmed the benefits of periodic hearing tests for workers exposed to hazardous noise and of otologic evaluation as part of the hearing conservation process. Research studies in laboratory animals, using scanning electron microscopical techniques, have demonstrated that damage to the inner ear and organ of hearing can occur even though subjective (conditioned) response to sound stimuli remains unaffected. Some investigators have employed an epidemiologic approach to identify risk factors and to develop profiles to susceptibility to noise-induced hearing loss. The need for joint involvement of workers and employers in the reduction and control of occupational noise hazards is evident. 19 references.

  12. Noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Mariola Sliwinska-Kowalska

    2012-01-01

    Full Text Available Noise-induced hearing loss (NIHL still remains a problem in developed countries, despite reduced occupational noise exposure, strict standards for hearing protection and extensive public health awareness campaigns. Therefore NIHL continues to be the focus of noise research activities. This paper summarizes progress achieved recently in our knowledge of NIHL. It includes papers published between the years 2008-2011 (in English, which were identified by a literature search of accessible medical and other relevant databases. A substantial part of this research has been concerned with the risk of NIHL in the entertainment sector, particularly in professional, orchestral musicians. There are also constant concerns regarding noise exposure and hearing risk in "hard to control" occupations, such as farming and construction work. Although occupational noise has decreased since the early 1980s, the number of young people subject to social noise exposure has tripled. If the exposure limits from the Noise at Work Regulations are applied, discotheque music, rock concerts, as well as music from personal music players are associated with the risk of hearing loss in teenagers and young adults. Several recent research studies have increased the understanding of the pathomechanisms of acoustic trauma, the genetics of NIHL, as well as possible dietary and pharmacologic otoprotection in acoustic trauma. The results of these studies are very promising and offer grounds to expect that targeted therapies might help prevent the loss of sensory hair cells and protect the hearing of noise-exposed individuals. These studies emphasize the need to launch an improved noise exposure policy for hearing protection along with developing more efficient norms of NIHL risk assessment.

  13. Correlations induced by depressing synapses in critically self-organized networks with quenched dynamics.

    Science.gov (United States)

    Campos, João Guilherme Ferreira; Costa, Ariadne de Andrade; Copelli, Mauro; Kinouchi, Osame

    2017-04-01

    In a recent work, mean-field analysis and computer simulations were employed to analyze critical self-organization in networks of excitable cellular automata where randomly chosen synapses in the network were depressed after each spike (the so-called annealed dynamics). Calculations agree with simulations of the annealed version, showing that the nominal branching ratio σ converges to unity in the thermodynamic limit, as expected of a self-organized critical system. However, the question remains whether the same results apply to the biological case where only the synapses of firing neurons are depressed (the so-called quenched dynamics). We show that simulations of the quenched model yield significant deviations from σ=1 due to spatial correlations. However, the model is shown to be critical, as the largest eigenvalue of the synaptic matrix approaches unity in the thermodynamic limit, that is, λ_{c}=1. We also study the finite size effects near the critical state as a function of the parameters of the synaptic dynamics.

  14. Long-term depression-associated signaling is required for an in vitro model of NMDA receptor-dependent synapse pruning.

    Science.gov (United States)

    Henson, Maile A; Tucker, Charles J; Zhao, Meilan; Dudek, Serena M

    2017-02-01

    Activity-dependent pruning of synaptic contacts plays a critical role in shaping neuronal circuitry in response to the environment during postnatal brain development. Although there is compelling evidence that shrinkage of dendritic spines coincides with synaptic long-term depression (LTD), and that LTD is accompanied by synapse loss, whether NMDA receptor (NMDAR)-dependent LTD is a required step in the progression toward synapse pruning is still unknown. Using repeated applications of NMDA to induce LTD in dissociated rat neuronal cultures, we found that synapse density, as measured by colocalization of fluorescent markers for pre- and postsynaptic structures, was decreased irrespective of the presynaptic marker used, post-treatment recovery time, and the dendritic location of synapses. Consistent with previous studies, we found that synapse loss could occur without apparent net spine loss or cell death. Furthermore, synapse loss was unlikely to require direct contact with microglia, as the number of these cells was minimal in our culture preparations. Supporting a model by which NMDAR-LTD is required for synapse loss, the effect of NMDA on fluorescence colocalization was prevented by phosphatase and caspase inhibitors. In addition, gene transcription and protein translation also appeared to be required for loss of putative synapses. These data support the idea that NMDAR-dependent LTD is a required step in synapse pruning and contribute to our understanding of the basic mechanisms of this developmental process. Published by Elsevier Inc.

  15. Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

    Directory of Open Access Journals (Sweden)

    Zilong Gao

    2016-12-01

    Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

  16. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation

    DEFF Research Database (Denmark)

    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano

    2018-01-01

    pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling......Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report...... the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation....

  17. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... Programs Recommendations & Guidelines Free Materials Parent’s Guide Multimedia & Tools My ... Hearing plays an essential role in communication, speech and language development, and learning. Even a small amount of hearing loss can ...

  18. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    Science.gov (United States)

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  19. Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain.

    Directory of Open Access Journals (Sweden)

    Mattu Chetana Shivaraj

    Full Text Available Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5 hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems.

  20. T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.

    Science.gov (United States)

    Barcia, Carlos; Sanderson, Nicholas S R; Barrett, Robert J; Wawrowsky, Kolja; Kroeger, Kurt M; Puntel, Mariana; Liu, Chunyan; Castro, Maria G; Lowenstein, Pedro R

    2008-08-20

    Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown. Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes. Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV infection), anti

  1. T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.

    Directory of Open Access Journals (Sweden)

    Carlos Barcia

    2008-08-01

    Full Text Available Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown.Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes.Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV

  2. Treatment of Noise-Induced Hearing Loss

    National Research Council Canada - National Science Library

    d'Aldin, Gervais

    1999-01-01

    .... Guinea pigs are subjected to an acoustic trauma. The recovery of the noise-induced hearing loss is followed up to 14 days post exposure by electrocochleography and morphologic examination of the cochlea is performed...

  3. Permanent brain ischemia induces marked increments in hsp72 expression and local protein synthesis in synapses of the ischemic hemisphere.

    Science.gov (United States)

    Mariucci, Giuseppina; Tantucci, Michela; Giuditta, Antonio; Ambrosini, Maria Vittoria

    2007-03-19

    Transient focal ischemia induced in rat brain by occlusion of the middle cerebral artery (MCAo) elicits a generalized induction of the 72 kDa heat-shock protein (hsp72) heralding functional recovery. As this effect implies activation of protein synthesis, and local systems of protein synthesis are present in brain synapses, and may be analyzed in preparations of brain synaptosomes, we evaluated hsp72 expression and protein synthesis in synaptosomal fractions of spontaneously hypertensive rats (SHRs) subjected to permanent MCAo. SHRs were randomly divided in ischemics and sham controls, anaesthesia controls and passive controls. Focal ischemia was induced under chloral hydrate anaesthesia by unilateral permanent MCAo. Protein synthesis was determined by [35S]methionine incorporation into synaptosomal proteins from ischemic and contralateral cortex/striatum, and from cerebellum. Hsp72 expression was measured in the same fractions by immunoblotting. Our data demonstrate that under these conditions synaptic hsp72 markedly increases in the ischemic hemisphere 1 and 2 days after MCAo, progressively declining in the following 2 days, while no significant change occurs in control rats. In addition, in the ischemic hemisphere the rate of synaptic protein synthesis increases more than two-fold between 1 and 4 days after MCAo, without showing signs of an impending decline. The present data provide the first demonstration that synaptic protein synthesis is massively involved in brain plastic events elicited by permanent focal ischemia.

  4. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

    Science.gov (United States)

    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

    2018-03-07

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Does erythropoietin augment noise induced hearing loss?

    DEFF Research Database (Denmark)

    Frederiksen, Birgitte Lidegaard; Cayé-Thomasen, Per; Lund, Søren Peter

    2007-01-01

    of EPO upon damage to the central nervous system and the retina. This paper reports three separate trials, conducted to investigate the hypothesis that noise-induced hearing loss is prevented or reduced by erythropoietin. The trials employed three different modes of drug application, different......Noise-induced hearing loss may result from excessive release of glutamate, nitrogen oxide and reactive oxygen species. The effects of these factors on the inner ear may potentially be prevented or reduced by erythropoietin (EPO), as indicated by previously demonstrated neuro-protective effects...... and auditory brainstem responses (at 16kHz) were recorded before and after noise exposure in all trials. The noise exposure induced a hearing loss in all animals. In trial 1, no recovery and no improvement of hearing occurred in any treatment group. In trial 2 and 3, a partial hearing recovery was seen...

  6. A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia

    Science.gov (United States)

    Lee, Sue-Hyun; Kwak, Chuljung; Shim, Jaehoon; Kim, Jung-Eun; Choi, Sun-Lim; Kim, Hyoung F.; Jang, Deok-Jin; Lee, Jin-A; Lee, Kyungmin; Lee, Chi-Hoon; Lee, Young-Don; Miniaci, Maria Concetta; Bailey, Craig H.; Kandel, Eric R.; Kaang, Bong-Kiun

    2012-01-01

    The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia, and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval. PMID:22893682

  7. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression.

    Science.gov (United States)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 10 9 asymmetric synapses, 1.06 × 10 8 symmetric synapses and 1.00 × 10 8 myelinated axons. The density of asymmetric synapses was 5.5/μm 3 and the density of symmetric synapses was 0.5/μm 3 . Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is

  8. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Science.gov (United States)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

  9. 'Ecstasy' enhances noise-induced hearing loss.

    Science.gov (United States)

    Church, Michael W; Zhang, Jinsheng S; Langford, Megan M; Perrine, Shane A

    2013-08-01

    'Ecstasy' or 3,4-methylenedioxy-N-methamphetamine (MDMA) is an amphetamine abused for its euphoric, empathogenic, hallucinatory, and stimulant effects. It is also used to treat certain psychiatric disorders. Common settings for Ecstasy use are nightclubs and "rave" parties where participants consume MDMA and dance to loud music. One concern with the club setting is that exposure to loud sounds can cause permanent sensorineural hearing loss. Another concern is that consumption of MDMA may enhance such hearing loss. Whereas this latter possibility has not been investigated, this study tested the hypothesis that MDMA enhances noise-induced hearing loss (NIHL) by exposing rats to either MDMA, noise trauma, both MDMA and noise, or neither treatment. MDMA was given in a binge pattern of 5 mg/kg per intraperitoneal injections every 2 h for a total of four injections to animals in the two MDMA-treated groups (MDMA-only and Noise + MDMA). Saline injections were given to the animals in the two non-MDMA groups (Control and Noise-only). Following the final injection, noise trauma was induced by a 10 kHz tone at 120 dB SPL for 1 h to animals in the two noise trauma-treated groups (Noise-only and Noise + MDMA). Hearing loss was assessed by the auditory brainstem response (ABR) and cochlear histology. Results showed that MDMA enhanced NIHL compared to Noise-only and that MDMA alone caused no hearing loss. This implies that "clubbers" and "rave-goers" are exacerbating the amount of NIHL when they consume MDMA and listen to loud sounds. In contrast to earlier reports, the present study found that MDMA by itself caused no changes in the click-evoked ABR's wave latencies or amplitudes. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Reduced synapse and axon numbers in the prefrontal cortex of rats subjected to a chronic stress model for depression

    DEFF Research Database (Denmark)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss...... have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected...... to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem...

  11. Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model.

    Science.gov (United States)

    Diniz, Luan Pereira; Tortelli, Vanessa; Matias, Isadora; Morgado, Juliana; Bérgamo Araujo, Ana Paula; Melo, Helen M; Seixas da Silva, Gisele S; Alves-Leon, Soniza V; de Souza, Jorge M; Ferreira, Sergio T; De Felice, Fernanda G; Gomes, Flávia Carvalho Alcantara

    2017-07-12

    Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses against AβOs. By demonstrating that AβOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AβOs in AD. SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-β oligomers (AβOs). Here, we investigated the impact of AβOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by A

  12. Noise Induced Hearing Loss among Khartoum International Airport ...

    African Journals Online (AJOL)

    Background: Noise-induced hearing loss [NIHL] was incriminated to be the second most common sensorineural hearing loss, after age-related hearing loss. Objective: This study aimed to investigate noise induced hearing loss among employees of Khartoum international air port. Material and Methods: The study ...

  13. Defects of the Glycinergic Synapse in Zebrafish

    OpenAIRE

    Ogino, Kazutoyo; Hirata, Hiromi

    2016-01-01

    Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nocicepti...

  14. Leupeptin reduces impulse noise induced hearing loss

    Directory of Open Access Journals (Sweden)

    Gavriel Haim

    2011-12-01

    Full Text Available Abstract Background Exposure to continuous and impulse noise can induce a hearing loss. Leupeptin is an inhibitor of the calpains, a family of calcium-activated proteases which promote cell death. The objective of this study is to assess whether Leupeptin could reduce the hearing loss resulting from rifle impulse noise. Methods A polyethelene tube was implanted into middle ear cavities of eight fat sand rats (16 ears. Following determination of auditory nerve brainstem evoked response (ABR threshold in each ear, the animals were exposed to the noise of 10 M16 rifle shots. Immediately after the exposure, saline was then applied to one (control ear and non-toxic concentrations of leupeptin determined in the first phase of the study were applied to the other ear, for four consecutive days. Results Eight days after the exposure, the threshold shift (ABR in the control ears was significantly greater (44 dB than in the leupeptin ears (27 dB. Conclusion Leupeptin applied to the middle ear cavity can reduce the hearing loss resulting from exposure to impulse noise.

  15. Occupational Noise-induced Hearing Loss

    Directory of Open Access Journals (Sweden)

    MH Azizi

    2010-06-01

    Full Text Available Noise-induced hearing loss (NIHL is a well-known entity in daily practice of otolaryngology. A wide variety of NIHLs are work-related. Occupational noise is the most common cause of NIHL in adults which is up to now considered incurable and the best approach to it is to utilize maximal protection. An effective noise exposure prevention program consists of identification of sources of noise and implementation of controlling measures and regulations at working environments as well as performing periodic audiologic evaluation of those who are working at noisy environments. The present paper, briefly reviews occupational NIHL mainly based on the related data available on PubMed up to early 2010.

  16. The pathogenesis of Noise Induced Hearing Loss

    Directory of Open Access Journals (Sweden)

    Seyyed Abbas Mir Vakili

    1999-03-01

    Full Text Available NIHL occurs when too much sound intensity is transmitted into and through the auditory system and can be occur following a shot gun or the exposure to a moderately intense sound for a long period of time. NIHL caused by acoustic trauma refers to permanent cochlear damage from a one-time exposure to excessive sound pressure. This form of NIHL commonly results from exposure to high-intensity sounds such as explosions, gunfire, a large drum hit loudly and firecrackers. Meanwhile the sound intensity, duration of exposure and personal hearing thresholds as the effective factors in the amount of noise induced hearing loss should not be overlooked.  Since numerous investigations have been performed about intense sudden sound we will discuss it in detail in the current article.

  17. Loss of GPRC5B impairs synapse formation of Purkinje cells with cerebellar nuclear neurons and disrupts cerebellar synaptic plasticity and motor learning.

    Science.gov (United States)

    Sano, Takamitsu; Kohyama-Koganeya, Ayako; Kinoshita, Masami O; Tatsukawa, Tetsuya; Shimizu, Chika; Oshima, Eriko; Yamada, Kazuyuki; Le, Tung Dinh; Akagi, Takumi; Tohyama, Koujiro; Nagao, Soichi; Hirabayashi, Yoshio

    2018-02-23

    GPRC5B is a membrane glycoprotein robustly expressed in mouse cerebellar Purkinje cells (PCs). Its function is unknown. In Gprc5b -/- mice that lack GPRC5B, PCs develop distal axonal swellings in deep cerebellar nuclei (DCN). Numerous misshapen mitochondria, which generated excessive amounts of reactive oxygen species (ROS), accumulated in these distal axonal swellings. In primary cell cultures of Gprc5b -/- PCs, pharmacological reduction of ROS prevented the appearance of such swellings. To examine the physiological role of GPRC5B in PCs, we analyzed cerebellar synaptic transmission and cerebellum-dependent motor learning in Gprc5b -/- mice. Patch-clamp recordings in cerebellum slices in vitro revealed that the induction of long-term depression (LTD) at parallel fiber-PC synapses was normal in adult Gprc5b -/- mice, whereas the induction of long-term potentiation (LTP) at mossy fiber-DCN neuron synapses was attenuated in juvenile Gprc5b -/- mice. In Gprc5b -/- mice, long-term motor learning was impaired in both the rotarod test and the horizontal optokinetic response eye movement (HOKR) test. These observations suggest that GPRC5B plays not only an important role in the development of distal axons of PCs and formation of synapses with DCN neurons, but also in the synaptic plasticity that underlies long-term motor learning. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

  18. Loss of Ca(2+)-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain.

    Science.gov (United States)

    Chen, Yishen; Derkach, Victor A; Smith, Peter A

    2016-05-01

    Synapses transmitting nociceptive information in the spinal dorsal horn undergo enduring changes following peripheral nerve injury. Indeed, such injury alters the expression of the GluA2 subunit of glutamatergic AMPA receptors (AMPARs) in the substantia gelatinosa and this predicts altered channel conductance and calcium permeability, leading to an altered function of excitatory synapses. We therefore investigated the functional properties of synaptic AMPA receptors in rat substantia gelatinosa neurons following 10-20d chronic constriction injury (CCI) of the sciatic nerve; a model of neuropathic pain. We measured their single-channel conductance and sensitivity to a blocker of calcium permeable AMPA receptors (CP-AMPARs), IEM1460 (50μM). In putative inhibitory, tonic firing neurons, CCI reduced the average single-channel conductance of synaptic AMPAR from 14.4±3.5pS (n=12) to 9.2±1.0pS (n=10, pinjury acting at synapses of inhibitory neurons to reduce their drive and therefore inhibitory tone in the spinal cord, therefore contributing to the central sensitization associated with neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The immunological synapse

    DEFF Research Database (Denmark)

    Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten

    2003-01-01

    . A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...

  20. CNS Neurons Deposit Laminin α5 to Stabilize Synapses

    Directory of Open Access Journals (Sweden)

    Mitchell H. Omar

    2017-10-01

    Full Text Available Summary: Synapses in the developing brain are structurally dynamic but become stable by early adulthood. We demonstrate here that an α5-subunit-containing laminin stabilizes synapses during this developmental transition. Hippocampal neurons deposit laminin α5 at synapses during adolescence as connections stabilize. Disruption of laminin α5 in neurons causes dramatic fluctuations in dendritic spine head size that can be rescued by exogenous α5-containing laminin. Conditional deletion of laminin α5 in vivo increases dendritic spine size and leads to an age-dependent loss of synapses accompanied by behavioral defects. Remaining synapses have larger postsynaptic densities and enhanced neurotransmission. Finally, we provide evidence that laminin α5 acts through an integrin α3β1-Abl2 kinase-p190RhoGAP signaling cascade and partners with laminin β2 to regulate dendritic spine density and behavior. Together, our results identify laminin α5 as a stabilizer of dendritic spines and synapses in the brain and elucidate key cellular and molecular mechanisms by which it acts. : In the developing brain, synaptic structure transitions from dynamic to stable by early adulthood. Omar et al. identify a laminin molecule deposited at synapses in the brain that is essential for dendritic spine structural regulation and synapse stability between early postnatal development and adulthood. Keywords: extracellular matrix, ECM, synapse maturation, adhesion, Lama5, Lamb2, synapse loss, stability, structural plasticity, motility

  1. Noise-induced and age-related hearing loss:  new perspectives and potential therapies [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    M Charles Liberman

    2017-06-01

    Full Text Available The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1 the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2 the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

  2. The space where aging acts: focus on the GABAergic synapse.

    Science.gov (United States)

    Rozycka, Aleksandra; Liguz-Lecznar, Monika

    2017-08-01

    As it was established that aging is not associated with massive neuronal loss, as was believed in the mid-20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging-related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging-related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging-induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Ventricular tachycardia induced by weight loss pills

    DEFF Research Database (Denmark)

    Pareek, Manan; Hansson, Nils Henrik; Grove, Erik Lerkevang

    2013-01-01

    A previously healthy 29-year-old man was admitted with palpitations, dizziness, and near-syncope after he had recently started taking weight loss pills purchased on the internet. The pills contained caffeine and ephedrine. An electrocardiogram and telemetry revealed multiple episodes of non......-sustained monomorphic ventricular tachycardia, which was successfully treated with amiodarone. In conclusion, unauthorized weight loss pills can be harmful. In particular, ephedrine-containing drugs carry a risk of ventricular tachycardia and should be discouraged....

  4. Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.

    Science.gov (United States)

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Wenyue; Yang, Jun

    2016-05-01

    Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin.

  5. Adsorption induced losses in interfacial cohesion

    International Nuclear Information System (INIS)

    Asaro, R.J.

    1977-07-01

    A model for interfacial cohesion is developed which describes the loss in the strength of an interface due to the segregation and adsorption of impurities on it. Distinctions are made between interface separations that occur too rapidly for any significant redistribution of adsorbing matter to take place and separations that are slow enough to allow full adsorption equilibrium. Expressions for the total work of complete decohesion are presented for both cases. The results are applied to well-known model adsorption isotherms and some experimental data for grain boundary adsorption of phosphorus in iron is analyzed with respect to the losses in intergranular cohesion

  6. Analysis of beam loss induced abort kicker instability

    Energy Technology Data Exchange (ETDEWEB)

    Zhang W.; Sandberg, J.; Ahrens, L.; Fischer, W.; Hahn, H.; Mi, J.; Pai, C.; Tan, Y.

    2012-05-20

    Through more than a decade of operation, we have noticed the phenomena of beam loss induced kicker instability in the RHIC beam abort systems. In this study, we analyze the short term beam loss before abort kicker pre-fire events and operation conditions before capacitor failures. Beam loss has caused capacitor failures and elevated radiation level concentrated at failed end of capacitor has been observed. We are interested in beam loss induced radiation and heat dissipation in large oil filled capacitors and beam triggered thyratron conduction. We hope the analysis result would lead to better protection of the abort systems and improved stability of the RHIC operation.

  7. A bionics chemical synapse.

    Science.gov (United States)

    Thanapitak, Surachoke; Toumazou, Christofer

    2013-06-01

    Implementation of the current mode CMOS circuit for chemical synapses (AMPA and NMDA receptors) with dynamic change of glutamate as the neurotransmitter input is presented in this paper. Additionally, circuit realisation for receptor GABA(A) and GABA(B) with an electrical signal which symbolises γ-Aminobutyric Acid (GABA) perturbation is introduced. The chemical sensor for glutamate sensing is the modified ISFET with enzyme (glutamate oxidase) immobilisation. The measured results from these biomimetics chemical synapse circuits closely match with the simulation result from the mathematical model. The total power consumption of the whole chip (four chemical synapse circuits and all auxiliary circuits) is 168.3 μW. The total chip area is 3 mm(2) in 0.35-μm AMS CMOS technology.

  8. A lack of immune system genes causes loss in high frequency hearing but does not disrupt cochlear synapse maturation in mice.

    Science.gov (United States)

    Calton, Melissa A; Lee, Dasom; Sundaresan, Srividya; Mendus, Diana; Leu, Rose; Wangsawihardja, Felix; Johnson, Kenneth R; Mustapha, Mirna

    2014-01-01

    Early cochlear development is marked by an exuberant outgrowth of neurites that innervate multiple targets. The establishment of mature cochlear neural circuits is, however, dependent on the pruning of inappropriate axons and synaptic connections. Such refinement also occurs in the central nervous system (CNS), and recently, genes ordinarily associated with immune and inflammatory processes have been shown to play roles in synaptic pruning in the brain. These molecules include the major histocompatibility complex class I (MHCI) genes, H2-K(b) and H2-D(b), and the complement cascade gene, C1qa. Since the mechanisms involved in synaptic refinement in the cochlea are not well understood, we investigated whether these immune system genes may be involved in this process and whether they are required for normal hearing function. Here we report that these genes are not necessary for normal synapse formation and refinement in the mouse cochlea. We further demonstrate that C1qa expression is not necessary for normal hearing in mice but the lack of expression of H2-K(b) and H2-D(b) causes hearing impairment. These data underscore the importance of the highly polymorphic family of MHCI genes in hearing in mice and also suggest that factors and mechanisms regulating synaptic refinement in the cochlea may be distinct from those in the CNS.

  9. SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

    Directory of Open Access Journals (Sweden)

    Lucas Matt

    2018-02-01

    Full Text Available Altering AMPA receptor (AMPAR content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1 encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1 modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP, while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity.

  10. Drug Induced Hearing Loss: Researchers Study Strategies to Preserve Hearing

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Drug-Induced Hearing Loss Researchers Study Strategies to Preserve ... brain there was a sound. What are ototoxic drugs and why are they important? Ototoxic drugs are ...

  11. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    Science.gov (United States)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeff; Shapiro, Jay; Lang, Tom; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; hide

    2011-01-01

    Experiment Hypothesis -- The combined effect of anti-resorptive drugs plus in-flight exercise regimen will have a measurable effect in preventing space flight induced bone mass and strength loss and reducing renal stone risk.

  12. Characteristics of noise induced hearing loss in gold miners: research

    African Journals Online (AJOL)

    The characteristics of Noise Induced Hearing Loss (NIHL) in gold miners of different ages and occupation types were examined and the incidence of tinnitus, vertigo/balance problems and nausea were determined. The results indicate that as a group these subjects had symmetrical bilateral, mild hearing loss in the ...

  13. Prevalence of noise induced hearing loss among employees at a ...

    African Journals Online (AJOL)

    Background: Noise induced hearing loss (NIHL) is within the top five occupational illnesses in Zimbabwe. Workers at a mining company complained about loss of hearing at the mine clinic. Objective: To determine the prevalence of NIHL among employees at the Mine. Methods: We conducted a descriptive cross sectional ...

  14. Mobile phone induced sensorineural hearing loss

    International Nuclear Information System (INIS)

    Al-Dousary, Surayie H.

    2007-01-01

    The increased use of mobile phones worldwide has focused interest on the biological effects and possible health outcomes of exposure to radiofrequency fields from mobile phones, and their base stations. Various reports suggest that mobile phone use can cause health problems like fatigue, headache, dizziness, tension and sleep disturbances, however, only limited research data is available in medical literature regarding interaction between electromagnetic fields emitted by mobile phones and auditory function and the possible impact on hearing. We report a case of sensorineural hearing loss due to Global System for Mobile Communication mobile phone use in a 42-year-old male. (author)

  15. Radiation induced ligand loss from cobalt complexes

    International Nuclear Information System (INIS)

    Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

    2000-01-01

    Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

  16. Massive weight loss-induced mechanical plasticity in obese gait

    NARCIS (Netherlands)

    Hortobagyi, Tibor; Herring, Cortney; Pories, Walter J.; Rider, Patrick; DeVita, Paul

    2011-01-01

    Hortobagyi T, Herring C, Pories WJ, Rider P, DeVita P. Massive weight loss-induced mechanical plasticity in obese gait. J Appl Physiol 111: 1391-1399, 2011. First published August 18, 2011; doi:10.1152/japplphysiol.00291.2011.-We examined the hypothesis that metabolic surgery-induced massive weight

  17. Recruitment of dynein to the Jurkat immunological synapse

    Science.gov (United States)

    Combs, Jeffrey; Kim, Soo Jin; Tan, Sarah; Ligon, Lee A.; Holzbaur, Erika L. F.; Kuhn, Jeffrey; Poenie, Martin

    2006-10-01

    Binding of T cells to antigen-presenting cells leads to the formation of the immunological synapse, translocation of the microtubule-organizing center (MTOC) to the synapse, and focused secretion of effector molecules. Here, we show that upon activation of Jurkat cells microtubules project from the MTOC to a ring of the scaffolding protein ADAP, localized at the synapse. Loss of ADAP, but not lymphocyte function-associated antigen 1, leads to a severe defect in MTOC polarization at the immunological synapse. The microtubule motor protein cytoplasmic dynein clusters into a ring at the synapse, colocalizing with the ADAP ring. ADAP coprecipitates with dynein from activated Jurkat cells, and loss of ADAP prevents MTOC translocation and the specific recruitment of dynein to the synapse. These results suggest a mechanism that links signaling through the T cell receptor to translocation of the MTOC, in which the minus end-directed motor cytoplasmic dynein, localized at the synapse through an interaction with ADAP, reels in the MTOC, allowing for directed secretion along the polarized microtubule cytoskeleton. microtubules | T cell polarization | -catenin | PLAC-24

  18. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Wood Richard J

    2006-05-01

    Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

  19. Loss of Ethanol Inhibition of N-Methyl-D-Aspartate Receptor-Mediated Currents and Plasticity of Cerebellar Synapses in Mice Expressing the GluN1(F639A) Subunit.

    Science.gov (United States)

    Zamudio-Bulcock, Paula A; Homanics, Gregg E; Woodward, John J

    2018-01-11

    Glutamatergic N-methyl-d-aspartate receptors (NMDARs) are well known for their sensitivity to ethanol (EtOH) inhibition. However, the specific manner in which EtOH inhibits channel activity and how such inhibition affects neurotransmission, and ultimately behavior, remains unclear. Replacement of phenylalanine 639 with alanine (F639A) in the GluN1 subunit reduces EtOH inhibition of recombinant NMDARs. Mice expressing this subunit show reduced EtOH-induced anxiolysis, blunted locomotor stimulation following low-dose EtOH administration, and faster recovery of motor function after moderate doses of EtOH, suggesting that cerebellar dysfunction may contribute to some of these behaviors. In the mature mouse cerebellum, NMDARs at the cerebellar climbing fiber (CF) to Purkinje cell (PC) synapse are inhibited by low concentrations of EtOH and the long-term depression (LTD) of parallel fiber (PF)-mediated currents induced by concurrent activation of PFs and CFs (PF-LTD) requires activation of EtOH-sensitive NMDARs. In this study, we examined cerebellar NMDA responses and NMDA-mediated synaptic plasticity in wild-type (WT) and GluN1(F639A) mice. Patch-clamp electrophysiological recordings were performed in acute cerebellar slices from adult WT and GluN1(F639A) mice. NMDAR-mediated currents at the CF-PC synapse and NMDAR-dependent PF-LTD induction were compared for genotype-dependent differences. Stimulation of CFs evoked robust NMDA-mediated excitatory postsynaptic currents (EPSCs) in PCs that were similar in amplitude and kinetics between WT and GluN1(F639A) mice. NMDA-mediated CF-PC EPSCs in WT mice were significantly inhibited by EtOH (50 mM) while those in mutant mice were unaffected. Concurrent stimulation of CF and PF inputs induced synaptic depression of PF-PC EPSCs in both WT and mutant mice, and this depression was blocked by the NMDA antagonist DL-APV. The synaptic depression of PF-PC EPSCs in WT mice was also blocked by a low concentration of EtOH (10 mM) that had

  20. Defects of the Glycinergic Synapse in Zebrafish

    Science.gov (United States)

    Ogino, Kazutoyo; Hirata, Hiromi

    2016-01-01

    Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nociceptive processing. The importance of the glycinergic synapse is conserved across vertebrate species. A teleost fish, the zebrafish, offers several advantages as a vertebrate model for research of glycinergic synapse. Mutagenesis screens in zebrafish have isolated two motor defective mutants that have pathogenic mutations in glycinergic synaptic transmission: bandoneon (beo) and shocked (sho). Beo mutants have a loss-of-function mutation of glycine receptor (GlyR) β-subunit b, alternatively, sho mutant is a glycinergic transporter 1 (GlyT1) defective mutant. These mutants are useful animal models for understanding of glycinergic synaptic transmission and for identification of novel therapeutic agents for human diseases arising from defect in glycinergic transmission, such as hyperekplexia or glycine encephalopathy. Recent advances in techniques for genome editing and for imaging and manipulating of a molecule or a physiological process make zebrafish more attractive model. In this review, we describe the glycinergic defective zebrafish mutants and the technical advances in both forward and reverse genetic approaches as well as in vivo visualization and manipulation approaches for the study of the glycinergic synapse in zebrafish. PMID:27445686

  1. IL4-induced gene 1 is secreted at the immune synapse and modulates TCR activation independently of its enzymatic activity.

    Science.gov (United States)

    Aubatin, Aude; Sako, Nouhoum; Decrouy, Xavier; Donnadieu, Emmanuel; Molinier-Frenkel, Valérie; Castellano, Flavia

    2018-01-01

    Amino-acid catabolizing enzymes produced by mononuclear phagocytes play a central role in regulating the immune response. The mammalian phenylalanine-catabolizing enzyme IL4-induced gene 1 (IL4I1) inhibits effector T lymphocyte proliferation and facilitates regulatory T-cell development. IL4I1 expression by macrophages of various human tumors may affect patient prognosis as it facilitates tumor escape from the T-cell response in murine models. Its enzymatic activity appears to participate in its effects, but some actions of IL4I1 remain unclear. Here, we show that the presence of IL4I1 during T-cell activation decreases early signaling events downstream of TCR stimulation, resulting in global T-cell inhibition which is more pronounced when there is CD28 costimulation. Surprisingly, the enzymatic activity of IL4I1 is not involved. Focal secretion of IL4I1 into the immune synaptic cleft and its binding to CD3 + lymphocytes could be important in IL4I1 immunosuppressive mechanism of action. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

    Science.gov (United States)

    Zamberletti, Erica; Gabaglio, Marina; Grilli, Massimo; Prini, Pamela; Catanese, Alberto; Pittaluga, Anna; Marchi, Mario; Rubino, Tiziana; Parolaro, Daniela

    2016-09-01

    Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its

  3. Dendrobium alkaloids prevent Aβ25–35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice

    Directory of Open Access Journals (Sweden)

    Jing Nie

    2016-12-01

    Full Text Available Background Neuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer’s disease (AD. In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA, a Chinese medicinal herb extract, on β-amyloid peptide segment 25–35 (Aβ25-35-induced neuron and synaptic loss in mice. Method Aβ25–35(10 µg was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF, glial cell line-derived neurotrophic factor (GDNF, and brain-derived neurotrophic factor (BDNF in the hippocampus and cortex. Results DNLA significantly attenuated Aβ25–35-induced spatial learning and memory impairments in mice. DNLA prevented Aβ25–35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex. Conclusions DNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aβ-induced spatial learning and memory impairment in mice.

  4. Glucocorticoid: A potential role in microgravity-induced bone loss

    Science.gov (United States)

    Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

    2017-11-01

    Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

  5. Welding-fume-induced transmission loss in tapered optical fibers

    Science.gov (United States)

    Yi, Ji-Haeng

    2015-09-01

    This paper presents a method for sensing welding fumes in real time. This method is based on the results of nanoparticle-induced optical-fiber loss experiments that show that the losses are determined by the nanoparticle density and the taper waist. The tapered fiber is obtained by applying heat radiated from hot quartz, and monitoring is done in real time. First, the durability of the tapered fiber during the welding process is proven. Then, the loss is categorized by using the sizes of welding fume particles. The sensitivity to welding fumes increases with increasing size of the particles; consequently, the dimension of the taper waist decreases.

  6. Localization of mineralocorticoid receptors at mammalian synapses.

    Directory of Open Access Journals (Sweden)

    Eric M Prager

    Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

  7. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    Science.gov (United States)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; hide

    2009-01-01

    Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.

  8. prevalence and awareness of noise induced hearing loss in two ...

    African Journals Online (AJOL)

    Global Journal

    Noise above a certain acceptable level or sustained noise may cause damage to the ears. The aim of this study is to determine the prevalence and level of awareness of noise induced hearing loss in Calabar. Seventy-five workers from two noise producing companies, in Calabar- Flour mill and Wartsilla were chosen for this ...

  9. Occupational noise-induced hearing loss among workers at Jomo ...

    African Journals Online (AJOL)

    Background: Occupational noise induced hearing loss (NIHL) occurs among workers exposed to excessive amounts of noise for long durations. The average level of noise in some locations at Jomo Kenyatta International Airport (JKIA) was above the safe limit of 85dB hence workers were thought to be at risk. Objective: To ...

  10. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

    Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A

    2003-01-01

    Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response...

  11. The noise-induced hearing loss milestones: past and future

    CSIR Research Space (South Africa)

    Edwards, AL

    2012-10-01

    Full Text Available At the 2003 Mine Health and Safety Summit, the milestones for elimination of Noise-induced Hearing Loss (NIHL) in the mining industry were agreed on. The first milestone, December 2008, has passed and the next one in 2013 is looming. The study...

  12. Noise-induced hearing loss milestones: Past and future

    CSIR Research Space (South Africa)

    Edwards, A

    2011-01-01

    Full Text Available At the 2003 Mine Health and Safety Summit, the milestones for elimination of Noise-induced Hearing Loss (NIHL) in the mining industry were agreed on. The first milestone, December 2008, has passed and the next one in 2013 is looming. The study...

  13. Prevalence of noise induced hearing loss in textile industries in ...

    African Journals Online (AJOL)

    This cross sectional study measured the prevalence of Noise Induced Hearing Loss (NIHL) in textile industries in Dar Es Salaam city and Morogoro municipality. Data were collected from 125 employees randomly selected from each of the textile factory mill in each region through structured questionnaires and audiogram ...

  14. Prevalence and awareness of noise induced hearing loss in two ...

    African Journals Online (AJOL)

    Noise above a certain acceptable level or sustained noise may cause damage to the ears. The aim of this study is to determine the prevalence and level of awareness of noise induced hearing loss in Calabar. Seventy-five workers from two noise producing companies, in Calabar- Flour mill and Wartsilla were chosen for this ...

  15. The sticky synapse

    DEFF Research Database (Denmark)

    Owczarek, Sylwia Elzbieta; Kristiansen, Lars Villiam; Hortsch, Michael

    NCAM-type proteins modulate multiple neuronal functions, including the outgrowth and guidance of neurites, the formation, maturation, and plasticity of synapses, and the induction of both long-term potentiation and long-term depression. The ectodomains of NCAM proteins have a basic structure...... signal transduction. A central feature of the synaptic function of NCAM proteins is the regulation of their extracellular interactions by adhesion-modulating glycoepitopes, their removal from the cell surface by endocytosis, and the elimination of their adhesion-mediating interactions by the proteolytic...

  16. Major rapid weight loss induces changes in cardiac repolarization

    DEFF Research Database (Denmark)

    Vedel-Larsen, Esben; Iepsen, Eva Pers Winning; Lundgren, Julie

    2016-01-01

    INTRODUCTION: Obesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology...... analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. METHODS AND RESULTS: Twenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss......A1c (pweight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight...

  17. Prevalence of occupational noise induced hearing loss amongst traffic police personnel

    OpenAIRE

    Singh, V K; Mehta, A K

    1999-01-01

    Traffic branch personnel of Pune traffic police were screened for presence of noise induced hearing loss. A very significant number (81.2%) showed sensorineural hearing loss. The various factors responsible for noise induced hearing loss are discussed.

  18. Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss.

    Science.gov (United States)

    Zhang, Yong; Guan, Hanfeng; Li, Jing; Fang, Zhong; Chen, Wenjian; Li, Feng

    2015-09-04

    The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis.

  19. Frequency loss induced quench protection system for high temperature superconductors

    Science.gov (United States)

    Ijagbemi, K.; Noyes, P.; Stiers, E.; Pamidi, S.

    2017-12-01

    A novel circuit design for Frequency Loss Induced Quench (FLIQ) protection system for safely driving REBCO coated conductor superconducting coils to quench is reported. The details of the H-bridge circuit design with Insulated Gate Bipolar Transistor (IGBT)s and the various elements used to build a prototype are reported. The results of a successful test of the circuit conducted to demonstrate the validity of the circuit design is presented.

  20. Controlling Mitochondrial Dynamics to Mitigate Noise-Induced Hearing Loss

    Science.gov (United States)

    2017-10-01

    the inner ear resulting from a single acute sound exposure. 15. SUBJECT TERMS Noise induced hearing loss, mitochondria, reactive oxygen species...application for a single loud sound exposure. Dates: 02/15/2016 – 08/14/2016 C. Major Task 3: Identify effective dosing regimen for intraperitoneal mdivi-1...ear canal mdivi-1 application for a single loud sound exposure. We have continued to make progress towards the completion of this Task that involves

  1. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  2. Silent Synapse-Based Circuitry Remodeling in Drug Addiction.

    Science.gov (United States)

    Dong, Yan

    2016-05-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  3. Ozone Induced Premature Mortality and Crop Yield Loss in China

    Science.gov (United States)

    Lin, Y.; Jiang, F.; Wang, H.

    2017-12-01

    Exposure to ambient ozone is a major risk factor for health impacts such as chronic obstructive pulmonary disease (COPD) and cause damage to plant and agricultural crops. But these impacts were usually evaluated separately in earlier studies. We apply Community Multi-scale Air Quality model to simulate the ambient O3 concentration at a resolution of 36 km×36 km across China. Then, we follow Global Burden of Diseases approach and AOT40 (i.e., above a threshold of 40 ppb) metric to estimate the premature mortalities and yield losses of major grain crops (i.e., winter wheat, rice and corn) across China due to surface ozone exposure, respectively. Our results show that ozone exposure leads to nearly 67,700 premature mortalities and 145 billion USD losses in 2014. The ozone induced yield losses of all crop production totaled 78 (49.9-112.6)million metric tons, worth 5.3 (3.4-7.6)billion USD, in China. The relative yield losses ranged from 8.5-14% for winter wheat, 3.9-15% for rice, and 2.2-5.5% for maize. We can see that the top four health affected provinces (Sichuan, Henan, Shandong, Jiangsu) are also ranking on the winter wheat and rice crop yield loss. Our results provide further evidence that surface ozone pollution is becoming urgent air pollution in China, and have important policy implications for China to alleviate the impacts of air pollution.

  4. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    Full Text Available The gut microbiota (GM modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L strain, L. paracasei DSM13434 (L. para or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  5. ‘Ecstasy’ Enhances Noise-Induced Hearing Loss

    Science.gov (United States)

    Church, Michael W.; Zhang, Jinsheng S.; Langford, Megan M.; Perrine, Shane A.

    2013-01-01

    ‘Ecstasy’ or 3,4-methylenedioxy-N-methamphetamine (MDMA) is an amphetamine abused for its euphoric, empathogenic, hallucinatory, and stimulant effects. It is also used to treat certain psychiatric disorders. Common settings for Ecstasy use are nightclubs and “rave” parties where participants consume MDMA and dance to loud music. One concern with the club setting is that exposure to loud sounds can cause permanent sensorineural hearing loss. Another concern is that consumption of MDMA may enhance such hearing loss. Whereas this latter possibility has not been investigated, this study tested the hypothesis that MDMA enhances noise-induced hearing loss (NIHL) by exposing rats to either MDMA, noise trauma, both MDMA and noise, or neither treatment. MDMA was given in a binge pattern of 5 mg/kg per intraperitoneal injections every 2 h for a total of four injections to animals in the two MDMA-treated groups (MDMA-only and Noise+MDMA). Saline injections were given to the animals in the two non-MDMA groups (Control and Noise-only). Following the final injection, noise trauma was induced by a 10 kHz tone at 120 dB SPL for 1 h to animals in the two noise trauma-treated groups (Noise-only and Noise+MDMA). Hearing loss was assessed by the auditory brainstem response (ABR) and cochlear histology. Results showed that MDMA enhanced NIHL compared to Noise-only and that MDMA alone caused no hearing loss. This implies that “clubbers” and “rave-goers” are exacerbating the amount of NIHL when they consume MDMA and listen to loud sounds. In contrast to earlier reports, the present study found that MDMA by itself caused no changes in the click-evoked ABR’s wave latencies or amplitudes. PMID:23711768

  6. ICRH induced particle losses in Wendelstein 7-X

    Science.gov (United States)

    Faustin, J. M.; Cooper, W. A.; Graves, J. P.; Pfefferlé, D.; Geiger, J.

    2016-07-01

    Fast ions in W7-X will be produced either by neutral beam injection (NBI) or by ion-cyclotron resonant heating (ICRH). The latter presents the advantage of depositing power locally and does not suffer from core accessibility issues (Drevlak et al 2014 Nucl. Fusion 54 073002). This work assesses the possibility of using ICRH as a fast ion source in W7-X relevant conditions. The SCENIC package is used to resolve the full wave propagation and absorption in a three-dimensional plasma equilibrium. The source of the ion-cyclotron range of frequency (ICRF) wave is modelled in this work by an antenna formulation allowing its localisation in both the poloidal and toroidal directions. The actual antenna dimension and localization is therefore approximated with good agreement. The local wave deposition breaks the five-fold periodicity of W7-X. It appears that generation of fast ions is hindered by high collisionality and significant particle losses. The particle trapping mechanism induced by ICRH is found to enhance drift induced losses caused by the finite orbit width of trapped particles. The inclusion of a neoclassically resolved radial electric field is also investigated and shows a significant reduction of particle losses.

  7. Novel Radiomitigator for Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

    2016-01-01

    Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

  8. Witnessing stressful events induces glutamatergic synapse pathway alterations and gene set enrichment of positive EPSP regulation within the VTA of adult mice: An ontology based approach

    Science.gov (United States)

    Brewer, Jacob S.

    It is well known that exposure to severe stress increases the risk for developing mood disorders. Currently, the neurobiological and genetic mechanisms underlying the functional effects of psychological stress are poorly understood. Presenting a major obstacle to the study of psychological stress is the inability of current animal models of stress to distinguish between physical and psychological stressors. A novel paradigm recently developed by Warren et al., is able to tease apart the effects of physical and psychological stress in adult mice by allowing these mice to "witness," the social defeat of another mouse thus removing confounding variables associated with physical stressors. Using this 'witness' model of stress and RNA-Seq technology, the current study aims to study the genetic effects of psychological stress. After, witnessing the social defeat of another mouse, VTA tissue was extracted, sequenced, and analyzed for differential expression. Since genes often work together in complex networks, a pathway and gene ontology (GO) analysis was performed using data from the differential expression analysis. The pathway and GO analyzes revealed a perturbation of the glutamatergic synapse pathway and an enrichment of positive excitatory post-synaptic potential regulation. This is consistent with the excitatory synapse theory of depression. Together these findings demonstrate a dysregulation of the mesolimbic reward pathway at the gene level as a result of psychological stress potentially contributing to depressive like behaviors.

  9. Effects of curcumin on synapses in APPswe/PS1dE9 mice.

    Science.gov (United States)

    He, Yingkun; Wang, Pengwen; Wei, Peng; Feng, Huili; Ren, Ying; Yang, Jinduo; Rao, Yingxue; Shi, Jing; Tian, Jinzhou

    2016-06-01

    Significant losses of synapses have been demonstrated in studies of Alzheimer's disease (AD), but structural and functional changes in synapses that depend on alterations of the postsynaptic density (PSD) area occur prior to synaptic loss and play a crucial role in the pathology of AD. Evidence suggests that curcumin can ameliorate the learning and memory deficits of AD. To investigate the effects of curcumin on synapses, APPswe/PS1dE9 double transgenic mice (an AD model) were used, and the ultra-structures of synapses and synapse-associated proteins were observed. Six months after administration, few abnormal synapses were observed upon electron microscopy in the hippocampal CA1 areas of the APPswe/PS1dE9 double transgenic mice. The treatment of the mice with curcumin resulted in improvements in the quantity and structure of the synapses. Immunohistochemistry and western blot analyses revealed that the expressions of PSD95 and Shank1 were reduced in the hippocampal CA1 areas of the APPswe/PS1dE9 double transgenic mice, but curcumin treatment increased the expressions of these proteins. Our findings suggest that curcumin improved the structure and function of the synapses by regulating the synapse-related proteins PSD95 and Shank1. © The Author(s) 2016.

  10. Diversity of Spine Synapses in Animals

    Science.gov (United States)

    Wang, Ya-Xian; Mattson, Mark P.; Yao, Pamela J.

    2016-01-01

    Here we examine the structure of the various types of spine synapses throughout the animal kingdom. Based on available evidence, we suggest that there are two major categories of spine synapses: invaginating and non-invaginating, with distributions that vary among different groups of animals. In the simplest living animals with definitive nerve cells and synapses, the cnidarians and ctenophores, most chemical synapses do not form spine synapses. But some cnidarians have invaginating spine synapses, especially in photoreceptor terminals of motile cnidarians with highly complex visual organs, and also in some mainly sessile cnidarians with rapid prey capture reflexes. This association of invaginating spine synapses with complex sensory inputs is retained in the evolution of higher animals in photoreceptor terminals and some mechanoreceptor synapses. In contrast to invaginating spine synapse, non-invaginating spine synapses have been described only in animals with bilateral symmetry, heads and brains, associated with greater complexity in neural connections. This is apparent already in the simplest bilaterians, the flatworms, which can have well-developed non-invaginating spine synapses in some cases. Non-invaginating spine synapses diversify in higher animal groups. We also discuss the functional advantages of having synapses on spines and more specifically, on invaginating spines. And finally we discuss pathologies associated with spine synapses, concentrating on those systems and diseases where invaginating spine synapses are involved. PMID:27230661

  11. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study

    DEFF Research Database (Denmark)

    Popov, Victor I; Medvedev, Nikolay I; Kraev, Igor V

    2008-01-01

    The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15-amino-acid-long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function...... through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22-month-old) rats that were injected subcutaneously (8 mg/kg) at 2-day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains...... structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes....

  12. First experience with the new Coupling Loss Induced Quench system

    CERN Document Server

    Ravaioli, E; Dudarev, A V; Kirby, G; Sperin, K A; ten Kate, H H J; Verweij, A P

    2014-01-01

    New-generation high-field superconducting magnets pose a challenge relating to the protection of the coil winding pack in the case of a quench. The high stored energy per unit volume calls for a very efficient quench detection and fast quench propagation in order to avoid damage due to overheating. A new protection system called Coupling-Loss Induced Quench (CLIQ) was recently, developed and tested at CERN. This method provokes a fast change in the magnet transport current by means of a capacitive discharge. The resulting change in the local magnetic field induces inter-filament and inter-strand coupling losses which heat up the superconductor and eventually initiate a quench in a large fraction of the coil winding pack. The method is extensively tested on a Nb-Ti single-wire test solenoid magnet in the CERN Cryogenic Laboratory in order to assess its performance, optimize its operating parameters, and study new electrical configurations. Each parameter is thoroughly analyzed and its impact on the quench effi...

  13. Noise-induced hearing loss: an occupational medicine perspective.

    Science.gov (United States)

    Stucken, Emily Z; Hong, Robert S

    2014-10-01

    Up to 30 million workers in the United States are exposed to potentially detrimental levels of noise. Although reliable medications for minimizing or reversing noise-induced hearing loss (NIHL) are not currently available, NIHL is entirely preventable. The purpose of this article is to review the epidemiology and pathophysiology of occupational NIHL. We will focus on at-risk populations and discuss prevention programs. Current prevention programs focus on reducing inner ear damage by minimizing environmental noise production and through the use of personal hearing protective devices. NIHL is the result of a complex interaction between environmental factors and patient factors, both genetic and acquired. The effects of noise exposure are specific to an individual. Trials are currently underway evaluating the role of antioxidants in protection from, and even reversal of, NIHL. Occupational NIHL is the most prevalent occupational disease in the United States. Occupational noise exposures may contribute to temporary or permanent threshold shifts, although even temporary threshold shifts may predispose an individual to eventual permanent hearing loss. Noise prevention programs are paramount in reducing hearing loss as a result of occupational exposures.

