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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. Stress-induced grey matter loss determined by MRI is primarily due to loss of dendrites and their synapses.

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    Kassem, Mustafa S; Lagopoulos, Jim; Stait-Gardner, Tim; Price, William S; Chohan, Tariq W; Arnold, Jonathon C; Hatton, Sean N; Bennett, Maxwell R

    2013-04-01

    Stress, unaccompanied by signs of post-traumatic stress disorder, is known to decrease grey matter volume (GMV) in the anterior cingulate cortex (ACC) and hippocampus but not the amygdala in humans. We sought to determine if this was the case in stressed mice using high-resolution magnetic resonance imaging (MRI) and to identify the cellular constituents of the grey matter that quantitatively give rise to such changes. Stressed mice showed grey matter losses of 10 and 15 % in the ACC and hippocampus, respectively but not in the amygdala or the retrosplenial granular area (RSG). Concurrently, no changes in the number or volumes of the somas of neurons, astrocytes or oligodendrocytes were detected. A loss of synaptic spine density of up to 60 % occurred on different-order dendrites in the ACC and hippocampus (CA1) but not in the amygdala or RSG. The loss of spines was accompanied by decreases in cumulative dendritic length of neurons of over 40 % in the ACC and hippocampus (CA1) giving rise to decreases in volume of dendrites of 2.6 mm(3) for the former and 0.6 mm(3) for the latter, with no change in the amygdala or RSG. These values are similar to the MRI-determined loss of GMV following stress of 3.0 and 0.8 mm(3) in ACC and hippocampus, respectively, with no changes in the amygdala or RSG. This quantitative study is the first to relate GMV changes in the cortex measured with MRI to volume changes in cellular constituents of the grey matter.

  3. Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

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    Elsworth, John D; Morrow, Bret A; Hajszan, Tibor; Leranth, Csaba; Roth, Robert H

    2011-01-01

    Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine. PMID:21677652

  4. miRNA-431 Prevents Amyloid-β-Induced Synapse Loss in Neuronal Cell Culture Model of Alzheimer's Disease by Silencing Kremen1.

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    Ross, Sean P; Baker, Kelly E; Fisher, Amanda; Hoff, Lee; Pak, Elena S; Murashov, Alexander K

    2018-01-01

    Synapse loss is well regarded as the underlying cause for the progressive decline of memory function over the course of Alzheimer's disease (AD) development. Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf-1 (Dkk1) in the AD brain plays a critical role in triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block the Wnt/β-catenin signaling pathway. Here, we show that silencing Krm1 with miR-431 prevents amyloid-β-mediated synapse loss in cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice. Exposure to AβDDL (an amyloid-β derived diffusive ligand) or Dkk1 reduced the number of pre- and post-synaptic puncta in primary neuronal cultures, while treatment with miR-431 prevented synapse loss. In addition, treatment with miR-431 also prevented neurite degeneration. Our findings demonstrate that miR-431 protects synapses and neurites from Aβ-toxicity in an AD cell culture model and may be a promising therapeutic target.

  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. Loss of Synapse Repressor MDGA1 Enhances Perisomatic Inhibition, Confers Resistance to Network Excitation, and Impairs Cognitive Function

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    Steven A. Connor

    2017-12-01

    Full Text Available Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses. Mdga1−/− hippocampal networks demonstrate muted responses to neural excitation, and Mdga1−/− mice are resistant to induced seizures. Mdga1−/− mice further demonstrate compromised hippocampal long-term potentiation, consistent with observed deficits in spatial and context-dependent learning and memory. These results suggest that mutations in MDGA1 may contribute to cognitive deficits through altered synaptic transmission and plasticity by loss of suppression of inhibitory synapse development in a subcellular domain- and cell-type-selective manner.

  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

    2014-07-01

    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.

  9. 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

  10. 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

  11. 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.

  12. 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.

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

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

    1996-01-01

    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 indiscriminat...... simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (P...

  15. Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease.

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    Jackson, Rosemary J; Rudinskiy, Nikita; Herrmann, Abigail G; Croft, Shaun; Kim, JeeSoo Monica; Petrova, Veselina; Ramos-Rodriguez, Juan Jose; Pitstick, Rose; Wegmann, Susanne; Garcia-Alloza, Monica; Carlson, George A; Hyman, Bradley T; Spires-Jones, Tara L

    2016-12-01

    Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Synaptic heterogeneity and stimulus-induced modulation of depression in central synapses.

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    Hunter, J D; Milton, J G

    2001-08-01

    Short-term plasticity is a pervasive feature of synapses. Synapses exhibit many forms of plasticity operating over a range of time scales. We develop an optimization method that allows rapid characterization of synapses with multiple time scales of facilitation and depression. Investigation of paired neurons that are postsynaptic to the same identified interneuron in the buccal ganglion of Aplysia reveals that the responses of the two neurons differ in the magnitude of synaptic depression. Also, for single neurons, prolonged stimulation of the presynaptic neuron causes stimulus-induced increases in the early phase of synaptic depression. These observations can be described by a model that incorporates two availability factors, e.g., depletable vesicle pools or desensitizing receptor populations, with different time courses of recovery, and a single facilitation component. This model accurately predicts the responses to novel stimuli. The source of synaptic heterogeneity is identified with variations in the relative sizes of the two availability factors, and the stimulus-induced decrement in the early synaptic response is explained by a slowing of the recovery rate of one of the availability factors. The synaptic heterogeneity and stimulus-induced modifications in synaptic depression observed here emphasize that synaptic efficacy depends on both the individual properties of synapses and their past history.

  17. 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

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

    International Nuclear Information System (INIS)

    Soricelli, A.; Postiglione, A.; Grivet-Fojaja, M.R.; Mainenti, P.P.; Discepolo, A.; Varrone, A.; Salvatore, M.; Lassen, N.A.

    1996-01-01

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABA A receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (V d ) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured V d 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 simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex V d was significantly (P d averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal V d averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlated closely with the mental deterioration in AD. (orig.)

  19. Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss

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    Lijuan Shi

    2016-01-01

    Full Text Available Recent studies on animal models have shown that noise exposure that does not lead to permanent threshold shift (PTS can cause considerable damage around the synapses between inner hair cells (IHCs and type-I afferent auditory nerve fibers (ANFs. Disruption of these synapses not only disables the innervated ANFs but also results in the slow degeneration of spiral ganglion neurons if the synapses are not reestablished. Such a loss of ANFs should result in signal coding deficits, which are exacerbated by the bias of the damage toward synapses connecting low-spontaneous-rate (SR ANFs, which are known to be vital for signal coding in noisy background. As there is no PTS, these functional deficits cannot be detected using routine audiological evaluations and may be unknown to subjects who have them. Such functional deficits in hearing without changes in sensitivity are generally called “noise-induced hidden hearing loss (NIHHL.” Here, we provide a brief review to address several critical issues related to NIHHL: (1 the mechanism of noise induced synaptic damage, (2 reversibility of the synaptic damage, (3 the functional deficits as the nature of NIHHL in animal studies, (4 evidence of NIHHL in human subjects, and (5 peripheral and central contribution of NIHHL.

  20. 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 ...

  1. Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

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    Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

    2012-01-01

    Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

  2. Drug-induced hair loss.

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    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  3. Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1.

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    Tachibana, Masaya; Shinohara, Mitsuru; Yamazaki, Yu; Liu, Chia-Chen; Rogers, Justin; Bu, Guojun; Kanekiyo, Takahisa

    2016-03-01

    Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1(-/-)) and littermate control mice were administered with bexarotene-formulated diet (100mg/kg/day) or control diet at the age of 20-24 months for 8 weeks. Upon bexarotene treatment, levels of brain apoE and ATP-binding cassette sub-family A member 1 (ABCA1) were significantly increased in both mice. While levels of PSD95, glutamate receptor 1 (GluR1), and N-methyl-d-aspartate receptor NR1 subunit (NR1), which are key postsynaptic proteins that regulate synaptic plasticity, were decreased with aging, they were restored by bexarotene treatment in the brains of control but not nLrp1(-/-) mice. These results indicate that the beneficial effects of bexarotene on synaptic integrity depend on the presence of neuronal LRP1. However, we also found that bexarotene treatment led to the activation of glial cells, weight loss and hepatomegaly, which are likely due to hepatic failure. Taken together, our results demonstrate that apoE-targeted treatment through the RXR pathway has a potential beneficial effect on synapses during aging; however, the therapeutic application of bexarotene requires extreme caution due to its toxic side effects. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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

  5. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction.

    Science.gov (United States)

    Tomàs, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomàs, Marta; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M 1 , M 2 and M 4 ), adenosine receptors (AR; A 1 and A 2A ) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A 1 , M 1 and TrkB operate mainly by stimulating PKC whereas A 2A , M 2 and M 4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and

  6. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Josep M. Tomàs

    2017-08-01

    Full Text Available Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh receptors (subtypes mAChR; M1, M2 and M4, adenosine receptors (AR; A1 and A2A and the tropomyosin-related kinase B receptor (TrkB, among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC, to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A1, M1 and TrkB operate mainly by stimulating PKC whereas A2A, M2 and M4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ. This hypothesis is supported by: (i the tonic effect (shown by using selective inhibitors of several membrane receptors that accelerates axon loss between postnatal days P5–P9; (ii the synergistic, antagonic and modulatory effects (shown by paired inhibition of the receptors on axonal loss; (iii the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and various

  7. 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. PMID:26788851

  8. Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis.

    Science.gov (United States)

    Azevedo, E P; Ledo, J H; Barbosa, G; Sobrinho, M; Diniz, L; Fonseca, A C C; Gomes, F; Romão, L; Lima, F R S; Palhano, F L; Ferreira, S T; Foguel, D

    2013-09-05

    Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.

  9. 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

  10. 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.

  11. Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression.

    Science.gov (United States)

    Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L; Szigeti-Buck, Klara; Sallam, Nermin L; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S

    2009-03-01

    Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

  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. On-chip photonic synapse.

    Science.gov (United States)

    Cheng, Zengguang; Ríos, Carlos; Pernice, Wolfram H P; Wright, C David; Bhaskaran, Harish

    2017-09-01

    The search for new "neuromorphic computing" architectures that mimic the brain's approach to simultaneous processing and storage of information is intense. Because, in real brains, neuronal synapses outnumber neurons by many orders of magnitude, the realization of hardware devices mimicking the functionality of a synapse is a first and essential step in such a search. We report the development of such a hardware synapse, implemented entirely in the optical domain via a photonic integrated-circuit approach. Using purely optical means brings the benefits of ultrafast operation speed, virtually unlimited bandwidth, and no electrical interconnect power losses. Our synapse uses phase-change materials combined with integrated silicon nitride waveguides. Crucially, we can randomly set the synaptic weight simply by varying the number of optical pulses sent down the waveguide, delivering an incredibly simple yet powerful approach that heralds systems with a continuously variable synaptic plasticity resembling the true analog nature of biological synapses.

  14. 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.

  15. 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

    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...... 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....

  16. 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

  17. 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

  18. 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

  19. 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...

  20. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    Science.gov (United States)

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-12-12

    Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain. Furthermore, the level of brain-derived neurotrophic factor (BDNF) was analyzed. Pregnant female Wistar rats received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring, while the control animals received drinking water. During the feeding of pups, mothers from the Pb-group were continuously receiving PbAc. Pups of both groups were weaned at postnatal day 21 and then until postnatal day 28 received only drinking water. 28-day old pups were sacrificed and the ultrastructural changes as well as expression of presynaptic (VAMP1/2, synaptophysin, synaptotagmin-1, SNAP25, syntaxin-1) and postsynaptic (PSD-95) proteins were analyzed in: forebrain cortex, cerebellum and hippocampus. Our data revealed that pre- and neonatal exposure to low dose of Pb promotes pathological changes in synapses, including nerve endings swelling, blurred and thickened synaptic cleft structure as well as enhanced density of synaptic vesicles in the presynaptic area. Moreover, synaptic mitochondria were elongated, swollen or shrunken in Pb-treated animals. These structural abnormalities were accompanied by decrease in the level of key synaptic proteins: synaptotagmin-1 in cerebellum, SNAP25 in hippocampus and syntaxin-1 in cerebellum and hippocampus. In turn, increased level of synaptophysin was

  1. 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.

  2. Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

    Science.gov (United States)

    Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

    2009-01-01

    Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

  3. [Hearing loss and idoneity--the segnalation of noise-induced hearing loss hearing Loss].

    Science.gov (United States)

    Albera, Roberto; Dagna, Federico; Cassandro, Claudia; Canale, Andrea

    2011-01-01

    Work idoneity in hearing loss must be related to working ability and evolution risks. Working ability is referred to the difficulties found in speech comprehension and in signals perception. As regards hearing loss evolution it is necessary to define if the subject is affected by conductive or neurosensorial hearing loss. In conductive hearing loss it is necessary to evaluate entity and frequential distribution of the deficit. In neurosensorial hearing loss it is necessary to distinguish between noise-induced hearing loss and extraprofessional hearing loss. In noise-induced hearing loss the evolution risk is high if the noise exposure is less than 10-15 years or the actual noise exposure is louder than the former. In case of extraprofessional hearing loss the evolution risk is higher in presbycusis, endolymphatic hydrops and toxic hearing loss. The necessity to report the presence on professionale noise-induced hearing loss arises if audiometric threshold is more than 25 dB at 0.5-1-2-3-4 kHz and if it is verified the professional origine of hearing loss.

  4. Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.

    Science.gov (United States)

    Adachi, Megumi; Lin, Pei-Yi; Pranav, Heena; Monteggia, Lisa M

    2016-07-15

    Myocyte enhancer factor 2 (MEF2) transcription factors play critical roles in diverse cellular processes during central nervous system development. Studies attempting to address the role of MEF2 in brain have largely relied on overexpression of a constitutive MEF2 construct that impairs memory formation or knockdown of MEF2 function that increases spine numbers and enhances memory formation. Genetic deletion of individual MEF2 isoforms in brain during embryogenesis demonstrated that Mef2c loss negatively regulates spine numbers resulting in learning and memory deficits, possibly as a result of its essential role in development. To investigate MEF2C function in brain further, we genetically deleted Mef2c during postnatal development in mice. We characterized these conditional Mef2c knockout mice in an array of behavioral paradigms and examined the impact of postnatal loss of Mef2c on long-term potentiation. We observed increased spine numbers in hippocampus of the conditional Mef2c knockout mice. However, the postnatal loss of Mef2c did not impact learning and memory, long-term potentiation, or social and repetitive behaviors. Our findings demonstrate a critical role for MEF2C in the regulation of spine numbers with a dissociation of learning and memory, synaptic plasticity, and measures of autism-related behaviors in postnatal brain. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. 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

    2012-08-28

    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.

  6. Does erythropoietin augment noise induced hearing loss?

    DEFF Research Database (Denmark)

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

    2007-01-01

    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 of...

  7. Rain-induced spring wheat harvest losses

    Science.gov (United States)

    Bauer, A.; Black, A. L. (Principal Investigator)

    1983-01-01

    When rain or a combination of rain and high humidity delay wheat harvest, losses can occur in grain yield and/or grain quality. Yield losses can result from shattering, from reduction in test weight, and in the case of windrowed grain, from rooting of sprouting grain at the soil: windrow contact. Losses in grain quality can result from reduction in test weight and from sprouting. Sprouting causes a degradation of grain proteins and starches, hence flour quality is reduced, and the grain price deteriorates to the value of feed grain. Although losses in grain yield and quality are rain-induced, these losses do not necessarily occur because a standing or windrowed crop is wetted by rain. Spike water concentration in hard red spring wheat must be increased to about 45-49% before sprouting is initiated in grain that has overcome dormancy. The time required to overcome this dormancy after the cultivar has dried to 12 to 14% water concentration differs with hard red spring cultivars. The effect of rain on threshing-ready standing and windrowed hard red spring wheat grain yeild and quality was evaluated. A goal was to develop the capability to forecast the extent of expected loss of grain yield and quality from specific climatic events that delay threshing.

  8. 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

    pits. Three-dimensional analysis showed a significant decrease in both post-synaptic density and apposition zone curvature of mushroom spines following FGL treatment, whereas for thin spines the convexity of the apposition zone increased. These data indicate that FGL induces large changes in the fine...... 100 serial ultrathin sections. FGL affected neither hippocampal volume nor spine or synaptic density in the middle molecular layer of the dentate gyrus. However, it increased the ratio of mushroom to thin spines, number of multivesicular bodies and also increased the frequency of appearance of coated...... structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes....

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Dávid Csabai

    2018-01-01

    Full Text Available 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

  11. A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

    Directory of Open Access Journals (Sweden)

    Wujie eYuan

    2013-04-01

    Full Text Available Microsaccades during fixation have been suggested to counteract visual fading. Recent experi- ments have also observed microsaccade-related neural responses from cellular record, scalp elec- troencephalogram (EEG and functional magnetic resonance imaging (fMRI. The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1 is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depres- sion (STD in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades.

  12. A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

    Science.gov (United States)

    Yuan, Wu-Jie; Dimigen, Olaf; Sommer, Werner; Zhou, Changsong

    2013-01-01

    Microsaccades during fixation have been suggested to counteract visual fading. Recent experiments have also observed microsaccade-related neural responses from cellular record, scalp electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI). The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1) is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depression (STD) in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades. PMID:23630494

  13. 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

  14. 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...

  15. 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...

  16. Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice.

    Science.gov (United States)

    Baglietto-Vargas, David; Chen, Yuncai; Suh, Dongjin; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Myczek, Kristoffer; Green, Kim N; Baram, Tallie Z; LaFerla, Frank M

    2015-09-01

    Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal 'modern life-like' stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. Epidemiological evidence indicates that life experiences, including chronic stress, are a risk for Alzheimer disease (AD). However, it is unknown if short stress in the range of hours influences the onset or progression of AD. Here, we determined the effect of short, multi-modal 'modern-lifelike'stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by

  17. Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

    Science.gov (United States)

    Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

    2017-03-15

    Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses

  18. 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.

  19. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

    NARCIS (Netherlands)

    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.

    2003-01-01

    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric

  20. 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.

  1. Ripple induced trapped particle loss in tokamaks

    International Nuclear Information System (INIS)

    White, R.B.

    1996-05-01

    The threshold for stochastic transport of high energy trapped particles in a tokamak due to toroidal field ripple is calculated by explicit construction of primary resonances, and a numerical examination of the route to chaos. Critical field ripple amplitude is determined for loss. The expression is given in magnetic coordinates and makes no assumptions regarding shape or up-down symmetry. An algorithm is developed including the effects of prompt axisymmetric orbit loss, ripple trapping, convective banana flow, and stochastic ripple loss, which gives accurate ripple loss predictions for representative Tokamak Fusion Test Reactor and International Thermonuclear Experimental Reactor equilibria. The algorithm is extended to include the effects of collisions and drag, allowing rapid estimation of alpha particle loss in tokamaks

  2. Hearing: Noise-Induced Hearing Loss

    Science.gov (United States)

    ... reduce your exposure to noise by choosing quiet leisure activities rather than noisy ones. Develop the habit ... the degree of your hearing loss, you may benefit from using a hearing aid (a device you ...

  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. 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.

  7. 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.

  8. Shaping Synapses by the Neural Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Maura Ferrer-Ferrer

    2018-05-01

    Full Text Available Accumulating data support the importance of interactions between pre- and postsynaptic neuronal elements with astroglial processes and extracellular matrix (ECM for formation and plasticity of chemical synapses, and thus validate the concept of a tetrapartite synapse. Here we outline the major mechanisms driving: (i synaptogenesis by secreted extracellular scaffolding molecules, like thrombospondins (TSPs, neuronal pentraxins (NPs and cerebellins, which respectively promote presynaptic, postsynaptic differentiation or both; (ii maturation of synapses via reelin and integrin ligands-mediated signaling; and (iii regulation of synaptic plasticity by ECM-dependent control of induction and consolidation of new synaptic configurations. Particularly, we focused on potential importance of activity-dependent concerted activation of multiple extracellular proteases, such as ADAMTS4/5/15, MMP9 and neurotrypsin, for permissive and instructive events in synaptic remodeling through localized degradation of perisynaptic ECM and generation of proteolytic fragments as inducers of synaptic plasticity.

  9. 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)

  10. 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

  11. Acute liver injury induced by weight-loss herbal supplements.

    Science.gov (United States)

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-11-27

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. The Physiological Bases of Hidden Noise-Induced Hearing Loss: Protocol for a Functional Neuroimaging Study.

    Science.gov (United States)

    Dewey, Rebecca Susan; Hall, Deborah A; Guest, Hannah; Prendergast, Garreth; Plack, Christopher J; Francis, Susan T

    2018-03-09

    Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as hidden hearing loss have been confirmed in several rodent species, but the implications for human hearing are unclear. Our Medical Research Council-funded program aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss; (2) investigate whether there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems; and (3) explore the relation between subcortical functional magnetic resonance imaging (fMRI) measures and the auditory brainstem response (ABR). Individuals aged 25 to 40 years with pure tone hearing thresholds ≤20 dB hearing level over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. This paper reports the study protocol. The funding was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. This challenging and comprehensive study will have the potential to impact diagnostic

  18. 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.

  19. Noise-induced hearing loss: a recreational noise perspective.

    Science.gov (United States)

    Ivory, Robert; Kane, Rebecca; Diaz, Rodney C

    2014-10-01

    This review will discuss the real-world risk factors involved in noise-induced hearing loss as a result of common and popular recreational activities prone to mid and high levels of noise exposure. Although there are currently no interventional measures available to reverse or mitigate preexisting hearing loss from noise, we discuss the vital importance of hearing loss prevention from noise exposure avoidance and reduction. Despite a seeming understanding of the effects of noise exposure from various recreational activities and devices, a large percentage of the general public who is at risk of such noise-induced hearing loss still chooses to refrain from using hearing protection instruments. While occupational exposures pose the greatest traditional risk to hearing conservation in selected workers, recreational risk factors for noise-induced hearing loss may be more insidious in overall effect given the indifferent attitude of much of the general public and particularly our youths toward hearing protection during recreational activities. Active counseling regarding the consequences of excessive noise exposure and the potential benefits to hearing from usage of hearing protection instruments is critical to providing best possible care in the hearing health professions.

  20. 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...

  1. 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 ...

  2. 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 ...

  3. 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...

  4. Minocycline attenuates noise-induced hearing loss in rats.

    Science.gov (United States)

    Zhang, Jing; Song, Yong-Li; Tian, Ke-Yong; Qiu, Jian-Hua

    2017-02-03

    Noise-induced hearing loss (NIHL) is a serious health concern and prevention of hair cell death or therapeutic intervention at the early stage of NIHL is critical to preserve hearing. Minocycline is a semi-synthetic derivative of tetracycline and has been shown to have otoprotective effects in ototoxic drug-induced hearing impairment, however, whether minocycline can protect against NIHL has not been investigated. The present study demonstrated elevated ABR (auditory brainstem response) thresholds and outer hair cell loss following traumatic noise exposure, which was mitigated by intraperitoneal administration of minocycline (45mg/kg/d) for 5 consecutive days. In conclusion, the present study demonstrated that minocycline, a clinically approved drug with a good safety profile, can attenuate NIHL in rats and may potentially be used for treatment of hearing loss in clinic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Major rapid weight loss induces changes in cardiac repolarization

    DEFF Research Database (Denmark)

    Vedel-Larsen, Esben; Iepsen, Eva 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...

