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  • 1
    Online Resource
    Online Resource
    Thermodynamic compatibility of actives encapsulated into PEG‐PLA nanoparticles: In Silic o predictions and experimental verification
    Wiley ; 2016
    In:  Journal of Computational Chemistry Vol. 37, No. 24 ( 2016-09-15), p. 2220-2227
    Details
    In: Journal of Computational Chemistry, Wiley, Vol. 37, No. 24 ( 2016-09-15), p. 2220-2227
    Abstract: Achieving optimal solubility of active substances in polymeric carriers is of fundamental importance for a number of industrial applications, including targeted drug delivery within the growing field of nanomedicine. However, its experimental optimization using a trial‐and‐error approach is cumbersome and time‐consuming. Here, an approach based on molecular dynamics (MD) simulations and the Flory–Huggins theory is proposed for rapid prediction of thermodynamic compatibility between active species and copolymers comprising hydrophilic and hydrophobic segments. In contrast to similar methods, our approach offers high computational efficiency by employing MD simulations that avoid explicit consideration of the actual copolymer chains. The accuracy of the method is demonstrated for compatibility predictions between pyrene and nile red as model dyes as well as indomethacin as model drug and copolymers containing blocks of poly(ethylene glycol) and poly(lactic acid) in different ratios. The results of the simulations are directly verified by comparison with the observed encapsulation efficiency of nanoparticles prepared by nanoprecipitation. © 2016 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0192-8651 , 1096-987X
    URL: Issue
    URL: Article
    DOI: 10.1002/jcc.v37.24
    DOI: 10.1002/jcc.24449
    RVK:
    VA 5105
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 1479181-X
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  • 2
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    Online Resource
    Combining two photon microscopy and CMOS MEA to uncover the mechanism of aberrant activity in blind retina
    Frontiers Media SA ; 2018
    In:  Frontiers in Cellular Neuroscience Vol. 12 ( 2018)
    Details
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 12 ( 2018)
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    DOI: 10.3389/conf.fncel.2018.38.00022
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2452963-1
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  • 3
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    Differential Regulation of Cone Calcium Signals by Different Horizontal Cell Feedback Mechanisms in the Mouse Retina
    Society for Neuroscience ; 2014
    In:  The Journal of Neuroscience Vol. 34, No. 35 ( 2014-08-27), p. 11826-11843
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 34, No. 35 ( 2014-08-27), p. 11826-11843
    Abstract: Controlling neurotransmitter release by modulating the presynaptic calcium level is a key mechanism to ensure reliable signal transmission from one neuron to the next. In this study, we investigated how the glutamatergic output of cone photoreceptors (cones) in the mouse retina is shaped by different feedback mechanisms from postsynaptic GABAergic horizontal cells (HCs) using a combination of two-photon calcium imaging and pharmacology at the level of individual cone axon terminals. We provide evidence that hemichannel-mediated (putative ephaptic) feedback sets the cone output gain by defining the basal calcium level, a mechanism that may be crucial for adapting cones to the ambient light level. In contrast, pH-mediated feedback did not modulate the cone basal calcium level but affected the size and shape of light-evoked cone calcium signals in a contrast-dependent way: low-contrast light responses were amplified, whereas high-contrast light responses were reduced. Finally, we provide functional evidence that GABA shapes light-evoked calcium signals in cones. Because we could not localize ionotropic GABA receptors on cone axon terminals using electron microscopy, we suggest that GABA may act through GABA autoreceptors on HCs, thereby possibly modulating hemichannel- and/or pH-mediated feedback. Together, our results suggest that at the cone synapse, hemichannel-mediated (ephaptic) and pH-mediated feedback fulfill distinct functions to adjust the output of cones to changing ambient light levels and stimulus contrasts and that the efficacy of these feedback mechanisms is likely modulated by GABA release in the outer retina.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.0272-14.2014
