24 results on '"Layer, N"'
Search Results
2. Überprüfung des Versorgungsergebnisses bei Kindern mit Hörgerät und Cochlea-Implantat mithilfe des mFAST-Hörtests
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Urban, A, Holube, I, Streicher, B, Lang-Roth, R, Kral, K, Pützer, E, Layer, N, Sandmann, P, Urban, A, Holube, I, Streicher, B, Lang-Roth, R, Kral, K, Pützer, E, Layer, N, and Sandmann, P
- Published
- 2023
3. Altered audio-visual interactions in cochlear-implant users: behavioral and electrophysiological evidence
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Sandmann, P, Layer, N, Weglage, A, Radecke, JO, Lang-Roth, R, Meister, H, Walger, M, Müller, V, Sandmann, P, Layer, N, Weglage, A, Radecke, JO, Lang-Roth, R, Meister, H, Walger, M, and Müller, V
- Published
- 2023
4. Translational modelling of gene therapy for pharmacoresistant epilepsy in human brain slice cultures
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Wuttke, TV, Schwarz, N, Santuy, A, Vial, LR, Layer, N, Honegger, JB, Ort, J, Bak, A, Delev, D, Hedrich, UBS, Koch, H, Wuttke, TV, Schwarz, N, Santuy, A, Vial, LR, Layer, N, Honegger, JB, Ort, J, Bak, A, Delev, D, Hedrich, UBS, and Koch, H
- Published
- 2022
5. Vorhersage des CI-Versorgungsergebnisses mit Hilfe von visuell evozierten Potenzialen
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Weglage, A, Layer, N, Müller, V, Walger, M, Lang-Roth, R, Meister, H, Sandmann, P, Weglage, A, Layer, N, Müller, V, Walger, M, Lang-Roth, R, Meister, H, and Sandmann, P
- Published
- 2022
6. Objektivierung des Einflusses von ForwardFocus auf die auditorische und audiovisuelle Sprachverarbeitung im Störgeräusch: Eine EEG-Studie
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Layer, N, Abdel-Latif, K, Hessel, H, Müller, V, Weglage, A, Walger, M, Lang-Roth, R, Sandmann, P, Layer, N, Abdel-Latif, K, Hessel, H, Müller, V, Weglage, A, Walger, M, Lang-Roth, R, and Sandmann, P
- Published
- 2022
7. Unterschiede in der audiovisuellen Sprachverarbeitung bei CI-Patienten mit einseitigem und beidseitigem Hörverlust: eine EEG-Studie
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Layer, N, Weglage, A, Müller, V, Walger, M, Lang-Roth, R, Meister, H, Sandmann, P, Layer, N, Weglage, A, Müller, V, Walger, M, Lang-Roth, R, Meister, H, and Sandmann, P
- Published
- 2022
8. Dravet variant SCN1AA1783V impairs interneuron firing predominantly by altered channel activation
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Layer, N., primary, Sonnenberg, L., additional, Pardo González, E., additional, Benda, J., additional, Lerche, H., additional, Koch, H., additional, and Wuttke, TV., additional
- Published
- 2021
- Full Text
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9. The Timed Tandem Walk as a Measure of Mild Impairment in Patients with Multiple Sclerosis.
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Herbert, Joseph, Russell, H., Kasten, L., Jakubowska-Sadowska, K., Layer, N., Fromm, J., and Del Bene, M.
- Published
- 2006
10. Neural deception: Breast cancer co-opts neuronal mechanisms to evade the immune system.
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Layer N, Bunse L, and Venkataramani V
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- Humans, Female, Immune System immunology, Animals, Breast Neoplasms immunology, Breast Neoplasms pathology, Neurons metabolism, Neurons immunology
- Abstract
Cellular mechanisms mediating immunotherapy resistances are incompletely understood. In this issue, Li et al. reveal how breast cancer hijacks neuronal mechanisms of neuroprotection to shield itself from the immune system. Secretion of N-acetylaspartate impairs immune synapse formation in both neuroinflammation and breast cancer models, paving the way for novel therapeutic approaches., Competing Interests: Declaration of interests L.B. is an inventor on the patent for T cell receptor-derived binding polypeptides PCT/EP2023/061716. L.B. received honoraria from Adaptive Biotechnologies., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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11. Changes in visually and auditory attended audiovisual speech processing in cochlear implant users: A longitudinal ERP study.