  6. Evidence for presynaptically silent synapses in the immature hippocampus

    International Nuclear Information System (INIS)

    Yoon, Jae Young; Choi, Sukwoo

    2017-01-01

    Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate only high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether mGluR-blockers alter

  7. 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.

  8. Protein kinase C involvement in the acetylcholine release reduction induced by amyloid-beta(25-35) aggregates on neuromuscular synapses.

    Science.gov (United States)

    Tomàs, Marta; Garcia, Neus; Santafé, Manuel M; Lanuza, Maria; Tomàs, Josep

    2009-01-01

    Using intracellular recording of the diaphragm muscle of adult rats, we have investigated the short-term functional effects of amyloid-beta (Abeta(25-35) peptide aggregates on the modulation of acetylcholine (ACh) release and the involvement of protein kinase C (PKC). The non-aggregated form of this peptide does not change the evoked and spontaneous transmitter release parameters on the neuromuscular synapse. However, the aggregated form of Abeta(25-35) acutely interferes with evoked quantal ACh release (approximately 40% reduction) when synaptic activity in the ex vivo neuromuscular preparation is maintained by low frequency (1 Hz) electrical stimulation. This effect is partially dependent on the activity of PKC that may have a permissive action. The end result of Abeta(25-35) is in opposition to the PKC-dependent maintenance effect on ACh release manifested in active synapses.

  9. Removal of area CA3 from hippocampal slices induces postsynaptic plasticity at Schaffer collateral synapses that normalizes CA1 pyramidal cell discharge.

    Science.gov (United States)

    Dumas, Theodore C; Uttaro, Michael R; Barriga, Carolina; Brinkley, Tiffany; Halavi, Maryam; Wright, Susan N; Ferrante, Michele; Evans, Rebekah C; Hawes, Sarah L; Sanders, Erin M

    2018-05-05

    Neural networks that undergo acute insults display remarkable reorganization. This injury related plasticity is thought to permit recovery of function in the face of damage that cannot be reversed. Previously, an increase in the transmission strength at Schaffer collateral to CA1 pyramidal cell synapses was observed after long-term activity reduction in organotypic hippocampal slices. Here we report that, following acute preparation of adult rat hippocampal slices and surgical removal of area CA3, input to area CA1 was reduced and Schaffer collateral synapses underwent functional strengthening. This increase in synaptic strength was limited to Schaffer collateral inputs (no alteration to temporoammonic synapses) and acted to normalize postsynaptic discharge, supporting a homeostatic or compensatory response. Short-term plasticity was not altered, but an increase in immunohistochemical labeling of GluA1 subunits was observed in the stratum radiatum (but not stratum moleculare), suggesting increased numbers of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and a postsynaptic locus of expression. Combined, these data support the idea that, in response to the reduction in presynaptic activity caused by removal of area CA3, Schaffer collateral synapses undergo a relatively rapid increase in functional efficacy likely supported by insertion of more AMPARs, which maintains postsynaptic excitability in CA1 pyramidal neurons. This novel fast compensatory plasticity exhibits properties that would allow it to maintain optimal network activity levels in the hippocampus, a brain structure lauded for its ongoing experience-dependent malleability. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. 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...... mediate cell-cell adhesion through homophilic interactions and bind to growth factors, growth factor receptors, glutamate receptors, other CAMs, and components of the extracellular matrix. Intracellularly, NCAM-type proteins interact with various cytoskeletal proteins and regulators of intracellular...... 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...

  11. 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.

  12. [Natural history of occupational hearing loss induced by noise].

    Science.gov (United States)

    de Almeida, S I; Albernaz, P L; Zaia, P A; Xavier, O G; Karazawa, E H

    2000-01-01

    To evaluate the clinical and audiometric characteristics of occupational hearing loss induced by noise, according to age and time of exposition in years. 222 patients with occupational sensorineural hearing loss induced by noise were studied retrospectively, correlating the auditive clinical claims, alterations of audiometric thresholds at frequencies of 250 Hz to 8000 Hz, speech discrimination indicator with age and time of exposure. As a control group were used the audiometric threshold of a population of same medium age, without morbid antecedents of hearing illness, as preconized by ISO 1999 (1990). The group were divided into subgroups and three decades of exposure were analyzed. It was verified that the clinical claims of hipoacusia increases according to the age and time of exposure. The frequency of tinnitus is constant. The audiometric thresholds in the second decade of exposure present variations that depend on the age. The several audiometric curves are parallel, but they are not horizontal. The worst thresholds were found in the high frequencies from 3000 Hz to 8000 Hz, as a clinical and physiopathological consequences of the commitment of basal areas of cochlea. The speech discrimination showed to be worst according to the increase of age and time of exposure. Patients with hearing loss disacusia induced by occupational noise present characteristic audiometric thresholds that vary according to age and time of exposure to noise. These characteristics defined and resumed in audiometric curves can constitute a standard of comparison, evaluation and control for exposed populations.

  13. 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.

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

    Science.gov (United States)

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    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.

  15. 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.

  16. Chlorophyll loss associated with heat-induced senescence in bentgrass.

    Science.gov (United States)

    Jespersen, David; Zhang, Jing; Huang, Bingru

    2016-08-01

    Heat stress-induced leaf senescence is characterized by the loss of chlorophyll from leaf tissues. The objectives of this study were to examine genetic variations in the level of heat-induced leaf senescence in hybrids of colonial (Agrostis capillaris)×creeping bentgrass (Agrostis stolonifera) contrasting in heat tolerance, and determine whether loss of leaf chlorophyll during heat-induced leaf senescence was due to suppressed chlorophyll synthesis and/or accelerated chlorophyll degradation in the cool-season perennial grass species. Plants of two hybrid backcross genotypes ('ColxCB169' and 'ColxCB190') were exposed to heat stress (38/33°C, day/night) for 28 d in growth chambers. The analysis of turf quality, membrane stability, photochemical efficiency, and chlorophyll content demonstrated significant variations in the level of leaf senescence induced by heat stress between the two genotypes, with ColXCB169 exhibiting a lesser degree of decline in chlorophyll content, photochemical efficiency and membrane stability than ColXCB190. The assays of enzymatic activity or gene expression of several major chlorophyll-synthesizing (porphobilinogen deaminase, Mg-chelatase, protochlorophyllide-reductase) and chlorophyll-degrading enzymes (chlorophyllase, pheophytinase, and chlorophyll-degrading peroxidase) indicated heat-induced decline in leaf chlorophyll content was mainly due to accelerated chlorophyll degradation, as manifested by increased gene expression levels of chlorophyllase and pheophytinase, and the activity of pheophytinase (PPH), while chlorophyll-synthesizing genes and enzymatic activities were not differentially altered by heat stress in the two genotypes. The analysis of heat-induced leaf senescence of pph mutants of Arabidopsis further confirmed that PPH could be one enzymes that plays key roles in regulating heat-accelerated chlorophyll degradation. Further research on enzymes responsible in part for the loss of chlorophyll during heat-induced

  17. 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.

  18. Zinc at glutamatergic synapses.

    Science.gov (United States)

    Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

    2009-01-12

    It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

  19. Chaos of radiative heat-loss-induced flame front instability.

    Science.gov (United States)

    Kinugawa, Hikaru; Ueda, Kazuhiro; Gotoda, Hiroshi

    2016-03-01

    We are intensively studying the chaos via the period-doubling bifurcation cascade in radiative heat-loss-induced flame front instability by analytical methods based on dynamical systems theory and complex networks. Significant changes in flame front dynamics in the chaotic region, which cannot be seen in the bifurcation diagrams, were successfully extracted from recurrence quantification analysis and nonlinear forecasting and from the network entropy. The temporal dynamics of the fuel concentration in the well-developed chaotic region is much more complicated than that of the flame front temperature. It exhibits self-affinity as a result of the scale-free structure in the constructed visibility graph.

  20. Account for fire induced loss of room cooling

    International Nuclear Information System (INIS)

    He Wei; Lin, J.

    2005-01-01

    A recent fire PRA, which evaluated equipment operability in relation to its ambient temperature, revealed that the operational temperature limit assumed in the internal events PRA was exceeded in selected fire scenarios. For the plant assessed, the environmental qualification (EQ) temperature (between 100 degree F to 120 degree F) was adopted as the operational temperature limit for internal events PRA, which was exceeded based on stringent criteria used in the internal events PRA. Using the HVAC dependency assumptions modeled in the internal events PRA and the EQ temperatures as the equipment failure limits, six fire areas were shown to have significant fire-induced risk largely because of the loss of cooling to certain areas and/or heat addition from a challenging fire. These fire areas included Control Room (122 A), Relay Room (100 A), 4 kV Switchgear Room (64 A), 480 V Switchgear Room (84 A), Electrical Penetration Area (78C), and Auxiliary Equipment Area (84B). This is due to 1) loss of HVAC caused by closing of the fire damper and other isolation mechanisms at the fire location, 2) loss of HVAC caused by closing of the fire damper and other isolation mechanisms outside the fire location, and 3) direct heat addition introduced by the fire. In comparison, it appeared that the fire PRA performed for IPEEE (PSE and G, 1996), and the majority of the IPEEE fire analyses, accounted for heat addition and HVAC loss associated with the fire location. However, potential accident scenarios caused by the fire-induced loss of HVAC outside the fire location were not carefully reviewed. This paper discusses modeling of the fire-induced loss of HVAC, equipment reliability at elevated temperatures, aggregated failure rates used in the fire PRA, and impact of HVAC failure on mitigation capability. Sensitivity analyses were performed for elevated ambient temperatures and the results show that the CDF/LERF are sensitive to: 1) temperature differences between the actual operating

  1. 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...

  2. Tetrahydroxystilbene Glucoside Effectively Prevents Apoptosis Induced Hair Loss

    Directory of Open Access Journals (Sweden)

    Lulu Chen

    2018-01-01

    Full Text Available The effect of Polygonum multiflorum against hair loss has been widely recognized. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG is the main component of Polygonum multiflorum; however, its role in hair regeneration has not been established. To evaluate the hair growth-promoting activity of TSG, depilated C57BL/6J mice were topically treated with normal saline, TSG, Pifithrin-α, Minoxidil for 2 weeks. In this study, we identified that p53, Caspase-3, Active Caspase-3, and Caspase-9 were obviously upregulated in the skin of human and mice with hair loss by western blot analysis. Depilated mice treated with TSG showed markedly hair regrowth. TUNEL+ cells were also reduced in mice with TSG. These changes were accompanied with inhibition of Fas, p53, Bax, Active Caspase-3, and Procaspase-9 activities. These results demonstrated that TSG exerts great hair regrowth effect on hair loss, which was probably mediated by inhibition of p53, Fas, and Bax induced apoptosis.

  3. 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.

  4. Toluene-induced hearing loss in the guinea pig.

    Science.gov (United States)

    Waniusiow, Delphine; Campo, Pierre; Venet, Thomas; Cossec, Benoît; Cosnier, Frédéric; Beydon, Dominique; Rieger, Benoît; Burgart, Manuella; Ferrari, Luc; Parietti-Winkler, Cécile

    2009-10-01

    Toluene is a high-production industrial solvent, which can disrupt the auditory system in rats. However, toluene-induced hearing loss is species dependent. For instance, despite long-lasting exposures to high concentrations of aromatic solvent, no study has yet succeeded in causing convincing hearing loss in the guinea pig. This latter species can be characterized by two metabolic particularities: a high amount of hepatic cytochrome P-450s (P-450s) and a high concentration of glutathione in the cochlea. It is therefore likely that the efficiency of both the hepatic and cochlear metabolisms plays a key role in the innocuousness of the hearing of guinea pigs to exposure to solvent. The present study was carried out to test the auditory resistance to toluene in glutathione-depleted guinea pigs whose the P-450 activity was partly inhibited. To this end, animals on a low-protein diet received a general P-450 inhibitor, namely SKF525-A. Meanwhile, they were exposed to 1750 ppm toluene for 4 weeks, 5 days/week, 6 h/day. Auditory function was tested by electrocochleography and completed by histological analyses. For the first time, a significant toluene-induced hearing loss was provoked in the P-450-inhibited guinea pigs. However, the ototoxic process caused by the solvent exposure was different from that observed in the rat. Only the stria vascularis and the spiral fibers were disrupted in the apical coil of the cochlea. The protective mechanisms developed by guinea pigs are discussed in the present publication.

  5. Clozapine-induced dysphagia with secondary substantial weight loss.

    Science.gov (United States)

    Osman, Mugtaba; Devadas, Vekneswaran

    2016-08-19

    Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight. 2016 BMJ Publishing Group Ltd.

  6. 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

  7. 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

  8. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2017-10-01

    Assessment of synapse regeneration : Twelve week old CBA/CaJ mice are exposed to a moderate noise that destroys synapses on inner hair cells (IHCs) but spares...result of excitotoxic trauma to cochlear synapses due to glutamate released from the hair cells . Excitotoxic trauma damages the postsynaptic cell by...components ............................................. 12 d) Quantitative analysis of effects of neurotrophic factors on synapse regeneration in vitro

  9. Examination of Icing Induced Loss of Control and Its Mitigations

    Science.gov (United States)

    Reehorst, Andrew L.; Addy, Harold E., Jr.; Colantonio, Renato O.

    2010-01-01

    Factors external to the aircraft are often a significant causal factor in loss of control (LOC) accidents. In today s aviation world, very few accidents stem from a single cause and typically have a number of causal factors that culminate in a LOC accident. Very often the "trigger" that initiates an accident sequence is an external environment factor. In a recent NASA statistical analysis of LOC accidents, aircraft icing was shown to be the most common external environmental LOC causal factor for scheduled operations. When investigating LOC accident or incidents aircraft icing causal factors can be categorized into groups of 1) in-flight encounter with super-cooled liquid water clouds, 2) take-off with ice contamination, or 3) in-flight encounter with high concentrations of ice crystals. As with other flight hazards, icing induced LOC accidents can be prevented through avoidance, detection, and recovery mitigations. For icing hazards, avoidance can take the form of avoiding flight into icing conditions or avoiding the hazard of icing by making the aircraft tolerant to icing conditions. Icing detection mitigations can take the form of detecting icing conditions or detecting early performance degradation caused by icing. Recovery from icing induced LOC requires flight crew or automated systems capable of accounting for reduced aircraft performance and degraded control authority during the recovery maneuvers. In this report we review the icing induced LOC accident mitigations defined in a recent LOC study and for each mitigation describe a research topic required to enable or strengthen the mitigation. Many of these research topics are already included in ongoing or planned NASA icing research activities or are being addressed by members of the icing research community. These research activities are described and the status of the ongoing or planned research to address the technology needs is discussed

  10. Stabilization of memory States by stochastic facilitating synapses.

    Science.gov (United States)

    Miller, Paul

    2013-12-06

    Bistability within a small neural circuit can arise through an appropriate strength of excitatory recurrent feedback. The stability of a state of neural activity, measured by the mean dwelling time before a noise-induced transition to another state, depends on the neural firing-rate curves, the net strength of excitatory feedback, the statistics of spike times, and increases exponentially with the number of equivalent neurons in the circuit. Here, we show that such stability is greatly enhanced by synaptic facilitation and reduced by synaptic depression. We take into account the alteration in times of synaptic vesicle release, by calculating distributions of inter-release intervals of a synapse, which differ from the distribution of its incoming interspike intervals when the synapse is dynamic. In particular, release intervals produced by a Poisson spike train have a coefficient of variation greater than one when synapses are probabilistic and facilitating, whereas the coefficient of variation is less than one when synapses are depressing. However, in spite of the increased variability in postsynaptic input produced by facilitating synapses, their dominant effect is reduced synaptic efficacy at low input rates compared to high rates, which increases the curvature of neural input-output functions, leading to wider regions of bistability in parameter space and enhanced lifetimes of memory states. Our results are based on analytic methods with approximate formulae and bolstered by simulations of both Poisson processes and of circuits of noisy spiking model neurons.

  11. 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.

  12. Stochastic Synapses Enable Efficient Brain-Inspired Learning Machines

    Science.gov (United States)

    Neftci, Emre O.; Pedroni, Bruno U.; Joshi, Siddharth; Al-Shedivat, Maruan; Cauwenberghs, Gert

    2016-01-01

    Recent studies have shown that synaptic unreliability is a robust and sufficient mechanism for inducing the stochasticity observed in cortex. Here, we introduce Synaptic Sampling Machines (S2Ms), a class of neural network models that uses synaptic stochasticity as a means to Monte Carlo sampling and unsupervised learning. Similar to the original formulation of Boltzmann machines, these models can be viewed as a stochastic counterpart of Hopfield networks, but where stochasticity is induced by a random mask over the connections. Synaptic stochasticity plays the dual role of an efficient mechanism for sampling, and a regularizer during learning akin to DropConnect. A local synaptic plasticity rule implementing an event-driven form of contrastive divergence enables the learning of generative models in an on-line fashion. S2Ms perform equally well using discrete-timed artificial units (as in Hopfield networks) or continuous-timed leaky integrate and fire neurons. The learned representations are remarkably sparse and robust to reductions in bit precision and synapse pruning: removal of more than 75% of the weakest connections followed by cursory re-learning causes a negligible performance loss on benchmark classification tasks. The spiking neuron-based S2Ms outperform existing spike-based unsupervised learners, while potentially offering substantial advantages in terms of power and complexity, and are thus promising models for on-line learning in brain-inspired hardware. PMID:27445650

  13. Fine structure of synapses on dendritic spines

    Directory of Open Access Journals (Sweden)

    Michael eFrotscher

    2014-09-01

    Full Text Available Camillo Golgi’s Reazione Nera led to the discovery of dendritic spines, small appendages originating from dendritic shafts. With the advent of electron microscopy (EM they were identified as sites of synaptic contact. Later it was found that changes in synaptic strength were associated with changes in the shape of dendritic spines. While live-cell imaging was advantageous in monitoring the time course of such changes in spine structure, EM is still the best method for the simultaneous visualization of all cellular components, including actual synaptic contacts, at high resolution. Immunogold labeling for EM reveals the precise localization of molecules in relation to synaptic structures. Previous EM studies of spines and synapses were performed in tissue subjected to aldehyde fixation and dehydration in ethanol, which is associated with protein denaturation and tissue shrinkage. It has remained an issue to what extent fine structural details are preserved when subjecting the tissue to these procedures. In the present review, we report recent studies on the fine structure of spines and synapses using high-pressure freezing (HPF, which avoids protein denaturation by aldehydes and results in an excellent preservation of ultrastructural detail. In these studies, HPF was used to monitor subtle fine-structural changes in spine shape associated with chemically induced long-term potentiation (cLTP at identified hippocampal mossy fiber synapses. Changes in spine shape result from reorganization of the actin cytoskeleton. We report that cLTP was associated with decreased immunogold labeling for phosphorylated cofilin (p-cofilin, an actin-depolymerizing protein. Phosphorylation of cofilin renders it unable to depolymerize F-actin, which stabilizes the actin cytoskeleton. Decreased levels of p-cofilin, in turn, suggest increased actin turnover, possibly underlying the changes in spine shape associated with cLTP. The findings reviewed here establish HPF as

  14. 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

  15. MHD induced fast-ion losses on ASDEX Upgrade

    International Nuclear Information System (INIS)

    GarcIa-Munoz, M.; Fahrbach, H.-U.; Bobkov, V.; Bruedgam, M.; Guenter, S.; Igochine, V.; Lauber, Ph.; Mantsinen, M.J.; Maraschek, M.; Poli, E.; Sassenberg, K.; Tardini, G.; Zohm, H.; Pinches, S.D.; Gobbin, M.; Marrelli, L.; Martin, P.; Piovesan, P.

    2009-01-01

    A detailed knowledge of the interplay between MHD instabilities and energetic particles has been gained from direct measurements of fast-ion losses (FILs). Time-resolved energy and pitch angle measurements of FIL caused by neoclassical tearing modes (NTMs) and toroidicity-induced Alfven eigenmodes (TAEs) have been obtained using a scintillator based FIL detector. The study of FIL due to TAEs has revealed the existence of a new core-localized MHD fluctuation, the Sierpes mode. The Sierpes mode is a non-pure Alfvenic fluctuation which appears in the acoustic branch, dominating the transport of fast-ions in ICRF heated discharges. The internal structure of both TAEs and Sierpes mode has been reconstructed by means of highly resolved multichord soft x-ray measurements. A spatial overlapping of their eigenfunctions leads to a FIL coupling, showing the strong influence that a core-localized fast-ion driven MHD instability may have on the fast-ion transport. We have identified the FIL mechanisms due to NTMs as well as due to TAEs. Drift islands formed by fast-ions in particle phase space are responsible for the loss of NBI fast-ions due to NTMs. In ICRF heated plasmas, a resonance condition fulfilled by the characteristic trapped fast-ion orbit frequencies leads to a phase matching between fast-ion orbit and NTM or TAE magnetic fluctuation. The banana tips of a resonant trapped fast-ion bounce radially due to an E x B drift in the TAE case. The NTM radial bounce of the fast-ion banana tips is caused by the radial component of the perturbed magnetic field lines.

  16. 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.

  17. The balancing act of GABAergic synapse organizers.

    Science.gov (United States)

    Ko, Jaewon; Choii, Gayoung; Um, Ji Won

    2015-04-01

    GABA (γ-aminobutyric acid) is the main neurotransmitter at inhibitory synapses in the mammalian brain. It is essential for maintaining the excitation and inhibition (E/I) ratio, whose imbalance underlies various brain diseases. Emerging information about inhibitory synapse organizers provides a novel molecular framework for understanding E/I balance at the synapse, circuit, and systems levels. This review highlights recent advances in deciphering these components of the inhibitory synapse and their roles in the development, transmission, and circuit properties of inhibitory synapses. We also discuss how their dysfunction may lead to a variety of brain disorders, suggesting new therapeutic strategies based on balancing the E/I ratio.

  18. Effects of topical application of EGCG on testosterone-induced hair loss in a mouse model.

    Science.gov (United States)

    Kim, Yoon Young; Up No, Sun; Kim, Min Ho; Kim, Hei Sung; Kang, Hoon; Kim, Hyung Ok; Park, Young Min

    2011-12-01

    We investigated the effect of topical epigallocatechin-3-gallate (EGCG) on testosterone (T)-induced hair loss in mice. Marked hair loss was observed at the T-injected site, and topical EGCG significantly reduced the hair loss (P hair loss by apoptosis of the hair follicles rather than through the androgen metabolic pathway and also saw that T-induced apoptosis of hair follicles was reduced by topical EGCG. © 2011 John Wiley & Sons A/S.

  19. 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.

  20. ICRF-induced fusion product loss in TFTR

    International Nuclear Information System (INIS)

    Darrow, D.S.; Chang, C.S.; Zweben, S.J.

    1994-01-01

    When ICRF power is applied to plasmas in which there is no externally-supplied minority species, an enhanced loss of DD fusion products results. The characteristics of the loss are consistent with particles at or near the birth energy having their perpendicular velocity increased by the ICRF such that those near the passing/trapped boundary are carried into the first orbit loss cone. A rudimentary model of this process predicts losses of a magnitude similar to those seen. Predictions based upon this data for hypothetical ICRF ash removal from reactor plasmas suggest that the technique will not be energy efficient

  1. ICRF-induced DD fusion product losses in TFTR

    International Nuclear Information System (INIS)

    Darrow, D.S.; Zweben, S.J.; Budny, R.V.

