Duque-Afonso, Carlos J.

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Dörje, Nele M."],["dc.contributor.author","Bahader, Iman"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Thirumalai, Anupriya"],["dc.contributor.author","Weber, Thomas"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:29:50Z"],["dc.date.available","2021-04-14T08:29:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (\\u0026lt;5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches."],["dc.identifier.doi","10.3389/fnmol.2020.600051"],["dc.identifier.pmid","33488357"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83002"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/123"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","10226"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Nanoscale"],["dc.bibliographiccitation.lastpage","10239"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Sograte-Idrissi, Shama"],["dc.contributor.author","Schlichthaerle, Thomas"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Alevra, Mihai"],["dc.contributor.author","Strauss, Sebastian"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Jungmann, Ralf"],["dc.contributor.author","Rizzoli, Silvio O."],["dc.contributor.author","Opazo, Felipe"],["dc.date.accessioned","2021-04-14T08:26:44Z"],["dc.date.available","2021-04-14T08:26:44Z"],["dc.date.issued","2020"],["dc.description.abstract","A standard procedure to study cellular elements is via immunostaining followed by optical imaging. This methodology typically requires target-specific primary antibodies (1.Abs), which are revealed by secondary antibodies (2.Abs). Unfortunately, the antibody bivalency, polyclonality, and large size can result in a series of artifacts. Alternatively, small, monovalent probes, such as single-domain antibodies (nanobodies) have been suggested to minimize these limitations. The discovery and validation of nanobodies against specific targets are challenging, thus only a minimal amount of them are currently available. Here, we used STED, DNA-PAINT, and light-sheet microscopy, to demonstrate that secondary nanobodies (1) increase localization accuracy compared to 2.Abs; (2) allow direct pre-mixing with 1.Abs before staining, reducing experimental time, and enabling the use of multiple 1.Abs from the same species; (3) penetrate thick tissues more efficiently; and (4) avoid probe-induced clustering of target molecules observed with conventional 2.Abs in living or poorly fixed samples. Altogether, we show how secondary nanobodies are a valuable alternative to 2.Abs."],["dc.identifier.doi","10.1039/d0nr00227e"],["dc.identifier.pmid","32356544"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82054"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/185"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2040-3372"],["dc.relation.haserratum","/handle/2/81970"],["dc.relation.issn","2040-3364"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Rizzoli (Quantitative Synaptology in Space and Time)"],["dc.rights","CC BY 3.0"],["dc.title","Circumvention of common labelling artefacts using secondary nanobodies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E4716"],["dc.bibliographiccitation.issue","32"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E4725"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Ohn, Tzu-Lun"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Scharinger, Anja"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:53:13Z"],["dc.date.available","2017-09-07T11:53:13Z"],["dc.date.issued","2016"],["dc.description.abstract","For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca2+ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over ∼20 mV. Ca2+ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca2+ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca2+ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca2+ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca2+ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs."],["dc.identifier.doi","10.1073/pnas.1605737113"],["dc.identifier.gro","3145053"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2747"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0027-8424"],["dc.title","Hair cells use active zones with different voltage dependence of Ca2+influx to decompose sounds into complementary neural codes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Sograte-Idrissi, Shama"],["dc.contributor.author","Schlichthaerle, Thomas"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Alevra, Mihai"],["dc.contributor.author","Strauss, Sebastian"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Jungmann, Ralf"],["dc.contributor.author","Rizzoli, Silvio O."],["dc.contributor.author","Opazo, Felipe"],["dc.date.accessioned","2021-04-29T08:36:32Z"],["dc.date.available","2021-04-29T08:36:32Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1101/818351"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84560"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/17"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Rizzoli (Quantitative Synaptology in Space and Time)"],["dc.title","Circumvention of common labeling artifacts using secondary nanobodies"],["dc.type","preprint"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","24543"],["dc.bibliographiccitation.issue","48"],["dc.bibliographiccitation.journal","Nanoscale"],["dc.bibliographiccitation.lastpage","24543"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Sograte-Idrissi, Shama"],["dc.contributor.author","Schlichthaerle, Thomas"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Alevra, Mihai"],["dc.contributor.author","Strauss, Sebastian"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Jungmann, Ralf"],["dc.contributor.author","Rizzoli, Silvio O."],["dc.contributor.author","Opazo, Felipe"],["dc.date.accessioned","2021-04-14T08:26:30Z"],["dc.date.available","2021-04-14T08:26:30Z"],["dc.date.issued","2020"],["dc.description.abstract","Correction for ‘Circumvention of common labelling artefacts using secondary nanobodies’ by Shama Sograte-Idrissi et al., Nanoscale, 2020, 12, 10226–10239, DOI: 10.1039/D0NR00227E."],["dc.identifier.doi","10.1039/d0nr90279a"],["dc.identifier.pmid","33306074"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81970"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/419"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2040-3372"],["dc.relation.iserratumof","/handle/2/82054"],["dc.relation.issn","2040-3364"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.relation.workinggroup","RG Rizzoli (Quantitative Synaptology in Space and Time)"],["dc.rights","CC BY 3.0"],["dc.title","Correction: Circumvention of common labelling artefacts using secondary nanobodies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","erratum_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","eaao0540"],["dc.bibliographiccitation.issue","449"],["dc.bibliographiccitation.journal","Science Translational Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Wrobel, Christian"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Huet, Antoine"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2020-12-10T18:36:47Z"],["dc.date.available","2020-12-10T18:36:47Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1126/scitranslmed.aao0540"],["dc.identifier.eissn","1946-6242"],["dc.identifier.issn","1946-6234"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76736"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1962"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Dieter, Alexander"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2019-07-09T11:51:25Z"],["dc.date.available","2019-07-09T11:51:25Z"],["dc.date.issued","2019"],["dc.description.abstract","Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) and partially restore hearing to half a million CI users. However, wide current spread from intracochlear electrodes limits spatial selectivity (i.e. spectral resolution) of electrical CIs. Optogenetic stimulation might become an alternative, since light can be confined in space, promising artificial sound encoding with increased spectral selectivity. Here we compare spectral selectivity of optogenetic, electric, and acoustic stimulation by multi-channel recordings in the inferior colliculus (IC) of gerbils. When projecting light onto tonotopically distinct SGNs, we observe corresponding tonotopically ordered IC activity. An activity-based comparison reveals that spectral selectivity of optogenetic stimulation is indistinguishable from acoustic stimulation for modest intensities. Moreover, optogenetic stimulation outperforms bipolar electric stimulation at medium and high intensities and monopolar electric stimulation at all intensities. In conclusion, we demonstrate better spectral selectivity of optogenetic over electric SGN stimulation, suggesting the potential for improved hearing restoration by optical CIs."],["dc.identifier.doi","10.1038/s41467-019-09980-7"],["dc.identifier.pmid","31036812"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16124"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59945"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/H2020/670759/EU//OptoHear"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Near physiological spectral selectivity of cochlear optogenetics"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]