  14. Effects of Dietary Induced Weight Loss on Exercise-Induced Bronchoconstriction in Overweight and Obese Children

    NARCIS (Netherlands)

    van Leeuwen, Janneke C.; Hoogstrate, Mira; Duiverman, Eric J.; Thio, Boony J.

    2014-01-01

    RationalePrevious studies showed that obesity in asthmatic children is associated with more severe exercise-induced bronchoconstriction (EIB), compared with non-obese asthmatic children. This study investigates the effect of weight loss on EIB in overweight and obese asthmatic children. MethodsIn

  15. Synapse Pathology in Psychiatric and Neurologic Disease

    NARCIS (Netherlands)

    M. van Spronsen (Myrrhe); C.C. Hoogenraad (Casper)

    2010-01-01

    textabstractInhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical

  16. Loss of cannabinoid receptor CB1 induces preterm birth.

    Directory of Open Access Journals (Sweden)

    Haibin Wang

    2008-10-01

    Full Text Available Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in

  17. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    Science.gov (United States)

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Invaginating Structures in Mammalian Synapses

    Science.gov (United States)

    Petralia, Ronald S.; Wang, Ya-Xian; Mattson, Mark P.; Yao, Pamela J.

    2018-01-01

    Invaginating structures at chemical synapses in the mammalian nervous system exist in presynaptic axon terminals, postsynaptic spines or dendrites, and glial processes. These invaginating structures can be divided into three categories. The first category includes slender protrusions invaginating into axonal terminals, postsynaptic spines, or glial processes. Best known examples of this category are spinules extending from postsynaptic spines into presynaptic terminals in forebrain synapses. Another example of this category are protrusions from inhibitory presynaptic terminals invaginating into postsynaptic neuronal somas. Regardless of the direction and location, the invaginating structures of the first category do not have synaptic active zones within the invagination. The second category includes postsynaptic spines invaginating into presynaptic terminals, whereas the third category includes presynaptic terminals invaginating into postsynaptic spines or dendrites. Unlike the first category, the second and third categories have active zones within the invagination. An example of the second category are mossy terminal synapses of the hippocampal CA3 region, in which enlarged spine-like structures invaginate partly or entirely into mossy terminals. An example of the third category is the neuromuscular junction (NMJ) where substantial invaginations of the presynaptic terminals invaginate into the muscle fibers. In the retina, rod and cone synapses have invaginating processes from horizontal and bipolar cells. Because horizontal cells act both as post and presynaptic structures, their invaginating processes represent both the second and third category. These invaginating structures likely play broad yet specialized roles in modulating neuronal cell signaling.

  19. Neuromuscular NMDA Receptors Modulate Developmental Synapse Elimination.

    Science.gov (United States)

    Personius, Kirkwood E; Slusher, Barbara S; Udin, Susan B

    2016-08-24

    At birth, each mammalian skeletal muscle fiber is innervated by multiple motor neurons, but in a few weeks, all but one of those axons retracts (Redfern, 1970) and differential activity between inputs controls this phenomenon (Personius and Balice-Gordon, 2001; Sanes and Lichtman, 2001; Personius et al., 2007; Favero et al., 2012). Acetylcholine, the primary neuromuscular transmitter, has long been presumed to mediate this activity-dependent process (O'Brien et al., 1978), but glutamatergic transmission also occurs at the neuromuscular junction (Berger et al., 1995; Grozdanovic and Gossrau, 1998; Mays et al., 2009). To test the role of neuromuscular NMDA receptors, we assessed their contribution to muscle calcium fluxes in mice and tested whether they influence removal of excess innervation at the end plate. Developmental synapse pruning was slowed by reduction of NMDA receptor activation or expression and by reduction of glutamate production. Conversely, pruning is accelerated by application of exogenous NMDA. We also found that NMDA induced increased muscle calcium only during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and synaptic pruning during development. In normal adult muscle, each muscle fiber is innervated by a single axon, but at birth, fibers are multiply innervated. Elimination of excess connections requires neural activity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been assumed to be the critical mediator of activity. However, glutamate receptors are also expressed at the NMJ. We found that axon removal in mice is slowed by pharmacological and molecular manipulations that decrease signaling through neuromuscular NMDA receptors, whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle calcium levels during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play

  20. Contemporary noise-induced hearing loss (NIHL) prevention.

    Science.gov (United States)

    Sułkowski, Wiesław; Owczarek, Kalina; Olszewski, Jurek

    2017-08-31

    Hearing impairment caused by noise, traditionally called - depending on the duration of exposure - acute or chronic acoustic trauma, includes, in addition to presbyacusis, the most common adult population of hearing impaired. In Poland - according to the report of the Central Statistical Office (GUS, 2011), the number of workers employed in NDN exceeded the noise level (85 dB) is about 200 thousand, the highest in the mining, metal and metal products production, textiles and wood production. According to the Regulation of the Council of Ministers of on June 30, 2009, on the list of occupational diseases (Journal of Laws No. 132, item 1115), it is defined as "bilateral permanent hearing loss of the cochlear or sensory-nerve type, expressed as an increase in hearing threshold of at least 45 dB in the ear better heard, calculated as an arithmetic mean for frequencies 1,2 and 3 kHz. Hearing impairments also occur in the military and police during field training and in combat where the source of acoustic injuries are firearms and pulse-inducing explosions (as in some industries) with high C peak levels (Lc peak) Time to rise to a maximum of <1 ms. The prevalence of loud music listening, particularly by personal stereo players, is also affecting children and adolescents with audiometric hearing loss, according to the World Health Organization (WHO) estimates of around 15-20%. The preventive action strategy is defined by the European Union legislation and the national implementing legislation that reduces or eliminates the risk and reduces (if not eliminated), taking into account available technical and organizational solutions to minimize the risk of hearing damage. If you can not reduce the noise levels with technical and organizational methods, you need individual hearing protectors. Ear protectors may be equipped with electronic systems with active noise reduction (which can improve low and medium frequency performance), adjustable attenuation (improves speech

  1. Surgery plus anesthesia induces loss of attention in mice

    Directory of Open Access Journals (Sweden)

    Quan eRen

    2015-09-01

    Full Text Available There is a need to develop animal models to study postoperative delirium. Inattention is one of the symptoms of delirium. Increases in the levels of α-synuclein and S100β have been reported to be associated with delirium. Therefore, we set out to determine the effects of surgery plus general anesthesia on the behavioral changes (including loss of attention in mice and on the levels of α-synuclein and S100β in the brain tissues of these mice. C57BL/6J mice (2- to 8-months-old had a simple laparotomy plus isoflurane anesthesia. The behavioral changes, including attention level and the speed of movements, were determined 12, 24 and 48 hours after the surgery plus anesthesia in the mice. The levels of α-synuclein and S100β in the cortex of these mice following the surgery plus anesthesia were determined by Western blot analysis.We found that there was a loss of attention at 24, but not 12 or 48, hours following the surgery plus anesthesia (49%+5 versus 33%+2.9, P=0.011, N=12 in the mice without significantly affecting the speed of their movements. There were increases in the levels of total α-synuclein (139%+33.5 versus 100%+13.7, P=0.037, N=6 and S100β (142%+7.7 versus 100%+6, P=0.002, N=6 in the cortex of the mice 12 hours following the surgery plus anesthesia.These findings suggested that the surgery plus isoflurane anesthesia might induce behavioral and biochemical/biochemical/cellular changes associated with delirium. We could use the surgery plus anesthesia in mice to develop an animal model to study postoperative delirium.

  2. N-cadherin relocalizes from the periphery to the center of the synapse after transient synaptic stimulation in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Patricia T Yam

    Full Text Available N-cadherin is a cell adhesion molecule which is enriched at synapses. Binding of N-cadherin molecules to each other across the synaptic cleft has been postulated to stabilize adhesion between the presynaptic bouton and the postsynaptic terminal. N-cadherin is also required for activity-induced changes at synapses, including hippocampal long term potentiation and activity-induced spine expansion and stabilization. We hypothesized that these activity-dependent changes might involve changes in N-cadherin localization within synapses. To determine whether synaptic activity changes the localization of N-cadherin, we used structured illumination microscopy, a super-resolution approach which overcomes the conventional resolution limits of light microscopy, to visualize the localization of N-cadherin within synapses of hippocampal neurons. We found that synaptic N-cadherin exhibits a spectrum of localization patterns, ranging from puncta at the periphery of the synapse adjacent to the active zone to an even distribution along the synaptic cleft. Furthermore, the N-cadherin localization pattern within synapses changes during KCl depolarization and after transient synaptic stimulation. During KCl depolarization, N-cadherin relocalizes away from the central region of the synaptic cleft to the periphery of the synapse. In contrast, after transient synaptic stimulation with KCl followed by a period of rest in normal media, fewer synapses have N-cadherin present as puncta at the periphery and more synapses have N-cadherin present more centrally and uniformly along the synapse compared to unstimulated cells. This indicates that transient synaptic stimulation modulates N-cadherin localization within the synapse. These results bring new information to the structural organization and activity-induced changes occurring at synapses, and suggest that N-cadherin relocalization may contribute to activity dependent changes at synapses.

  3. Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

    Science.gov (United States)

    Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

  4. Murine CMV-induced hearing loss is associated with inner ear inflammation and loss of spiral ganglia neurons.

    Directory of Open Access Journals (Sweden)

    Russell D Bradford

    2015-04-01

    Full Text Available Congenital human cytomegalovirus (HCMV occurs in 0.5-1% of live births and approximately 10% of infected infants develop hearing loss. The mechanism(s of hearing loss remain unknown. We developed a murine model of CMV induced hearing loss in which murine cytomegalovirus (MCMV infection of newborn mice leads to hematogenous spread of virus to the inner ear, induction of inflammatory responses, and hearing loss. Characteristics of the hearing loss described in infants with congenital HCMV infection were observed including, delayed onset, progressive hearing loss, and unilateral hearing loss in this model and, these characteristics were viral inoculum dependent. Viral antigens were present in the inner ear as were CD(3+ mononuclear cells in the spiral ganglion and stria vascularis. Spiral ganglion neuron density was decreased after infection, thus providing a mechanism for hearing loss. The lack of significant inner ear histopathology and persistence of inflammation in cochlea of mice with hearing loss raised the possibility that inflammation was a major component of the mechanism(s of hearing loss in MCMV infected mice.

  5. Silent Synapses Speak Up: Updates of the Neural Rejuvenation Hypothesis of Drug Addiction.

    Science.gov (United States)

    Huang, Yanhua H; Schlüter, Oliver M; Dong, Yan

    2015-10-01

    A transient but prominent increase in the level of "silent synapses"--a signature of immature glutamatergic synapses that contain only NMDA receptors without stably expressed AMPA receptors--has been identified in the nucleus accumbens (NAc) following exposure to cocaine. As the NAc is a critical forebrain region implicated in forming addiction-associated behaviors, the initial discoveries have raised speculations about whether and how these drug-induced synapses mature and potentially contribute to addiction-related behaviors. Here, we summarize recent progress in recognizing the pathway-specific regulations of silent synapse maturation, and its diverse impacts on behavior. We provide an update of the guiding hypothesis--the "neural rejuvenation hypothesis"--with recently emerged evidence of silent synapses in cocaine craving and relapse. © The Author(s) 2015.

  6. Microglial interactions with synapses are modulated by visual experience.

    Directory of Open Access Journals (Sweden)

    Marie-Ève Tremblay

    2010-11-01

    Full Text Available Microglia are the immune cells of the brain. In the absence of pathological insult, their highly motile processes continually survey the brain parenchyma and transiently contact synaptic elements. Aside from monitoring, their physiological roles at synapses are not known. To gain insight into possible roles of microglia in the modification of synaptic structures, we used immunocytochemical electron microscopy, serial section electron microscopy with three-dimensional reconstructions, and two-photon in vivo imaging to characterize microglial interactions with synapses during normal and altered sensory experience, in the visual cortex of juvenile mice. During normal visual experience, most microglial processes displayed direct apposition with multiple synapse-associated elements, including synaptic clefts. Microglial processes were also distinctively surrounded by pockets of extracellular space. In terms of dynamics, microglial processes localized to the vicinity of small and transiently growing dendritic spines, which were typically lost over 2 d. When experience was manipulated through light deprivation and reexposure, microglial processes changed their morphology, showed altered distributions of extracellular space, displayed phagocytic structures, apposed synaptic clefts more frequently, and enveloped synapse-associated elements more extensively. While light deprivation induced microglia to become less motile and changed their preference of localization to the vicinity of a subset of larger dendritic spines that persistently shrank, light reexposure reversed these behaviors. Taken together, these findings reveal different modalities of microglial interactions with synapses that are subtly altered by sensory experience. These findings suggest that microglia may actively contribute to the experience-dependent modification or elimination of a specific subset of synapses in the healthy brain.

  7. Noise induced hearing loss among industrial workers in Dar es ...

    African Journals Online (AJOL)

    Objectives: To determine whether sound in the study areas was of sufficient intensity to cause hearing loss and if so whether those exposed have been affected and to determine whether workers/employees in the study areas were aware that sound can cause hearing loss and if so whether they knew that this can be ...

  8. The State of Synapses in Fragile X Syndrome

    OpenAIRE

    Pfeiffer, Brad E.; Huber, Kimberly M.

    2009-01-01

    Fragile X Syndrome is the most common inherited form of mental retardation and a leading genetic cause of autism. There is increasing evidence in both FXS and other forms of autism that alterations in synapse number, structure and function are associated and contribute to these prevalent diseases. FXS is caused by loss of function of the Fmr1 gene which encodes the RNA binding protein, FMRP. Therefore, FXS is a tractable model to understand synaptic dysfunction in cognitive disorders. FMRP is...

  9. Organization of central synapses by adhesion molecules

    OpenAIRE

    Tallafuss, Alexandra; Constable, John R.L.; Washbourne, Philip

    2010-01-01

    Synapses are the primary means for transmitting information from one neuron to the next. They are formed during development of the nervous system, and formation of appropriate synapses is crucial for establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies ...

  10. Interventions to prevent occupational noise induced hearing loss

    NARCIS (Netherlands)

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wout; Sorgdrager, Bas

    2009-01-01

    BACKGROUND: Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. OBJECTIVES: To assess the effectiveness of non-pharmaceutical interventions for preventing

  11. Interventions to prevent occupational noise-induced hearing loss

    NARCIS (Netherlands)

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Mischke, Christina

    2012-01-01

    Background Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. Objectives To assess the effectiveness of non-pharmaceutical interventions for preventing

  12. Reducing disorder-induced losses for slow light photonic crystal waveguides through Bloch mode engineering

    DEFF Research Database (Denmark)

    Mann, Nishan; Combrié, Sylvian; Colman, Pierre

    2013-01-01

    We present theory and measurements ofdisorder-induced losses for low loss 1.5 mmlong slow light photonic crystal waveguides. A recent class of dispersion engineered waveguides increases the bandwidth of slow light and shows lower propagation losses for the same group index. Our theory and experim...... and experiments explain how Bloch mode engineering can substantially reduce scattering losses for the same slow light group velocity regime....

  13. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

    International Nuclear Information System (INIS)

    Cheon, Yoon-Hee; Kim, Ju-Young; Baek, Jong Min; Ahn, Sung-Jun; So, Hong-Seob; Oh, Jaemin

    2016-01-01

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine 727 . Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser 727 signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.

  14. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Yoon-Hee [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Baek, Jong Min; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2016-02-05

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine{sup 727}. Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser{sup 727} signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.

  15. Dose passive smoking induce sensorineural hearing loss in children?

    Science.gov (United States)

    Talaat, Hossam Sanyelbhaa; Metwaly, Mohamed Akram; Khafagy, Ahmed Hafez; Abdelraouf, Hatem Ragaa

    2014-01-01

    Smoking plays major role in development of vascular and respiratory serious diseases. It has been reported that negative smoker children are prone for conductive hearing impairment due to repeated attacks of Eustachian tube dysfunction and middle ear effusion. This study aims to identify negative smoking as potential risk factor for development of sensorineural hearing loss. This study was done between January 2010 and November 2012. 411 children aged 5-11 years (8.2 ± 1.5) participated in this study; they were children attending the Ear, Nose, and Throat clinic of a tertiary care hospital and their siblings. The inclusion criteria were: (i) normal speech and language, (ii) absence of any disease or condition that may cause sensorineural hearing loss, and (iii) normal middle ear function on the day of hearing assessment. They were divided into three groups according to the exposure to second-hand smoke at home; group of "no exposure" whereas no smoker in the family (131 children), group of 'mild exposure" whereas the father was the only smoking parent and smoking was prohibited at home (155 children), and group of "heavy exposure", whereas the mother was smoking, or the father was freely smoking at home and in the presence of his children (125 children). Audiological evaluation in the form of pure tone and speech audiometry and immitancemetry was done for the study group. Audiological evaluation revealed that the prevalence of hearing loss was 3.8%, 4.5% and 12% in the "no exposure", "mild exposure", and "heavy exposure" groups, respectively. Significant difference was only detected between the high exposure group and the other two groups. All children had minimal sensorineural hearing loss, i.e. threshold of frequencies showing hearing loss was 20 or 25 dB HL. The risk ratios (95% confidence interval) for hearing loss in the study subgroups were 1.18 (0.38, 3.64) for mild exposure group (p>0.05), 3.14 (1.18, 8.3) for heavy exposure group (phearing loss, and it is

  16. Face classification using electronic synapses

    Science.gov (United States)

    Yao, Peng; Wu, Huaqiang; Gao, Bin; Eryilmaz, Sukru Burc; Huang, Xueyao; Zhang, Wenqiang; Zhang, Qingtian; Deng, Ning; Shi, Luping; Wong, H.-S. Philip; Qian, He

    2017-05-01

    Conventional hardware platforms consume huge amount of energy for cognitive learning due to the data movement between the processor and the off-chip memory. Brain-inspired device technologies using analogue weight storage allow to complete cognitive tasks more efficiently. Here we present an analogue non-volatile resistive memory (an electronic synapse) with foundry friendly materials. The device shows bidirectional continuous weight modulation behaviour. Grey-scale face classification is experimentally demonstrated using an integrated 1024-cell array with parallel online training. The energy consumption within the analogue synapses for each iteration is 1,000 × (20 ×) lower compared to an implementation using Intel Xeon Phi processor with off-chip memory (with hypothetical on-chip digital resistive random access memory). The accuracy on test sets is close to the result using a central processing unit. These experimental results consolidate the feasibility of analogue synaptic array and pave the way toward building an energy efficient and large-scale neuromorphic system.

  17. Platinum-induced hearing loss after treatment for childhood cancer

    NARCIS (Netherlands)

    van As, Jorrit W.; van den Berg, Henk; van Dalen, Elvira C.

    2016-01-01

    Background Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most important adverse effects is the occurrence of hearing loss or ototoxicity. There is a wide variation in

  18. Interventions to prevent occupational noise-induced hearing loss

    NARCIS (Netherlands)

    Tikka, Christina; Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Ferrite, Silvia

    2017-01-01

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of

  19. Chloramphenicol Induced Hearing Loss | Ogisi | Nigerian Journal of ...

    African Journals Online (AJOL)

    Background: With the widespread use of the drug Chloramphenicol in treatment of typhoid fever, a number of cases of deafness are coming to light following such ... tragedy by limiting the use of this drug is stressed. (Nig J Surg Res 2001; 3: 75 – 80) KEY WORDS: Hearing Loss, Chloramphenicol, Typhoid Fever, Handicap ...

  20. Prevalence of noise-induced hearing loss in drivers

    Directory of Open Access Journals (Sweden)

    Andréa Cintra Lopes1, , , ,

    2012-01-01

    Full Text Available Introduction: Work-related hearing loss is one of the most common occupational illness progresses over the years of noise exposure associated with the work environment, may cause damage to undertake physical activity, the individual's physiological and mental besides causing hearing damage irreversible interfering with communication and quality of life. With high prevalence of male evaluates which is the second leading cause of hearing loss. Since there is no medical treatment for this type of hearing loss, it is evident the importance of preventive and conferences aimed at preserving hearing and health as a whole. Objective: To assess the prevalence of hearing loss in audiometry admission of drivers. Methods: Retrospective study. By 76 charts of professional drivers in leased transport companies. We analyzed data from specific interview and pure tone audiometry. Results: The prevalence of abnormal tests was 22.36% with the lowest thresholds for tritonal average of 3,000, 4,000 and 6,000 Hz. The higher the age, the higher thresholds. Conclusion: This study has highlighted the occurrence of hearing in the absence of complaints. Considering that PAIR is preventable, justifies the importance of coordinated and multidisciplinary involving not only health teams and safety, but also the institutions involved in preserving the health of workers, as the team SESMET, unions or prosecutors.

  1. Cellular mechanisms of cyclophosphamide-induced taste loss in mice.

    Directory of Open Access Journals (Sweden)

    Nabanita Mukherjee

    Full Text Available Many commonly prescribed chemotherapy drugs such as cyclophosphamide (CYP have adverse side effects including disruptions in taste which can result in loss of appetite, malnutrition, poorer recovery and reduced quality of life. Previous studies in mice found evidence that CYP has a two-phase disturbance in taste behavior: a disturbance immediately following drug administration and a second which emerges several days later. In this study, we examined the processes by which CYP disturbs the taste system by examining the effects of the drug on taste buds and cells responsible for taste cell renewal using immunohistochemical assays. Data reported here suggest CYP has direct cytotoxic effects on lingual epithelium immediately following administration, causing an early loss of taste sensory cells. Types II and III cells in fungiform taste buds appear to be more susceptible to this effect than circumvallate cells. In addition, CYP disrupts the population of rapidly dividing cells in the basal layer of taste epithelium responsible for taste cell renewal, manifesting a disturbance days later. The loss of these cells temporarily retards the system's capacity to replace Type II and Type III taste sensory cells that survived the cytotoxic effects of CYP and died at the end of their natural lifespan. The timing of an immediate, direct loss of taste cells and a delayed, indirect loss without replacement of taste sensory cells are broadly congruent with previously published behavioral data reporting two periods of elevated detection thresholds for umami and sucrose stimuli. These findings suggest that chemotherapeutic disturbances in the peripheral mechanisms of the taste system may cause dietary challenges at a time when the cancer patient has significant need for well balanced, high energy nutritional intake.

  2. Cellular and deafness mechanisms underlying connexin mutation induced hearing loss – A common hereditary deafness

    Directory of Open Access Journals (Sweden)

    Jeffrey C Wingard

    2015-05-01

    Full Text Available Hearing loss due to mutations in the connexin gene family which encodes gap junctional proteins is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2 mutations are responsible for ~50% of nonsyndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential (EP reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Additionally, there is no clear relationship between specific changes in connexin (channel functions and the phenotypes of mutation-induced hearing loss. Cx30, Cx29, Cx31, and Cx43 mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes and pathogeneses of specific-mutation induced hearing loss remain unclear. Finally, little information is available for humans. Further studies to address these deficiencies are urgently required.

  3. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Organization of central synapses by adhesion molecules.

    Science.gov (United States)

    Tallafuss, Alexandra; Constable, John R L; Washbourne, Philip

    2010-07-01

    Synapses are the primary means for transmitting information from one neuron to the next. They are formed during the development of the nervous system, and the formation of appropriate synapses is crucial for the establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules that are present at the synapse. It is now important to untangle this large array of proteins and determine how it assembles into a functioning unit. Here we focus on recent reports describing how synaptic cell adhesion molecules interact with and organize the presynaptic and postsynaptic specializations of both excitatory and inhibitory central synapses. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Hydrogen induced ductility losses in austenitic stainless steel welds

    Energy Technology Data Exchange (ETDEWEB)

    Brooks, J.A.; West, A.J.

    1978-06-01

    The effect of hydrogen on the tensile behavior of austenitic stainless steel welds was studied in two AISI 300 series alloys and two nitrogen strengthened alloys. The microstructure of these welds typically contained several percent ferrite in an austenite matrix. Hydrogen was found to reduce the ductility of all welds; however, the severity of ductility loss decreased with increasing stacking fault energy, as observed in previous studies on wrought material. In the lowest stacking fault energy welds, 304L and 308L, hydrogen changed the fracture mode from simple rupture to a mixed mode of ductile and brittle fracture associated with the austenite ferrite interface. Higher stacking fault energy welds, 309S and 22-13-5, showed smaller losses in ductility. In these materials hydrogen assisted the ductile rupture process by aiding void growth and coalescence, without changing the fracture mode. Varying the amount of ferrite from approximately one to 10 percent had no significant effect on performance in hydrogen.

  6. ‘Ecstasy’ Enhances Noise-Induced Hearing Loss

    OpenAIRE

    Church, Michael W.; Zhang, Jinsheng S.; Langford, Megan M.; Perrine, Shane A.

    2013-01-01

    ‘Ecstasy’ or 3,4-methylenedioxy-N-methamphetamine (MDMA) is an amphetamine abused for its euphoric, empathogenic, hallucinatory, and stimulant effects. It is also used to treat certain psychiatric disorders. Common settings for Ecstasy use are nightclubs and “rave” parties where participants consume MDMA and dance to loud music. One concern with the club setting is that exposure to loud sounds can cause permanent sensorineural hearing loss. Another concern is that consumption of MDMA may enha...

  7. Towards a Molecular Understanding of Noise-Induced Hearing Loss

    Science.gov (United States)

    2015-10-01

    the entire cochlea is performed by assembling consecutive images using Photoshop (Adobe, San Jose, CA) or PowerPoint (Microsoft). Once reconstituted...ears). Figure 4 – (A) representative image of a cytocochleogram. The area shown is between 70% and 80% from the apex; (B) Average hair cell loss as...Tamoxifen per 40 g of body weight using a 30G1/2 ultrafine needle insulin syringe (Becton Dickinson) containing a 10mg/ml Tamoxifen solution (Tamoxifen

  8. Historical review of efforts to reduce noise-induced hearing loss in the United States.

    Science.gov (United States)

    Kerr, Madeleine J; Neitzel, Richard L; Hong, OiSaeng; Sataloff, Robert T

    2017-06-01

    Noise-induced hearing loss is a centuries-old problem that is still prevalent in the United States and worldwide. To describe highlights in the development of hearing loss prevention in the U.S. from World War II to the present. Literature review. Approaches to occupational noise-induced hearing loss prevention in the United States over the past seven decades are described using a hierarchy of controls framework and an interdisciplinary perspective. Historical timelines and developmental milestones related to occupational noise-induced hearing loss prevention are summarized as a life course. Lessons are drawn for other countries in their hearing conservation efforts. Future developments building on the hearing loss prevention work of the past 70 years can prevent the problem of occupational NIHL in the 21st century. Am. J. Ind. Med. 60:569-577, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Interventions to prevent occupational noise-induced hearing loss.

    Science.gov (United States)

    Tikka, Christina; Verbeek, Jos H; Kateman, Erik; Morata, Thais C; Dreschler, Wouter A; Ferrite, Silvia

    2017-07-07

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of non-pharmaceutical interventions for preventing occupational noise exposure or occupational hearing loss compared to no intervention or alternative interventions. We searched the CENTRAL; PubMed; Embase; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; and OSH UPDATE to 3 October 2016. We included randomised controlled trials (RCT), controlled before-after studies (CBA) and interrupted time-series (ITS) of non-clinical interventions under field conditions among workers to prevent or reduce noise exposure and hearing loss. We also collected uncontrolled case studies of engineering controls about the effect on noise exposure. Two authors independently assessed study eligibility and risk of bias and extracted data. We categorised interventions as engineering controls, administrative controls, personal hearing protection devices, and hearing surveillance. We included 29 studies. One study evaluated legislation to reduce noise exposure in a 12-year time-series analysis but there were no controlled studies on engineering controls for noise exposure. Eleven studies with 3725 participants evaluated effects of personal hearing protection devices and 17 studies with 84,028 participants evaluated effects of hearing loss prevention programmes (HLPPs). Effects on noise exposure Engineering interventions following legislationOne ITS study found that new legislation in the mining industry reduced the median personal noise exposure dose in underground coal mining by 27.7 percentage points (95% confidence interval (CI) -36.1 to -19.3 percentage points) immediately after the implementation of stricter legislation. This roughly translates to a 4.5 dB(A) decrease in

  10. Sex Differences in Susceptibility and Resistance to Noise-Induced Hearing Loss in Chinchillas

    National Research Council Canada - National Science Library

    McFadden, Sandra

    1999-01-01

    .... The reasons for individual differences in susceptibility to noise-induced hearing loss (NIHL) are largely unknown, but may include factors such as levels of endogenous antioxidant enzymes or steroid hormones...

  11. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss.

    Science.gov (United States)

    Cheon, Yoon-Hee; Kim, Ju-Young; Baek, Jong Min; Ahn, Sung-Jun; So, Hong-Seob; Oh, Jaemin

    2016-02-05

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine-threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine(727). Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction.

    Science.gov (United States)

    Pastel, Emilie; McCulloch, Laura J; Ward, Rebecca; Joshi, Shivam; Gooding, Kim M; Shore, Angela C; Kos, Katarina

    2017-03-01

    Glucagon-like peptide-1 (GLP-1) analogues aid weight loss that improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT that expresses the GLP-1 receptor (GLP-1R). The present study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT (SCAT) inflammatory and fibrotic responses, compared with weight loss by calorie reduction (control). Among the 39 participants with Type 2 diabetes recruited, 30 age-matched participants were randomized to 4 months treatment with Liraglutide ( n =22) or calorie restriction based on dietetic counselling ( n =8). Assessments included clinical characteristics and repeated subcutaneous abdominal AT biopsies. Liraglutide resulted in weight loss in most participants (-3.12±1.72 kg, P =0.007) and significant reduction in visceral AT (VAT). It was more effective in lowering fasting glucose, in comparison with weight loss by dieting. However, tumour necrosis factor-α ( TNFA ) AT-expression ( P =0.0005), macrophage chemoattractant protein-1 ( MCP-1 ) expression ( P =0.027) and its serum levels ( P =0.048) increased with Liraglutide, suggestive of an inflammatory response unlike in the diet arm in which a trend of lower cluster of differentiation 14 ( CD14 ) expression ( P =0.09) was found. Liraglutide treatment also increased expression of factors involved in extracellular matrix (ECM) deposition, transforming growth factor-β ( TGFB ) and collagen type 1 alpha 1 chain ( COL1A1 ) ( TGFB1 : before 0.73±0.09 arbitrary units (AU), after 1.00±0.13 AU, P =0.006; COL1A1 : 0.84±0.09 AU compared with 1.49±0.26 AU, P =0.026). Liraglutide thus appears to induce an inflammatory response in AT and influences ECM remodelling. Despite its superior effect on glycaemia, Liraglutide does not improve obesity-associated AT dysfunction in subcutaneous tissue. It is yet unclear whether this limits AT storage capacity for lipids. This may be of importance in patients being re

  13. Alcohol-induced bone loss is blocked in p47phox -/- mice lacking functional nadph oxidases

    Science.gov (United States)

    Chronic ethanol (EtOH) consumption produces bone loss. Previous data suggest a role for NADPH oxidase enzymes (Nox) since the pan-Nox inhibitor diphenylene iodonium (DPI) blocks EtOH-induced bone loss in rats. The current study utilized mice in which Nox enzymes 1,2,3 and 5 are inactivated as a resu...

  14. Noise-Induced Hearing Loss - A Preventable Disease?

    DEFF Research Database (Denmark)

    Frederiksen, Thomas W.; Ramlau-Hansen, Cecilia H.; Stokholm, Zara A.

    2017-01-01

    statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22). CONCLUSIONS: We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which...... insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (-0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI): -0.36; 0.16)). The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only...

  15. Visual Loss Induced by Adalimumab Used for Plaque Psoriasis

    Directory of Open Access Journals (Sweden)

    Norman Saffra

    2017-03-01

    Full Text Available A 61-year-old Caucasian male with severe plaque psoriasis without joint involvement was initiated on adalimumab therapy. Shortly thereafter he presented to the emergency room with acute loss of vision in the right eye. A comprehensive systemic workup was instituted which included magnetic resonance imaging (MRI with and without gadolinium of the brain and orbits. MRI revealed findings that were consistent with CNS demyelination and retrobulbar optic neuritis. Immediate cessation of adalimumab was instituted without any other systemic therapy. Complete return of vision occurred within 6 weeks. No additional psoriatic or neurologic treatment was instituted, and the patient has remained stable now for 14 months.

  16. Noise Induced Hearing Loss in Iran: (1997-2012): Systematic Review Article.

    Science.gov (United States)

    Soltanzadeh, Ahmad; Ebrahimi, Hossein; Fallahi, Majid; Kamalinia, Mojtaba; Ghassemi, Shadi; Golmohammadi, Rostam

    2014-12-01

    Noise-induced hearing loss, which is one of the 10 leading occupational diseases, is a debilitating and irreversible disease. During the recent 15-years period (1997-2012), several studies have investigated the association between noise, hearing damage and other side effects of noise in Iran. The aim of this study was to review systematically the relevant literature related to noise-induced hearing loss, lead to developing noise exposure limits. In this systematic review, two researchers independently extracted the data from 31 past studies that had considered noise-induced hearing loss (including hearing loss, temporary and permanent hearing threshold shift and auditory trauma). The data were then recorded in a modified form and Statistical analyses were performed using SPSS, version 16.0. In analyzed studies the weighted average equivalent sound pressure level [L Aeq ] was 90.29 dB(A) and average hearing loss was 26.44 dB(A). The Highest degree of hearing loss in the right ear was associated at 4000 Hz, and the highest degree of hearing loss in the left ear was associated to 1000 and 4000 Hz. The majority of the reviewed studies have confirmed that exposure to a noise level above 85 dB (A) can lead to an increased chance of hearing loss. Furthermore, the results of the present review indicated that as L Aeq increased up to 85 dB(A), so did the severity of the hearing loss.

  17. Noise Induced Hearing Loss in Iran: (1997–2012): Systematic Review Article

    Science.gov (United States)

    SOLTANZADEH, Ahmad; EBRAHIMI, Hossein; FALLAHI, Majid; KAMALINIA, Mojtaba; GHASSEMI, Shadi; GOLMOHAMMADI, Rostam

    2014-01-01

    Noise-induced hearing loss, which is one of the 10 leading occupational diseases, is a debilitating and irreversible disease. During the recent 15-years period (1997–2012), several studies have investigated the association between noise, hearing damage and other side effects of noise in Iran. The aim of this study was to review systematically the relevant literature related to noise-induced hearing loss, lead to developing noise exposure limits. In this systematic review, two researchers independently extracted the data from 31 past studies that had considered noise-induced hearing loss (including hearing loss, temporary and permanent hearing threshold shift and auditory trauma). The data were then recorded in a modified form and Statistical analyses were performed using SPSS, version 16.0. In analyzed studies the weighted average equivalent sound pressure level [L Aeq ] was 90.29 dB(A) and average hearing loss was 26.44 dB(A). The Highest degree of hearing loss in the right ear was associated at 4000 Hz, and the highest degree of hearing loss in the left ear was associated to 1000 and 4000 Hz. The majority of the reviewed studies have confirmed that exposure to a noise level above 85 dB (A) can lead to an increased chance of hearing loss. Furthermore, the results of the present review indicated that as L Aeq increased up to 85 dB(A), so did the severity of the hearing loss. PMID:26171352

  18. TFH-derived dopamine accelerates productive synapses in germinal centres.

    Science.gov (United States)

    Papa, Ilenia; Saliba, David; Ponzoni, Maurilio; Bustamante, Sonia; Canete, Pablo F; Gonzalez-Figueroa, Paula; McNamara, Hayley A; Valvo, Salvatore; Grimbaldeston, Michele; Sweet, Rebecca A; Vohra, Harpreet; Cockburn, Ian A; Meyer-Hermann, Michael; Dustin, Michael L; Doglioni, Claudio; Vinuesa, Carola G

    2017-07-20

    Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T FH ) cells in germinal centres. The rapid T-B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human T FH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T FH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human T FH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T-B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T-B-cell synapse may be advantageous in the face of infection.

  19. Multiple synchronization transitions in scale-free neuronal networks with electrical and chemical hybrid synapses

    International Nuclear Information System (INIS)

    Liu, Chen; Wang, Jiang; Wang, Lin; Yu, Haitao; Deng, Bin; Wei, Xile; Tsang, Kaiming; Chan, Wailok

    2014-01-01

    Highlights: • Synchronization transitions in hybrid scale-free neuronal networks are investigated. • Multiple synchronization transitions can be induced by the time delay. • Effect of synchronization transitions depends on the ratio of the electrical and chemical synapses. • Coupling strength and the density of inter-neuronal links can enhance the synchronization. -- Abstract: The impacts of information transmission delay on the synchronization transitions in scale-free neuronal networks with electrical and chemical hybrid synapses are investigated. Numerical results show that multiple appearances of synchronization regions transitions can be induced by different information transmission delays. With the time delay increasing, the synchronization of neuronal activities can be enhanced or destroyed, irrespective of the probability of chemical synapses in the whole hybrid neuronal network. In particular, for larger probability of electrical synapses, the regions of synchronous activities appear broader with stronger synchronization ability of electrical synapses compared with chemical ones. Moreover, it can be found that increasing the coupling strength can promote synchronization monotonously, playing the similar role of the increasing the probability of the electrical synapses. Interestingly, the structures and parameters of the scale-free neuronal networks, especially the structural evolvement plays a more subtle role in the synchronization transitions. In the network formation process, it is found that every new vertex is attached to the more old vertices already present in the network, the more synchronous activities will be emerge

  20. The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease

    NARCIS (Netherlands)

    De Winter, Fred; Vo, Tam; Stam, Floor J; Wisman, Liselijn A B; Bär, Peter R; Niclou, Simone P; van Muiswinkel, Freek L; Verhaagen, J.

    2006-01-01

    Neuromuscular synapses differ markedly in their plasticity. Motor nerve terminals innervating slow muscle fibers sprout vigorously following synaptic blockage, while those innervating fast-fatigable muscle fibers fail to exhibit any sprouting. Here, we show that the axon repellent Semaphorin 3A is

  1. Suppression of NADPH oxidases prevents chronic ethanol-induced bone loss

    Science.gov (United States)

    Since the molecular mechanisms through which chronic excessive alcohol consumption induces osteopenia and osteoporosis are largely unknown, potential treatments for prevention of alcohol-induced bone loss remain unclear. We have previously demonstrated that, chronic ethanol (EtOH) treatment leads to...

  2. Microglia actively regulate the number of functional synapses.

    Directory of Open Access Journals (Sweden)

    Kyungmin Ji

    Full Text Available Microglia are the immunocompetent cells of the central nervous system. In the physiological setting, their highly motile processes continually survey the local brain parenchyma and transiently contact synaptic elements. Although recent work has shown that the interaction of microglia with synapses contributes to synaptic remodeling during development, the role of microglia in synaptic physiology is just starting to get explored. To assess this question, we employed an electrophysiological approach using two methods to manipulate microglia in culture: organotypic hippocampal brain slices in which microglia were depleted using clodronate liposomes, and cultured hippocampal neurons to which microglia were added. We show here that the frequency of excitatory postsynaptic current increases in microglia-depleted brain slices, consistent with a higher synaptic density, and that this enhancement ensures from the loss of microglia since it is reversed when the microglia are replenished. Conversely, the addition of microglia to neuronal cultures decreases synaptic activity and reduces the density of synapses, spine numbers, surface expression of AMPA receptor (GluA1, and levels of synaptic adhesion molecules. Taken together, our findings demonstrate that non-activated microglia acutely modulate synaptic activity by regulating the number of functional synapses in the central nervous system.

  3. Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

    Science.gov (United States)

    2014-07-01

    Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time ...Real- time PCR evaluation of transcripts related to the resorption axis revealed no Botox-induced chang- es in M-Csf expression, significant...injected limbs.  Similar effects were noted for femoral BMC.  We were unable to  detect any Botox‐related changes in the distal femur  metaphyseal

  4. Mechanism for Prenatal LPS-Induced DA Neuron Loss

    Science.gov (United States)

    2006-09-01

    to the skull with the aid of screws and dental cement . The tubing was threaded subcutaneously to the nape of the neck and then connected to a mini-pump...adult rat brain: the effects of 6-hydroxydop- amine lesions in adult brain. Dev. Brain Res. 97, 297–303. 6-Hydroxydopamine-induced alterations in...L. Neuronal uptake processes for amines and amino acids. Adv. Biochem. Psychopharmacol. 2:109– 62. McNaught, K. S.; Perl, D. P.; Brownell, A. L

  5. Assessment of thermal treatment via irrigation of external ear to reduce cisplatin-induced hearing loss.

    Science.gov (United States)

    Spankovich, Christopher; Lobarinas, Edward; Ding, Dalian; Salvi, Richard; Le Prell, Colleen G

    2016-02-01

    Systemic and local changes in body temperature can have a profound effect on traumatic injuries including those to the inner ear. Therefore, we investigated the effects of acutely increasing or decreasing the temperature of the external ear canal on cisplatin-induced hearing loss. The external auditory canals of male guinea pigs were acutely irrigated with warm (44 °C), euthermic (37 °C), or cool (30 °C) water and subsequently injected with cisplatin (12 mg/kg, i.p.). Hearing was assessed by the auditory brainstem response and cochleograms were prepared to determine loss of hair cells. Ear canal irrigation with warm water potentiated cisplatin-induced hearing loss and outer hair cell loss whereas cool ear canal irrigation showed significant protection from cisplatin-induced hearing loss and outer hair cell loss. These results suggest that non-invasive cool water ear canal irrigation may be highly effective clinical procedure for protecting against cisplatin-induced hearing loss. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy

    DEFF Research Database (Denmark)

    Nørgaard, Sisse A; Sand, Fredrik W; Sørensen, Dorte B

    2018-01-01

    these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight loss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we...... without this supplement reached this humane endpoint ( p = 0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow ( p = 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did...... demonstrated that diabetic male mice receiving softened chow had reduced acute weight loss following STZ treatment ( p = 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice...

  7. Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

    Science.gov (United States)

    Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

    2007-11-01

    Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

  8. The role of Ca2+-dependent K+- channels at the rat corticostriatal synapses revealed by paired pulse stimulation.

    Science.gov (United States)

    Robles Gómez, Angel A; Vega, Ana V; Gónzalez-Sandoval, Carolina; Barral, Jaime

    2018-02-01

    Potassium channels play an important role in modulating synaptic activity both at presynaptic and postsynaptic levels. We have shown before that presynaptically located K V and K IR channels modulate the strength of corticostriatal synapses in rat brain, but the role of other types of potassium channels at these synapses remains largely unknown. Here, we show that calcium-dependent potassium channels BK-type but not SK-type channels are located presynaptically in corticostriatal synapses. We stimulated cortical neurons in rat brain slices and recorded postsynaptic excitatory potentials (EPSP) in medium spiny neurons (MSN) in dorsal neostriatum. By using a paired pulse protocol, we induced synaptic facilitation before applying either BK- or SK-specific toxins. Thus, we found that blockage of BK Ca with iberiotoxin (10 nM) reduces synaptic facilitation and increases the amplitude of the EPSP, while exposure to SK-blocker apamin (100 nM) has no effect. Additionally, we induced train action potentials on striatal MSN by current injection before and after the exposure to K Ca toxins. We found that the action potential becomes broader when the MSN is exposed to iberiotoxin, although it has no impact on frequency. In contrast, exposure to apamin results in loss of afterhyperpolarization phase and an increase of spike frequency. Therefore, we concluded that postsynaptic SK channels are involved in afterhyperpolarization and modulation of spike frequency while the BK channels are involved on the late repolarization phase of the action potential. Altogether, our results show that calcium-dependent potassium channels modulate both input towards and output from the striatum. © 2017 Wiley Periodicals, Inc.

  9. Potassium channel activator attenuates salicylate-induced cochlear hearing loss potentially ameliorating tinnitus.

    Science.gov (United States)

    Sun, Wei; Liu, Jun; Zhang, Chao; Zhou, Na; Manohar, Senthilvelan; Winchester, Wendy; Miranda, Jason A; Salvi, Richard J

    2015-01-01

    High dose sodium salicylate causes moderate, reversible hearing loss and tinnitus. Salicylate-induced hearing loss is believed to arise from a reduction in the electromotile response of outer hair cells (OHCs) and/or reduction of KCNQ4 potassium currents in OHCs, which decreases the driving force for the transduction current. Therefore, enhancing OHC potassium currents could potentially prevent salicylate-induced temporary hearing loss. In this study, we tested whether opening voltage-gated potassium channels using ICA-105665, a novel small molecule that opens KCNQ2/3 and KCNQ3/5 channels, can reduce salicylate-induced hearing loss. We found that systemic application of ICA-105665 at 10 mg/kg prevented the salicylate-induced amplitude reduction and threshold shift in the compound action potentials recorded at the round window of the cochlea. ICA-105665 also prevented the salicylate-induced reduction of distortion-product otoacoustic emission. These results suggest that ICA-105665 partially compensates for salicylate-induced cochlear hearing loss by enhancing KCNQ2/3 and KCNQ3/5 potassium currents and the motility of OHCs.

  10. Constraint-induced sound therapy for sudden sensorineural hearing loss--behavioral and neurophysiological outcomes.

    Science.gov (United States)

    Okamoto, Hidehiko; Fukushima, Munehisa; Teismann, Henning; Lagemann, Lothar; Kitahara, Tadashi; Inohara, Hidenori; Kakigi, Ryusuke; Pantev, Christo

    2014-01-29

    Sudden sensorineural hearing loss is characterized by acute, idiopathic hearing deterioration. We report here the development and evaluation of "constraint-induced sound therapy", which is based on a well-established neuro-rehabilitation approach, and which is characterized by the plugging of the intact ear ("constraint") and the simultaneous, extensive stimulation of the affected ear with music. The sudden sensorineural hearing loss patients who received the constraint-induced sound therapy in addition to the standard corticosteroid therapy showed significantly better recovery of hearing function compared to those who had only received corticosteroid treatments. Additionally, the brain activity obtained in a subgroup of patients suggested that the constraint-induced sound therapy could have prevented maladaptive auditory cortex reorganization. Constraint-induced sound therapy thus appears to be an effective, practical, and safe treatment option for sudden sensorineural hearing loss.

  11. Constraint-induced sound therapy for sudden sensorineural hearing loss – behavioral and neurophysiological outcomes

    Science.gov (United States)

    Okamoto, Hidehiko; Fukushima, Munehisa; Teismann, Henning; Lagemann, Lothar; Kitahara, Tadashi; Inohara, Hidenori; Kakigi, Ryusuke; Pantev, Christo

    2014-01-01

    Sudden sensorineural hearing loss is characterized by acute, idiopathic hearing deterioration. We report here the development and evaluation of “constraint-induced sound therapy”, which is based on a well-established neuro-rehabilitation approach, and which is characterized by the plugging of the intact ear (“constraint”) and the simultaneous, extensive stimulation of the affected ear with music. The sudden sensorineural hearing loss patients who received the constraint-induced sound therapy in addition to the standard corticosteroid therapy showed significantly better recovery of hearing function compared to those who had only received corticosteroid treatments. Additionally, the brain activity obtained in a subgroup of patients suggested that the constraint-induced sound therapy could have prevented maladaptive auditory cortex reorganization. Constraint-induced sound therapy thus appears to be an effective, practical, and safe treatment option for sudden sensorineural hearing loss. PMID:24473277

  12. A new measure for the strength of electrical synapses

    Directory of Open Access Journals (Sweden)

    Julie S Haas

    2015-09-01

    Full Text Available Electrical synapses, like chemical synapses, mediate intraneuronal communication. Electrical synapses are typically quantified by subthreshold measurements of coupling, which fall short in describing their impact on spiking activity in coupled neighbors. Here we describe a novel measurement for electrical synapse strength that directly evaluates the effect of synaptically transmitted activity on spike timing. This method, also applicable to neurotransmitter-based synapses, communicates the considerable strength of electrical synapses. For electrical synapses measured in rodent slices of the thalamic reticular nucleus, spike timing is modulated by tens of ms by activity in a coupled neighbor.

  13. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  14. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  15. Synapse proteomics: current status and quantitative applications

    NARCIS (Netherlands)

    Li, K.W.; Jimenez, C.R.

    2008-01-01

    Chemical synapses are key organelles for neurotransmission. The coordinated actions of protein networks in diverse synaptic subdomains drive the sequential molecular events of transmitter release from the presynaptic bouton, activation of transmitter receptors located in the postsynaptic density and

  16. Comparative anatomy of phagocytic and immunological synapses

    Directory of Open Access Journals (Sweden)

    Florence eNiedergang

    2016-01-01

    Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

  17. Acute visual loss following dapsone-induced methemoglobinemia and hemolysis.

    Science.gov (United States)

    Hanuschk, Delphine; Kozyreff, Alexandra; Tafzi, Naima; Tennstedt, Dominique; Hantson, Philippe; Saint-Marcoux, Franck

    2015-06-01

    While methemoglobinemia is a possible complication of chronic dapsone therapy or of acute overdose, serious adverse manifestations related to methemoglobin formation remain rare. We present an unusual case with severe ischemic retinal injury. A 30-year-old African woman presented with a sudden decrease of visual acuity secondary to retinal ischemia. She was chronically treated with dapsone (50 mg/day) for a dermatologic disease and denied any drug overdose. However, the determination of serum dapsone level on admission revealed a largely supratherapeutic concentration (20,044 μg/ml compared with 1-3.5 ± 0.5 μg/ml for therapeutic levels). The methemoglobin level at admission was 32% (sulfhemoglobin 1.2%), with hemoglobin level, 7.4 g/dl, schistocytes count, 2-5%, lactate dehydrogenase level, 580 IU/l, and haptoglobin level, dapsone, the severity of visual injury was associated with dapsone-induced methemoglobinemia and hemolysis, and perhaps also with some hematologic predisposing factors.

  18. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2016-10-01

    neurotrophic factor CNTF in promoting synapse regeneration. KEYWORDS Anandamide Auditory Brainstem Response Calcium Ion Calcium-Permeable AMPA Receptors...excitotoxic trauma (kainic acid) in vitro? f) Does CNTF promote synapse regeneration in vitro as does NT-3? W81XWH-14-1-0494 Annual Progress Report 29... CNTF ) is expressed in the organ of Corti at high levels, comparable to NT-3. We have also found that CNTF is approximately as effective as NT-3 in

  19. The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss.

    Science.gov (United States)

    Xu, Zi; Sun, Weijia; Li, Yuheng; Ling, Shukuan; Zhao, Chenyang; Zhong, Guohui; Zhao, Dingsheng; Song, Jinping; Song, Hailin; Li, Jinqiao; You, Linhao; Nie, Guangjun; Chang, Yanzhong; Li, Yingxian

    2017-01-01

    Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1+IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Noise-induced hearing loss in small-scale metal industry in Nepal.

    Science.gov (United States)

    Whittaker, J D; Robinson, T; Acharya, A; Singh, D; Smith, M

    2014-10-01

    There has been no previous research to demonstrate the risk of noise-induced hearing loss in industry in Nepal. Limited research on occupational noise-induced hearing loss has been conducted within small-scale industry worldwide, despite it being a substantial and growing cause of deafness in the developing world. The study involved a cross-sectional audiometric assessment, with questionnaire-based examinations of noise and occupational history, and workplace noise level assessment. A total of 115 metal workers and 123 hotel workers (control subjects) were recruited. Noise-induced hearing loss prevalence was 30.4 per cent in metal workers and 4.1 per cent in hotel workers, with a significant odds ratio of 10.3. Except for age and time in occupation, none of the demographic factors were significant in predicting outcomes in regression analyses. When adjusted for this finding, and previous noise-exposed occupations, the odds ratio was 13.8. Workplace noise was significantly different between the groups, ranging from 65.3 to 84.7 dBA in metal worker sites, and from 51.4 to 68.6 dBA in the control sites. Metal workers appear to have a greater risk of noise-induced hearing loss than controls. Additional research on occupational noise-induced hearing loss in Nepal and small-scale industry globally is needed.