    1994-10-01

    When ICRF power is applied to TFTR plasmas in which there is no externally-supplied minority species, an enhanced loss of DD fusion products results. The characteristics of the loss are consistent with particles at or near the birth energy having their perpendicular velocity increased by the ICRF such that those near the passing/trapped boundary are carried into the first orbit loss cone. A rudimentary model of this process predicts losses of a magnitude similar to those seen. Extrapolations based upon this data for hypothetical ICRF ash removal from reactor plasmas suggest that the technique will not be energy efficient

  2. Preservation of beam loss induced quenches, beam lifetime and beam loss measurements with the HERA-p beam-loss-monitor system

    International Nuclear Information System (INIS)

    Wittenburg, K.

    1994-01-01

    The beam-loss-monitors (BLMs) in the HERA-Proton-ring (HERAp) must fulfil the following requirements: They have to measure losses sensitive and fast enough to prevent the superconducting magnets from beam loss induced quenching; the dynamic range of the monitors must exceed several decades in order to measure losses during beam lifetimes of hundreds of hours as well as the much stronger losses that may quench superconducting magnets; they have to be insensitive to the synchrotron radiation of the adjacent electron-ring (HERAe); and their radiation hardness must allow a monitor-lifetime of a few years of HERA operation. These requirements are well satisfied by the HERAp-BLM-System. (orig.)

  3. 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...

  4. 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 ...

  5. Merkel disc is a serotonergic synapse in the epidermis for transmitting tactile signals in mammals.

    Science.gov (United States)

    Chang, Weipang; Kanda, Hirosato; Ikeda, Ryo; Ling, Jennifer; DeBerry, Jennifer J; Gu, Jianguo G

    2016-09-13

    The evolution of sensory systems has let mammals develop complicated tactile end organs to enable sophisticated sensory tasks, including social interaction, environmental exploration, and tactile discrimination. The Merkel disc, a main type of tactile end organ consisting of Merkel cells (MCs) and Aβ-afferent endings, are highly abundant in fingertips, touch domes, and whisker hair follicles of mammals. The Merkel disc has high tactile acuity for an object's physical features, such as texture, shape, and edges. Mechanisms underlying the tactile function of Merkel discs are obscured as to how MCs transmit tactile signals to Aβ-afferent endings leading to tactile sensations. Using mouse whisker hair follicles, we show herein that tactile stimuli are transduced by MCs into excitatory signals that trigger vesicular serotonin release from MCs. We identify that both ionotropic and metabotropic 5-hydroxytryptamine (5-HT) receptors are expressed on whisker Aβ-afferent endings and that their activation by serotonin released from MCs initiates Aβ-afferent impulses. Moreover, we demonstrate that these ionotropic and metabotropic 5-HT receptors have a synergistic effect that is critical to both electrophysiological and behavioral tactile responses. These findings elucidate that the Merkel disc is a unique serotonergic synapse located in the epidermis and plays a key role in tactile transmission. The epidermal serotonergic synapse may have important clinical implications in sensory dysfunctions, such as the loss of tactile sensitivity and tactile allodynia seen in patients who have diabetes, inflammatory diseases, and undergo chemotherapy. It may also have implications in the exaggerated tactile sensations induced by recreational drugs that act on serotoninergic synapses.

  6. Loss of Consciousness Induced by a Single Dose Flurbiprofen

    Directory of Open Access Journals (Sweden)

    Bulent Yıldız

    2012-01-01

    Full Text Available Loss of consciousness after the administration of flurbiprofen has not been reported. In this case report, we describe loss of consciousness due to the administration of one oral dosage of flurbiprofen. A 17 year-old girl without a remarkable neurologic and atopic medical history had an loss of consciousness after ingestion of flurbiprofen mg 100 mg tablet. Patient was treated successfully. This report emphasies that this complication may be seen with flurobiprofen and underlying mechanisms and therapeutic approach are discussed.

  7. 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

  8. 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

  9. Sawtooth-induced loss of runaway electrons in tokamaks

    International Nuclear Information System (INIS)

    Yan Longwen; Shi Bingren; Jiao Yiming

    2001-01-01

    A model based on banana orbit loss has been proposed to explain the sawtooth effect on the loss of the runaway electrons in tokamaks. Circulating runaway electrons can be transferred into the trapped ones due to magnetic perturbation during sawtooth crashes, then they are repelled to the limiter via toroidal precession drift with a time delay. This model may also clarify the hard X-ray oscillations correlated with the m = 2 mode and the hard X-ray bursts during outer disruptions

  10. Zonisamide-induced weight loss in schizophrenia: case series.

    Science.gov (United States)

    Yang, Jaewon; Lee, Moon-Soo; Joe, Sook-Haeng; Jung, In-Kwa; Kim, Seung-Hyun

    2010-01-01

    Weight gain and metabolic disturbances constitute bothersome problems in schizophrenic patients treated with atypical antipsychotics. Several medications, exercise regimens, and lifestyle changes have been used in attempts to ameliorate these problems. We describe 3 patients with schizophrenia who manifested distinct weight loss and reduction in waist circumference during medication with zonisamide. This report suggests that zonisamide might be associated with weight loss in patients with schizophrenia.

  11. Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent α-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization*

    Science.gov (United States)

    Wang, Hansen; Kim, Susan S.; Zhuo, Min

    2010-01-01

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of α-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome. PMID:20457613

  12. Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) receptor internalization.

    Science.gov (United States)

    Wang, Hansen; Kim, Susan S; Zhuo, Min

    2010-07-09

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

  13. Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

    Science.gov (United States)

    Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

    2018-08-01

    Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Recent progress on MHD-induced loss of D-D fusion products in TFTR

    International Nuclear Information System (INIS)

    Zweben, S.J.; Darrow, D.S.; Budny, R.V.; Cheng, C.Z.; Fredrickson, E.D.; Herrmann, H.; Mynick, H.E.; Schivell, J.

    1993-08-01

    This paper reviews the recent progress made toward understanding the MHD-induced loss of D-D fusion products which has been seen on TFTR since 1988. These measurements have been made using the ''lost alpha'' diagnostic, which is described briefly. The largest MHD- induced loss occurs with coherent 3/2 or 2/1 MHD activity (kink/tearing modes), which can cause up to ∼3--5 times the first-orbit loss at I∼1.6--1.8 MA, roughly a ∼20--30% global los of D-D fusion products. Modeling of these MHD-induced losses has progressed to the point where the basic loss mechanism can be accounted for qualitatively, but the experimental results can not yet be understood quantitatively. Several alpha loss codes are being developed to improve the quantitative comparison between experiment and theory

  15. 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

    The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome...... 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...... 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...

  16. 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.

  17. Atom-loss-induced quantum optical bi-stability switch

    International Nuclear Information System (INIS)

    Wu Bao-Jun; Cui Fu-Cheng

    2012-01-01

    We investigate the nonlinear dynamics of a system composed of a cigar-shaped Bose—Einstein condensate and an optical cavity with the two sides coupled dispersively. By adopting discrete-mode approximation for the condensate, taking atom loss as a necessary part of the model to analyze the evolution of the system, while using trial and error method to find out steady states of the system as a reference, numerical simulation demonstrates that with a constant pump, atom loss will trigger a quantum optical bi-stability switch, which predicts a new interesting phenomenon for experiments to verify

  18. Use of Otoacoustic emissions in noise induced hearing loss prevention

    CSIR Research Space (South Africa)

    Edwards, A

    2010-10-01

    Full Text Available in laboratory- main clinical use on identification of hearing loss in newborn babies • Clinically sensitive tool for assessing NIHL and the outer hair cells (OHC) • repeatable results • identify cochlear damage before evidenced on an audiogram – normal... audiogram but evidence of OHC loss • Feasible method of evaluating HPD effectiveness using temporary emission shift (TES) • CSIR research developed a prediction model for Hearing Threshold Levels Copy of dancing hair cell.wm © CSIR 2010 Slide 6...

  19. 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.

  20. 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 ...

  1. 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.

  2. 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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    AIMS: To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD) over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and...

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

    Science.gov (United States)

    Mukherjee, Nabanita; Pal Choudhuri, Shreoshi; Delay, Rona J.

    2017-01-01

    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. PMID:28950008

  5. 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.

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

    Science.gov (United States)

    Mukherjee, Nabanita; Pal Choudhuri, Shreoshi; Delay, Rona J; Delay, Eugene R

    2017-01-01

    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.

  7. Presynaptic proteoglycans: sweet organizers of synapse development.

    Science.gov (United States)

    Song, Yoo Sung; Kim, Eunjoon

    2013-08-21

    Synaptic adhesion molecules control neuronal synapse development. In this issue of Neuron, Siddiqui et al. (2013) and de Wit et al. (2013) demonstrate that LRRTM4, a postsynaptic adhesion molecule, trans-synaptically interacts with presynaptic heparan sulfate proteoglycans (HSPGs) to promote synapse development. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. 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.

  9. Organizers of inhibitory synapses come of age.

    Science.gov (United States)

    Krueger-Burg, Dilja; Papadopoulos, Theofilos; Brose, Nils

    2017-08-01

    While the postsynaptic density of excitatory synapses is known to encompass a highly complex molecular machinery, the equivalent organizational structure of inhibitory synapses has long remained largely undefined. In recent years, however, substantial progress has been made towards identifying the full complement of organizational proteins present at inhibitory synapses, including submembranous scaffolds, intracellular signaling proteins, transsynaptic adhesion proteins, and secreted factors. Here, we summarize these findings and discuss future challenges in assigning synapse-specific functions to the newly discovered catalog of proteins, an endeavor that will depend heavily on newly developed technologies such as proximity biotinylation. Further advances are made all the more essential by growing evidence that links inhibitory synapses to psychiatric and neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Metaplasticity at CA1 Synapses by Homeostatic Control of Presynaptic Release Dynamics

    Directory of Open Access Journals (Sweden)

    Cary Soares

    2017-10-01

    Full Text Available Summary: Hebbian and homeostatic forms of plasticity operate on different timescales to regulate synaptic strength. The degree of mechanistic overlap between these processes and their mutual influence are still incompletely understood. Here, we report that homeostatic synaptic strengthening induced by prolonged network inactivity compromised the ability of CA1 synapses to exhibit LTP. This effect could not be accounted for by an obvious deficit in the postsynaptic capacity for LTP expression, since neither the fraction of silent synapses nor the ability to induce LTP by two-photon glutamate uncaging were reduced by the homeostatic process. Rather, optical quantal analysis reveals that homeostatically strengthened synapses display a reduced capacity to maintain glutamate release fidelity during repetitive stimulation, ultimately impeding the induction, and thus expression, of LTP. By regulating the short-term dynamics of glutamate release, the homeostatic process thus influences key aspects of dynamic network function and exhibits features of metaplasticity. : Several forms of synaptic plasticity operating over distinct spatiotemporal scales have been described at hippocampal synapses. Whether these distinct plasticity mechanisms interact and influence one another remains incompletely understood. Here, Soares et al. show that homeostatic plasticity induced by network silencing influences short-term release dynamics and Hebbian plasticity rules at hippocampal synapses. Keywords: synapse, LTP, homeostatic plasticity, metaplasticity, iGluSNFR

  11. 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.

  12. Radiation-induced cell death by chromatin loss

    International Nuclear Information System (INIS)

    Campbell, I.R.; Warenius, H.M.

    1989-01-01

    A model is proposed which relates reproductive death of cells caused by radiation to loss of chromatin at cell division. This loss of chromatin can occur through chromosomal deletions or through the formation of asymmetrical chromosomal exchanges. It is proposed that smaller doses of radiation produce fewer chromatin breaks, which are more likely to be accurately repaired, compared with larger doses. Consequently, smaller doses of radiation are less efficient in causing cell death, leading to a shoulder on the cell survival curve. Experimental evidence supports this model, and the fit between the derived formula and experimental cell survival curves is good. The derived formula approximates to the linear-quadratic equation at low doses of radiation. (author)

  13. 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

  14. 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.

  15. Novel method of evaluating miners at risk for noise-induced hearing loss

    CSIR Research Space (South Africa)

    Edwards, AL

    2010-08-31

    Full Text Available Noise-induced hearing loss (NIHL) negatively affects the quality of life of mine employees and costs mining companies large amounts in compensation claims. The prevention of NIHL requires early identification and recent evidence about the ability...

  16. 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...

  17. Mechanism for Prenatal LPS-Induced DA Neuron Loss

    Science.gov (United States)

    2005-03-01

    Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chan- 26. drasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson Yurek DM, Fletcher- Tumer A...diethylstilbestrol-induced cancers . Ann. N. Y. Acad. Sci. Capobianco, L., Battaglia, G., De Blasi, A., Nicoletti, F., Paparelli, 983, 161-169. A., 2004

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

    OpenAIRE

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

    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 ...

  19. Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.

    Science.gov (United States)

    Shin, Angela H; Thayer, Stanley A

    2013-05-01

    Human immunodeficiency virus (HIV) infection of the CNS produces dendritic damage that correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). HIV-induced neurotoxicity results in part from viral proteins shed from infected cells, including the HIV transactivator of transcription (Tat). We previously showed that Tat binds to the low density lipoprotein receptor-related protein (LRP), resulting in overactivation of NMDA receptors, activation of the ubiquitin-proteasome pathway, and subsequent loss of postsynaptic densities. Here, we show that Tat also induces a loss of presynaptic terminals. The number of presynaptic terminals was quantified using confocal imaging of synaptophysin fused to green fluorescent protein (Syn-GFP). Tat-induced loss of presynaptic terminals was secondary to excitatory postsynaptic mechanisms because treatment with an LRP antagonist or an NMDA receptor antagonist inhibited this loss. Treatment with nutlin-3, an E3 ligase inhibitor, prevented Tat-induced loss of presynaptic terminals. These data suggest that Tat-induced loss of presynaptic terminals is a consequence of excitotoxic postsynaptic activity. We previously found that ifenprodil, an NR2B subunit-selective NMDA receptor antagonist, induced recovery of postsynaptic densities. Here we show that Tat-induced loss of presynaptic terminals was reversed by ifenprodil treatment. Thus, Tat-induced loss of presynaptic terminals is reversible, and this recovery can be initiated by inhibiting a subset of postsynaptic NMDA receptors. Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. 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.

  1. Fast-ion losses induced by ACs and TAEs in the ASDEX Upgrade tokamak

    NARCIS (Netherlands)

    M. García-Muñoz,; Hicks, N.; van Voornveld, R.; Classen, I.G.J.; Bilato, R.; Bobkov, V.; Brambilla, M.; Bruedgam, M.; Fahrbach, H. U.; Igochine, V.; Jaemsae, S.; Maraschek, M.; Sassenberg, K.

    2010-01-01

    The phase-space of convective and diffusive fast-ion losses induced by shear Alfven eigenmodes has been characterized in the ASDEX Upgrade tokamak. Time-resolved energy and pitch-angle measurements of fast-ion losses correlated in frequency and phase with toroidal Alfven eigenmodes (TAEs) and Alfven

  2. Fast-ion losses induced by ACs and TAEs in the ASDEX Upgrade tokamak

    NARCIS (Netherlands)

    García-Munoz, M.; Hicks, N.; Voornveld, van R.; Classen, I.G.J.; Bilato, R.; Bobkov, V.; Brambilla, M.; Bruedgam, M.; Fahrbach, H. -U.; Igochine, V.; Jaemsae, S.; Maraschek, M.; Sassenberg, K.

    2010-01-01

    The phase-space of convective and diffusive fast-ion losses induced by shear Alfv´en eigenmodes has been characterized in the ASDEX Upgrade tokamak. Time-resolved energy and pitch-angle measurements of fast-ion losses correlated in frequency and phase with toroidal Alfv´en eigenmodes (TAEs) and

  3. Pitch and Loudness from Tinnitus in Individuals with Noise-induced Hearing Loss

    Directory of Open Access Journals (Sweden)

    Flores, Leticia Sousa

    2015-08-01

    Full Text Available Introduction Tinnitus is one of the symptoms that affects individuals suffering from noise induced hearing loss. This condition can be disabling, leading the affected individual to turn away from work. Objective This literature review aims to analyze the possible association between gender and tinnitus pitch and loudness, the degree of hearing loss and the frequencies affected in subjects with noise-induced hearing loss. Methods This contemporary cohort study was conducted through a cross-sectional analysis. The study sample consisted of adults with unilateral or bilateral tinnitus, who had been diagnosed with noise-induced hearing loss. The patients under analysis underwent an otorhinolaryngological evaluation, pure tone audiometry, and acuphenometry. Results The study included 33 subjects with noise-induced hearing loss diagnoses, of which 22 (66.7% were men. Authors observed no statistical difference between gender and loudness/pitch tinnitus and loudness/pitch in subjects with bilateral tinnitus. Authors found an inverse relation between tinnitus loudness with intensity greater hearing threshold and the average of the thresholds and the grade of hearing loss. The tinnitus pitch showed no association with higher frequency of hearing threshold. Conclusion Data analysis shows that, among the individuals evaluated, the greater the hearing loss, the lower the loudness of tinnitus. We did not observe an association between hearing loss and tinnitus pitch.

  4. 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

  5. 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.

  6. Natural killer cell signal integration balances synapse symmetry and migration.

    Directory of Open Access Journals (Sweden)

    Fiona J Culley

    2009-07-01

    Full Text Available Natural killer (NK cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.

  7. Mechanism for Prenatal LPS-Induced DA Neuron Loss

    Science.gov (United States)

    2006-09-01

    Neurol 355:479–489. rooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ (1999) Paraquat elicited neurobehavioral syndrome caused by do...Stadler, J., Chandran, J., Klinefelter , G. R., Blackstone, C., and Cookson, M. R. (2003) J. Biol. Chem. 278, 36588–36595 4. Macedo, M. G., Anar, B...fluctuations Reserpine induced a parkinsonism-like syndrome in some PROGRESSION IN PD 241 Table 2. Comparison of Human PD Characteristics With Animal Models

  8. 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

  9. Transitory endolymph leakage induced hearing loss and tinnitus: depolarization, biphasic shortening and loss of electromotility of outer hair cells

    Science.gov (United States)

    Zenner, H. P.; Reuter, G.; Zimmermann, U.; Gitter, A. H.; Fermin, C.; LePage, E. L.

    1994-01-01

    There are types of deafness and tinnitus in which ruptures or massive changes in the ionic permeability of the membranes lining the endolymphatic space [e.g., of the reticular lamina (RL)] are believed to allow potassium-rich endolymph to deluge the low [K+] perilymphatic fluid (e.g., in the small spaces of Nuel). This would result in a K+ intoxication of sensory and neural structures. Acute attacks of Meniere's disease have been suggested to be an important example for this event. The present study investigated the effects of transiently elevated [K+] due to the addition of artificial endolymph to the basolateral cell surface of outer hair cells (OHC) in replicating endolymph-induced K+ intoxication of the perilymph in the small spaces of Nuel. The influence of K+ intoxication of the basolateral OHC cell surface on the transduction was then examined. Intoxication resulted in an inhibition of the physiological repolarizing K+ efflux from hair cells. This induced unwanted depolarizations of the hair cells, interfering with mechanoelectrical transduction. A pathological longitudinal OHC shortening was also found, with subsequent compression of the organ of Corti possibly influencing the micromechanics of the mechanically active OHC. Both micromechanical and electrophysiological alterations are proposed to contribute to endolymph leakage induced attacks of deafness and possibly also to tinnitus. Moreover, repeated or long-lasting K+ intoxications of OHC resulted in a chronic and complete loss of OHC motility. This is suggested to be a pathophysiological basis in some patients with chronic hearing loss resulting from Meniere's syndrome.

  10. 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.

  11. Serum drug level-related sodium valproate-induced hair loss.

    Science.gov (United States)

    Ramakrishnappa, Suresh K; Belhekar, Mahesh N

    2013-01-01

    Sodium valproate is a well-established treatment in epilepsy and mood disorders. Its utility is compromised by its adverse effects such as tremor, weight gain, hair loss, and liver dysfunction. Hair loss may occur when drug is used in higher dose. Drug-induced hair loss is diffused and non-scarring, which is reversible upon withdrawal. But there are no case reports showing relation between serum levels of valproate and occurrence of hair loss. So we took interest in reporting this case report.

  12. Economic networks: Heterogeneity-induced vulnerability and loss of synchronization

    Science.gov (United States)

    Colon, Célian; Ghil, Michael

    2017-12-01

    Interconnected systems are prone to propagation of disturbances, which can undermine their resilience to external perturbations. Propagation dynamics can clearly be affected by potential time delays in the underlying processes. We investigate how such delays influence the resilience of production networks facing disruption of supply. Interdependencies between economic agents are modeled using systems of Boolean delay equations (BDEs); doing so allows us to introduce heterogeneity in production delays and in inventories. Complex network topologies are considered that reproduce realistic economic features, including a network of networks. Perturbations that would otherwise vanish can, because of delay heterogeneity, amplify and lead to permanent disruptions. This phenomenon is enabled by the interactions between short cyclic structures. Difference in delays between two interacting, and otherwise resilient, structures can in turn lead to loss of synchronization in damage propagation and thus prevent recovery. Finally, this study also shows that BDEs on complex networks can lead to metastable relaxation oscillations, which are damped out in one part of a network while moving on to another part.

  13. 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.

  14. 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

  15. 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.

  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. The biochemical anatomy of cortical inhibitory synapses.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Heller

    Full Text Available Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell-scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain.

  18. Memory Synapses Are Defined by Distinct Molecular Complexes: A Proposal.

    Science.gov (United States)

    Sossin, Wayne S

    2018-01-01

    Synapses are diverse in form and function. While there are strong evidential and theoretical reasons for believing that memories are stored at synapses, the concept of a specialized "memory synapse" is rarely discussed. Here, we review the evidence that memories are stored at the synapse and consider the opposing possibilities. We argue that if memories are stored in an active fashion at synapses, then these memory synapses must have distinct molecular complexes that distinguish them from other synapses. In particular, examples from Aplysia sensory-motor neuron synapses and synapses on defined engram neurons in rodent models are discussed. Specific hypotheses for molecular complexes that define memory synapses are presented, including persistently active kinases, transmitter receptor complexes and trans-synaptic adhesion proteins.

  19. Communication, the centrosome and the immunological synapse.

    Science.gov (United States)

    Stinchcombe, Jane C; Griffiths, Gillian M

    2014-09-05

    Recent findings on the behaviour of the centrosome at the immunological synapse suggest a critical role for centrosome polarization in controlling the communication between immune cells required to generate an effective immune response. The features observed at the immunological synapse show parallels to centrosome (basal body) polarization seen in cilia and flagella, and the cellular communication that is now known to occur at all of these sites.

