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  1. Article ; Online: ER stress and slit diaphragms: is there a connection?

    Hermle, Tobias / Simons, Matias

    Kidney international

    2023  Volume 103, Issue 5, Page(s) 830–832

    Abstract: Galloway-Mowat syndrome is a neurorenal syndrome that has been linked with defective transfer RNA and protein translation caused by variants in the multiprotein complex KEOPS. In the kidney, this syndrome seems to primarily affect the podocytes, but the ... ...

    Abstract Galloway-Mowat syndrome is a neurorenal syndrome that has been linked with defective transfer RNA and protein translation caused by variants in the multiprotein complex KEOPS. In the kidney, this syndrome seems to primarily affect the podocytes, but the pathogenesis has remained unclear. In this issue of Kidney International, Krausel et al. use Drosophila nephrocytes to link endoplasmic reticulum stress with defects in the slit diaphragm.
    MeSH term(s) Animals ; Membrane Proteins/genetics ; Drosophila/metabolism ; Podocytes/metabolism ; Nephrosis/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism
    Chemical Substances Membrane Proteins ; Drosophila Proteins
    Language English
    Publishing date 2023-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2023.01.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 797: Show issues Location:
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  2. Article ; Online: Nitrogen-vacancy center magnetic imaging of Fe

    Mathes, Niklas / Comas, Maria / Bleul, Regina / Everaert, Katrijn / Hermle, Tobias / Wiekhorst, Frank / Knittel, Peter / Sperling, Ralph A / Vidal, Xavier

    Nanoscale advances

    2023  Volume 6, Issue 1, Page(s) 247–255

    Abstract: Widefield magnetometry based on nitrogen-vacancy centers enables high spatial resolution imaging of magnetic field distributions without a need for spatial scanning. In this work, we show nitrogen-vacancy center magnetic imaging of ... ...

    Abstract Widefield magnetometry based on nitrogen-vacancy centers enables high spatial resolution imaging of magnetic field distributions without a need for spatial scanning. In this work, we show nitrogen-vacancy center magnetic imaging of Fe
    Language English
    Publishing date 2023-12-05
    Publishing country England
    Document type Journal Article
    ISSN 2516-0230
    ISSN (online) 2516-0230
    DOI 10.1039/d3na00684k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: mTOR-Dependent Autophagy Regulates Slit Diaphragm Density in Podocyte-like

    Spitz, Dominik / Comas, Maria / Gerstner, Lea / Kayser, Séverine / Helmstädter, Martin / Walz, Gerd / Hermle, Tobias

    Cells

    2022  Volume 11, Issue 13

    Abstract: Both mTOR signaling and autophagy are important modulators of podocyte homeostasis, regeneration, and aging and have been implicated in glomerular diseases. However, the mechanistic role of these pathways for the glomerular filtration barrier remains ... ...

    Abstract Both mTOR signaling and autophagy are important modulators of podocyte homeostasis, regeneration, and aging and have been implicated in glomerular diseases. However, the mechanistic role of these pathways for the glomerular filtration barrier remains poorly understood. We used
    MeSH term(s) Animals ; Autophagy ; Drosophila/metabolism ; Drosophila Proteins/metabolism ; Podocytes/metabolism ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances Drosophila Proteins ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-07-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11132103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Using the

    Helmstädter, Martin / Huber, Tobias B / Hermle, Tobias

    Frontiers in pediatrics

    2017  Volume 5, Page(s) 262

    Abstract: Glomerular disorders are a major cause of end-stage renal disease and effective therapies are often lacking. Nephrocytes are considered to be part of ... ...

    Abstract Glomerular disorders are a major cause of end-stage renal disease and effective therapies are often lacking. Nephrocytes are considered to be part of the
    Language English
    Publishing date 2017-12-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2017.00262
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Online ; Thesis: <dc:title>Mutations in TBC1D8B affect Rab11-activity and cause nephrotic syndrome</dc:title>

    Kampf, Lina L. [Verfasser] / Hermle, Tobias Franz [Akademischer Betreuer] / Walz, Gerd [Akademischer Betreuer] / Walz, Gerd [Sonstige] / Simons, Matias [Sonstige]