  1. Creatine supplementation prevents acute strength loss induced by concurrent exercise.

    Science.gov (United States)

    de Salles Painelli, Vítor; Alves, Victor Tavares; Ugrinowitsch, Carlos; Benatti, Fabiana Braga; Artioli, Guilherme Giannini; Lancha, Antonio Herbert; Gualano, Bruno; Roschel, Hamilton

    2014-08-01

    To investigate the effect of creatine (CR) supplementation on the acute interference induced by aerobic exercise on subsequent maximum dynamic strength (1RM) and strength endurance (SE, total number of repetitions) performance. Thirty-two recreationally strength-trained men were submitted to a graded exercise test to determine maximal oxygen consumption (VO2max: 41.56 ± 5.24 ml kg(-1) min(-1)), anaerobic threshold velocity (ATv: 8.3 ± 1.18 km h(-1)), and baseline performance (control) on the 1RM and SE (4 × 80 % 1RM to failure) tests. After the control tests, participants were randomly assigned to either a CR (20 g day(-1) for 7 days followed by 5 g day(-1) throughout the study) or a placebo (PL-dextrose) group, and then completed 4 experimental sessions, consisting of a 5-km run on a treadmill either continuously (90 % ATv) or intermittently (1:1 min at vVO2max) followed by either a leg- or bench-press SE/1RM test. CR was able to maintain the leg-press SE performance after the intermittent aerobic exercise when compared with C (p > 0.05). On the other hand, the PL group showed a significant decrease in leg-press SE (p ≤ 0.05). CR supplementation significantly increased bench-press SE after both aerobic exercise modes, while the bench-press SE was not affected by either mode of aerobic exercise in the PL group. Although small increases in 1RM were observed after either continuous (bench press and leg press) or intermittent (bench press) aerobic exercise in the CR group, they were within the range of variability of the measurement. The PL group only maintained their 1RM. In conclusion, the acute interference effect on strength performance observed in concurrent exercise may be counteracted by CR supplementation.

  2. Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

    Directory of Open Access Journals (Sweden)

    Xiaoling Lu

    2016-01-01

    Full Text Available Hair cells (HCs are the sensory preceptor cells in the inner ear, which play an important role in hearing and balance. The HCs of organ of Corti are susceptible to noise, ototoxic drugs, and infections, thus resulting in permanent hearing loss. Recent approaches of HCs regeneration provide new directions for finding the treatment of sensor neural deafness. To have normal hearing function, the regenerated HCs must be reinnervated by nerve fibers and reform ribbon synapse with the dendrite of spiral ganglion neuron through nerve regeneration. In this review, we discuss the research progress in HC regeneration, the synaptic plasticity, and the reinnervation of new regenerated HCs in mammalian inner ear.

  3. Spiking Neural P Systems With Scheduled Synapses.

    Science.gov (United States)

    Cabarle, Francis George C; Adorna, Henry N; Jiang, Min; Zeng, Xiangxiang

    2017-12-01

    Spiking neural P systems (SN P systems) are models of computation inspired by biological spiking neurons. SN P systems have neurons as spike processors, which are placed on the nodes of a directed and static graph (the edges in the graph are the synapses). In this paper, we introduce a variant called SN P systems with scheduled synapses (SSN P systems). SSN P systems are inspired and motivated by the structural dynamism of biological synapses, while incorporating ideas from nonstatic (i.e., dynamic) graphs and networks. In particular, synapses in SSN P systems are available only at specific durations according to their schedules. The SSN P systems model is a response to the problem of introducing durations to synapses of SN P systems. Since SN P systems are in essence static graphs, it is natural to consider them for dynamic graphs also. We introduce local and global schedule types, also taking inspiration from the above-mentioned sources. We prove that SSN P systems are computationally universal as number generators and acceptors for both schedule types, under a normal form (i.e., a simplifying set of restrictions). The introduction of synapse schedules for either schedule type proves useful in programming the system, despite restrictions in the normal form.

  4. Loss-induced Enhanced Transmission in Anisotropic Density-near-zero Acoustic Metamaterials.

    Science.gov (United States)

    Shen, Chen; Jing, Yun

    2016-11-25

    Anisotropic density-near-zero (ADNZ) acoustic metamaterials are investigated theoretically and numerically in this paper and are shown to exhibit extraordinary transmission enhancement when material loss is induced. The enhanced transmission is due to the enhanced propagating and evanescent wave modes inside the ADNZ medium thanks to the interplay of near-zero density, material loss, and high wave impedance matching in the propagation direction. The equi-frequency contour (EFC) is used to reveal whether the propagating wave mode is allowed in ADNZ metamaterials. Numerical simulations based on plate-type acoustic metamaterials with different material losses were performed to demonstrate collimation and subwavelength imaging enabled by the induced loss in ADNZ media. This work provides a different way for manipulating acoustic waves.

  5. Lack of correlation between fecal blood loss and drug-induced gastric mucosal lesions

    International Nuclear Information System (INIS)

    Hedenbro, J.L.; Wetterberg, P.; Vallgren, S.; Bergqvist, L.

    1988-01-01

    Increased fecal blood loss was produced in healthy volunteers by the administration of two nonsteroidal anti-inflammatory drugs (NSAID), naproxen or fenflumizole. Basal as well as drug-induced gastrointestinal blood loss was measured using 51 Cr erythrocyte labeling. Median rise in daily fecal blood loss was 432%. All subjects were endoscoped at the initiation and at the completion of the study. Endoscopic findings were assessed quantitatively by two observers in two different ways. All subjects but three had gastric mucosal lesions at follow-up endoscopy. There was a good correlation between the endoscopic assessments but no statistical correlation between the endoscopic assessment and the increase in fecal blood loss. The data suggest that factors other than gastric mucosal lesions have to be taken into account when investigating NSAID-induced gastrointestinal bleeding

  6. Noise Induced Hearing Loss Among Cotton Textile and Carpet Mill Workers

    OpenAIRE

    ERTEM, Melikşah

    1998-01-01

    In industry increased mechanisation results in increased noise levels. Operation of textile machines carries a high risk of hearing loss. In this study the evaluation of textile worker's noise induced hearing loss was reviewed cross sectionally. The hearing of 260 textile workers exposed to noise levels between 85-95 dB(A) in carpet and cotton textile factories was assessed by means of air and bone conductance audiograms obtained. The subjects were grouped into five hearin...

  7. Induced abortion, pregnancy loss and intimate partner violence in Tanzania: a population based study

    Directory of Open Access Journals (Sweden)

    Stöckl Heidi

    2012-03-01

    Full Text Available Abstract Background Violence by an intimate partner is increasingly recognized as an important public and reproductive health issue. The aim of this study is to investigate the extent to which physical and/or sexual intimate partner violence is associated with induced abortion and pregnancy loss from other causes and to compare this with other, more commonly recognized explanatory factors. Methods This study analyzes the data of the Tanzania section of the WHO Multi-Country Study on Women's Health and Domestic Violence, a large population-based cross-sectional survey of women of reproductive age in Dar es Salaam and Mbeya, Tanzania, conducted from 2001 to 2002. All women who answered positively to at least one of the questions about specific acts of physical or sexual violence committed by a partner towards her at any point in her life were considered to have experienced intimate partner violence. Associations between self reported induced abortion and pregnancy loss with intimate partner violence were analysed using multiple regression models. Results Lifetime physical and/or sexual intimate partner violence was reported by 41% and 56% of ever partnered, ever pregnant women in Dar es Salaam and Mbeya respectively. Among the ever pregnant, ever partnered women, 23% experienced involuntary pregnancy loss, while 7% reported induced abortion. Even after adjusting for other explanatory factors, women who experienced intimate partner violence were 1.6 (95%CI: 1.06,1.60 times more likely to report an pregnancy loss and 1.9 (95%CI: 1.30,2.89 times more likely to report an induced abortion. Intimate partner violence had a stronger influence on induced abortion and pregnancy loss than women's age, socio-economic status, and number of live born children. Conclusions Intimate partner violence is likely to be an important influence on levels of induced abortion and pregnancy loss in Tanzania. Preventing intimate partner violence may therefore be beneficial

  8. Fusobacterium nucleatum and Tannerella forsythia Induce Synergistic Alveolar Bone Loss in a Mouse Periodontitis Model

    Science.gov (United States)

    Settem, Rajendra P.; El-Hassan, Ahmed Taher; Honma, Kiyonobu; Stafford, Graham P.

    2012-01-01

    Tannerella forsythia is strongly associated with chronic periodontitis, an inflammatory disease of the tooth-supporting tissues, leading to tooth loss. Fusobacterium nucleatum, an opportunistic pathogen, is thought to promote dental plaque formation by serving as a bridge bacterium between early- and late-colonizing species of the oral cavity. Previous studies have shown that F. nucleatum species synergize with T. forsythia during biofilm formation and pathogenesis. In the present study, we showed that coinfection of F. nucleatum and T. forsythia is more potent than infection with either species alone in inducing NF-κB activity and proinflammatory cytokine secretion in monocytic cells and primary murine macrophages. Moreover, in a murine model of periodontitis, mixed infection with the two species induces synergistic alveolar bone loss, characterized by bone loss which is greater than the additive alveolar bone losses induced by each species alone. Further, in comparison to the single-species infection, mixed infection caused significantly increased inflammatory cell infiltration in the gingivae and osteoclastic activity in the jaw bones. These data show that F. nucleatum subspecies and T. forsythia synergistically stimulate the host immune response and induce alveolar bone loss in a murine experimental periodontitis model. PMID:22547549

  9. Noise-Induced Hearing Loss (NIHL): literature review with a focus on occupational medicine.

    Science.gov (United States)

    Metidieri, Mirella Melo; Rodrigues, Hugo Fernandes Santos; Filho, Francisco José Motta Barros de Oliveira; Ferraz, Daniela Pereira; Neto, Antonio Fausto de Almeida; Torres, Sandro

    2013-04-01

    According to the Ministry of Health (2006), Noise-Induced Hearing Loss (NIHL) is hearing loss caused by prolonged exposure to noise. It is characterized as sensorineural hearing loss and is usually bilateral, irreversible, and progressive while the exposure to noise continues. A NIHL is a predictable and preventable disease with an epidemiologically relevant prevalence in urban communities. The hearing loss begins and predominates in the frequencies of 3, 4, and 6 kHz and eventually progresses to 8, 2, 1, 0.5, and 0.25 kHz. In Brazil, regulatory standard 15 limits the exposure to continuous noise to no more than 4 hours' exposure to 90 dBA and a maximum level of 85 dB for a full 8-hour working period. As NIHL is a preventable and predictable disease, preventive action by professionals may be able to change the prevalence of hearing loss in noisy environments.

  10. Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

    Science.gov (United States)

    Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

    2013-09-01

    To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

  11. Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations

    Directory of Open Access Journals (Sweden)

    Gabriela Hurtado-Alvarado

    2013-01-01

    Full Text Available A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis. Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002–2013 on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.

  12. [Analysis on occupational noise-induced hearing loss of different type workers in underground mining].

    Science.gov (United States)

    Liu, Q C; Duo, C H; Wang, Z; Yan, K; Zhang, J; Xiong, W; Zhu, M

    2017-11-20

    Objective: To investigate hearing loss status of blasters, drillers mechanics and so on in underground mining, and put forward suggestion diagnosis of occupational explosive deafness and occupational deafness. Methods: Underground excavation workers in a metal mine were recruited in this study, those with a history of ear disease and non-occupational deafness were all excluded. Finally, the features of pure tone audiometry of 459 noise-exposed workers were analyzed. Results: High-frequency hearing loss occurred on 351workers and the positive detection rate was 74.29%, workers who had both high-frequency and linguistic frequency hearing loss were 51 and the positive detection rate was 11.11%. The positive detection of high-frequency hearing loss in right ear (χ(2)=9.427 and P = 0.024) and in left ear (χ(2)=14.375, P =0.002) was significantly different between different exposure age groups. The positive detection of high-frequency hearing loss of driving group was the highest, followed by blasting group, mining group and machine repair group. The characteristics of the hearing loss caused by drilling noise of the blasting workers with no accident occurred were in line with that of noise-induced hearing loss. Conclusion: The diagnosis grading should be carried out according to the diagnostic criteria of occupational noise-induced deafness for the employees who engaged in the blasting operation with no record of blast accident.

  13. Presynaptic [Ca2+] and GCAPs: aspects on the structure and function of photoreceptor ribbon synapses

    Directory of Open Access Journals (Sweden)

    Frank eSchmitz

    2014-02-01

    Full Text Available Changes in intracellular calcium ions [Ca2+] play important roles in photoreceptor signalling. Consequently, intracellular [Ca2+] levels need to be tightly controlled. In the light-sensitive outer segments (OS of photoreceptors, Ca2+ regulates the activity of retinal guanylate cyclases (ret-GCs thus playing a central role in phototransduction and light-adaptation by restoring light-induced decreases in cGMP. In the synaptic terminals, changes of intracellular Ca2+ trigger various aspects of neurotransmission. Photoreceptors employ tonically active ribbon synapses that encode light-induced, graded changes of membrane potential into different rates of synaptic vesicle exocytosis. The active zones of ribbon synapses contain large electron-dense structures, synaptic ribbons, that are associated with large numbers of synaptic vesicles. Synaptic coding at ribbon synapses differs from synaptic coding at conventional (phasic synapses. Recent studies revealed new insights how synaptic ribbons are involved in this process. This review focuses on the regulation of [Ca2+] in presynaptic photoreceptor terminals and on the function of a particular Ca2+-regulated protein, the neuronal calcium sensor protein GCAP2 (guanylate cyclase-activating protein-2 in the photoreceptor ribbon synapse. GCAP2, an EF hand-containing protein plays multiple roles in the OS and in the photoreceptor synapse. In the OS, GCAP2 works as a Ca2+-sensor within a Ca2+-regulated feedback loop that adjusts cGMP levels. In the photoreceptor synapse, GCAP2 binds to RIBEYE, a component of synaptic ribbons, and mediates Ca2+-dependent plasticity at that site. Possible mechanisms are discussed.

  14. Autophagy Attenuates the Adaptive Immune Response by Destabilizing the Immunologic Synapse

    NARCIS (Netherlands)

    Wildenberg, Manon E.; Vos, Anne Christine W.; Wolfkamp, Simone C. S.; Duijvestein, Marjolijn; Verhaar, Auke P.; te Velde, Anje A.; van den Brink, Gijs R.; Hommes, Daniel W.

    2012-01-01

    BACKGROUND & AIMS: Variants in the genes ATG16L1 and IRGM affect autophagy and are associated with the development of Crohn's disease. It is not clear how autophagy is linked to loss of immune tolerance in the intestine. We investigated the involvement of the immunologic synapse-the site of contact

  15. Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling.

    Science.gov (United States)

    Zhai, Zanjing; Qu, Xinhua; Yan, Wei; Li, Haowei; Liu, Guangwang; Liu, Xuqiang; Tang, Tingting; Qin, An; Dai, Kerong

    2014-02-01

    Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a significant role in cancer-associated bone loss. In this study, we examined the efficacy of the natural compound andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata, in reducing breast cancer-induced osteolysis. AP prevented human breast cancer-induced bone loss by suppressing RANKL-mediated and human breast cancer cell-induced osteoclast differentiation. Molecular analysis revealed that AP prevented osteoclast function by inhibiting RANKL-induced NF-κB and ERK signaling pathway in lower dose (20 μM), as well as inducing apoptosis at higher dose (40 μM). Thus, AP is a potent inhibitor of breast cancer-induced bone metastasis.

  16. Multiassociative Memory: Recurrent Synapses Increase Storage Capacity.

    Science.gov (United States)

    Gauy, Marcelo Matheus; Meier, Florian; Steger, Angelika

    2017-05-01

    The connection density of nearby neurons in the cortex has been observed to be around 0.1, whereas the longer-range connections are present with much sparser density (Kalisman, Silberberg, & Markram, 2005 ). We propose a memory association model that qualitatively explains these empirical observations. The model we consider is a multiassociative, sparse, Willshaw-like model consisting of binary threshold neurons and binary synapses. It uses recurrent synapses for iterative retrieval of stored memories. We quantify the usefulness of recurrent synapses by simulating the model for small network sizes and by doing a precise mathematical analysis for large network sizes. Given the network parameters, we can determine the precise values of recurrent and afferent synapse densities that optimize the storage capacity of the network. If the network size is like that of a cortical column, then the predicted optimal recurrent density lies in a range that is compatible with biological measurements. Furthermore, we show that our model is able to surpass the standard Willshaw model in the multiassociative case if the information capacity is normalized per strong synapse or per bits required to store the model, as considered in Knoblauch, Palm, and Sommer ( 2010 ).

  17. Glutamate synapses in human cognitive disorders.

    Science.gov (United States)

    Volk, Lenora; Chiu, Shu-Ling; Sharma, Kamal; Huganir, Richard L

    2015-07-08

    Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

  18. The importance of rapid, disturbance-induced losses in carbon management and sequestration

    Science.gov (United States)

    Breshears, D.D.; Allen, Craig D.

    2002-01-01

    Management of terrestrial carbon fluxes is being proposed as a means of increasing the amount of carbon sequestered in the terrestrial biosphere. This approach is generally viewed only as an interim strategy for the coming decades while other longer-term strategies are developed and implemented — the most important being the direct reduction of carbon emissions. We are concerned that the potential for rapid, disturbance-induced losses may be much greater than is currently appreciated, especially by the decision-making community. Here we wish to: (1) highlight the complex and threshold-like nature of disturbances — such as fire and drought, as well as the erosion associated with each — that could lead to carbon losses; (2) note the global extent of ecosystems that are at risk of such disturbance-induced carbon losses; and (3) call for increased consideration of and research on the mechanisms by which large, rapid disturbance-induced losses of terrestrial carbon could occur. Our lack of ability as a scientific community to predict such ecosystem dynamics is precluding the effective consideration of these processes into strategies and policies related to carbon management and sequestration. Consequently, scientists need to do more to improve quantification of these potential losses and to integrate them into sound, sustainable policy options.

  19. Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota.

    Science.gov (United States)

    Corrêa, Jôice Dias; Saraiva, Adriana Machado; Queiroz-Junior, Celso Martins; Madeira, Mila Fernandes Moreira; Duarte, Poliana Mendes; Teixeira, Mauro Martins; Souza, Danielle Glória; da Silva, Tarcília Aparecida

    2016-06-01

    Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Partitioning the variance in calorie restriction-induced weight and fat loss in outbred mice.

    Science.gov (United States)

    Vaanholt, Lobke M; Lane, Jeffrey E; Garner, Bethany; Speakman, John R

    2016-10-01

    An increased understanding of the factors influencing interindividual variation in calorie restriction (CR)-induced weight loss is necessary to combat the current obesity epidemic. This study investigated the partitioning of the phenotypic variation in CR-induced wight loss. Two generations of male and female outbred MF1 mice raised by their biological mother or a foster mother were studied. Mice were exposed to 4 weeks of 30% CR when 6 months old. Heritability was estimated at 0.43 ± 0.12 for CR-induced changes in body mass and 0.24 ± 0.10 for fat mass using mid-parent-offspring regressions. No significant relationships between weight loss in fathers or foster mothers and offspring were observed. Partitioning of phenotypic variance in weight loss using maximum likelihood modeling indicated 19 ± 17% of the variation could be attributed to additive genetic effects, 8 ± 14% to maternal effects during pregnancy, and weight loss could be attributed to additive genetic and maternal effects during pregnancy, but not to maternal effects in lactation. Genetic differences in food intake and general activity may play a role in determining these effects. © 2016 The Obesity Society.

  1. Prevention of adolescents' music-induced hearing loss due to discotheque attendance: a Delphi study

    NARCIS (Netherlands)

    Vogel, I.; Brug, J.; Ploeg, van der C.P.B.; Raat, H.

    2009-01-01

    Noise-induced hearing loss is a significant social and public health problem, which is found in increasing numbers of adolescents. Young people are particularly likely to expose themselves to potentially damaging loud sounds during leisure activities. Visiting discotheques is one of the most popular

  2. Effects of noise-induced hearing loss within Port Harcourt metropolis ...

    African Journals Online (AJOL)

    This paper investigates the effects of Noise-Induced Hearing Loss within Port Harcourt Metropolis using a micro-controlled diagnostic audiometer (Kamplex KLD21).The data was obtained at two specific locations namely: Rivers State University of Science and Technology and Port Harcourt International Airport.

  3. Predictors of diet-induced weight loss in overweight adults with type 2 diabetes

    NARCIS (Netherlands)

    K.A.C. Berk (Kirsten); M.T. Mulder (Monique); A.J.M. Verhoeven; Van Wietmarschen, H. (Herman); Boessen, R. (Ruud); Pellis, L.P. (Linette P.); Van Spijker, A.T. (Adriaan T); R. Timman (Reinier); B. Özcan (Behiye); E.J.G. Sijbrands (Eric)

    2016-01-01

    textabstractAims A very low calorie diet improves the metabolic regulation of obesity related type 2 diabetes, but not for all patients, which leads to frustration in patients and professionals alike. The aim of this study was to develop a prediction model of diet-induced weight loss in type 2

  4. Predictors of diet-induced weight loss in overweight adults with type 2 diabetes

    NARCIS (Netherlands)

    Berk, K.A.; Mulder, M.T.; Verhoeven, A.J.M.; Wietmarschen, H. van; Boessen, R.; Pellis, L.P.; Spijker, A.T. van; Timman, R.; Ozcan, B.; Sijbrands, E.J.G.

    2016-01-01

    Aims A very low calorie diet improves the metabolic regulation of obesity related type 2 diabetes, but not for all patients, which leads to frustration in patients and professionals alike. The aim of this study was to develop a prediction model of diet-induced weight loss in type 2 diabetes. Methods

  5. Green Tea Catechin Consumption Enhances Exercise-Induced Abdominal Fat Loss

    Science.gov (United States)

    Aim: This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercised-induced weight loss. Methods: Participants (N=132) were randomly assigned to receive a 500 mL beverage containing approximately 625 mg of...

  6. Radiation-induced loss studies in Er-doped fiber amplifier systems

    Science.gov (United States)

    Goltsos, William C.

    1996-04-01

    Radiation-induced loss in erbium-doped fiber and fiber-based components used in optical amplifiers at 1.5 micrometer has been studied under electron and gamma irradiation up to total doses of 100 krad(Si). Radiation sources used to simulate the natural space environment were a Van de Graaff generator for 1.5 MeV electrons, and Cobalt-60 for 1.17 and 1.33 MeV photons. Induced-loss and 60-hour anneal were measured in Er-doped fiber while simultaneously illuminated with 0.7 W of 980-nm pump, and 1 mW of 1550-nm signal light in an operating amplifier configuration. Initial induced loss from electron irradiation was found to decrease under intense photoillumination to 0.010 dB/m-krad at 980 nm and .007 dB/m- krad at 1550 nm, versus 0.017 dB/m-krad and 0.008 dB/m-krad respectively when unilluminated, and showed a more rapid anneal in some tested fibers. Individual components of an optical isolator were tested for gamma-irradiation sensitivity. A 1 degree change in polarization rotation angle was found in a garnet-film Faraday rotator after exposure, and the GRIN lens showed an initial induced loss of 0.5 dB that annealed to 0.1 dB after 2 weeks under conditions of 1 mW, 1550-nm photoillumination.

  7. Noise induced hearing loss: Screening with pure-tone audiometry and speech-in-noise testing

    NARCIS (Netherlands)

    Leensen, M.C.J.

    2013-01-01

    Noise-induced hearing loss (NIHL) is a highly prevalent public health problem, caused by exposure to loud noises both during leisure time, e.g. by listening to loud music, and during work. In the past years NIHL was the most commonly reported occupational disease in the Netherlands. Hearing damage

  8. Noise.Induced Hearing Loss Still a Problem in Shipbuilders: A Cross ...

    African Journals Online (AJOL)

    Background: Workplace safety regulations seek to mitigate noise.induced hearing loss (NIHL), conventionally associated with the shipbuilding industry. Despite this, are workers still predisposed to NIHL? Aims: To study the prevalence of NIHL among noise.exposed subjects in the shipbuilding industry in Goa and to ...

  9. Raman and loss induced quantum noise in depleted fiber optical parametric amplifiers

    DEFF Research Database (Denmark)

    Friis, Søren Michael Mørk; Rottwitt, Karsten; McKinstrie, C. J.

    2013-01-01

    We present a semi-classical approach for predicting the quantum noise properties of fiber optical parametric amplifiers. The unavoidable contributors of noise, vacuum fluctuations, loss-induced noise, and spontaneous Raman scattering, are included in the analysis of both phase-insensitive and phase...

  10. Radiation induced cell loss in rat submandibular gland and its relation to gland function

    NARCIS (Netherlands)

    Zeilstra, LJW; Vissink, A; Konings, AWT; Coppes, RP

    Purpose: To understand early and late radiation-induced loss of function of the submandibular gland, changes in cell number were documented and correlated with data on gland function. Modulation of the radiation effect by sialogogues was used to investigate possible mechanisms of action. Materials

  11. Changes in taste perception and eating behavior after bariatric surgery-induced weight loss in women.

    Science.gov (United States)

    Pepino, Marta Yanina; Bradley, David; Eagon, J Christopher; Sullivan, Shelby; Abumrad, Nada A; Klein, Samuel

    2014-05-01

    Roux-en-Y gastric bypass (RYGB) surgery causes greater weight loss than laparoscopic adjustable gastric banding (LAGB). We tested the hypothesis that RYGB has weight loss-independent effects on taste perception, which influence eating behavior and contribute to the greater weight loss. Subjects were studied before and after ∼20% weight loss induced by RYGB (n = 17) or LAGB (n = 10). The following have been evaluated: taste sensitivity for sweet, salty and savory stimuli, sucrose and monosodium glutamate (MSG) preferences, sweetness palatability, eating behavior, and expression of taste-related genes in biopsies of fungiform papillae. Weight loss induced by both procedures caused the same decrease in: preferred sucrose concentration (-12 ± 10%), perceived sweetness of sucrose (-7 ± 5%), cravings for sweets and fast-foods (-22 ± 5%), influence of emotions (-27 ± 5%), and external food cues (-30 ± 4%) on eating behavior, and expression of α-gustducin in fungiform papillae (all P values cause similar alterations in eating behaviors, when weight loss is matched. These changes in eating behavior were not associated with changes in taste sensitivity, suggesting other, as yet unknown, mechanisms are involved. Copyright © 2013 The Obesity Society.

  12. Effect of induced diabetes mellitus on alveolar bone loss after 30 days of ligature-induced periodontal disease.

    Science.gov (United States)

    Gomes, Débora Aline Silva; Spolidorio, Denise Madalena Palomari; Pepato, Maria Teresa; Zuza, Elizangela Partata; de Toledo, Benedicto Egbert Corrêa; Gonçalves, Andréa; Spolidorio, Luis Carlos; Pires, Juliana Rico

    2009-04-01

    Several studies have shown that diabetics are more susceptible to the development of severe periodontal disease. Currently, the use of animal models can be considered a feasible alternative in radiographic assessments of these two pathologies. The purpose of this radiographic study was to evaluate the effect of induced diabetes mellitus on alveolar bone loss after 30 days of ligature-induced periodontal disease. Sixty-four Wistar rats were randomly distributed into four experimental groups. Diabetes was induced in Groups II and IV, while periodontal disease was induced in Groups III and IV; Group I was used as control. In order to perform the radiographic assessment of the specimens, the rats were killed on the 3rd and 30th days of the study. Radiographic measurements were assessed with ANOVA and Tukey's test to determine statistically significant differences (p diabetic group with periodontal disease (Group IV) featured statistically significant greater bone loss when compared to the other groups. These results suggested that the alveolar bone loss resulting from the periodontal disease installation is greater when associated to the diabetes mellitus.

  13. Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis.

    Science.gov (United States)

    Garimella, Manasa G; Kour, Supinder; Piprode, Vikrant; Mittal, Monika; Kumar, Anil; Rani, Lekha; Pote, Satish T; Mishra, Gyan C; Chattopadhyay, Naibedya; Wani, Mohan R

    2015-12-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance. Copyright © 2015 by The American Association of Immunologists, Inc.

  14. Swept-sine noise-induced damage as a hearing loss model for preclinical assays

    Directory of Open Access Journals (Sweden)

    Lorena eSanz

    2015-02-01

    Full Text Available Mouse models are key tools for studying cochlear alterations in noise-induced hearing loss and for evaluating new therapies. Stimuli used to induce deafness in mice are usually white and octave band noises that include very low frequencies, considering the large mouse auditory range. We designed different sound stimuli, enriched in frequencies up to 20 kHz (violet noises to examine their impact on hearing thresholds and cochlear cytoarchitecture after short exposure. In addition, we developed a cytocochleogram to quantitatively assess the ensuing structural degeneration and its functional correlation. Finally, we used this mouse model and cochleogram procedure to evaluate the potential therapeutic effect of transforming growth factor β1 inhibitors P17 and P144 on noise-induced hearing loss. CBA mice were exposed to violet swept-sine noise with different frequency ranges (2-20 or 9-13 kHz and levels (105 or 120 dB SPL for 30 minutes. Mice were evaluated by auditory brainstem response and otoacoustic emission tests prior to and 2, 14 and 28 days after noise exposure. Cochlear pathology was assessed with gross histology; hair cell number was estimated by a stereological counting method. Our results indicate that functional and morphological changes induced by violet swept-sine noise depend on the sound level and frequency composition. Partial hearing recovery followed the exposure to 105 dB SPL, whereas permanent cochlear damage resulted from the exposure to 120 dB SPL. Exposure to 9-13 kHz noise caused an auditory threshold shift in those frequencies that correlated with hair cell loss in the corresponding areas of the cochlea that were spotted on the cytocochleogram. In summary, we present mouse models of noise-induced hearing loss, which depending on the sound properties of the noise, cause different degrees of cochlear damage, and could therefore be used to study molecules which are potential players in hearing loss protection and repair.

  15. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Wei, E-mail: weiming@xiyi.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Department of Pharmacology, Xi’an Medical University, Xi’an 710021 (China); Lu, Gan, E-mail: leonming99@163.com [Department of Gynecology of Shaanxi Provincial People’s Hospital, Xi’an, 710068 (China); Xin, Sha, E-mail: 248967979@qq.com [Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Huanyu, Lu, E-mail: 2366927258@qq.com [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an 710032 (China); Yinghao, Jiang, E-mail: jiangyh@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Xiaoying, Lei, E-mail: leixiaoy@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Chengming, Xu, E-mail: chengmingxu@yeah.net [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Banjun, Ruan, E-mail: running@163.com [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Li, Wang, E-mail: wanglifw@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); and others

    2016-08-05

    Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.

  16. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation

    International Nuclear Information System (INIS)

    Ming, Wei; Lu, Gan; Xin, Sha; Huanyu, Lu; Yinghao, Jiang; Xiaoying, Lei; Chengming, Xu; Banjun, Ruan; Li, Wang

    2016-01-01

    Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.

  17. Cell Biology of Astrocyte-Synapse Interactions.

    Science.gov (United States)

    Allen, Nicola J; Eroglu, Cagla

    2017-11-01

    Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the establishment and maintenance of proper synaptic connectivity, our understanding of their role in brain function is still in its infancy. We propose that this is at least in part due to large gaps in our knowledge of the cell biology of astrocytes and the mechanisms they use to interact with synapses. In this review, we summarize some of the seminal findings that yield important insight into the cellular and molecular basis of astrocyte-neuron communication, focusing on the role of astrocytes in the development and remodeling of synapses. Furthermore, we pose some pressing questions that need to be addressed to advance our mechanistic understanding of the role of astrocytes in regulating synaptic development. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Resolution of methylphenidate osmotic release oral system-induced hair loss in two siblings after dose escalation.

    Science.gov (United States)

    Ardic, Ulku Akyol; Ercan, Eyup Sabri

    2017-11-01

    This report describes the cases of two siblings who experienced hair loss after treatment with methylphenidate (MPH) osmotic release oral system (OROS). Hair loss was resolved after discontinuation of the drug, but the children re-initiated treatment, after which hair loss again occurred, but they continued the treatment. After dose escalation, the hair loss resolved. This is the first report to describe resolution of OROS-MPH-induced hair loss after dose escalation. © 2017 Japan Pediatric Society.

  19. Salicylate-Induced Hearing Loss Trigger Structural Synaptic Modifications in the Ventral Cochlear Nucleus of Rats via Medial Olivocochlear (MOC) Feedback Circuit.

    Science.gov (United States)

    Fang, Lian; Fu, YaoYao; Zhang, Tian-Yu

    2016-06-01

    Lesion-induced cochlear damage can result in synaptic outgrowth in the ventral cochlear nucleus (VCN). Tinnitus may be associated with the synaptic outgrowth and hyperactivity in the VCN. However, it remains unclear how hearing loss triggers structural synaptic modifications in the VCN of rats subjected to salicylate-induced tinnitus. To address this issue, we evaluated tinnitus-like behavior in rats after salicylate treatment and compared the amplitude of the distortion product evoked otoacoustic emission (DPOAE) and auditory brainstem response (ABR) between control and treated rats. Moreover, we observed the changes in the synaptic ultrastructure and in the expression levels of growth-associated protein (GAP-43), brain-derived neurotrophic factor (BDNF), the microglial marker Iba-1 and glial fibrillary acidic protein (GFAP) in the VCN. After salicylate treatment (300 mg/kg/day for 4 and 8 days), analysis of the gap prepulse inhibition of the acoustic startle showed that the rats were experiencing tinnitus. The changes in the DPOAE and ABR amplitude indicated an improvement in cochlear sensitivity and a reduction in auditory input following salicylate treatment. The treated rats displayed more synaptic vesicles and longer postsynaptic density in the VCN than the control rats. We observed that the GAP-43 expression, predominantly from medial olivocochlear (MOC) neurons, was significantly up-regulated, and that BDNF- and Iba-1-immunoreactive cells were persistently decreased after salicylate administration. Furthermore, GFAP-immunoreactive astrocytes, which is associated with synaptic regrowth, was significantly increased in the treated groups. Our study revealed that reduced auditory nerve activity triggers synaptic outgrowth and hyperactivity in the VCN via a MOC neural feedback circuit. Structural synaptic modifications may be a reflexive process that compensates for the reduced auditory input after salicylate administration. However, massive increases in

  20. Epidermal growth factor receptor is a preferred target for treating amyloid-β-induced memory loss.

    Science.gov (United States)

    Wang, Lei; Chiang, Hsueh-Cheng; Wu, Wenjuan; Liang, Bin; Xie, Zuolei; Yao, Xinsheng; Ma, Weiwei; Du, Shuwen; Zhong, Yi

    2012-10-09

    Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer's disease. We took two independent approaches, including synaptic-plasticity-based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic compounds not only showed positive effects in behavioral tests but also antagonized the Aβ oligomers-induced activation of the epidermal growth factor receptor (EGFR). Such surprising converging outcomes from two parallel approaches lead us to conclude that EGFR is a preferred target for treating Aβ-induced memory loss.

  1. Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice.

    Directory of Open Access Journals (Sweden)

    Ali A Almishaal

    2017-08-01

    Full Text Available Congenital cytomegalovirus (CMV infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL yet the mechanisms of hearing loss remain obscure. Natural Killer (NK cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.

  2. Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals.

    Science.gov (United States)

    Charpentier, Caroline J; De Martino, Benedetto; Sim, Alena L; Sharot, Tali; Roiser, Jonathan P

    2016-04-01

    Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology. © The Author (2015). Published by Oxford University Press.

  3. Functional hallmarks of GABAergic synapse maturation and the diverse roles of neurotrophins

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    Rosemarie eGrantyn

    2011-07-01

    Full Text Available Functional impairment of the adult brain can result from deficits in the ontogeny of GABAergic synaptic transmission. Gene defects underlying autism spectrum disorders, Rett’s syndrome or some forms of epilepsy, but also a diverse set of syndromes accompanying perinatal trauma, hormonal imbalances, intake of sleep-inducing or mood-improving drugs or, quite common, alcohol intake during pregnancy can alter GABA signaling early in life. The search for therapeutically relevant endogenous molecules or exogenous compounds able to alleviate the consequences of dysfunction of GABAergic transmission in the embryonic or postnatal brain requires a clear understanding of its site- and state-dependent development. At the level of single synapses, it is necessary to discriminate between presynaptic and postsynaptic alterations, and to define parameters that can be regarded as both suitable and accessible for the quantification of developmental changes. Here we focus on the performance of GABAergic synapses in two brain structures, the hippocampus and the superior colliculus, describe some novel aspects of neurotrophin effects during the development of GABAergic synaptic transmission and examine the applicability of the following rules: 1 Synaptic transmission starts with GABA, 2 Nascent/immature GABAergic synapses operate in a ballistic mode (multivesicular release, 3 Immature synaptic terminals release vesicles with higher probability than mature synapses, 4 Immature GABAergic synapses are prone to paired pulse and tetanic depression, 5 Synapse maturation is characterized by an increasing dominance of synchronous over asynchronous release, 6 In immature neurons GABA acts as a depolarizing transmitter, 7 Synapse maturation implies IPSC shortening due to an increase in alpha1 subunit expression, 8 Extrasynaptic (tonic conductances can inhibit the development of synaptic (phasic GABA actions.

  4. Quantitative 3D Ultrastructure of Thalamocortical Synapses from the "Lemniscal" Ventral Posteromedial Nucleus in Mouse Barrel Cortex.

    Science.gov (United States)

    Rodriguez-Moreno, Javier; Rollenhagen, Astrid; Arlandis, Jaime; Santuy, Andrea; Merchan-Pérez, Angel; DeFelipe, Javier; Lübke, Joachim H R; Clasca, Francisco

    2017-07-28

    Thalamocortical synapses from "lemniscal" neurons of the dorsomedial portion of the rodent ventral posteromedial nucleus (VPMdm) are able to induce with remarkable efficacy, despite their relative low numbers, the firing of primary somatosensory cortex (S1) layer 4 (L4) neurons. To which extent this high efficacy depends on structural synaptic features remains unclear. Using both serial transmission (TEM) and focused ion beam milling scanning electron microscopy (FIB/SEM), we 3D-reconstructed and quantitatively analyzed anterogradely labeled VPMdm axons in L4 of adult mouse S1. All VPMdm synapses are asymmetric. Virtually all are established by axonal boutons, 53% of which contact multiple (2-4) elements (overall synapse/bouton ratio = 1.6). Most boutons are large (mean 0.47 μm3), and contain 1-3 mitochondria. Vesicle pools and postsynaptic density (PSD) surface areas are large compared to others in rodent cortex. Most PSDs are complex. Most synapses (83%) are established on dendritic spine heads. Furthermore, 15% of the postsynaptic spines receive a second, symmetric synapse. In addition, 13% of the spine heads have a large protrusion inserted into a membrane pouch of the VPMdm bouton. The unusual combination of structural features in VPMdm synapses is likely to contribute significantly to the high efficacy, strength, and plasticity of these thalamocortical synapses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss.

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    Kujawa, Sharon G; Liberman, M Charles

    2015-12-01

    The classic view of sensorineural hearing loss (SNHL) is that the "primary" targets are hair cells, and that cochlear-nerve loss is "secondary" to hair cell degeneration. Our recent work in mouse and guinea pig has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear-nerve/hair-cell synapses. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained hidden for three reasons: 1) the spiral ganglion cells, the cochlear neural elements commonly assessed in studies of SNHL, survive for years despite loss of synaptic connection with hair cells, 2) the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to see in the light microscope, and 3) the degeneration is selective for cochlear-nerve fibers with high thresholds. Although not required for threshold detection in quiet (e.g. threshold audiometry or auditory brainstem response threshold), these high-threshold fibers are critical for hearing in noisy environments. Our research suggests that 1) primary neural degeneration is an important contributor to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons and re-establishment of their peripheral synapses. This article is part of a Special Issue entitled . Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Synthetic PreImplantation Factor (PIF prevents fetal loss by modulating LPS induced inflammatory response.

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    Nicoletta Di Simone

    Full Text Available Maternal control of inflammation is essential during pregnancy and an exaggerated response is one of the underlying causes of fetal loss. Inflammatory response is mediated by multiple factors and Toll-like receptors (TLRs are central. Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated speck-like protein containing a CARD (ASC and caspase-1 into the inflammasome and production of pro-inflammatory cytokines IL-1β and IL-18. Given that preventing measures are lacking, we investigated PreImplantation Factor (PIF as therapeutic option as PIF modulates Inflammation in pregnancy. Additionally, synthetic PIF (PIF analog protects against multiple immune disorders. We used a LPS induced murine model of fetal loss and synthetic PIF reduced this fetal loss and increased the embryo weight significantly. We detected increased PIF expression in the placentae after LPS insult. The LPS induced serum and placenta cytokines were abolished by synthetic PIF treatment and importantly synthetic PIF modulated key members of inflammasome complex NALP-3, ASC, and caspase-1 as well. In conclusion our results indicate that synthetic PIF protects against LPS induced fetal loss, likely through modulation of inflammatory response especially the inflammasome complex. Given that synthetic PIF is currently tested in autoimmune diseases of non-pregnant subjects (clinicaltrials.gov, NCT02239562, therapeutic approach during pregnancy can be envisioned.

  7. Omega-3 Fatty Acid Intervention Suppresses Lipopolysaccharide-Induced Inflammation and Weight Loss in Mice

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    Ying-Hua Liu

    2015-02-01

    Full Text Available Bacterial endotoxin lipopolysaccharide (LPS-induced sepsis is a critical medical condition, characterized by a severe systemic inflammation and rapid loss of muscle mass. Preventive and therapeutic strategies for this complex disease are still lacking. Here, we evaluated the effect of omega-3 (n-3 polyunsaturated fatty acid (PUFA intervention on LPS-challenged mice with respect to inflammation, body weight and the expression of Toll-like receptor 4 (TLR4 pathway components. LPS administration induced a dramatic loss of body weight within two days. Treatment with n-3 PUFA not only stopped loss of body weight but also gradually reversed it back to baseline levels within one week. Accordingly, the animals treated with n-3 PUFA exhibited markedly lower levels of inflammatory cytokines or markers in plasma and tissues, as well as down-regulation of TLR4 pathway components compared to animals without n-3 PUFA treatment or those treated with omega-6 PUFA. Our data demonstrate that n-3 PUFA intervention can suppress LPS-induced inflammation and weight loss via, at least in part, down-regulation of pro-inflammatory targets of the TLR4 signaling pathway, and highlight the therapeutic potential of n-3 PUFA in the management of sepsis.

  8. Spermatorrhea and Loss of Libido Induced by Topiramate: First Case Report and Review of Literature.

    Science.gov (United States)

    Wu, Mengqian; Hao, Nanya; Zhou, Dong

    Topiramate (TPM) is a broad-spectrum antiepileptic drug used for a variety of clinical conditions, including migraine prophylaxis and mood disorders. Spermatorrhea accompanied by loss of libido severely lowers quality of life for men, but had never been reported as a possible adverse effect of TPM. Here, we present a case of a 39-year-old Chinese man who was diagnosed with partial epilepsy and treated with TPM (100 mg/d). Eleven days after initiating TPM treatment, he began to experience spermatorrhea every 2 to 3 days, accompanied by loss of libido, lack of energy, lassitude, irascibility, weakness, poor appetite, frequent urination, and nocturia. The symptoms continued for 2 months. After withdrawal of TPM, symptoms disappeared and did not recur. This is the first case report of TPM-induced spermatorrhea and loss of libido in China. Spermatorrhea and loss of libido are probably rare adverse effects of TPM treatment. When these symptoms occur in a patient taking TPM, the possibility that they are adverse effects to this drug should be considered, and switching the patient to a different drug may be a good option. The underlying mechanism by which TPM induces spermatorrhea may be related to increased serotonin level, and loss of libido may be related to changes in serotonin and hormone levels.

  9. Occupational noise-induced hearing loss in Indian steel industry workers: an exploratory study.

    Science.gov (United States)

    Singh, Lakhwinder Pal; Bhardwaj, Arvind; Deepak, Kishore Kumar

    2013-04-01

    The present study focused on exploring the current level of hearing protection and subsequently determined the prevalence of occupational noise-induced hearing loss among casting and forging industry workers. The casting and forging industry provides employment to a significant portion of the population. The level of hearing protection was assessed through questionnaire survey of 572 workers. Out of these workers, 165 and another control group of 57 participants were assessed by formal audiometry. Audiometric tests were conducted at frequencies of 1.0 KHz to 8.0 KHz.The occurrence of hearing loss was determined on the basis of a hearing threshold level with a low fence of 25 dB. Student's test and ANOVA were used to compare the various groups; a p value workers sampled showed significant hearing loss at medium and high frequencies. The analyses revealed a higher prevalence of significant hearing loss among the forging workers compared with the workers associated with the other activities. The workers of the Indian steel industry are highly exposed to occupational noise. The majority of workers are not protected from noise-induced hearing loss. There is a need to provide special ear protectors for workers engaged in forging. A complete hearing protection program, including training, audiometry, job rotation, and the use of hearing protection devices, needs to be introduced.

  10. Reversible, non-plaque-induced loss of osseointegration of successfully loaded dental implants.

    Science.gov (United States)

    Mattheos, Nikos; Schittek Janda, Martin; Zampelis, Antonios; Chronopoulos, Vasilios

    2013-03-01

    Excess loading has been often cited as a reason for the failure of dental implants or bone loss post-osseointegration. The available data from animal studies have failed to show a clear role for excessive loading in the loss of osseointegration. The present case documentations aimed at providing a deeper insight into the medium- to long-term influence of occlusal loading on osseointegrated implants, and describe the clinical manifestations of such pathology. Two cases of loss of osseointegration are documented with single implants in the posterior maxilla. Implant mobility was in both cases the first and only sign of pathology, with the absence of plaque-induced inflammation and marginal bone loss. Re-osseointegration of the implants was achieved after the removal of the prosthetic reconstruction. The two cases reported that the loss of osseointegration in the absence of plaque-induced peri-implant inflammation is possible, although the clinical manifestations were very different to these of peri-implantitis. Once the occlusal loading was withdrawn, re-osseointegration was clinically confirmed in a period of 6-8 months. © 2012 John Wiley & Sons A/S.

  11. Ultrafine carbon particles promote rotenone-induced dopamine neuronal loss through activating microglial NADPH oxidase

    International Nuclear Information System (INIS)

    Wang, Yinxi; Liu, Dan; Zhang, Huifeng; Wang, Yixin; Wei, Ling; Liu, Yutong; Liao, Jieying; Gao, Hui-Ming; Zhou, Hui

    2017-01-01

    Background: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. Methods: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures. Immunochemistry using antibody against tyrosine hydroxylase was performed to detect DA neuronal loss. Measurement of extracellular superoxide and intracellular reactive oxygen species (ROS) were performed to examine activation of NADPH oxidase. Genetic deletion and pharmacological inhibition of NADPH oxidase and MAC-1 receptor in microglia were employed to examine their role in DA neuronal loss triggered by ufCB and rotenone. Results: In rodent midbrain neuron-glia cultures, ufCB and rotenone alone caused neuronal death in a dose-dependent manner. In particularly, ufCB at doses of 50 and 100 μg/cm 2 induced significant loss of DA neurons. More importantly, nontoxic doses of ufCB (10 μg/cm 2 ) and rotenone (2 nM) induced synergistic toxicity to DA neurons. Microglial activation was essential in this process. Furthermore, superoxide production from microglial NADPH oxidase was critical in ufCB/rotenone-induced neurotoxicity. Studies in mix-glia cultures showed that ufCB treatment activated microglial NADPH oxidase to induce superoxide production. Firstly, ufCB enhanced the expression of NADPH oxidase subunits (gp91 phox , p47 phox and p40 phox ); secondly, ufCB was recognized by microglial surface MAC-1 receptor and consequently promoted rotenone-induced p47 phox and p67 phox translocation assembling active NADPH oxidase. Conclusion: ufCB and rotenone worked in synergy to activate NADPH oxidase in microglia, leading to oxidative damage to DA neurons. Our

  12. Transforming growth factor β1 inhibition protects from noise-induced hearing loss

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    Silvia eMurillo-Cuesta

    2015-03-01

    Full Text Available Excessive exposure to noise damages the principal cochlear structures leading to hearing impairment. Inflammatory and immune responses are central mechanisms in cochlear defensive response to noise but, if unregulated, they contribute to inner ear damage and hearing loss. Transforming growth factor ß (TGF-ß is a key regulator of both responses and high levels of this factor have been associated with cochlear injury in hearing loss animal models. To evaluate the potential of targeting TGF-ß as a therapeutic strategy for preventing or ameliorating noise-induced hearing loss, we studied the auditory function, cochlear morphology, gene expression and oxidative stress markers in mice exposed to noise and treated with TGF-ß1 peptidic inhibitors P17 and P144, just before or immediately after noise insult. Our results indicate that systemic administration of both peptides significantly improved both the evolution of hearing thresholds and the degenerative changes induced by noise-exposure in lateral wall structures. Moreover, treatments ameliorated the inflammatory state and redox balance. These therapeutic effects were dose-dependent and more effective if the TGF-ß1 inhibitors were administered prior to inducing the injury. In conclusion, inhibition of TGF-ß1 actions with antagonistic peptides represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage.

  13. Role of glucocorticoid-induced leucine zipper (GILZ in inflammatory bone loss.

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    Nianlan Yang

    Full Text Available TNF-α plays a key role in the development of rheumatoid arthritis (RA and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ, a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3.6kb rat type I collagen promoter fragment. Results showed that overexpression of GILZ in bone marrow mesenchymal stem/progenitor cells protected mice from TNF-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12-15. However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.

  14. Musicians′ ability to judge the risk of acquiring noise induced hearing loss

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    Björn Hagerman

    2013-01-01

    Full Text Available The objective of this research was to study musicians′ abilities to estimate the risk to obtain a hearing loss. Twenty-two professional musicians mainly playing classical music wore dosimeters during 2 working weeks. They also wrote a diary describing all their musical activities and tried to judge the percentage of time that every activity was harmful to their hearing. Half of the musicians seemed to be capable to reasonably judge the harmfulness of the music that they were exposed to. They started to judge the levels to be risky at 80 dB(A and regarded themselves as sligthly more susceptible to noise induced hearing loss than normal.

