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Book ; Thesis: Circuits of the facial and hypoglossal nuclei in the rat

Popratiloff, Anastas

stereotaxic study with neuronal tracers

2000

Author's details	vorgelegt von Anastas Popratiloff
Language	English
Size	48 S. : Ill.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Köln, Univ., Diss., 2000
HBZ-ID	HT012798179
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Article ; Online: A unique cell population expressing the Epithelial-Mesenchymal Transition-transcription factor Snail moderates microglial and astrocyte injury responses.

Clarkson-Paredes, Cheryl / Karl, Molly T / Popratiloff, Anastas / Miller, Robert H

PNAS nexus

2023 Volume 2, Issue 10, Page(s) pgad334

Abstract: Insults to the central nervous system (CNS) elicit common glial responses including microglial activation evidenced by functional, morphological, and phenotypic changes, as well as astrocyte reactions including hypertrophy, altered process orientation, ... ...

Abstract	Insults to the central nervous system (CNS) elicit common glial responses including microglial activation evidenced by functional, morphological, and phenotypic changes, as well as astrocyte reactions including hypertrophy, altered process orientation, and changes in gene expression and function. However, the cellular and molecular mechanisms that initiate and modulate such glial response are less well-defined. Here we show that an adult cortical lesion generates a population of ultrastructurally unique microglial-like cells that express Epithelial-Mesenchymal Transcription factors including Snail. Knockdown of Snail with antisense oligonucleotides results in a postinjury increase in activated microglial cells, elevation in astrocyte reactivity with increased expression of C3 and phagocytosis, disruption of astrocyte junctions and neurovascular structure, increases in neuronal cell death, and reduction in cortical synapses. These changes were associated with alterations in pro-inflammatory cytokine expression. By contrast, overexpression of Snail through microglia-targeted an adeno-associated virus (AAV) improved many of the injury characteristics. Together, our results suggest that the coordination of glial responses to CNS injury is partly mediated by epithelial-mesenchymal transition-factors (EMT-Fsl).
Language	English
Publishing date	2023-10-12
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgad334
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Article ; Online: Large-field-of-view scanning electron microscopy of the paraventricular nucleus of the hypothalamus during diet-induced obesity.

Arestakesyan, Hovhannes / Blackmore, Katherine / Smith, Hannah C / Popratiloff, Anastas / Young, Colin N

Journal of neurophysiology

2023 Volume 130, Issue 2, Page(s) 345–352

Abstract: Dysregulation in the paraventricular nucleus of the hypothalamus (PVN) is associated with a variety of diseases including those related to obesity. Although most investigations have focused on molecular changes, structural alterations in PVN neurons can ... ...

Abstract	Dysregulation in the paraventricular nucleus of the hypothalamus (PVN) is associated with a variety of diseases including those related to obesity. Although most investigations have focused on molecular changes, structural alterations in PVN neurons can reveal underlying functional disruptions. Although electron microscopy (EM) can provide nanometer resolution of brain structures, an inherent limitation of traditional transmission EM is the single field of view nature of data collection. To overcome this, we used large-field-of-view high-resolution backscatter scanning electron microscopy (bSEM) of the PVN. By stitching high-resolution bSEM images, taken from normal chow and high-fat diet mice, we achieved interactive, zoomable maps that allow for low-magnification screening of the entire PVN and high-resolution analyses of ultrastructure at the level of the smallest cellular organelle. Using this approach, quantitative analysis across the PVN revealed marked electron-dense regions within neuronal nucleoplasm following high-fat diet feeding, with an increase in kurtosis, indicative of a shift away from a normal distribution. Furthermore, measures of skewness indicated a shift toward darker clustered electron-dense regions, potentially indicative of heterochromatin clusters. We further demonstrate the utility to map out healthy and altered neurons throughout the PVN and the ability to remotely perform bSEM imaging in situations that require social distancing, such as the COVID-19 pandemic. Collectively, these findings present an approach that allows for the precise placement of PVN cells within an overall structural and functional map of the PVN. Moreover, they suggest that obesity may disrupt PVN neuronal chromatin structure.
MeSH term(s)	Mice ; Animals ; Humans ; Paraventricular Hypothalamic Nucleus ; Microscopy, Electron, Scanning ; Pandemics ; COVID-19 ; Hypothalamus ; Obesity ; Diet, High-Fat/adverse effects
Language	English
Publishing date	2023-07-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00208.2023
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Article: Understanding the Pathophysiology of Congenital Vestibular Disorders: Current Challenges and Future Directions.