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2014
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 4
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    Online Resource
    Intracellular Calcium Is Regulated by Different Pathways in Horizontal Cells of the Mouse Retina
    American Physiological Society ; 2006
    In:  Journal of Neurophysiology Vol. 96, No. 3 ( 2006-09), p. 1278-1292
    Details
    In: Journal of Neurophysiology, American Physiological Society, Vol. 96, No. 3 ( 2006-09), p. 1278-1292
    Abstract: Horizontal cells modulate the output of the photoreceptor to bipolar cell synapse, thereby providing the first level of lateral information processing in the vertebrate retina. Because horizontal cells do not generate sodium-based action potentials, calcium is likely to play an important role for graded potential changes as well as for intracellular events involved in the modulatory role of horizontal cells within the retinal network. Therefore we wanted to determine how the activation of glutamate receptors, voltage-gated calcium channels, and release of calcium from internal stores shape the calcium signal in horizontal cells. All horizontal cells responded to depolarizing voltage steps with sustained inward currents, which activated at around –20 mV, reached a peak amplitude of –79.1 pA at 5 mV, and reversed sign at around 66 mV. The current was insensitive to tetrodotoxin, and it was partially blocked by the L-type channel antagonists verapamil and nifedipine. The N-type channel blocker ω-conotoxin GVIA induced an additional reduction of current amplitudes. Calcium influx through ionotropic glutamate receptors was mediated by both AMPA and kainate but not by N-methyl-d-aspartate receptors. Two agonists at group I metabotropic glutamate receptor, trans-1-amino-1,3-cyclopentanedicarboxylic acid and quisqualate, had no effect. However, intracellular calcium was increased by caffeine, indicating release of calcium from internal stores via ryanodine receptors. These data show that intracellular calcium in horizontal cells is regulated by voltage-dependent L- and N-type calcium channels, ionotropic AMPA and kainate receptors, and release of calcium from internal stores after activation of ryanodine receptors.
    Type of Medium: Online Resource
    ISSN: 0022-3077 , 1522-1598
    URL: Article
    DOI: 10.1152/jn.00191.2006
    RVK:
    XA 10000 ; XA 552555
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2006
    detail.hit.zdb_id: 80161-6
    detail.hit.zdb_id: 1467889-5
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  • 5
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    Prevention of invasive ventilation (PRiVENT)—a prospective, mixed-methods interventional, multicentre study with a parallel comparison group: study protocol
    Springer Science and Business Media LLC ; 2023
    In:  BMC Health Services Research Vol. 23, No. 1 ( 2023-03-30)
    Details
    In: BMC Health Services Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-03-30)
    Abstract: Invasive mechanical ventilation (IMV) is a standard therapy for intensive care patients with respiratory failure. With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV increases, resulting in impaired quality of life and high costs. In addition, human resources are tied up in the care of these patients. Methods The PRiVENT intervention is a prospective, mixed-methods interventional, multicentre study with a parallel comparison group selected from insurance claims data of the health insurer Allgemeine Ortskrankenkasse Baden-Württemberg (AOK-BW) conducted in Baden-Württemberg, Germany, over 24 months. Four weaning centres supervise 40 intensive care units (ICUs), that are responsible for patient recruitment. The primary outcome, successful weaning from IMV, will be evaluated using a mixed logistic regression model. Secondary outcomes will be evaluated using mixed regression models. Discussion The overall objective of the PRiVENT project is the evaluation of strategies to prevent long-term IMV. Additional objectives aim to improve weaning expertise in and cooperation with the adjacent Intensive Care Units. Trial registration This study is registered at ClinicalTrials.gov (NCT05260853).