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Weglage A, Layer N, Meister H, Müller V, Lang-Roth R, Walger M, and Sandmann P
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- Humans, Male, Female, Middle Aged, Adult, Prospective Studies, Longitudinal Studies, Case-Control Studies, Aged, Visual Perception, Lipreading, Time Factors, Hearing, Evoked Potentials, Auditory, Auditory Cortex physiopathology, Evoked Potentials, Cochlear Implants, Speech Perception, Cochlear Implantation instrumentation, Electroencephalography, Acoustic Stimulation, Persons With Hearing Impairments psychology, Persons With Hearing Impairments rehabilitation, Deafness physiopathology, Deafness rehabilitation, Deafness psychology, Attention, Photic Stimulation
- Abstract
Limited auditory input, whether caused by hearing loss or by electrical stimulation through a cochlear implant (CI), can be compensated by the remaining senses. Specifically for CI users, previous studies reported not only improved visual skills, but also altered cortical processing of unisensory visual and auditory stimuli. However, in multisensory scenarios, it is still unclear how auditory deprivation (before implantation) and electrical hearing experience (after implantation) affect cortical audiovisual speech processing. Here, we present a prospective longitudinal electroencephalography (EEG) study which systematically examined the deprivation- and CI-induced alterations of cortical processing of audiovisual words by comparing event-related potentials (ERPs) in postlingually deafened CI users before and after implantation (five weeks and six months of CI use). A group of matched normal-hearing (NH) listeners served as controls. The participants performed a word-identification task with congruent and incongruent audiovisual words, focusing their attention on either the visual (lip movement) or the auditory speech signal. This allowed us to study the (top-down) attention effect on the (bottom-up) sensory cortical processing of audiovisual speech. When compared to the NH listeners, the CI candidates (before implantation) and the CI users (after implantation) exhibited enhanced lipreading abilities and an altered cortical response at the N1 latency range (90-150 ms) that was characterized by a decreased theta oscillation power (4-8 Hz) and a smaller amplitude in the auditory cortex. After implantation, however, the auditory-cortex response gradually increased and developed a stronger intra-modal connectivity. Nevertheless, task efficiency and activation in the visual cortex was significantly modulated in both groups by focusing attention on the visual as compared to the auditory speech signal, with the NH listeners additionally showing an attention-dependent decrease in beta oscillation power (13-30 Hz). In sum, these results suggest remarkable deprivation effects on audiovisual speech processing in the auditory cortex, which partially reverse after implantation. Although even experienced CI users still show distinct audiovisual speech processing compared to NH listeners, pronounced effects of (top-down) direction of attention on (bottom-up) audiovisual processing can be observed in both groups. However, NH listeners but not CI users appear to show enhanced allocation of cognitive resources in visually as compared to auditory attended audiovisual speech conditions, which supports our behavioural observations of poorer lipreading abilities and reduced visual influence on audition in NH listeners as compared to CI users., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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12. Effects of noise and noise reduction on audiovisual speech perception in cochlear implant users: An ERP study.