  20. Diversity in immunological synapse structure

    Science.gov (United States)

    Thauland, Timothy J; Parker, David C

    2010-01-01

    Immunological synapses (ISs) are formed at the T cell–antigen-presenting cell (APC) interface during antigen recognition, and play a central role in T-cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T-cell receptor (TCR)–peptide major histocompatibility complex (pMHC) interactions. Although the structure of these ‘classical’ ISs has been the subject of intense study, non-classical ISs have also been observed under a variety of conditions. Multifocal ISs, characterized by adhesion molecules dispersed among numerous small accumulations of TCR–pMHC, and motile ‘immunological kinapses’ have both been described. In this review, we discuss the conditions under which non-classical ISs are formed. Specifically, we explore the profound effect that the phenotypes of both T cells and APCs have on IS structure. We also comment on the role that IS structure may play in T-cell function. PMID:21039474

  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. 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.

  3. 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.

  4. Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

    Science.gov (United States)

    Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

    2016-01-01

    Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro

  5. Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice

    Directory of Open Access Journals (Sweden)

    Xiaolong Fu

    2016-01-01

    Full Text Available MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.

  6. Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2

    Directory of Open Access Journals (Sweden)

    Elodie De Bruyckere

    2018-04-01

    Full Text Available Structural and functional plasticity of synapses are critical neuronal mechanisms underlying learning and memory. While activity-dependent regulation of synaptic strength has been extensively studied, much less is known about the transcriptional control of synapse maintenance and plasticity. Hippocampal mossy fiber (MF synapses connect dentate granule cells to CA3 pyramidal neurons and are important for spatial memory formation and consolidation. The transcription factor Bcl11b/Ctip2 is expressed in dentate granule cells and required for postnatal hippocampal development. Ablation of Bcl11b/Ctip2 in the adult hippocampus results in impaired adult neurogenesis and spatial memory. The molecular mechanisms underlying the behavioral impairment remained unclear. Here we show that selective deletion of Bcl11b/Ctip2 in the adult mouse hippocampus leads to a rapid loss of excitatory synapses in CA3 as well as reduced ultrastructural complexity of remaining mossy fiber boutons (MFBs. Moreover, a dramatic decline of long-term potentiation (LTP of the dentate gyrus-CA3 (DG-CA3 projection is caused by adult loss of Bcl11b/Ctip2. Differential transcriptomics revealed the deregulation of genes associated with synaptic transmission in mutants. Together, our data suggest Bcl11b/Ctip2 to regulate maintenance and function of MF synapses in the adult hippocampus.

  7. Low-loss metamaterial electromagnetically induced transparency based on electric toroidal dipolar response

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hai-ming; Liu, Shao-bin, E-mail: lsb@nuaa.edu.cn; Liu, Si-yuan; Ding, Guo-wen; Yang, Hua; Yu, Zhi-yang; Zhang, Hai-feng [Key Laboratory of Radar Imaging and Microwave Photonics, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016 (China); Wang, Shen-yun [Research Center of Applied Electromagnetic, Nanjing University of Information Science and Technology, Nanjing, 210044 (China)

    2015-02-23

    In this paper, a low-loss and high transmission analogy of electromagnetically induced transparency based on electric toroidal dipolar response is numerically and experimentally demonstrated. It is obtained by the excitation of the low-loss electric toroidal dipolar response, which confines the magnetic field inside a dielectric substrate with toroidal geometry. The metamaterial electromagnetically induced transparency (EIT) structure is composed of the cut wire and asymmetric split-ring resonators. The transmission level is as high as 0.88, and the radiation loss is greatly suppressed, which can be proved by the surface currents distributions, the magnetic field distributions, and the imaginary parts of the effective permeability and permittivity. It offers an effective way to produce low-loss and high transmission metamaterial EIT.

  8. 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...

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Metidieri, Mirella Melo

    2013-04-01

    Full Text Available 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.

  11. 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.

  12. 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.

  13. Numerical simulations of fast ion loss measurements induced by magnetic islands in the ASDEX Upgrade tokamak

    International Nuclear Information System (INIS)

    Gobbin, M.; Marrelli, L.; Martin, P.; Fahrbach, H.U.; Garcia-Munoz, M.; Guenter, S.; White, R.B.

    2009-01-01

    A test particle approach, implemented with the Hamiltonian code ORBIT, is used to simulate measurements of fast ion losses induced by magnetic islands in the ASDEX Upgrade tokamak. In particular, the numerical simulations reproduce the toroidal localization of losses and the lost ions pitch angle and energy distribution experimentally measured with the fast ion losses detector (FILD) in the presence of a neoclassical tearing mode (NTM). The simulated NTM induced losses occurring on time scales longer than 100 μs are composed of mainly trapped or barely passing particles, consistently with the slow decay of the experimental signal from one FILD channel after the beam switch-off. The numerical simulations have been performed by taking into account the D-shaped plasma geometry, the collision mechanisms, the losses due to ripple effects and the rotation of the mode. The radial profile of the magnetic perturbation is adjusted in order to match ECE measurements. While statistical properties of FILD measurements are rather well reproduced, the simulated total amount of losses is found to be significantly affected by edge details of the magnetic perturbation as it determines the loss mechanism.

  14. [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.

  15. 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.

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

    Science.gov (United States)

    Nørgaard, Sisse A; Sand, Fredrik W; Sørensen, Dorte B; Abelson, Klas Sp; Søndergaard, Henrik

    2018-01-01

    The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome 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 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 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 not significantly affect the induction of key disease parameters, i.e. %HbA1C and albuminuria nor result in abnormal teeth wear. In conclusion, supplementation of softened food is refining the STZ-induced diabetic mouse model significantly by reducing stress, weight loss and the number of animals sacrificed due to humane endpoints, while maintaining the key phenotypes of diabetes and nephropathy.

  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. Gastrointestinal blood loss induced by three different non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Bidlingmaier, A; Hammermaier, A; Nagyiványi, P; Pabst, G; Waitzinger, J

    1995-04-01

    A clinical study was performed on 18 healthy volunteers to compare the gastrointestinal daily blood loss induced by oral intake of three different non-steroidal anti-inflammatory drugs, lysine clonixinate (CAS 55837-30-4), ibuprofen (CAS 15687-27-1) and acetylsalicylic acid (CAS 50-78-2 ASA). For quantitative determination of gastrointestinal blood loss, autologous erythrocytes were radiolabelled in vitro with 51Cr and reinfused at study start. The amount of radioactivity excreted in faeces was measured during a placebo baseline phase of three days, a treatment phase of five days with thrice daily dosing of ASA, ibuprofen or lysine clonixinate and a subsequent wash-out phase of five days. The highest increase of mean daily blood loss over baseline was observed after treatment with ASA (+ 1.66 ml/d versus baseline). Treatment with ibuprofen led to an increase of mean daily blood loss by + 0.52 ml/d. During treatment with lysine clonixinate the mean increase of daily blood loss was +0.32 ml/d versus baseline. In the ibuprofen and lysine clonixinate treatment groups the values of mean daily blood loss decreased during the wash-out phase with respect to the verum phase, whereas the mean daily blood loss during the wash-out phase after treatment with ASA even increased in comparison to the verum phase (mean daily blood loss: +2.07 ml/d versus baseline.

  19. Fast-ion losses induced by ACs and TAEs in the ASDEX Upgrade tokamak

    International Nuclear Information System (INIS)

    GarcIa-Munoz, M.; Hicks, N.; Classen, I.G.J.; Bilato, R.; Bobkov, V.; Brambilla, M.; Bruedgam, M.; Fahrbach, H.-U.; Igochine, V.; Maraschek, M.; Sassenberg, K.; Van Voornveld, R.; Jaemsae, S.

    2010-01-01

    The phase-space of convective and diffusive fast-ion losses induced by shear Alfven eigenmodes has been characterized in the ASDEX Upgrade tokamak. Time-resolved energy and pitch-angle measurements of fast-ion losses correlated in frequency and phase with toroidal Alfven eigenmodes (TAEs) and Alfven cascades (ACs) have allowed to identify both loss mechanisms. While single ACs and TAEs eject resonant fast-ions in a convective process, the overlapping of AC and TAE spatial structures leads to a large fast-ion diffusion and loss. The threshold for diffusive fast-ion losses depends on the ion energy (gyroradius). Diffusive fast-ion losses with gyroradius ∼70 mm have been observed with a single TAE for local radial displacements of the magnetic field lines larger than ∼2 mm. Multiple frequency chirping ACs cause an enhancement of the diffusive losses. The ACs and TAEs radial structures have been reconstructed by means of cross-correlation techniques between the fast-ion loss detector and the electron cyclotron emission radiometer.

  20. Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway.

    Science.gov (United States)

    Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

    2014-02-18

    Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed. Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylation. Loss of Smad4 activated Akt pathway that resulted in upregulation of anti-apoptotic proteins, Bcl-2 and Bcl-w, and Survivin. Suppression of phosphatidylinositol-3-kinase (PI3K)/Akt pathway by LY294002 restored chemosensitivity of Smad4-deficient cells to 5-FU. Vascular endothelial growth factor-induced angiogenesis in Smad4-deficient cells might also lead to chemoresistance. Low levels of Smad4 expression in CRC tissues correlated with higher levels of Bcl-2 and Bcl-w and with poor overall survival as observed in immunohistochemical staining of tissue microarrays. Loss of Smad4 in CRC patients induces resistance to 5-FU-based therapy through activation of Akt pathway and inhibitors of this pathway may sensitise these patients to 5-FU.

  1. 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.

  2. Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions toward Clinical Reality.

    Science.gov (United States)

    Botchkarev, Vladimir A; Sharov, Andrey A

    2016-03-01

    Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy-induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. 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 ...

  4. 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...

  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. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Economic Impact of Hearing Loss and Reduction of Noise-Induced Hearing Loss in the United States.

    Science.gov (United States)

    Neitzel, Richard L; Swinburn, Tracy K; Hammer, Monica S; Eisenberg, Daniel

    2017-01-01

    Hearing loss (HL) is pervasive and debilitating, and noise-induced HL is preventable by reducing environmental noise. Lack of economic analyses of HL impacts means that prevention and treatment remain a low priority for public health and environmental investment. This article estimates the costs of HL on productivity by building on established estimates for HL prevalence and wage and employment differentials between those with and without HL. We estimate that HL affects more than 13% of the working population. Not all HL can be prevented or treated, but if the 20% of HL resulting from excessive noise exposure were prevented, the economic benefit would be substantial-we estimate a range of $58 billion to $152 billion annually, with a core estimate of $123 billion. We believe this is a conservative estimate, because consideration of additional costs of HL, including health care and special education, would likely further increase the benefits associated with HL prevention. HL is costly and warrants additional emphasis in public and environmental health programs. This study represents an important first step in valuing HL prevention-in particular, prevention of noise-induced HL-where new policies and technologies appear promising.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. Wireless synapses in bio-inspired neural networks

    Science.gov (United States)

    Jannson, Tomasz; Forrester, Thomas; Degrood, Kevin

    2009-05-01

    Wireless (virtual) synapses represent a novel approach to bio-inspired neural networks that follow the infrastructure of the biological brain, except that biological (physical) synapses are replaced by virtual ones based on cellular telephony modeling. Such synapses are of two types: intracluster synapses are based on IR wireless ones, while intercluster synapses are based on RF wireless ones. Such synapses have three unique features, atypical of conventional artificial ones: very high parallelism (close to that of the human brain), very high reconfigurability (easy to kill and to create), and very high plasticity (easy to modify or upgrade). In this paper we analyze the general concept of wireless synapses with special emphasis on RF wireless synapses. Also, biological mammalian (vertebrate) neural models are discussed for comparison, and a novel neural lensing effect is discussed in detail.

  20. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yinxi; Liu, Dan; Zhang, Huifeng; Wang, Yixin [Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, 100191 (China); Wei, Ling [Beijing Center for Physical & Chemical Analysis, Beijing 100089 (China); Liu, Yutong [School of Life Science, Beijing Normal University, Beijing 100875 (China); Liao, Jieying [Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024 (China); Gao, Hui-Ming [Model Animal Research Center of Nanjing University, Nanjing 211800 (China); Zhou, Hui, E-mail: hardhui@gmail.com [Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, 100191 (China)

    2017-05-01

    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{sup 2} induced significant loss of DA neurons. More importantly, nontoxic doses of ufCB (10 μg/cm{sup 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{sup phox}, p47{sup phox} and p40{sup phox}); secondly, ufCB was recognized by microglial surface MAC-1 receptor and consequently promoted rotenone-induced p47{sup phox} and p67{sup phox} translocation assembling active NADPH oxidase. Conclusion: ufCB and rotenone worked in synergy to activate NADPH oxidase in microglia, leading to

  2. Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice.

    Science.gov (United States)

    Bächinger, David; Horvath, Lukas; Eckhard, Andreas; Goosmann, Madeline M; Honegger, Tim; Gassmann, Max; Vogel, Johannes; Naldi, Arianne Monge

    2018-07-01

    Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish

    Science.gov (United States)

    2012-01-01

    Background Astragali Radix has been used widely for the treatment of cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide constituents of Astragali Radix (ARP) are considered as one of the major constituents contributing to the multiple pharmacological effects of this medicinal plant. The purpose of the study is to evaluate the vascular regenerative activities of ARPs in a chemically-induced blood vessel loss model in zebrafish. Methods Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1 and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish larvae were observed under the fluorescence microscope and measured quantitatively. The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR. Results Two polysaccharide fractions, P4 (50000 D 0.1 μm), isolated from Astragali Radix by ultrafiltration, produced a significant and dose-dependent recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down-regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by treatment with P4. Conclusion The present study demonstrates that P4 isolated from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis. PMID:22357377

  6. 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

  7. 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)…

  8. 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.

  9. 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)

  10. 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.

  11. Silent synapses in neuromuscular junction development.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Lanuza, Maria A; García, Neus; Besalduch, Nuria; Tomàs, Marta

    2011-01-01

    In the last few years, evidence has been found to suggest that some synaptic contacts become silent but can be functionally recruited before they completely retract during postnatal synapse elimination in muscle. The physiological mechanism of developmental synapse elimination may be better understood by studying this synapse recruitment. This Mini-Review collects previously published data and new results to propose a molecular mechanism for axonal disconnection. The mechanism is based on protein kinase C (PKC)-dependent inhibition of acetylcholine (ACh) release. PKC activity may be stimulated by a methoctramine-sensitive M2-type muscarinic receptor and by calcium inflow though P/Q- and L-type voltage-dependent calcium channels. In addition, tropomyosin-related tyrosine kinase B (trkB) receptor-mediated brain-derived neurotrophic factor (BDNF) activity may oppose the PKC-mediated ACh release depression. Thus, a balance between trkB and muscarinic pathways may contribute to the final functional suppression of some neuromuscular synapses during development. © 2010 Wiley-Liss, Inc.

  12. Neural Activity During The Formation Of A Giant Auditory Synapse

    NARCIS (Netherlands)

    M.C. Sierksma (Martijn)

    2018-01-01

    markdownabstractThe formation of synapses is a critical step in the development of the brain. During this developmental stage neural activity propagates across the brain from synapse to synapse. This activity is thought to instruct the precise, topological connectivity found in the sensory central

  13. 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.

  14. 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.

  15. 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

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

    Science.gov (United States)

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

    2013-11-20

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

    Science.gov (United States)

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

  18. Natural Disaster Induced Losses at Household Level: A Study on the Disaster Affected Migrants

    Science.gov (United States)

    Ishtiaque, A.; Nazem, N. I.; Jerin, T.

    2015-12-01

    Given its geographical location Bangladesh frequently confronts natural disasters. Disaster induced losses often obligate socio-economic dislocation from rural areas to large urban centers. After incurring what type/amount of losses people migrate is still unknown. In this paper we focus on migrants who migrated due to natural disasters. Thus, the objectives of this paper are, first, ascertaining the proportion of disaster migrants in Dhaka city; second, determining types of natural disasters which compel rural out-migration; third, assessing the resource and economic losses stem from these disasters at household level. Using the slum database (N = 4966), we select eight slums randomly with a purpose to include migrants from maximum districts available. In order to identify the proportion of disaster affected migrants a census is conducted in 407 households of those 8 slums and the result demonstrates that 18.43% of the migrants are disaster affected, which was only 5% in 1993. Out of all hydro-meteorological disasters, river bank erosion (RBE), followed by flood, drives most people out of their abode. However, unlike RBE migrants, migrants affected by flood usually return to their origin after certain period. In-depth interviews on the disaster migrants reveal that RBE claims total loss of homestead land & agricultural land while flood causes 20% and 23% loss respectively. Agricultural income decreases 96% because of RBE whereas flood victims encounter 98% decrease. People also incur 79% & 69% loss in livestock owing to RBE and flood severally. These disasters cause more than eighty percent reduction in total monthly income. Albeit RBE appears more vigorous but total economic loss is greater in flood- on average each household experiences a loss of BDT 350,555 due to flood and BDT 300,000 on account of RBE. Receiving no substantial support from community or government the affected people are compelled to migrate.

  19. 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)

  20. Validation of Noise Induced Hearing Loss Questionnaire Among Malay Sawmill Workers in Kelantan Malaysia

    OpenAIRE

    Razman, MR; Naing, L; Aziah, D; Kamarul, IM

    2010-01-01

    Exposure to excessive noise is the major avoidable cause of permanent hearing impairment. Sawmill is one of the workplaces where workers are exposed to hazardous noise level. This study was conducted to determine the reliability and validity of noise-induced hearing loss questionnaire among sawmill workers. Materials and Methods: This cross sectional study was conducted in March 2007 among 35 consented sawmill workers. A total of 40 items; 10 items for knowledge (8 areas), 20 items for attitu...

  1. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  2. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development

    Directory of Open Access Journals (Sweden)

    Josep Tomàs

    2017-05-01

    Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  3. 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.

  4. Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

    Directory of Open Access Journals (Sweden)

    Marlène Gallet

    Full Text Available ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation, but not early (commitment, negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

  5. Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

    Science.gov (United States)

    Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

    2013-01-01

    ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

  6. Noise-induced hearing loss induces loudness intolerance in a rat Active Sound Avoidance Paradigm (ASAP).

    Science.gov (United States)

    Manohar, Senthilvelan; Spoth, Jaclyn; Radziwon, Kelly; Auerbach, Benjamin D; Salvi, Richard

    2017-09-01

    Hyperacusis is a loudness hypersensitivity disorder in which moderate-intensity sounds are perceived as extremely loud, aversive and/or painful. To assess the aversive nature of sounds, we developed an Active Sound Avoidance Paradigm (ASAP) in which rats altered their place preference in a Light/Dark shuttle box in response to sound. When no sound (NS) was present, rats spent more than 95% of the time in the Dark Box versus the transparent Light Box. However, when a 60 or 90 dB SPL noise (2-20 kHz, 2-8 kHz, or 16-20 kHz bandwidth) was presented in the Dark Box, the rats'' preference for the Dark Box significantly decreased. Percent time in the dark decreased as sound intensity in the Dark Box increased from 60 dB to 90 dB SPL. Interestingly, the magnitude of the decrease was not a monotonic function of intensity for the 16-20 kHz noise and not related to the bandwidth of the 2-20 kHz and 2-8 kHz noise bands, suggesting that sound avoidance is not solely dependent on loudness but the aversive quality of the noise as well. Afterwards, we exposed the rats for 28 days to a 16-20 kHz noise at 102 dB SPL; this exposure produced a 30-40 dB permanent threshold shift at 16 and 32 kHz. Following the noise exposure, the rats were then retested on the ASAP paradigm. High-frequency hearing loss did not alter Dark Box preference in the no-sound condition. However, when the 2-20 kHz or 2-8 kHz noise was presented at 60 or 90 dB SPL, the rats avoided the Dark Box significantly more than they did before the exposure, indicating these two noise bands with energy below the region of hearing loss were perceived as more aversive. In contrast, when the 16-20 kHz noise was presented at 60 or 90 dB SPL, the rats remained in the Dark Box presumably because the high-frequency hearing loss made 16-20 kHz noise less audible and less aversive. These results indicate that when rats develop a high-frequency hearing loss, they become less tolerant of low frequency noise, i

  7. 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.

  8. 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.

  9. 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...

  10. Evidence for the involvement of 5-lipoxygenase products in ethanol-induced intestinal plasma protein loss

    International Nuclear Information System (INIS)

    Beck, I.T.; Boyd, A.J.; Dinda, P.K.

    1988-01-01

    In this study the authors investigated whether the products of 5-lipoxygenase (5-LO) were involved in the jejunal microvascular injury induced by intraluminal ethanol (ETH). A group of rabbits was given orally a selective inhibitor of 5-LO in two 10-mg doses, 24, and 2 h before the experiments. A jejunal segment was perfused with a control solution (control segment) and an adjacent segment with an ETH-containing solution (ETH-perfused segment). In a series of experiments, they measured 5-LO activity of the jejunal segments of both groups using the generation of leukotriene B 4 (LTB 4 ) as an index. In a second series of experiments, they determined the ETH-induced intraluminal protein loss, which was taken as a measure of mucosal microvascular damage. The ETH-induced increase in protein loss was significantly lower in the treated than in the untreated group. These findings suggest that products of 5-LO are involved in the ETH-induced jejunal microvascular injury

  11. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

    Science.gov (United States)

    Chung, Won-Suk; Clarke, Laura E.; Wang, Gordon X.; Stafford, Benjamin K.; Sher, Alexander; Chakraborty, Chandrani; Joung, Julia; Foo, Lynette C.; Thompson, Andrew; Chen, Chinfei; Smith, Stephen J.; Barres, Ben A.

    2013-12-01

    To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.

  12. 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.

  13. 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.

  14. 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

  15. Making of a Synapse: Recurrent Roles of Drebrin A at Excitatory Synapses Throughout Life.

    Science.gov (United States)

    Aoki, Chiye; Sherpa, Ang D

    2017-01-01

    Mature excitatory synapses are composed of more than 1500 proteins postsynaptically and hundreds more that operate presynaptically. Among them, drebrin is an F-actin-binding protein that increases noticeably during juvenile synaptogenesis. Electron microscopic analysis reveals that drebrin is highly enriched specifically on the postsynaptic side of excitatory synapses. Since dendritic spines are structures specialized for excitatory synaptic transmission, the function of drebrin was probed by analyzing the ultrastructural characteristics of dendritic spines of animals with genetic deletion of drebrin A (DAKO), the adult isoform of drebrin. Electron microscopic analyses revealed that these brains are surprisingly intact, in that axo-spinous synaptic junctions are well-formed and not significantly altered in number. This normal ultrastructure may be because drebrin E, the alternate embryonic isoform, compensates for the genetic deletion of drebrin A. However, DAKO results in the loss of homeostatic plasticity of N-methyl-D-aspartate receptors (NMDARs). The NMDAR activation-dependent trafficking of the NR2A subunit-containing NMDARs from dendritic shafts into spine head cytoplasm is greatly diminished within brains of DAKO. Conversely, within brains of wild-type rodents, spines respond to NMDAR blockade with influx of F-actin, drebrin A, and NR2A subunits of NMDARs. These observations indicate that drebrin A facilitates the trafficking of NMDAR cargos in an F-actin-dependent manner to mediate homeostatic plasticity. Analysis of the brains of transgenic mice used as models of Alzheimer's disease (AD) reveals that the loss of drebrin from dendritic spines predates the emergence of synaptic dysfunction and cognitive impairment, suggesting that this form of homeostatic plasticity contributes toward cognition. Two studies suggest that the nature of drebrin's interaction with NMDARs is dependent on the receptor's subunit composition. Drebrin A can be found co

  16. 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.