    2023  

    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Universität
    Publishing place Freiburg
    Document type Book ; Online ; Thesis
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  6. Book ; Online ; Thesis: <dc:title>Using transgenic Drosophila model to study the mechanism of APOL1-associated cytotoxicity</dc:title>

    Chen, Mengmeng [Verfasser] / Walz, Gerd [Akademischer Betreuer] / Hermle, Tobias Franz [Akademischer Betreuer] / Walz, Gerd [Sonstige] / Sekula, Peggy [Sonstige]

    2022  

    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Universität
    Publishing place Freiburg
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  7. Article ; Online: mTOR-Dependent Autophagy Regulates Slit Diaphragm Density in Podocyte-like Drosophila Nephrocytes

    Dominik Spitz / Maria Comas / Lea Gerstner / Séverine Kayser / Martin Helmstädter / Gerd Walz / Tobias Hermle

    Cells, Vol 11, Iss 2103, p

    2022  Volume 2103

    Abstract: Both mTOR signaling and autophagy are important modulators of podocyte homeostasis, regeneration, and aging and have been implicated in glomerular diseases. However, the mechanistic role of these pathways for the glomerular filtration barrier remains ... ...

    Abstract Both mTOR signaling and autophagy are important modulators of podocyte homeostasis, regeneration, and aging and have been implicated in glomerular diseases. However, the mechanistic role of these pathways for the glomerular filtration barrier remains poorly understood. We used Drosophila nephrocytes as an established podocyte model and found that inhibition of mTOR signaling resulted in increased spacing between slit diaphragms. Gain-of-function of mTOR signaling did not affect spacing, suggesting that additional cues limit the maximal slit diaphragm density. Interestingly, both activation and inhibition of mTOR signaling led to decreased nephrocyte function, indicating that a fine balance of signaling activity is needed for proper function. Furthermore, mTOR positively controlled cell size, survival, and the extent of the subcortical actin network. We also showed that basal autophagy in nephrocytes is required for survival and limits the expression of the sns (nephrin) but does not directly affect slit diaphragm formation or endocytic activity. However, using a genetic rescue approach, we demonstrated that excessive, mTOR-dependent autophagy is primarily responsible for slit diaphragm misspacing. In conclusion, we established this invertebrate podocyte model for mechanistic studies on the role of mTOR signaling and autophagy, and we discovered a direct mTOR/autophagy-dependent regulation of the slit diaphragm architecture.
    Keywords nephrocyte ; Drosophila ; podocyte ; mTOR ; autophagy ; slit diaphragm ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Development of Nivolumab/Ipilimumab-Associated Autoimmune Nephritis during Steroid Therapy.

    Gebauer, Ellen / Bechtel-Walz, Wibke / Schell, Christoph / Erbel, Michelle / Walz, Gerd / Hermle, Tobias

    Case reports in nephrology and dialysis

    2021  Volume 11, Issue 3, Page(s) 270–274

    Abstract: Immunotherapy using immune checkpoint inhibitors revolutionized therapies for a variety of malignancies. Nivolumab, an antibody blocking programmed cell death 1 protein, and ipilimumab that blocks cytotoxic T-lymphocyte-associated protein 4 effectively ... ...

    Abstract Immunotherapy using immune checkpoint inhibitors revolutionized therapies for a variety of malignancies. Nivolumab, an antibody blocking programmed cell death 1 protein, and ipilimumab that blocks cytotoxic T-lymphocyte-associated protein 4 effectively target tumor cells by disinhibiting the endogenous immune response. At the same time, unrestrained T-cell activation may trigger a range of immune-mediated side effects including kidney injury. Steroid therapy constitutes the mainstay of treatment of these adverse events, but dosage, route of administration, and approach to nivolumab re-exposure remain unclear. Here, we report the case of a 72-year-old male patient who developed severe nivolumab/ipilimumab-associated acute kidney injury while on oral steroid therapy for immune-mediated colitis. Acute interstitial nephritis was confirmed by renal biopsy. Administration of high-dose intravenous steroid doses was required to revert declining renal function.
    Language English
    Publishing date 2021-09-09
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2809879-1
    ISSN 2296-9705
    ISSN 2296-9705
    DOI 10.1159/000517502
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Selective endocytosis controls slit diaphragm maintenance and dynamics in

    Lang, Konrad / Milosavljevic, Julian / Heinkele, Helena / Chen, Mengmeng / Gerstner, Lea / Spitz, Dominik / Kayser, Severine / Helmstädter, Martin / Walz, Gerd / Köttgen, Michael / Spracklen, Andrew / Poulton, John / Hermle, Tobias

    eLife

    2022  Volume 11

    Abstract: The kidneys generate about 180 l of primary urine per day by filtration of plasma. An essential part of the filtration barrier is the slit diaphragm, a multiprotein complex containing nephrin as major component. Filter dysfunction typically manifests ... ...