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Layer N, Abdel-Latif KHA, Radecke JO, Müller V, Weglage A, Lang-Roth R, Walger M, and Sandmann P
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- Humans, Evoked Potentials, Noise adverse effects, Cochlear Implants, Speech Perception physiology, Cochlear Implantation
- Abstract
Objective: Hearing with a cochlear implant (CI) is difficult in noisy environments, but the use of noise reduction algorithms, specifically ForwardFocus, can improve speech intelligibility. The current event-related potentials (ERP) study examined the electrophysiological correlates of this perceptual improvement., Methods: Ten bimodal CI users performed a syllable-identification task in auditory and audiovisual conditions, with syllables presented from the front and stationary noise presented from the sides. Brainstorm was used for spatio-temporal evaluation of ERPs., Results: CI users revealed an audiovisual benefit as reflected by shorter response times and greater activation in temporal and occipital regions at P2 latency. However, in auditory and audiovisual conditions, background noise hampered speech processing, leading to longer response times and delayed auditory-cortex-activation at N1 latency. Nevertheless, activating ForwardFocus resulted in shorter response times, reduced listening effort and enhanced superior-frontal-cortex-activation at P2 latency, particularly in audiovisual conditions., Conclusions: ForwardFocus enhances speech intelligibility in audiovisual speech conditions by potentially allowing the reallocation of attentional resources to relevant auditory speech cues., Significance: This study shows for CI users that background noise and ForwardFocus differentially affect spatio-temporal cortical response patterns, both in auditory and audiovisual speech conditions., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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13. Electrophysiological differences and similarities in audiovisual speech processing in CI users with unilateral and bilateral hearing loss.
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Layer N, Weglage A, Müller V, Meister H, Lang-Roth R, Walger M, Murray MM, and Sandmann P
- Abstract
Hearing with a cochlear implant (CI) is limited compared to natural hearing. Although CI users may develop compensatory strategies, it is currently unknown whether these extend from auditory to visual functions, and whether compensatory strategies vary between different CI user groups. To better understand the experience-dependent contributions to multisensory plasticity in audiovisual speech perception, the current event-related potential (ERP) study presented syllables in auditory, visual, and audiovisual conditions to CI users with unilateral or bilateral hearing loss, as well as to normal-hearing (NH) controls. Behavioural results revealed shorter audiovisual response times compared to unisensory conditions for all groups. Multisensory integration was confirmed by electrical neuroimaging, including topographic and ERP source analysis, showing a visual modulation of the auditory-cortex response at N1 and P2 latency. However, CI users with bilateral hearing loss showed a distinct pattern of N1 topography, indicating a stronger visual impact on auditory speech processing compared to CI users with unilateral hearing loss and NH listeners. Furthermore, both CI user groups showed a delayed auditory-cortex activation and an additional recruitment of the visual cortex, and a better lip-reading ability compared to NH listeners. In sum, these results extend previous findings by showing distinct multisensory processes not only between NH listeners and CI users in general, but even between CI users with unilateral and bilateral hearing loss. However, the comparably enhanced lip-reading ability and visual-cortex activation in both CI user groups suggest that these visual improvements are evident regardless of the hearing status of the contralateral ear., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
- Published
- 2022
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14. Side-of-Implantation Effect on Functional Asymmetry in the Auditory Cortex of Single-Sided Deaf Cochlear-Implant Users.
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Weglage A, Müller V, Layer N, Abdel-Latif KHA, Lang-Roth R, Walger M, and Sandmann P
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- Humans, Auditory Cortex, Cochlear Implantation methods, Cochlear Implants, Deafness, Hearing Loss, Unilateral, Speech Perception physiology
- Abstract
Cochlear implants (CIs) allow to restore the hearing function in profoundly deaf individuals. Due to the degradation of the stimulus by CI signal processing, implanted individuals with single-sided deafness (SSD) have the specific challenge that the input highly differs between their ears. The present study compared normal-hearing (NH) listeners (N = 10) and left- and right-ear implanted SSD CI users (N = 10 left, N = 9 right), to evaluate cortical speech processing between CI- and NH-ears and to explore for side-of-implantation effects. The participants performed a two-deviant oddball task, separately with the left and the right ear. Auditory event-related potentials (ERPs) in response to syllables were compared between proficient and non-proficient CI users, as well as between CI and NH ears. The effect of the side of implantation was analysed on the sensor and the source level. CI proficiency could be distinguished based on the ERP amplitudes of the N1 and the P3b. Moreover, syllable processing via the CI ear, when compared to the NH ear, resulted in attenuated and delayed ERPs. In addition, the left-ear implanted SSD CI users revealed an enhanced functional asymmetry in the auditory cortex than right-ear implanted SSD CI users, regardless of whether the syllables were perceived via the CI or the NH ear. Our findings reveal that speech-discrimination proficiency in SSD CI users can be assessed by N1 and P3b ERPs. The results contribute to a better understanding of the rehabilitation success in SSD CI users by showing that cortical speech processing in SSD CI users is affected by CI-related stimulus degradation and experience-related functional changes in the auditory cortex., (© 2022. The Author(s).)