  17. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

    Science.gov (United States)

    Yuzaki, Michisuke

    2010-07-01

    Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. © The Author (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  18. 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.

  19. Suppressor of cytokine signaling 1 expression during LPS-induced inflammation and bone loss in rats

    Directory of Open Access Journals (Sweden)

    João Antonio Chaves de SOUZA

    2017-10-01

    Full Text Available Abstract This study aimed to characterize the dynamics of suppressor of cytokine signaling (SOCS1 expression in a rat model of lipopolysaccharide-induced periodontitis. Wistar rats in the experimental groups were injected three times/week with LPS from Escherichia coli on the palatal aspect of the first molars, and control animals were injected with vehicle (phosphate-buffered saline. Animals were sacrificed 7, 15, and 30 days after the first injection to analyze inflammation (stereometric analysis, bone loss (macroscopic analysis, gene expression (qRT-PCR, and protein expression/activation (Western blotting. The severity of inflammation and bone loss associated with LPS-induced periodontitis increased from day 7 to day 15, and it was sustained through day 30. Significant (p < 0.05 increases in SOCS1, RANKL, OPG, and IFN-γ gene expression were observed in the experimental group versus the control group at day 15. SOCS1 protein expression and STAT1 and NF-κB activation were increased throughout the 30-day experimental period. Gingival tissues affected by experimental periodontitis express SOCS1, indicating that this protein may potentially downregulate signaling events involved in inflammatory reactions and bone loss and thus may play a relevant role in the development and progression of periodontal disease.

  20. Prevention of noise-induced hearing loss in the Canadian military.

    Science.gov (United States)

    Pelausa, E O; Abel, S M; Simard, J; Dempsey, I

    1995-10-01

    A prospective study was undertaken to investigate the development of noise-induced hearing loss in Canadian military recruits, and to assess the effectiveness of the hearing conservation program currently in place. The participants were 134 men and women, 20 to 30 years of age, employed in four trades, three of these (infantry, artillery, and armour) associated with high noise levels. The data comprised audiometric measurements made at the time of entry and after 3 years of employment, and responses to a questionnaire mainly relating to noise exposure in the workplace and during leisure activities, and the utilization of personal hearing protective devices. The findings showed that group audiograms at entry and at the 3-year recall were characterized by a 6-kHz notch that was indicative of noise-induced hearing loss, although mean threshold values were within normal limits. By the 3-year recall, 11% of the infantry had sustained a mild-to-moderate hearing loss in the left ear, greater than 25-dB HL, that was consistent with the use of small-calibre weapons. Responses to the questionnaire indicated that, while subjects appreciated the potential benefit of wearing hearing protectors, instructions in their proper use and education on the hazards of noise exposure were poor. The results suggested methods to strengthen the existing scheme for hearing conservation to further minimize risk.

  1. 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].

  2. 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

  3. 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 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.

  4. Mitochondria and Neurotransmission: Evacuating the Synapse

    OpenAIRE

    Hollenbeck, Peter J.

    2005-01-01

    An abundance of mitochondria has been the hallmark of synapses since their first ultrastructural description 50 years ago. Mitochondria have been shown to be essential for synaptic form and function in many systems, but until recently it has not been clear exactly what role(s) they play in neurotransmission. Now, evidence from the nervous system of Drosophila identifies the specific subcellular events that are most dependent upon nearby mitochondria.

  5. Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss in rats.

    Science.gov (United States)

    Durkin, Sarah; Prendergast, Alison; Harkin, Andrew

    2008-12-12

    Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern associated with recreational use of the substituted amphetamine 3,4 methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic considering that psychiatric disorders such as depression and anxiety and responses to first line treatments for these disorders are associated with 5-HT. In this study the effects of prior exposure to MDMA on behavioural and central neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and antidepressant fluoxetine were examined in rats. Animals were administered MDMA (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine treatment groups received either acute (saline injections for 20 days followed by 3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days) drug administration. Prior exposure to MDMA resulted in an attenuation of fluoxetine-induced swimming behaviour in the modified forced swimming test (FST); a behavioural test of antidepressant action. In parallel MDMA treatment resulted in significant regional depletions of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [3H] paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss was enhanced in animals following chronic fluoxetine administration. Elimination of fluoxetine and its metabolite norfluoxetine from the brain abolished this interaction between MDMA and fluoxetine treatment. Fluoxetine administration reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in animals pre-treated with MDMA. Overall the results show that MDMA induces long-term 5-HT loss in the rodent brain and consequently diminishes behaviour and reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These results have potential clinical relevance

  6. Weight Loss and Melatonin Reduce Obesity-Induced Oxidative Damage in Rat Testis

    Directory of Open Access Journals (Sweden)

    Dogan Atilgan

    2013-01-01

    Full Text Available Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes. Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1, obesity group (Group 2, obesity + MLT group (Group 3, and weight loss group (Group 4. Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD, malondialdehyde (MDA, and protein carbonyl (PC levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system. Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P<0.05. Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P<0.05. There was no significant difference between groups in terms of mean Johnsen score (P=0.727. Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.

  7. 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.

  8. SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

    2016-01-01

    In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

  9. 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.

  10. 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.

  11. 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.

  12. Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

    Science.gov (United States)

    Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

    2017-07-01

    Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

  13. 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

  14. 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...

  15. Ca(2+) influx and neurotransmitter release at ribbon synapses.

    Science.gov (United States)

    Cho, Soyoun; von Gersdorff, Henrique

    2012-01-01

    Ca(2+) influx through voltage-gated Ca(2+) channels triggers the release of neurotransmitters at presynaptic terminals. Some sensory receptor cells in the peripheral auditory and visual systems have specialized synapses that express an electron-dense organelle called a synaptic ribbon. Like conventional synapses, ribbon synapses exhibit SNARE-mediated exocytosis, clathrin-mediated endocytosis, and short-term plasticity. However, unlike non-ribbon synapses, voltage-gated L-type Ca(2+) channel opening at ribbon synapses triggers a form of multiquantal release that can be highly synchronous. Furthermore, ribbon synapses appear to be specialized for fast and high throughput exocytosis controlled by graded membrane potential changes. Here we will discuss some of the basic aspects of synaptic transmission at different types of ribbon synapses, and we will emphasize recent evidence that auditory and retinal ribbon synapses have marked differences. This will lead us to suggest that ribbon synapses are specialized for particular operating ranges and frequencies of stimulation. We propose that different types of ribbon synapses transfer diverse rates of sensory information by expressing a particular repertoire of critical components, and by placing them at precise and strategic locations, so that a continuous supply of primed vesicles and Ca(2+) influx leads to fast, accurate, and ongoing exocytosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

    Science.gov (United States)

    Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

    2012-10-01

    Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

    Science.gov (United States)

    Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

    2016-01-01

    Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

  18. GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.

    Science.gov (United States)

    Saha, Rinki; Knapp, Stephanie; Chakraborty, Darpan; Horovitz, Omer; Albrecht, Anne; Kriebel, Martin; Kaphzan, Hanoch; Ehrlich, Ingrid; Volkmer, Hansjürgen; Richter-Levin, Gal

    2017-01-01

    Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum-BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum-BLA-LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.

  19. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  20. 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.

  1. Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

    Science.gov (United States)

    Chang, Zuoyang

    1996-11-01

    Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

  2. 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.

  3. 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.

  4. [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.

  5. Predictors of Diet-Induced Weight Loss in Overweight Adults with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Kirsten A Berk

    Full Text Available 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.192 patients with type 2 diabetes and BMI>27 kg/m2 from the outpatient diabetes clinic of the Erasmus Medical Center underwent an 8-week very low calorie diet. Baseline demographic, psychological and physiological parameters were measured and the C-index was calculated of the model with the largest explained variance of relative weight loss using backward linear regression analysis. The model was internally validated using bootstrapping techniques.Weight loss after the diet was 7.8±4.6 kg (95%CI 7.2-8.5; p<0.001 and was independently associated with the baseline variables fasting glucose (B = -0.33 (95%CI -0.49, -0.18, p = 0.001, anxiety (HADS; B = -0.22 (95%CI -0.34, -0.11, p = 0.001, numb feeling in extremities (B = 1.86 (95%CI 0.85, 2.87, p = 0.002, insulin dose (B = 0.01 (95%CI 0.00, 0.02, p = 0.014 and waist-to-hip ratio (B = 6.79 (95%CI 2.10, 11.78, p = 0.003. This model explained 25% of the variance in weight loss. The C-index of this model to predict successful (≥5% weight loss was 0.74 (95%CI 0.67-0.82, with a sensitivity of 0.93 (95% CI 0.89-0.97 and specificity of 0.29 (95% CI 0.16-0.42. When only the obese T2D patients (BMI≥30 kg/m2; n = 181 were considered, age also contributed to the model (B = 0.06 (95%CI 0.02, 0.11, p = 0.008, whereas waist-to-hip ratio did not.Diet-induced weight loss in overweight adults with T2D was predicted by five baseline parameters, which were predominantly diabetes related. However, failure seems difficult to predict. We propose to test this prediction model in future prospective diet intervention studies in patients with type 2 diabetes.

  6. 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...

  7. 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

  8. 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

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

    Science.gov (United States)

    Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun

    2018-01-01

    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. PMID:29620520

  10. 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

  11. Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

    Science.gov (United States)

    Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

    2011-09-01

    The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

  12. 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

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

    Science.gov (United States)

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

    2004-10-01

    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.

  14. Energy-efficient neuron, synapse and STDP integrated circuits.

    Science.gov (United States)

    Cruz-Albrecht, Jose M; Yung, Michael W; Srinivasa, Narayan

    2012-06-01

    Ultra-low energy biologically-inspired neuron and synapse integrated circuits are presented. The synapse includes a spike timing dependent plasticity (STDP) learning rule circuit. These circuits have been designed, fabricated and tested using a 90 nm CMOS process. Experimental measurements demonstrate proper operation. The neuron and the synapse with STDP circuits have an energy consumption of around 0.4 pJ per spike and synaptic operation respectively.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. The worker's ear: a history of noise-induced hearing loss.

    Science.gov (United States)

    Thurston, Floyd E

    2013-03-01

    Hearing loss afflicts millions of people throughout the world, and many of those millions are workers who have been exposed to excessive noise. People have always been surrounded by a variety of sounds in their environments, but the invention of gunpowder and the Industrial Revolution introduced new sounds of greater intensity than ever before. It is only within the past 40 years that serious efforts to reduce excessive noise at work sites have been initiated. In the latter half of the 20th century, many governments imposed regulations to limit workers' exposure to loud sounds. Because of this recent action, some people may believe that the recognition of occupational noise-induced hearing loss (NIHL) is relatively new. However, a review of selected historical and medical manuscripts, books, and articles show that the association of hearing changes with loud noise exposure was recognized for centuries before systematic attempts were made to limit the exposure. Delays in implementing controls to limit noise exposure were due to cultural reasons, technical problems in controlling noise generation, and a lack of understanding of the mechanics of hearing loss. A historical perspective on this issue may remind health care providers that they need to continue to emphasize hearing conservation measures as occupational noise exposures change with the shift of industrial activities between countries. Copyright © 2012 Wiley Periodicals, Inc.

  1. The consequences of noise-induced hearing loss on dairy farm communities in New Zealand.

    Science.gov (United States)

    Canton, Karen; Williams, Warwick

    2012-01-01

    The objective of this study was to investigate how noise-induced hearing loss (NIHL) or noise injury (NI) affects individuals and others of dairy farm communities in New Zealand. Using "grab" or opportunistic sampling at DairyNZ discussion groups and a recreational function, a survey questionnaire was completed by 74 participants from two dairy farming communities in New Zealand. Self-reported hearing difficulties were highlighted by 48% (42) of the 74 participants. The effects of NI on individuals and others included communication difficulties leading to the development of coping strategies, social isolation; decreased employment opportunities, loss of productivity, and increased effort and adjustments by family and work colleagues. Frustration, anxiety, stress, resentment, depression, and fatigue are also negative consequences that may contribute to a loss of quality of life and contribute to further health costs. Increased lateness, absenteeism, sickness and other behavioral aspects were not expressed as normal issues in the workplace, as the majority of the individuals are/were self-employed or working in a family business. This study shows that each year in New Zealand NI results in significant negative social, psychological, and economic consequences for those individuals affected, along with their families, friends, and work colleagues.

  2. 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.

  3. Orchestrating cytoskeleton and intracellular vesicle traffic to build functional immunological synapses.

    Science.gov (United States)

    Soares, Helena; Lasserre, Rémi; Alcover, Andrés

    2013-11-01

    Immunological synapses are specialized cell-cell contacts formed between T lymphocytes and antigen-presenting cells. They are induced upon antigen recognition and are crucial for T-cell activation and effector functions. The generation and function of immunological synapses depend on an active T-cell polarization process, which results from a finely orchestrated crosstalk between the antigen receptor signal transduction machinery, the actin and microtubule cytoskeletons, and controlled vesicle traffic. Although we understand how some of these particular events are regulated, we still lack knowledge on how these multiple cellular elements are harmonized to ensure appropriate T-cell responses. We discuss here our view on how T-cell receptor signal transduction initially commands cytoskeletal and vesicle traffic polarization, which in turn sets the immunological synapse molecular design that regulates T-cell activation. We also discuss how the human immunodeficiency virus (HIV-1) hijacks some of these processes impairing immunological synapse generation and function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Ethanol extract of Piper longum L. attenuates gentamicin-induced hair cell loss in neonatal cochlea cultures.

    Science.gov (United States)

    Du, Xiao Fei; Song, Jae-Jun; Hong, Seungug; Kim, Jihye

    2012-06-01

    Piper longum L. (PL), also as known as long pepper, a well-known spice and traditional medicine in Asia and Pacific islands, has been reported to exhibit wide spectrum activity including antioxidant activity. However, little information is available on its protective effect on gentamicin (GM) induced ototoxicity which is commonly regarded as being mediated by reactive oxygen species and reactive nitrogen species. This study was undertaken to investigate the protective effect of PL ethanol extract on gentamicin-induced hair cell loss in neonatal cochlea cultures. Cochlea cultures from postnatal day 2-3 mice were used for analysis of the protective effects of PL against gentamicin-induced hair cell loss by phalloidin staining. E. coil cultures were used to determine whether PL interferes with the antibiotic activity of GM. Nitric oxide (NO)-scavenging activity of PL was also measured in vitro. GM induced significant dose-dependent hair cell loss in cochlea cultures. However, without interfering with the antibiotic activity of GM, PL showed a significant and concentration-dependent protective effect against GM-induced hair cell loss, and hair cells retained their stereocilia well. In addition, PL expressed direct scavenging activity toward NO radical liberated within solution of sodium nitroprusside. These findings demonstrate the protective effect of PL on GM-induced hair cell loss in neonatal cochlea cultures, and suggest that it might be of therapeutic benefit for treatment of GM-induced ototoxicity.

  5. 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.

  6. Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model.

    Science.gov (United States)

    Jung, Yong Gi; Lane, Andrew P

    2016-06-01

    To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model. An in vivo study using a transgenic mouse model. Research laboratory. To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group. Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed. Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  7. 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.

  8. Communication Breakdown: The Impact of Ageing on Synapse Structure

    Science.gov (United States)

    Petralia, Ronald S.; Mattson, Mark P.; Yao, Pamela J.

    2014-01-01

    Impaired synaptic plasticity is implicated in the functional decline of the nervous system associated with ageing. Understanding the structure of ageing synapses is essential to understanding the functions of these synapses and their role in the ageing nervous system. In this review, we summarize studies on ageing synapses in vertebrates and invertebrates, focusing on changes in morphology and ultrastructure. We cover different parts of the nervous system, including the brain, the retina, the cochlea, and the neuromuscular junction. The morphological characteristics of aged synapses could shed light on the underlying molecular changes and their functional consequences. PMID:24495392

  9. 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.

  10. 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 ...

  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. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Gabriele G. Schiattarella

    2018-05-01

    Full Text Available Left ventricular hypertrophy (LVH is a major contributor to the development of heart failure (HF. Alterations in cyclic adenosine monophosphate (cAMP-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA anchor proteins (AKAPs, tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-, Akap1 heterozygous (Akap1+/-, and their wild-type (wt littermates underwent transverse aortic constriction (TAC or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2 knockout mice (Siah2-/-. Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  14. Hwangryun-Haedok-Tang Fermented with Lactobacillus casei Suppresses Ovariectomy-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Ki-Shuk Shim

    2012-01-01

    Full Text Available Hwangryun-haedok-tang (HRT is the common recipe in traditional Asian medicine, and microbial fermentation is used for the conventional methods for processing traditional medicine. We investigated the inhibitory effect of the n-butanol fraction of HRT (HRT-BU and fHRT (fHRT-BU on the RANKL-induced osteoclastogenesis in bone-marrow-derived macrophages. mRNA expression of osteoclastogenesis-related genes were evaluated by real-time QPCR. The activation of signaling pathways was determined by western blot analysis. The marker compounds of HRT-BU and fHRT-BU were analyzed by HPLC. The inhibitory effect of HRT or fHRT on ovariectomy-induced bone loss were evaluated using OVX rats with orally administered HRT, fHRT (300, 1000 mg/kg, or its vehicle for 12 weeks. fHRT-BU significantly inhibited RANKL-induced osteoclastogenesis, and phosphorylation of p38, IKKα/β, and NF-κBp65 compared to HRT-BU. In addition, fHRT-BU also significantly inhibited the mRNA expression of Nfκb2, TNF-α, NFATc1, TRAP, ATPv0d2, and cathepsin K. Furthermore, administration of fHRT had a greater effect on the increase of BMD, and greater improved bone microstructure of the femora than that of HRT in ovariectomy rats. This study demonstrated that bacterial fermentation enhances the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial effects on bone disease by inhibiting osteoclastogenesis.

  15. Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.

    Science.gov (United States)

    Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

    2012-06-01

    Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss.

  16. Maitotoxin-induced liver cell death involving loss of cell ATP following influx of calcium

    International Nuclear Information System (INIS)

    Kutty, R.K.; Singh, Y.; Santostasi, G.; Krishna, G.

    1989-01-01

    Maitotoxin, one of the most potent marine toxins known, produced cell death in cultures of rat hepatocytes with a TD50 of 80 pM at 24 hr. The cell death, as indicated by a dose- and time-dependent leakage of lactate dehydrogenase (LDH), was also associated with the leakage of [14C]adenine nucleotides from hepatocytes prelabeled with [14C]-adenine. The toxic effect of maitotoxin was completely abolished by the omission of calcium from the culture medium. The cell death induced by maitotoxin increased with increasing concentrations of calcium in the medium. Treatment of hepatocytes with low concentrations of the toxin (less than 0.5 ng/ml) resulted in increases in 45Ca influx into the cells. At higher concentrations of maitotoxin (greater than 1ng/ml), the initial increase in 45Ca influx was followed by the release of the 45Ca from the cells into the medium. Since the 45Ca release paralleled the LDH leakage, the release of calcium was due to cell death. The 45Ca influx, [14C]adenine nucleotide leakage, and LDH leakage were effectively inhibited by verapamil, a calcium channel blocker. Maitotoxin also induced a time- and dose-dependent loss of ATP from hepatocytes, which preceded the [14C]adenine nucleotide and LDH leakage. Thus, it appears that the cell death resulting from maitotoxin treatment is caused by the elevated intracellular calcium, which in turn inhibits mitochondrial oxidative phosphorylation causing depletion of cell ATP. Loss of cell ATP may be the causative event in the maitotoxin-induced cell death

  17. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

    Science.gov (United States)

    Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

    2018-01-01

    Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  18. 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.

  19. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Radhika V Seimon

    Full Text Available Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled.Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change ÷ [(total energy intake of mice on CD or ID-(total average energy intake of controls]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding.Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05. There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01. Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups.Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative

  20. Radiation-induced loss of unsaturation in 1,2-polybutadiene

    International Nuclear Information System (INIS)

    Golub, M.A.; Cormia, R.D.

    1982-01-01

    The radiation induced loss of unsaturation and methyl production in 1,2-polybutadiene (VB) was studied using IR spectroscopy. It was found that G(-1,2), which depends on the initial vinyl content, decreased from approximately 550 for VB with 98.5% 1,2 initially, to approximately 270 for VB with 85% 1,2 initially. G(-trans-1,4) ranged from approximately 21 for VB with 14% trans-1,4 to nearly zero for VB with less than 1% trans-1,4 initially. Methyl production was found to equal one methyl group formed for every 4-5 vinyl units consumed in the radiation-cyclized VB, in contrast to one methyl formed for every two vinyls reacted during cationic cyclization to give monocyclic structures. The IR spectra of gamma-irradiated VB were very similar to the spectra of UV-irradiated or thermally-treated VB at the same residual vinyl contents. It is suggested that the radiation-induced cyclization of VB occurs by a nonionic, nonradical 'energy chain' mechanism, which apparently holds for the cyclization of VB, whether induced by gamma-rays, UV radiation, or heat

  1. 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.

  2. 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

  3. Impaired Compensation for Salt-Induced Urinary Calcium Loss in a Space Flight Model

    Science.gov (United States)

    Navidi, Meena; Harper, J. S.; Evans, J.; Fung, P.; Wolinsky, I.; Arnaud, S. B.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    The loss of urinary calcium (UCa) induced by high sodium (HiNa) diets is compensated for by an increase in net intestinal Ca absorption (abs.). To determine the capacity of the intestine to absorb Ca in a space flight model in which the formation of 1,25-dihydroxyvitamin D (1,25-D) is suppressed, we induced Ca loss with HiNa diets (8%) and restricted dietary Ca (0.2%). In 200 g rats with hind limbs unloaded by tail suspension (S), we examined intestinal Ca abs. by direct measurement in the duodenum (everted gut sac or S/M), vitamin D receptors (VDR) and Ca balance. We also measured serum ionized calcium (ICa), pH, parathyroid hormone (PTH) and 1,25D. PTH was related to ICa (r = -0.44, p is less than 0.02), pH (r = -0.47, p is less than 0.02) and %Ca abs. (r = -0.40, p is less than 0.05). 1,25-D was related to %Ca abs. (r = 0.60, p is less than 0.001) but not VDR or S/M. Effects of the model were lower serum 1,25-D (110 +/- 59 vs. 199 +/- 80 pg/ml, p is less than 0.005), %Ca abs. (83 +/- 6.9 vs. 93 +/- 3.2, p is less than 0.03) and Ca balance (27 +/- 0.2 vs. 30 +/- 0.3 mg/d, p is less than 0.001) in S than controls (C). The HiNa diet increased UCa excretion from 2 to 13% of dietary Ca. Responses to HiNa diets, compared to normal Na, revealed no differences in 1,25-D, Ca abs. or VDR. Ca balances were lower in HiNa (27 +/- 0.3 vs. 30 +/- 0.4 mg/d, p is less than 0.001) in spite of higher Ca intakes. The failure of S rats fed HiNa diets to increase Ca abs. in response to Na-induced Ca loss appears to be related to suppressed 1,25-D in the space flight model, the cause of which remains obscure.

