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  1. Article ; Online: Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM)

    Kenji Tsuji / Hani Suleiman / Jeffrey H. Miner / James M. Daley / Diane E. Capen / Teodor G. Păunescu / Hua A. Jenny Lu

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 13

    Abstract: Abstract The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular ... ...

    Abstract Abstract The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases. Here we report the application of newly developed helium ion scanning microscopy (HIM) to examine the glomerulopathy in a Col4a3 mutant/Alport syndrome mouse model. Our study revealed unprecedented details of glomerular abnormalities in Col4a3 mutants including distorted podocyte cell bodies and disorganized primary processes. Strikingly, we observed abundant filamentous microprojections arising from podocyte cell bodies and processes, and presence of unique bridging processes that connect the primary processes and foot processes in Alport mice. Furthermore, we detected an altered glomerular endothelium with disrupted sub-endothelial integrity. More importantly, we were able to clearly visualize the complex, three-dimensional podocyte and endothelial interface by HIM. Our study demonstrates that HIM provides nanometer resolution to uncover and rediscover critical ultrastructural characteristics of the glomerulopathy in Col4a3 mutant mice.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease

    Sang Su Kwak / Kevin J. Washicosky / Emma Brand / Djuna von Maydell / Jenna Aronson / Susan Kim / Diane E. Capen / Murat Cetinbas / Ruslan Sadreyev / Shen Ning / Enjana Bylykbashi / Weiming Xia / Steven L. Wagner / Se Hoon Choi / Rudolph E. Tanzi / Doo Yeon Kim

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: The relationship between amyloid-β species and tau pathology in Alzheimer’s disease is not fully understood. Here, the authors show that it is the increased ratio of amyloid-β42 and 40 isoforms drives tau pathology in 3D human neural cell culture models ... ...

    Abstract The relationship between amyloid-β species and tau pathology in Alzheimer’s disease is not fully understood. Here, the authors show that it is the increased ratio of amyloid-β42 and 40 isoforms drives tau pathology in 3D human neural cell culture models of the disease.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease

    Sang Su Kwak / Kevin J. Washicosky / Emma Brand / Djuna von Maydell / Jenna Aronson / Susan Kim / Diane E. Capen / Murat Cetinbas / Ruslan Sadreyev / Shen Ning / Enjana Bylykbashi / Weiming Xia / Steven L. Wagner / Se Hoon Choi / Rudolph E. Tanzi / Doo Yeon Kim

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: The relationship between amyloid-β species and tau pathology in Alzheimer’s disease is not fully understood. Here, the authors show that it is the increased ratio of amyloid-β42 and 40 isoforms drives tau pathology in 3D human neural cell culture models ... ...

    Abstract The relationship between amyloid-β species and tau pathology in Alzheimer’s disease is not fully understood. Here, the authors show that it is the increased ratio of amyloid-β42 and 40 isoforms drives tau pathology in 3D human neural cell culture models of the disease.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine

    Carlos Sebastian / Christina Ferrer / Maria Serra / Jee-Eun Choi / Nadia Ducano / Alessia Mira / Manasvi S. Shah / Sylwia A. Stopka / Andrew J. Perciaccante / Claudio Isella / Daniel Moya-Rull / Marianela Vara-Messler / Silvia Giordano / Elena Maldi / Niyati Desai / Diane E. Capen / Enzo Medico / Murat Cetinbas / Ruslan I. Sadreyev /
    Dennis Brown / Miguel N. Rivera / Anna Sapino / David T. Breault / Nathalie Y. R. Agar / Raul Mostoslavsky

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 13

    Abstract: Metabolic reprogramming upon SIRT6 loss induces tumour formation in the intestine but the mechanism is unclear. Here, the authors show that loss of SIRT6 leads to the expansion of epithelial cells with high pyruvate dehydrogenase kinase activity ... ...

    Abstract Metabolic reprogramming upon SIRT6 loss induces tumour formation in the intestine but the mechanism is unclear. Here, the authors show that loss of SIRT6 leads to the expansion of epithelial cells with high pyruvate dehydrogenase kinase activity resulting in enhanced stem cell activity and tumour-initiating potential
    Keywords Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy.

    Aneesh Alex / Airong Li / Xianxu Zeng / Rebecca E Tate / Mary L McKee / Diane E Capen / Zhan Zhang / Rudolph E Tanzi / Chao Zhou

    PLoS ONE, Vol 10, Iss 9, p e

    2015  Volume 0137236

    Abstract: Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been ... ...

    Abstract Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential role in heart morphogenesis and function.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Macrophages Facilitate Electrical Conduction in the Heart

    Hulsmans, Maarten / Aaron D. Aguirre / Alan Hanley / Andrej J. Savol / Christine E. Seidman / Claudio Vinegoni / David J. Milan / Dennis Brown / Diane E. Capen / Eike M. Wülfers / Filip K. Swirski / Gabriel Courties / Gregory A. Fishbein / Gunnar Seemann / Hendrik B. Sager / Hiroko Wakimoto / Jonathan G. Seidman / Kamila Naxerova / Kevin R. King /
    Kory J. Lavine / Ling Xiao / Lucile Miquerol / Matthias Nahrendorf / Nicolas Da Silva / Patrick T. Ellinor / Peter Kohl / Peter Libby / Ralph Weissleder / Richard N. Mitchell / Ruslan I. Sadreyev / Sebastian Clauss / William J. Hucker / Yoshiko Iwamoto / Yuan Sun

    Cell. 2017 Apr. 20, v. 169

    2017  

    Abstract: Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse ... ...

    Abstract Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.
    Keywords cardiomyocytes ; connexins ; electrical conductivity ; gap junctions ; macrophages ; membrane potential ; mice ; models
    Language English
    Dates of publication 2017-0420
    Size p. 510-522.e20.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.03.050
    Database NAL-Catalogue (AGRICOLA)

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