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- 2022
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15. The timecourse of multisensory speech processing in unilaterally stimulated cochlear implant users revealed by ERPs.
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Layer N, Weglage A, Müller V, Meister H, Lang-Roth R, Walger M, Murray MM, and Sandmann P
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- Acoustic Stimulation methods, Auditory Perception physiology, Evoked Potentials, Humans, Speech, Visual Perception physiology, Cochlear Implantation, Cochlear Implants, Speech Perception physiology
- Abstract
A cochlear implant (CI) is an auditory prosthesis which can partially restore the auditory function in patients with severe to profound hearing loss. However, this bionic device provides only limited auditory information, and CI patients may compensate for this limitation by means of a stronger interaction between the auditory and visual system. To better understand the electrophysiological correlates of audiovisual speech perception, the present study used electroencephalography (EEG) and a redundant target paradigm. Postlingually deafened CI users and normal-hearing (NH) listeners were compared in auditory, visual and audiovisual speech conditions. The behavioural results revealed multisensory integration for both groups, as indicated by shortened response times for the audiovisual as compared to the two unisensory conditions. The analysis of the N1 and P2 event-related potentials (ERPs), including topographic and source analyses, confirmed a multisensory effect for both groups and showed a cortical auditory response which was modulated by the simultaneous processing of the visual stimulus. Nevertheless, the CI users in particular revealed a distinct pattern of N1 topography, pointing to a strong visual impact on auditory speech processing. Apart from these condition effects, the results revealed ERP differences between CI users and NH listeners, not only in N1/P2 ERP topographies, but also in the cortical source configuration. When compared to the NH listeners, the CI users showed an additional activation in the visual cortex at N1 latency, which was positively correlated with CI experience, and a delayed auditory-cortex activation with a reversed, rightward functional lateralisation. In sum, our behavioural and ERP findings demonstrate a clear audiovisual benefit for both groups, and a CI-specific alteration in cortical activation at N1 latency when auditory and visual input is combined. These cortical alterations may reflect a compensatory strategy to overcome the limited CI input, which allows the CI users to improve the lip-reading skills and to approximate the behavioural performance of NH listeners in audiovisual speech conditions. Our results are clinically relevant, as they highlight the importance of assessing the CI outcome not only in auditory-only, but also in audiovisual speech conditions., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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16. The effect of lamotrigine and other antiepileptic drugs on respiratory rhythm generation in the pre-Bötzinger complex.