Peusner, Kenna D / Bell, Nina M / Hirsch, June C / Beraneck, Mathieu / Popratiloff, Anastas

Frontiers in neurology

2021 Volume 12, Page(s) 708395

Abstract: In congenital vestibular disorders (CVDs), children develop an abnormal inner ear before birth and face postnatal challenges to maintain posture, balance, walking, eye-hand coordination, eye tracking, or reading. Only limited information on inner ear ... ...

Abstract	In congenital vestibular disorders (CVDs), children develop an abnormal inner ear before birth and face postnatal challenges to maintain posture, balance, walking, eye-hand coordination, eye tracking, or reading. Only limited information on inner ear pathology is acquired from clinical imaging of the temporal bone or studying histological slides of the temporal bone. A more comprehensive and precise assessment and determination of the underlying mechanisms necessitate analyses of the disorders at the
Language	English
Publishing date	2021-09-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.708395
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Article ; Online: Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome.

Wang, Xin / Popratiloff, Anastas / Motahari, Zahra / LaMantia, Anthony-Samuel / Mendelowitz, David

eNeuro

2020 Volume 7, Issue 5

Abstract: We asked whether the physiological and morphologic properties of hypoglossal motor neurons (CNXII MNs) that innervate protruder or retractor tongue muscles are disrupted in ... ...

Abstract	We asked whether the physiological and morphologic properties of hypoglossal motor neurons (CNXII MNs) that innervate protruder or retractor tongue muscles are disrupted in neonatal
MeSH term(s)	Animals ; Child ; Deglutition Disorders ; DiGeorge Syndrome/complications ; DiGeorge Syndrome/genetics ; Disease Models, Animal ; Humans ; Medulla Oblongata ; Mice ; Motor Neurons
Language	English
Publishing date	2020-10-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0520-19.2020
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Article ; Online: Aberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic models of 22q11.2 deletion syndrome.

Motahari, Zahra / Maynard, Thomas M / Popratiloff, Anastas / Moody, Sally A / LaMantia, Anthony-S

Human molecular genetics

2020 Volume 29, Issue 18, Page(s) 3081–3093

Abstract: We identified divergent modes of initial axon growth that prefigure disrupted differentiation of the trigeminal nerve (CN V), a cranial nerve essential for suckling, feeding and swallowing (S/F/S), a key innate behavior compromised in multiple genetic ... ...

Abstract	We identified divergent modes of initial axon growth that prefigure disrupted differentiation of the trigeminal nerve (CN V), a cranial nerve essential for suckling, feeding and swallowing (S/F/S), a key innate behavior compromised in multiple genetic developmental disorders including DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS). We combined rapid in vivo labeling of single CN V axons in LgDel+/- mouse embryos, a genomically accurate 22q11.2DS model, and 3D imaging to identify and quantify phenotypes that could not be resolved using existing methods. We assessed these phenotypes in three 22q11.2-related genotypes to determine whether individual CN V motor and sensory axons wander, branch and sprout aberrantly in register with altered anterior-posterior hindbrain patterning and gross morphological disruption of CN V seen in LgDel+/-. In the additional 22q11.2-related genotypes: Tbx1+/-, Ranbp1-/-, Ranbp1+/- and LgDel+/-:Raldh2+/-; axon phenotypes are seen when hindbrain patterning and CN V gross morphology is altered, but not when it is normal or restored toward WT. This disordered growth of CN V sensory and motor axons, whose appropriate targeting is critical for optimal S/F/S, may be an early, critical determinant of imprecise innervation leading to inefficient oropharyngeal function associated with 22q11.2 deletion from birth onward.
MeSH term(s)	Aldehyde Oxidoreductases/genetics ; Animals ; Axons/metabolism ; Axons/pathology ; Chromosome Deletion ; DiGeorge Syndrome/genetics ; DiGeorge Syndrome/physiopathology ; Disease Models, Animal ; Humans ; Mice ; Mice, Knockout ; Motor Activity/genetics ; Nuclear Proteins/genetics ; Phenotype ; Rhombencephalon/growth & development ; Rhombencephalon/physiopathology ; T-Box Domain Proteins/genetics ; Trigeminal Nerve/pathology
Chemical Substances	Nuclear Proteins ; T-Box Domain Proteins ; Tbx1 protein, mouse ; ran-binding protein 1 ; Aldehyde Oxidoreductases (EC 1.2.-) ; RALDH2 protein, mouse (EC 1.2.1.36)
Keywords	covid19
Language	English
Publishing date	2020-09-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddaa199
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Article ; Online: Functional analysis of vasa/PL10-like genes in the ovary of Schistosoma mansoni.