    Abstract The kidneys generate about 180 l of primary urine per day by filtration of plasma. An essential part of the filtration barrier is the slit diaphragm, a multiprotein complex containing nephrin as major component. Filter dysfunction typically manifests with proteinuria and mutations in endocytosis regulating genes were discovered as causes of proteinuria. However, it is unclear how endocytosis regulates the slit diaphragm and how the filtration barrier is maintained without either protein leakage or filter clogging. Here, we study nephrin dynamics in podocyte-like nephrocytes of
    MeSH term(s) Animals ; Drosophila ; Endocytosis/physiology ; Intercellular Junctions/metabolism ; Mice ; Podocytes/metabolism ; Proteinuria/metabolism
    Language English
    Publishing date 2022-07-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.79037
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  10. Article ; Online: Inhibition of endoplasmic reticulum stress signaling rescues cytotoxicity of human apolipoprotein-L1 risk variants in Drosophila.

    Gerstner, Lea / Chen, Mengmeng / Kampf, Lina L / Milosavljevic, Julian / Lang, Konrad / Schneider, Ronen / Hildebrandt, Friedhelm / Helmstädter, Martin / Walz, Gerd / Hermle, Tobias

    Kidney international

    2022  Volume 101, Issue 6, Page(s) 1216–1231

    Abstract: Risk variants of the apolipoprotein-L1 (APOL1) gene are associated with severe kidney disease, putting homozygous carriers at risk. Since APOL1 lacks orthologs in all major model organisms, a wide range of mechanisms frequently in conflict have been ... ...

    Abstract Risk variants of the apolipoprotein-L1 (APOL1) gene are associated with severe kidney disease, putting homozygous carriers at risk. Since APOL1 lacks orthologs in all major model organisms, a wide range of mechanisms frequently in conflict have been described for APOL1-associated nephropathies. The genetic toolkit in Drosophila allows unique in vivo insights into disrupted cellular homeostasis. To perform a mechanistic analysis, we expressed human APOL1 control and gain-of-function kidney risk variants in the podocyte-like garland cells of Drosophila nephrocytes and a wing precursor tissue. Expression of APOL1 risk variants was found to elevate endocytic function of garland cell nephrocytes that simultaneously showed early signs of cell death. Wild-type APOL1 had a significantly milder effect, while a control transgene with deletion of the short BH3 domain showed no overt phenotype. Nephrocyte endo-lysosomal function and slit diaphragm architecture remained unaffected by APOL1 risk variants, but endoplasmic reticulum (ER) swelling, chaperone induction, and expression of the reporter Xbp1-EGFP suggested an ER stress response. Pharmacological inhibition of ER stress diminished APOL1-mediated cell death and direct ER stress induction enhanced nephrocyte endocytic function similar to expression of APOL1 risk variants. We confirmed APOL1-dependent ER stress in the Drosophila wing precursor where silencing the IRE1-dependent branch of ER stress signaling by inhibition with Xbp1-RNAi abrogated cell death, representing the first rescue of APOL1-associated cytotoxicity in vivo. Thus, we uncovered ER stress as an essential consequence of APOL1 risk variant expression in vivo in Drosophila, suggesting a central role of this pathway in the pathogenesis of APOL1-associated nephropathies.
    MeSH term(s) Animals ; Apolipoprotein L1/genetics ; Drosophila/genetics ; Endoplasmic Reticulum Stress/genetics ; Humans ; Kidney Diseases/pathology ; Podocytes/pathology
    Chemical Substances APOL1 protein, human ; Apolipoprotein L1
    Language English
    Publishing date 2022-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.12.031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 797: Show issues Location:
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