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Layer N, Brandes J, Lührs PJ, Wuttke TV, and Koch H
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- Animals, Hypoxia, Lamotrigine, Mice, Sodium, Sodium Channel Blockers pharmacology, Sodium Channel Blockers therapeutic use, Anticonvulsants adverse effects, Sudden Unexpected Death in Epilepsy
- Abstract
Objective: Lamotrigine and other sodium-channel blocking agents are among the most commonly used antiepileptic drugs (AEDs). Because other sodium channel blockers, such as riluzole, can severely alter respiratory rhythm generation during hypoxia, we wanted to investigate if AEDs can have similar effects. This is especially important in the context of sudden unexpected death in epilepsy (SUDEP), the major cause of death in patients suffering from therapy-resistant epilepsy. Although the mechanism of action is not entirely understood, respiratory dysfunction after generalized tonic-clonic seizures seems to play a major role., Methods: We used transverse brainstem slice preparations from neonatal and juvenile mice containing the pre-Bötzinger complex (PreBötC) and measured population as well as intracellular activity of the rhythm-generating network under normoxia and hypoxia in the presence or absence of AEDs., Results: We found a substantial inhibition of the gasping response induced by the application of sodium channel blockers (lamotrigine and carbamazepine). In contrast, levetiracetam, an AED-modulating synaptic function, had a much smaller effect. The inhibition of gasping by lamotrigine was accompanied by a significant reduction of the persistent sodium current (INap) in PreBötC neurons. Surprisingly, the suppression of persistent sodium currents by lamotrigine did not affect the voltage-dependent bursting activity in PreBötC pacemaker neurons, but led to a hypoxia-dependent shift of the action potential rheobase in all measured PreBötC neurons., Significance: Our results contribute to the understanding of the effects of AEDs on the vital respiratory functions of the central nervous system. Moreover, our study adds further insight into sodium-dependent changes occurring during hypoxia and the contribution of cellular properties to the respiratory rhythm generation in the pre-Bötzinger complex. It raises the question of whether sodium channel blocking AEDs could, in conditions of extreme hypoxia, contribute to SUDEP, an important issue that warrants further studies., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
- Published
- 2021
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17. Dravet Variant SCN1A A 1783 V Impairs Interneuron Firing Predominantly by Altered Channel Activation.
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Layer N, Sonnenberg L, Pardo González E, Benda J, Hedrich UBS, Lerche H, Koch H, and Wuttke TV
- Abstract
Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional Na
V 1.1 haploinsufficiency in inhibitory interneurons. Recently, a new conditional mouse model expressing the recurrent human p.(Ala1783Val) missense variant has become available. In this study, we provided an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Based on these data, simulated interneuron (IN) firing properties in a conductance-based single-compartment model suggested surprisingly similar firing deficits for NaV 1.1A1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired NaV 1.1A1783V channel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditional Scn1aA 1783 V mice. Pan-neuronal activation of the p.Ala1783V in vitro confirmed a predicted IN firing deficit and revealed an accompanying reduction of interneuronal input resistance while demonstrating normal excitability of pyramidal neurons. Altered input resistance was fed back into the model for further refinement. Taken together these data demonstrate that primary loss of function (LOF) gating properties accompanied by altered membrane characteristics may match effects of full haploinsufficiency on the neuronal level despite maintaining physiological peak current density, thereby causing DS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Layer, Sonnenberg, Pardo González, Benda, Hedrich, Lerche, Koch and Wuttke.)- Published
- 2021
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18. Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices.
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Wickham J, Corna A, Schwarz N, Uysal B, Layer N, Honegger JB, Wuttke TV, Koch H, and Zeck G
- Abstract
Human cerebrospinal fluid (hCSF) has proven advantageous over conventional medium for culturing both rodent and human brain tissue. In addition, increased activity and synchrony, closer to the dynamic states exclusively recorded in vivo , were reported in rodent slices and cell cultures switching from artificial cerebrospinal fluid (aCSF) to hCSF. This indicates that hCSF possesses properties that are not matched by the aCSF, which is generally used for most electrophysiological recordings. To evaluate the possible significance of using hCSF as an electrophysiological recording medium, also for human brain tissue, we compared the network and single-cell firing properties of human brain slice cultures during perfusion with hCSF and aCSF. For measuring the overall activity from a majority of neurons within neocortical and hippocampal human slices, we used a microelectrode array (MEA) recording technique with 252 electrodes covering an area of 3.2 × 3.2 mm
2 . A second CMOS-based MEA with 4225 sensors on a 2 × 2 mm2 area was used for detailed mapping of action potential waveforms and cell identification. We found that hCSF increased the number of active electrodes and neurons and the firing rate of the neurons in the slices and induced an increase in the numbers of single channel and population bursts. Interestingly, not only an increase in the overall activity in the slices was observed, but a reconfiguration of the network could also be detected with specific activation and inactivation of subpopulations of neuronal ensembles. In conclusion, hCSF is an important component to consider for future human brain slice studies, especially for experiments designed to mimic parts of physiology and disease observed in vivo ., (Copyright © 2020 Wickham, Corna, Schwarz, Uysal, Layer, Honegger, Wuttke, Koch and Zeck.)- Published
- 2020
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19. Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease.