Skinner, Danielle E / Popratiloff, Anastas / Alrefaei, Yousef N / Mann, Victoria H / Rinaldi, Gabriel / Brindley, Paul J

Molecular and biochemical parasitology

2020 Volume 236, Page(s) 111259

Abstract: The RNA helicase Vasa plays a pivotal role in the development of the germ line. To decipher the functional roles of vasa/PL10-like genes in the human blood fluke Schistosoma mansoni, we performed RNA interference followed by the analysis of the ovary in ... ...

Abstract	The RNA helicase Vasa plays a pivotal role in the development of the germ line. To decipher the functional roles of vasa/PL10-like genes in the human blood fluke Schistosoma mansoni, we performed RNA interference followed by the analysis of the ovary in the adult female. Double-stranded RNA targeting the schistosome vasa-like gene Smvlg1 reduced the volume of the ovary. Changes in morphology of the ovary were analysed using carmine red-staining of the parasites followed by a novel confocal laser scanning microscopy (CLSM)-based approach to control for natural autofluorescence in female schistosome tissues. The reduction in the ovary volume may have been promoted by the loss of germ cells. By contrast, significant differences were not apparent in the number of eggs produced or hatching rate of eggs laid by the female schistosomes transfected with Smvlg1-specific dsRNA. The findings suggested a role for S. mansoni vasa/PL10-like gene -1 in germ cell development within the schistosome ovary that might impact in the pathogenesis and disease transmission by this neglected tropical disease pathogen.
MeSH term(s)	Animals ; DEAD-box RNA Helicases/genetics ; Female ; Gene Expression ; Genes, Helminth ; Genitalia ; Microscopy, Confocal/methods ; Ovary/anatomy & histology ; Ovary/cytology ; Ovary/metabolism ; RNA Interference ; Schistosoma mansoni/genetics ; Schistosoma mansoni/metabolism ; Transfection/methods
Chemical Substances	DDX4 protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2020-01-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	756166-0
ISSN	1872-9428 ; 0166-6851
ISSN (online)	1872-9428
ISSN	0166-6851
DOI	10.1016/j.molbiopara.2020.111259
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Zs.B 2437: Show issues

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Article ; Online: Analytic comparison of talc in commercially available baby powder and in pelvic tissues resected from ovarian carcinoma patients.

Johnson, Kurt E / Popratiloff, Anastas / Fan, Yuwei / McDonald, Sandra / Godleski, John J

Gynecologic oncology

2020 Volume 159, Issue 2, Page(s) 527–533

Abstract: Objective: Measure the size and shape of talc particles in talcum powder and compare this data to the size and shape of talc particles found in surgically resected tissues from patients with ovarian carcinoma.: Methods: Using polarized light ... ...

Abstract	Objective: Measure the size and shape of talc particles in talcum powder and compare this data to the size and shape of talc particles found in surgically resected tissues from patients with ovarian carcinoma. Methods: Using polarized light microscopy (PLM) and scanning electron microscopy (SEM), we measured the size and shape of talc particles in samples of talc-containing baby powder (TCBP) and surgically resected pelvic tissues (hysterectomies) from talc-exposed patients with ovarian carcinoma. Results: The most frequent class of particles in TCBP can be unequivocally identified as talc, using both polarized light microscopy and scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX). The talc particles found in resected tissues from ovarian carcinoma patients are similar in size and shape to the most abundant morphological class of particles in TCBP. Conclusions: This finding, combined with previous epidemiological literature and tissue-based analytical studies, provides further evidence that the small, isodiametric particles that dominate TCBP can migrate from the perineum and become lodged in distal structures in the female reproductive tract, where they may lead to an increased risk of developing ovarian carcinoma.
MeSH term(s)	Adult ; Aged ; Carcinoma, Ovarian Epithelial/pathology ; Female ; Humans ; Lymph Nodes/chemistry ; Lymph Nodes/ultrastructure ; Microscopy, Electron, Scanning ; Middle Aged ; Omentum/chemistry ; Omentum/ultrastructure ; Ovarian Neoplasms/pathology ; Ovary/chemistry ; Ovary/ultrastructure ; Talc/adverse effects ; Talc/analysis ; Talc/pharmacokinetics
Chemical Substances	Talc (14807-96-6)
Language	English
Publishing date	2020-09-22
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2020.09.028
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Article ; Online: Axonal debris accumulates in corneal epithelial cells after intraepithelial corneal nerves are damaged: A focused Ion Beam Scanning Electron Microscopy (FIB-SEM) study.