  15. Deoxynivalenol-induced weight loss in the diet-induced obese mouse is reversible and PKR-independent.

    Science.gov (United States)

    Flannery, Brenna M; He, Kaiyu; Pestka, James J

    2013-07-31

    The trichothecene deoxynivalenol (DON), a potent ribotoxic mycotoxin produced by the cereal blight fungus Fusarium graminearum, commonly contaminates grain-based foods. Oral exposure to DON causes decreased food intake, reduced weight gain and body weight loss in experimental animals - effects that have been linked to dysregulation of hormones responsible for mediating satiety at the central nervous system level. When diet-induced obese (DIO) mice are fed DON, they consume less food, eventually achieving body weights of control diet-fed mice. Here, we extended these findings by characterizing: (1) reversibility of DON-induced body weight loss and anorexia in DIO mice and (2) the role of double-stranded RNA-activated protein kinase (PKR) which has been previously linked to initiation of the ribotoxic stress response. The results demonstrated that DON-induced weight loss was reversible in DIO mice and this effect corresponded to initiation of a robust hyperphagic response. When DIO mice deficient in PKR were exposed to DON, they exhibited weight suppression similar to DIO wild-type fed the toxin, suggesting the toxin's weight effects were not dependent on PKR. Taken together, DON's effects on food consumption and body weight are not permanent and, furthermore, PKR is not an essential signaling molecule for DON's anorectic and weight effects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

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    Marta Esteves da Silva

    2015-11-01

    Full Text Available Lateral diffusion in the membrane and endosomal trafficking both contribute to the addition and removal of AMPA receptors (AMPARs at postsynaptic sites. However, the spatial coordination between these mechanisms has remained unclear, because little is known about the dynamics of AMPAR-containing endosomes. In addition, how the positioning of AMPAR-containing endosomes affects synapse organization and functioning has never been directly explored. Here, we used live-cell imaging in hippocampal neuron cultures to show that intracellular AMPARs are transported in Rab11-positive recycling endosomes, which frequently enter dendritic spines and depend on the microtubule and actin cytoskeleton. By using chemically induced dimerization systems to recruit kinesin (KIF1C or myosin (MyosinV/VI motors to Rab11-positive recycling endosomes, we controlled their trafficking and found that induced removal of recycling endosomes from spines decreases surface AMPAR expression and PSD-95 clusters at synapses. Our data suggest a mechanistic link between endosome positioning and postsynaptic structure and composition.

  17. Induced abortion, pregnancy loss and intimate partner violence in Tanzania: a population based study.

    Science.gov (United States)

    Stöckl, Heidi; Filippi, Veronique; Watts, Charlotte; Mbwambo, Jessie K K

    2012-03-05

    Violence by an intimate partner is increasingly recognized as an important public and reproductive health issue. The aim of this study is to investigate the extent to which physical and/or sexual intimate partner violence is associated with induced abortion and pregnancy loss from other causes and to compare this with other, more commonly recognized explanatory factors. This study analyzes the data of the Tanzania section of the WHO Multi-Country Study on Women's Health and Domestic Violence, a large population-based cross-sectional survey of women of reproductive age in Dar es Salaam and Mbeya, Tanzania, conducted from 2001 to 2002. All women who answered positively to at least one of the questions about specific acts of physical or sexual violence committed by a partner towards her at any point in her life were considered to have experienced intimate partner violence. Associations between self reported induced abortion and pregnancy loss with intimate partner violence were analysed using multiple regression models. Lifetime physical and/or sexual intimate partner violence was reported by 41% and 56% of ever partnered, ever pregnant women in Dar es Salaam and Mbeya respectively. Among the ever pregnant, ever partnered women, 23% experienced involuntary pregnancy loss, while 7% reported induced abortion. Even after adjusting for other explanatory factors, women who experienced intimate partner violence were 1.6 (95%CI: 1.06,1.60) times more likely to report an pregnancy loss and 1.9 (95%CI: 1.30,2.89) times more likely to report an induced abortion. Intimate partner violence had a stronger influence on induced abortion and pregnancy loss than women's age, socio-economic status, and number of live born children. Intimate partner violence is likely to be an important influence on levels of induced abortion and pregnancy loss in Tanzania. Preventing intimate partner violence may therefore be beneficial for maternal health and pregnancy outcomes. © 2012 Stöckl et al

  18. Experience-Dependent Regulation of Presynaptic NMDARs Enhances Neurotransmitter Release at Neocortical Synapses

    Science.gov (United States)

    Urban-Ciecko, Joanna; Wen, Jing A.; Parekh, Puja K.; Barth, Alison L.

    2015-01-01

    Sensory experience can selectively alter excitatory synaptic strength at neocortical synapses. The rapid increase in synaptic strength induced by selective whisker stimulation (single-row experience/SRE, where all but one row of whiskers has been removed from the mouse face) is due, at least in part, to the trafficking of AMPA receptors (AMPARs)…

  19. ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory.

    Science.gov (United States)

    Chiang, Po-Han; Chien, Ta-Chun; Chen, Chih-Cheng; Yanagawa, Yuchio; Lien, Cheng-Chang

    2015-05-19

    Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons.

  20. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury

    Science.gov (United States)

    Martens, Lauren Herl; Zhang, Jiasheng; Barmada, Sami J.; Zhou, Ping; Kamiya, Sherry; Sun, Binggui; Min, Sang-Won; Gan, Li; Finkbeiner, Steven; Huang, Eric J.; Farese, Robert V.

    2012-01-01

    Progranulin (PGRN) is a widely expressed secreted protein that is linked to inflammation. In humans, PGRN haploinsufficiency is a major inherited cause of frontotemporal dementia (FTD), but how PGRN deficiency causes neurodegeneration is unknown. Here we show that loss of PGRN results in increased neuron loss in response to injury in the CNS. When exposed acutely to 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydrophine (MPTP), mice lacking PGRN (Grn–/–) showed more neuron loss and increased microgliosis compared with wild-type mice. The exacerbated neuron loss was due not to selective vulnerability of Grn–/– neurons to MPTP, but rather to an increased microglial inflammatory response. Consistent with this, conditional mutants lacking PGRN in microglia exhibited MPTP-induced phenotypes similar to Grn–/– mice. Selective depletion of PGRN from microglia in mixed cortical cultures resulted in increased death of wild-type neurons in the absence of injury. Furthermore, Grn–/– microglia treated with LPS/IFN-γ exhibited an amplified inflammatory response, and conditioned media from these microglia promoted death of cultured neurons. Our results indicate that PGRN deficiency leads to dysregulated microglial activation and thereby contributes to increased neuron loss with injury. These findings suggest that PGRN deficiency may cause increased neuron loss in other forms of CNS injury accompanied by neuroinflammation. PMID:23041626

  1. Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.

    Directory of Open Access Journals (Sweden)

    Kristoffer Myczek

    Full Text Available Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease and brain traumas (stroke, epilepsy, and traumatic brain injury. One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery.

  2. Tinnitus and temporary hearing loss result in differential noise-induced spatial reorganization of brain activity.

    Science.gov (United States)

    Muca, Antonela; Standafer, Emily; Apawu, Aaron K; Ahmad, Farhan; Ghoddoussi, Farhad; Hali, Mirabela; Warila, James; Berkowitz, Bruce A; Holt, Avril Genene

    2018-02-27

    Loud noise frequently results in hyperacusis or hearing loss (i.e., increased or decreased sensitivity to sound). These conditions are often accompanied by tinnitus (ringing in the ears) and changes in spontaneous neuronal activity (SNA). The ability to differentiate the contributions of hyperacusis and hearing loss to neural correlates of tinnitus has yet to be achieved. Towards this purpose, we used a combination of behavior, electrophysiology, and imaging tools to investigate two models of noise-induced tinnitus (either with temporary hearing loss or with permanent hearing loss). Manganese (Mn 2+ ) uptake was used as a measure of calcium channel function and as an index of SNA. Manganese uptake was examined in vivo with manganese-enhanced magnetic resonance imaging (MEMRI) in key auditory brain regions implicated in tinnitus. Following acoustic trauma, MEMRI, the SNA index, showed evidence of spatially dependent rearrangement of Mn 2+ uptake within specific brain nuclei (i.e., reorganization). Reorganization of Mn 2+ uptake in the superior olivary complex and cochlear nucleus was dependent upon tinnitus status. However, reorganization of Mn 2+ uptake in the inferior colliculus was dependent upon hearing sensitivity. Furthermore, following permanent hearing loss, reduced Mn 2+ uptake was observed. Overall, by combining testing for hearing sensitivity, tinnitus, and SNA, our data move forward the possibility of discriminating the contributions of hyperacusis and hearing loss to tinnitus.

  3. Occupational noise-induced hearing loss in auto part factory workers in welding units in Thailand.

    Science.gov (United States)

    Sriopas, Apiradee; Chapman, Robert S; Sutammasa, Saravudh; Siriwong, Wattasit

    2017-01-24

    Most workers in auto part factories in Thailand are usually exposed to excessive noise in their workplace. This study aimed to assess the level of occupational noise-induced hearing loss and investigate risk factors causing hearing loss in auto part factory workers in the welding units in Thailand. This was a cross-sectional study. One hundred eighty subjects were recruited from 356 workers in the welding unit of three factories. Sixty eligible subjects in each factory were selected by systemic random sampling. The subjects were interviewed using a face-to-face questionnaire. Noise exposure levels and audiograms were measured by a noise dosimeter and an audiometer, respectively. The findings confirmed that noise exposure levels of 86-90 dB (A) and exceeding 90 dB (A) significantly increased the risk of hearing loss in either ear. A noise exposure level exceeding 90 dB (A) significantly increased the prevalence of hearing loss in both ears. Regarding, a 10-pack-year smoking history increased the prevalence of hearing loss in either ear or both ears. In addition, subjects with employment duration exceeding 10 years significantly developed hearing loss in either ear. The engineering control or personal control by wearing hearing protection device should be used to decrease noise exposure levels lower than 85 dB (A) for 8 h. Moreover, if the exposure level reaches 85 dB (A) for 8 h, the employer needs to implement a hearing conservation program in the workplace.

  4. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses

    Science.gov (United States)

    Trouche, Stéphanie; Sasaki, Jennifer M.; Tu, Tiffany; Reijmers, Leon G.

    2013-01-01

    SUMMARY A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. PMID:24183705

  5. Otanps synapse linear relation multiplier circuit

    International Nuclear Information System (INIS)

    Chible, H.

    2008-01-01

    In this paper, a four quadrant VLSI analog multiplier will be proposed, in order to be used in the implementation of the neurons and synapses modules of the artificial neural networks. The main characteristics of this multiplier are the small silicon area and the low power consumption and the high value of the weight input voltage. (author)

  6. Intercellular protein-protein interactions at synapses.

    Science.gov (United States)

    Yang, Xiaofei; Hou, Dongmei; Jiang, Wei; Zhang, Chen

    2014-06-01

    Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer's disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.

  7. Integrated protective systems for operational acceleration-induced loss of consciousness.

    Science.gov (United States)

    Whitley, P E

    1991-01-01

    Systems that can protect pilots from not only acceleration-induced loss of consciousness (G-LOC) but also from exposure to chemical, biological, and nuclear weapons are discussed. Hazards such as fire, drowning, and ballistic injury are not considered. Physiological stresses, protection methods, and their impact on G capability at increased altitudes are examined, as are stresses induced by the environment (heat stress, cold stress, and cold water immersion). Sustained and short-duration acceleration effects are described. Requirements for protection against chemical, biological, radiological, and laser weapons and the incorporation of mission-enhancement devices are addressed. Concepts for integration of all of these elements are discussed.

  8. [New aspects of hearing aid fitting in noise-induced hearing loss].

    Science.gov (United States)

    Kiessling, J

    2006-07-01

    In the past hearing aid fitting frequently turned out to be a problem in patients with noise-induced hearing loss. Selective amplification in the high frequency range and at the same time natural sound and appropriate wearing comfort (open fitting) could not be achieved in numerous cases. Today these problems can be tackled by modern hearing aid technology providing us with efficient feedback suppression algorithms making open fittings possible for many more patients. This development is particularly beneficial for patients with noise-induced hearing loss. Unfortunately, open fitting is in opposition to wearing hearing aids at noisy workplaces. Tight fittings, however, can be used at work if a special listening program for noisy conditions is available. This dilemma is discussed and possible solutions are pointed out.

  9. Endothelial function in hypertensive obese patients: 1 year after surgically induced weight loss.

    Science.gov (United States)

    Flores, L; Núñez, I; Vidal, J; Rueda, S; Viaplana, J; Rodríguez, L; Esmatjes, E

    2014-09-01

    The aim of this study was to describe the effect of surgically induced weight loss on vascular function measured by flow-mediated dilatation (FMD) in hypertensive obese patients. This prospective study included 33 patients (78 % females, mean age 53 (9) years) undergoing bariatric surgery (BS). Before and 12 months postoperatively, the BMI, 24-h ambulatory BP, high-sensitivity C-reactive protein (hs-CRP), leptin, homeostasis model assessment (HOMA IR), and abdominal fat were measured. Endothelial function was assessed by FMD. After BS, the excess body weight loss was 71 %; the 24-h [systolic 18(11)//diastolic 7(7) mmHg] BP values, hs-CRP, leptin, HOMA, and abdominal fat significantly decreased, with no changes in endothelial function. Weight loss achieved by BS was associated with a significant improvement in BP and metabolic and inflammation parameters, but FMD did not improve.

  10. Wave-induced loss of ultra-relativistic electrons in the Van Allen radiation belts.

    Science.gov (United States)

    Shprits, Yuri Y; Drozdov, Alexander Y; Spasojevic, Maria; Kellerman, Adam C; Usanova, Maria E; Engebretson, Mark J; Agapitov, Oleksiy V; Zhelavskaya, Irina S; Raita, Tero J; Spence, Harlan E; Baker, Daniel N; Zhu, Hui; Aseev, Nikita A

    2016-09-28

    The dipole configuration of the Earth's magnetic field allows for the trapping of highly energetic particles, which form the radiation belts. Although significant advances have been made in understanding the acceleration mechanisms in the radiation belts, the loss processes remain poorly understood. Unique observations on 17 January 2013 provide detailed information throughout the belts on the energy spectrum and pitch angle (angle between the velocity of a particle and the magnetic field) distribution of electrons up to ultra-relativistic energies. Here we show that although relativistic electrons are enhanced, ultra-relativistic electrons become depleted and distributions of particles show very clear telltale signatures of electromagnetic ion cyclotron wave-induced loss. Comparisons between observations and modelling of the evolution of the electron flux and pitch angle show that electromagnetic ion cyclotron waves provide the dominant loss mechanism at ultra-relativistic energies and produce a profound dropout of the ultra-relativistic radiation belt fluxes.

  11. Defect production and subsequent effects induced by electronic energy loss of swift heavy ion

    International Nuclear Information System (INIS)

    Hou Mingdong; Liu Jie; Sun Youmei; Yin Jingmin; Yao Huijun; Duan Jinglai; Mo Dan; Zhang Ling; Chen Yanfeng; Chinese Academy of Sciences, Beijing

    2008-01-01

    Swift heavy ion in matter is one of forfront fields of nuclear physics in the world. A series of new phenomena were discovered in recent years. The history and sta- tus on the development of this field were reviewed. Electronic energy loss effects induced by swift heavy ion irradiation, such as defect production and evolution, ion latent track formation, phase transformation and anisotropy plastic deformation were introduced emphatically. A trend of future investigation was explored. (authors)

  12. Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway

    OpenAIRE

    Gu, Sun Mi; Park, Mi Hee; Hwang, Chul Ju; Song, Ho Sueb; Lee, Ung Soo; Han, Sang Bae; Oh, Ki Wan; Ham, Young Wan; Song, Min Jong; Son, Dong Ju; Hong, Jin Tae

    2015-01-01

    Background Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer?s disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-?B) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-?B. Methods A mouse model of LPS-induced me...

  13. Sappanone A inhibits RANKL-induced osteoclastogenesis in BMMs and prevents inflammation-mediated bone loss.

    Science.gov (United States)

    Choo, Young-Yeon; Tran, Phuong Thao; Min, Byung-Sun; Kim, Okwha; Nguyen, Hai Dang; Kwon, Seung-Hae; Lee, Jeong-Hyung

    2017-11-01

    Receptor activator of nuclear factor-kB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Suppressing osteoclastogenesis is considered an effective therapeutic approach for bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Sappanone A (SPNA), a homoisoflavanone compound isolated from the heartwood of Caesalpinia sappan, has been reported to exert anti-inflammatory effects; however, the effects of SPNA on osteoclastogenesis have not been investigated. In the present study, we describe for the first time that SPNA inhibits RANKL-induced osteoclastogenesis in mouse bone marrow macrophages (BMMs) and suppresses inflammation-induced bone loss in a mouse model. SPNA inhibited the formation of osteoclasts from BMMs, osteoclast actin-ring formation, and bone resorption in a concentration-dependent manner. At the molecular level, SPNA significantly inhibited RANKL-induced activation of the AKT/glycogen synthase kinase-3β (GSK-3β) signaling pathway without affecting its activation of the mitogen-activated protein kinases (MAPKs) JNK, p38, and ERK. In addition, SPNA suppressed the induction of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which is a crucial transcription factor in osteoclast differentiation. As a result, SPNA decreased osteoclastogenesis-related marker gene expression, including CtsK, TRAP, dendritic cell-specific transmembrane protein (DC-STAMP), MMP-9 and osteoclast-associated receptor (OSCAR). In a mouse inflammatory bone loss model, SPNA significantly inhibited lipopolysaccharide (LPS)-induced bone loss by suppressing the number of osteoclasts. Taken together, these findings suggest that SPNA inhibits osteoclastogenesis and bone resorption by inhibiting the AKT/GSK-3β signaling pathway and may be a potential candidate compound for the prevention and/or treatment of inflammatory bone loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Regional atmospheric cooling and wetting effect of permafrost thaw-induced boreal forest loss.

    Science.gov (United States)

    Helbig, Manuel; Wischnewski, Karoline; Kljun, Natascha; Chasmer, Laura E; Quinton, William L; Detto, Matteo; Sonnentag, Oliver

    2016-12-01

    In the sporadic permafrost zone of North America, thaw-induced boreal forest loss is leading to permafrost-free wetland expansion. These land cover changes alter landscape-scale surface properties with potentially large, however, still unknown impacts on regional climates. In this study, we combine nested eddy covariance flux tower measurements with satellite remote sensing to characterize the impacts of boreal forest loss on albedo, eco-physiological and aerodynamic surface properties, and turbulent energy fluxes of a lowland boreal forest region in the Northwest Territories, Canada. Planetary boundary layer modelling is used to estimate the potential forest loss impact on regional air temperature and atmospheric moisture. We show that thaw-induced conversion of forests to wetlands increases albedo: and bulk surface conductance for water vapour and decreases aerodynamic surface temperature. At the same time, heat transfer efficiency is reduced. These shifts in land surface properties increase latent at the expense of sensible heat fluxes, thus, drastically reducing Bowen ratios. Due to the lower albedo of forests and their masking effect of highly reflective snow, available energy is lower in wetlands, especially in late winter. Modelling results demonstrate that a conversion of a present-day boreal forest-wetland to a hypothetical homogeneous wetland landscape could induce a near-surface cooling effect on regional air temperatures of up to 3-4 °C in late winter and 1-2 °C in summer. An atmospheric wetting effect in summer is indicated by a maximum increase in water vapour mixing ratios of 2 mmol mol -1 . At the same time, maximum boundary layer heights are reduced by about a third of the original height. In fall, simulated air temperature and atmospheric moisture between the two scenarios do not differ. Therefore, permafrost thaw-induced boreal forest loss may modify regional precipitation patterns and slow down regional warming trends. © 2016 John Wiley

  15. Reconciliation of Halogen-Induced Ozone Loss with the Total-Column Ozone Record

    Science.gov (United States)

    Shepherd, T. G.; Plummer, D. A.; Scinocca, J. F.; Hegglin, M. I.; Fioletov, V. E.; Reader, M. C.; Remsberg, E.; von Clarmann, T.; Wang, H. J.

    2014-01-01

    The observed depletion of the ozone layer from the 1980s onwards is attributed to halogen source gases emitted by human activities. However, the precision of this attribution is complicated by year-to-year variations in meteorology, that is, dynamical variability, and by changes in tropospheric ozone concentrations. As such, key aspects of the total-column ozone record, which combines changes in both tropospheric and stratospheric ozone, remain unexplained, such as the apparent absence of a decline in total-column ozone levels before 1980, and of any long-term decline in total-column ozone levels in the tropics. Here we use a chemistry-climate model to estimate changes in halogen-induced ozone loss between 1960 and 2010; the model is constrained by observed meteorology to remove the eects of dynamical variability, and driven by emissions of tropospheric ozone precursors to separate out changes in tropospheric ozone. We show that halogen-induced ozone loss closely followed stratospheric halogen loading over the studied period. Pronounced enhancements in ozone loss were apparent in both hemispheres following the volcanic eruptions of El Chichon and, in particular, Mount Pinatubo, which significantly enhanced stratospheric aerosol loads. We further show that approximately 40% of the long-term non-volcanic ozone loss occurred before 1980, and that long-term ozone loss also occurred in the tropical stratosphere. Finally, we show that halogeninduced ozone loss has declined by over 10% since stratospheric halogen loading peaked in the late 1990s, indicating that the recovery of the ozone layer is well underway.

  16. British university students' attitudes towards noise-induced hearing loss caused by nightclub attendance.

    Science.gov (United States)

    Johnson, O; Andrew, B; Walker, D; Morgan, S; Aldren, A

    2014-01-01

    Over the past 30 years, the prevalence of noise-induced hearing loss among adolescents and young adults has increased. This study aimed to address the current dearth of literature implicating excessive nightclub sound levels (more than 85 dB) as a direct cause of auditory symptoms related to noise-induced hearing loss. A questionnaire was completed by 325 students to gauge the frequency of auditory symptoms after nightclub attendance, and to explore knowledge and opinions about noise levels in nightclubs. The findings showed that 88.3 per cent of students experienced tinnitus after leaving a nightclub and 66.2 per cent suffered impaired hearing the following morning. In terms of behaviour, 73.2 per cent of students said that the risk of hearing damage would not affect their nightclub attendance, but most students (70.2 per cent) felt that noise levels in nightclubs should be limited to safe volumes. A high proportion of students reported experiencing symptoms related to noise-induced hearing loss after attending a nightclub. These findings are relevant to policy makers.

  17. Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

    Science.gov (United States)

    Zhang, Xiangming; Wang, Ping; Wang, Ya

    2015-11-01

    Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts.

  18. Noise-induced hearing loss in construction workers being assessed for hand-arm vibration syndrome.

    Science.gov (United States)

    House, Ronald A; Sauvé, John T; Jiang, Depeng

    2010-01-01

    Construction workers are at risk of noise-induced hearing loss (NIHL) but often have no periodic audiometric testing. The participants were construction workers assessed for Hand-Arm Vibration Syndrome (HAVS) at the Occupational Health Clinic, St. Michael's Hospital, Toronto, Ontario. Audiometry was offered and 169 of the 191 workers assessed for HAVS agreed to have the audiometric test. The objective was to examine the prevalence of hearing loss in these 169 workers and to determine the effect on hearing of duration of work in construction (as a proxy for noise exposure) and the severity of vibration white finger (VWF) which previous studies have suggested is a marker for increased individual susceptibility for NIHL. VWF was measured by the Stockholm vascular scale. All participants were men, median age of 57 (range: 28-75), median number of years worked in construction of 35 (range: 4-52). All of the Spearman rank correlations between years worked in construction and the hearing levels at each audiometric frequency were statistically significant (p hearing loss at or above the level at which a workers' compensation pension would be granted in Ontario and the prevalence of this auditory outcome had a statistically significant increase as years worked in construction increased. Multivariate linear regression indicated that VWF also had a statistically significant effect on hearing loss for all audiometric frequencies combined after controlling for years worked in construction. Improved prevention of hearing loss in construction workers is needed.

  19. High-frequency audiometry: A means for early diagnosis of noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Amir H Mehrparvar

    2011-01-01

    Full Text Available Noise-induced hearing loss (NIHL, an irreversible disorder, is a common problem in industrial settings. Early diagnosis of NIHL can help prevent the progression of hearing loss, especially in speech frequencies. For early diagnosis of NIHL, audiometry is performed routinely in conventional frequencies. We designed this study to compare the effect of noise on high-frequency audiometry (HFA and conventional audiometry. In a historical cohort study, we compared hearing threshold and prevalence of hearing loss in conventional and high frequencies of audiometry among textile workers divided into two groups: With and without exposure to noise more than 85 dB. The highest hearing threshold was observed at 4000 Hz, 6000 Hz and 16000 Hz in conventional right ear audiometry, conventional left ear audiometry and HFA in each ear, respectively. The hearing threshold was significantly higher at 16000 Hz compared to 4000. Hearing loss was more common in HFA than conventional audiometry. HFA is more sensitive to detect NIHL than conventional audiometry. It can be useful for early diagnosis of hearing sensitivity to noise, and thus preventing hearing loss in lower frequencies especially speech frequencies.

  20. Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus.

    Science.gov (United States)

    Tohda, C; Tamura, T; Matsuyama, S; Komatsu, K

    2006-11-01

    Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons. We investigated the effects of extracts of Astragalus mongholicus on the cognitive defect in mice caused by injection with the amyloid peptide Abeta(25-35). We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by Abeta(25-35). A. mongholicus extract (1 g kg(-1) day(-1) for 15 days, p.o.) reversed Abeta(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Abeta(25-35) (10 microM) induced axonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 microg/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of Abeta(25-35)-induced neuronal death. Similar extracts of A. membranaceus had no effect on axonal atrophy, synaptic loss, or neuronal death. The major known components of the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the activity of the extracts did not correlate with their content of these three astragalosides. A. mongholicus is an important candidate for the treatment of memory disorders and the main active constituents may not be the known astragalosides.

  1. Prevention of the Evolution of Workers' Hearing Loss from Noise-Induced Hearing Loss in Noisy Environments through a Hearing Conservation Program

    OpenAIRE

    Fonseca, Vinicius Ribas; Marques, Jair; Panegalli, Flavio; Gonçalves, Claudia Giglio de Oliveira; Souza, Wesley

    2016-01-01

    Introduction Noise-induced hearing loss (NIHL) is a serious problem for workers and therefore for businesses. The hearing conservation program (HCP) is a set of coordinated measures to prevent the development or evolution of occupational hearing loss, which involves a continuous and dynamic process of implementation of hearing conservation routines through anticipation, recognition, evaluation, and subsequent control of the occurrence of existing environmental risks or of those thatmay exist...

  2. Residual activity induced by heavy ions and beam-loss criteria for heavy-ion accelerators

    Directory of Open Access Journals (Sweden)

    I. Strašík

    2010-07-01

    Full Text Available The paper presents results of FLUKA simulations of the residual activity induced by heavy ions in two target configurations representing: (1 a beam pipe of an accelerator and (2 a bulky accelerator structure like a magnet yoke or a coil. The target materials were stainless steel and copper representing the most common construction materials used for basic accelerator components. For these two materials, the inventory of the induced isotopes depends mainly on the target material and much less on the projectile species. Time evolution of the induced activity can be described by means of a generic curve that is independent from the projectile mass. Dependence of the induced residual activity on selected ion beam parameters was studied. The main goal of the study was establishing a scaling law expanding the existing proton beam-loss tolerance to heavy-ion beams. This scaling law enables specifying beam-loss criteria for projectile species from proton up to uranium at energies from 200  MeV/u up to 1  GeV/u.

  3. Green foliage losses from ponderosa pines induced by Abert squirrels and snowstorms: A comparison. [Sciurus aberti; Pinus pondersosa

    Energy Technology Data Exchange (ETDEWEB)

    Allred, W.S.; Gaud, W.S. (Northern Arizona Univ., Flagstaff (United States))

    1993-01-01

    Abert squirrels (Sciurus aberti) are obligate herbivores on ponderosa pine (Pinus ponderosa). The inner bark of pine shoots is considered one of the predominant food resources obtained by foraging squirrels. As squirrels forage for this resource they induce green needle losses from chosen feed trees. Amounts of induced green needle losses appear to vary according to the availability of alternative foods and squirrel population densities. Weather also induces green needle losses to ponderosa pines. Results of this study indicate that, at least in some years, heavy snowstorms can induce greater amounts of green needle losses than squirrels. Squirrel herbivory was not indicated as a factor in any tree mortality. However, losses due to snowstorms are more severe since they may cause the actual depletion of trees in the forest because of the tree mortality they inflict.

  4. The Effect of the Cholesterol Levels on Noise-Induced Hearing Loss.

    Science.gov (United States)

    Demir, Mehmet Gokhan; Aydin, Sedat

    2018-01-01

    Introduction  Noise-induced hearing loss (NIHL), which is one of the most common occupational diseases among industrialized populations, is associated with longstanding exposure to high levels of noise. The pathogenesis of NIHL is not clear, but some genes and their activity at the tissue level have been investigated. Hypercholesterolemia, which can disturb the microcirculation, can be one of the underlying pathologies in hearing loss. Objective  To investigate the relationship between NIHL and hypercholesterolemia. Methods  The study group was selected among workers who had an occupational exposure of 85 dB of noise for at least 10 years. The audiologic assessment was recorded at seven frequencies (500 Hz, 1,000 Hz, 2,000 Hz, 3,000 Hz, 4,000 Hz, 6,000 Hz and 8,000 Hz). A total of 456 workers were included in the study and divided into two groups: the control group (252 patients) and the NIHL group (204 patients). After the audiologic measurement, blood samples were taken and investigated for blood cholesterol levels. According to these results, the groups were compared. Results  Both groups were similarly distributed regarding age and occupational exposure time ( p  > 0.05). We could not detect any association between cholesterol levels and noise-induced hearing loss ( p   0.05). Conclusion  Noise-induced hearing loss is still a common occupational problem that can be prevented by hearing conservation programs and occupational health and safety training. Still, we know little about the relationship between NIHL and hypercholesterolemia. According to our findings, we cannot detect any relationship. Controlled studies and studies with human individuals can be made possible in the future with diagnostic innovations in tissue imaging and tissue microcircular sampling.

  5. Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration.

    Science.gov (United States)

    Sun, Changling; Wang, Xueling; Chen, Dongye; Lin, Xin; Yu, Dehong; Wu, Hao

    2016-04-21

    Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Circulating cytokines as determinants of weight loss-induced improvements in insulin sensitivity.

    Science.gov (United States)

    Weiss, Edward P; Reeds, Dominic N; Ezekiel, Uthayashanker R; Albert, Stewart G; Villareal, Dennis T

    2017-01-01

    Dietary calorie restriction and exercise promote weight loss and may have additive effects for improving insulin sensitivity, independent of weight loss. It is not known if these effects are attributable to changes in circulating cytokines. We evaluated the hypothesis that modest, matched weight loss induced by calorie restriction and exercise have additive effects on circulating cytokines and these changes correlate with improvements in insulin sensitivity. Overweight and sedentary women and men (n = 52, 45-65 years) were randomized to undergo 7 % weight loss by using 3-6 months of calorie restriction, exercise, or a combination of both calorie restriction and exercise. Concentrations of cytokines and hormones were measured in fasting and oral glucose tolerance test blood samples. Insulin sensitivity was estimated based on oral glucose tolerance test for glucose and insulin. With all groups combined, fasting leptin (p weight adiponectin (p = 0.04) decreased and pentraxin-3 increased (p calorie restriction had additive effects on leptin, with a similar trend for high molecular weight adiponectin. Monocyte chemoattractant protein-1 and C-reactive protein concentrations did not change. Calorie restriction and exercise had opposite effects on soluble tumor necrosis factor receptor-1. Modest weight loss in overweight adults decreases serum leptin and high molecular weight adiponectin, and increases pentraxin-3 concentrations in a manner that correlates with increased insulin sensitivity. Exercise has additive effects to those induced by calorie restriction for reductions in leptin and possibly adiponectin. These changes may contribute to the additive effects of calorie restriction and exercise for improving insulin sensitivity.

  7. CFD analysis of thermally induced thermodynamic losses in the reciprocating compression and expansion of real gases

    Science.gov (United States)

    Taleb, Aly I.; Sapin, Paul; Barfuß, Christoph; Fabris, Drazen; Markides, Christos N.

    2017-03-01

    The efficiency of expanders is of prime importance in determining the overall performance of a variety of thermodynamic power systems, with reciprocating-piston expanders favoured at intermediate-scales of application (typically 10-100 kW). Once the mechanical losses in reciprocating machines are minimized (e.g. through careful valve design and operation), losses due to the unsteady thermal-energy exchange between the working fluid and the solid walls of the containing device can become the dominant loss mechanism. In this work, gas-spring devices are investigated numerically in order to focus explicitly on the thermodynamic losses that arise due to this unsteady heat transfer. The specific aim of the study is to investigate the behaviour of real gases in gas springs and to compare this to that of ideal gases in order to attain a better understanding of the impact of real-gas effects on the thermally induced losses in reciprocating expanders and compressors. A CFD-model of a gas spring is developed in OpenFOAM. Three different fluid models are compared: (1) an ideal-gas model with constant thermodynamic and transport properties; (2) an ideal-gas model with temperature-dependent properties; and (3) a real-gas model using the Peng-Robinson equation-of-state with temperature and pressure-dependent properties. Results indicate that, for simple, mono- and diatomic gases, like helium or nitrogen, there is a negligible difference in the pressure and temperature oscillations over a cycle between the ideal and real-gas models. However, when considering heavier (organic) molecules, such as propane, the ideal-gas model tends to overestimate the pressure compared to the real-gas model, especially if the temperature and pressure dependency of the thermodynamic properties is not taken into account. In fact, the ideal-gas model predicts higher pressures by as much as 25% (compared to the real-gas model). Additionally, both ideal-gas models underestimate the thermally induced loss

  8. Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

    Science.gov (United States)

    Rancillac, Armelle; Crépel, Francis

    2004-02-01

    Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy. In the present study, we show that long-term potentiation (LTP) and long-term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre- and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF-SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF-PC synapses for presynaptic LTP induced in the same conditions. Thus, long-term changes in synaptic efficacy can be accomplished by PF-SCs synapses as well as by PF-PC synapses, suggesting that both types of plasticity might co-operate during cerebellar motor learning.

  9. Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase.

    Science.gov (United States)

    Sato, Tsuyoshi; Enoki, Yuichiro; Sakamoto, Yasushi; Yokota, Kazuhiro; Okubo, Masahiko; Matsumoto, Masahito; Hayashi, Naoki; Usui, Michihiko; Kokabu, Shoichiro; Mimura, Toshihide; Nakazato, Yoshihiko; Araki, Nobuo; Fukuda, Toru; Okazaki, Yasushi; Suda, Tatsuo; Takeda, Shu; Yoda, Tetsuya

    2015-09-01

    Donepezil, an inhibitor of acetylcholinesterase (AChE) targeting the brain, is a common medication for Alzheimer's disease. Interestingly, a recent clinical study found that administration of this agent is associated with lower risk of hip fracture independently of falling, suggesting its direct effect on bone tissues as well. AChE has been reported to be involved in osteoblast function, but the role of AChE on osteoclastogenesis still remains unclear. We analyzed the effect of AChE and donepezil on osteoclastogenesis in vivo and in vitro. Cell-based assays were conducted using osteoclasts generated in cultures of murine bone marrow macrophages (BMMs) with receptor activator of nuclear factor-kappa B ligand (RANKL). The effect of donepezil was also determined in vivo using a mouse model of RANKL-induced bone loss. Recombinant AChE in BMMs cultured with RANKL further promoted RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation. RANKL also upregulated AChE expression in BMMs. RNA interference-mediated knockdown of AChE significantly inhibited RANKL-induced osteoclast differentiation and suppressed gene expression specific for osteoclasts. AChE upregulated expression of RANK, the receptor of RANKL, in BMMs. Donepezil decreased cathepsin K expression in BMMs and the resorptive function of osteoclasts on dentine slices. Donepezil decreased RANK expression in BMMs, resulting in the inhibition of osteoclast differentiation with downregulation of c-Fos and upregulation of Id2. Moreover, administration of donepezil prevented RANKL-induced bone loss in vivo, which was associated with the inhibition of bone resorption by osteoclasts. AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

  10. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis

    Science.gov (United States)

    Chen, Xiao; Zhi, Xin; Pan, Panpan; Cui, Jin; Cao, Liehu; Weng, Weizong; Zhou, Qirong; Wang, Lin; Zhai, Xiao; Zhao, Qingiie; Hu, Honggang; Huang, Biaotong; Su, Jiacan

    2017-01-01

    Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-κB ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-κB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.—Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis. PMID:28739641

  11. D-serine and serine racemase are associated with PSD-95 and glutamatergic synapse stability

    Directory of Open Access Journals (Sweden)

    Hong eLin

    2016-02-01

    Full Text Available D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs, synthesized by serine racemase (SR through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking alpha7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1, in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5 and 7-chlorokynurenic acid (7-CK, a specific antagonist at the glycine site of NMDARs

  12. Inherent losses induced absorptive acoustic rainbow trapping with a gradient metasurface

    Science.gov (United States)

    Liu, Tuo; Liang, Shanjun; Chen, Fei; Zhu, Jie

    2018-03-01

    Acoustic rainbow trapping represents the phenomenon of strong acoustic dispersion similar to the optical "trapped rainbow," which allows spatial-spectral modulation and broadband trapping of sound. It can be realized with metamaterials that provide the required strong dispersion absent in natural materials. However, as the group velocity cannot be reduced to exactly zero before the forward mode being coupled to the backward mode, such trapping is temporary and the local sound oscillation ultimately radiates backward. Here, we propose a gradient metasurface, a rigid surface structured with gradient perforation along the wave propagation direction, in which the inherent thermal and viscous losses inside the holes are considered. We show that the gradually diminished group velocity of the structure-induced surface acoustic waves (SSAWs) supported by the metasurface becomes anomalous at the trapping position, induced by the existence of the inherent losses, which implies that the system's absorption reaches its maximum. Together with the progressively increased attenuation of the SSAWs along the gradient direction, reflectionless spatial-spectral modulation and sound enhancement are achieved in simulation. Such phenomenon, which we call as absorptive trapped rainbow, results from the balanced interplay among the local resonance inside individual holes, the mutual coupling of adjacent unit cells, and the inherent losses due to thermal conductivity and viscosity. This study deepens the understanding of the SSAWs propagation at a lossy metasurface and may contribute to the practical design of acoustic devices for high performance sensing and filtering.

  13. X-ray induced stellar mass loss near active galactic nuclei

    International Nuclear Information System (INIS)

    Voit, G.M.; Shull, J.M.

    1988-01-01

    The effects of UV and X-ray radiation on stars in active galactic nuclei (AGN) are critically evaluated. Mass loss rates in X-ray-induced winds are evaluated for realistic red giant models, and the effects of the ablation of stellar envelopes by radiation pressure are considered. The importance of X-ray-induced mass loss in the standard quasar model is evaluated and whether it can provide a source of accretion fuel or emission-line clouds is discussed. It is concluded that thermal winds driven by X-ray heating are a minor total supply of mass to AGN, but that thermal plus line-driven winds and stellar ablation may increase the mass loss and improve the chances for supplying a fraction of the necessary mass supply to the central object. It is speculated that when steady winds are inefficient, complex time-dependent processes due to X-ray energy injection deep into a stellar atmosphere could still release significant mass from stars. 49 references

  14. Linking two opposites of pregnancy loss: Induced abortion and infertility in Yoruba society, Nigeria.

    Science.gov (United States)

    Koster, Winny

    2010-11-01

    Involuntary infertility and induced abortion exist on opposite sides of the spectrum: the first being the unwanted loss of childbearing potential while the second is the intentional termination of pregnancy. However, this paper proposes that these two poles of pregnancy loss are in fact related in Yoruba society, Nigeria. This argument is supported by qualitative and quantitative data drawn from an applied research project in communities and health institutions of Lagos State, from 1996 to 1999, where a total of 693 women recounted 1114 personal abortion experiences, and 233 women shared their experiences of fertility problems. Study statistics show that 37% of secondary infertility was most probably the result of induced abortion and that half of women with abortion complications interviewed in a referral hospital will have fertility problems. This paper provides insight into the reasons why single and married women decide to abort, and use unsafe methods, despite awareness of the serious health risks, including infertility. This is paradoxical given that fear of infertility is a major reason why women do not use modern contraceptives when trying to prevent unwanted pregnancy. By analysing the relations between infertility and abortion within the socio-cultural, economic, and services-related structures that influence women's decisions, this paper suggests ways of addressing the problems related to both types of pregnancy loss. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Combination therapy using antioxidants and low level laser therapy (LLLT) on noise induced hearing loss (NIHL)

    Science.gov (United States)

    Chang, So-Young; Lim, Sung Kyu; Lee, Min young; Chung, Phil-Sang; Jung, Jae-Yun; Rhee, Chung-Ku

    2016-02-01

    One of the most common factors that cause hearing disorders is noise trauma. Noise is an increasing hazard and it is pervasive, which makes it difficult to take precautions and prevent noise-induced hearing loss (NIHL). The prevalence of hearing loss among factory workers to be 42 %[1]. Ocupational noise induced hearing loss (ONIHL) continues to be a significant occupational hazard. ONIHL is permanent and may cause significant disability, for which there currently exists no cure, but is largely preventable. More than 30 million Americans are potentially exposed to hazardous noise levels in occupations such as transportation, construction, and coal mining, as well as recreationally. In the mainstream setting, exposure avoidance strategies aimed to reduce the incidence of ONIHL remain the focus of public health and occupational medicine approaches[2]. In military conditions this is most often caused by such things as explosions, blasts, or loud noises from vehicles ranging from 100 to 140 dB[3] and military weapons generating approximately 140-185 dB peak sound pressure levels[4].

  16. Medical surveillance of occupational Noise Induced Hearing Loss (NIHL) at RAPS hospital

    International Nuclear Information System (INIS)

    Manuwal, A.K.; Ganesan, S.

    2009-01-01

    Full text: One of the most challenging roles of a Certifying Surgeon is to act as catalyst for change. This paper is a presentation of the impact of such an effort. Noise is the insidious of all industrial pollutants, involving every industry and causing severe hearing loss. Exposure to excessive noise is the major avoidable cause of permanent hearing impairment. Noise - induced hearing loss (NIHL) is bilateral and symmetrical, usually affecting the higher frequencies 3 k, 4 k or 6 kHz ) and then spreading to the lower frequencies (0.5 k,1 k or 2 kHz). The major health effects are lack of concentration, irritation, fatigue, headache, sleep disturbances etc. Hearing protectors should be used when engineering controls and work practices are not feasible for reducing noise exposure to safe levels. Ear muffs, ear plugs and ear canal caps are the main types of hearing protectors. Awareness should be created among workers about the harmful effects of noise on hearing and other body systems by implementing compulsory education noise conservation programmes. The practice followed at RAPS Hospital for medical surveillance of Occupational Noise Induced Hearing Loss is being briefed

  17. Does Diet-Induced Weight Loss Lead to Bone Loss in Overweight or Obese Adults? A Systematic Review and Meta-Analysis of Clinical Trials.

    Science.gov (United States)

    Zibellini, Jessica; Seimon, Radhika V; Lee, Crystal M Y; Gibson, Alice A; Hsu, Michelle S H; Shapses, Sue A; Nguyen, Tuan V; Sainsbury, Amanda

    2015-12-01

    Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm(2) in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], -0.014 to -0.005, -0.021 to -0.008, and -0.024 to -0.000 g/cm(2), at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (-0.011 g/cm(2); 95% CI, -0.018 to -0.003 g/cm(2)) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet-induced weight-loss intervention induces a small decrease in total hip BMD, but not lumbar spine

  18. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2017-10-01

    difference We therefore conclude that it is more likely that female hormones are protecting against susceptibility as opposed to male hormones...of synapse counts among all experimental conditions, those in A as well as saline/vehicle and systemic 4 mg/Kg IEM-1460 (IEMs4mg). There is no... animals at the approximate level of the animals ’ ears. The variation of the noise level across the animals ’ ears and across time is ə dB

  19. Protection from impulse noise-induced hearing loss with novel Src-protein tyrosine kinase inhibitors.

    Science.gov (United States)

    Bielefeld, Eric C; Hangauer, David; Henderson, Donald

    2011-12-01

    Apoptosis is a significant mechanism of cochlear hair cell loss from noise. Molecules that inhibit apoptotic intracellular signaling reduce cochlear damage and hearing loss from noise. The current study is an extension of a previous study of the protective value of Src-protein tyrosine kinase inhibitors against noise (Harris et al., 2005). The current study tested three Src-inhibitors: the indole-based KX1-141, the biaryl-based KX2-329, and the ATP-competitive KX2-328. Each of the three drugs was delivered into the chinchillas' cochleae by allowing the solutions to diffuse across the round window membrane thirty minutes prior to exposure to impulse noise. Hearing thresholds were measured using auditory evoked responses from electrodes in the inferior colliculi. Ears treated with KX2-329 showed significantly lower threshold shifts and outer hair cell losses than the control group. The cochleae treated with KX1-141 and KX2-328 did not show statistically significant protection from the impulse noise. The finding of protection with KX2-329 demonstrates that a biaryl-based Src inhibitor has protective capacity against noise-induced hearing loss that is as good as that demonstrated by KX1-004, a Src inhibitor drug that has been studied extensively as an otoprotectant against noise, and suggests that KX2-329 could be useful for protection against noise. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  20. Risk of hearing loss among workers with vibration-induced white fingers.

    Science.gov (United States)

    Pettersson, Hans; Burström, Lage; Hagberg, Mats; Lundström, Ronnie; Nilsson, Tohr

    2014-12-01

    We examined the risk of hearing loss for workers who use hand-held vibrating tools with vibration-induced white fingers (VWF) compared to workers without VWF. Data on 184 participants from a 21-year cohort were gathered with questionnaires and measurements. The effects on hearing status of VWF, hand-arm vibration exposure, smoking habits, age and two-way interactions of these independent variables were examined with binary logistic regression. Analyses were made for the right hand and ear as well as for the hand with VWF and the ear with worse categorized hearing status. Workers with VWF in their right hand had an increased risk of hearing loss (odds ratio 2.2-2.3) in the right ear. Workers with VWF in any hand did not have any increased risk of hearing loss in the ear with worse hearing status. This study supports the hypothesis that VWF increases the risk of hearing loss among workers who use hand-held vibrating tools in a noisy environment. © 2014 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Akram Pourbakht

    2012-10-01

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

  2. Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

    Directory of Open Access Journals (Sweden)

    Chen-he Zhou

    2018-03-01

    Full Text Available Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK and phosphatidylinositol 3-kinase (PI3K-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist and/or SC79 (an AKT agonist in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

  3. Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by promoting osteoblast survival.

    Science.gov (United States)

    Adhikary, Sulekha; Choudhary, Dharmendra; Ahmad, Naseer; Karvande, Anirudha; Kumar, Avinash; Banala, Venkatesh Teja; Mishra, Prabhat Ranjan; Trivedi, Ritu

    2018-02-13

    Kaempferol, a dietary flavonoid found in fruits and vegetables, has been reported to reverse osteopenic condition in ovariectomized rats. Because kaempferol is endowed with osteogenic activity, the aim of this study was to determine whether it has a beneficial effect on glucocorticoid (GC)-induced bone loss. Adult female rats were divided into four groups as control (vehicle; distilled water), methylprednisolone (MP; 5 mg•kg•d, subcutaneously), MP + kaempferol (5 mg•kg•d, oral), and MP + human parathyroid 1-34 (30 µg/kg, 5 times/wk, subcutaneously) and treated for 4 wk. To study the antagonizing effect of kaempferol on GC-induced inhibition of fracture healing, drill-hole injury was performed on control and GC-treated rats. An oral dose of kaempferol was given for 14 d to observe the effect on callus formation at the site of injury. After treatment, bones were collected for further analysis. GC was associated with a decreased bone mineral density and impaired bone microarchitecture parameters. Consumption of kaempferol induced bone-sparing effects in GC-induced osteopenic condition. Additionally, improved callus formation at site of drill injury in femur diaphysis was observed with kaempferol consumption in animals on GC. Consistent with the in vivo data, kaempferol elicited a higher expression of osteogenic markers in vitro and antagonized the apoptotic effect of dexamethasone on calvarial osteoblasts. These results suggested that kaempferol reduced GC-induced bone loss and enhanced bone regeneration at fractured site, thus emphasizing the positive role of flavonoids on bone health. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Loss of Roquin induces early death and immune deregulation but not autoimmunity

    Science.gov (United States)

    Bertossi, Arianna; Aichinger, Martin; Sansonetti, Paola; Lech, Maciej; Neff, Frauke; Pal, Martin; Wunderlich, F. Thomas; Anders, Hans-Joachim; Klein, Ludger

    2011-01-01

    The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell–intrinsic and –extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector–like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism. PMID:21844204

  5. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Göllner, Stefanie; Oellerich, Thomas; Agrawal-Singh, Shuchi

    2017-01-01

    In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction...... of histone H3K27 trimethylation as a novel pathway of acquired resistance to tyrosine kinase inhibitors (TKIs) and cytotoxic drugs in AML. Low EZH2 protein levels correlated with poor prognosis in AML patients. Suppression of EZH2 protein expression induced chemoresistance of AML cell lines and primary cells...... in vitro and in vivo. Low EZH2 levels resulted in derepression of HOX genes, and knockdown of HOXB7 and HOXA9 in the resistant cells was sufficient to improve sensitivity to TKIs and cytotoxic drugs. The endogenous loss of EZH2 expression in resistant cells and primary blasts from a subset of relapsed AML...

  6. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

    Science.gov (United States)

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-11-04

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

  7. CLIQ – Coupling-Loss Induced Quench System for Protecting Superconducting Magnets

    CERN Multimedia

    Ravaioli, E; Kirby, G; ten Kate, H H J; Verweij, A P

    2014-01-01

    The recently developed Coupling-Loss-Induced Quench (CLIQ) protection system is a new method for initiating a fast and voluminous transition to the normal state for protecting high energy density superconducting magnets. Upon quench detection, CLIQ is triggered to generate an oscillating current in the magnet coil by means of a capacitive discharge. This in turn introduces a high coupling loss in the superconductor which provokes a quick transition to the normal state of the coil windings. The system is now implemented for the protection of a two meter long superconducting quadrupole magnet and characterized in the CERN magnet test facility. Various CLIQ configurations with different current injection points are tested and the results compared to similar transients lately measured with a not optimized configuration. Test results convincingly show that the newly tested design allows for a more global quench initiation and thus a faster discharge of the magnet energy. Moreover, the performance of CLIQ for reduc...

  8. An Experimental Study of Pile-Supported OWC-Type Breakwaters: Energy Extraction and Vortex-Induced Energy Loss

    Directory of Open Access Journals (Sweden)

    Fang He

    2016-07-01

    Full Text Available Integrating wave energy converters with breakwaters is a promising concept for wave energy utilization. On the basis of fulfilling the wave protection demands, pile-supported Oscillating Water Column (OWC-type breakwaters can also meet the local needs of electricity far from the lands. In the present study, the wave energy extraction and vortex-induced energy loss of pile-supported OWC-type breakwaters were analyzed based on a two-point measurement method. The importance of energy extraction and vortex-induced energy loss on the wave energy dissipation of pile-supported OWC-type breakwaters were experimentally investigated. It was found that the trends of energy extraction and vortex-induced energy loss were generally correlated. The effects of the pneumatic damping induced by top opening affected the vortex-induced energy loss more than the energy extraction. Results showed that a larger pneumatic damping was preferable for the purpose of increasing energy extraction, whereas for a smaller pneumatic damping the vortex-induced energy loss was more important to the energy dissipation. With increasing draft, the energy extraction decreased, but the vortex-induced energy loss complementally contributed to the total energy dissipation and made the energy dissipation at the same level as that for a shallower draft.

  9. α₂-Antiplasmin is involved in bone loss induced by ovariectomy in mice.