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Schwarz N, Uysal B, Welzer M, Bahr JC, Layer N, Löffler H, Stanaitis K, Pa H, Weber YG, Hedrich UB, Honegger JB, Skodras A, Becker AJ, Wuttke TV, and Koch H
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- Adult, Brain pathology, Brain physiopathology, Humans, Intravital Microscopy methods, Pyramidal Cells pathology, Pyramidal Cells physiology, Brain anatomy & histology, Brain physiology, Organ Culture Techniques methods
- Abstract
Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling 'high throughput' fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro . This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry., Competing Interests: NS, BU, MW, JB, NL, HL, KS, HP, YW, UH, JH, AS, AB, TW, HK No competing interests declared, (© 2019, Schwarz et al.)
- Published
- 2019
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20. Energy depletion and not ROS formation is a crucial step of glucolipotoxicity (GLTx) in pancreatic beta cells.
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Barroso Oquendo M, Layer N, Wagner R, Krippeit-Drews P, and Drews G
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- Adenosine Triphosphate metabolism, Animals, Cells, Cultured, Gliclazide pharmacology, Glucose metabolism, Hypoglycemic Agents pharmacology, Insulin metabolism, Insulin-Secreting Cells drug effects, KATP Channels metabolism, Membrane Potential, Mitochondrial, Mice, Mice, Inbred C57BL, Tolbutamide pharmacology, Apoptosis, Energy Metabolism, Insulin-Secreting Cells metabolism, Reactive Oxygen Species metabolism
- Abstract
We have shown previously that genetic or pharmacological deletion of K
ATP channels protect against beta cell dysfunction induced by reactive oxygen species (ROS). Since it is assumed that glucolipotoxicity (GLTx) causes ROS production, we aimed to evaluate whether suppression of KATP channel activity can also prevent beta cell damage evoked by GLTx. We used an in vitro model of GLTx and measured distinct parameters of stimulus-secretion coupling. GLTx gradually induced disturbances of Ca2+ oscillations over 3 days. This impairment in Ca2+ dynamics was partially reversed in beta cells without functional KATP channels (SUR1-/- ) and by the sulfonylurea gliclazide but not by tolbutamide. By contrast, the GLTx-induced suppression of glucose-induced insulin secretion could not be rescued by decreased KATP channel activity pointing to a direct interaction of GLTx with the secretory capacity. Accordingly, GLTx also suppressed KCl-induced insulin secretion. GLTx was not accompanied by decisively increased ROS production or enhanced apoptosis. Insulin content of beta cells was markedly reduced by GLTx, an effect not prevented by gliclazide. Since GLTx markedly diminished the mitochondrial membrane potential and cellular ATP content, lack of ATP is assumed to decrease insulin biosynthesis. The deleterious effect of GLTx is therefore caused by direct interference with the secretory capacity whereby reduction of insulin content is one important parameter. These findings deepen our understanding how GLTx damages beta cells and reveal that GLTx is disconnected from ROS formation, a notion important for targeting beta cells in the treatment of diabetes. Overall, GLTx-induced energy depletion may be a primary step in the cascade of events leading to loss of beta cell function in type-2 diabetes mellitus.- Published
- 2018
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21. Neuroprotective, Neurogenic, and Amyloid Beta Reducing Effect of a Novel Alpha 2-Adrenoblocker, Mesedin, on Astroglia and Neuronal Progenitors upon Hypoxia and Glutamate Exposure.