  4. Cadmium action in synapses in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

    2001-05-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  5. Cadmium action in synapses in the brain

    International Nuclear Information System (INIS)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto

    2001-01-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of 109 CdCl 2 into the amygdala of rats, 109 Cd release into the extracellular space was facilitated by stimulation with high K + , suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 μM CdCl 2 . The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and γ-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  6. 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

  7. 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

  8. Study on severe accident induced by large break loss of coolant accident for pressureized water reactor

    International Nuclear Information System (INIS)

    Zhang Longfei; Zhang Dafa; Wang Shaoming

    2007-01-01

    Using the best estimate computer code SCDAP/RELAP5/MOD3.2 and taking US Westinghouse corporation Surry nuclear power plant as the reference object, a typical three-loop pressurized water reactor severe accident calculation model was established and 25 cm large break loss of coolant accident (LBLOCA) in cold and hot leg of primary loop induced core melt accident was analyzed. The calculated results show that core melt progression is fast and most of the core material melt and relocated to the lower plenum. The lower head of reactor pressure vessel failed at an early time and the cold leg break is more severe than the hot leg break in primary loop during LBLOCA. (authors)

  9. Improved Wojcik's eavesdropping attack on ping-pong protocol without eavesdropping-induced channel loss

    International Nuclear Information System (INIS)

    Zhang Zhanjun; Li Yong; Man Zhongxiao

    2005-01-01

    The eavesdropping scheme proposed by Wojcik [Phys. Rev. Lett. 90 (2003) 157901] on the ping-pong protocol [Phys. Rev. Lett. 89 (2002) 187902] is improved by constituting a new set of attack operations. The improved scheme has a zero eavesdropping-induced channel loss and produces perfect anticorrelation. Therefore, the eavesdropper Eve can safely attack all the transmitted bits and the eavesdropping information gain can always exceed the legitimate user's information gain in the whole domain of the quantum channel transmission efficiency η, i.e., [0,100%]. This means that the ping-pong protocol can be completely eavesdropped in its original version. But the improvement of the ping-pong protocol security produced by Wojcik is also suitable for our eavesdropping attack

  10. 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.

  11. 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

  12. Low-doses of cisplatin injure hippocampal synapses: a mechanism for 'chemo' brain?

    Science.gov (United States)

    Andres, Adrienne L; Gong, Xing; Di, Kaijun; Bota, Daniela A

    2014-05-01

    Chemotherapy-related cognitive deficits are a major neurological problem, but the underlying mechanisms are unclear. The death of neural stem/precursor cell (NSC) by cisplatin has been reported as a potential cause, but this requires high doses of chemotherapeutic agents. Cisplatin is frequently used in modern oncology, and it achieves high concentrations in the patient's brain. Here we report that exposure to low concentrations of cisplatin (0.1μM) causes the loss of dendritic spines and synapses within 30min. Longer exposures injured dendritic branches and reduced dendritic complexity. At this low concentration, cisplatin did not affect NSC viability nor provoke apoptosis. However, higher cisplatin levels (1μM) led to the rapid loss of synapses and dendritic disintegration, and neuronal-but not NSC-apoptosis. In-vivo treatment with cisplatin at clinically relevant doses also caused a reduction of dendritic branches and decreased spine density in CA1 and CA3 hippocampal neurons. An acute increase in cell death was measured in the CA1 and CA3 neurons, as well as in the NSC population located in the subgranular zone of the dentate gyrus in the cisplatin treated animals. The density of dendritic spines is related to the degree of neuronal connectivity and function, and pathological changes in spine number or structure have significant consequences for brain function. Therefore, this synapse and dendritic damage might contribute to the cognitive impairment observed after cisplatin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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.

  14. Blast induces oxidative stress, inflammation, neuronal loss and subsequent short-term memory impairment in rats.

    Science.gov (United States)

    Cho, H J; Sajja, V S S S; Vandevord, P J; Lee, Y W

    2013-12-03

    Molecular and cellular mechanisms of brain injury after exposure to blast overpressure (BOP) are not clearly known. The present study hypothesizes that pro-oxidative and pro-inflammatory pathways in the brain may be responsible for neuronal loss and behavioral deficits following BOP exposure. Male Sprague-Dawley rats were anesthetized and exposed to calibrated BOP of 129.23±3.01kPa while controls received only anesthesia. In situ dihydroethidium fluorescence staining revealed that BOP significantly increased the production of reactive oxygen species in the brain. In addition, real-time reverse transcriptase-polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assay demonstrated a significant up-regulation of mRNA and protein expressions of pro-inflammatory mediators, such as interferon-γ and monocyte chemoattractant protein-1, in brains collected from BOP-exposed animals compared with the controls. Furthermore, immunoreactivity of neuronal nuclei in brains indicated that fewer neurons were present following BOP exposure. Moreover, novel object recognition paradigm showed a significant impairment in the short-term memory at 2weeks following BOP exposure. These results suggest that pro-oxidative and pro-inflammatory environments in the brain could play a potential role in BOP-induced neuronal loss and behavioral deficits. It may provide a foundation for defining a molecular and cellular basis of the pathophysiology of blast-induced neurotrauma (BINT). It will also contribute to the development of new therapeutic approaches selectively targeting these pathways, which have great potential in the diagnosis and therapy of BINT. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Safety and otoprotection of metformin in radiation-induced sensorineural hearing loss in the guinea pig.

    Science.gov (United States)

    Mujica-Mota, Mario A; Salehi, Pezhman; Devic, Slobodan; Daniel, Sam J

    2014-05-01

    There is currently no treatment available to prevent radiation-induced sensorineural hearing loss. Metformin has antineoplastic effects and is able to regulate the mitochondrial production of reactive oxygen species after cellular stress, which is one of the mechanisms involved in apoptosis after radiation damage. The objective of this study was to determine the safety and radioprotective properties of metformin against radiation-induced cochlear damage both in vitro and in vivo. In vitro and prospective animal study. Animal Care Facilities of the Montreal Children's Hospital Research Institute. Cultured auditory hair cells (HEI-OC1) were exposed to different concentrations of metformin to determine its safety. Cells were incubated with different metformin concentrations and subjected to radiation. Cell viability after experiments was determined with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Sixteen guinea pigs were divided in 2 groups: drinking tap water (n = 8) and drinking water containing metformin (n = 8). The animals were unilaterally irradiated for 20 days (total dose 70 Gy), and the ears were divided in 4 groups: control (n = 8), irradiated (n = 8), metformin (n = 8), and experimental (n = 8). Auditory brainstem responses were assessed before and 1, 6, and 16 weeks after completion of radiotherapy. Metformin was not cytotoxic or radioprotective in cultured auditory hair cells. Experimental ears had less hearing loss than radiated ones; however, differences were not statistically significant (P > .05). Metformin is not ototoxic or radioprotective in vitro or in vivo. Ears solely subjected to metformin had better hearing thresholds than the rest of the groups.

  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. 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.

  18. Safflower bud inhibits RANKL-induced osteoclast differentiation and prevents bone loss in ovariectomized mice.

    Science.gov (United States)

    Choi, Joo-Hee; Lim, Seul-Ki; Kim, Dong-Il; Park, Min-Jung; Kim, Young-Kuk; Lee, An-Chul; Kim, Young-Min; Yang, Soo-Jin; Park, Jong-Hwan

    2017-10-15

    The powder and extract of safflower seeds are known to be effective in the prevention of bone loss in ovariectomized animals. However, the inhibitory effect and molecular mechanisms of safflower bud (SB), the germinated safflower, on bone destruction is unclear. The present study was designed to investigate the inhibitory effect and molecular mechanism of SB on osteoclastic differentiation and on bone loss in ovarietomized (OVX) mice. Osteoclastogenesis was determined by TRAP staining, F-actin ring formation, and bone resorption assay. NF-κB and MAPKs activation was analyzed by transfection assay and Western blot, respectively. Real-time PCR was performed to examine the expression of osteoclastogenesis-related genes. Histological changes, increases in TRAP-positive cells, and cathepsin K expression were examined in the metaphysis of OVX mice. Density of bone marrow was evaluated by µCT. SB inhibited the RANKL-induced differentiation of BMDMs into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by SB in RANKL-treated BMDMs. In addition, SB decreased the activation of NF-κB and MAPKs and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. Feeding of SB-included diet prevented bone loss in OVX mice. The number of TRAP-positive cells and level of protein expression of cathepsin K was reduced and bone mineral density was increased in the metaphysis of mice fed SB compared with OVX mice. These findings suggest that SB can be a preventive and therapeutic candidate for destructive bone diseases. Copyright © 2017. Published by Elsevier GmbH.

  19. 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.

  20. Functional consequences of climate change-induced plant species loss in a tallgrass prairie.

    Science.gov (United States)

    Craine, Joseph M; Nippert, Jesse B; Towne, E Gene; Tucker, Sally; Kembel, Steven W; Skibbe, Adam; McLauchlan, Kendra K

    2011-04-01

    Future climate change is likely to reduce the floristic diversity of grasslands. Yet the potential consequences of climate-induced plant species losses for the functioning of these ecosystems are poorly understood. We investigated how climate change might alter the functional composition of grasslands for Konza Prairie, a diverse tallgrass prairie in central North America. With species-specific climate envelopes, we show that a reduction in mean annual precipitation would preferentially remove species that are more abundant in the more productive lowland positions at Konza. As such, decreases in precipitation could reduce productivity not only by reducing water availability but by also removing species that inhabit the most productive areas and respond the most to climate variability. In support of this prediction, data on species abundance at Konza over 16 years show that species that are more abundant in lowlands than uplands are preferentially reduced in years with low precipitation. Climate change is likely to also preferentially remove species from particular functional groups and clades. For example, warming is forecast to preferentially remove perennials over annuals as well as Cyperaceae species. Despite these predictions, climate change is unlikely to unilaterally alter the functional composition of the tallgrass prairie flora, as many functional traits such as physiological drought tolerance and maximum photosynthetic rates showed little relationship with climate envelope parameters. In all, although climatic drying would indirectly alter grassland productivity through species loss patterns, the insurance afforded by biodiversity to ecosystem function is likely to be sustained in the face of climate change.

  1. Falls risk and hospitalization among retired workers with occupational noise-induced hearing loss.

    Science.gov (United States)

    Girard, Serge André; Leroux, Tony; Verreault, René; Courteau, Marilène; Picard, Michel; Turcotte, Fernand; Baril, Julie

    2014-03-01

    This study sought to ascertain whether occupational noise-induced hearing loss (NIHL) increased the risk of falls requiring hospitalization among retired workers. The study population consisted of males (age ≥ 65) with an average occupational noise exposure of 30.6 years and whose mean bilateral hearing loss was 42.2 dB HL at 3, 4, and 6 kHz. Seventy-two retired workers admitted to hospitals after a fall were matched with 216 controls from the same industrial sectors. Conditional logistic regression models were used to estimate the risk (odds ratio; [OR]) of falls leading to hospitalization by NIHL categories. Results showed a relationship between severe NIHL (≥ 52.5 dB HL) and the occurrence of a fall (OR: 1.97, CI95%: 1.001-3.876). Reducing falls among seniors fosters the maintenance of their autonomy. There is a definite need to acquire knowledge about harmful effects of occupational noise to support the prevention of NIHL and ensure healthier workplaces.

  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. Topiramate-induced weight loss in schizophrenia: a retrospective case series study.

    Science.gov (United States)

    Lévy, Emmanuel; Agbokou, Catherine; Ferreri, Florian; Chouinard, Guy; Margolese, Howard C

    2007-01-01

    Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain. A 2-year retrospective case analysis was performed in all 300 patients of the outpatient Special Follow-up Clinic for chronic schizophrenia and related psychoses at the Allan Memorial Institute, McGill University Health Centre (Montreal, Canada), a tertiary care University teaching hospital. 10 patients met study inclusion criteria. Mean daily topiramate dose was 197.5 mg (A+/-77) (range, 125-400 mg). Topiramate produced continued weight loss throughout the study duration without tolerance. Patients treated for 6 months and more had significantly higher Body Mass Index (BMI) differences than those treated for shorter durations (BMI-d6 months=-4.7A+/-2.4; BMI-d2 months=-3.2A+/-2.3; P=0.015). BMI changes were similar across genders. This study supports topiramate use to target weight loss in stable overweight schizophrenic patients as a potential therapy that requires further investigation.

  4. 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.

  5. Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts.

    Science.gov (United States)

    Xu, Lu-lu; Lu, Yun-tao; Zhang, Jing; Wu, Lian; Merrilees, Mervyn J; Qu, Jie-ming

    2015-08-15

    COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican V1 (V1). V1 is a known inhibitor of elastic fiber deposition and this study investigates the effects of knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast proliferation, viability, tropoelastin synthesis, and elastin deposition, and increased V1 synthesis and secretion. V1 siRNA decreased V1 and constituent CS, did not affect tropoelastin production, but blocked the CSE-induced loss in insoluble elastin. Exogenous CS reduced insoluble elastin, even in the presence of V1 siRNA. These findings confirm that V1 and CS impair the assembly of tropoelastin monomers into insoluble fibers, and further demonstrate that specific knockdown of V1 alleviates the impaired assembly of elastin seen in cultures of pulmonary fibroblasts exposed to CSE, indicating a regulatory role for this protein in the pathophysiology of COPD. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 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.

  7. 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.

  8. 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.

  9. Murine CMV-Induced Hearing Loss Is Associated with Inner Ear Inflammation and Loss of Spiral Ganglia Neurons

    OpenAIRE

    Bradford, Russell D.; Yoo, Young-Gun; Golemac, Mijo; Pugel, Ester Pernjak; Jonjic, Stipan; Britt, William J.

    2015-01-01

    Author Summary Congenital infection with human cytomegalovirus (HCMV) is the most common viral infection of the fetus and occurs in 0.5?2.0% of all live births in most regions in the world. Infection of the fetus can result in a spectrum of end-organ disease, including long term damage to the central nervous system (CNS). Although less than 10% of infected infants exhibit clinical evidence of end-organ disease, up to 10% of the total number of infected infants develop hearing loss. Mechanisms...

  10. 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.

  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

    2015-01-01

    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. PMID:26722345

  12. IR wireless cluster synapses of HYDRA very large neural networks

    Science.gov (United States)

    Jannson, Tomasz; Forrester, Thomas

    2008-04-01

    RF/IR wireless (virtual) synapses are critical components of HYDRA (Hyper-Distributed Robotic Autonomy) neural networks, already discussed in two earlier papers. The HYDRA network has the potential to be very large, up to 10 11-neurons and 10 18-synapses, based on already established technologies (cellular RF telephony and IR-wireless LANs). It is organized into almost fully connected IR-wireless clusters. The HYDRA neurons and synapses are very flexible, simple, and low-cost. They can be modified into a broad variety of biologically-inspired brain-like computing capabilities. In this third paper, we focus on neural hardware in general, and on IR-wireless synapses in particular. Such synapses, based on LED/LD-connections, dominate the HYDRA neural cluster.

  13. Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

    International Nuclear Information System (INIS)

    Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

    2015-01-01

    Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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....

  20. 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

  1. 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.

  2. Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.

    Directory of Open Access Journals (Sweden)

    Yuka Okada

    Full Text Available 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.

  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

    2015-11-17

    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.

  4. 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.

  5. Heat deposition on the first wall due to ICRF-induced loss of fast ions in JT-60U

    International Nuclear Information System (INIS)

    Kusama, Y.; Tobita, K.; Kimura, H.; Hamamatsu, K.; Fujii, T.; Nemoto, M.; Saigusa, M.; Moriyama, S.; Tani, K.; Koide, Y.; Sakasai, A.; Nishitani, T.; Ushigusa, K.

    1995-01-01

    In JT-60U, the heat deposition on the first wall due to the ICRF-induced loss of fast ions was investigated by changing the position of the resonance layer in the ripple-trapping region. A heat spot appears on the first wall of the same major radius as the resonance layer of the ICRF waves. The broadening of the heat spot in the major radius direction is consistent with that of the resonance layer due to the Doppler broadening. The heat spot is considered to be formed by the ICRF-induced ripple-trapped loss of fast ions. Although the total ICRF-induced loss power to the heat spot is as low as 2% of the total ICRF power, the additional heat flux will become a new issue because of the localized heat deposition on the first wall. ((orig.))

  6. Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    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.

  7. The Role of Interleukin-6 in Lipopolysaccharide-Induced Weight Loss, Hypoglycemia and Fibrinogen Production, in Vivo

    Science.gov (United States)

    1994-07-01

    result in chronic wasting or cachexia. In neoplastic severe weight loss in syngeneic hosts.6 In this model, diseases, the presence of wasting of muscle...48 h post-endotoxin). Anti-TNF MAb tribution of TNF and IL-6 in several metabolic changes reduced by c. 50% the LPS-induced weight loss, but...similar results. Also, the addi- hypertriglyceridemia , hypoglycemia as well as stimu- tion of fresh 20F3 MAb to diluted serum sample from late the

  8. 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.

  9. 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

  10. MHD-induced Energetic Ion Loss during H-mode Discharges in the National Spherical Torus Experiment (NSTX)

    International Nuclear Information System (INIS)

    Medley, S.S.; Gorelenkov, N.N.; Andre, R.; Bell, R.E.; Darrow, D.S.; Fredrickson, E.D.; Kaye, S.M.; LeBlanc, B.P.; Roquemore, A.L.

    2004-01-01

    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 ∼ 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, and

  11. 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; Sha, Su-Hua

    2016-07-13

    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. 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. Copyright © 2016 the authors 0270-6474/16/367497-14$15.00/0.

  12. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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.

  15. Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue

    Directory of Open Access Journals (Sweden)

    Connor Bronwen

    2009-11-01

    Full Text Available Abstract Background Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel. Results After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; P P P = 0.82, NF-M (-1%, P = 0.96 or NF-H (0%; P = 0.93 after oxaliplatin treatment, although the sizes of parvalbumin (-29%, P = 0.047, NF-M (-11%, P = 0.038 and NF-H (-28%; P = 0.0033 immunoreactive neurons were reduced. In an independent comparison of different chemotherapeutic agents, the number of pNF-H-immunoreactive neurons was significantly altered by oxaliplatin (-77.2%; P P = 0.03 but not by carboplatin or paclitaxel, and their mean cell body area was significantly changed by oxaliplatin (-31.1%; P = 0.008 but not by cisplatin, carboplatin or paclitaxel. Conclusion This study has demonstrated a specific pattern of loss of pNF-H immunoreactivity in rat DRG tissue that corresponds with the relative neurotoxicity of oxaliplatin, cisplatin and carboplatin. Loss of pNF-H may be mechanistically linked to oxaliplatin-induced neuronal atrophy, and serves as a readily measureable endpoint of its neurotoxicity in the rat model.

  16. 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.

  17. High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. 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.

  20. 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.

  1. Subchronic JP-8 jet fuel exposure enhances vulnerability to noise-induced hearing loss in rats.

    Science.gov (United States)

    Fechter, L D; Fisher, J W; Chapman, G D; Mokashi, V P; Ortiz, P A; Reboulet, J E; Stubbs, J E; Lear, A M; McInturf, S M; Prues, S L; Gearhart, C A; Fulton, S; Mattie, D R

    2012-01-01

    Both laboratory and epidemiological studies published over the past two decades have identified the risk of excess hearing loss when specific chemical contaminants are present along with noise. The objective of this study was to evaluate the potency of JP-8 jet fuel to enhance noise-induced hearing loss (NIHL) using inhalation exposure to fuel and simultaneous exposure to either continuous or intermittent noise exposure over a 4-wk exposure period using both male and female Fischer 344 rats. In the initial study, male (n = 5) and female (n = 5) rats received inhalation exposure to JP-8 fuel for 6 h/d, 5 d/wk for 4 wk at concentrations of 200, 750, or 1500 mg/m³. Parallel groups of rats also received nondamaging noise (constant octave band noise at 85 dB(lin)) in combination with the fuel, noise alone (75, 85, or 95 dB), or no exposure to fuel or noise. Significant concentration-related impairment of auditory function measured by distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) threshold was seen in rats exposed to combined JP-8 plus noise exposure when JP-8 levels of 1500 mg/m³ were presented with trends toward impairment seen with 750 mg/m³ JP-8 + noise. JP-8 alone exerted no significant effect on auditory function. In addition, noise was able to disrupt the DPOAE and increase auditory thresholds only when noise exposure was at 95 dB. In a subsequent study, male (n = 5 per group) and female (n = 5 per group) rats received 1000 mg/m³ JP-8 for 6 h/d, 5 d/wk for 4 wk with and without exposure to 102 dB octave band noise that was present for 15 min out of each hour (total noise duration 90 min). Comparisons were made to rats receiving only noise, and thosereceiving no experimental treatment. Significant impairment of auditory thresholds especially for high-frequency tones was identified in the male rats receiving combined treatment. This study provides a basis for estimating excessive hearing loss under

  2. 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

  3. The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss.

    Science.gov (United States)

    Fetoni, Anna R; Eramo, Sara Letizia Maria; Di Pino, Antonella; Rolesi, Rolando; Paciello, Fabiola; Grassi, Claudio; Troiani, Diana; Paludetti, Gaetano

    2018-03-01

    Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo. ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures. RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups. Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels. The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.

  4. 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.

  5. The immunological synapse: a focal point for endocytosis and exocytosis.

    Science.gov (United States)

    Griffiths, Gillian M; Tsun, Andy; Stinchcombe, Jane C

    2010-05-03

    There are many different cells in the immune system. To mount an effective immune response, they need to communicate with each other. One way in which this is done is by the formation of immunological synapses between cells. Recent developments show that the immune synapse serves as a focal point for exocytosis and endocytosis, directed by centrosomal docking at the plasma membrane. In this respect, formation of the immunological synapse bears striking similarities to cilia formation and cytokinesis. These intriguing observations suggest that the centrosome may play a conserved role in designating a specialized area of membrane for localized endocytosis and exocytosis.

  6. The cytotoxic T lymphocyte immune synapse at a glance.

    Science.gov (United States)

    Dieckmann, Nele M G; Frazer, Gordon L; Asano, Yukako; Stinchcombe, Jane C; Griffiths, Gillian M

    2016-08-01

    The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers. © 2016. Published by The Company of Biologists Ltd.

  7. 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.

  8. Improved nutritional status and bone health after diet-induced weight loss in sedentary osteoarthritis patients: a prospective cohort study.

    Science.gov (United States)

    Christensen, P; Bartels, E M; Riecke, B F; Bliddal, H; Leeds, A R; Astrup, A; Winther, K; Christensen, R

    2012-04-01

    Obese subjects are commonly deficient in several micronutrients. Weight loss, although beneficial, may also lead to adverse changes in micronutrient status and body composition. The objective of the study is to assess changes in micronutrient status and body composition in obese individuals after a dietary weight loss program. As part of a dietary weight loss trial, enrolling 192 obese patients (body mass index >30 kg/m2) with knee osteoarthritis (>50 years of age), vitamin D, ferritin, vitamin B12 and body composition were measured at baseline and after 16 weeks. All followed an 8-week formula weight-loss diet 415-810 kcal per day, followed by 8 weeks on a hypo-energetic 1200 kcal per day diet with a combination of normal food and formula products. Statistical analyses were based on paired samples in the completer population. A total of 175 patients (142 women), 91%, completed the 16-week program and had a body weight loss of 14.0 kg (95% confidence interval: 13.3-14.7; Pdiet resulted in increased BMD and improved vitamin D and B12 levels. Ferritin and BMC were unchanged and loss of LBM was only 13% of the total weight loss. This observational evidence supports use of formula diet-induced weight loss therapy in obese osteoarthritis patients.