    Science.gov (United States)

    Shiomi, Akihito; Kawao, Naoyuki; Yano, Masato; Okada, Kiyotaka; Tamura, Yukinori; Okumoto, Katsumi; Matsuo, Osamu; Akagi, Masao; Kaji, Hiroshi

    2015-10-01

    The mechanism of postmenopausal osteoporosis is not fully understood. α2-Antiplasmin (α2-AP) is the primary inhibitor of plasmin in the fibrinolytic system, but is known to have activities beyond fibrinolysis. However, its role in bone metabolism and the pathogenesis of osteoporosis remains unknown. In the current study, we therefore examined the effects of α2-AP deficiency on ovariectomy (OVX)-induced bone loss by using wild-type and α2-AP-deficient mice. Quantitative computed tomography analysis revealed that α2-AP deficiency blunted OVX-induced trabecular bone loss in mice. Moreover, α2-AP deficiency significantly blunted serum levels of bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen, and interleukin (IL)-1β elevated by OVX. α2-AP treatment elevated the levels of IL-1β and tumor necrosis factor (TNF)-α mRNA in RAW 264.7 cells, although it suppressed osteoclast formation induced by receptor activator of nuclear factor-κB ligand. α2-AP treatment activated ERK1/2 and p38 MAP kinase pathways in RAW 264.7 cells, and these MAP kinase inhibitors antagonized the levels of IL-1β mRNA elevated by α2-AP. The data demonstrate that α2-AP is linked to bone loss due to OVX, through a mechanism that depends in part on the production of IL-1β and TNF-α in monocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. NeuroD2 regulates the development of hippocampal mossy fiber synapses

    Directory of Open Access Journals (Sweden)

    Wilke Scott A

    2012-02-01

    Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

  11. Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

    Directory of Open Access Journals (Sweden)

    Catherine J Knowles

    Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

  12. [Criteria for the assessment of the noise-induced occupational hearing loss: international and national standards].

    Science.gov (United States)

    Izmerov, N F; Denisov, É I; Adeninskaia, E E; Gorblianskiĭ, Iu Iu

    2014-01-01

    The objective of the present paper was to review international and national standards for the criteria of assessment of the noise-induced occupational loss of hearing. The importance of healthy hearing for the occupational safety is emphasized which implies the necessity of the more rigorous criteria for hearing conservation in the workers engaged in the noisy technological environment compared with those for the general population. A rationale for the development of the standard program of hearing conservation in the workers engaged in the noisy technological environment is proposed including hygienic norms and rules or national state standards.

  13. Evaluation of the risk of noise-induced hearing loss among unscreened male industrial workers

    Science.gov (United States)

    Prince, Mary M.; Gilbert, Stephen J.; Smith, Randall J.; Stayner, Leslie T.

    2003-02-01

    Variability in background risk and distribution of various risk factors for hearing loss may explain some of the diversity in excess risk of noise-induced hearing loss (NIHL). This paper examines the impact of various risk factors on excess risk estimates of NIHL using data from the 1968-1972 NIOSH Occupational Noise and Hearing Survey (ONHS). Previous analyses of a subset of these data focused on 1172 highly ``screened'' workers. In the current analysis, an additional 894 white males (609 noise-exposed and 285 controls), who were excluded for various reasons (i.e., nonoccupational noise exposure, otologic or medical conditions affecting hearing, prior occupational noise exposure) have been added (n=2066) to assess excess risk of noise-induced material impairment in an unscreened population. Data are analyzed by age, duration of exposure, and sound level (8-h TWA) for four different definitions of noise-induced hearing impairment, defined as the binaural pure-tone average (PTA) hearing threshold level greater than 25 dB for the following frequencies: (a) 1-4 kHz (PTA1234), (b) 1-3 kHz (PTA123), (c) 0.5, 1, and 2 kHz (PTA512), and (d) 3, 4, and 6 kHz (PTA346). Results indicate that populations with higher background risks of hearing loss may show lower excess risks attributable to noise relative to highly screened populations. Estimates of lifetime excess risk of hearing impairment were found to be significantly different between screened and unscreened population for noise levels greater than 90 dBA. Predicted age-related risk of material hearing impairment in the ONHS unscreened population was similar to that predicted from Annex B and C of ANSI S3.44 for ages less than 60 years. Results underscore the importance of understanding differential risk patterns for hearing loss and the use of appropriate reference (control) populations when evaluating risk of noise-induced hearing impairment among contemporary industrial populations.

  14. JAK2/STAT3 Inhibition Attenuates Noise-Induced Hearing Loss

    OpenAIRE

    Wilson, Teresa; Omelchenko, Irina; Foster, Sarah; Zhang, Yuan; Shi, Xiaorui; Nuttall, Alfred L.

    2014-01-01

    Signal transducers and activators of transcription 3 (STAT3) is a stress responsive transcription factor that plays a key role in oxidative stress-mediated tissue injury. As reactive oxygen species (ROS) are a known source of damage to tissues of the inner ear following loud sound exposure, we examined the role of the Janus kinase 2 (JAK2)/STAT3 signaling pathway in noise induce hearing loss using the pathway specific inhibitor, JSI-124. Mice were exposed to a moderately damaging level of lou...

  15. Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

    Science.gov (United States)

    Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.; hide

    2009-01-01

    The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space

  16. Strategies for the prevention of MP3-induced hearing loss among adolescents : Expert opinions from a Delphi study

    NARCIS (Netherlands)

    Vogel, I.; Brug, J.; Ploeg, C.P.B. van der; Raat, H.

    2009-01-01

    OBJECTIVE. To identify parties involved in the prevention of MP3-induced hearing loss among adolescents and potentially effective prevention strategies and interventions. METHODS. Thirty experts in fields such as scientific research, medical practice, community health professions, education, youth

  17. Model for Estimating Noise-Induced Hearing Loss Associated With Occupational Noise Exposure in a Specified US Navy Population

    National Research Council Canada - National Science Library

    Tufts, Jennifer; Weathersby, Paul K; Marshall, Lynne; Sachs, Felix

    2007-01-01

    This report details the initial steps in the development of a method for modeling the noise-induced hearing loss accrued by a population of Sailors exposed to high-level steady-state occupational noise...

  18. Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice.

    Science.gov (United States)

    Motyl, Katherine J; DeMambro, Victoria E; Barlow, Deborah; Olshan, David; Nagano, Kenichi; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

    2015-07-01

    Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and clinical data are emerging that demonstrate increased fracture risk and bone loss after treatment with the AA, risperidone (RIS). The pharmacology underlying the adverse effects on bone is unknown. However, RIS action in the central nervous system could be responsible because the sympathetic nervous system (SNS) is known to uncouple bone remodeling. RIS treatment in mice significantly lowered trabecular bone volume fraction (bone volume/total volume), owing to increased osteoclast-mediated erosion and reduced osteoblast-mediated bone formation. Daytime energy expenditure was also increased and was temporally associated with the plasma concentration of RIS. Even a single dose of RIS transiently elevated expression of brown adipose tissue markers of SNS activity and thermogenesis, Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was also increased 1 hour after a single dose of RIS. Thus, we inferred that bone loss from RIS was regulated, at least in part, by the SNS. To test this, we administered RIS or vehicle to mice that were also receiving the nonselective β-blocker propranolol. Strikingly, RIS did not cause any changes in trabecular bone volume/total volume, erosion, or formation while propranolol was present. Furthermore, β2-adrenergic receptor null (Adrb2(-/-)) mice were also protected from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated bone loss from any AA. Because AA medications are widely prescribed, especially to young adults, clinical studies are needed to assess whether β-blockers will prevent bone loss in this vulnerable population.

  19. Simplified risk assessment of noise induced hearing loss by means of 2 spreadsheet models

    Directory of Open Access Journals (Sweden)

    Arve Lie

    2016-12-01

    Full Text Available Objectives: The objective of this study has been to test 2 spreadsheet models to compare the observed with the expected hearing loss for a Norwegian reference population. Material and Methods: The prevalence rates of the Norwegian and the National Institute for Occupational Safety and Health (NIOSH definitions of hearing outcomes were calculated in terms of sex and age, 20–64 years old, for a screened (with no occupational noise exposure (N = 18 858 and unscreened (N = 38 333 Norwegian reference population from the Nord-Trøndelag Hearing Loss Study (NTHLS. Based on the prevalence rates, 2 different spreadsheet models were constructed in order to compare the prevalence rates of various groups of workers with the expected rates. The spreadsheets were then tested on 10 different occupational groups with varying degrees of hearing loss as compared to a reference population. Results: Hearing of office workers, train drivers, conductors and teachers differed little from the screened reference values based on the Norwegian and the NIOSH criterion. The construction workers, miners, farmers and military had an impaired hearing and railway maintenance workers and bus drivers had a mildly impaired hearing. The spreadsheet models give a valid assessment of the hearing loss. Conclusions: The use of spreadsheet models to compare hearing in occupational groups with that of a reference population is a simple and quick method. The results are in line with comparable hearing thresholds, and allow for significance testing. The method is believed to be useful for occupational health services in the assessment of risk of noise induced hearing loss (NIHL and the preventive potential in groups of noise-exposed workers. Int J Occup Med Environ Health 2016;29(6:991–999

  20. Simplified risk assessment of noise induced hearing loss by means of 2 spreadsheet models.

    Science.gov (United States)

    Lie, Arve; Engdahl, Bo; Tambs, Kristian

    2016-11-18

    The objective of this study has been to test 2 spreadsheet models to compare the observed with the expected hearing loss for a Norwegian reference population. The prevalence rates of the Norwegian and the National Institute for Occupational Safety and Health (NIOSH) definitions of hearing outcomes were calculated in terms of sex and age, 20-64 years old, for a screened (with no occupational noise exposure) (N = 18 858) and unscreened (N = 38 333) Norwegian reference population from the Nord-Trøndelag Hearing Loss Study (NTHLS). Based on the prevalence rates, 2 different spreadsheet models were constructed in order to compare the prevalence rates of various groups of workers with the expected rates. The spreadsheets were then tested on 10 different occupational groups with varying degrees of hearing loss as compared to a reference population. Hearing of office workers, train drivers, conductors and teachers differed little from the screened reference values based on the Norwegian and the NIOSH criterion. The construction workers, miners, farmers and military had an impaired hearing and railway maintenance workers and bus drivers had a mildly impaired hearing. The spreadsheet models give a valid assessment of the hearing loss. The use of spreadsheet models to compare hearing in occupational groups with that of a reference population is a simple and quick method. The results are in line with comparable hearing thresholds, and allow for significance testing. The method is believed to be useful for occupational health services in the assessment of risk of noise induced hearing loss (NIHL) and the preventive potential in groups of noise-exposed workers. Int J Occup Med Environ Health 2016;29(6):991-999. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  1. Role of Zinc Supplementation in the Treatment of Levetiracetam-Induced Hair Loss: A Case Series

    Directory of Open Access Journals (Sweden)

    Vajiheh Aghamollaii

    2017-09-01

    Full Text Available Objective: Cosmetic side effects are of important causes for non-compliance in patients on anti-epileptics. TE is among the most encountered cosmetic adverse effects. Method: This report presents three patients with seizure disorder who developed levetiracetam- induced TE. Levetiracetam was considered the best therapeutic option for the treatment of the presented patients and therefore, was not changed to other anti-epileptics. To manage TE, it was decided to add Zinc sulfate to the therapeutic levetiracetam regimen. Results:  All three patients reported improvement in their hair condition while their seizure was controlled. Significance: Levetiracetam has favorable safety and efficacy profiles. However; the hair loss caused by this medication is a major drawback. Zinc supplementation is suggested to be safe and cost effective when considering management of levetiracetam-induced TE.

  2. Could driving safety be compromised by noise exposure at work and noise-induced hearing loss?

    Science.gov (United States)

    Picard, Michel; Girard, Serge André; Courteau, Marilène; Leroux, Tony; Larocque, Richard; Turcotte, Fernand; Lavoie, Michel; Simard, Marc

    2008-10-01

    A study was conducted to verify if there is an association between occupational noise exposure, noise-induced hearing loss and driving safety expanding on previous findings by Picard, et al. (2008) that the two factors did increase accident risk in the workplace. This study was made possible when driving records of all Quebec drivers were made available by the Societe de l'assurance automobile du Quebec (SAAQ is the state monopoly responsible for the provision of motor vehicle insurance and the compensation of victims of traffic accidents). These records were linked with personal records maintained by the Quebec National Institute of Public Health as part of its mission to prevent noise induced hearing loss in the workplace. Individualized information on occupational noise exposure and hearing sensitivity was available for 46,030 male workers employed in noisy industries who also held a valid driver's permit. The observation period is of five years duration, starting with the most recent audiometric examination. The associations between occupational noise exposure levels, hearing status, and personal driving record were examined by log-binomial regression on data adjusted for age and duration of exposure. Daily noise exposures and bilateral average hearing threshold levels at 3, 4, and 6 kHz were used as independent variables while the dependent variables were 1) the number of motor vehicle accidents experienced by participants during the study period and 2) participants' records of registered traffic violations of the highway safety code. The findings are reported as prevalence ratios (PRs) with their 95% confidence intervals (CIs). Attributable numbers of events were computed with the relevant PRs, lesser-noise, exposed workers and those with normal hearing levels making the group of reference. Adjusting for age confirmed that experienced workers had fewer traffic accidents. The data show that occupational noise exposure and hearing loss have the same effect on

  3. Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK

    Science.gov (United States)

    Hill, Kayla; Yuan, Hu; Wang, Xianren

    2016-01-01

    Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL. SIGNIFICANCE STATEMENT Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy. PMID:27413159

  4. Autophagy attenuates noise-induced hearing loss by reducing oxidative stress.

    Science.gov (United States)

    Yuan, Hu; Wang, Xianren; Hill, Kayla; Chen, Jun; Lemasters, John; Yang, Shi-Ming; Sha, Su-Hua

    2015-05-20

    Reactive oxygen species play a dual role in mediating both cell stress and defense pathways. Here, we used pharmacological manipulations and siRNA silencing to investigate the relationship between autophagy and oxidative stress under conditions of noise-induced temporary, permanent, and severe permanent auditory threshold shifts (temporary threshold shift [TTS], permanent threshold shift [PTS], and severe PTS [sPTS], respectively) in adult CBA/J mice. Levels of oxidative stress markers (4-hydroxynonenal [4-HNE] and 3-nitrotyrosine [3-NT]) increased in outer hair cells (OHCs) in a noise-dose-dependent manner, whereas levels of the autophagy marker microtubule-associated protein light chain 3 B (LC3B) were sharply elevated after TTS but rose only slightly in response to PTS and were unaltered by sPTS noise. Furthermore, green fluorescent protein (GFP) intensity increased in GFP-LC3 mice after TTS-noise exposure. Treatment with rapamycin, an autophagy activator, significantly increased LC3B expression, while diminishing 4-HNE and 3-NT levels, reducing noise-induced hair cell loss, and, subsequently, noise-induced hearing loss (NIHL). In contrast, treatment with either the autophagy inhibitor 3-methyladenine (3MA) or LC3B siRNA reduced LC3B expression, increased 3-NT and 4-HNE levels, and exacerbated TTS to PTS. This study demonstrates a relationship between oxidative stress and autophagy in OHCs and reveals that autophagy is an intrinsic cellular process that protects against NIHL by attenuating oxidative stress. The results suggest that the lower levels of oxidative stress incurred by TTS-noise exposure induce autophagy, which promotes OHC survival. However, excessive oxidative stress under sPTS-noise conditions overwhelms the beneficial potential of autophagy in OHCs and leads to OHC death and NIHL.

  5. Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation.

    Science.gov (United States)

    Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun; Dickman, Dion K

    2018-04-05

    Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic Homeostatic Plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments. © 2018, Li et al.

  6. The effect of temperature on eccentric contraction-induced isometric force loss in isolated perfused rat medial gastrocnemius muscle

    OpenAIRE

    Vasaghi Gharamaleki B; Keshavarz M; Gharibzadeh Sh; Marvi H; Mosayebnejad J; Ebrahimi Takamjani E

    2008-01-01

    "nBackground: The typical features of eccentric exercise-induced muscle damage are delayed-onset muscle soreness (DOMS) and prolonged loss of muscle strength. It has been shown that passive warmth is effective in reducing muscle injury. Due to the interaction of different systems in vivo, we used isolated perfused medial gastrocnemius skeletal muscle to study the direct effect of temperature on the eccentric contraction-induced force loss. "nMethods: After femoral artery cannulation...

  7. New Nordic Diet induced weight loss is accompanied by changes in metabolism and AMPK signalling in adipose tissue

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Lundsgaard, Annemarie; Jordy, Andreas Børsting

    2015-01-01

    CONTEXT: The molecular mechanisms behind diet-induced metabolic improvements remain to be studied. The Objective was to investigate whether expression of proteins in skeletal muscle or adipose tissue could explain improvements in glucose and lipid homeostasis after weight loss. DESIGN: Volunteers...... muscle. NND induced greater reduction in fat mass than ADD (-6±1 kg and -2±1 kg, p... regulation of key glucose and lipid handling proteins suggests an improved metabolic capacity in adipose tissue after weight loss....

  8. Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis

    International Nuclear Information System (INIS)

    Graaf, Aniek O. de; Heuvel, Lambert P. van den; Dijkman, Henry B.P.M.; Abreu, Ronney A. de; Birkenkamp, Kim U.; Witte, Theo de; Reijden, Bert A. van der; Smeitink, Jan A.M.; Jansen, Joop H.

    2004-01-01

    Bcl-2 family proteins regulate apoptosis at the level of mitochondria. To examine the mechanism of Bcl-2 function, we investigated the effects of the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on two hematopoietic cell lines and Bcl-2 overexpressing transfectants. CCCP directly interferes with mitochondrial function and induces apoptosis. We show that Bcl-2 inhibits apoptosis and that the antiapoptotic effect of Bcl-2 takes place upstream of caspase activation and nuclear changes associated with apoptosis, since these were markedly inhibited in cells overexpressing Bcl-2. Bcl-2 does not prevent the decrease in mitochondrial membrane potential nor the alterations in cellular ATP content induced by CCCP in FL5.12 and Jurkat cells. A higher number of mitochondria was observed in untreated Bcl-2 transfected cells compared to parental cells, as shown by electron microscopy. Exposure to CCCP induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, with apparent swelling and loss of cristae in parental cells. Bcl-2 clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. These data suggest that CCCP induces apoptosis by structural disruption of mitochondria and that Bcl-2 prevents apoptosis and mitochondrial degeneration by preserving mitochondrial integrity

  9. Serum vaspin concentrations in relation to insulin sensitivity following RYGB-induced weight loss.

    Science.gov (United States)

    Handisurya, Ammon; Riedl, Michaela; Vila, Greisa; Maier, Christina; Clodi, Martin; Prikoszovich, Thomas; Ludvik, Bernhard; Prager, Gerhard; Luger, Anton; Kautzky-Willer, Alexandra

    2010-02-01

    Recently, vaspin was identified as a novel adipokine with insulin-sensitizing effects that might be implicated in endogenous glucose regulation. Our objective was to evaluate the impact of acute weight loss and metabolic changes on serum vaspin concentrations in morbidly obese subjects following laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. Longitudinal, clinical intervention study in 33 morbidly obese subjects before and 12 months after RYGB was conducted. Fasting serum concentrations of vaspin were measured by a commercially available ELISA and correlated with BMI, parameters of insulin sensitivity, and other biochemical measurements. Fasting insulin sensitivity was estimated using the homeostasis model assessment (HOMA) of insulin resistance. RYGB-induced weight loss resulted in a reduction of circulating vaspin, leptin, insulin, and C-peptide levels as well as of BMI, HbA1c, and HOMA (p RYGB-induced changes in BMI. Following RYGB surgery, changes in serum vaspin concentrations correlate significantly with the reduction of circulating leptin, insulin, and C-peptide levels and with the amelioration of insulin sensitivity. However, further studies have to elucidate whether vaspin is only a biomarker for body-weight-related changes of insulin sensitivity or whether it is implicated in the regulation of human glucose homeostasis.

  10. Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF.

    Science.gov (United States)

    Zou, Jing; Pyykkö, Ilmari; Sutinen, Päivi; Toppila, Esko

    2005-04-01

    Transcranial vibration was applied for seven animals at a frequency of 250 Hz for 15 min, and five animals were used as normal controls to investigate cellular and molecular mechanism linked to vibration-induced hearing loss in animal model. Compound action potential (CAP) thresholds were measured by round window niche electrode. The expression of tumour necrosis factor alpha (TNF-alpha) and its receptors (TNF R1, TNF R2), vascular endothelium growth factor (VEGF) and its receptors (VEGF R1, VEGF R2) were analysed by immunohistochemistry. Transcranial vibration caused expression of TNF-alpha, TNF R1 and TNF R2 in the cochlea and the expression of TNF R2 was stronger than that of TNF R1. Vibration also induced VEGF and VEGF R2 expression in the cochlea. The average immediate hearing loss was 62 dB and after three days still 48 dB. It is concluded that transcranial vibration as during temporal bone drilling produces cochlear shear stress that is connected with up-regulation of TNF-alpha and its receptors. Also VEGF and VEGF R2 are up-regulated. These responses may be linked to both the damage and repair process of the cochlea.

  11. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  12. JAK2/STAT3 inhibition attenuates noise-induced hearing loss.

    Science.gov (United States)

    Wilson, Teresa; Omelchenko, Irina; Foster, Sarah; Zhang, Yuan; Shi, Xiaorui; Nuttall, Alfred L

    2014-01-01

    Signal transducers and activators of transcription 3 (STAT3) is a stress responsive transcription factor that plays a key role in oxidative stress-mediated tissue injury. As reactive oxygen species (ROS) are a known source of damage to tissues of the inner ear following loud sound exposure, we examined the role of the Janus kinase 2 (JAK2)/STAT3 signaling pathway in noise induce hearing loss using the pathway specific inhibitor, JSI-124. Mice were exposed to a moderately damaging level of loud sound revealing the phosphorylation of STAT3 tyrosine 705 residues and nuclear localization in many cell types in the inner ear including the marginal cells of the stria vascularis, type II, III, and IV fibrocytes, spiral ganglion cells, and in the inner hair cells. Treatment of the mice with the JAK2/STAT3 inhibitor before noise exposure reduced levels of phosphorylated STAT3 Y705. We performed auditory brain stem response and distortion product otoacoustic emission measurements and found increased recovery of hearing sensitivity at two weeks after noise exposure with JAK2/STAT3 inhibition. Performance of cytocochleograms revealed improved outer hair cell survival in JSI-124 treated mice relative to control. Finally, JAK2/STAT3 inhibition reduced levels of ROS detected in outer hair cells at two hours post noise exposure. Together, these findings demonstrate that inhibiting the JAK2/STAT3 signaling pathway is protective against noise-induced cochlear tissue damage and loss of hearing sensitivity.

  13. JAK2/STAT3 inhibition attenuates noise-induced hearing loss.

    Directory of Open Access Journals (Sweden)

    Teresa Wilson

    Full Text Available Signal transducers and activators of transcription 3 (STAT3 is a stress responsive transcription factor that plays a key role in oxidative stress-mediated tissue injury. As reactive oxygen species (ROS are a known source of damage to tissues of the inner ear following loud sound exposure, we examined the role of the Janus kinase 2 (JAK2/STAT3 signaling pathway in noise induce hearing loss using the pathway specific inhibitor, JSI-124. Mice were exposed to a moderately damaging level of loud sound revealing the phosphorylation of STAT3 tyrosine 705 residues and nuclear localization in many cell types in the inner ear including the marginal cells of the stria vascularis, type II, III, and IV fibrocytes, spiral ganglion cells, and in the inner hair cells. Treatment of the mice with the JAK2/STAT3 inhibitor before noise exposure reduced levels of phosphorylated STAT3 Y705. We performed auditory brain stem response and distortion product otoacoustic emission measurements and found increased recovery of hearing sensitivity at two weeks after noise exposure with JAK2/STAT3 inhibition. Performance of cytocochleograms revealed improved outer hair cell survival in JSI-124 treated mice relative to control. Finally, JAK2/STAT3 inhibition reduced levels of ROS detected in outer hair cells at two hours post noise exposure. Together, these findings demonstrate that inhibiting the JAK2/STAT3 signaling pathway is protective against noise-induced cochlear tissue damage and loss of hearing sensitivity.

  14. Thermal Stress-Induced Depolarization Loss in Conventional and Panda-Shaped Photonic Crystal Fiber Lasers

    Science.gov (United States)

    Mousavi, Seyedeh Laleh; Sabaeian, Mohammad

    2016-10-01

    We report on the modeling of the depolarization loss in the conventional and panda-shaped photonic crystal fiber lasers (PCFLs) due to the self-heating of the fiber, which we call it thermal stress-induced depolarization loss (TSIDL). We first calculated the temperature distribution over the fiber cross sections and then calculated the thermal stresses/strains as a function of heat load per meter. Thermal stress-induced birefringence (TSIB), which is defined as | n x - n y |, in the core and cladding regions was calculated. Finally, TSIDL was calculated for the conventional and panda-shaped PCFLs as a function of fiber length and, respectively, saturated values of 22 and 25 % were obtained which were independent of heat load per meter. For panda-shaped PCFLs, prior to being saturated, an oscillating and damping behavior against the fiber length was seen where in some lengths reached 35 %. The results are close to an experimental value of 30 % reported for a pulsed PCFL (Limpert et al., Opt Express 12:1313-1319, 2004) where the authors reported a degree of polarization of 70 % (i.e., a depolarization of 30 %). The most important result of this work is a saturation behavior of TSIDL at long-enough lengths of the fiber laser which is independent of heat load per meter. To our knowledge, this the first report of TSIBL for PCFLs.

  15. Fatigue Modeling via Mammalian Auditory System for Prediction of Noise Induced Hearing Loss.

    Science.gov (United States)

    Sun, Pengfei; Qin, Jun; Campbell, Kathleen

    2015-01-01

    Noise induced hearing loss (NIHL) remains as a severe health problem worldwide. Existing noise metrics and modeling for evaluation of NIHL are limited on prediction of gradually developing NIHL (GDHL) caused by high-level occupational noise. In this study, we proposed two auditory fatigue based models, including equal velocity level (EVL) and complex velocity level (CVL), which combine the high-cycle fatigue theory with the mammalian auditory model, to predict GDHL. The mammalian auditory model is introduced by combining the transfer function of the external-middle ear and the triple-path nonlinear (TRNL) filter to obtain velocities of basilar membrane (BM) in cochlea. The high-cycle fatigue theory is based on the assumption that GDHL can be considered as a process of long-cycle mechanical fatigue failure of organ of Corti. Furthermore, a series of chinchilla experimental data are used to validate the effectiveness of the proposed fatigue models. The regression analysis results show that both proposed fatigue models have high corrections with four hearing loss indices. It indicates that the proposed models can accurately predict hearing loss in chinchilla. Results suggest that the CVL model is more accurate compared to the EVL model on prediction of the auditory risk of exposure to hazardous occupational noise.

  16. Fatigue Modeling via Mammalian Auditory System for Prediction of Noise Induced Hearing Loss

    Directory of Open Access Journals (Sweden)

    Pengfei Sun

    2015-01-01

    Full Text Available Noise induced hearing loss (NIHL remains as a severe health problem worldwide. Existing noise metrics and modeling for evaluation of NIHL are limited on prediction of gradually developing NIHL (GDHL caused by high-level occupational noise. In this study, we proposed two auditory fatigue based models, including equal velocity level (EVL and complex velocity level (CVL, which combine the high-cycle fatigue theory with the mammalian auditory model, to predict GDHL. The mammalian auditory model is introduced by combining the transfer function of the external-middle ear and the triple-path nonlinear (TRNL filter to obtain velocities of basilar membrane (BM in cochlea. The high-cycle fatigue theory is based on the assumption that GDHL can be considered as a process of long-cycle mechanical fatigue failure of organ of Corti. Furthermore, a series of chinchilla experimental data are used to validate the effectiveness of the proposed fatigue models. The regression analysis results show that both proposed fatigue models have high corrections with four hearing loss indices. It indicates that the proposed models can accurately predict hearing loss in chinchilla. Results suggest that the CVL model is more accurate compared to the EVL model on prediction of the auditory risk of exposure to hazardous occupational noise.

  17. [The metabolic syndrome: effects of a pronounced weight loss induced by bariatric surgery].

    Science.gov (United States)

    Engl, Julia; Hanusch-Enserer, Ursula; Prager, Rudolf; Patsch, Josef R; Ebenbichler, Christoph

    2005-04-01

    The prevalence of obesity is rising worldwide dramatically, affecting up to 50 percent of the population. The epidemic of obesity leads to a marked increase in the metabolic syndrome, a cluster of cardiovascular risk factors characterized by visceral obesity, insulin resistance, low HDL-Cholesterol, hypertriglyceridemia, and a subclinical proinflammatory state. In the last years, the NCEP and the WHO highlighted and defined the key features of the metabolic syndrome to facilitate the clinical diagnosis and preventive interventions. The conservative therapy of obesity and the metabolic syndrome by life style intervention and pharmacological interventions leads only to moderate weight loss with inconstant long-term success. Intervention by bariatric surgery can serve as a model for the metabolic effects of permanent weight loss. In several studies the pronounced weight loss induced a reduction of almost all components of the metabolic syndrome, including glucose and lipid status and is followed by an improvement in the quality of life. Recent research suggested a decrease in mortality rate in addition to cost effectiveness of bariatric surgery.

  18. Low-loss planar metamaterials electromagnetically induced transparency for sensitive refractive index sensing

    Science.gov (United States)

    Tian, Ying; Hu, Sen; Huang, Xiaojun; Yu, Zetai; Lin, Hai; Yang, Helin

    2017-10-01

    A low-loss and high transmission electromagnetically induced transparency like (EIT- like) structure is experimentally and numerically demonstrated in this paper. The proposed planar structure based on EIT-like metamaterial consists of two separate split-ring resonators, and its resulting transmission level can maximally reach 0.89 with significant suppression of radiation loss. According to the effective medium theory, the imaginary parts of the effective permittivity and permeability of the metamaterial are used as the evidence of low-loss. In the analysis, the simulated surface current, magnetic field distribution and coupled oscillator model reveal the principle of high transmittance EIT-effect. Furthermore, the peak of transparency frequency is highly sensitive to the variation of refractive index in the background medium. The sensor based on the proposed EIT structure can achieve a sensitivity of 1.69 GHz/RIU (refractive index unit) and a figure of merit of 11.66. Such metamaterials have potential perspectives in sensing and chiral slow light devices.

  19. Evidence of noise-induced hearing loss in young people studying popular music.

    Science.gov (United States)

    Barlow, Christopher

    2011-06-01

    The number of students studying popular music, music technology, and sound engineering courses at both school and university to has increased rapidly in the last few years. These students are generally involved in music-making/recording and listening to a high level, usually in environments with amplified music. Recent studies have shown that these students are potentially exposed to a high risk of noise-induced hearing loss (NIHL( and are not covered by the same regulatory framework as employees. This study examined the pure tone air conduction hearing thresholds of 50 undergraduate students, including recent school leavers, on a range of popular music courses, to assess if there was evidence of hearing loss. Forty-four percent of students showed evidence of audiometric notch at 4-6 kHz, and 16% were classified under the UK Occupational Health and Safety guidelines as exhibiting mild hearing loss. Instance of audiometric notch was considerably higher than reported from studies of the general population but was around the same level or lower than that reported from studies of "traditional" music courses and conservatoires, suggesting no higher risk for popular music students than for "classical" music students. No relationship with age was present, suggesting that younger students were as likely to exhibit audiometric notch as mature students. This indicates that these students may be damaging their hearing through leisure activities while still at school, suggesting a need for robust education measures to focus on noise exposure of young people.

  20. Reduction of aspirin-induced fecal blood loss with low-dose misoprostol tablets in man

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, M.M.; Clark, L.; Armstrong, L.; D' Souza, J.

    1985-07-01

    Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the /sup 51/Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75 to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients.

  1. BEND-INDUCED LOSSES IN A SINGLE-MODE MICROSTRUCTURED FIBER WITH A LARGE CORE

    Directory of Open Access Journals (Sweden)

    Y. A. Gatchin

    2015-03-01

    Full Text Available A study of bend-induced losses in a silica-based single-mode microstructured fiber with a core diameter ranging from 20 to 35 microns and increased relative air content in the holey cladding has been conducted. With the use of the equivalent step-index profile method in approximation of waveguide parameters of microstructured fiber (normalized frequency and normalized transverse attenuation constant the effect of bending on the spectral position of the fundamentalmode short-wavelength leakage boundary has been analyzed. Upon measurement of spectral characteristics of attenuation in the considered fibers good accordance of numerical and experimental data has been found out. It is shown that increase of the air content in the holey cladding leads to expansion of the mentioned boundary to lower wavelengths for the value from 150 to 800 nm depending on the core size and bending conditions. A single-transverse-mode propagation is achieved on fiber length of 5-10 meters due to a substantial difference in losses of fundamental and higher-order guided modes attained by bending. Optical losses in all studied samples are less than 10 dB/km at the wavelength λ = 1550 nm. The results of the study can be applied in the design of high-power laser systems having such basic requirements as a relatively large mode spot and high beam quality.

  2. Reduction of aspirin-induced fecal blood loss with low-dose misoprostol tablets in man

    International Nuclear Information System (INIS)

    Cohen, M.M.; Clark, L.; Armstrong, L.; D'Souza, J.

    1985-01-01

    Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the 51 Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75 to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients

  3. Effect of physical activity on weight loss, energy expenditure, and energy intake during diet induced weight loss.

    Science.gov (United States)

    DeLany, James P; Kelley, David E; Hames, Kazanna C; Jakicic, John M; Goodpaster, Bret H

    2014-02-01

    Objective measurements of physical activity (PA), energy expenditure (EE) and energy intake can provide valuable information regarding appropriate strategies for successful sustained weight loss. The total EE was examined by doubly labeled water, resting metabolic rate by indirect calorimetry, PA with activity monitors, and energy intake by the intake/balance technique in 116 severely obese undergoing intervention with diet alone (DO) or diet plus PA (D-PA). Weight loss of 9.6 ± 6.8 kg resulted in decreased EE which was not minimized in the D-PA group. Comparing the highest and lowest quartiles of increase in PA revealed a lower decrease in TDEE (-122 ± 319 vs. -376 ± 305 kcal day⁻¹), elimination of the drop in AEE (83 ± 279 vs. -211 ± 284 kcal day⁻¹) and greater weight loss (13.0 ± 7.0 vs. 8.1 ± 6.3 kg). Increased PA was associated with greater adherence to energy restriction and maintenance of greater weight loss during months 7-12. Noncompliance to prescribed PA in the DO and D-PA groups partially masked the effects of PA to increase weight loss and to minimize the reduced EE. Increased PA was also associated with improved adherence to prescribed caloric restriction. A strong recommendation needs to be made to improve interventions that promote PA within the context of behavioral weight loss interventions. Copyright © 2013 The Obesity Society.

  4. Climate-induced glacier and snow loss imperils alpine stream insects

    Science.gov (United States)

    Giersch, J. Joseph; Hotaling, Scott; Kovach, Ryan; Jones, Leslie A.; Muhlfeld, Clint C.

    2017-01-01

    Climate warming is causing rapid loss of glaciers and snowpack in mountainous regions worldwide. These changes are predicted to negatively impact the habitats of many range-restricted species, particularly endemic, mountaintop species dependent on the unique thermal and hydrologic conditions found only in glacier-fed and snowmelt-driven alpine streams. Though progress has been made, existing understanding of the status, distribution, and ecology of alpine aquatic species, particularly in North America, is lacking, thereby hindering conservation and management programs. Two aquatic insects – the meltwater stonefly Lednia tumana and the glacier stonefly Zapada glacier – were recently proposed for listing under the U.S. Endangered Species Act due to climate-change-induced habitat loss. Using a large dataset (272 streams, 482 total sites) with high-resolution climate and habitat information, we describe the distribution, status, and key environmental features that limit L. tumana and Z. glacier across the northern Rocky Mountains. Lednia tumana was detected in 113 streams (175 sites) within Glacier National Park (GNP) and surrounding areas. The probability of L. tumana occurrence increased with cold stream temperatures and close proximity to glaciers and permanent snowfields. Similarly, densities of L. tumana declined with increasing distance from stream source. Zapada glacier was only detected in 10 streams (20 sites), six in GNP and four in mountain ranges up to ~600 km southwest. Our results show that both L. tumana and Z. glacier inhabit an extremely narrow distribution, restricted to short sections of cold, alpine streams often below glaciers predicted to disappear over the next two decades. Climate warming-induced glacier and snow loss clearly imperils the persistence of L. tumana and Z. glacier throughout their ranges, highlighting the role of mountaintop aquatic invertebrates as sentinels of climate change in mid-latitude regions.

  5. Occupational noise-induced hearing loss among workers at Jomo Kenyatta International Airport, Nairobi.

    Science.gov (United States)

    Anino, J O; Afullo, A; Otieno, F

    2010-02-01

    Occupational noise induced hearing loss (NIHL) occurs among workers exposed to excessive amounts of noise for long durations. The average level of noise in some locations at Jomo Kenyatta International Airport (JKIA) was above the safe limit of 85dB hence workers were thought to be at risk. To determine the occurrence and socio demographic attributes for NIHL at JKIA. Cross sectional descriptive study. Jomo Kenyatta International Airport, Nairobi, Kenya. Mean age of respondents was 37 years with range 22 to 62, SD 8.98. Mean duration of exposure to noise was 10.7 years with range 1 to 40, SD 8.15. Prevalence of NIHL was 15.3%, with ground crew at 14.8% and air crew 16.1%. Ground crew had significantly poorer mean hearing threshold level at 3, 4 and 6 kHz than air crew (p = 0.015). Male workers were affected more than female counterparts with a male to female ratio of 4:3. 97% of those affected were non-managers, 3% managers while 68% of those affected resided in Embakasi Division close to the airport. Hearing threshold level at 4 kHz deteriorated with increasing age whereby those aged 50 years and above had a 13.7 times higher relative risk than those aged 20 to 29 years. Duration of exposure more than 10 years also had significantly higher risk (p hearing loss at 4 kHz. Occupational noise induced hearing loss occurs atJKIA and that ground crew and older workers are more vulnerable. We recommend that prevention programmes be put in place.

  6. Steps in the formation of neurites and synapses studied in cultured leech neurons

    Directory of Open Access Journals (Sweden)

    De-Miguel F.F.

    2000-01-01

    Full Text Available Leech neurons in culture have provided novel insights into the steps in the formation of neurite outgrowth patterns, target recognition and synapse formation. Identified adult neurons from the central nervous system of the leech can be removed individually and plated in culture under well-controlled conditions, where they retain their characteristic physiological properties, grow neurites and form specific chemical or electrical synapses. Different identified neurons develop distinctive outgrowth patterns that depend on their identities and on the molecular composition of the substrate. On native substrates, the patterns displayed by these neurons reproduce characteristics from the adult or the developing neurons. In addition, the substrate may induce selective directed growth between pairs of neurons that normally make contact in the ganglion. Upon contact, pairs of cultured leech neurons form chemical or electrical synapses, or both types depending on the neuronal identities. Anterograde and retrograde signals during membrane contact and synapse formation modify the distribution of synaptic terminals, calcium currents, and responses to 5-hydroxytryptamine.

  7. Puerarin decreases bone loss and collagen destruction in rats with ligature-induced periodontitis.

    Science.gov (United States)

    Yang, X; Zhang, H; Wang, J; Zhang, Z; Li, C

    2015-12-01

    Puerarin, the most abundant isoflavonoid in kudzu root, shows various bioactivities, including bone-sparing, anti-inflammatory and antiproteinase properties. This study aimed to evaluate the effects of puerarin in a rat model of ligature-induced periodontitis. Rat models of periodontitis were developed by bilaterally placing ligatures around the first mandibular molars. Puerarin was administrated daily by gavage at doses of 100, 200 and 400 mg/kg, starting a day before the placement of ligatures. Rats were humanely killed 7 d after the induction of periodontitis. Micro-computed tomography and sirius red staining were used to evaluate alveolar bone loss and collagen destruction, respectively. Histomorphometrical analysis was used to assess the inflammatory cell infiltration. Immunohistochemistry and tartrate-resistant acid phosphatase were used to detect receptor activator of nuclear factor kappa B ligand and osteoprotegerin expressions, and osteoclast activity in the gingiva and alveolar bone. The activation of nuclear factor-kappa B, production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, glycosylation of extracellular matrix metalloproteinase inducer, and production of matrix metalloproteinase (MMP)-2 and MMP-9 in the gingiva were assessed by Western blot. Puerarin at doses of 200 and 400 mg/kg significantly reduced the alveolar bone loss compared with the vehicle group. Collagen destruction and inflammatory cell infiltration were significantly less in the puerarin-treated group (200 mg/kg) compared with that of the vehicle group. Puerarin (200 mg/kg) also reduced the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin and osteoclast activity. Western blot analysis showed that puerarin (200 mg/kg) inhibited the activation of nuclear factor-kappa B p65, which is associated with lower IL-1β and TNF-α production, and reduced the glycosylation of extracellular matrix metalloproteinase inducer, which is associated with lower

  8. Independent origins of neurons and synapses: insights from ctenophores.

    Science.gov (United States)

    Moroz, Leonid L; Kohn, Andrea B

    2016-01-05

    There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses

  9. Microglia-Synapse Pathways: Promising Therapeutic Strategy for Alzheimer's Disease

    Science.gov (United States)

    Xie, Jingdun; Wang, Haitao

    2017-01-01

    The main hallmarks of Alzheimer's disease (AD) are extracellular deposits of amyloid plaques and intracellular accumulation of hyperphosphorylated neurofibrillary tangles (tau). However, the mechanisms underlying these neuropathological changes remain largely unclear. To date, plenty of studies have shown that microglia-mediated neuroinflammation contributes to the pathogenesis of AD, and the microglia-synapse pathways have been repeatedly identified as the crucial factor in the disease process. In this review, evidences from microglia and synapse studies are presented, and the role of microglia in the pathogenesis of AD, the contributing factors to synapse dysfunction, and the role and mechanisms of microglia-synapse pathways will be discussed. PMID:28473983

  10. How synapses can enhance sensibility of a neural network

    Science.gov (United States)

    Protachevicz, P. R.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Baptista, M. S.; Viana, R. L.; Lameu, E. L.; Macau, E. E. N.; Batista, A. M.

    2018-02-01

    In this work, we study the dynamic range in a neural network modelled by cellular automaton. We consider deterministic and non-deterministic rules to simulate electrical and chemical synapses. Chemical synapses have an intrinsic time-delay and are susceptible to parameter variations guided by learning Hebbian rules of behaviour. The learning rules are related to neuroplasticity that describes change to the neural connections in the brain. Our results show that chemical synapses can abruptly enhance sensibility of the neural network, a manifestation that can become even more predominant if learning rules of evolution are applied to the chemical synapses.

  11. Development of an Evaluation Methodology for Loss of Large Area induced from extreme events

    International Nuclear Information System (INIS)

    Kim, Sok Chul; Park, Jong Seuk; Kim, Byung Soon; Jang, Dong Ju; Lee, Seung Woo

    2015-01-01

    USNRC announced several regulatory requirements and guidance documents regarding the event of loss of large area including 10CFR 50.54(hh), Regulatory Guide 1.214 and SRP 19.4. In Korea, consideration of loss of large area has been limitedly taken into account for newly constructing NPPs as voluntary based. In general, it is hardly possible to find available information on methodology and key assumptions for the assessment of LOLA due to 'need to know based approach'. Urgent needs exists for developing country specific regulatory requirements, guidance and evaluation methodology by themselves with the consideration of their own geographical and nuclear safety and security environments. Currently, Korea Hydro and Nuclear Power Company (KHNP) has developed an Extended Damage Mitigation Guideline (EDMG) for APR1400 under contract with foreign consulting company. The submittal guidance NEI 06-12 related to B.5.b Phase 2 and 3 focused on unit-wise mitigation strategy instead of site level mitigation or response strategy. Phase 1 mitigating strategy and guideline for LOLA (Loss of Large Area) provides emphasis on site level arrangement including cooperative networking outside organizations and agile command and control system. Korea Institute of Nuclear Safety has carried out a pilot in-house research project to develop the methodology and guideline for evaluation of LOLA since 2014. This paper introduces the summary of major results and outcomes of the aforementioned research project. After Fukushima Dai-Ichi accident, the awareness on countering the event of loss of large area induced from extreme man-made hazards or extreme beyond design basis external event. Urgent need exists to develop regulatory guidance for coping with this undesirable situation, which has been out of consideration at existing nuclear safety regulatory framework due to the expectation of rare possibility of occurrence

  12. Noise-induced hearing loss and combined noise and vibration exposure.

    Science.gov (United States)

    Turcot, A; Girard, S A; Courteau, M; Baril, J; Larocque, R

    2015-04-01

    While there is a wide body of literature addressing noise-induced hearing loss (NIHL) and hand-arm vibration syndrome (HAVS) independently, relatively few studies have considered the combined effects of noise and vibration. These studies have suggested an increased risk of NIHL in workers with vibration white finger (VWF), though the relationship remains poorly understood. To determine whether hearing impairment is worse in noise-exposed workers with VWF than in workers with similar noise exposures but without VWF. The Quebec National Institute of Public Health audiometric database was used in conjunction with work-related accident and occupational diseases data from the Quebec workers' compensation board to analyse differences in audiometry results between vibration-exposed workers in the mining and forestry industries and the overall source population, and between mining and forestry workers with documented VWF and those without VWF. The International Organization for Standardization (ISO) 7029 standards were used to calculate hearing loss not attributable to age. 15751 vibration-exposed workers were identified in an overall source population of 59339. Workers with VWF (n = 96) had significantly worse hearing at every frequency studied (500, 1000, 2000 4000 Hz) compared with other mining and forestry workers without VWF. This study confirms previous findings of greater hearing loss at higher frequencies in workers with VWF, but also found a significant difference in hearing loss at low frequencies. It therefore supports the association between combined noise and hand-arm vibration (HAV) exposure and NIHL. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology.

    Science.gov (United States)

    Sheppard, A; Hayes, S H; Chen, G-D; Ralli, M; Salvi, R

    2014-04-01

    Salicylate's ototoxic properties have been well established, inducing tinnitus and a sensory hearing loss when administered in high doses. Peripherally, acute dosing of salicylate causes frequency dependent reductions in DPOAEs and CAP amplitudes in low (20 kHz) frequencies more than mid frequencies (10-20 kHz), which interestingly corresponds to the pitch of behaviourally-matched salicylate-induced tinnitus. Chronic salicylate dosing affects the peripheral system by causing a compensatory temporary enhancement in DPOAE amplitudes and up-regulation of prestin mRNA and protein expression. Despite salicylate's antioxidant properties, cultured cochlea studies indicate it also impairs spiral ganglion neurons (SGNs) by paradoxically causing an upsurge of superoxide radicals leading to apoptosis. Centrally, salicylate alters γ-aminobutyric acid (GABA) and serotonin mediated neurotransmission in the central nervous system (CNS), which results in classical and non-classical auditory regions showing hyperactivity after salicylate administration. In the auditory cortex (AC) and lateral amygdala (LA), neuron characteristic frequencies (CF) shift upward and downward to mid frequencies (10-20 kHz) altering tonotopy following salicylate administration. Additionally, current source density (CSD) analysis showed enhanced current flow into the supergranular layer of the auditory cortex after a high systemic dose of salicylate. In humans, auditory perception changes following salicylate or aspirin, including decreased word discrimination and temporal integration ability. The results of previous studies have partially identified the mechanisms that are involved in salicylate-induced tinnitus and hearing loss, however to date some interactions remain convoluted. This review discusses current knowledge of salicylate ototoxicity and interactions.

  14. Renexin as a rescue regimen for noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    So Young Park

    2014-01-01

    Full Text Available Renexin, a compound of cilostazol and ginkgo biloba extract, has been reported to produce neuroprotective effects through antioxidant, antiplatelet, and vasodilatory mechanisms. This study was designed to investigate the protective effects of renexin on hearing, the organ of Corti (OC, and medial olivocochlear efferents against noise-induced damage. C57BL/6 mice were exposed to 110 dB SPL white noise for 60 min and then randomly divided into three groups: high- and low-dose renexin-treated groups and noise only group. Renexin were administered for 7 days: 90 mg/kg to the low-dose, and 180 mg/kg to the high-dose groups. All mice, including the controls underwent hearing tests on postnoise day 8 and were killed for cochlear harvest. We compared the hearing thresholds and morphology of the OC and cochlear efferents across the groups. The renexin-treated groups recovered from the immediate threshold shifts in a dose-dependent manner, while the noise group showed a permanent hearing loss. The renexin-treated ears demonstrated less degeneration of the OC. The diameters of the efferent terminals labeled with α-synuclein were preserved in the high-dose renexin-treated group. In the western blot assay of the cochlear homogenates, the treated groups displayed stronger expressions of α-synuclein than the noise and control groups, which may indicate that noise-induced enhanced activity of the cochlear efferent system was protected by renexin. Our results suggest that pharmacologic treatment with renexin is hopeful to reduce or prevent noise-induced hearing loss as a rescue regimen after noise exposure.

  15. Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

    Science.gov (United States)

    The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

  16. Triheteromeric NMDA Receptors at Hippocampal Synapses

    Science.gov (United States)

    Tovar, Kenneth R.; McGinley, Matthew J.; Westbrook, Gary L.

    2013-01-01

    NMDA receptors are composed of two GluN1 (N1) and two GluN2 (N2) subunits. Constituent N2 subunits control the pharmacological and kinetic characteristics of the receptor. NMDA receptors in hippocampal or cortical neurons are often thought of as diheteromeric, i.e., containing only one type of N2 subunit. However, triheteromeric receptors with more than one type of N2 subunit also have been reported and the relative contribution of di- and triheteromeric NMDA receptors at synapses has been difficult to assess. Because wild-type hippocampal principal neurons express N1, N2A and N2B, we used cultured hippocampal principal neurons from N2A and N2B-knockout mice as templates for diheteromeric synaptic receptors. Summation of N1/N2B and N1/N2A excitatory postsynaptic currents could not account for the deactivation kinetics of wild-type excitatory postsynaptic currents (EPSCs) however. To make a quantitative estimate of NMDA receptor subtypes at wild-type synapses, we used the deactivation kinetics, as well as the effects of the competitive antagonist NVP-AAM077. Our results indicate that three types of NMDA receptors contribute to the wild-type EPSC, with at least two-thirds being triheteromeric receptors. Functional isolation of synaptic triheteromeric receptors revealed deactivation kinetics and pharmacology distinct from either diheteromeric receptor subtype. Because of differences in open probability, synaptic triheteromeric receptors outnumbered N1/N2A receptors by 5.8 to 1 and N1/N2B receptors by 3.2 to 1. Our results suggest that triheteromeric NMDA receptors must be either preferentially assembled or preferentially localized at synapses. PMID:23699525

  17. Test and Simulation Results for Quenches Induced by Fast Losses on a LHC Quadrupole

    CERN Document Server

    Bracco, Ch; Bartmann, W; Bednarek, M; Lechner, A; Sapinski, M; Vittal Shetty, N; Schmidt, R; Solfaroli Camillocci, M; Verweij, A

    2014-01-01

    A test program for beam induced quenches was started in the LHC in 2011 in order to reduce as much as possible BLM-triggered beam dumps, without jeopardising the safety of the superconducting magnets. A first measurement was performed to asses the quench level of a quadrupole located in the LHC injection region in case of fast (ns) losses. It consisted in dumping single bunches onto an injection protection collimator located right upstream of the quadrupole, varying the bunch intensity up to 3×1010 protons and ramping the quadrupole current up to 2200 A. No quench was recorded at that time. The test was repeated in 2013 with increased bunch intensity (6.5×1010 protons); a quench occurred when powering the magnet at 2500 A. The comparison between measurements during beam induced and quench heaters induced quenches is shown. Results of FLUKA simulations on energy deposition, calculations on quench behaviour using the QP3 code and the respective estimates of quench levels are also presented.