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Melkonyan MM, Hunanyan L, Lourhmati A, Layer N, Beer-Hammer S, Yenkoyan K, Schwab M, and Danielyan L
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- Adrenergic alpha-2 Receptor Antagonists chemistry, Adrenergic alpha-2 Receptor Antagonists therapeutic use, Alzheimer Disease drug therapy, Animals, Astrocytes cytology, Biomarkers, Pharmacological analysis, Cell Survival drug effects, Dioxanes chemistry, Glutamic Acid metabolism, Hypoxia metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons cytology, Neuroprotective Agents chemistry, Neuroprotective Agents therapeutic use, Primary Cell Culture, Thiazoles chemistry, Adrenergic alpha-2 Receptor Antagonists pharmacology, Amyloid beta-Peptides antagonists & inhibitors, Astrocytes drug effects, Dioxanes pharmacology, Dioxanes therapeutic use, Neurogenesis drug effects, Neurons drug effects, Neuroprotective Agents pharmacology, Thiazoles pharmacology, Thiazoles therapeutic use
- Abstract
Locus coeruleus-noradrenergic system dysfunction is known to contribute to the progression of Alzheimer's disease (AD). Besides a variety of reports showing the involvement of norepinephrine and its receptor systems in cognition, amyloid β (Aβ) metabolism, neuroinflammation, and neurogenesis, little is known about the contribution of the specific receptors to these actions. Here, we investigated the neurogenic and neuroprotective properties of a new α2 adrenoblocker, mesedin, in astroglial primary cultures (APC) from C57BL/6 and 3×Tg-AD mice. Our results demonstrate that mesedin rescues neuronal precursors and young neurons, and reduces the lactate dehydrogenase (LDH) release from astroglia under hypoxic and normoxic conditions. Mesedin also increased choline acetyltransferase, postsynaptic density marker 95 (PSD95), and Aβ-degrading enzyme neprilysin in the wild type APC, while in the 3×Tg-AD APC exposed to glutamate, it decreased the intracellular content of Aβ and enhanced the survival of synaptophysin-positive astroglia and neurons. These effects in APC can at least partially be attributed to the mesedin's ability of increasing the expression of Interleukine(IL)-10, which is a potent anti-inflammatory, neuroprotective neurogenic, and Aβ metabolism enhancing factor. In summary, our data identify the neurogenic, neuroprotective, and anti-amyloidogenic action of mesedin in APC. Further in vivo studies are needed to estimate the therapeutic value of mesedin for AD., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
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22. Efficacy and safety of antifungal additives in Optisol-GS corneal storage medium.
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Layer N, Cevallos V, Maxwell AJ, Hoover C, Keenan JD, and Jeng BH
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- Amphotericin B adverse effects, Amphotericin B pharmacology, Antifungal Agents adverse effects, Candida albicans drug effects, Candida glabrata drug effects, Candidiasis microbiology, Cell Count, Chondroitin Sulfates adverse effects, Colony Count, Microbial, Complex Mixtures adverse effects, Complex Mixtures pharmacology, Culture Media, Serum-Free adverse effects, Culture Media, Serum-Free pharmacology, Dextrans adverse effects, Drug Combinations, Endothelium, Corneal drug effects, Endothelium, Corneal microbiology, Endothelium, Corneal pathology, Gentamicins adverse effects, Humans, Microbial Sensitivity Tests, Organ Preservation, Organ Preservation Solutions adverse effects, Pyrimidines adverse effects, Pyrimidines pharmacology, Tissue Donors, Treatment Outcome, Triazoles adverse effects, Triazoles pharmacology, Voriconazole, Antifungal Agents pharmacology, Candidiasis prevention & control, Chondroitin Sulfates pharmacology, Cornea, Dextrans pharmacology, Drug Contamination prevention & control, Gentamicins pharmacology, Organ Preservation Solutions pharmacology
- Abstract