  9. [Protective effect of indirect activator of calcium pump on noise-induced hearing loss].

    Science.gov (United States)

    Liu, Jun; Yu, Ning; Han, Dongyi; Yang, Weiyan; Li, Xingqi

    2002-12-01

    To investigate the possible protective effect of phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C (PKC) and indirect activator of Ca2+ pump, on noise-induced hearing loss (NIHL). Twenty guinea pigs were divided randomly into two groups, and then perfused with artificial perilymph solutions in one group and with artificial perilymph solutions containing 3 mumol/L PMA in the other one, respectively. All animals were exposed with 100 dB SPL white noise for 2 hours. Cochlear microphonics (CM) and compound action potential (CAP) were recorded from the round window (RW) before noise exposure and 2 hours after noise exposure. There was no significant difference in CAP threshold and CM amplitude between two groups before noise exposure. A significant difference was observed in CAP threshold and CM amplitude between two groups after noise exposure. The amplitude of CM decreased and the threshold of CAP increased in both group after noise exposure, but in the PMA group the decrease of the amplitude of CM was higher while the increase of threshold of CAP lower than that in control (P < 0.05). PMA might have partly protective effect on NIHL. These findings indirectly proved that intracellular Ca2+ overload might involve in the mechanism of NIHL.

  10. 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: prestriction did not exaggerate bone resorption during HDBR.

  11. 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/

  12. 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...

  13. 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.

  14. 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.

  15. 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....

  16. 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...

  17. Protecting a full-scale Nb3Sn magnet with CLIQ, the new coupling-loss-induced quench system

    NARCIS (Netherlands)

    Ravaioli, Emanuele; Bajas, H.; Datskov, V.I.; Desbiolles, V.; Feuvrier, J.; Kirby, G.; Maciejewski, M.; Sabbi, G.; ten Kate, Herman H.J.; Verweij, A.P.

    2015-01-01

    A new protection system for superconducting magnets called coupling-loss induced quench system (CLIQ) has been recently developed at CERN. Recent tests on Nb-Ti coils have shown that CLIQ is a valid, efficient, and promising method for the protection of high-magnetic-field superconducting magnets.

  18. 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...

  19. 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.

  20. 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

  1. Spontaneous and induced loss of chromosomes in slow-growing somatic hybrid calli of Solanum tuberosum and Nicotiana plumbaginifolia

    NARCIS (Netherlands)

    Tempelaar, MJ; Drenth - Diephuis, L.J.; SAAT, TAWM; Jacobsen, E.

    Rate and extent of spontaneous and induced chromosome loss have been determined at the callus level of somatic hybrids of mutants of Solanum tuberosum and Nicotiana plumbaginifolia. AEC (amino ethyl cystein) resistance in potato and Nitrate-Reductase deficiency in N. plumbaginifolia have been used

  2. [Hydroxychloroquine-induced hearing loss: First case of positive rechallenge and analysis of the French pharmacovigilance database].

    Science.gov (United States)

    Chatelet, J-N; Auffret, M; Combret, S; Bondon-Guitton, E; Lambert, M; Gautier, S

    2017-05-01

    Several cases of hearing loss induced by hydroxychloroquine have been reported in the literature but the role of hydroxychloroquine still remains debated. We report the first case, to our knowledge, of hearing loss induced by hydroxychloroquine with a positive re challenge in a woman treated for systemic lupus. An analysis of the French pharmacovigilance database allowed to identify 23 additional cases of hearing loss in patients treated with hydroxychloroquine and, among them, 8 had systemic lupus. Despite an excellent tolerance and high efficacy-side effect ratio, this case report adds some evidence for an otoxicity of hydroxychloroquine. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  3. DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Mahmood, Amer

    2011-01-01

    . In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of proinflammatory bone-resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of Dlk1...... in the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1...... production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss....

  4. Neurotrophin-3 Regulates Synapse Development by Modulating TrkC-PTPσ Synaptic Adhesion and Intracellular Signaling Pathways.

    Science.gov (United States)

    Han, Kyung Ah; Woo, Doyeon; Kim, Seungjoon; Choii, Gayoung; Jeon, Sangmin; Won, Seoung Youn; Kim, Ho Min; Heo, Won Do; Um, Ji Won; Ko, Jaewon

    2016-04-27

    Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10-25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes. In this study, we present several lines of experimental evidences to support the conclusion that

  5. 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.

  6. 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

  7. Advances in synapse formation: forging connections in the worm.

    Science.gov (United States)

    Cherra, Salvatore J; Jin, Yishi

    2015-01-01

    Synapse formation is the quintessential process by which neurons form specific connections with their targets to enable the development of functional circuits. Over the past few decades, intense research efforts have identified thousands of proteins that localize to the pre- and postsynaptic compartments. Genetic dissection has provided important insights into the nexus of the molecular and cellular network, and has greatly advanced our knowledge about how synapses form and function physiologically. Moreover, recent studies have highlighted the complex regulation of synapse formation with the identification of novel mechanisms involving cell interactions from non-neuronal sources. In this review, we cover the conserved pathways required for synaptogenesis and place specific focus on new themes of synapse modulation arising from studies in Caenorhabditis elegans. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 Wiley Periodicals, Inc.

  8. 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...

  9. Contextual Learning Requires Functional Diversity at Excitatory and Inhibitory Synapses onto CA1 Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Dai Mitsushima

    2015-01-01

    Full Text Available Although the hippocampus is processing temporal and spatial information in particular context, the encoding rule creating memory is completely unknown. To examine the mechanism, we trained rats on an inhibitory avoidance (IA task, a hippocampus-dependent rapid one-trial contextual learning paradigm. By combining Herpes virus-mediated in vivo gene delivery with in vitro patch-clamp recordings, I reported contextual learning drives GluR1-containing AMPA receptors into CA3-CA1 synapses. The molecular event is required for contextual memory, since bilateral expression of delivery blocker in CA1 successfully blocked IA learning. Moreover, I found a logarithmic correlation between the number of delivery blocking cells and learning performance. Considering that one all-or-none device can process 1-bit of data per clock (Nobert Wiener 1961, the logarithmic correlation may provides evidence that CA1 neurons transmit essential data of contextual information. Further, I recently reported critical role of acetylcholine as an intrinsic trigger of learning-dependent synaptic plasticity. IA training induced ACh release in CA1 that strengthened not only AMPA receptor-mediated excitatory synapses, but also GABAA receptor-mediated inhibitory synapses on each CA1 neuron. More importantly, IA-trained rats showed individually different excitatory and inhibitory synaptic inputs with wide variation on each CA1 neuron. Here I propose a new hypothesis that the diversity of synaptic inputs on CA1 neurons may depict cell-specific outputs processing experienced episodes after training.

  10. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

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    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.

  11. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

    Science.gov (United States)

    Davenport, A J; Cross, R S; Watson, K A; Liao, Y; Shi, W; Prince, H M; Beavis, P A; Trapani, J A; Kershaw, M H; Ritchie, D S; Darcy, P K; Neeson, P J; Jenkins, M R

    2018-02-27

    Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Copyright © 2018 the Author(s). Published by PNAS.

  12. When is an Inhibitory Synapse Effective?

    Science.gov (United States)

    Qian, Ning; Sejnowski, Terrence J.

    1990-10-01

    Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl^- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl^- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl^-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K^+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K^+ through GABA_B receptors.

  13. 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.

  14. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Science.gov (United States)

    Zabouri, Nawal; Haverkamp, Silke

    2013-01-01

    Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(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(V)1.4(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(V)1.4 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(V)1.4 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(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  15. Three-terminal ferroelectric synapse device with concurrent learning function for artificial neural networks

    International Nuclear Information System (INIS)

    Nishitani, Y.; Kaneko, Y.; Ueda, M.; Fujii, E.; Morie, T.

    2012-01-01

    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 3 (PZT)/SrRuO 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.

  16. Emerging roles of the neurotrophin receptor TrkC in synapse organization.

    Science.gov (United States)

    Naito, Yusuke; Lee, Alfred Kihoon; Takahashi, Hideto

    2017-03-01

    Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ). TrkC-PTPσ specifically induces excitatory synapses in a kinase domain-independent manner. TrkC has distinct extracellular domains for PTPσ- and NT-3-binding and thus may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPσ interaction, thus facilitating synapse induction at the pre-synaptic side and increasing pre-synaptic vesicle recycling in a kinase-independent fashion. A crystal structure study has revealed the detailed structure of the TrkC-PTPσ complex as well as competitive modulation of TrkC-mediated synaptogenesis by heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as PTPσ. Thus, there is strong evidence supporting a role for the TrkC-PTPσ complex in mechanisms underlying the fine turning of neural connectivity. Furthermore, disruption of the TrkC-PTPσ complex may be the underlying cause of certain psychiatric disorders caused by mutations in the gene encoding TrkC (NTRK3), supporting its role in cognitive functions. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

    Science.gov (United States)

    Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

    2015-01-01

    Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

  1. 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.

  2. Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Yoo-Ri Chung

    2017-01-01

    Full Text Available Loss of pericytes, an early hallmark of diabetic retinopathy (DR, results in breakdown of the blood-retinal barrier. Endoplasmic reticulum (ER stress may be involved in this process. The purpose of this study was to examine the effects of ursodeoxycholic acid (UDCA, a known ameliorator of ER stress, on pericyte loss in DR of streptozotocin- (STZ- induced diabetic mice. To assess the extent of DR, the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice were evaluated. Additionally, induction of ER stress and the unfolded protein response (UPR were assessed in diabetic mice and human retinal pericytes exposed to advanced glycation end products (AGE or modified low-density lipoprotein (mLDL. Fluorescein dye leakage during angiography and retinal capillary density were improved in UDCA-treated diabetic mice, compared to the nontreated diabetic group. Among the UPR markers, those involved in the protein kinase-like ER kinase (PERK pathway were increased, while UDCA attenuated UPR in STZ-induced diabetic mice as well as AGE- or mLDL-exposed retinal pericytes in culture. Consequently, vascular integrity was improved and pericyte loss reduced in the retina of STZ-induced diabetic mice. Our findings suggest that UDCA might be effective in protecting against DR.

  3. 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.

  4. Characterizing Peptide Neutral Losses Induced by Negative Electron-Transfer Dissociation (NETD)

    Science.gov (United States)

    Rumachik, Neil G.; McAlister, Graeme C.; Russell, Jason D.; Bailey, Derek J.; Wenger, Craig D.; Coon, Joshua J.

    2012-01-01

    We implemented negative electron-transfer dissociation (NETD) on a hybrid ion trap/Orbitrap mass spectrometer to conduct ion/ion reactions using peptide anions and radical reagent cations. In addition to sequence-informative ladders of a•- and x-type fragment ions, NETD generated intense neutral loss peaks corresponding to the entire or partial side-chain cleavage from amino acids constituting a given peptide. Thus, a critical step towards the characterization of this recently introduced fragmentation technique is a systematic study of synthetic peptides to identify common neutral losses and preferential fragmentation pathways. Examining 46 synthetic peptides with high mass accuracy and high resolution analysis permitted facile determination of the chemical composition of each neutral loss. We identified 19 unique neutral losses from 14 amino acids and three modified amino acids, and assessed the specificity and sensitivity of each neutral loss using a database of 1542 confidently identified peptides generated from NETD shotgun experiments employing high-pH separations and negative electrospray ionization. As residue-specific neutral losses indicate the presence of certain amino acids, we determined that many neutral losses have potential diagnostic utility. We envision this catalogue of neutral losses being incorporated into database search algorithms to improve peptide identification specificity and to further advance characterization of the acidic proteome. PMID:22290482

  5. 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

  6. 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 ).

  7. Fast-ion losses induced by ELMs and externally applied magnetic perturbations in the ASDEX Upgrade tokamak

    International Nuclear Information System (INIS)

    Garcia-Munoz, M; Rodriguez-Ramos, M; Äkäslompolo, S; De Marne, P; Dunne, M G; Dux, R; Fietz, S; Fuchs, C; Geiger, B; Herrmann, A; Hoelzl, M; Kurzan, B; McDermott, R M; Strumberger, E; Evans, T E; Ferraro, N M; Pace, D C; Lazanyi, N; Nocente, M; Shinohara, K

    2013-01-01

    Phase-space time-resolved measurements of fast-ion losses induced by edge localized modes (ELMs) and ELM mitigation coils have been obtained in the ASDEX Upgrade tokamak by means of multiple fast-ion loss detectors (FILDs). Filament-like bursts of fast-ion losses are measured during ELMs by several FILDs at different toroidal and poloidal positions. Externally applied magnetic perturbations (MPs) have little effect on plasma profiles, including fast-ions, in high collisionality plasmas with mitigated ELMs. A strong impact on plasma density, rotation and fast-ions is observed, however, in low density/collisionality and q 95 plasmas with externally applied MPs. During the mitigation/suppression of type-I ELMs by externally applied MPs, the large fast-ion bursts observed during ELMs are replaced by a steady loss of fast-ions with a broad-band frequency and an amplitude of up to an order of magnitude higher than the neutral beam injection (NBI) prompt loss signal without MPs. Multiple FILD measurements at different positions, indicate that the fast-ion losses due to static 3D fields are localized on certain parts of the first wall rather than being toroidally/poloidally homogeneously distributed. Measured fast-ion losses show a broad energy and pitch-angle range and are typically on banana orbits that explore the entire pedestal/scrape-off-layer (SOL). Infra-red measurements are used to estimate the heat load associated with the MP-induced fast-ion losses. The heat load on the FILD detector head and surrounding wall can be up to six times higher with MPs than without 3D fields. When 3D fields are applied and density pump-out is observed, an enhancement of the fast-ion content in the plasma is typically measured by fast-ion D-alpha (FIDA) spectroscopy. The lower density during the MP phase also leads to a deeper beam deposition with an inward radial displacement of ≈2 cm in the maximum of the beam emission. Orbit simulations are used to test different models for 3D

  8. 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.

  9. 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; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    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) (HIF2α(Δ/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 HIF2α(Δ/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 HIF2α(Δ/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.

  10. 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

  11. 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.

  12. 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

    , and LMW). The HMW form was suggested to be closely associated with insulin sensitivity. This study investigated whether diet-induced changes in insulin sensitivity were associated with changes in adiponectin multimeric complexes. SUBJECTS: Twenty obese women with highest and twenty obese women with lowest...... 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...

  13. [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

  14. Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model.

    Science.gov (United States)

    Han, Song-Hee; Kim, Sung-June; Yun, Young Won; Nam, Sang Yoon; Lee, Hu-Jang; Lee, Beom-Jun

    2018-03-01

    This study was performed to investigate the effect of a concentrate of fermented wild ginseng root culture (HLJG0701) on memory improvement in the scopolamine (SPL)-induced memory-deficient mouse model. Eight-week-old male ICR mice were used to evaluate the protective effect of HLJG0701 against the SPL-induced memory loss animal model. The Morris water maze test, which measures hippocampus-dependent learning ability, and the Y-maze test, a short-term memory assessment test, were performed and related markers were analyzed. HLJG0701-treated groups displayed significantly reduced acetylcholinesterase activity and increased acetylcholine level compared with the SPL-administered group (SPL-G) ( P memory loss by inhibiting acetylcholinesterase activity and preventing acetylcholine deficiency.

  15. 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.

  16. 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.

  17. Alpha-driven magnetohydrodynamics (MHD) and MHD-induced alpha loss in the Tokamak Fusion Test Reactor

    International Nuclear Information System (INIS)

    Chang, Z.; Nazikian, R.; Fu, G.Y.

    1997-02-01

    Alpha-driven toroidal Alfven eigenmodes (TAEs) are observed as predicted by theory in the post neutral beam phase in high central q (safety factor) deuterium-tritium (D-T) plasmas in the Tokamak Fusion Test Reactor (TFTR). The mode location, poloidal structure and the importance of q profile for TAE instability are discussed. So far no alpha particle loss due to these modes was detected due to the small mode amplitude. However, alpha loss induced by kinetic ballooning modes (KBMs) was observed in high confinement D-T discharges. Particle orbit simulation demonstrates that the wave-particle resonant interaction can explain the observed correlation between the increase in alpha loss and appearance of multiple high-n (n ≥ 6, n is the toroidal mode number) modes

  18. Improved W\\'{o}jcik's Eavesdropping Attack on Ping-Pong Protocol Without Eavesdropping-Induced Channel Loss

    OpenAIRE

    Zhang, Zhan-jun; Li, Yong; Man, Zhong-xiao

    2004-01-01

    The eavesdropping scheme proposed by W\\'{o}jcik [Phys. Rev. Lett. {\\bf 90},157901(2003)] on the ping-pong protocol [Phys. Rev. Lett. {\\bf 89}, 187902(2002)] is improved by constituting a new set of attack operations. The improved scheme has a zero eavesdropping-induced channel loss and produces perfect anticorrelation. Therefore, the eavesdropper Eve can safely attack all the transmitted bits and the eavesdropping information gain can always exceed the legitimate user's information gain in th...

  19. 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.

  20. Sleep loss and structural plasticity.

    Science.gov (United States)

    Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

    2017-06-01

    Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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...

  2. 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...

  3. 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.

  4. Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway

    OpenAIRE

    Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

    2014-01-01

    Background: Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. Methods: We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistoche...

  5. 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...

  6. 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

    2015-01-01

    Objective To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. Design 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. Study sample 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. Results 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. Conclusions 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. PMID:24564697

  7. 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.

  8. Raynaud′s phenomenon among men and women with noise-induced hearing loss in relation to vibration exposure

    Directory of Open Access Journals (Sweden)

    Hans Pettersson

    2014-01-01

    Full Text Available 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.

  9. BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

    Science.gov (United States)

    Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

    2017-05-01

    Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

  10. [A cohort study on occupational noise induced hearing loss in workers at an iron and steel plant].

    Science.gov (United States)

    Yu, S F; Chen, G S; Jiao, J; Gu, G Z; Zhang, H L; Wang, X M; Zhou, W H; Wu, H; Li, Y H; Zheng, Y X

    2017-01-06

    Objective: To analyze the incidence rate of occupational noise-induced hearing loss in noise-exposed workers in an iron and steel plant from 2006 to 2015. Methods: Using a cohort study method, workers exposed to occupational noise from Jan 1, 2006 to Dec 12, 2015 were followed up and the pure tone hearing test was conducted. In total, 6 297 subjects completed two or more physical checks and the pure tone hearing test and were included in the analysis. The noise exposure level at the workplace and the equivalent continuous A-weighted sound pressure level for workers was monitored and the cumulative noise exposure dose was evaluated. The subjects were divided into low, middle and high exposure groups according to the noise exposure level, and the equivalent continuous A-weighted sound pressure level for 8 hours for each group was 80.6-85.0, 85.1-90.0 and 90.1-103.4 dB (A), respectively. While the RR and 95% CI were derived from unconditional logistic regression models. In logistic regression analysis, confounding factors such as age, gender, smoking habit, drinking habit, high temperature exposure and chemical hazards exposure level were controlled. Results: During the follow-up period, 392 cases of occupational noise-induced hearing loss were diagnosed among the 6 297 subjects, with an incidence rate of 6.23%; 318 cases of high-frequency hearing loss were diagnosed, with an incidence rate of 5.05%; and 74 cases of occupational noise-induced deafness were diagnosed, with an incidence rate of 1.18% . The incidence rates of hearing loss among the high, medium and low exposure groups were 9.22% (158/1 737), 6.49% (204/3 142) and 2.08% (30/1 442), respectively; the rates of high-frequency hearing loss were 7.41% (127/1 737), 5.25% (165/3 142) and 1.80% (26/1 442), respectively; and the rates of occupational noise-induced deafness were 1.81% (31/1 737), 1.24% (39/3 142) and 0.28% (4/1 442), respectively. For the groups corresponding to cumulative noise exposure doses of

  11. Persistent Associative Plasticity at an Identified Synapse Underlying Classical Conditioning Becomes Labile with Short-Term Homosynaptic Activation.

    Science.gov (United States)

    Hu, Jiangyuan; Schacher, Samuel

    2015-12-09

    Synapses express different forms of plasticity that contribute to different forms of memory, and both memory and plasticity can become labile after reactivation. We previously reported that a persistent form of nonassociative long-term facilitation (PNA-LTF) of the sensorimotor synapses in Aplysia californica, a cellular analog of long-term sensitization, became labile with short-term heterosynaptic reactivation and reversed when the reactivation was followed by incubation with the protein synthesis inhibitor rapamycin. Here we examined the reciprocal impact of different forms of short-term plasticity (reactivations) on a persistent form of associative long-term facilitation (PA-LTF), a cellular analog of classical conditioning, which was expressed at Aplysia sensorimotor synapses when a tetanic stimulation of the sensory neurons was paired with a brief application of serotonin on 2 consecutive days. The expression of short-term homosynaptic plasticity [post-tetanic potentiation or homosynaptic depression (HSD)], or short-term heterosynaptic plasticity [serotonin-induced facilitation or neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa)-induced depression], at synapses expressing PA-LTF did not affect the maintenance of PA-LTF. The kinetics of HSD was attenuated at synapses expressing PA-LTF, which required activation of protein kinase C (PKC). Both PA-LTF and the attenuated kinetics of HSD were reversed by either a transient blockade of PKC activity or a homosynaptic, but not heterosynaptic, reactivation when paired with rapamycin. These results indicate that two different forms of persistent synaptic plasticity, PA-LTF and PNA-LTF, expressed at the same synapse become labile when reactivated by different stimuli. Activity-dependent changes in neural circuits mediate long-term memories. Some forms of long-term memories become labile and can be reversed with specific types of reactivations, but the mechanism is complex. At the cellular level, reactivations that induce a

  12. Radiotherapy-induced hearing loss in patients with laryngeal and hypopharyngeal carcinomas.

    Science.gov (United States)

    Gudelj, Goran; Trotić, Robert; Herceg, Tonko; Parazajder, Domagoj; Vagić, Davor; Geber, Goran

    2014-09-01

    The purpose of this study was to investigate a hypothesized correlation of development of a sensorineural hearing loss and radiotherapy in patients with laryngeal and hypopharyngeal carcinoma. This prospective study included a total of 50 patients, which after strict exclusion critera (audiologic problems before RT primary tumors of the auditory system, spread of the primary tumor to any part of the auditory system) resulted in 23 analyzed patients, ranging between 50 and 76 years of age, with a mean age of 60. Audiometry measuring frequency-specific thresholds was performed in three time points: one month before radiotherapy, one and six months after radiotherapy. A significant statistical difference in hearing tresholds after radiotherapy was found in 6 out of 23 patients. An obvious tendency towards hearing loss without statistical significance at 250 and 4000 Hz was found for a whole tested population (p < or = 0.3 with Bonferroni correction). Observed tendency towards hearing loss after radiotherapy of laryngeal carcinoma was related to side of the tumor and less severe when chemotherapy was not added as adjuvant therapy. These results should help to decrease a rate of hearing loss by careful planing of ear protection, by using observed frequencies as relevant markers of hearing loss and by reconsidering adjuvant chemoterapy during radiotherapy of laryngeal carcinoma.