  18. Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats

    International Nuclear Information System (INIS)

    Pouyatos, BenoIt; Gearhart, Caroline A.; Fechter, Laurence D.

    2005-01-01

    The diversity of chemical and drugs that can potentiate noise-induced hearing loss (NIHL) has impeded efforts to predict such interactions. We have hypothesized that chemical contaminants that disrupt intrinsic antioxidant defenses hold significant risk for potentiating NIHL. If this is true, then acrylonitrile (ACN) would be expected to potentiate NIHL. ACN, one of the 50 most commonly used chemicals in the United States, is metabolized via two pathways that are likely to disrupt intrinsic reactive oxygen species (ROS) buffering systems: (1) it conjugates glutathione, depleting this important antioxidant rapidly; (2) a second pathway involves the formation of cyanide, which can inhibit superoxide dismutase. We hypothesized that moderate noise exposure, that does not produce permanent hearing loss by itself, could initiate oxidative stress and that ACN could render the inner ear more sensitive to noise by disrupting intrinsic antioxidant defenses. Temporary and persistent effects of ACN alone (50 mg/kg, sc 5 days), noise alone (95 or 97 dB octave band noise, 4 h/day for 5 days), or ACN in combination with noise were determined using distortion product otoacoustic emissions (DPOAEs) and compound action potential (CAP) amplitudes. Histopathological damage to hair cells resulting from these treatments was also investigated using surface preparations of the organ of Corti. Individually, neither ACN nor noise exposures caused any permanent hearing or hair cell loss; only a reversible temporary threshold shift was measured in noise-exposed animals. However, when given in combination, ACN and noise induced permanent threshold shifts (13-16 dB between 7 and 40 kHz) and a decrease in DPOAE amplitudes (up to 25 dB at 19 kHz), as well as significant outer hair cell (OHC) loss (up to 20% in the first row between 13 and 47 kHz). This investigation demonstrates that ACN can potentiate NIHL at noise levels that are realistic in terms of human exposure, and that the OHCs are the

  19. Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats.

    Science.gov (United States)

    Pouyatos, Benoît; Gearhart, Caroline A; Fechter, Laurence D

    2005-04-01

    The diversity of chemical and drugs that can potentiate noise-induced hearing loss (NIHL) has impeded efforts to predict such interactions. We have hypothesized that chemical contaminants that disrupt intrinsic antioxidant defenses hold significant risk for potentiating NIHL. If this is true, then acrylonitrile (ACN) would be expected to potentiate NIHL. ACN, one of the 50 most commonly used chemicals in the United States, is metabolized via two pathways that are likely to disrupt intrinsic reactive oxygen species (ROS) buffering systems: (1) it conjugates glutathione, depleting this important antioxidant rapidly; (2) a second pathway involves the formation of cyanide, which can inhibit superoxide dismutase. We hypothesized that moderate noise exposure, that does not produce permanent hearing loss by itself, could initiate oxidative stress and that ACN could render the inner ear more sensitive to noise by disrupting intrinsic antioxidant defenses. Temporary and persistent effects of ACN alone (50 mg/kg, sc 5 days), noise alone (95 or 97 dB octave band noise, 4 h/day for 5 days), or ACN in combination with noise were determined using distortion product otoacoustic emissions (DPOAEs) and compound action potential (CAP) amplitudes. Histopathological damage to hair cells resulting from these treatments was also investigated using surface preparations of the organ of Corti. Individually, neither ACN nor noise exposures caused any permanent hearing or hair cell loss; only a reversible temporary threshold shift was measured in noise-exposed animals. However, when given in combination, ACN and noise induced permanent threshold shifts (13-16 dB between 7 and 40 kHz) and a decrease in DPOAE amplitudes (up to 25 dB at 19 kHz), as well as significant outer hair cell (OHC) loss (up to 20% in the first row between 13 and 47 kHz). This investigation demonstrates that ACN can potentiate NIHL at noise levels that are realistic in terms of human exposure, and that the OHCs are the

  20. Prestin regulation and function in residual outer hair cells after noise-induced hearing loss.

    Directory of Open Access Journals (Sweden)

    Anping Xia

    Full Text Available The outer hair cell (OHC motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. Tecta(C1509G transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9-12 kHz region, where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30-40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9-12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32-58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in

  1. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study.

    Science.gov (United States)

    Wadden, T A; Hollander, P; Klein, S; Niswender, K; Woo, V; Hale, P M; Aronne, L

    2013-11-01

    Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD). Obese/overweight participants (≥18 years, body mass index ≥30 kg m(-2) or ≥27 kg m(-2) with comorbidities) who lost ≥5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ≥5% weight loss, and the proportion that lost ≥5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937. Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference -6.1% (95% class intervals -7.5 to -4.6), Pweight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), Pweight (estimated odds ratio 3.9 (2.4; 6.1), Pweight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some cardiovascular disease-risk factors were also observed. Liraglutide, prescribed as 3.0 mg per day, holds promise for improving the maintenance of lost weight.

  2. Hydrogen peroxide induced loss of heterozygosity correlates with replicative lifespan and mitotic asymmetry in Saccharomyces cerevisiae

    Science.gov (United States)

    Jackson, Erin D.; Parker, Meighan C.; Gupta, Nilin; Rodrigues, Jenny

    2016-01-01

    Cellular aging in Saccharomyces cerevisiae can lead to genomic instability and impaired mitotic asymmetry. To investigate the role of oxidative stress in cellular aging, we examined the effect of exogenous hydrogen peroxide on genomic instability and mitotic asymmetry in a collection of yeast strains with diverse backgrounds. We treated yeast cells with hydrogen peroxide and monitored the changes of viability and the frequencies of loss of heterozygosity (LOH) in response to hydrogen peroxide doses. The mid-transition points of viability and LOH were quantified using sigmoid mathematical functions. We found that the increase of hydrogen peroxide dependent genomic instability often occurs before a drop in viability. We previously observed that elevation of genomic instability generally lags behind the drop in viability during chronological aging. Hence, onset of genomic instability induced by exogenous hydrogen peroxide treatment is opposite to that induced by endogenous oxidative stress during chronological aging, with regards to the midpoint of viability. This contrast argues that the effect of endogenous oxidative stress on genome integrity is well suppressed up to the dying-off phase during chronological aging. We found that the leadoff of exogenous hydrogen peroxide induced genomic instability to viability significantly correlated with replicative lifespan (RLS), indicating that yeast cells’ ability to counter oxidative stress contributes to their replicative longevity. Surprisingly, this leadoff is positively correlated with an inverse measure of endogenous mitotic asymmetry, indicating a trade-off between mitotic asymmetry and cell’s ability to fend off hydrogen peroxide induced oxidative stress. Overall, our results demonstrate strong associations of oxidative stress to genomic instability and mitotic asymmetry at the population level of budding yeast. PMID:27833823

  3. Toll-Like Receptor 4 Signaling Pathway Mediates Inhalant Organic Dust-Induced Bone Loss.

    Directory of Open Access Journals (Sweden)

    Elizabeth Staab

    Full Text Available Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2 and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO, but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT, analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures.

  4. Chronic Conductive Hearing Loss Leads to Cochlear Degeneration.

    Science.gov (United States)

    Liberman, M Charles; Liberman, Leslie D; Maison, Stéphane F

    2015-01-01

    Synapses between cochlear nerve terminals and hair cells are the most vulnerable elements in the inner ear in both noise-induced and age-related hearing loss, and this neuropathy is exacerbated in the absence of efferent feedback from the olivocochlear bundle. If age-related loss is dominated by a lifetime of exposure to environmental sounds, reduction of acoustic drive to the inner ear might improve cochlear preservation throughout life. To test this, we removed the tympanic membrane unilaterally in one group of young adult mice, removed the olivocochlear bundle in another group and compared their cochlear function and innervation to age-matched controls one year later. Results showed that tympanic membrane removal, and the associated threshold elevation, was counterproductive: cochlear efferent innervation was dramatically reduced, especially the lateral olivocochlear terminals to the inner hair cell area, and there was a corresponding reduction in the number of cochlear nerve synapses. This loss led to a decrease in the amplitude of the suprathreshold cochlear neural responses. Similar results were seen in two cases with conductive hearing loss due to chronic otitis media. Outer hair cell death was increased only in ears lacking medial olivocochlear innervation following olivocochlear bundle cuts. Results suggest the novel ideas that 1) the olivocochlear efferent pathway has a dramatic use-dependent plasticity even in the adult ear and 2) a component of the lingering auditory processing disorder seen in humans after persistent middle-ear infections is cochlear in origin.

  5. Cell adhesion and matricellular support by astrocytes of the tripartite synapse

    NARCIS (Netherlands)

    Hillen, Anne E J; Burbach, J Peter H; Hol, Elly M

    2018-01-01

    Astrocytes contribute to the formation, function, and plasticity of synapses. Their processes enwrap the neuronal components of the tripartite synapse, and due to this close interaction they are perfectly positioned to modulate neuronal communication. The interaction between astrocytes and synapses

  6. Personal cassette players ('Walkman'). Do they cause noise-induced hearing loss?

    Science.gov (United States)

    Turunen-Rise, I; Flottorp, G; Tvete, O

    1991-01-01

    Playing selected types of music on five different personal cassette players (PCPs) and using different gain (volume) settings, A-weighted maximum and equivalent sound pressure levels (SPLs) were measured on KEMAR (Knowles Electronics Manikin for Acoustic Research). The octave band SPLs were measured on KEMAR ear and transformed to field values in order to compare measured values with the Norwegian noise risk criteria. Temporary threshold shifts (TTS) measured in 6 subjects after listening to two different pop music cassettes on one PCP in two separate sessions, are presented. Based upon these studies we conclude that the risk of acquiring permanent noise-induced hearing loss (NIHL) from use of PCP is very small for what we found to be normal listening conditions.

  7. Distorted wave calculations for electron loss process induced by bare ion impact on biological targets

    International Nuclear Information System (INIS)

    Monti, J.M.; Tachino, C.A.; Hanssen, J.; Fojón, O.A.; Galassi, M.E.; Champion, C.; Rivarola, R.D.

    2014-01-01

    Distorted wave models are employed to investigate the electron loss process induced by bare ions on biological targets. The two main reactions which contribute to this process, namely, the single electron ionization as well as the single electron capture are here studied. In order to further assess the validity of the theoretical descriptions used, the influence of particular mechanisms are studied, like dynamic screening for the case of electron ionization and energy deposition on the target by the impacting projectile for the electron capture one. Results are compared with existing experimental data. - Highlights: ► Distorted wave models are used to investigate ion-molecule collisions. ► Differential and total cross-sections for capture and ionization are evaluated. ► The influence of dynamic screening is determined. ► Capture reaction dominates the mean energy deposited by the projectile on the target

  8. The role of the tripartite glutamatergic synapse in the pathophysiology of Alzheimer's disease.

    Science.gov (United States)

    Rudy, Carolyn C; Hunsberger, Holly C; Weitzner, Daniel S; Reed, Miranda N

    2015-03-01

    Alzheimer's disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear. A growing body of evidence suggests perturbations in the glutamatergic tripartite synapse, comprised of a presynaptic terminal, a postsynaptic spine, and an astrocytic process, may underlie the pathogenic mechanisms of AD. Glutamate is the primary excitatory neurotransmitter in the brain and plays an important role in learning and memory, but alterations in glutamatergic signaling can lead to excitotoxicity. This review discusses the ways in which both beta-amyloid (Aβ) and tau act alone and in concert to perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of N-methyl-D-aspartate (NMDA) as a possible convergence point for Aβ and tau toxicity.

  9. Chaos analysis of EEG during isoflurane-induced loss of righting in rats.

    Science.gov (United States)

    MacIver, M B; Bland, Brian H

    2014-01-01

    It has long been known that electroencephalogram (EEG) signals generate chaotic strange attractors and the shape of these attractors correlate with depth of anesthesia. We applied chaos analysis to frontal cortical and hippocampal micro-EEG signals from implanted microelectrodes (layer 4 and CA1, respectively). Rats were taken to and from loss of righting reflex (LORR) with isoflurane and behavioral measures were compared to attractor shape. Resting EEG signals at LORR differed markedly from awake signals, more similar to slow wave sleep signals, and easily discerned in raw recordings (high amplitude slow waves), and in fast Fourier transform analysis (FFT; increased delta power), in good agreement with previous studies. EEG activation stimulated by turning rats on their side, to test righting, produced signals quite similar to awake resting state EEG signals. That is, the high amplitude slow wave activity changed to low amplitude fast activity that lasted for several seconds, before returning to slow wave activity. This occurred regardless of whether the rat was able to right itself, or not. Testing paw pinch and tail clamp responses produced similar EEG activations, even from deep anesthesia when burst suppression dominated the spontaneous EEG. Chaotic attractor shape was far better at discerning between these awake-like signals, at loss of responses, than was FFT analysis. Comparisons are provided between FFT and chaos analysis of EEG during awake walking, slow wave sleep, and isoflurane-induced effects at several depths of anesthesia. Attractors readily discriminated between natural sleep and isoflurane-induced "delta" activity. Chaotic attractor shapes changed gradually through the transition from awake to LORR, indicating that this was not an on/off like transition, but rather a point along a continuum of brain states.

  10. Chaos analysis of EEG during isoflurane-induced loss of righting in rats

    Directory of Open Access Journals (Sweden)

    Bruce eMaciver

    2014-10-01

    Full Text Available It has long been known that electroencephalogram (EEG signals generate chaotic strange attractors and the shape of these attractors correlate with depth of anesthesia. We applied chaos analysis to frontal cortical and hippocampal micro-EEG signals from implanted microelectrodes (layer 4 and CA1, respectively. Rats were taken to and from loss of righting reflex (LORR with isoflurane and behavioral measures were compared to attractor shape. Resting EEG signals at LORR differed markedly from awake signals, more similar to slow wave sleep signals, and easily discerned in raw recordings (high amplitude slow waves, and in fast Fourier transform analysis (FFT; increased delta power, in good agreement with previous studies. EEG activation stimulated by turning rats on their side, to test righting, produced signals quite similar to awake resting state EEG signals. That is, the high amplitude slow wave activity changed to low amplitude fast activity that lasted for several seconds, before returning to slow wave activity. This occurred regardless of whether the rat was able to right itself, or not. Testing paw pinch and tail clamp responses produced similar EEG activations, even from deep anesthesia when burst suppression dominated the spontaneous EEG. Chaotic attractor shape was far better at discerning between these awake-like signals, at loss of responses, than was FFT analysis. Comparisons are provided between FFT and chaos analysis of EEG during awake walking, slow wave sleep, and isoflurane-induced effects at several depths of anesthesia. Attractors readily discriminated between natural sleep and isoflurane-induced ‘delta’ activity. Chaotic attractor shapes changed gradually through the transition from awake to LORR, indicating that this was not an on/off like transition, but rather a point along a continuum of brain states.

  11. Prior heat acclimation confers protection against noise-induced hearing loss.

    Science.gov (United States)

    Paz, Ziv; Freeman, Sharon; Horowitz, Michal; Sohmer, Haim

    2004-01-01

    Exposure to intense noise stress can cause a permanent noise-induced hearing loss which is thought to be due to elevation of reactive oxygen species in excess of the inherent antioxidant mechanisms of the cell. However, preconditioning to low levels of stress of one type can activate cellular mechanisms leading to the elevation of antioxidant levels so that the cell is then better able to tolerate subsequent severe stress of a different type. This has been called cross-tolerance. Here, we tested this hypothesis by acclimating rats to a moderate heat stress (30 days at 34 degrees C). The rats were exposed to 113 dB SPL noise for 3 days (12 h/day) in three different groups: heat acclimated then noise exposed; noise exposed and then heat acclimated; heat acclimated, then noise exposed and then heat acclimated again. Permanent changes in auditory function--auditory nerve brainstem evoked responses (ABR) and distortion product otoacoustic emissions (DPOAEs)--were evaluated in each of these animals and compared with those in rats exposed to noise only and in control groups of rats. Statistical evaluation of the results showed that when assessed with ABR, each of the heat-acclimated, noise-exposed groups was protected from the noise, even the group that was heat-acclimated after the noise exposure. When assessed with DPOAE, protection was statistically apparent only in the group that was heat acclimated, then exposed to noise, and not in the other groups. Thus, heat acclimation provides protection against permanent noise-induced hearing loss.

  12. The effect of temperature on eccentric contraction-induced isometric force loss in isolated perfused rat medial gastrocnemius muscle

    Directory of Open Access Journals (Sweden)

    Vasaghi Gharamaleki B

    2008-09-01

    Full Text Available "nBackground: The typical features of eccentric exercise-induced muscle damage are delayed-onset muscle soreness (DOMS and prolonged loss of muscle strength. It has been shown that passive warmth is effective in reducing muscle injury. Due to the interaction of different systems in vivo, we used isolated perfused medial gastrocnemius skeletal muscle to study the direct effect of temperature on the eccentric contraction-induced force loss. "nMethods: After femoral artery cannulation of a rat, the left medial gastrocnemius muscle was separated and then the entire lower limb was transferred into a prewarmed (35oC chamber. With the chamber temperature at 31, 35 and 39oC before and during eccentric contraction. Isometric force loss was measured after 15 eccentric contractions (N=7-9. "nResults: Maximum contraction force reduction has been used as an index for eccentric contraction-induced force loss. In this study eccentric contraction caused a significant reduction in maximum isometric tension (p<0.01, but no significant difference was seen in isometric force loss at 31oC and 39oC compared with that at 35oC. "nConclusions: Our results suggest that temperature changes before or during eccentric contractions have no effect on eccentric contraction-induced force loss. "nKeywords: Isolated perfused muscle, skeletal muscle, eccentric contractions, isometric force, gastrocnemius muscle, temperature.

  13. Involvement of the α1-adrenoceptor in sleep-waking and sleep loss-induced anxiety behavior in zebrafish.

    Science.gov (United States)

    Singh, A; Subhashini, N; Sharma, S; Mallick, B N

    2013-08-15

    Sleep is a universal phenomenon in vertebrates, and its loss affects various behaviors. Independent studies have reported that sleep loss increases anxiety; however, the detailed mechanism is unknown. Because sleep deprivation increases noradrenalin (NA), which modulates many behaviors and induces patho-physiological changes, this study utilized zebrafish as a model to investigate whether sleep loss-induced increased anxiety is modulated by NA. Continuous behavioral quiescence for at least 6s was considered to represent sleep in zebrafish; although some authors termed it as a sleep-like state, in this study we have termed it as sleep. The activity of fish that signified sleep-waking was recorded in light-dark, during continuous dark and light; the latter induced sleep loss in fish. The latency, number of entries, time spent and distance travelled in the light chamber were assessed in a light-dark box test to estimate the anxiety behavior of normal, sleep-deprived and prazosin (PRZ)-treated fish. Zebrafish showed increased waking during light and complete loss of sleep upon continuous exposure to light for 24h. PRZ significantly increased sleep in normal fish. Sleep-deprived fish showed an increased preference for dark (expression of increased anxiety), and this effect was prevented by PRZ, which increased sleep as well. Our findings suggest that sleep loss-induced anxiety-like behavior in zebrafish is likely to be mediated by NA's action on the α1-adrenoceptor. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Alpha-1 Antitrypsin Gene Therapy Ameliorates Bone Loss in Ovariectomy-Induced Osteoporosis Mouse Model.

    Science.gov (United States)

    Akbar, Mohammad Ahsanul; Cao, Jay J; Lu, Yuanqing; Nardo, David; Chen, Mong-Jen; Elshikha, Ahmed S; Ahamed, Rubina; Brantly, Mark; Holliday, L Shannon; Song, Sihong

    2016-09-01

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at menopause. Therefore, anti-inflammatory strategies hold a great potential for the prevention of postmenopausal osteoporosis. In this study, we investigated the effect of gene therapy of recombinant adeno-associated virus (rAAV)-mediated human alpha-1 antitrypsin (hAAT), a multifunctional protein that has anti-inflammatory property, on bone loss in an ovariectomy-induced osteoporosis mouse model. Adult ovariectomized (OVX) mice were intraperitoneally (i.p.) injected with hAAT (protein therapy), rAAV8-CB-hAAT (gene therapy), or phosphate buffer saline (PBS). Age-matched and sham-operated animals were used as controls. Eight weeks after the treatment, animals were sacrificed and bone-related biomarkers and vertebral bone structure were evaluated. Results showed that hAAT gene therapy significantly decreased serum IL-6 level and receptor activator of NF-κB (RANK) gene expression in bone. Importantly, hAAT gene therapy increased bone volume/total volume and decreased structure model index (SMI) compared to PBS injection in OVX mice. These results demonstrate that hAAT gene therapy by rAAV vector efficiently mitigates bone loss possibly through inhibition of proinflammatory cytokine IL-6 and RANK gene expression. Considering the safety profile of hAAT and rAAV vector in humans, our results provide a new alternative for the treatment of osteoporosis.

  15. Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced alveolar bone loss in rats.

    Science.gov (United States)

    Li, Xianxian; Wu, Xiangnan; Ma, Yuanyuan; Hao, Zhichao; Chen, Shenyuan; Fu, Taozi; Chen, Helin; Wang, Hang

    2015-05-01

    5-Hydroxytryptophan (5-HTP) is the precursor of serotonin and 5-HTP has been widely used as a dietary supplement to raise serotonin level. Serotonin has recently been discovered to be a novel and important player in bone metabolism. As peripheral serotonin negatively regulates bone, the regular take of 5-HTP may affect the alveolar bone metabolism and therefore influence the alveolar bone loss induced by periodontitis. The aim of this study was to investigate the effect of 5-HTP on alveolar bone destruction in periodontitis. Male Sprague-Dawley rats were randomly divided into the following four groups: (1) the control group (without ligature); (2) the 5-HTP group (5-HTP at 25 mg/kg/day without ligature); (3) the L group (ligature+saline placebo); and (4) the L+5-HTP group (ligature+5-HTP at 25 mg/kg/day). Serum serotonin levels were determined by ELISA. The alveolar bones were evaluated with micro-computed tomography and histology. Tartrate-resistant acid phosphatase staining was used to assess osteoclastogenesis. The receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) expression in the periodontium as well as the interleukin-6 positive osteocytes were analysed immunohistochemically. 5-HTP significantly increased serum serotonin levels. In rats with experimental periodontitis, 5-HTP increased alveolar bone resorption and worsened the micro-structural destruction of the alveolar bone. 5-HTP also stimulated osteoclastogenesis and increased RANKL/OPG ratio and the number of IL-6 positive osteocytes. However, 5-HTP treatment alone did not cause alveolar bone loss in healthy rats. The present study showed that 5-HTP aggravated alveolar bone loss, deteriorated alveolar bone micro-structure in the presence of periodontitis, which suggests 5-HTP administration may increase the severity of periodontitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling

    Directory of Open Access Journals (Sweden)

    F.A. Pereira

    2007-04-01

    Full Text Available Data about the impact of bariatric surgery (BS and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD, bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16. The data were compared to those obtained for women of normal weight (CG, N = 11 and for obese women (OG, N = 12. Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 ± 62 vs OG = 230 ± 37 vs OGg = 128 ± 19 ng/mL were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

  17. Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

    Science.gov (United States)

    Mulugeta, L.; Werner, C. R.; Pennline, J. A.

    2015-01-01

    During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

  18. Predictive factors of occupational noise-induced hearing loss in Spanish workers: A prospective study.

    Science.gov (United States)

    Pelegrin, Armando Carballo; Canuet, Leonides; Rodríguez, Ángeles Arias; Morales, Maria Pilar Arévalo

    2015-01-01

    The purpose of our study was to identify the main factors associated with objective noise-induced hearing loss (NIHL), as indicated by abnormal audiometric testing, in Spanish workers exposed to occupational noise in the construction industry. We carried out a prospective study in Tenerife, Spain, using 150 employees exposed to occupational noise and 150 age-matched controls who were not working in noisy environments. The variables analyzed included sociodemographic data, noise-related factors, types of hearing protection, self-report hearing loss, and auditory-related symptoms (e.g., tinnitus, vertigo). Workers with pathological audiograms had significantly longer noise-exposure duration (16.2 ± 11.4 years) relative to those with normal audiograms (10.2 ± 7.0 years; t = 3.99, P hearing protection measures had audiometric abnormalities (94.1%). Additionally, workers using at least one of the protection devices (earplugs or earmuffs) had significantly more audiometric abnormalities than those using both protection measures simultaneously (Chi square = 16.07; P hearing protection measures [odds ratio (OR) = 12.30, confidence interval (CI) = 4.36-13.81, P hearing protection measures, in particular earplugs and earmuffs, associates with a lower rate of audiometric abnormalities in subjects with high occupational noise exposure. The use of hearing protection measures at work and noise-exposure duration are best predictive factors of NIHL. Auditory-related symptoms and self-report hearing loss do not represent good indicators of objective NIHL. Routine monitoring of noise levels and hearing status are of great importance as part of effective hearing conservation programs.

  19. Toxoplasma gondii Infections Alter GABAergic Synapses and Signaling in the Central Nervous System

    Science.gov (United States)

    Brooks, Justin M.; Carrillo, Gabriela L.; Su, Jianmin; Lindsay, David S.; Blader, Ira J.

    2015-01-01

    ABSTRACT During infections with the protozoan parasite Toxoplasma gondii, gamma-aminobutyric acid (GABA) is utilized as a carbon source for parasite metabolism and also to facilitate parasite dissemination by stimulating dendritic-cell motility. The best-recognized function for GABA, however, is its role in the nervous system as an inhibitory neurotransmitter that regulates the flow and timing of excitatory neurotransmission. When this pathway is altered, seizures develop. Human toxoplasmosis patients suffer from seizures, suggesting that Toxoplasma interferes with GABA signaling in the brain. Here, we show that while excitatory glutamatergic presynaptic proteins appeared normal, infection with type II ME49 Toxoplasma tissue cysts led to global changes in the distribution of glutamic acid decarboxylase 67 (GAD67), a key enzyme that catalyzes GABA synthesis in the brain. Alterations in GAD67 staining were not due to decreased expression but rather to a change from GAD67 clustering at presynaptic termini to a more diffuse localization throughout the neuropil. Consistent with a loss of GAD67 from the synaptic terminals, Toxoplasma-infected mice develop spontaneous seizures and are more susceptible to drugs that induce seizures by antagonizing GABA receptors. Interestingly, GABAergic protein mislocalization and the response to seizure-inducing drugs were observed in mice infected with type II ME49 but not type III CEP strain parasites, indicating a role for a polymorphic parasite factor(s) in regulating GABAergic synapses. Taken together, these data support a model in which seizures and other neurological complications seen in Toxoplasma-infected individuals are due, at least in part, to changes in GABAergic signaling. PMID:26507232

  20. Melanin precursors prevent premature age-related and noise-induced hearing loss in albino mice.

    Science.gov (United States)

    Murillo-Cuesta, Silvia; Contreras, Julio; Zurita, Esther; Cediel, Rafael; Cantero, Marta; Varela-Nieto, Isabel; Montoliu, Lluís

    2010-02-01

    Strial melanocytes are required for normal development and correct functioning of the cochlea. Hearing deficits have been reported in albino individuals from different species, although melanin appears to be not essential for normal auditory function. We have analyzed the auditory brainstem responses (ABR) of two transgenic mice: YRT2, carrying the entire mouse tyrosinase (Tyr) gene expression-domain and undistinguishable from wild-type pigmented animals; and TyrTH, non-pigmented but ectopically expressing tyrosine hydroxylase (Th) in melanocytes, which generate the precursor metabolite, L-DOPA, but not melanin. We show that young albino mice present a higher prevalence of profound sensorineural deafness and a poorer recovery of auditory thresholds after noise-exposure than transgenic mice. Hearing loss was associated with absence of cochlear melanin or its precursor metabolites and latencies of the central auditory pathway were unaltered. In summary, albino mice show impaired hearing responses during ageing and after noise damage when compared to YRT2 and TyrTH transgenic mice, which do not show the albino-associated ABR alterations. These results demonstrate that melanin precursors, such as L-DOPA, have a protective role in the mammalian cochlea in age-related and noise-induced hearing loss.

  1. Hearing loss induced by loud music among musicians of symphonic orchestra

    Directory of Open Access Journals (Sweden)

    Tanja Carli

    2012-12-01

    Full Text Available Noise-induced hearing loss is an important public health issue, especially among musicians who are, more than any other occupation, dependent on their hearing. For them, hearing impairment is due to too loud music, the effect of which, if exceeding the limit depending on the individual sensitivity of one’s ear, can be compared with theeffect of noise on the ear. Risk factors for its development are: the type of musical instrument and sound character, the way of playing, music genre or composition, duration of exposure to loud music, sound source and its distance from the ear, intervals of acoustic stimuli, individual factors and the musician’s position in the orchestra. Hearing impairment is greater at higher frequencies; in pure tone audiogram it is shown as notches between 3000 and 6000 Hz and is most frequent in the wind and brass section. Hearing loss is greater among violinists and typically affects the left ear owing to the sound source proximity and their position in the orchestra. The most common health problems take the form of diplacusis, algiacusis and tinnitus, as exposure to the loud acoustic stimulus above 90 dB(A cause damage to the inner ear, the so-called acoustic trauma. Use of personal protective equipment among musicians is low especially because of too much high-frequency attenuation and occlusion effect.

  2. Implementation of a method to visualize noise-induced hearing loss in mass stranded cetaceans

    Science.gov (United States)

    Morell, Maria; Brownlow, Andrew; McGovern, Barry; Raverty, Stephen A.; Shadwick, Robert E.; André, Michel

    2017-02-01

    Assessment of the impact of noise over-exposure in stranded cetaceans is challenging, as the lesions that lead to hearing loss occur at the cellular level and inner ear cells are very sensitive to autolysis. Distinguishing ante-mortem pathology from post-mortem change has been a major constraint in diagnosing potential impact. Here, we outline a methodology applicable to the detection of noise-induced hearing loss in stranded cetaceans. Inner ears from two mass strandings of long-finned pilot whales in Scotland were processed for scanning electron microscopy observation. In one case, a juvenile animal, whose ears were fixed within 4 hours of death, revealed that many sensory cells at the apex of the cochlear spiral were missing. In this case, the absence of outer hair cells would be compatible with overexposure to underwater noise, affecting the region which transduces the lowest frequencies of the pilot whales hearing spectrum. Perfusion of cochlea with fixative greatly improved preservation and enabled diagnostic imaging of the organ of Corti, even 30 hours after death. This finding supports adopting a routine protocol to detect the pathological legacy of noise overexposure in mass stranded cetaceans as a key to understanding the complex processes and implications that lie behind such stranding events.

  3. Simultaneous bilateral laser therapy accelerates recovery after noise-induced hearing loss in a rat model

    Directory of Open Access Journals (Sweden)

    Jae-Hun Lee

    2016-07-01

    Full Text Available Noise-induced hearing loss is a common type of hearing loss. The effects of laser therapy have been investigated from various perspectives, including in wound healing, inflammation reduction, and nerve regeneration, as well as in hearing research. A promising feature of the laser is its capability to penetrate soft tissue; depending on the wavelength, laser energy can penetrate into the deepest part of the body without damaging non-target soft tissues. Based on this idea, we developed bilateral transtympanic laser therapy, which uses simultaneous laser irradiation in both ears, and evaluated the effects of bilateral laser therapy on cochlear damage caused by noise overexposure. Thus, the purpose of this research was to assess the benefits of simultaneous bilateral laser therapy compared with unilateral laser therapy and a control. Eighteen Sprague-Dawley rats were exposed to narrow-band noise at 115 dB SPL for 6 h. Multiple auditory brainstem responses were measured after each laser irradiation, and cochlear hair cells were counted after the 15th such irradiation. The penetration depth of the 808 nm laser was also measured after sacrifice. Approximately 5% of the laser energy reached the contralateral cochlea. Both bilateral and unilateral laser therapy decreased the hearing threshold after noise overstimulation in the rat model. The bilateral laser therapy group showed faster functional recovery at all tested frequencies compared with the unilateral laser therapy group. However, there was no difference in the endpoint ABR results or final hair cell survival, which was analyzed histologically.

  4. Characteristic of Noise-induced Hearing Loss among Workers in Construction Industries

    Directory of Open Access Journals (Sweden)

    Mazlan Ain Naadia

    2018-01-01

    Full Text Available Noise-induced hearing loss (NIHL is among the most common occupational disease in industries. This paper investigates NIHL in construction related industries in Malaysia with particular emphasis on its relation with risk factors. The objectives of this research were to (1 quantify the prevalence of NIHL in construction related industries, and (2 assess the relationship between hearing loss and risk factors and it’s characteristic. The study was conducted using 110 NIHL compensation record collected from Social Security Organisation (SOCSO, Malaysia. Risk factors namely area noise, age, temperature, smoking habit, hobby, diabetic and cardiovascular disease were identified and analysed. Results showed that there was no direct relationship between area noise with hearing impairment while there was only low relationship between age and hearing impairment. The range for area noise and age were between 70 to 140 dB(A and 20 to 70 years, respectively. The other risk factors classified as categorical data and analysed using frequency method. Grade of impairment does not depend solely on area noise but also in combination with age and other risk factors. Characteristic of NIHL prevailed in construction related industries were presented using scatterplots and can serve as a references for future hazard control on site.

  5. Electronic energy loss effects on chemical modification of polyimide induced by high energy xenon ions

    International Nuclear Information System (INIS)

    Sun Youmei; Zhu Zhiyong; Jin Yunfan; Wang Zhiguang; Hou Mingdong

    2004-01-01

    Stacked polyimide (PI) films of about 25 μm in thickness were irradiated with 1.755 GeV xenon ions under vacuum at room temperature. The chemical changes of modified PI films were studied by Fourier transform infrared (FTIR) and ultraviolet/visible (UV/Vis) absorption spectroscopy. The FTIR results show that the absorbance of the typical function groups decreases exponentially as a function of fluence. Under 8.8 keV/nm (minimum) and 11.5 keV/nm (maximum) electronic energy loss of 136 Xe irradiation, the mean degradation radius of all function groups in PI is 3.6 and 4.1 nm, respectively. The alkyne end group was found after irradiation and its formation radius was 5.6 nm and 5.9 nm corresponding to 8.8 keV/nm and 11.5 keV/nm, respectively. the UV/Vis analysis indicates the radiation induced absorbance change follows a linear relation with fluence, and the production efficiency of chromospheres depends strongly on the electronic energy loss (dE/dX) e . (authors)

  6. T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss.

    Science.gov (United States)

    Furmanski, Anna L; O'Shaughnessy, Ryan F L; Saldana, Jose Ignacio; Blundell, Michael P; Thrasher, Adrian J; Sebire, Neil J; Davies, E Graham; Crompton, Tessa

    2013-05-01

    Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisingly, we did not detect multiorgan autoimmune disease. However, in all transplanted mice, we noted a striking depigmentation and loss of hair follicles. Transfer of T cells from transplanted nudes to syngeneic black-coated RAG(-/-) recipients caused progressive, persistent coat-hair whitening, which preceded patchy hair loss in depigmented areas. Further transfer experiments revealed that these phenomena could be induced by CD4+ T cells alone. Immunofluorescent analysis suggested that Trp2+ melanocyte-lineage cells were decreased in depigmented hair follicles, and pathogenic T cells upregulated activation markers when exposed to C57BL/6 melanocytes in vitro, suggesting that these T cells are not tolerant to self-melanocyte antigens. Our data raise interesting questions about the mechanisms underlying tissue-specific tolerance to skin antigens.

  7. Estimates of Workers with Noise-Induced Hearing Loss and Population at Risk

    Science.gov (United States)

    Miyakita, T.; Ueda, A.

    1997-08-01

    Towards the goal of protecting workers from damage due to noise exposure, a vast store of knowledge has been generated about its nature, etiology and time course. There still exists, however, a strong need to reclarify the locations, nature and magnitude of the problem of noise-induced hearing loss (NIHL). Based on the rate of positive results in a hearing screening test in the workplace, this paper presents an attempt to estimate the total number of workers with more than 40 dB hearing loss at 4 kHz caused by occupational noise exposure. The estimated values in major industry groups were as follows: about 780 000 in manufacturing; 410 000 in construction; 360 000 in agriculture; forestry and fishing; and around 2 million in total. Although it is rather difficult to estimate the number of workers exposed to noise above 85 dB(A), it may be reasonable to believe that at least several million workers exposed to noise should be covered by the 1992 guidelines for the prevention of noise hazards.

  8. Characteristic of Noise-induced Hearing Loss among Workers in Construction Industries

    Science.gov (United States)

    Naadia Mazlan, Ain; Yahya, Khairulzan; Haron, Zaiton; Amsharija Mohamed, Nik; Rasib, Edrin Nazri Abdul; Jamaludin, Nizam; Darus, Nadirah

    2018-03-01

    Noise-induced hearing loss (NIHL) is among the most common occupational disease in industries. This paper investigates NIHL in construction related industries in Malaysia with particular emphasis on its relation with risk factors. The objectives of this research were to (1) quantify the prevalence of NIHL in construction related industries, and (2) assess the relationship between hearing loss and risk factors and it's characteristic. The study was conducted using 110 NIHL compensation record collected from Social Security Organisation (SOCSO), Malaysia. Risk factors namely area noise, age, temperature, smoking habit, hobby, diabetic and cardiovascular disease were identified and analysed. Results showed that there was no direct relationship between area noise with hearing impairment while there was only low relationship between age and hearing impairment. The range for area noise and age were between 70 to 140 dB(A) and 20 to 70 years, respectively. The other risk factors classified as categorical data and analysed using frequency method. Grade of impairment does not depend solely on area noise but also in combination with age and other risk factors. Characteristic of NIHL prevailed in construction related industries were presented using scatterplots and can serve as a references for future hazard control on site.

  9. Experimental study of plant specific head loss induced by LOCA-generated debris at containment sump of PWR

    International Nuclear Information System (INIS)

    Young Wook, Chung; Young Mook, Hwang; Jong Uk, Kim; Byung Gi, Park; Byung Chul, Lee; Jong Woon, Park

    2007-01-01

    A LOCA in PWR would generate debris from thermal insulation and other materials in the vicinity of the break. A fraction of the LOCA-generated debris and pre-LOCA debris will be transported into the sump and accumulated on the sump screens resulting in adverse blockage effects that are degradation or loss of NPSH (Net Positive Suction Head) margin. To assess debris-induced head loss in the sump screen, experimental studies have been widely conducted and the results have exhibited that head loss depends on amount of debris, specific surface area, mixture porosity of debris bed, debris types, and so on. Based on the experimental results, empirical correlations have been developed. NUREG/CR-6224 head loss correlation among them has been widely used to estimate the debris-induced head loss for PWR sump performance evaluation. However, in order to apply this correlation for estimating head loss in specific PWR plant, plant-specific head loss data are required because of a different composition of debris sources between PWRs. Plant specific head loss data were obtained with a test facility that is a closed-loop types. A vertical test section of test facility was fabricated with 6 inch CPVC (Chlorinated Polyvinyl Chloride) pipe. A ratio of length to diameter at the vertical test section was about 30. Experimental results exhibited that the head loss across NUKON debris bed with theoretical thickness greater than 4 inch was predicted conservatively by NUREG/CR-6224 correlation. Head loss test with debris composition of Westinghouse two loop plant showed that NUREG/CR-6224 correlation predicted higher head loss than experimentally measured head loss. (authors)

  10. Rhythmic changes in synapse numbers in Drosophila melanogaster motor terminals.

    Directory of Open Access Journals (Sweden)

    Santiago Ruiz

    Full Text Available Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in Drosophila melanogaster undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD cycles and constant darkness (DD. We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons.

  11. Prevention of the Evolution of Workers' Hearing Loss from Noise-Induced Hearing Loss in Noisy Environments through a Hearing Conservation Program.

    Science.gov (United States)

    Fonseca, Vinicius Ribas; Marques, Jair; Panegalli, Flavio; Gonçalves, Claudia Giglio de Oliveira; Souza, Wesley

    2016-01-01

    Introduction Noise-induced hearing loss (NIHL) is a serious problem for workers and therefore for businesses. The hearing conservation program (HCP) is a set of coordinated measures to prevent the development or evolution of occupational hearing loss, which involves a continuous and dynamic process of implementation of hearing conservation routines through anticipation, recognition, evaluation, and subsequent control of the occurrence of existing environmental risks or of those that may exist in the workplace and lead to workers' hearing damage. Objective The aim of this study was to evaluate the effectiveness of the HCP in preventing further hearing loss in workers with audiograms suggestive of NIHL. The audiometric tests and medical records of 28 furniture company workers exposed to noise were reviewed and monitored for 2 years. Methods This retrospective, cross-sectional study examined five audiometric tests in the medical records (on admission and every semester) of 28 workers in a furniture company (totaling 140 audiometric exams) following the introduction of the HCP. Results Data analysis showed no differences between the audiometric tests conducted on admission and those performed every semester. Conclusions The HCP implemented was effective in preventing the worsening of hearing loss in workers already with NIHL when exposed to occupational noise. Therefore, such a measure could be useful for the employment of workers with hearing loss in job sectors that have noise exposure.

  12. Salicylate-induced hearing loss and gap detection deficits in rats.

    Science.gov (United States)

    Radziwon, Kelly E; Stolzberg, Daniel J; Urban, Maxwell E; Bowler, Rachael A; Salvi, Richard J

    2015-01-01

    To test the "tinnitus gap-filling" hypothesis in an animal psychoacoustic paradigm, rats were tested using a go/no-go operant gap detection task in which silent intervals of various durations were embedded within a continuous noise. Gap detection thresholds were measured before and after treatment with a dose of sodium salicylate (200 mg/kg) that reliably induces tinnitus in rats. Noise-burst detection thresholds were also measured to document the amount of hearing loss and aid in interpreting the gap detection results. As in the previous human psychophysical experiments, salicylate had little or no effect on gap thresholds measured in broadband noise presented at high-stimulus levels (30-60 dB SPL); gap detection thresholds were always 10 ms or less. Salicylate also did not affect gap thresholds presented in narrowband noise at 60 dB SPL. Therefore, rats treated with a dose of salicylate that reliably induces tinnitus have no difficulty detecting silent gaps as long as the noise in which they are embedded is clearly audible.

  13. Salicylate-Induced Hearing Loss and Gap Detection Deficits in Rats

    Science.gov (United States)

    Radziwon, Kelly E.; Stolzberg, Daniel J.; Urban, Maxwell E.; Bowler, Rachael A.; Salvi, Richard J.

    2015-01-01

    To test the “tinnitus gap-filling” hypothesis in an animal psychoacoustic paradigm, rats were tested using a go/no-go operant gap detection task in which silent intervals of various durations were embedded within a continuous noise. Gap detection thresholds were measured before and after treatment with a dose of sodium salicylate (200 mg/kg) that reliably induces tinnitus in rats. Noise-burst detection thresholds were also measured to document the amount of hearing loss and aid in interpreting the gap detection results. As in the previous human psychophysical experiments, salicylate had little or no effect on gap thresholds measured in broadband noise presented at high-stimulus levels (30–60 dB SPL); gap detection thresholds were always 10 ms or less. Salicylate also did not affect gap thresholds presented in narrowband noise at 60 dB SPL. Therefore, rats treated with a dose of salicylate that reliably induces tinnitus have no difficulty detecting silent gaps as long as the noise in which they are embedded is clearly audible. PMID:25750635

  14. [Radiation-induced temporary hair loss after endovascular embolization of the cerebral arteries: six cases].

    Science.gov (United States)

    D'incan, M; Roger, H; Gabrillargues, J; Mansard, S; Parent, S; Chazal, J; Irthum, B; Souteyrand, P

    2002-05-01

    Intraoperative fluoroscopy imaging during coronaroplasty or transjugular intrahepatic portosystemic shunt may induce chronic radiodermatitis. Temporary hair loss is a peculiar form of radiodermatitis following endovascular surgery of the cerebral arteries. Six patients (2 women, 4 men, age range: 27-47 years old) were seen for a solitary plaque of alopecia. In all of the cases, the plaque had appeared two weeks after a neuroradiologically guided embolization procedure. No other skin lesions were seen. Alopecia spontaneously and completely regressed within three to four months. However, it reappeared after a subsequent embolization (one case) but not after arteriographies (five cases). Five similar cases have been reported in the literature. Transient alopecia often occurs after neurologically guided endovascular surgery of the cerebral arteries. This side-effect is well known by neurosurgeons and thus, these patients are rarely referred to a dermatologist. Two differential diagnoses must be evoqued: alopecia aerata and anticonvulsant - induced alopecia. The role played as cofactor by carbamazepine which is a photosensitivant drug, is discussed.

  15. Animal models of extinction-induced depression: loss of reward and its consequences.

    Science.gov (United States)

    Huston, Joseph P; Silva, Maria A de Souza; Komorowski, Mara; Schulz, Daniela; Topic, Bianca

    2013-11-01

    The absence or loss of rewards or reinforcers holds a major role in the development of depression in humans. In spite of the prevalence of extinction-induced depression (EID) in humans, few attempts have been made to establish animal models thereof. Here we present the concept of extinction-related depression and summarize the results of two sets of studies in our attempt to create animal models of EID, one set based on extinction after positive reinforcement in the Skinner-box, the other on extinction after negative reinforcement - escape from water. We found various behaviors emitted during the extinction trials that responded to treatment with antidepressant drugs: Accordingly, the important behavioral marker for EID during extinction of escape from the water was immobility. During extinction after positive reinforcement the important indices for extinction-induced depression are the withdrawal from the former site of reward, biting behavior and rearing up on the hind legs. Avoidance behavior and biting may model aspects of human depressive behavior, which may include withdrawal or avoidance as well as aggressive-like behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Reducing Risk of Noise-Induced Hearing Loss in Collegiate Music Ensembles Using Ambient Technology.

    Science.gov (United States)

    Powell, Jason; Chesky, Kris

    2017-09-01

    Student musicians are at risk for noise-induced hearing loss (NIHL) as they develop skills and perform during instructional activities. Studies using longitudinal dosimeter data show that pedagogical procedures and instructor behaviors are highly predictive of NIHL risk, thus implying the need for innovative approaches to increase instructor competency in managing instructional activities without interfering with artistic and academic freedom. Ambient information systems, an emerging trend in human-computer interaction that infuses psychological behavioral theories into technologies, can help construct informative risk-regulating systems. The purpose of this study was to determine the effects of introducing an ambient information system into the ensemble setting. The system used two ambient displays and a counterbalanced within-subjects treatment study design with six jazz ensemble instructors to determine if the system could induce a behavior change that alters trends in measures resulting from dosimeter data. This study assessed efficacy using time series analysis to determine changes in eight statistical measures of behavior over a 9-wk period. Analysis showed that the system was effective, as all instructors showed changes in a combination of measures. This study is in an important step in developing non-interfering technology to reduce NIHL among academic musicians.

  17. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  18. Caspase-Dependent Apoptosis Induced by Telomere Cleavage and TRF2 Loss

    Directory of Open Access Journals (Sweden)

    Asha S. Multani

    2000-07-01

    Full Text Available Chromosomal abnormalities involving telomeric associations (TAs often precede replicative senescence and abnormal chromosome configurations. We report here that telomere cleavage following exposure to proapoptotic agents is an early event in apoptosis. Exposure of human and murine cancer cells to a variety of pro-apoptotic stimuli (staurosporine, thapsigargin, anti-Fas antibody, cancer chemotherapeutic agents resulted in telomere cleavage and aggregation, finally their extrusion from the nuclei. Telomere loss was associated with arrest of cells in G2/M phase and preceded DNA fragmentation. Telomere erosion and subsequent large-scale chromatin cleavage were inhibited by overexpression of the anti -apoptotic protein, bcl-2, two peptide caspase inhibitors (BACMK and zVADfmk, indicating that both events are regulated by caspase activation. The results demonstrate that telomere cleavage is an early chromatin alteration detected in various cancer cell lines leading to drug-induced apoptosis, suggest that this event contributes to mitotic catastrophe and induction of cell death. Results also suggest that the decrease of telomeric-repeat binding factor 2 (TRF2 may be the earliest event in the ara-C-induced telomere shortening, induction of endoreduplication and chromosomal fragmentation leading to cell death.

  19. Deterioration of noise-induced hearing loss among bottling factory workers.

    Science.gov (United States)

    Ologe, F E; Olajide, T G; Nwawolo, C C; Oyejola, B A

    2008-08-01

    monitoring hearing deterioration. It is necessary to enforce existing occupational health laws in our industries in order to prevent noise-induced hearing loss, since it is eminently preventable.

  20. Water extract of Rumex crispus prevents bone loss by inhibiting osteoclastogenesis and inducing osteoblast mineralization.

    Science.gov (United States)

    Shim, Ki-Shuk; Lee, Bohyoung; Ma, Jin Yeul

    2017-10-26

    Rumex crispus root has traditionally been used in Asian medicine for the treatment of hemorrhage and dermatolosis. The aim of this study was to explore the pharmaceutical effects of water extract of Rumex crispus (WERC) on osteoblast and osteoclast differentiation. We also studied the effect of WERC on the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced trabecular bone destruction mice model. High performance liquid chromatography analysis was used to identify three compounds (emodin, chrysophanol, and physcion) of WERC. The in vivo effect of WERC was examined using an administration of WERC or vehicle on the ICR mice with bone loss induced by intraperitoneal RANKL injection on day 0 and 1. All mice were sacrificed by cervical dislocation at day 7 and the femurs of mice were isolated for soft X-ray and Micro-CT analysis. The in vitro effect of WERC on osteoblast mineralization or osteoclast differentiation was examined by alizarin red S staining or by tartrate-resistant acid phosphatase staining and assay. To determine the transcription level of osteoblast or osteoclast-specific genes, real-time quantitative polymerase chain reaction was used. Western blot analysis was performed to study the effect of WERC on mitogen-activated protein kinases (MAPK) or nuclear factor-κB (NF-κB) signaling molecules. The presence of three compounds in WERC was determined. WERC significantly suppressed RANKL-induced trabecular bone loss by preventing microstructural deterioration. In vitro, WERC increased osteoblast mineralization by enhancing the transcription of runt-related transcription factor 2 and its transcriptional coactivators, and by stimulating extracellular signal-regulated kinase phosphorylation. Furthermore, WERC significantly inhibited osteoclast differentiation by suppressing the activation of the RANKL signalings (MAPK and NF-κB) and the increasing inhibitory factors of nuclear factor of activated T cells cytoplasmic 1. This study showed that

  1. Repetitive activation of the corticospinal pathway by means of rTMS may reduce the efficiency of corticomotoneuronal synapses

    DEFF Research Database (Denmark)

    Taube, Wolfgang; Leukel, Christian; Nielsen, Jens Bo

    2015-01-01

    Low-frequency rTMS applied to the primary motor cortex (M1) may produce depression of motor-evoked potentials (MEPs). This depression is commonly assumed to reflect changes in cortical circuits. However, little is known about rTMS-induced effects on subcortical circuits. Therefore, the present st......-either at M1 and/or the CM synapse. As the early facilitation reflects activation of direct CM projections, the most likely site of action is the synapse of the CM neurons onto spinal motoneurons....

  2. Synaptotagmin 7 confers frequency invariance onto specialized depressing synapses

    Science.gov (United States)

    Turecek, Josef; Jackman, Skyler L.; Regehr, Wade G.