Parlanti, Paola / Pal-Ghosh, Sonali / Williams, Alexa / Tadvalkar, Gauri / Popratiloff, Anastas / Stepp, Mary Ann

Experimental eye research

2020 Volume 194, Page(s) 107998

Abstract: The intraepithelial corneal nerves (ICNs) that innervate the corneal epithelium are maintained through interactions with corneal epithelial cells and the extracellular matrix they produce. One to several axons bundle together within the basal cell layer ... ...

Abstract	The intraepithelial corneal nerves (ICNs) that innervate the corneal epithelium are maintained through interactions with corneal epithelial cells and the extracellular matrix they produce. One to several axons bundle together within the basal cell layer and extend parallel to the ocular surface or branch and extend apically. Here we use 3-dimentional (3D) ultrastructural reconstructions of control and trephine injured mouse corneal epithelium and stroma produced using Focused Ion Beam Scanning Electron Microscope (FIB-SEM) to determine whether corneal epithelial or immune cells resident in the epithelium remove axonal debris and degrade it in their lysosomes after trephine injury to the cornea. We demonstrate that axonal fragments are internalized in the corneal epithelium and accumulate within electron dense structures consistent with lysosomes 3 h after trephine injury in both epithelial and immune cells located among the basal cells of the trephine injured cornea. Confocal imaging showed fewer CD45
MeSH term(s)	Animals ; Axons/ultrastructure ; Corneal Injuries/metabolism ; Corneal Injuries/pathology ; Disease Models, Animal ; Epithelium, Corneal/innervation ; Epithelium, Corneal/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Microscopy, Electron, Scanning/methods ; Nerve Fibers/ultrastructure
Language	English
Publishing date	2020-03-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2020.107998
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Article: Ebola Virus NP Binding to Host Protein Phosphatase-1 Regulates Capsid Formation.

Ahmad, Asrar / Tigabu, Bersabeh / Ivanov, Andrey / Jerebtsova, Marina / Ammosova, Tatiana / Ramanathan, Palaniappan / Kumari, Namita / Brantner, Christine A / Pietzsch, Colette A / Abdullah, Ghadeer / Popratiloff, Anastas / Widen, Steve / Bukreyev, Alexander / Nekhai, Sergei

Research square

2023

Abstract: The Ebola virus (EBOV) transcriptional regulation involves host protein phosphatases PP1 and PP2A, which dephosphorylate the transcriptional cofactor of EBOV polymerase VP30. The 1E7-03 compound, which targets PP1, induces VP30 phosphorylation and ... ...

Abstract	The Ebola virus (EBOV) transcriptional regulation involves host protein phosphatases PP1 and PP2A, which dephosphorylate the transcriptional cofactor of EBOV polymerase VP30. The 1E7-03 compound, which targets PP1, induces VP30 phosphorylation and inhibits EBOV infection. This study aimed to investigate the role of PP1 in EBOV replication. When EBOV-infected cells were continuously treated with 1E7-03, the NP E619K mutation was selected. This mutation moderately reduced EBOV minigenome transcription, which was restored by the treatment with 1E7-03. Formation of EBOV capsids, when NP was co-expressed with VP24 and VP35, was impaired with NPE 619K. Treatment with 1E7-03 restored capsid formation by NP E619K mutation, but inhibited capsids formed by WT NP. The dimerization of NP E619K, tested in a split NanoBiT assay, was significantly decreased (~ 15-fold) compared to WT NP. NP E619K bound more efficiently to PP1 (~ 3-fold) but not B56 subunit of PP2A or VP30. Cross-linking and co-immunoprecipitation experiments showed fewer monomers and dimers for NP E619K which were increased with 1E7-03 treatment. NP E619K showed increased co-localization with PP1α compared to WT NP. Mutations of potential PP1 binding sites and NP deletions disrupted its interaction with PP1. Collectively, our findings suggest that PP1 binding to the NP regulates NP dimerization and capsid formation, and that NP E619K mutation, which has the enhanced PP1 binding, disrupts these processes. Our results point to a new role for PP1 in EBOV replication in which NP binding to PP1 may facilitate viral transcription by delaying capsid formation and EBOV replication.
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2963943/v1
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