  13. Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction

    Science.gov (United States)

    Furda, Amy M.; Marrangoni, Adele M.; Lokshin, Anna; Van Houten, Bennett

    2013-01-01

    Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H2O2) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer. We show that a 60 min treatment with H2O2 causes persistent mtDNA lesions, mtDNA loss, decreased levels of a nuclear-encoded mitochondrial subunit, a loss of ATP-linked oxidative phosphorylation and a loss of total reserve capacity. Conversely, a 60 min treatment with 2 mM MMS causes persistent mtDNA lesions but no mtDNA loss, no decrease in levels of a nuclear-encoded mitochondrial subunit, and no mitochondrial dysfunction. These results suggest that persistent mtDNA damage is not sufficient to cause mitochondrial dysfunction. PMID:22766155

  14. [Association between variations in protocadherin 15 gene and occupational noise-induced hearing loss].

    Science.gov (United States)

    Xu, X R; Yang, Q Y; 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: The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population. Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscan TM Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL. Results: The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years M ( P 25 , P 75 ) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups ( P= 0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% CI: 1.06- 3.40). After stratified these data by the noise exposure level

  15. The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes

    DEFF Research Database (Denmark)

    Hansen, Merethe; Lund, Michael Taulo; Jørgensen, Anne Line Kjærholm

    2016-01-01

    AIMS: The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N = 16) and without (OB, N = 27) type 2 diabetes was studied. METHODS: At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition......, and approximately one-third of the total improvement in GIR in T2DM was observed after the diet-induced weight loss of only ~6 kg (B). Insulin clearance, visceral fat and fasting plasma insulin also improved significantly after the diet (P ... not change significantly, but IMTG decreased significantly consistent with significant increases in GIR. Metabolic flexibility and hepatic insulin sensitivity improved after RYGB. CONCLUSIONS: Metabolic improvements of RYGB are present already after the diet-induced weight loss prior to surgery. GLUT4...

  16. Ligand mobility modulates immunological synapse formation and T cell activation.

    Directory of Open Access Journals (Sweden)

    Chih-Jung Hsu

    Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

  17. Spatially restricted actin-regulatory signaling contributes to synapse morphology

    Science.gov (United States)

    Nicholson, Daniel A.; Cahill, Michael E.; Tulisiak, Christopher T.; Geinisman, Yuri; Penzes, Peter

    2012-01-01

    The actin cytoskeleton in dendritic spines is organized into microdomains, but how signaling molecules that regulate actin are spatially governed is incompletely understood. Here we examine how the localization of the RacGEF kalirin-7, a well-characterized regulator of actin in spines, varies as a function of postsynaptic density (PSD) area and spine volume. Using serial section electron microscopy (EM), we find that extrasynaptic, but not synaptic, expression of kalirin-7 varies directly with synapse size and spine volume. Moreover, we find that overall expression levels of kalirin-7 differ in spines bearing perforated and non-perforated synapses, due primarily to extrasynaptic pools of kalirin-7 expression in the former. Overall, our findings indicate that kalirin-7 is differentially compartmentalized in spines as a function of both synapse morphology and spine size. PMID:22458534

  18. Dynamic mobility of functional GABAA receptors at inhibitory synapses.

    Science.gov (United States)

    Thomas, Philip; Mortensen, Martin; Hosie, Alastair M; Smart, Trevor G

    2005-07-01

    Importing functional GABAA receptors into synapses is fundamental for establishing and maintaining inhibitory transmission and for controlling neuronal excitability. By introducing a binding site for an irreversible inhibitor into the GABAA receptor alpha1 subunit channel lining region that can be accessed only when the receptor is activated, we have determined the dynamics of receptor mobility between synaptic and extrasynaptic locations in hippocampal pyramidal neurons. We demonstrate that the cell surface GABAA receptor population shows no fast recovery after irreversible inhibition. In contrast, after selective inhibition, the synaptic receptor population rapidly recovers by the import of new functional entities within minutes. The trafficking pathways that promote rapid importation of synaptic receptors do not involve insertion from intracellular pools, but reflect receptor diffusion within the plane of the membrane. This process offers the synapse a rapid mechanism to replenish functional GABAA receptors at inhibitory synapses and a means to control synaptic efficacy.

  19. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  20. Neuromorphic function learning with carbon nanotube based synapses

    International Nuclear Information System (INIS)

    Gacem, Karim; Filoramo, Arianna; Derycke, Vincent; Retrouvey, Jean-Marie; Chabi, Djaafar; Zhao, Weisheng; Klein, Jacques-Olivier

    2013-01-01

    The principle of using nanoscale memory devices as artificial synapses in neuromorphic circuits is recognized as a promising way to build ground-breaking circuit architectures tolerant to defects and variability. Yet, actual experimental demonstrations of the neural network type of circuits based on non-conventional/non-CMOS memory devices and displaying function learning capabilities remain very scarce. We show here that carbon-nanotube-based memory elements can be used as artificial synapses, combined with conventional neurons and trained to perform functions through the application of a supervised learning algorithm. The same ensemble of eight devices can notably be trained multiple times to code successively any three-input linearly separable Boolean logic function despite device-to-device variability. This work thus represents one of the very few demonstrations of actual function learning with synapses based on nanoscale building blocks. The potential of such an approach for the parallel learning of multiple and more complex functions is also evaluated. (paper)

  1. Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2011-08-01

    Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

  2. Dynamic Information Encoding With Dynamic Synapses in Neural Adaptation

    Science.gov (United States)

    Li, Luozheng; Mi, Yuanyuan; Zhang, Wenhao; Wang, Da-Hui; Wu, Si

    2018-01-01

    Adaptation refers to the general phenomenon that the neural system dynamically adjusts its response property according to the statistics of external inputs. In response to an invariant stimulation, neuronal firing rates first increase dramatically and then decrease gradually to a low level close to the background activity. This prompts a question: during the adaptation, how does the neural system encode the repeated stimulation with attenuated firing rates? It has been suggested that the neural system may employ a dynamical encoding strategy during the adaptation, the information of stimulus is mainly encoded by the strong independent spiking of neurons at the early stage of the adaptation; while the weak but synchronized activity of neurons encodes the stimulus information at the later stage of the adaptation. The previous study demonstrated that short-term facilitation (STF) of electrical synapses, which increases the synchronization between neurons, can provide a mechanism to realize dynamical encoding. In the present study, we further explore whether short-term plasticity (STP) of chemical synapses, an interaction form more common than electrical synapse in the cortex, can support dynamical encoding. We build a large-size network with chemical synapses between neurons. Notably, facilitation of chemical synapses only enhances pair-wise correlations between neurons mildly, but its effect on increasing synchronization of the network can be significant, and hence it can serve as a mechanism to convey the stimulus information. To read-out the stimulus information, we consider that a downstream neuron receives balanced excitatory and inhibitory inputs from the network, so that the downstream neuron only responds to synchronized firings of the network. Therefore, the response of the downstream neuron indicates the presence of the repeated stimulation. Overall, our study demonstrates that STP of chemical synapse can serve as a mechanism to realize dynamical neural

  3. Investigation of magnetic fluids exhibiting field-induced increasing loss peaks

    International Nuclear Information System (INIS)

    Fannin, P.C.; Marin, C.N.; Couper, C.

    2010-01-01

    A theoretical analysis to explain an increase of the Brownian loss peak with increasing polarizing field, H, in a magnetic fluid, is presented. The model is based on the competition between the Brownian and Neel relaxation processes. It is demonstrated that in magnetic fluids with particles having small anisotropy constant, small average magnetic diameter and narrow particle size distribution an increase of the Brownian loss peak with the polarizing field can be observed. The theoretical results are compared with the experimental results of an Isopar M-based magnetic fluid with magnetite particles stabilized with oleic acid and the model explains qualitatively the main characteristics of the experimental results.

  4. Distinct transmitter release properties determine differences in short-term plasticity at functional and silent synapses.

    Science.gov (United States)

    Cabezas, Carolina; Buño, Washington

    2006-05-01

    Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+ stores influenced the release properties of these synapses. Ryanodine (100 microM) and thapsigargin (1 microM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.

  5. Mutations in Cockayne Syndrome-Associated Genes (Csa and Csb) Predispose to Cisplatin-Induced Hearing Loss in Mice

    Science.gov (United States)

    Rainey, Robert N.; Ng, Sum-yan; Llamas, Juan; van der Horst, Gijsbertus T. J.

    2016-01-01

    Cisplatin is a common and effective chemotherapeutic agent, yet it often causes permanent hearing loss as a result of sensory hair cell death. The causes of sensitivity to DNA-damaging agents in nondividing cell populations, such as cochlear hair and supporting cells, are poorly understood, as are the specific DNA repair pathways that protect these cells. Nucleotide excision repair (NER) is a conserved and versatile DNA repair pathway for many DNA-distorting lesions, including cisplatin-DNA adducts. Progressive sensorineural hearing loss is observed in a subset of NER-associated DNA repair disorders including Cockayne syndrome and some forms of xeroderma pigmentosum. We investigated whether either of the two overlapping branches that encompass NER, transcription-coupled repair or global genome repair, which are implicated in Cockayne syndrome and xeroderma pigmentosum group C, respectively, modulates cisplatin-induced hearing loss and cell death in the organ of Corti, the auditory sensory epithelium of mammals. We report that cochlear hair cells and supporting cells in transcription-coupled repair-deficient Cockayne syndrome group A (Csa−/−) and group B (Csb−/−) mice are hypersensitive to cisplatin, in contrast to global genome repair-deficient Xpc−/− mice, both in vitro and in vivo. We show that sensory hair cells in Csa−/− and Csb−/− mice fail to remove cisplatin-DNA adducts efficiently in vitro; and unlike Xpc−/− mice, Csa−/− and Csb−/− mice lose hearing and manifest outer hair cell degeneration after systemic cisplatin treatment. Our results demonstrate that Csa and Csb deficiencies predispose to cisplatin-induced hearing loss and hair/supporting cell damage in the mammalian organ of Corti, and emphasize the importance of transcription-coupled DNA repair in the protection against cisplatin ototoxicity. SIGNIFICANCE STATEMENT The utility of cisplatin in chemotherapy remains limited due to serious side effects, including

  6. Respective roles of direct GHG radiative forcing and induced Arctic sea ice loss on the Northern Hemisphere atmospheric circulation

    Science.gov (United States)

    Oudar, Thomas; Sanchez-Gomez, Emilia; Chauvin, Fabrice; Cattiaux, Julien; Terray, Laurent; Cassou, Christophe

    2017-12-01

    The large-scale and synoptic-scale Northern Hemisphere atmospheric circulation responses to projected late twenty-first century Arctic sea ice decline induced by increasing Greenhouse Gases (GHGs) concentrations are investigated using the CNRM-CM5 coupled model. An original protocol, based on a flux correction technique, allows isolating the respective roles of GHG direct radiative effect and induced Arctic sea ice loss under RCP8.5 scenario. In winter, the surface atmospheric response clearly exhibits opposing effects between GHGs increase and Arctic sea ice loss, leading to no significant pattern in the total response (particularly in the North Atlantic region). An analysis based on Eady growth rate shows that Arctic sea ice loss drives the weakening in the low-level meridional temperature gradient, causing a general decrease of the baroclinicity in the mid and high latitudes, whereas the direct impact of GHGs increase is more located in the mid-to-high troposphere. Changes in the flow waviness, evaluated from sinuosity and blocking frequency metrics, are found to be small relative to inter-annual variability.

  7. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Tae-Ho Kim

    2016-01-01

    Full Text Available Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr cocoons spun by Rhus javanica (Bell. Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr or 100% ethanolic extract (eeGr on ovariectomy- (OVX- induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks augmented the inhibition of femoral bone mineral density (BMD, bone mineral content (BMC, and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

  8. Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.

    Science.gov (United States)

    Velázquez, Kandy T; Enos, Reilly T; Carson, Meredith S; Cranford, Taryn L; Bader, Jackie E; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi; Davis, J Mark; Carson, James A; Murphy, E Angela

    2016-10-01

    Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80 + CD206 + macrophages and activated T cells (CD4 + CD69 + ) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms. Copyright © 2016 the American Physiological Society.

  9. Study on TAE-induced fast-ion loss process in LHD

    International Nuclear Information System (INIS)

    Ogawa, K.; Isobe, M.; Toi, K.; Shimizu, A.; Osakabe, M.; Spong, D.A.; Yamamoto, S.

    2013-01-01

    In this paper, we report experimentally observed characteristics of fast-ion loss caused by TAE in non-axisymmetric system. We also make a comparison between experiment and simulation with the aid of orbit-following particle calculation that incorporates TAE magnetic fluctuations. (J.P.N.)

  10. Acute drug induced hepatitis secondary to a weight loss product purchased over the internet

    Directory of Open Access Journals (Sweden)

    Cross Tim JS

    2007-06-01

    Full Text Available Abstract Background Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet. Case Presentation A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L. A chronic liver disease screen was negative. The patient had started a weight loss product (Pro-Lean, purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product. Conclusion This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis.

  11. Surgically Induced Interpregnancy Weight Loss and Prevalence of Overweight and Obesity in Offspring

    DEFF Research Database (Denmark)

    Willmer, Mikaela; Berglind, Daniel; Sørensen, Thorkild I.A.

    2013-01-01

    According to the fetal overnutrition hypothesis, obesity in pregnancy predisposes the offspring to obesity. Previous studies have suggested that after biliopancreatic surgery for obesity, the offspring is less likely to be obese. This study aims to further compare the BMI development of children...... born before and after maternal surgical weight loss....

  12. A Study of Moisture Induced Material Loss of Hot Mix Asphalt (HMA)

    Science.gov (United States)

    2017-10-31

    Maine Department of Transportation has noticed the partial or complete loss of material within 2-3 years of construction in the traffic wheel path in the presence of moisture in few of their mixes. Regularly used moisture susceptibility tests are una...

  13. Noise‑Induced Hearing Loss Still a Problem in Shipbuilders: A ...

    African Journals Online (AJOL)

    relevant factors implicated in the multi‑factorial aetiology of NIHL (age, duration of .... metal fragments entering the ear was also asked in view of ... Pure tone thresholds for bone ... disease (two with Grade I and one with Grade II hearing loss).

  14. Effects of Urbanization-Induced Cultivated Land Loss on Ecosystem Services in the North China Plain

    Directory of Open Access Journals (Sweden)

    Wei Song

    2015-06-01

    Full Text Available Since the implementation of market oriented economic reform in 1978, China has been on the track of rapid urbanization. The unprecedented urbanization in China has resulted in substantial cultivated land loss and rapid expansion of urban areas. The cultivated land loss due to urbanization not only threatens food security in China, but has also led to ecological system degradation to which close attention should be paid. Therefore, we examined the effects of the conversion from cultivated to urban areas on the ecosystem service in the North China Plain on the basis of a net primary productivity based ecosystem service model (NESM and a buffer comparison method. Cultivated land loss due to urbanization in the North China Plain led to a total loss of ecosystem service value of 34.66% during the period 1988–2008. Urban expansion significantly decreased the ecosystem service function of water conservation (–124.03%, nutrient cycling (–31.91%, gas regulation (−7.18%, and organic production (–7.18%, while it improved the soil conservation function (2.40%. Land use change accounted for 57.40% of the changes in ecosystem service and had a major influence on the changes in nutrient cycling and water conservation. However, climate change mainly determined the changes in gas regulation, organic production, and soil conservation.

  15. Interventions to prevent occupational noise-induced hearing loss: a Cochrane systematic review

    NARCIS (Netherlands)

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

    2014-01-01

    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

  16. Loss of inducible photorepair in a frog cell line hypersensitive to solar UV light

    International Nuclear Information System (INIS)

    Chao, C.C.-K.

    1987-01-01

    The induction of enzymatic photorepair (EPR) in ICR 2A frog cells and a derived mutant cell line DRP36 hypersensitive to solar UV was studied. Using clonogenic assays, when induced wild-type cells demonstrated an 8-fold increase of EPR the mutant cells displayed a near-background level of inducible EPR. The constitutive EPR in mutant cells, however, was the same as in wild-type cells. A mixed culture of ICR 2A and DRP36 cells showed an intermediate inducible EPR depending upon the cell ratio. Inducible EPR was also detected at the DNA level in wild-type cells, but not in mutant cells. 29 refs.; 2 figs.; 2 tabs

  17. RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans.

    Science.gov (United States)

    Grill, Brock; Chen, Lizhen; Tulgren, Erik D; Baker, Scott T; Bienvenut, Willy; Anderson, Matthew; Quadroni, Manfredo; Jin, Yishi; Garner, Craig C

    2012-02-22

    Previous studies in Caenorhabditis elegans showed that RPM-1 (Regulator of Presynaptic Morphology-1) regulates axon termination and synapse formation. To understand the mechanism of how rpm-1 functions, we have used mass spectrometry to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein-1) as an evolutionarily conserved binding partner. We define a RAE-1 binding region in RPM-1, and show that this binding interaction is conserved and also occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein associated with Myc). rae-1 loss of function causes similar axon and synapse defects, and synergizes genetically with two other RPM-1 binding proteins, GLO-4 and FSN-1. Further, we show that RAE-1 colocalizes with RPM-1 in neurons, and that rae-1 functions downstream of rpm-1. These studies establish a novel postmitotic function for rae-1 in neuronal development.

  18. The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.

    Science.gov (United States)

    Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E; Johnson, Jo Anne; McGraw, Constance; Block, Michelle L

    2013-06-01

    Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson's disease-like pathology. To begin to address how DEP may exert CNS effects, microglia and neuron-glia cultures were treated with either nanometer-sized DEP (neuron function was assessed. All three treatments showed enhanced ameboid microglia morphology, increased H2 O2 production, and decreased DA uptake. Mechanistic inquiry revealed that the scavenger receptor inhibitor fucoidan blocked DEP internalization in microglia, but failed to alter DEP-induced H2 O2 production in microglia. However, pre-treatment with the MAC1/CD11b inhibitor antibody blocked microglial H2 O2 production in response to DEP. MAC1(-/-) mesencephalic neuron-glia cultures were protected from DEP-induced loss of DA neuron function, as measured by DA uptake. These findings support that DEP may activate microglia through multiple mechanisms, where scavenger receptors regulate internalization of DEP and the MAC1 receptor is mandatory for both DEP-induced microglial H2 O2 production and loss of DA neuron function. © 2013 International Society for Neurochemistry.

  19. Effects of noise-induced hearing loss on parvalbumin and perineuronal net expression in the mouse primary auditory cortex.

    Science.gov (United States)

    Nguyen, Anna; Khaleel, Haroun M; Razak, Khaleel A

    2017-07-01

    Noise induced hearing loss is associated with increased excitability in the central auditory system but the cellular correlates of such changes remain to be characterized. Here we tested the hypothesis that noise-induced hearing loss causes deterioration of perineuronal nets (PNNs) in the auditory cortex of mice. PNNs are specialized extracellular matrix components that commonly enwrap cortical parvalbumin (PV) containing GABAergic interneurons. Compared to somatosensory and visual cortex, relatively less is known about PV/PNN expression patterns in the primary auditory cortex (A1). Whether changes to cortical PNNs follow acoustic trauma remains unclear. The first aim of this study was to characterize PV/PNN expression in A1 of adult mice. PNNs increase excitability of PV+ inhibitory neurons and confer protection to these neurons against oxidative stress. Decreased PV/PNN expression may therefore lead to a reduction in cortical inhibition. The second aim of this study was to examine PV/PNN expression in superficial (I-IV) and deep cortical layers (V-VI) following noise trauma. Exposing mice to loud noise caused an increase in hearing threshold that lasted at least 30 days. PV and PNN expression in A1 was analyzed at 1, 10 and 30 days following the exposure. No significant changes were observed in the density of PV+, PNN+, or PV/PNN co-localized cells following hearing loss. However, a significant layer- and cell type-specific decrease in PNN intensity was seen following hearing loss. Some changes were present even at 1 day following noise exposure. Attenuation of PNN may contribute to changes in excitability in cortex following noise trauma. The regulation of PNN may open up a temporal window for altered excitability in the adult brain that is then stabilized at a new and potentially pathological level such as in tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Results and analysis of a loss-of-feedwater induced ATWS experiment in the LOFT Facility

    International Nuclear Information System (INIS)

    Grush, W.H.; Koizumi, Y.; Woerth, S.C.

    1983-01-01

    An anticipated transient without scram (ATWS), initiated by a loss of feedwater, was experimentally simulated in the Loss-of-Fluid Test (LOFT) pressurized water reactor (PWR). Primary system pressure was controlled using a two-position actuator relief valve to simulate a scaled power-operated relief valve (PORV) and safety relief valve (SRV) representative of those in a commercial PWR. Auxiliary feedwater injection was delayed during the experiment until the plant recovery phase where long-term shutdown was achieved by an operator-controlled plant recovery procedure without inserting the control rods. The system transient response predicted by the RELAP5/MOD1 computer code showed good agreement with the experimental data

  1. The influence of single bursts vs. single spikes at excitatory dendrodendritic synapses

    Science.gov (United States)

    Masurkar, Arjun V.; Chen, Wei R.

    2015-01-01

    The synchronization of neuronal activity is thought to enhance information processing. There is much evidence supporting rhythmically bursting external tufted cells (ETCs) of the rodent olfactory bulb glomeruli coordinating the activation of glomerular interneurons and mitral cells via dendrodendritic excitation. However, as bursting has variable significance at axodendritic cortical synapses, it is not clear if ETC bursting imparts a specific functional advantage over the preliminary spike in dendrodendritic synaptic networks. To answer this question, we investigated the influence of single ETC bursts and spikes with the in-vitro rat olfactory bulb preparation at different levels of processing, via calcium imaging of presynaptic ETC dendrites, dual electrical recording of ETC–interneuron synaptic pairs, and multicellular calcium imaging of ETC-induced population activity. Our findings supported single ETC bursts, vs. single spikes, driving robust presynaptic calcium signaling, which in turn was associated with profound extension of the initial monosynaptic spike-driven dendrodendritic excitatory postsynaptic potential. This extension could be driven by either the spike-dependent or spike-independent components of the burst. At the population level, burst-induced excitation was more widespread and reliable compared with single spikes. This further supports the ETC network, in part due to a functional advantage of bursting at excitatory dendrodendritic synapses, coordinating synchronous activity at behaviorally relevant frequencies related to odor processing in vivo. PMID:22277089

  2. The influence of single bursts versus single spikes at excitatory dendrodendritic synapses.

    Science.gov (United States)

    Masurkar, Arjun V; Chen, Wei R

    2012-02-01

    The synchronization of neuronal activity is thought to enhance information processing. There is much evidence supporting rhythmically bursting external tufted cells (ETCs) of the rodent olfactory bulb glomeruli coordinating the activation of glomerular interneurons and mitral cells via dendrodendritic excitation. However, as bursting has variable significance at axodendritic cortical synapses, it is not clear if ETC bursting imparts a specific functional advantage over the preliminary spike in dendrodendritic synaptic networks. To answer this question, we investigated the influence of single ETC bursts and spikes with the in vitro rat olfactory bulb preparation at different levels of processing, via calcium imaging of presynaptic ETC dendrites, dual electrical recording of ETC -interneuron synaptic pairs, and multicellular calcium imaging of ETC-induced population activity. Our findings supported single ETC bursts, versus single spikes, driving robust presynaptic calcium signaling, which in turn was associated with profound extension of the initial monosynaptic spike-driven dendrodendritic excitatory postsynap