    2017-11-01

    At most synapses in the brain, short-term plasticity dynamically modulates synaptic strength. Rapid frequency-dependent changes in synaptic strength have key roles in sensory adaptation, gain control and many other neural computations. However, some auditory, vestibular and cerebellar synapses maintain constant strength over a wide range of firing frequencies, and as a result efficiently encode firing rates. Despite its apparent simplicity, frequency-invariant transmission is difficult to achieve because of inherent synaptic nonlinearities. Here we study frequency-invariant transmission at synapses from Purkinje cells to deep cerebellar nuclei and at vestibular synapses in mice. Prolonged activation of these synapses leads to initial depression, which is followed by steady-state responses that are frequency invariant for their physiological activity range. We find that synaptotagmin 7 (Syt7), a calcium sensor for short-term facilitation, is present at both synapses. It was unclear why a sensor for facilitation would be present at these and other depressing synapses. We find that at Purkinje cell and vestibular synapses, Syt7 supports facilitation that is normally masked by depression, which can be revealed in wild-type mice but is absent in Syt7 knockout mice. In wild-type mice, facilitation increases with firing frequency and counteracts depression to produce frequency-invariant transmission. In Syt7-knockout mice, Purkinje cell and vestibular synapses exhibit conventional use-dependent depression, weakening to a greater extent as the firing frequency is increased. Presynaptic rescue of Syt7 expression restores both facilitation and frequency-invariant transmission. Our results identify a function for Syt7 at synapses that exhibit overall depression, and demonstrate that facilitation has an unexpected and important function in producing frequency-invariant transmission.

  3. Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways

    Science.gov (United States)

    Wang, Tao; Liu, Qian; Zhou, Lin; Yuan, Jin Bo; Lin, Xixi; Zeng, Rong; Liang, Xiaonan; Zhao, Jinmin; Xu, Jiake

    2015-01-01

    Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis. PMID:26593901

  4. Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2015-11-01

    Full Text Available Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP, a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT. Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV, trabecular thickness (Tb.Th, and trabecular number (Tb.N compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk, TRACP (Acp5, and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis.

  5. Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.

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    Zhai, Z J; Li, H W; Liu, G W; Qu, X H; Tian, B; Yan, W; Lin, Z; Tang, T T; Qin, A; Dai, K R

    2014-02-01

    Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. Here, we examined changes in osteoclastogenesis and LPS-induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata. Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT-PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis. AP concentration-dependently suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast-specific markers, including tartrate-resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL-induced NF-κB signalling by inhibiting the phosphorylation of TGF-β-activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. AP suppressed RANKL-induced osteoclastogenesis through attenuating NF-κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast-related bone diseases. © 2013 The British Pharmacological Society.

  6. Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.

    Science.gov (United States)

    Okada, Yuka; Shirai, Kumi; Miyajima, Masayasu; Reinach, Peter S; Yamanaka, Osamu; Sumioka, Takayoshi; Kokado, Masahide; Tomoyose, Katsuo; Saika, Shizuya

    2016-01-01

    In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4) channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT) mice are different than those in their TRPV4-null (KO) counterpart. Stromal opacification due to fibrosis in KO (n = 128) mice was markedly reduced after 20 days relative to that in WT (n = 157) mice. Immunohistochemistry revealed that increases in polymorphonuclear leukocytes and macrophage infiltration declined in KO mice. Semi-quantitative real time RT-PCR of ocular KO fibroblast cultures identified increases in proinflammatory and monocyte chemoattractant protein-1 chemoattractant gene expression after injury. Biomarker gene expression of fibrosis, collagen1a1 and α-smooth muscle actin were attenuated along with macrophage release of interleukin-6 whereas transforming growth factor β, release was unchanged. Tail vein reciprocal bone marrow transplantation between WT and KO chimera mouse models mice showed that reduced scarring and inflammation in KO mice are due to loss of TRPV4 expression on both corneal resident immune cells, fibroblasts and infiltrating polymorphonuclear leukocytes and macrophages. Intraperitoneal TRPV4 receptor antagonist injection of HC-067047 (10 mg/kg, daily) into WT mice reproduced the KO-phenotype. Taken together, alkali-induced TRPV4 activation contributes to inducing fibrosis and inflammation since corneal transparency recovery was markedly improved in KO mice.

  7. Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease.

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    Sulei Wang

    Full Text Available Synaptic loss induced by beta-amyloid (Aβ plays a critical role in the pathophysiology of Alzheimer's disease (AD, but the mechanisms underlying this process remain unknown. In this study, we found that oridonin (Ori rescued synaptic loss induced by Aβ1-42 in vivo and in vitro and attenuated the alterations in dendritic structure and spine density observed in the hippocampus of AD mice. In addition, Ori increased the expression of PSD-95 and synaptophysin and promoted mitochondrial activity in the synaptosomes of AD mice. Ori also activated the BDNF/TrkB/CREB signaling pathway in the hippocampus of AD mice. Furthermore, in the Morris water maze test, Ori reduced latency and searching distance and increased the number of platform crosses in AD mice. These data suggest that Ori might prevent synaptic loss and improve behavioral symptoms in Aβ1-42-induced AD mice.

  8. Nonlinear Synapses for Large-Scale Models: An Efficient Representation Enables Complex Synapse Dynamics Modeling in Large-Scale Simulations

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    Eric eHu

    2015-09-01

    Full Text Available Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO synapse model capable of generating complex nonlinear dynamics while maintaining low computational complexity. This IO synapse model is an extension of a detailed mechanistic glutamatergic synapse model capable of capturing the input-output relationships of the mechanistic model using the Volterra functional power series. We demonstrate that the IO synapse model is able to successfully track the nonlinear dynamics of the synapse up to the third order with high accuracy. We also evaluate the accuracy of the IO synapse model at different input frequencies and compared its performance with that of kinetic models in compartmental neuron models. Our results demonstrate that the IO synapse model is capable of efficiently replicating complex nonlinear dynamics that were represented in the original mechanistic model and provide a method to replicate complex and diverse synaptic transmission within neuron network simulations.

  9. The ecological and evolutionary consequences of noise-induced acoustic habitat loss

    Science.gov (United States)

    Tennessen, Jennifer Beissinger

    negative physiological consequences, and that populations have adapted over short timescales to minimize the detrimental impacts of this novel pressure. Finally, I present results from a field acoustic playback experiment that show that noise from the invasive Cuban treefrog (Osteopilus septentrionalis ) differentially affects the vocal behavior of native anurans, with those with more similar calls being disproportionally more affected. Green treefrogs (Hyla cinerea) shortened their calls, called louder, and maintained call spacing (e.g. continued actively calling) during noise stimuli whereas pine woods treefrogs (H. femoralis) did not modify vocal behavior in response to any noise stimuli. Collectively, the results of these investigations (1) provide insight into the extent of noise-induced acoustic habitat loss in space and time, (2) reveal fitness-relevant individual- and population-level consequences of this form of habitat loss, and (3) show resiliency within ecological systems through the individual- and population-level responses to this novel pressure over short time-scales. These findings advance the field by illustrating how the spatiotemporal extent of anthropogenic noise impacts important ecological processes, and by demonstrating the resiliency of some species in responding rapidly to novel pressures.

  10. MHD-induced Energetic Ion Loss during H-mode Discharges in the National Spherical Torus Experiment (NSTX)

    Energy Technology Data Exchange (ETDEWEB)

    S.S. Medley; N.N. Gorelenkov; R. Andre; R.E. Bell; D.S. Darrow; E.D. Fredrickson; S.M. Kaye; B.P. LeBlanc; A.L. Roquemore; and the NSTX Team

    2004-03-15

    MHD-induced energetic ion loss in neutral-beam-heated H-mode [high-confinement mode] discharges in NSTX [National Spherical Torus Experiment] is discussed. A rich variety of energetic ion behavior resulting from magnetohydrodynamic (MHD) activity is observed in the NSTX using a horizontally scanning Neutral Particle Analyzer (NPA) whose sightline views across the three co-injected neutral beams. For example, onset of an n = 2 mode leads to relatively slow decay of the energetic ion population (E {approx} 10-100 keV) and consequently the neutron yield. The effect of reconnection events, sawteeth, and bounce fishbones differs from that observed for low-n, low-frequency, tearing-type MHD modes. In this case, prompt loss of the energetic ion population occurs on a time scale of less than or equal to 1 ms and a precipitous drop in the neutron yield occurs. This paper focuses on MHD-induced ion loss during H-mode operation in NSTX. After H-mode onset, the NPA charge-exchange spectrum usually exhibits a significant loss of energetic ions only for E > E(sub)b/2 where E(sub)b is the beam injection energy. The magnitude of the energetic ion loss was observed to decrease with increasing tangency radius, R(sub)tan, of the NPA sightline, increasing toroidal field, B(sub)T, and increasing neutral-beam injection energy, E(sub)b. TRANSP modeling suggests that MHD-induced ion loss is enhanced during H-mode operation due to an evolution of the q and beam deposition profiles that feeds both passing and trapped ions into the region of low-n MHD activity. ORBIT code analysis of particle interaction with a model magnetic perturbation supported the energy selectivity of the MHD-induced loss observed in the NPA measurements. Transport analysis with the TRANSP code using a fast-ion diffusion tool to emulate the observed MHD-induced energetic ion loss showed significant modifications of the neutral- beam heating as well as the power balance, thermal diffusivities, energy confinement times

  11. Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity.

    Science.gov (United States)

    Hu, Jiang-Yuan; Schacher, Samuel

    2014-04-02

    Short-term and long-term synaptic plasticity are cellular correlates of learning and memory of different durations. Little is known, however, how these two forms of plasticity interact at the same synaptic connection. We examined the reciprocal impact of short-term heterosynaptic or homosynaptic plasticity at sensorimotor synapses of Aplysia in cell culture when expressing persistent long-term facilitation (P-LTF) evoked by serotonin [5-hydroxytryptamine (5-HT)]. Short-term heterosynaptic plasticity induced by 5-HT (facilitation) or the neuropeptide FMRFa (depression) and short-term homosynaptic plasticity induced by tetanus [post-tetanic potentiation (PTP)] or low-frequency stimulation [homosynaptic depression (HSD)] of the sensory neuron were expressed in both control synapses and synapses expressing P-LTF in the absence or presence of protein synthesis inhibitors. All forms of short-term plasticity failed to significantly affect ongoing P-LTF in the absence of protein synthesis inhibitors. However, P-LTF reversed to control levels when either 5-HT or FMRFa was applied in the presence of rapamycin. In contrast, P-LTF was unaffected when either PTP or HSD was evoked in the presence of either rapamycin or anisomycin. These results indicate that synapses expressing persistent plasticity acquire a "new" baseline and functionally express short-term changes as naive synapses, but the new baseline becomes labile following selective activations-heterosynaptic stimuli that evoke opposite forms of plasticity-such that when presented in the presence of protein synthesis inhibitors produce a rapid reversal of the persistent plasticity. Activity-selective induction of a labile state at synapses expressing persistent plasticity may facilitate the development of therapies for reversing inappropriate memories.

  12. FVB/NJ mice demonstrate a youthful sensitivity to noise-induced hearing loss and provide a useful genetic model for the study of neural hearing loss.

    Science.gov (United States)

    Ho, Maria K; Li, Xin; Wang, Juemei; Ohmen, Jeffrey D; Friedman, Rick A

    2014-01-01

    The hybrid mouse diversity panel (HMDP), a panel of 100 strains, has been employed in genome wide association studies (GWAS) to study complex traits in mice. Hearing is a complex trait and the CBA/CaJ mouse strain is a widely used model for age-related hearing loss (ARHI) and noise induced hearing loss (NIHL). The CBA/CaJ strain's youthful sensitivity to noise and limited age-related loss led us to attempt to identify additional strains segregating a similar phenotype for our panel. FVB/NJ is part of the HMDP and has been previously described as having a similar ARHI phenotype to CBA/CaJ. For these reasons, we have studied the FVB/NJ mouse for ARHI and NIHL phenotypes in hopes of incorporating its phenotype into HMDP studies. We demonstrate that FVB/NJ exhibits ARHI at an earlier age than CBA/CaJ and young FVB/NJ mice are vulnerable to NIHL up until 10 to 12 weeks. This suggests that FVB/NJ may be used as an additional genetic model for neural forms of progressive hearing loss and for the study of youthful sensitivity to noise.

  13. Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.

    Science.gov (United States)

    Gray, Nora E; Zweig, Jonathan A; Murchison, Charles; Caruso, Maya; Matthews, Donald G; Kawamoto, Colleen; Harris, Christopher J; Quinn, Joseph F; Soumyanath, Amala

    2017-04-12

    The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer's disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Loss of neuron-astroglial interaction rapidly induces protective CNTF expression after stroke in mice

    Science.gov (United States)

    Kang, Seong Su; Keasey, Matthew P.; Cai, Jun; Hagg, Theo

    2012-01-01

    Ciliary neurotrophic factor (CNTF) is a potent neural cytokine with very low expression in the CNS, predominantly by astrocytes. CNTF increases rapidly and greatly following traumatic or ischemic injury. Understanding the underlying mechanisms would help to design pharmacological treatments to increase endogenous CNTF levels for neuroprotection. Here, we show that astroglial CNTF expression in the adult mouse striatum is increased two-fold within 1 hour and increases up to >30 fold over two weeks following a focal stroke caused by a transient middle cerebral artery occlusion (MCAO). Selective neuronal loss caused by intrastriatal injection of quinolinic acid resulted in a comparable increase. Co-cultured neurons reduced CNTF expression in astrocytes which was prevented by light trypsinization. RGD blocking peptides induced CNTF expression which was dependent on transcription. Astroglial CNTF expression was not affected by diffusible neuronal molecules or by neurotransmitters. The transient ischemia does not seem to directly increase CNTF, as intrastriatal injection of an ischemic solution or exposure of naive mice or cultured cells to severe hypoxia had minimal effects. Inflammatory mechanisms were probably also not involved, as intrastriatal injection of pro-inflammatory cytokines (IFNγ, IL6) in naive mice had no or small effects, and anti-inflammatory treatments did not diminish the increase in CNTF after MCAO. CNTF−/− mice had more extensive tissue loss and similar astrocyte activation after MCAO than their wildtype littermates. These data suggest that contact-mediated integrin signaling between neurons and astrocytes normally represses CNTF expression and that neuronal dysfunction causes a rapid protective response by the CNS. PMID:22764235

  15. Prophylactic and therapeutic functions of drug combinations against noise-induced hearing loss.

    Science.gov (United States)

    Bao, Jianxin; Hungerford, Michelle; Luxmore, Randi; Ding, Dalian; Qiu, Ziyu; Lei, Debin; Yang, Aizhen; Liang, Ruqiang; Ohlemiller, Kevin K

    2013-10-01

    Noise is the most common occupational and environmental hazard. Noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit, after age-related hearing loss (presbycusis). Although promising approaches have been identified for reducing NIHL, currently there are no effective medications to prevent NIHL. Development of an efficacious treatment has been hampered by the complex array of cellular and molecular pathways involved in NIHL. We turned this difficulty into an advantage by asking whether NIHL could be effectively prevented by targeting multiple signaling pathways with a combination of drugs already approved by U.S. Food and Drug Administration (FDA). We previously found that antiepileptic drugs blocking T-type calcium channels had both prophylactic and therapeutic effects for NIHL. NIHL can also be reduced by an up-regulation of glucocorticoid (GC) signaling pathways. Based on these findings, we tested a combination therapy for NIHL that included ethosuximide and zonisamide (anticonvulsants) and dexamethasone and methylprednisolone (synthetic GCs) in mice under exposure conditions typically associated with dramatic permanent threshold shifts (PTS). We first examined possible prophylactic effects for each drug when administered alone 2 h before noise, and calculated the median effective dose (ED50). We then tested for synergistic effects of two-drug combinations (anticonvulsant + GC), and identified combinations with the strongest synergy against NIHL, based on a previously established combination index (CI) metric. We repeated similar tests to determine their therapeutic effects when administered the same drugs 24 h after the noise exposure. Our study shows the feasibility of developing pharmacological intervention in multiple pathways, and discovering drug combinations with optimal synergistic effects in preventing permanent NIHL. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott

    2015-04-01

    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

  17. Effect of Ascorbic Acid on Noise Induced Hearing Loss in Rats

    Directory of Open Access Journals (Sweden)

    Ziba Loukzadeh

    2015-07-01

    Full Text Available Introduction: After presbycusis, noise-induced hearing loss is the second most common cause of acquired hearing loss. Numerous studies have shown that high-intensity noise exposure increases free radical species; therefore, use of antioxidants to detoxify the free radicals can prevent cellular damage in the cochlea. We studied the potential hearing protective effect of different doses of ascorbic acid administered prior to noise exposure in rats.   Materials and Methods: Twenty-four male albino Wistar rats were randomly allocated into four groups: groups A, B, and C received 1250, 250, and 50 mg/kg/day of ascorbic acid, respectively, and group D acted as the control group. After 14 days of ascorbic acid administration, the rats were exposed to noise (105 dB sound pressure level for 2 h. Distortion product otoacoustic emissions (DPOAE were recorded prior to starting the ascorbic acid as baseline and 1 h after the noise exposure.   Results: The amplitude decrease was 14.99 dB for group A, 16.11 dB for group B, 28.82 dB for group C, and 29.91 dB for the control group. Moderate and high doses of ascorbic acid significantly reduced the transient threshold shift in the rats.   Conclusion:  The results of present study support the concept of cochlea protection by antioxidant agents. This dose-dependent protective effect was shown through the use of ascorbic acid treatment prior to noise exposure.

  18. High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women

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    Gordon I. Smith

    2016-10-01

    Full Text Available High-protein (HP intake during weight loss (WL therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake could have adverse effects on metabolic function, because protein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8 g protein/kg/day and a hypocaloric diet containing 1.2 g protein/kg/day on muscle insulin action in postmenopausal women with obesity. We found that HP intake reduced the WL-induced decline in lean tissue mass by ∼45%. However, HP intake also prevented the WL-induced improvements in muscle insulin signaling and insulin-stimulated glucose uptake, as well as the WL-induced adaptations in oxidative stress and cell structural biology pathways. Our data demonstrate that the protein content of a WL diet can have profound effects on metabolic function and underscore the importance of considering dietary macronutrient composition during WL therapy for people with obesity.

  19. Astrocytic Gliotransmitter: Diffusion Dynamics and Induction of Information Processing on Tripartite Synapses

    Science.gov (United States)

    Li, Jia-Jia; Du, Meng-Meng; Wang, Rong; Lei, Jin-Zhi; Wu, Ying

    Astrocytes have important functions in the central nervous system (CNS) and are significant in our understanding of the neuronal network. Astrocytes modulate neuronal firings at both single cell level of tripartite synapses and the neuron-glial network level. Astrocytes release adenosine triphosphate (ATP) and glutamate into the neuron-glial network. These gliotransmitters diffuse over the network to form long distance signals to regulate neuron firings. In this paper, we study a neuron-glial network model that includes a diffusion of astrocytic ATP and glutamate to investigate how long distance diffusion of the gliotransmitters affects the information processing in a neuronal network. We find that gliotransmitters diffusion can compensate for the failure of information processing of interneuron network firings induced by defectively coupled synapses. Moreover, we find that calcium waves in astrocyte network and firings in interneuron network are both sensitive to the glutamate diffusion rate and feedback intensities of astrocytes on interneurons.

  20. High dietary calcium intake does not counteract disuse-induced bone loss

    Science.gov (United States)

    Baecker, N.; Boese, A.; Smith, S. M.; Heer, M.

    Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation, increases osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization and space flight are common causes of disuse osteoporosis. There are sufficient data supporting the use of calcium in combination with vitamin D in the prevention and treatment of postmenopausal osteoporosis. In our study we examined the potential of high dietary calcium intake as a nutrition therapy for disuse-induced bone loss during head-down bed rest in healthy young men. In 2 identical metabolic ward, head-down bed rest (HDBR) experiments (crossover design), we studied the effect of high dietary calcium intake (2000 mg/d) in comparison to the recommended calcium intake of 1000 mg/d on markers of bone turnover. Experiment A (EA) was a 6-day randomized, controlled HDBR study. Experiment B (EB) was a 14-day randomized, controlled HDBR study. In both experiments, the test subjects stayed under well-controlled environmental conditions in our metabolic ward. Subjects' diets in the relevant study phases (HDBR versus Ambulatory Control) of EA and EB were identical except for the calcium intake. The subjects obtained 2000 mg/d Calcium in EA and 2000 mg/d in EB. Blood was drawn at baseline, before entering the relevant intervention period, on day 5 in study EA, and on days 6, 11 and 14 in study EB. Serum calcium, bone formation markers - Procollagen-I-C-Propeptide (PICP) and bone alkaline phosphatase (bAP) were analyzed in serum. 24h-urine was collected throughout the studies for determination of the excretion of calcium (UCaV) and a bone resorption marker, C-terminal telopeptide of collagen type I (UCTX). In both studies, serum calcium levels were unchanged. PICP tended to decrease in EA (p=0.08). In EB PICP decreased significantly over time (p=0.003) in both the control and HDBR periods, and tended to further decrease in the HDBR period (p

  1. The effects of a novel botanical agent on lipopolysaccharide-induced alveolar bone loss in rats.

    Science.gov (United States)

    Lee, Bo-Ah; Lee, Hwa-Sun; Jung, Young-Suk; Kim, Se-Won; Lee, Yong-Wook; Chang, Sun-Hwa; Chung, Hyun-Ju; Kim, Ok-Su; Kim, Young-Joon

    2013-08-01

    The development of host-modulatory agents with low risk of adverse effects has been needed to treat periodontitis, a chronic inflammatory disease. A botanical mixture of extracts from two natural substances, Panax notoginseng and Rehmannia glutinosa Libosch, was developed as a novel botanical agent synthesized with anti-inflammatory effect. The aim of this study is to evaluate the effects of the botanical mixture on the release of inflammatory cytokines and its inhibitory effect on lipopolysaccharide (LPS)-induced alveolar bone loss (ABL) in a rat model. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay using human gingival fibroblast (hGF) and human periodontal ligament (hPDL) cells. Human acute monocytic leukemia cell line and hGF cells were cultured to assay tumor necrosis factor (TNF)-α and interleukin (IL)-6, respectively. Microcomputed tomography analysis and immunofluoresence analysis were performed to evaluate the efficacy of the botanical mixture to inhibit the destruction of alveolar bone and connective tissue in a rat model. The botanical mixture is cytotoxic at concentrations exceeding 2.5 mg/mL (P botanical mixture to be used in all subsequent in vitro and in vivo experiments. The botanical mixture reduced the release of TNF-α and IL-6 from human monocytic cells and hGF cells in a dose-dependent manner (P botanical mixture significantly reduced the alveolar bone loss in a rat model (P botanical mixture, matrix metalloproteinase (MMP)-9 was detected along the alveolar bone crest (ABC), but not around the gingival connective tissue, while in the group with LPS-induced ABL, pronounced expression of MMP-9 around the ABC, periodontal ligament, and gingival connective tissue was found. The botanical mixture showed a potential adjunctive effect in the treatment of periodontitis. However, the present findings are obtained in vitro and in a rat model, so further clinical study is needed

  2. Caffeine Ingestion Attenuates Fatigue-induced Loss of Muscle Torque Complexity.

    Science.gov (United States)

    Pethick, Jamie; Winter, Samantha L; Burnley, Mark

    2018-02-01

    The temporal structure, or complexity, of muscle torque output decreases with neuromuscular fatigue. The role of central fatigue in this process is unclear. We tested the hypothesis that caffeine administration would attenuate the fatigue-induced loss of torque complexity. Eleven healthy participants performed intermittent isometric contractions of the knee extensors to task failure at a target torque of 50% maximal voluntary contraction, with a 60% duty factor (6-s contraction, 4-s rest), 60 min after ingesting 6 mg·kg caffeine or a placebo. Torque and surface EMG signals were sampled continuously. Complexity and fractal scaling of torque were quantified using approximate entropy (ApEn) and the detrended fluctuation analysis (DFA) α scaling exponent. Global, central, and peripheral fatigue was quantified using maximal voluntary contractions with femoral nerve stimulation. Caffeine ingestion increased endurance by 30% ± 16% (mean ± SD; P = 0.019). Complexity decreased in both trials (decreased ApEn, increased DFA α; both P < 0.01), as global, central, and peripheral fatigue developed (all P < 0.01). Complexity decreased significantly more slowly after caffeine ingestion (ApEn, -0.04 ± 0.02 vs -0.06 ± 0.01 (P = 0.004); DFA α, 0.03 ± 0.02 vs 0.04 ± 0.03 (P = 0.024)), as did the rates of global (-18.2 ± 14.1 vs -23.0 ± 17.4 N·m·min, P = 0.004) and central (-3.5 ± 3.4 vs -5.7 ± 3.9 %·min, P = 0.02) but not peripheral (-6.1 ± 4.1 vs -7.9 ± 6.3 N·m·min, P = 0.06) fatigue. Caffeine ingestion slowed the fatigue-induced loss of torque complexity and increased the time to task failure during intermittent isometric contractions, most likely through central mechanisms.

  3. Effectiveness of Earplugs in Preventing Recreational Noise-Induced Hearing Loss: A Randomized Clinical Trial.

    Science.gov (United States)

    Ramakers, Geerte G J; Kraaijenga, Véronique J C; Cattani, Guido; van Zanten, Gijsbert A; Grolman, Wilko

    2016-06-01

    The incidence of hearing loss has risen in past years. Attendance at music festivals and concerts may contribute to this increasing problem. To assess the effectiveness of earplugs in preventing temporary hearing loss immediately following music exposure. A randomized, single-blind clinical trial was conducted on September 5, 2015, at an outdoor music festival in Amsterdam, the Netherlands. Normal-hearing adult volunteers were recruited via social media. An exclusion criterion was the participants' intention to wear earplugs. Of the 86 volunteers assessed, 51 were included in the study. All analyses were performed on an intention-to-treat basis. Participants were randomly assigned to a group using earplugs or an unprotected group during a 4½-hour festival visit. The primary study outcome was a temporary threshold shift (TTS) on the audiogram, primarily for frequencies at 3 and 4 kHz. Secondary study outcomes included distortion product otoacoustic emission (DPOAE) measurements and claims of tinnitus using a questionnaire and tinnitus matching experiments. Of 51 participants included, 25 were randomized to the earplug group and 26 to the unprotected group. Nine in each group (36% and 35%, respectively) were men, and the mean (SD) ages were 27.3 (5.6) years in the earplug group and 27.0 (6.2) years in the unprotected group. Baseline demographics were similar in both groups. The time-averaged, equivalent A-weighted sound pressure level experienced was 100 dBA during the festival. A TTS over frequencies at 3 and 4 kHz after exposure was seen in 4 of 50 ears (8%) in the earplug group compared with 22 of 52 ears (42%) in the unprotected group (P preventing 1 TTS was 2.9. The DPOAE amplitudes decreased significantly more over the frequencies 2 to 8 kHz in the unprotected group: the mean (SD) decrease in magnitude was 0.6 (2.8) dB in the earplug group vs 2.2 (1.9) dB in the unprotected group (P = .04). Newly induced tinnitus following sound exposure occurred in 3 of

  4. Occupationally-acquired noise-induced hearing loss: a senseless workplace hazard.

    Science.gov (United States)

    Kurmis, Andrew P; Apps, Stacey A

    2007-01-01

    Occupational noise-induced hearing loss (ONIHL) describes an acquired hearing deficiency directly attributable to excessive workplace noise exposure. Data suggest that excessive noise attributes to approximately 37% of all adult causes of hearing loss and remains a significant contributor to employment-related morbidity internationally. Typically insidiously-acquired, often without frank progressive symptomatology, regional medical agencies continue to struggle with this potentially debilitating condition. The aim of the study was to provide a synopsis of the current understanding of ONIHL, its impact on individual workers and the wider international community, and to identify barriers to more uniform adoption of personal hearing protection. A review of the contemporary literature was performed using defined keyword searches and OVID, PubMed, and Google Scholar as primary electronic search engines. A number of published works were identified, describing aspects of the relationship between workplace-related noise exposure and subsequent development of employee hearing impairment, which demonstrate an overwhelming gender imbalance, with up to 97% of affected individuals being male. Industry-specific associations (e.g., mining, manufacturing and heavy construction) were well documented, as were links to toxin-specific exposures, in the recognized development of hearing loss. However, evidence of integration of appraisal of the topically-current area of genetic susceptibility was often lacking. Much discordance still exists among international agencies in the prescriptive regulation and enforcement of "safe" exposure limits. Despite a high level of public awareness regarding the importance of hearing preservation and increasingly stringent international occupational health, safety and welfare requirements mandating provision of safer work environments, ONIHL continues to be a significant occupational hazard. ONIHL is permanent and may cause significant disability, for

  5. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  6. A shared synapse architecture for efficient FPGA implementation of autoencoders.

    Science.gov (United States)

    Suzuki, Akihiro; Morie, Takashi; Tamukoh, Hakaru

    2018-01-01

    This paper proposes a shared synapse architecture for autoencoders (AEs), and implements an AE with the proposed architecture as a digital circuit on a field-programmable gate array (FPGA). In the proposed architecture, the values of the synapse weights are shared between the synapses of an input and a hidden layer, and between the synapses of a hidden and an output layer. This architecture utilizes less of the limited resources of an FPGA than an architecture which does not share the synapse weights, and reduces the amount of synapse modules used by half. For the proposed circuit to be implemented into various types of AEs, it utilizes three kinds of parameters; one to change the number of layers' units, one to change the bit width of an internal value, and a learning rate. By altering a network configuration using these parameters, the proposed architecture can be used to construct a stacked AE. The proposed circuits are logically synthesized, and the number of their resources is determined. Our experimental results show that single and stacked AE circuits utilizing the proposed shared synapse architecture operate as regular AEs and as regular stacked AEs. The scalability of the proposed circuit and the relationship between the bit widths and the learning results are also determined. The clock cycles of the proposed circuits are formulated, and this formula is used to estimate the theoretical performance of the circuit when the circuit is used to construct arbitrary networks.

  7. Diet-induced weight loss and exercise alone and in combination enhance the expression of adiponectin receptors in adipose tissue and skeletal muscle, but only diet-induced weight loss enhanced circulating adiponectin

    DEFF Research Database (Denmark)

    Christiansen, Tore; Paulsen, Søren K; Bruun, Jens M

    2009-01-01

    by the intervention. Conclusion: Exercise alone and in combination with a diet-induced weight loss enhance the mRNA expression of adiponectin receptors in AT and in SM but only a pronounced hypocaloric-induced weight-loss increases circulating adiponectin in obese subjects.......Objective: The aim of the study was to investigate the effect of weight loss and exercise independently and in combination on circulating levels of adiponectin including low molecular weight, medium molecular weight, and high molecular weight adiponectin and expression of adiponectin...... and adiponectin receptors (AdipoR) in adipose tissue (AT) and skeletal muscle (SM). Design and Methods: Seventy-nine obese males and females were randomized into the following: 1) exercise only (12 wk of exercise without diet restriction); 2) hypocaloric diet [8 wk of very low energy diet (600 kcal/d) followed...

  8. Intragenomic conflict in populations infected by Parthenogenesis Inducing Wolbachia ends with irreversible loss of sexual reproduction.

    Science.gov (United States)

    Stouthamer, Richard; Russell, James E; Vavre, Fabrice; Nunney, Leonard

    2010-07-28

    The maternally inherited, bacterial symbiont, parthenogenesis inducing (PI) Wolbachia, causes females in some haplodiploid insects to produce daughters from both fertilized and unfertilized eggs. The symbionts, with their maternal inheritance, benefit from inducing the production of exclusively daughters, however the optimal sex ratio for the nuclear genome is more male-biased. Here we examine through models how an infection with PI-Wolbachia in a previously uninfected population leads to a genomic conflict between PI-Wolbachia and the nuclear genome. In most natural populations infected with PI-Wolbachia the infection has gone to fixation and sexual reproduction is impossible, specifically because the females have lost their ability to fertilize eggs, even when mated with functional males. The PI Wolbachia infection by itself does not interfere with the fertilization process in infected eggs, fertilized infected eggs develop into biparental infected females. Because of the increasingly female-biased sex ratio in the population during a spreading PI-Wolbachia infection, sex allocation alleles in the host that cause the production of more sons are rapidly selected. In haplodiploid species a reduced fertilization rate leads to the production of more sons. Selection for the reduced fertilization rate leads to a spread of these alleles through both the infected and uninfected population, eventually resulting in the population becoming fixed for both the PI-Wolbachia infection and the reduced fertilization rate. Fertilization rate alleles that completely interfere with fertilization ("virginity alleles") will be selected over alleles that still allow for some fertilization. This drives the final resolution of the conflict: the irreversible loss of sexual reproduction and the complete dependence of the host on its symbiont. This study shows that dependence among organisms can evolve rapidly due to the resolution of the conflicts between cytoplasmic and nuclear genes, and

  9. Intragenomic conflict in populations infected by Parthenogenesis Inducing Wolbachia ends with irreversible loss of sexual reproduction

    Science.gov (United States)

    2010-01-01

    Background The maternally inherited, bacterial symbiont, parthenogenesis inducing (PI) Wolbachia, causes females in some haplodiploid insects to produce daughters from both fertilized and unfertilized eggs. The symbionts, with their maternal inheritance, benefit from inducing the production of exclusively daughters, however the optimal sex ratio for the nuclear genome is more male-biased. Here we examine through models how an infection with PI-Wolbachia in a previously uninfected population leads to a genomic conflict between PI-Wolbachia and the nuclear genome. In most natural populations infected with PI-Wolbachia the infection has gone to fixation and sexual reproduction is impossible, specifically because the females have lost their ability to fertilize eggs, even when mated with functional males. Results The PI Wolbachia infection by itself does not interfere with the fertilization process in infected eggs, fertilized infected eggs develop into biparental infected females. Because of the increasingly female-biased sex ratio in the population during a spreading PI-Wolbachia infection, sex allocation alleles in the host that cause the production of more sons are rapidly selected. In haplodiploid species a reduced fertilization rate leads to the production of more sons. Selection for the reduced fertilization rate leads to a spread of these alleles through both the infected and uninfected population, eventually resulting in the population becoming fixed for both the PI-Wolbachia infection and the reduced fertilization rate. Fertilization rate alleles that completely interfere with fertilization ("virginity alleles") will be selected over alleles that still allow for some fertilization. This drives the final resolution of the conflict: the irreversible loss of sexual reproduction and the complete dependence of the host on its symbiont. Conclusions This study shows that dependence among organisms can evolve rapidly due to the resolution of the conflicts between

  10. Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors.

    Science.gov (United States)

    Mota, Sandra I; Ferreira, Ildete L; Rego, A Cristina

    2014-01-01

    Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. Alterations capable of causing brain circuitry dysfunctions in AD may take several years to develop. Oligomeric amyloid-beta peptide (Aβ) plays a complex role in the molecular events that lead to progressive loss of function and eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D-aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD-related synaptic dysfunction. Thus, in this review we focus on glutamatergic neurotransmission impairment and the changes in NMDAR regulation in AD, following the description on the role and location of NMDARs at pre- and post-synaptic sites under physiological conditions. In addition, considering that there is currently no effective ways to cure AD or stop its progression, we further discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This review posits additional information on the role played by Aβ in AD and the importance of targeting the tripartite glutamatergic synapse in early asymptomatic and possible reversible stages of the disease through preventive and/or disease-modifying therapeutic strategies. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Velocity space resolved absolute measurement of fast ion losses induced by a tearing mode in the ASDEX Upgrade tokamak

    Science.gov (United States)

    Galdon-Quiroga, J.; Garcia-Munoz, M.; Sanchis-Sanchez, L.; Mantsinen, M.; Fietz, S.; Igochine, V.; Maraschek, M.; Rodriguez-Ramos, M.; Sieglin, B.; Snicker, A.; Tardini, G.; Vezinet, D.; Weiland, M.; Eriksson, L. G.; The ASDEX Upgrade Team; The EUROfusion MST1 Team

    2018-03-01

    Absolute flux of fast ion losses induced by tearing modes have been measured by means of fast ion loss detectors (FILD) for the first time in RF heated plasmas in the ASDEX Upgrade tokamak. Up to 30 MW m‑2 of fast ion losses are measured by FILD at 5 cm from the separatrix, consistent with infra-red camera measurements, with energies in the range of 250–500 keV and pitch angles corresponding to large trapped orbits. A resonant interaction between the fast ions in the high energy tail of the ICRF distribution and a m/n  =  5/4 tearing mode leads to enhanced fast ion losses. Around 9.3 +/- 0.7 % of the fast ion losses are found to be coherent with the mode and scale linearly with its amplitude, indicating the convective nature of the transport mechanism. Simulations have been carried out to estimate the contribution of the prompt losses. A good agreement is found between the simulated and the measured velocity space of the losses. The velocity space resonances that may be responsible for the enhanced fast ion losses are identified.

  12. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Jensen, Majbrit M; Overgaard, Agnete

    2013-01-01

    is not clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity. This is interesting, as obese patients have reduced central......, tesofensine produces weight loss together with reversal of lowered forebrain dopamine levels in DIO rats, suggesting that tesofensine's anti-obesity effects, at least in part, are associated with positive modulation of central dopaminergic activity....

  13. Preventive treatment of intrauterine device-induced menstrual blood loss with tranexamic acid in Chinese women.

    Science.gov (United States)

    Lin, X; Gao, E S; Li, D; Zhang, M; Dou, L X; Yuan, W

    2007-01-01

    To investigate whether tranexamic acid (Transamin) therapy reduces the amount of menstrual blood loss (MBL) and occurrence of menorrhagia after intrauterine device (IUD) insertion. Some 175 Chinese women attending for IUD insertion were equally assigned into 2 Transamin groups (1,000 and 500 mg, twice daily) and a placebo group. Their MBL was recorded with a pictorial chart in 3 subsequent menstrual cycles after insertion, while the MBL of 64 patients, collecting used sanitary towels, was also measured by an alkaline hematin method. A significant decline in post-insertion MBL and occurrence of menorrhagia was found in the 2 Transamin groups compared with the placebo group (p<0.05), whereas the difference in the results from the pictorial chart score was not statistically significant between the 1 g group and placebo group. Transamin treatment with a generally recommended dosage can effectively reduce the amount of IUD-induced MBL and prevent menorrhagia in Chinese women. A lower dosage than recommended (50% of recommended dosage) may have a similar preventive effect.

  14. New, Coupling Loss Induced, Quench Protection System for Superconducting Accelerator Magnets

    CERN Document Server

    Ravaioli, E; Giloux, C; Kirby, G; ten Kate, H H J; Verweij, A P

    2014-01-01

    Email Print Request Permissions Save to Project A new and promising method for the protection of superconducting high-field magnets is developed and tested on the so-called MQXC quadrupole magnet at the CERN magnet test facility. The method relies on a capacitive discharge system inducing, during a few periods, an oscillation of the transport current in the superconducting cable of the coil. The corresponding fast change of the local magnetic field introduces a high coupling-current loss, which, in turn, causes a fast quench of a large fraction of the coil due to enhanced temperature. Results of measured discharges at various levels of transport current are presented and compared to discharges by quenching the coils using conventional quench heaters and an energy extraction system. The hot-spot temperature in the quenching coil is deduced from the coil voltage and current. The results are compared to simulations carried out using a lumped-element dynamic electro-thermal model of the so-called MQX...

  15. Can Rh antigens be a risk factor in noise-induced hearing loss?

    Science.gov (United States)

    Ayçiçek, Abdullah; Sargin, Ramazan; Kenar, Fethullah; Dereköy, F Sefa

    2009-03-01

    Noise-induced hearing loss (NIHL) is one of the most common occupational problems and is one of the main causes of deafness. Many factors cause NIHL. Individual susceptibility is one of them. Rhesus (Rh) antigens and ABO blood groups can be factors in determining individual susceptibility. We aim to investigate the relationship between the Rh antigens and NIHL. The study was conducted in 438 factory workers who had been exposed to a noise level more than 85 dB for 8 h a day for a period of >/=15 years. The audiologic results and blood groups were obtained from the individual health records of the factory workers. We determined NIHL in 236 (53.9%) workers. Two hundred and nineteen (55.4%) of Rh-positive workers and seventeen (39.5%) of Rh-negative workers have NIHL, and the difference between the two groups was statistically significant (P Rh-positive blood group are more prone to develop NIHL.

  16. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

    Science.gov (United States)

    Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

    2015-01-01

    It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

  17. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

    Directory of Open Access Journals (Sweden)

    Carl-Johan Boraxbekk

    2015-07-01

    Full Text Available Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010 after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA. Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  18. Cadmium-induced bone loss: Increased susceptibility in female beagles after ovariectomy

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Sacco-Gibson, N.A.; Peterson, D.P.

    1991-01-01

    Bone resorption, as measured by release of bone {sup 45}Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/L Cd in drinking water. The {sup 45}Ca response was greater in ovariecotomized (OV) animals than in sham-operated (SO) controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood Cd concentrations were 3--8 {mu}g/L during the earliest bone resorption response and 13--15 {mu}g/L at the end of the study. During 7 mo of Cd exposure, bone mineral densities decreased most in the OV animals exposed to Cd: {minus}15.4 {plus minus} 4.3% for the tibia distal end and {minus}7.2 {plus minus} 1.2% for the lumbar vertebrae (L2-L4) (mean {plus minus} SE, n=4). Results indicate that Cd may act directly on bone and that postmenopausal women exposed to Cd in industry or via cigarette smoke may be at increased risk of Cd-induced bone loss. 21 refs., 4 figs.

  19. Loss of TFF1 promotes Helicobacter pylori-induced β-catenin activation and gastric tumorigenesis.

    Science.gov (United States)

    Soutto, Mohammed; Romero-Gallo, Judith; Krishna, Uma; Piazuelo, M Blanca; Washington, M Kay; Belkhiri, Abbes; Peek, Richard M; El-Rifai, Wael

    2015-07-20

    Using in vitro and in vivo models, we investigated the role of TFF1 in suppressing H. pylori-mediated activation of oncogenic β-catenin in gastric tumorigenesis. A reconstitution of TFF1 expression in gastric cancer cells decreased H. pylori-induced β-catenin nuclear translocation, as compared to control (p PMSS1 H. pylori strain, we detected an increase in the nuclear staining for β-catenin and Ki-67 with a significant induction in the levels of Ccnd1 and c-Myc in the stomach of the Tff1-KO, as compared to Tff1-WT mice (p < 0.05). Only 10% of uninfected Tff1-KO mice, as opposed to one-third of H. pylori-infected Tff1-KO mice, developed invasive adenocarcinoma (p = 0.03). These findings suggest that loss of TFF1 could be a critical step in promoting the H. pylori-mediated oncogenic activation of β-catenin and gastric tumorigenesis.

  20. Patients with vestibular loss, tullio phenomenon, and pressure-induced nystagmus: vestibular atelectasis?

    Science.gov (United States)

    Wenzel, Angela; Ward, Bryan K; Schubert, Michael C; Kheradmand, Amir; Zee, David S; Mantokoudis, Georgios; Carey, John Patrick

    2014-06-01

    To propose an etiology for a syndrome of bilateral vestibular hypofunction and sound and/or pressure-evoked eye movements with normal hearing thresholds. Retrospective case series. Tertiary care referral center. Four patients with bilateral vestibular hypofunction, sound and/or pressure-evoked nystagmus and normal hearing thresholds were identified over a 3-year period. No evidence of other known vestibular disorders was identified. None of these patients presented with a history of exposure to toxins, radiation, aminoglycosides or chemotherapy; head trauma; or a family history of inherited vestibular loss. All patients underwent high-resolution CT scan of the temporal bones to evaluate for labyrinthine dehiscence. Additionally, all individuals underwent audiometric testing to ANSI standards, vestibular-evoked myogenic potentials (VEMP) testing using either click stimulus cervical VEMPs (cVEMPs), or tone burst ocular VEMPs (oVEMPs). Bithermal caloric stimulation was used to measure horizontal semicircular canal function, with either videonystagmography (VNG) or electronystagmography (ENG) to record eye movements. Individual responses of each of the 6 semicircular canals (SCC) to rapid head rotations were tested with the bedside head impulse test. We identified 4 patients with a combination of bilateral vestibular hypofunction and sound and/or pressure-induced eye movements, normal-hearing thresholds and no evidence for any other vestibular disorder. We suggest that this unique combination of symptoms should be considered as the clinical presentation of vestibular atelectasis, which has been previously described histologically as collapse of the endolymph-containing portions of the labyrinth.

  1. Chia induces clinically discrete weight loss and improves lipid profile only in altered previous values.

    Science.gov (United States)

    Tavares Toscano, Luciana; Tavares Toscano, Lydiane; Leite Tavares, Renata; da Oliveira Silva, Cássia Surama; Silva, Alexandre Sérgio

    2014-12-14

    chia (Salvia hispanica L.) has an elevated concentration of dietary fiber, it has been used to weight loss and enhance blood glucose and lipid profile. However, data in human are still scarce or do not exist, according to the analyzed variable. to evaluate the effect of chia supplementation in body composition, lipid profile and blood glucose in overweight or obese individuals. men and women were randomly allocated in groups that ingested 35 g of chia flour/day (CHIA; n=19; 48.8±1.8 years) or placebo (PLA; n=7; 51.4±3.1 years) for 12 weeks. Body composition and food intake were evaluated in each four weeks. Lipid profile and blood glucose were measured in the beginning and in the end of the study. Chia induced significant intragroup reduction in body weight (-1.1±0.4 kg; pCHIA group (p chia flour and presented abnormal initial values. Triglycerides, blood glucose and LDL-C showed no changes for either group. consumption of chia for 12 weeks promotes significant but discrete reduction in weight and waist circumference, and enhances lipid profile dependent of initial values. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. Inactivity-induced bone loss is not exacerbated by moderate energy restriction

    Science.gov (United States)

    Heer, M.; Boese, A.; Baecker, N.; Zittermann, A.; Smith, S. M.

    Severe energy restriction leads to decreased bone mineral density (BMD) in postmenopausal women, adolescent females, and in male athletes. Astronauts in space also lose bone mass, and most of them have reduced energy intake (about 25 % below requirements). The aim of our study was to examine if bone loss in space is partly induced by moderate energy restriction. Physiological changes of space flight were simulated by 6 head-down tilt bed rest (HDBR). Nine healthy male subjects (age: 23.6 ± 3.0 years; BMI: 23.0 ± 2.9 kg/m2, mean ± SD) finished four study phases, two of normocaloric nutrition, either ambulatory or HDBR, and two of hypocaloric nutrition, either ambulatory or HDBR. Urine samples (24 h) were analyzed for calcium excretion (UCaV) and bone resorption markers (C-Telopeptide, CTX, and N-Telopeptide, NTX). Serum calcium, parathyroid hormone (PTH) and bone formation markers (Procollagen-I-C-terminal-Peptide, PICP, Procollagen-I-N-terminal-Peptide, PINP, and bone-specific alkaline phosphatase, bAP) were analyzed. No significant changes in serum calcium or PTH were noted either during HDBR or during hypocaloric nutrition. PICP, but not PINP or bAP, decreased significantly during HDBR (normocaloric: pnutrition or both (pnutrition in ambulatory and HDBR phases. In conclusion, moderate energy restriction did not exaggerate bone resorption during HDBR.

  3. Sauna-Induced Body Mass Loss in Young Sedentary Women and Men

    Directory of Open Access Journals (Sweden)

    Robert Podstawski

    2014-01-01

    Full Text Available The aim of the study was to evaluate the relationship between body mass index (BMI and body mass loss (BML induced by thermal stress in a dry sauna. The study was conducted on a group of 674 sedentary students, 326 women and 348 men aged 19-20. The correlations between BMI scores and BML were determined. The subjects were placed in supine position in a dry sauna for two sessions of 10 minutes each with a 5-minute break. The influence of BMI on the amount of BML in the sauna was determined by nonlinear stepwise regression. The smallest BML was noted in underweight subjects; students with normal weight lost more weight, whereas the greatest BML was reported in overweight and obese subjects. Persons with a high BMI are at higher risk of dehydration, and they should pay particular attention to replenishing fluids during a visit to the sauna. The proposed equations for calculating BML based on a person's BMI can be useful in estimating the amount of fluids that should be replenished by both men and women during a visit to a dry sauna.

  4. Noise-induced hearing loss and associated factors among vector control workers in a Malaysian state.

    Science.gov (United States)

    Masilamani, Retneswari; Rasib, Abdul; Darus, Azlan; Ting, Anselm Su

    2014-11-01

    This study aims to determine the prevalence and associated factors of noise-induced hearing loss (NIHL) among vector control workers in the state of Negeri Sembilan, Malaysia. This was an analytical cross-sectional study conducted on 181 vector control workers who were working in district health offices in a state in Malaysia. Data were collected using a self-administered questionnaire and audiometry. Prevalence of NIHL was 26% among this group of workers. NIHL was significantly associated with the age-group of 40 years and older, length of service of 10 or more years, current occupational noise exposure, listening to loud music, history of firearms use, and history of mumps/measles infection. Following logistic regression, age of more than 40 years and noise exposure in current occupation were associated with NIHL with an odds ratio of 3.45 (95% confidence interval = 1.68-7.07) and 6.87 (95% confidence interval = 1.54-30.69), respectively, among this group of vector control workers. © 2012 APJPH.

  5. Noise-induced hearing loss in a longitudinal study of Norwegian railway workers.

    Science.gov (United States)

    Lie, Arve; Skogstad, Marit; Johnsen, Torstein Seip; Engdahl, Bo; Tambs, Kristian

    2016-09-02

    The aim of this study was to analyse longitudinal data to assess the risk of noise-induced hearing loss (NIHL) in Norwegian railway workers. Longitudinal. A major Norwegian railway company. We examined data from the first and last audiograms for the period 1991-2014, from 9640 railway workers with varying occupational noise exposure and with an average observation period of 10 years. The course of hearing acuity in seven groups of railway workers (train drivers, conductors, bus drivers, traffic controllers, train maintenance workers, track maintenance workers and others) were compared with each other and with ISO standards (ISO 1999). The change in hearing threshold during the observation period was 2-3 dB in the 0.5-4 kHz range and 6-7 dB in the 3-6 kHz range adjusted for age and sex, for all occupational groups, which is slightly less than expected (8 dB) according to ISO 1999. The risk of NIHL in Norwegian railway workers during the period 1991-2014 has been negligible. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Chromosome 11 loss from thymic lymphomas induced in heterozygous Trp53 mice by phenolphthalein.

    Science.gov (United States)

    Hulla, J E; French, J E; Dunnick, J K

    2001-04-01

    C57BL/6 p53 (+/-) N5 mice heterozygous for a null p53 allele were given phenolphthalein to learn more about mechanisms of carcinogenesis and to evaluate the p53-deficient mouse as a tool for identifying potential human carcinogens. DNA samples isolated from 10 phenolphthalein-induced thymic lymphomas were analyzed for loss of heterozygosity (LOH) at the Trp53 locus and simple sequence length polymorphic (SSLP) loci. The initial screening revealed remarkable results from only chromosome 11. Allelotyping at approximately five centiMorgan intervals, we found SSLP heterozygosity for C57BL/6 and 129Sv over much of chromosome 11. In the tumors, treatment-related LOH was apparent on chromosome 11 at each of the 28 informative loci examined. The strain-specific polymorphism lost from individual tumors allowed us to deduce the distribution of alleles along the length of the maternal and paternal chromosomes 11. The allelic patterns indicate that mitotic homologous recombination occurred during embryogenesis if breeding protocols were carried out as described. The mitotic recombination observed may be attributable to p53 haploinsufficiency for normal suppression of mitotic recombination.