Importance: Optisol-GS, the most common corneal storage medium in the United States, contains antibacterial but no antifungal supplementation. Most postkeratoplasty endophthalmitis and keratitis cases are now of a fungal origin., Objective: To assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions., Design, Setting, and Participants: In vitro laboratory study using 15 pairs of research-grade donor corneas and 20-mL vials of Optisol-GS., Interventions: Twenty vials of Optisol-GS were supplemented with either voriconazole at 1×, 10×, 25×, or 50× minimum inhibitory concentration (MIC) or amphotericin B at 0.25×, 0.5×, 1×, or 10× MIC. Known concentrations of Candida albicans and Candida glabrata were each added to a set of vials. Safety studies were performed by separating 15 pairs of donor corneas into unsupplemented Optisol-GS or Optisol-GS plus an antifungal., Main Outcomes and Measures: Efficacy outcomes were viable fungal colony counts determined from samples taken on days 2, 7, and 14 immediately after removal from refrigeration and after warming to room temperature for 2 hours. Safety outcomes included percentage of intact epithelium and endothelial cell density on days 0, 7, and 14, as well as percentage of nonviable endothelial cells by vital dye staining on day 14., Results: Growth of C albicans and C glabrata was observed in all voriconazole-supplemented vials. In contrast, there was no growth of either organism in amphotericin B-supplemented vials, except at 0.25× and 0.5× MIC on day 2, when viable counts of C glabrata were reduced by 99% and 96%, respectively. Compared with paired controls, with the exception of Optisol-GS plus amphotericin B at 10× MIC, donor corneas in supplemented Optisol-GS appeared to have no difference in endothelial cell density reduction, percentage of intact epithelium, or percentage of nonviable endothelial cells., Conclusions and Relevance: The addition of amphotericin B to Optisol-GS may significantly improve activity against contamination with Candida species, the primary cause of fungal infection after corneal transplantation. This study found significant endothelial toxic effects at the maximal concentration of amphotericin B.
- Published
- 2014
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23. Retinal dysplasia of holoprosencephaly.
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Gorovoy IR, Layer N, and de Alba Campomanes AG
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- Fatal Outcome, Female, Gestational Age, Humans, Infant, Newborn, Magnetic Resonance Imaging, Abnormalities, Multiple, Coloboma diagnosis, Holoprosencephaly diagnosis, Optic Nerve abnormalities, Retinal Dysplasia diagnosis
- Abstract
Retinal dysplasia occurs in the setting of sporadic and syndromic holoprosencephaly, which often has associated ocular malformations. The pathology of this dysplasia, which includes rosettes, has been previously described. However, its funduscopic findings have not been well documented. The authors present the fundus images of a patient with severe holoprosencephaly with retinal dysplasia and bilateral optic nerve colobomas that resulted in death 2 weeks after birth., (Copyright 2014, SLACK Incorporated.)
- Published
- 2014
- Full Text
- View/download PDF
24. Pilomatrixoma in a patient with bilateral retinoblastoma.
- Author
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Gorovoy IR, Layer N, Kim HJ, Nobles SM, Stewart PJ, Vagefi MR, and Kersten RC
- Subjects
- Antineoplastic Agents, Alkylating therapeutic use, Child, Preschool, Eyelids, Female, Hair Diseases diagnostic imaging, Hair Diseases surgery, Humans, Melphalan therapeutic use, Pilomatrixoma diagnostic imaging, Pilomatrixoma surgery, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Skin Neoplasms diagnostic imaging, Skin Neoplasms surgery, Ultrasonography, Hair Diseases complications, Pilomatrixoma complications, Retinal Neoplasms complications, Retinoblastoma chemically induced, Skin Neoplasms complications
- Abstract
A 3-year-old girl with a history of bilateral retinoblastoma presented with a new right lower periorbital mass that showed calcifications on ultrasound. She had previously undergone systemic and intra-arterial chemotherapy for retinoblastoma but had no evidence of active disease for at least 6 months previously. Her family and oncologists feared that this mass was an extraocular metastasis of her retinoblastoma. On excision, it was diagnosed as a pilomatrixoma, an uncommon benign neoplasm that originates from the matrix of the hair root. This is the first reported case of pilomatrixoma in a patient with retinoblastoma., (Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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