    Type of Medium: Online Resource
    ISSN: 1472-6963
    URL: Article
    DOI: 10.1186/s12913-023-09283-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2050434-2
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  • 6
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    How do horizontal cells ‘talk’ to cone photoreceptors? Different levels of complexity at the cone–horizontal cell synapse
    Wiley ; 2017
    In:  The Journal of Physiology Vol. 595, No. 16 ( 2017-08-15), p. 5495-5506
    Details
    In: The Journal of Physiology, Wiley, Vol. 595, No. 16 ( 2017-08-15), p. 5495-5506
    Abstract: The first synapse of the retina plays a fundamental role in the visual system. Due to its importance, it is critical that it encodes information from the outside world with the greatest accuracy and precision possible. Cone photoreceptor axon terminals contain many individual synaptic sites, each represented by a presynaptic structure called a ‘ribbon’. These synapses are both highly sophisticated and conserved. Each ribbon relays the light signal to one ON cone bipolar cell and several OFF cone bipolar cells, while two dendritic processes from a GABAergic interneuron, the horizontal cell, modulate the cone output via parallel feedback mechanisms. The presence of these three partners within a single synapse has raised numerous questions, and its anatomical and functional complexity is still only partially understood. However, the understanding of this synapse has recently evolved, as a consequence of progress in understanding dendritic signal processing and its role in facilitating global versus local signalling. Indeed, for the downstream retinal network, dendritic processing in horizontal cells may be essential, as they must support important functional operations such as contrast enhancement, which requires spatial averaging of the photoreceptor array, while at the same time preserving accurate spatial information. Here, we review recent progress made towards a better understanding of the cone synapse, with an emphasis on horizontal cell function, and discuss why such complexity might be necessary for early visual processing. image
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    URL: Article
    DOI: 10.1113/tjp.2017.595.issue-16
    DOI: 10.1113/JP274177
    RVK:
    WA 15000
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 7
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    Minimal genetically encoded tags for fluorescent protein labeling in living neurons
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-01-14)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-01-14)
    Abstract: Modern light microscopy, including super-resolution techniques, has brought about a demand for small labeling tags that bring the fluorophore closer to the target. This challenge can be addressed by labeling unnatural amino acids (UAAs) with bioorthogonal click chemistry. The minimal size of the UAA and the possibility to couple the fluorophores directly to the protein of interest with single-residue precision in living cells make click labeling unique. Here, we establish click labeling in living primary neurons and use it for fixed-cell, live-cell, dual-color pulse–chase, and super-resolution microscopy of neurofilament light chain (NFL). We also show that click labeling can be combined with CRISPR/Cas9 genome engineering for tagging endogenous NFL. Due to its versatile nature and compatibility with advanced multicolor microscopy techniques, we anticipate that click labeling will contribute to novel discoveries in the neurobiology field.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-27956-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 8
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    Center-surround interactions underlie bipolar cell motion sensitivity in the mouse retina
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-09-26)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-09-26)
    Abstract: Motion sensing is a critical aspect of vision. We studied the representation of motion in mouse retinal bipolar cells and found that some bipolar cells are radially direction selective, preferring the origin of small object motion trajectories. Using a glutamate sensor, we directly observed bipolar cells synaptic output and found that there are radial direction selective and non-selective bipolar cell types, the majority being selective, and that radial direction selectivity relies on properties of the center-surround receptive field. We used these bipolar cell receptive fields along with connectomics to design biophysical models of downstream cells. The models and additional experiments demonstrated that bipolar cells pass radial direction selective excitation to starburst amacrine cells, which contributes to their directional tuning. As bipolar cells provide excitation to most amacrine and ganglion cells, their radial direction selectivity may contribute to motion processing throughout the visual system.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-32762-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 9
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    Erratum for Litschko et al., “A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens”
    American Society for Microbiology ; 2020
    In:  mBio Vol. 11, No. 5 ( 2020-10-27)
    Details
    In: mBio, American Society for Microbiology, Vol. 11, No. 5 ( 2020-10-27)
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.02433-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 2557172-2
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  • 10
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    The temporal structure of the inner retina at a single glance
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-03-10)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-03-10)
    Abstract: The retina decomposes visual stimuli into parallel channels that encode different features of the visual environment. Central to this computation is the synaptic processing in a dense layer of neuropil, the so-called inner plexiform layer (IPL). Here, different types of bipolar cells stratifying at distinct depths relay the excitatory feedforward drive from photoreceptors to amacrine and ganglion cells. Current experimental techniques for studying processing in the IPL do not allow imaging the entire IPL simultaneously in the intact tissue. Here, we extend a two-photon microscope with an electrically tunable lens allowing us to obtain optical vertical slices of the IPL, which provide a complete picture of the response diversity of bipolar cells at a “single glance”. The nature of these axial recordings additionally allowed us to isolate and investigate batch effects, i.e. inter-experimental variations resulting in systematic differences in response speed. As a proof of principle, we developed a simple model that disentangles biological from experimental causes of variability and allowed us to recover the characteristic gradient of response speeds across the IPL with higher precision than before. Our new framework will make it possible to study the computations performed in the central synaptic layer of the retina more efficiently.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-60214-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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