  7. Administration of DNA Plasmid Coding Protein Aggregating Domain Induces Inflammatory Bone Loss.

    Science.gov (United States)

    Agas, Dimitrios; Concetti, Fabio; Capitani, Melania; Lacava, Giovanna; Concetti, Antonio; Marchetti, Luigi; Laus, Fulvio; Marchegiani, Andrea; Azevedo, Vasco; Sabbieti, Maria Giovanna; Venanzi, Franco Maria

    2016-01-01

    Plasmids coding protein aggregation polypeptides from different sources have been proposed as genetic adjuvants for DNA vaccines. We reported that a plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates and subsequent cell death. In the present study we addressed the question of whether there is any substantial immunotoxicity associated with the use of self-aggregating proteins as genetic adjuvants. Here we report, by mean of histology, X-ray and molecular examinations of bone specimens, the unexpected finding that intramuscular injection of pATRex in mice triggers, per se, severe bone loss (osteoporosis) independently from the sex and genotype of the treated animals. Even though the study suggests that proteinaceous "sticky " adjuvants are unlikely to find their way into practical vaccination, the information gained is of value as ATRex injections could provide an additional, simplified, mouse model of osteoporosis. Moreover, our results provide experimental support to the hypothesis that proteotoxic aggregates chronically activate the innate immune system in amyloid and aggregosome associated disorders.

  8. Prognostic markers for diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Astrup, A; Buemann, B; Gluud, C

    1995-01-01

    To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women.......To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women....

  9. Evaluation of the current practices of noise-induced hearing loss (NIHL) awareness training in the South African mining industry

    CSIR Research Space (South Africa)

    Edwards, AL

    2015-01-01

    Full Text Available This study aimed to evaluate the current practices in relation to best practice criteria and make recommendations for improvements to noise-induced hearing loss (NIHL) awareness training in the South African mining industry. A survey tool based...

  10. RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT BY EXOGENOUS PROGESTERONE AND HCG

    Science.gov (United States)

    Rescue of bromodichloromethane-induced pregnancy loss in the F344 rat by exogenous progesterone and hCG.Susan R. Bielmeier1, Deborah S. Best2 and Michael G. Narotsky21 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA2 Reproductive Toxico...

  11. The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat

    DEFF Research Database (Denmark)

    Martins, Cecilia; Kulseng, B; King, N A

    2010-01-01

    The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic ...

  12. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

    Science.gov (United States)

    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  13. Fasting and meal-suppressed ghrelin levels before and after intragastric balloons and balloon-induced weight loss

    NARCIS (Netherlands)

    Mathus-Vliegen, E. M. H.; Eichenberger, R. I.

    2014-01-01

    Intragastric balloons may be an option for obese patients with weight loss failure. Its mode of action remains enigmatic. We hypothesised depressed fasting ghrelin concentrations and enhanced meal suppression of ghrelin secretion by the gastric fundus through balloon contact and balloon-induced

  14. Noise induced hearing loss in dance music disc jockeys and an examination of sound levels in nightclubs.

    Science.gov (United States)

    Bray, Adam; Szymański, Marcin; Mills, Robert

    2004-02-01

    Noise exposure, hearing loss and associated otological symptoms have been studied in a group of 23 disc jockeys using a questionnaire and pure tone audiometry. The level of noise exposure in the venues where they work has also been studied using Ametek Mk-3 audio dosimeters. Three members of the study group showed clear evidence of noise-induced hearing loss on audiometry, 70 per cent reported temporary threshold shift after sessions and 74 per cent reported tinnitus. Sound levels of up to 108 dB(A) were recorded in the nightclubs. The average level for a typical session was 96 dB(A) which is above the level at which the provision of ear protection is mandatory for employers in industry. It can be concluded that DJs are at substantial risk of developing noise-induced hearing loss and noise exposure in nightclubs frequently exceeds safe levels.

  15. Raynaud's phenomenon among men and women with noise-induced hearing loss in relation to vibration exposure.

    Science.gov (United States)

    Pettersson, Hans; Burström, Lage; Nilsson, Tohr

    2014-01-01

    Raynaud's phenomenon is characterized by constriction in blood supply to the fingers causing finger blanching, of white fingers (WF) and is triggered by cold. Earlier studies found that workers using vibrating hand-held tools and who had vibration-induced white fingers (VWF) had an increased risk for hearing loss compared with workers without VWF. This study examined the occurrence of Raynaud's phenomenon among men and women with noise-induced hearing loss in relation to vibration exposure. All 342 participants had a confirmed noise-induced hearing loss medico legally accepted as work-related by AFA Insurance. Each subject answered a questionnaire concerning their health status and the kinds of exposures they had at the time when their hearing loss was first discovered. The questionnaire covered types of exposures, discomforts in the hands or fingers, diseases and medications affecting the blood circulation, the use of alcohol and tobacco and for women, the use of hormones and whether they had been pregnant. The participation rate was 41% (n = 133) with 38% (n = 94) for men and 50% (n = 39) for women. 84 men and 36 women specified if they had Raynaud's phenomenon and also if they had used hand-held vibrating machines. Nearly 41% of them had used hand-held vibrating machines and 18% had used vibrating machines at least 2 h each workday. There were 23 men/6 women with Raynaud's phenomenon. 37% reported WF among those participants who were exposed to hand-arm vibration (HAV) and 15% among those not exposed to HAV. Among the participants with hearing loss with daily use of vibrating hand-held tools more than twice as many reports WF compared with participants that did not use vibrating hand-held tools. This could be interpreted as Raynaud's phenomenon could be associated with an increased risk for noise-induced hearing loss. However, the low participation rate limits the generalization of the results from this study.

  16. Cocaine potentiates ketamine-induced loss of the righting reflex and sleeping time in mice. Role of catecholamines.

    Science.gov (United States)

    Vanderwende, C; Spoerlein, M T; Lapollo, J

    1982-07-01

    Cocaine in graded doses potentiated ketamine-induced loss of the righting reflex and sleeping time. Potentiation of drug-induced sleep with cocaine was not a generalized phenomenon inasmuch as it had no effect on sleep induced by pentobarbital or hexobarbital and decreased sleep induced by phenobarbital. Pentylenetetrazole reduced ketamine sleep but d-amphetamine had a potentiative action. dl-alpha-Methyl-p-tyrosine methyl ester itself increased both the number losing the righting reflex and the sleeping time induced by ketamine. However, the effect cocaine on sleeping time was blocked 3 h after the dl-alpha-methyl-p-tyrosine methyl ester was given. The alpha and beta adrenergic blocking drugs, phenoxybenzamine and propranolol, increased the number of animals losing the righting reflex with ketamine, and phenoxybenzamine lengthened the sleeping time. Alpha and beta adrenergic agonists, l-phenylephrine and isoproterenol, increased the number of animals going to sleep with ketamine but did not significantly alter how long they would sleep. The agonists had no effect on the cocaine interaction with ketamine, whereas the antagonists blocked the effect of cocaine. Both stimulation and blockade of dopamine receptors led to increased loss of the righting reflex and sleeping time with ketamine but only receptor blockade antagonized the effect of cocaine on ketamine-induced sleep. Thus, both the noradrenergic and dopaminergic systems appear to be involved in the ability of cocaine to potentiate ketamine-induced sleep.

  17. Herpes Virus Entry Mediator Signaling in the Brain Is Imperative in Acute Inflammation-Induced Anorexia and Body Weight Loss

    Directory of Open Access Journals (Sweden)

    Kwang Kon Kim

    2013-09-01

    Full Text Available BackgroundReduced appetite and body weight loss are typical symptoms of inflammatory diseases. A number of inflammatory stimuli are responsible for the imbalance in energy homeostasis, leading to metabolic disorders. The herpes virus entry mediator (HVEM protein plays an important role in the development of various inflammatory diseases, such as intestinal inflammation and diet-induced obesity. However, the role of HVEM in the brain is largely unknown. This study aims to investigate whether HVEM signaling in the brain is involved in inflammation-induced anorexia and body weight loss.MethodsFood intake and body weight were measured at 24 hours after intraperitoneal injection of lipopolysaccharide (LPS or intracerebroventricular injection of recombinant mouse LIGHT (also called tumor necrosis factor receptor superfamily 14, TNFSF14, an HVEM ligand, into 8- to 10-week-old male C57BL/6 mice and mice lacking HVEM expression (HVEM-/-. We also assessed LPS-induced change in hypothalamic expression of HVEM using immunohistochemistry.ResultsAdministration of LPS significantly reduced food intake and body weight, and moreover, increased expression of HVEM in the hypothalamic arcuate nucleus. However, LPS induced only minor decreases in food intake and body weight in HVEM-/- mice. Administration of LIGHT into the brain was very effective at decreasing food intake and body weight in wild-type mice, but was less effective in HVEM-/- mice.ConclusionActivation of brain HVEM signaling is responsible for inflammation-induced anorexia and body weight loss.

  18. Using personality as a predictor of diet induced weight loss and weight management

    Directory of Open Access Journals (Sweden)

    Munro Irene A

    2011-11-01

    Full Text Available Abstract Background A major challenge for successful weight management is tailoring weight loss programs to individual needs. The aim of this study was to investigate whether personality traits could be used to match individuals to a compatible weight loss program that would maximize weight loss. Method Two different weight loss trials were conducted, both with a weight loss greater than 5% the measure of success. Fifty-four individuals, BMI 30-40 kg/m2, either followed a slow, healthy eating weight loss diet (HEWLD of 5000-6000 kJ/day for 12 weeks (n = 22, or a fast, very low energy diet (VLED of 3000 kJ/day for 4 weeks (n = 32. Anthropometric measurements were recorded at baseline, at the end of the weight loss period and, for VLED, at the end of 10 weeks of weight maintenance. Personality traits were measured at baseline using the Tangney Self Control Scale plus 3 of the scales from the Five Factor Model - Neuroticism, Conscientiousness and Extraversion. Results The percentage weight loss was significantly greater in VLED (-7.38% compared to HEWLD (-4.11%, (p Conclusion The personality factor, Neuroticism, was linked to successful weight loss (that is ≥ 5% with a particular weight loss treatment, suggesting that there is a potential to use measures of personality to identify appropriate weight loss/management strategies for individuals. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12611000716965

  19. Role of neuron-glia interactions in developmental synapse elimination.

    Science.gov (United States)

    Terni, Beatrice; López-Murcia, Francisco José; Llobet, Artur

    2017-03-01

    During the embryonic development of the nervous system there is a massive formation of synapses. However, the exuberant connectivity present after birth must be pruned during postnatal growth to optimize the function of neuronal circuits. Whilst glial cells play a fundamental role in the formation of early synaptic contacts, their contribution to developmental modifications of established synapses is not well understood. The present review aims to highlight the various roles of glia in the developmental refinement of embryonic synaptic connectivity. We summarize recent evidences linking secretory abilities of glial cells to the disassembly of synaptic contacts that are complementary of a well-established phagocytic role. Considering a theoretical framework, it is discussed how release of glial molecules could be relevant to the developmental refinement of synaptic connectivity. Finally, we propose a three-stage model of synapse elimination in which neurons and glia are functionally associated to timely eliminate synapses. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

    Directory of Open Access Journals (Sweden)

    Tanaka Mika

    2013-01-01

    Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

  1. Changes in rat hippocampal CA1 synapses following imipramine treatment

    DEFF Research Database (Denmark)

    Chen, Fenghua; Madsen, Torsten M; Wegener, Gregers

    2008-01-01

    Neuronal plasticity in hippocampus is hypothesized to play an important role in both the pathophysiology of depressive disorders and the treatment. In this study, we investigated the consequences of imipramine treatment on neuroplasticity (including neurogenesis, synaptogenesis, and remodelling...... and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group. Our...

  2. Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

    Science.gov (United States)

    Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

    2009-11-01

    Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

  3. Three-terminal ferroelectric synapse device with concurrent learning function for artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Nishitani, Y.; Kaneko, Y.; Ueda, M.; Fujii, E. [Advanced Technology Research Laboratories, Panasonic Corporation, Seika, Kyoto 619-0237 (Japan); Morie, T. [Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Wakamatsu-ku, Kitakyushu 808-0196 (Japan)

    2012-06-15

    Spike-timing-dependent synaptic plasticity (STDP) is demonstrated in a synapse device based on a ferroelectric-gate field-effect transistor (FeFET). STDP is a key of the learning functions observed in human brains, where the synaptic weight changes only depending on the spike timing of the pre- and post-neurons. The FeFET is composed of the stacked oxide materials with ZnO/Pr(Zr,Ti)O{sub 3} (PZT)/SrRuO{sub 3}. In the FeFET, the channel conductance can be altered depending on the density of electrons induced by the polarization of PZT film, which can be controlled by applying the gate voltage in a non-volatile manner. Applying a pulse gate voltage enables the multi-valued modulation of the conductance, which is expected to be caused by a change in PZT polarization. This variation depends on the height and the duration of the pulse gate voltage. Utilizing these characteristics, symmetric and asymmetric STDP learning functions are successfully implemented in the FeFET-based synapse device by applying the non-linear pulse gate voltage generated from a set of two pulses in a sampling circuit, in which the two pulses correspond to the spikes from the pre- and post-neurons. The three-terminal structure of the synapse device enables the concurrent learning, in which the weight update can be performed without canceling signal transmission among neurons, while the neural networks using the previously reported two-terminal synapse devices need to stop signal transmission for learning.

  4. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Directory of Open Access Journals (Sweden)

    Nawal Zabouri

    Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  5. Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Amanda V. Sardeli

    2018-03-01

    Full Text Available It remains unclear as to what extent resistance training (RT can attenuate muscle loss during caloric restriction (CR interventions in humans. The objective here is to address if RT could attenuate muscle loss induced by CR in obese elderly individuals, through summarized effects of previous studies. Databases MEDLINE, Embase and Web of Science were used to perform a systematic search between July and August 2017. Were included in the review randomized clinical trials (RCT comparing the effects of CR with (CRRT or without RT on lean body mass (LBM, fat body mass (FBM, and total body mass (BM, measured by dual-energy X-ray absorptiometry, on obese elderly individuals. The six RCTs included in the review applied RT three times per week, for 12 to 24 weeks, and most CR interventions followed diets of 55% carbohydrate, 15% protein, and 30% fat. RT reduced 93.5% of CR-induced LBM loss (0.819 kg [0.364 to 1.273], with similar reduction in FBM and BM, compared with CR. Furthermore, to address muscle quality, the change in strength/LBM ratio tended to be different (p = 0.07 following CRRT (20.9 ± 23.1% and CR interventions (−7.5 ± 9.9%. Our conclusion is that CRRT is able to prevent almost 100% of CR-induced muscle loss, while resulting in FBM and BM reductions that do not significantly differ from CR.

  6. Strategies for the prevention of MP3-induced hearing loss among adolescents: expert opinions from a Delphi study.

    Science.gov (United States)

    Vogel, Ineke; Brug, Johannes; van der Ploeg, Catharina P B; Raat, Hein

    2009-05-01

    To identify parties involved in the prevention of MP3-induced hearing loss among adolescents and potentially effective prevention strategies and interventions. Thirty experts in fields such as scientific research, medical practice, community health professions, education, youth work, music entertainment, and enforcement authorities participated in a qualitative, electronic, 3-round, Web-based Delphi study. Multiple parties involved in the prevention of MP3-induced hearing loss among adolescents were identified; the most relevant are the adolescents themselves, their parents, manufacturers of MP3 players and earphones, and the authorities. The experts did not expect that adolescents in general would perform the necessary protective behaviors to prevent MP3-induced hearing loss. Two environmental health protection measures were identified as both relevant and feasible to be implemented (ie, authorities encourage manufacturers to produce safer products, and public health campaigns will be held to improve knowledge of the risks of high-volume music, possible protective measures, and consequences of hearing loss). Authorities, the music industry in general, and especially manufacturers of MP3 players and earphones should recognize their responsibility and create a safer MP3-listening environment by taking measures to protect today's youth from the dangers of listening to high-volume music on MP3 players.

  7. Acute failure of action potential conduction in mdx muscle reveals new mechanism of contraction-induced force loss

    Science.gov (United States)

    Call, Jarrod A; Warren, Gordon L; Verma, Mayank; Lowe, Dawn A

    2013-01-01

    A primary feature of skeletal muscle lacking the protein dystrophin, as occurring in Duchenne muscular dystrophy, is a hypersensitivity to contraction-induced strength loss. We tested the hypothesis that the extensive strength loss results from an impairment in the electrophysiological function of the plasmalemma specifically impaired action potential development. Anterior crural muscles from mdx and wildtype mice performed a single bout of 100 electrically stimulated eccentric contractions in vivo. Electromyography, specifically the M-wave, was analysed during muscle contraction to assess the ability of the tibialis anterior muscle plasmalemma to generate and conduct action potentials. During eccentric contractions, wildtype mice exhibited a 36% loss in torque about the ankle but mdx mice exhibited a greater torque loss of 73% (P eccentric contractions. These findings (i) suggest a major plasmalemma-based mechanism of strength loss underlying contraction-induced injury in Duchenne muscular dystrophy distinctly different from that for healthy muscle, and (ii) demonstrate dystrophin is critical for maintaining action potential generation and conduction after eccentric contractions. PMID:23753524

  8. Iguratimod prevents ovariectomy‑induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator‑activated receptor‑γ.

    Science.gov (United States)

    Wu, Ying-Xing; Sun, Yue; Ye, Ya-Ping; Zhang, Peng; Guo, Jia-Chao; Huang, Jun-Ming; Jing, Xing-Zhi; Xiang, Wei; Yu, Shi-Ying; Guo, Feng-Jing

    2017-12-01

    Iguratimod is known for its anti‑inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell‑induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast‑associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy‑induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL‑induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator‑activated receptor‑γ (PPAR‑γ)/c‑Fos pathway, which is essential in RANKL‑induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy‑induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis.

  9. Regulatory Effect of Catalpol on Th1/Th2 cells in Mice with Bone Loss Induced by Estrogen Deficiency.

    Science.gov (United States)

    Lai, Nannan; Zhang, Jianhai; Ma, Xingyan; Wang, Bin; Miao, Xiuming; Wang, Zhaoxia; Guo, Yuqi; Wang, Li; Yao, Chengfang; Li, Xia; Jiang, Guosheng

    2015-12-01

    Estradiol (E2 ) deficiency can cause bone loss and the skew of Th1/Th2 cells. However, the correlation between the Th1/Th2 cells and the bone loss induced by estrogen deficiency remains unclear. Our aim was to investigate the role of Th1/Th2 in bone loss induced by estrogen deficiency and elucidated the therapeutical effect of catalpol in this condition. Young, sham-operated (Sham), ovariectomized (Ovx), and naturally aged mice, treated with catalpol at different doses or control vehicle, were used in this study as indicated in each experiment. ELISA assay, dual-energy X-ray absorptiometry, and flow cytometry were used to analyze E2 , C-terminal telopeptides of type I collagen (CTx-I), bone mineral density (BMD), and Th1/Th2 subsets, respectively. The mRNA and protein expressions of specific transcription factors for Th1/Th2 cells (T-bet and GATA-3) were analyzed using real-time quantitative PCR and Western blot, respectively. Bone mineral density and E2 levels positively correlated with the proportion of Th2 subset while negatively correlated with that of Th1 subset and the ratio of Th1/Th2. Catalpol alleviated bone loss effectively by regulating Th1/Th2 polarization. Catalpol promoted the expression of Th2-specific transcription factors while inhibited that associated with Th1. Th1/Th2 skew is involved in bone loss induced by estrogen deficiency. Catalpol alleviates bone loss effectively by regulating Th1/Th2 paradigm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

    Science.gov (United States)

    Nguyen, Margaret U; Kwong, Jereen; Chang, Julia; Gillet, Victoria G; Lee, Rachel M; Johnson, Karl Gregory

    2016-01-01

    The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS) sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ). To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.

  11. The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Margaret U Nguyen

    Full Text Available The heparan sulfate proteoglycan (HSPG Syndecan (Sdc is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ. To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.

  12. Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.

    Directory of Open Access Journals (Sweden)

    Yves Brand

    Full Text Available Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.

  13. Total adiponectin and adiponectin multimeric complexes in relation to weight loss-induced improvements in insulin sensitivity in obese women

    DEFF Research Database (Denmark)

    Polak, J.; Kovacova, Z.; Holst, C.

    2008-01-01

    diet induced changes in insulin sensitivity (responders and non-responders respectively), matched for weight loss (body mass index (BMI)=34.5 (s.d. 2.9) resp. 36.5 kg/m(2) (s.d. 4.0) for responders and non-responders), were selected from 292 women who underwent a 10-week low-caloric diet (LCD; 600 kcal......, and LMW were negatively associated with fasting insulin levels at baseline. CONCLUSION: No differences in total plasma adiponectin, HMW, MMW, and LMW forms were observed between responders and non-responders following 10-week LCD, suggesting that adiponectin is not a major determinant of weight loss...

  14. A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination.

    Science.gov (United States)

    Wilkerson, Julia R; Tsai, Nien-Pei; Maksimova, Marina A; Wu, Hao; Cabalo, Nicole P; Loerwald, Kristofer W; Dictenberg, Jason B; Gibson, Jay R; Huber, Kimberly M

    2014-06-12

    Experience refines synaptic connectivity through neural activity-dependent regulation of transcription factors. Although activity-dependent regulation of transcription factors has been well described, it is unknown whether synaptic activity and local, dendritic regulation of the induced transcripts are necessary for mammalian synaptic plasticity in response to transcription factor activation. Neuronal depolarization activates the myocyte enhancer factor 2 (MEF2) family of transcription factors that suppresses excitatory synapse number. We report that activation of metabotropic glutamate receptor 5 (mGluR5) on the dendrites, but not cell soma, of hippocampal CA1 neurons is required for MEF2-induced functional and structural synapse elimination. We present evidence that mGluR5 is necessary for synapse elimination to stimulate dendritic translation of the MEF2 target gene Arc/Arg3.1. Activity-regulated cytoskeletal-associated protein (Arc) is required for MEF2-induced synapse elimination, where it plays an acute, cell-autonomous, and postsynaptic role. This work reveals a role for dendritic activity in local translation of specific transcripts in synapse refinement. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. A Role for Dendritic mGluR5-Mediated Local Translation of Arc/Arg3.1 in MEF2-Dependent Synapse Elimination

    Directory of Open Access Journals (Sweden)

    Julia R. Wilkerson

    2014-06-01

    Full Text Available Experience refines synaptic connectivity through neural activity-dependent regulation of transcription factors. Although activity-dependent regulation of transcription factors has been well described, it is unknown whether synaptic activity and local, dendritic regulation of the induced transcripts are necessary for mammalian synaptic plasticity in response to transcription factor activation. Neuronal depolarization activates the myocyte enhancer factor 2 (MEF2 family of transcription factors that suppresses excitatory synapse number. We report that activation of metabotropic glutamate receptor 5 (mGluR5 on the dendrites, but not cell soma, of hippocampal CA1 neurons is required for MEF2-induced functional and structural synapse elimination. We present evidence that mGluR5 is necessary for synapse elimination to stimulate dendritic translation of the MEF2 target gene Arc/Arg3.1. Activity-regulated cytoskeletal-associated protein (Arc is required for MEF2-induced synapse elimination, where it plays an acute, cell-autonomous, and postsynaptic role. This work reveals a role for dendritic activity in local translation of specific transcripts in synapse refinement.

  16. The protective effect of melanocortins on cisplatin-induced hearing loss

    NARCIS (Netherlands)

    Wolters, Francisca Louisa Carolina

    2003-01-01

    Cisplatin is widely used for the treatment of a variety of tumors. Unfortunately, the therapeutic effect of cisplatin is limited because patients can develop a high frequency hearing loss in both ears. Recovery of this hearing loss is observed sporadically. Animal studies have shown that chronic

  17. Effectiveness of Earplugs in Preventing Recreational Noise-Induced Hearing Loss : A Randomized Clinical Trial

    NARCIS (Netherlands)

    Ramakers, Geerte G J; Kraaijenga, Véronique J C; Cattani, Guido; van Zanten, Gijsbert A.; Grolman, Wilko

    IMPORTANCE: The incidence of hearing loss has risen in past years. Attendance at music festivals and concerts may contribute to this increasing problem. OBJECTIVE: To assess the effectiveness of earplugs in preventing temporary hearing loss immediately following music exposure. DESIGN, SETTING, AND

  18. The prevalence of noise-induced occupational hearing loss in dentistry personnel.

    Science.gov (United States)

    Khaimook, Wandee; Suksamae, Puwanai; Choosong, Thitiworn; Chayarpham, Satit; Tantisarasart, Ratchada

    2014-09-01

    Occupational hearing loss is the second most common health problem in the industrialized world. Dental personnel exposed to occupational noise may experience hearing loss. This article compares the prevalence of hearing loss in the general population to that of dental personnel exposed to noise during work hours and identifies risk factors for hearing loss among workers at a dental school. This prospective study included 76 dental personnel on the faculty of dentistry at a major university in Asia who were exposed to noise and 76 individuals in a control group. Nearly 16% of the study group and 21% of the control group had lost hearing, a nonsignificant difference (p = .09). Hearing loss was significantly related to work tenure longer than 15 years and age older than 40 years (p < .001 ).

  19. Loss of Hypoxia-Inducible Factor 2 Alpha in the Lung Alveolar Epithelium of Mice Leads to Enhanced Eosinophilic Inflammation in Cobalt-Induced Lung Injury

    Science.gov (United States)

    Proper, Steven P.; Saini, Yogesh; LaPres, John J.

    2014-01-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2αΔ/Δ) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2αΔ/Δ mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2αΔ/Δ and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung. PMID:24218148

  20. Characteristics of Soil and Organic Carbon Loss Induced by Water Erosion on the Loess Plateau in China.

    Science.gov (United States)

    Li, Zhongwu; Nie, Xiaodong; Chang, Xiaofeng; Liu, Lin; Sun, Liying

    2016-01-01

    Soil erosion has been a common environmental problem in the Loess Plateau in China. This study aims to better understand the losses of soil organic carbon (SOC) induced by water erosion. Laboratory-simulated rainfall experiments were conducted to investigate the characteristics of SOC loss induced by water erosion. The applied treatments included two rainfall intensities (90 and 120 mm h-1), four slope gradients (10°, 15°, 20°, and 25°), and two typical soil types- silty clay loam and silty loam. Results showed that the sediment OC enrichment ratios (ERoc) in all the events were relative stable with values ranged from 0.85 to1.21 and 0.64 to 1.52 and mean values of 0.98 and 1.01 for silty clay loam and silty loam, respectively. Similar to the ERoc, the proportions of different sized particles in sediment showed tiny variations during erosion processes. No significant correlation was observed between ERoc values and the proportions of sediment particles. Slope, rainfall intensity and soil type almost had no impact on ERoc. These results indicate that the transportation of SOC during erosion processes was nonselective. While the mean SOC loss rates for the events of silty clay loam and silty loam were 0.30 and 0.08 g m-2 min-1, respectively. Greater differences in SOC loss rates were found in events among different soil types. Meanwhile, significant correlations between SOC loss and soil loss for all the events were observed. These results indicated that the amount of SOC loss was influenced primarily by soil loss and the SOC content of the original soil. Erosion pattern and original SOC content are two main factors by which different soils can influence SOC loss. It seems that soil type has a greater impact on SOC loss than rainfall characteristics on the Loess Plateau of China. However, more kinds of soils should be further studied due to the special formation processes in the Loess Plateau.

  1. Characteristics of Soil and Organic Carbon Loss Induced by Water Erosion on the Loess Plateau in China

    Science.gov (United States)

    Li, Zhongwu; Nie, Xiaodong; Chang, Xiaofeng; Liu, Lin; Sun, Liying

    2016-01-01

    Soil erosion has been a common environmental problem in the Loess Plateau in China. This study aims to better understand the losses of soil organic carbon (SOC) induced by water erosion. Laboratory-simulated rainfall experiments were conducted to investigate the characteristics of SOC loss induced by water erosion. The applied treatments included two rainfall intensities (90 and 120 mm h-1), four slope gradients (10°, 15°, 20°, and 25°), and two typical soil types- silty clay loam and silty loam. Results showed that the sediment OC enrichment ratios (ERoc) in all the events were relative stable with values ranged from 0.85 to1.21 and 0.64 to 1.52 and mean values of 0.98 and 1.01 for silty clay loam and silty loam, respectively. Similar to the ERoc, the proportions of different sized particles in sediment showed tiny variations during erosion processes. No significant correlation was observed between ERoc values and the proportions of sediment particles. Slope, rainfall intensity and soil type almost had no impact on ERoc. These results indicate that the transportation of SOC during erosion processes was nonselective. While the mean SOC loss rates for the events of silty clay loam and silty loam were 0.30 and 0.08 g m-2 min-1, respectively. Greater differences in SOC loss rates were found in events among different soil types. Meanwhile, significant correlations between SOC loss and soil loss for all the events were observed. These results indicated that the amount of SOC loss was influenced primarily by soil loss and the SOC content of the original soil. Erosion pattern and original SOC content are two main factors by which different soils can influence SOC loss. It seems that soil type has a greater impact on SOC loss than rainfall characteristics on the Loess Plateau of China. However, more kinds of soils should be further studied due to the special formation processes in the Loess Plateau. PMID:27124482

  2. Predicting hearing thresholds in occupational noise-induced hearing loss by auditory steady state responses.

    Science.gov (United States)

    Attias, Joseph; Karawani, Hanin; Shemesh, Rafi; Nageris, Ben

    2014-01-01

    Currently available behavioral tools for the assessment of noise-induced hearing loss (NIHL) depend on the reliable cooperation of the subject. Furthermore, in workers' compensation cases, there is considerable financial gain to be had from exaggerating symptoms, such that accurate assessment of true hearing threshold levels is essential. An alternative objective physiologic tool for assessing NIHL is the auditory steady state response (ASSR) test, which combines frequency specificity with a high level of auditory stimulation, making it applicable for the evaluation of subjects with a moderate to severe deficit. The primary aim of the study was to assess the value of the multifrequency ASSR test in predicting the behavioral warble-tone audiogram in a large sample of young subjects with NIHL of varying severity or with normal hearing. The secondary goal was to assess suprathreshold ASSR growth functions in these two groups. The study group included 157 subjects regularly exposed to high levels of occupational noise, who attended a university-associated audiological clinic for evaluation of NIHL from 2009 through 2011. All underwent a behavioral audiogram, and on the basis of the findings, were divided into those with NIHL (108 subjects, 216 ears) or normal hearing (49 subjects, 98 ears). The accuracy of the ASSR threshold estimations for frequencies of 500, 1000, 2000, and 4000 Hz was compared between groups, and the specificity and sensitivity of the ASSR test in differentiating ears with or without NIHL was calculated using receiver operating characteristic analysis. Linear regression analysis was used to formulate an equation to predict the behavioral warble-tone audiogram at each test frequency using ASSR thresholds. Multifrequency ASSR amplitude growth as a function of stimulus intensity was compared between the NIHL and normal-hearing groups for 1000 Hz and 4000 Hz carrier frequencies. In the subjects with NIHL, ASSR thresholds to various frequencies were

  3. Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Yamanaka

    Full Text Available Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS. Recent studies have established the significance of atypical protein kinase C (aPKC and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation.

  4. Osteoprotegerin is an effective countermeasure for spaceflight-induced bone loss in mice.

    Science.gov (United States)

    Lloyd, Shane A; Morony, Sean E; Ferguson, Virginia L; Simske, Steven J; Stodieck, Louis S; Warmington, Kelly S; Livingston, Eric W; Lacey, David L; Kostenuik, Paul J; Bateman, Ted A

    2015-12-01

    Bone loss associated with microgravity exposure poses a significant barrier to long-duration spaceflight. Osteoprotegerin-Fc (OPG-Fc) is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that causes sustained inhibition of bone resorption after a single subcutaneous injection. We tested the ability of OPG-Fc to preserve bone mass during 12 days of spaceflight (SF). 64-day-old female C57BL/6J mice (n=12/group) were injected subcutaneously with OPG-Fc (20mg/kg) or an inert vehicle (VEH), 24h prior to launch. Ground control (GC) mice (VEH or OPG-Fc) were maintained under environmental conditions that mimicked those in the space shuttle middeck. Age-matched baseline (BL) controls were sacrificed at launch. GC/VEH, but not SF/VEH mice, gained tibia BMD and trabecular volume fraction (BV/TV) during the mission (P<0.05 vs. BL). SF/VEH mice had lower BV/TV vs. GC/VEH mice, while SF/OPG-Fc mice had greater BV/TV than SF/VEH or GC/VEH. SF reduced femur elastic and maximum strength in VEH mice, with OPG-Fc increasing elastic strength in SF mice. Serum TRAP5b was elevated in SF/VEH mice vs. GC/VEH mice. Conversely, SF/OPG-Fc mice had lower TRAP5b levels, suggesting that OPG-Fc preserved bone during spaceflight via inhibition of osteoclast-mediated bone resorption. Decreased bone formation also contributed to the observed osteopenia, based on the reduced femur periosteal bone formation rate and serum osteocalcin level. Overall, these observations suggest that the beneficial effects of OPG-Fc during SF are primarily due to dramatic and sustained suppression of bone resorption. In growing mice, this effect appears to compensate for the SF-related inhibition of bone formation, while preventing any SF-related increase in bone resorption. We have demonstrated that the young mouse is an appropriate new model for SF-induced osteopenia, and that a single pre-flight treatment with OPG-Fc can effectively prevent the deleterious effects of SF on mouse bone. Copyright

  5. [Association between eye absent homolog 4 gene polymorphisms and occupational noise-induced hearing loss].

    Science.gov (United States)

    Yang, Q Y; Xu, X R; Jiao, J; Zheng, Y X; He, L H; Yu, S F; Gu, G Z; Chen, G S; Zhou, W H; Wu, H; Li, Y H; Zhang, H L; Zhang, Z R

    2017-01-06

    Objective: To identify the association between genetic polymorphisms in the eye absent homolog 4 (EYA4) gene and noise-induced hearing loss (NIHL). Method: A nested case control study was conducted based on a cohort of noise-exposed subjects. In total, 292 cases were selected from a steel factory from 6 297 subjects during Jan 1, 2006 to Dec 12, 2015,who had an average hearing threshold of more than 40 dB(A); 584 matched control subjects for each case were designated on the basis of matched criteria including same gender, age (±5 years) and duration of exposure to noise (±2 years). What's more, the control group had an average hearing threshold of less than 35 dB(A) in high frequency and less than 25 dB(A) in speech frequency. Four single nucleotide polymorphisms (SNPs) of the EYA4 gene were genotyped using a SNPscan TM multiplex SNP genotyping kit. Hardy-Weinberg equilibrium tests were performed using a χ 2 test for goodness-of-fit for each SNP among the control group, and the effects of genotypes of the EYA4 gene on NIHL were analyzed by logistic regression. The haplotypes were established and their frequencies in the two groups were assessed using Haploview 4.2 and Phase 2.1 software, and interactive effects between haplotypes and cumulative noise exposure were analyzed. Results: The average age of the subjects was (40.1±8.4) years and the average number of noise-exposed working years was 20.3 (8.4, 27.3) years. The range of noise exposure levels and the cumulative noise exposure were 80.2- 98.8 dB (A) and 86.6- 111.2 dB(A) · year, respectively. After adjustment for covariates including height, blood pressure, drinking status and smoking status, in the noise intensity>85 dB (A) group, subjects carrying the rs3813346 TT genotype had a higher NIHL risk than those carrying the GG genotype, and the adjusted OR (95% CI ) value was 2.12 (1.21- 3.69). In the cumulative noise exposure>98 dB (A) · year group, compared with haplotype TGC, haplotype CGT showed a

  6. Dynamic change of global and local information processing in propofol-induced loss and recovery of consciousness.

    Directory of Open Access Journals (Sweden)

    Martin M Monti

    Full Text Available Whether unique to humans or not, consciousness is a central aspect of our experience of the world. The neural fingerprint of this experience, however, remains one of the least understood aspects of the human brain. In this paper we employ graph-theoretic measures and support vector machine classification to assess, in 12 healthy volunteers, the dynamic reconfiguration of functional connectivity during wakefulness, propofol-induced sedation and loss of consciousness, and the recovery of wakefulness. Our main findings, based on resting-state fMRI, are three-fold. First, we find that propofol-induced anesthesia does not bear differently on long-range versus short-range connections. Second, our multi-stage design dissociated an initial phase of thalamo-cortical and cortico-cortical hyperconnectivity, present during sedation, from a phase of cortico-cortical hypoconnectivity, apparent during loss of consciousness. Finally, we show that while clustering is increased during loss of consciousness, as recently suggested, it also remains significantly elevated during wakefulness recovery. Conversely, the characteristic path length of brain networks (i.e., the average functional distance between any two regions of the brain appears significantly increased only during loss of consciousness, marking a decrease of global information-processing efficiency uniquely associated with unconsciousness. These findings suggest that propofol-induced loss of consciousness is mainly tied to cortico-cortical and not thalamo-cortical mechanisms, and that decreased efficiency of information flow is the main feature differentiating the conscious from the unconscious brain.

  7. Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Figeac, Florence; Andersen, Ditte C.; Nipper Nielsen, Casper A.

    2018-01-01

    /TV) and inhibition of bone resorption. No significant changes were observed in total fat mass or in the number of bone marrow adipocytes. These results support the potential use of anti-DLK1 antibody therapy as a novel intervention to protect from E deficiency associated bone loss....... deficiency-associated bone loss in mice. Thus, we generated mouse monoclonal anti-mouse DLK1 antibodies (MAb DLK1) that enabled us to reduce and also quantitate the levels of bioavailable serum DLK1 in vivo. Ovariectomized (ovx) mice were injected intraperitoneally twice weekly with MAb DLK1 over a period...... of one month. DEXA-, microCT scanning, and bone histomorphometric analyses were performed. Compared to controls, MAb DLK1 treated ovx mice were protected against ovx-induced bone loss, as revealed by significantly increased total bone mass (BMD) due to increased trabecular bone volume fraction (BV...

  8. Using the extended parallel process model to prevent noise-induced hearing loss among coal miners in Appalachia

    Energy Technology Data Exchange (ETDEWEB)

    Murray-Johnson, L.; Witte, K.; Patel, D.; Orrego, V.; Zuckerman, C.; Maxfield, A.M.; Thimons, E.D. [Ohio State University, Columbus, OH (US)

    2004-12-15

    Occupational noise-induced hearing loss is the second most self-reported occupational illness or injury in the United States. Among coal miners, more than 90% of the population reports a hearing deficit by age 55. In this formative evaluation, focus groups were conducted with coal miners in Appalachia to ascertain whether miners perceive hearing loss as a major health risk and if so, what would motivate the consistent wearing of hearing protection devices (HPDs). The theoretical framework of the Extended Parallel Process Model was used to identify the miners' knowledge, attitudes, beliefs, and current behaviors regarding hearing protection. Focus group participants had strong perceived severity and varying levels of perceived susceptibility to hearing loss. Various barriers significantly reduced the self-efficacy and the response efficacy of using hearing protection.

  9. Epidermal growth factor receptor is a preferred target for treating Amyloid-β–induced memory loss

    OpenAIRE

    Wang, Lei; Chiang, Hsueh-Cheng; Wu, Wenjuan; Liang, Bin; Xie, Zuolei; Yao, Xinsheng; Ma, Weiwei; Du, Shuwen; Zhong, Yi

    2012-01-01

    Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer’s disease. We took two independent approaches, including synaptic-plasticity–based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic co...

  10. Apoptosis of Corneal Epithelial Cells Caused by Ultraviolet B-induced Loss of K+ is Inhibited by Ba2+

    Science.gov (United States)

    Glupker, Courtney D.; Boersma, Peter M.; Schotanus, Mark P.; Haarsma, Loren D.; Ubels, John L.

    2017-01-01

    UVB exposure at ambient outdoor levels triggers rapid K+ loss and apoptosis in human corneal limbal epithelial (HCLE) cells cultured in medium containing 5.5 mM K+, but considerably less apoptosis occurs when the medium contains the high K+ concentration that is present in tears (25 mM). Since Ba2+ blocks several K+ channels, we tested whether Ba2+-sensitive K+ channels are responsible for some or all of the UVB-activated K+ loss and subsequent activation of the caspase cascade and apoptosis. Corneal epithelial cells in culture were exposed to UVB at 80 or 150 mJ/cm2. Patch-clamp recording was used to measure UVB-induced K+ currents. Caspase-activity and TUNEL assays were performed on HCLE cells exposed to UVB followed by incubation in the presence or absence of Ba2+. K+ currents were activated in HCLE cells following UVB-exposure. These currents were reversibly blocked by 5 mM Ba2+. When HCLE cells were incubated with 5 mM Ba2+ after exposure to UVB, activation of caspases-9, -8, and -3 and DNA fragmentation were significantly decreased. The data confirm that UVB-induced K+ current activation and loss of intracellular K+ leads to activation of the caspase cascade and apoptosis. Extracellular Ba2+ inhibits UVB-induced apoptosis by preventing loss of intracellular K+ when K+ channels are activated. Ba2+ therefore has effects similar to elevated extracellular K+ in protecting HCLE cells from UVB-induced apoptosis. This supports our overall hypothesis that elevated K+ in tears contributes to protection of the corneal epithelium from adverse effects of ambient outdoor UVB. PMID:27189864

  11. The effect of weight loss on serum concentrations of nitric oxide induced by short - term exercise in obese women

    Directory of Open Access Journals (Sweden)

    M Olszanecka-Glinianowicz

    2009-07-01

    Full Text Available Objective: The aim of present study was to examine the effect of weight loss comprising regular moderate physical activity on resting serum concentrations of nitric oxide metabolites and exercise induced NO release. Materials and Methods: The study was carried out in 43 obese women without additional diseases (age 41.8±11.9y, body weight 94.5±15.1kg, BMI 36.5±4.6kg/m2. All obese patients participated in a 3-month weight reduction programme that consisted of 1 a group instruction in behavioural and dietary methods of weight control every two weeks; 2 1000-1400kcal/day balanced diet, and 3 moderate physical exercises (30 minutes, 3 times a week. Before and after treatment body mass and height were measured, body mass index (BMI was calculated. Body composition was determined by impedance analysis using a Bodystat analyser. The serum concentration of nitric oxide metabolites before and after exercise was measured using spectrophotometry method by Griess. The serum concentrations of lactate before and after exercise were measured with the use of strip test (ACCUSPORT analyzer. Serum concentration of insulin was measured with the use of RIA. Plasma glucose, cholesterol, HDL cholesterol and triglicerydes were determined by enzymatic procedure. Results: The mean weight loss during treatment was 8.3±4.3 kg. We did not observe differences between resting serum concentrations of NO and lactate before and after weight loss. During exercise serum NO concentrations increased significantly both before and after weight loss treatment. After the weight reduction treatment, the time of exercise test increased significantly P<0.005, but there were no significant differences between the value of NO before and after weight loss. Conclusion: 3 – month regular physical activity and weight loss did not influence exercise-induced nitric oxide production.

  12. Loss of bone strength in response to exercise-induced weight loss in obese postmenopausal women: results from a pilot study.

    Science.gov (United States)

    Shea, K L; Gozansky, W S; Sherk, V D; Swibas, T A; Wolfe, P; Scherzinger, A; Stamm, E; Kohrt, W M

    2014-06-01

    Exercise-induced weight loss (WL) can lead to decreased areal bone mineral density (aBMD). It is unknown whether this translates into decreased volumetric BMD (vBMD) or bone strength. The purpose of this pilot study was to determine whether exercise-induced WL results in decreased vBMD and bone strength in postmenopausal women. Fourteen subjects participated in a 4-month endurance exercise WL intervention. A weight stable (WS) control group (n=10) was followed for 4 months. Proximal femur aBMD was measured by DXA. Femoral neck vBMD and estimates of bone strength (cross-sectional moment of inertia (CSMI) and section modulus (SM)) were measured by quantitative CT. Women were 54.6±2.4 years, BMI 32.1±5.9 kg/m(2) and 54.4±2.9 years, BMI 27.9±3.6 kg/m(2) in the WL and WS groups, respectively. The WL group lost 3.0±2.6 kg which was predominately fat mass. There was a significant decrease in SMmax. Changes in CSMImax and total hip aBMD were not significant. Total hip vBMD did not decrease significantly in response to WL. There were no significant changes in the WS group. WL may lead to decreased bone strength before changes in BMD are detected. Further studies are needed to determine whether bone-targeted exercise can preserve bone strength during WL.

  13. The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Hansen, Gitte; Tang-Christensen, Mads

    2010-01-01

    Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of diet-induced obesity. Sibutramine and rimonabant were used as reference comparators....... Compared to baseline, long-term treatment with tesofensine (28 days, 1.0 or 2.5mg/kg, p.o.) resulted in a significant, dose-dependent and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5mg/kg, p.o.) treatment caused a sustained weight loss of 7.6%, whereas the employed dose...... of rimonabant (10mg/kg, p.o.) only produced a transient weight reduction. While all compounds exhibited a significant inhibitory effect on food intake which gradually wore off, the hypophagic effect of tesofensine was longer lasting than sibutramine and rimonabant. In contrast to tesofensine, the body weight...

  14. Radiation-induced magnetization reversal causing a large flux loss in undulator permanent magnets.

    Science.gov (United States)

    Bizen, Teruhiko; Kinjo, Ryota; Hasegawa, Teruaki; Kagamihata, Akihiro; Kida, Yuichiro; Seike, Takamitsu; Watanabe, Takahiro; Hara, Toru; Itoga, Toshiro; Asano, Yoshihiro; Tanaka, Takashi

    2016-11-29

    We report an unexpectedly large flux loss observed in permanent magnets in one of the undulators operated in SACLA, the x-ray free electron laser facility in Japan. Characterizations of individual magnets extracted from the relevant undulator have revealed that the flux loss was caused by a homogeneous magnetization reversal extending over a wide area, but not by demagnetization of individual magnets damaged by radiation. We show that the estimated flux-loss rate is much higher than what is reported in previous papers, and its distribution is much more localized to the upstream side. Results of numerical and experimental studies carried out to validate the magnetization reversal and quantify the flux loss are presented, together with possible countermeasures against rapid degradation of the undulator performance.

  15. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  16. Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Sato

    2015-09-01

    Conclusions: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

  17. Antiepileptic drug-induced bone loss in young male patients who have seizures.

    Science.gov (United States)

    Andress, Dennis L; Ozuna, Judy; Tirschwell, David; Grande, Lucinda; Johnson, Meshell; Jacobson, Arnold F; Spain, William

    2002-05-01

    Long-term antiepileptic drug (AED) therapy is a known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures. To determine whether men who have seizures, but who are otherwise healthy, suffer substantial bone loss in the hip while taking AEDs. We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years old (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time. Multivariate linear regression analysis revealed that age (P<.001) and time receiving AEDs (P<.003) were the 2 important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake were associated with low BMD after correcting for age and time on AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25-44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, -3.1 to -0.9; P<.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group although most patients were taking phenytoin sodium or carbamazepine during the longitudinal assessment. Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs.

  18. Heterogeneous Association of Alzheimer's Disease-Linked Amyloid-β and Amyloid-β Protein Precursor with Synapses.

    Science.gov (United States)

    Willén, Katarina; Sroka, Agnieszka; Takahashi, Reisuke H; Gouras, Gunnar K

    2017-01-01

    Alzheimer's disease (AD) is increasingly viewed as a disease of synapses. Loss of synapses correlates better with cognitive decline than amyloid plaques and neurofibrillary tangles, the hallmark neuropathological lesions of AD. Soluble forms of amyloid-β (Aβ) have emerged as mediators of synapse dysfunction. Aβ binds to, accumulates, and aggregates in synapses. However, the anatomical and neurotransmitter specificity of Aβ and the amyloid-β protein precursor (AβPP) in AD remain poorly understood. In addition, the relative roles of Aβ and AβPP in the development of AD, at pre- versus post-synaptic compartments and axons versus dendrites, respectively, remain unclear. Here we use immunogold electron microscopy and confocal microscopy to provide evidence for heterogeneity in the localization of Aβ/AβPP. We demonstrate that Aβ binds to a subset of synapses in cultured neurons, with preferential binding to glutamatergic compared to GABAergic neurons. We also highlight the challenge of defining pre- versus post-synaptic localization of this binding by confocal microscopy. Further, endogenous Aβ42 accumulates in both glutamatergic and GABAergic AβPP/PS1 transgenic primary neurons, but at varying levels. Moreover, upon knock-out of presenilin 1 or inhibition of γ-secretase AβPP C-terminal fragments accumulate both pre- and post-synaptically; however earlier pre-synaptically, consistent with a higher rate of AβPP processing in axons. A better understanding of the synaptic and anatomical selectivity of Aβ/AβPP in AD can be important for the development of more effective new therapies for this major disease of aging.

  19. Heterogeneous Association of Alzheimer’s Disease-Linked Amyloid-β and Amyloid-β Protein Precursor with Synapses

    Science.gov (United States)

    Willén, Katarina; Sroka, Agnieszka; Takahashi, Reisuke H.; Gouras, Gunnar K.

    2017-01-01

    Alzheimer’s disease (AD) is increasingly viewed as a disease of synapses. Loss of synapses correlates better with cognitive decline than amyloid plaques and neurofibrillary tangles, the hallmark neuropathological lesions of AD. Soluble forms of amyloid-β (Aβ) have emerged as mediators of synapse dysfunction. Aβ binds to, accumulates, and aggregates in synapses. However, the anatomical and neurotransmitter specificity of Aβ and the amyloid-β protein precursor (AβPP) in AD remain poorly understood. In addition, the relative roles of Aβ and AβPP in the development of AD, at pre- versus post-synaptic compartments and axons versus dendrites, respectively, remain unclear. Here we use immunogold electron microscopy and confocal microscopy to provide evidence for heterogeneity in the localization of Aβ/AβPP. We demonstrate that Aβ binds to a subset of synapses in cultured neurons, with preferential binding to glutamatergic compared to GABAergic neurons. We also highlight the challenge of defining pre- versus post-synaptic localization of this binding by confocal microscopy. Further, endogenous Aβ42 accumulates in both glutamatergic and GABAergic AβPP/PS1 transgenic primary neurons, but at varying levels. Moreover, upon knock-out of presenilin 1 or inhibition of γ-secretase AβPP C-terminal fragments accumulate both pre- and post-synaptically; however earlier pre-synaptically, consistent with a higher rate of AβPP processing in axons. A better understanding of the synaptic and anatomical selectivity of Aβ/AβPP in AD can be important for the development of more effective new therapies for this major disease of aging. PMID:28869466

  20. Interventions to prevent occupational noise-induced hearing loss: a Cochrane systematic review.

    Science.gov (United States)

    Verbeek, Jos H; Kateman, Erik; Morata, Thais C; Dreschler, Wouter A; Mischke, Christina

    2014-03-01

    To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. We searched biomedical databases up to 25 January 2012 for randomized controlled trials (RCT), controlled before-after studies and interrupted time-series of hearing loss prevention among workers exposed to noise. We included 19 studies with 82 794 participants evaluating effects of hearing loss prevention programs (HLPP). The overall quality of studies was low to very low, as rated using the GRADE approach. One study of stricter legislation showed a favorable effect on noise levels. Three studies, of which two RCTs, did not find an effect of a HLPP. Four studies showed that better use of hearing protection devices in HLPPs decreased the risk of hearing loss. In four other studies, workers in a HLPP still had a 0.5 dB greater hearing loss at 4 kHz (95% CI - 0.5 to 1.7) than non-exposed workers. In two similar studies there was a substantial risk of hearing loss in spite of a HLPP. Stricter enforcement of legislation and better implementation of HLPPs can reduce noise levels in workplaces. Better evaluations of technical interventions and long-term effects are needed.