Publications by authors named "D A Davydova"

12 Publications

In vivo multimodal optical imaging of dermoscopic equivocal melanocytic skin lesions.

Sci Rep 2021 01 14;11(1):1405. Epub 2021 Jan 14.

Privolzhsky Research Medical University, Minin and Pozharsky Square 10/1, Nizhny Novgorod, Russia, 603950.

There is a wide range of equivocal melanocytic lesions that can be clinically and dermoscopically indistinguishable from early melanoma. In the present work, we assessed the possibilities of combined using of multiphoton microscopy (MPM) and optical coherence angiography (OCA) for differential diagnosis of the equivocal melanocytic lesions. Clinical and dermoscopic examinations of 60 melanocytic lesions revealed 10 benign lesions and 32 melanomas, while 18 lesions remained difficult to diagnose. Histopathological analysis of these lesions revealed 4 intradermal, 3 compound and 3 junctional nevi in the "benign" group, 7 superficial spreading, 14 lentigo maligna and 11 nodular melanomas in the "melanoma" group and 2 lentigo simplex, 4 dysplastic nevi, 6 melanomas in situ, 4 invasive lentigo melanomas and 2 invasive superficial spreading melanomas in the "equivocal" group. On the basis of MPM, a multiphoton microscopy score (MPMS) has been developed for quantitative assessment of melanoma features at the cellular level, that showed lower score for benign lesions compare with malignant ones. OCA revealed that the invasive melanoma has a higher vessel density and thicker blood vessels than melanoma in situ and benign lesions. Discriminant functions analysis of MPM and OCA data allowed to differentiate correctly between all equivocal melanocytic lesions. Therefore, we demonstrate, for the first time, that a combined use of MPM and OCA has the potential to improve early diagnosis of melanoma.
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http://dx.doi.org/10.1038/s41598-020-80744-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809210PMC
January 2021

Disruption of a Structurally Important Extracellular Element in the Glycine Receptor Leads to Decreased Synaptic Integration and Signaling Resulting in Severe Startle Disease.

J Neurosci 2017 08 19;37(33):7948-7961. Epub 2017 Jul 19.

Institute of Clinical Neurobiology, Julius-Maximilians-University of Würzburg, 97078 Würzburg, Germany,

Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorders. We found that a lack of synaptic integration of GlyRs, together with disrupted receptor function, is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant , caused by a missense mutation, Q177K, located in the extracellular β8-β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8-β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in Cys-loop receptors. We identified the underlying neuropathological mechanisms in male and female mice through a combination of protein biochemistry, immunocytochemistry, and both and in electrophysiology. Increased expression of the mutant GlyR α1 subunit was not sufficient to compensate for a decrease in synaptic integration of α1β GlyRs. The remaining synaptic heteromeric α1β GlyRs had decreased current amplitudes with significantly faster decay times. This functional disruption reveals an important role for the GlyR α1 subunit β8-β9 loop in initiating rearrangements within the extracellular-transmembrane GlyR interface and that this structural element is vital for inhibitory GlyR function, signaling, and synaptic clustering. GlyR dysfunction underlies neuromotor deficits in startle disease and autism spectrum disorders. We describe an extracellular GlyR α1 subunit mutation (Q177K) in a novel mouse startle disease mutant Structural data suggest that during signal transduction, large transitions of the β8-β9 loop occur in response to neurotransmitter binding. Disruption of the β8-β9 loop by the Q177K mutation results in a disruption of hydrogen bonds between Q177 and the ligand-binding residue R65. Functionally, the Q177K change resulted in decreased current amplitudes, altered desensitization decay time constants, and reduced GlyR clustering and synaptic strength. The GlyR β8-β9 loop is therefore an essential regulator of conformational rearrangements during ion channel opening and closing.
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http://dx.doi.org/10.1523/JNEUROSCI.0009-17.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559766PMC
August 2017

Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels.

Sci Signal 2017 07 11;10(487). Epub 2017 Jul 11.

Developmental Biochemistry, Theodor Boveri Institute (Biocenter), University of Wuerzburg, Wuerzburg D-97074, Germany.

The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier, we also compared the brain endothelial translatome of wild-type mice with that of mice lacking the transcriptional cofactor β-catenin (). Our analysis revealed extensive molecular changes during the embryonic development of the brain endothelium. We identified genes encoding brain endothelium-specific transcription factors (, , , , , , and ) that are associated with maturation of the blood-brain barrier and act downstream of the Wnt-β-catenin signaling pathway. Profiling of individual brain endothelial cells revealed substantial heterogeneity in the population. Nevertheless, the high abundance of , , , or transcripts correlated with the increased expression of genes encoding markers of brain endothelial cell differentiation. Expression of and in human umbilical vein endothelial cells induced the production of blood-brain barrier differentiation markers. This comprehensive data set may help to improve the engineering of in vitro blood-brain barrier models.
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http://dx.doi.org/10.1126/scisignal.aag2476DOI Listing
July 2017

Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz](2.).

Sci Rep 2016 09 20;6:33547. Epub 2016 Sep 20.

Leibniz-Institute of Photonic Technology Jena, Albert-Einstein-Straße 9, 07745 Jena, Germany.

An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz](2+) by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz](2+) in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a (3)MLCT state suggests that the [Ru(bpy)2dppz](2+) complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment.
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http://dx.doi.org/10.1038/srep33547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028833PMC
September 2016

Bassoon specifically controls presynaptic P/Q-type Ca(2+) channels via RIM-binding protein.

Neuron 2014 Apr;82(1):181-94

Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Presynaptic Plasticity Group, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany. Electronic address:

Voltage-dependent Ca(2+) channels (CaVs) represent the principal source of Ca(2+) ions that trigger evoked neurotransmitter release from presynaptic boutons. Ca(2+) influx is mediated mainly via CaV2.1 (P/Q-type) and CaV2.2 (N-type) channels, which differ in their properties. Their relative contribution to synaptic transmission changes during development and tunes neurotransmission during synaptic plasticity. The mechanism of differential recruitment of CaV2.1 and CaV2.2 to release sites is largely unknown. Here, we show that the presynaptic scaffolding protein Bassoon localizes specifically CaV2.1 to active zones via molecular interaction with the RIM-binding proteins (RBPs). A genetic deletion of Bassoon or an acute interference with Bassoon-RBP interaction reduces synaptic abundance of CaV2.1, weakens P/Q-type Ca(2+) current-driven synaptic transmission, and results in higher relative contribution of neurotransmission dependent on CaV2.2. These data establish Bassoon as a major regulator of the molecular composition of the presynaptic neurotransmitter release sites.
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http://dx.doi.org/10.1016/j.neuron.2014.02.012DOI Listing
April 2014
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