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  1. Article ; Online: Thin air - thick science.

    Wenger, Roland H

    Nature reviews. Molecular cell biology

    2020  Volume 21, Issue 10, Page(s) 567

    Language English
    Publishing date 2020-07-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-020-0277-1
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    Zs.A 5446: Show issues Location:
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  2. Article ; Online: Selective Hypoxia-Sensitive Oxomer Formation by FIH Prevents Binding of the NF-κB Inhibitor IκBβ to NF-κB Subunits.

    Volkova, Yulia L / Jucht, Agnieszka E / Oechsler, Nina / Krishnankutty, Roopesh / von Kriegsheim, Alex / Wenger, Roland H / Scholz, Carsten C

    Molecular and cellular biology

    2024  , Page(s) 1–11

    Abstract: Pharmacologic inhibitors of cellular hydroxylase oxygen sensors are protective in multiple ... ...

    Abstract Pharmacologic inhibitors of cellular hydroxylase oxygen sensors are protective in multiple preclinical
    Language English
    Publishing date 2024-04-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1080/10985549.2024.2338727
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    Zs.A 1666: Show issues Location:
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  3. Article ; Online: Interfering with Tumor Hypoxia for Radiotherapy Optimization.

    Telarovic, Irma / Wenger, Roland H / Pruschy, Martin

    Journal of experimental & clinical cancer research : CR

    2021  Volume 40, Issue 1, Page(s) 197

    Abstract: Hypoxia in solid tumors is an important predictor of treatment resistance and poor clinical outcome. The significance of hypoxia in the development of resistance to radiotherapy has been recognized for decades and the search for hypoxia-targeting, ... ...

    Abstract Hypoxia in solid tumors is an important predictor of treatment resistance and poor clinical outcome. The significance of hypoxia in the development of resistance to radiotherapy has been recognized for decades and the search for hypoxia-targeting, radiosensitizing agents continues. This review summarizes the main hypoxia-related processes relevant for radiotherapy on the subcellular, cellular and tissue level and discusses the significance of hypoxia in radiation oncology, especially with regard to the current shift towards hypofractionated treatment regimens. Furthermore, we discuss the strategies to interfere with hypoxia for radiotherapy optimization, and we highlight novel insights into the molecular pathways involved in hypoxia that might be utilized to increase the efficacy of radiotherapy.
    MeSH term(s) Humans ; Neoplasms/radiotherapy ; Radiation Oncology/methods ; Tumor Hypoxia/immunology
    Language English
    Publishing date 2021-06-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-021-02000-x
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    Zs.A 2065: Show issues Location:
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  4. Article ; Online: The Asparagine Hydroxylase FIH: A Unique Oxygen Sensor.

    Volkova, Yulia L / Pickel, Christina / Jucht, Agnieszka E / Wenger, Roland H / Scholz, Carsten C

    Antioxidants & redox signaling

    2022  Volume 37, Issue 13-15, Page(s) 913–935

    Abstract: Significance: ...

    Abstract Significance:
    MeSH term(s) Humans ; Asparagine ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mixed Function Oxygenases/metabolism ; Oxygen/metabolism ; Repressor Proteins/metabolism ; Transcription Factors/metabolism
    Chemical Substances Asparagine (7006-34-0) ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mixed Function Oxygenases (EC 1.-) ; Oxygen (S88TT14065) ; Repressor Proteins ; Transcription Factors ; HIF1AN protein, human (EC 1.14.11.-)
    Language English
    Publishing date 2022-04-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1483836-9
    ISSN 1557-7716 ; 1523-0864
    ISSN (online) 1557-7716
    ISSN 1523-0864
    DOI 10.1089/ars.2022.0003
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    Zs.A 5488: Show issues Location:
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  5. Article ; Online: Source and microenvironmental regulation of erythropoietin in the kidney.

    Nolan, Karen A / Wenger, Roland H

    Current opinion in nephrology and hypertension

    2018  Volume 27, Issue 4, Page(s) 277–282

    Abstract: Purpose of review: Historically, the identity of O2-sensing renal erythropoietin (Epo)-producing (REP) cells was a matter of debate. This review summarizes how recent breakthroughs in transgenic mouse and in-situ hybridization techniques have ... ...

    Abstract Purpose of review: Historically, the identity of O2-sensing renal erythropoietin (Epo)-producing (REP) cells was a matter of debate. This review summarizes how recent breakthroughs in transgenic mouse and in-situ hybridization techniques have facilitated sensitive and specific detection of REP cells and accelerated advancements in the understanding of the regulation of renal Epo production in health and disease.
    Recent findings: REP cells are a dynamically regulated unique subpopulation of tubulointerstitial cells with features of fibroblasts, pericytes and neurons. Under normal conditions, REP cells are located in the corticomedullary border region within a steep decrement in O2 availability. During the progression of chronic kidney disease (CKD), REP cells cease Epo production, dedifferentiate and contribute to the progression of renal fibrosis. However, CKD patients with renal anaemia still respond with elevated Epo production following treatment with hypoxia-mimicking agents.
    Summary: We hypothesize that REP cells are neuron-like setpoint providers and controllers, which integrate information about blood O2 concentration and local O2 consumption via tissue pO2, and combine these inputs with intrinsic negative feedback loops and perhaps tubular cross-talk, converging in Epo regulation.
    MeSH term(s) Anemia/metabolism ; Animals ; Cell Dedifferentiation ; Erythropoietin/biosynthesis ; Fibrosis ; Humans ; Kidney/metabolism ; Kidney/pathology ; Mice, Transgenic ; Oxygen/metabolism ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/pathology ; Renal Insufficiency, Chronic/physiopathology
    Chemical Substances Erythropoietin (11096-26-7) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2018-05-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1151092-4
    ISSN 1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
    ISSN (online) 1473-6543 ; 1535-3842
    ISSN 1062-4813 ; 1062-4821
    DOI 10.1097/MNH.0000000000000420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3686: Show issues Location:
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  6. Article ; Online: Inhibition of firefly luciferase activity by a HIF prolyl hydroxylase inhibitor.

    Günter, Julia / Wenger, Roland H / Scholz, Carsten C

    Journal of photochemistry and photobiology. B, Biology

    2020  Volume 210, Page(s) 111980

    Abstract: The three hypoxia-inducible factor (HIF) prolyl-4-hydroxylase domain (PHD) 1-3 enzymes confer oxygen sensitivity to the HIF pathway and are novel therapeutic targets for treatment of renal anemia. Inhibition of the PHDs may further be beneficial in other ...

    Abstract The three hypoxia-inducible factor (HIF) prolyl-4-hydroxylase domain (PHD) 1-3 enzymes confer oxygen sensitivity to the HIF pathway and are novel therapeutic targets for treatment of renal anemia. Inhibition of the PHDs may further be beneficial in other hypoxia-associated diseases, including ischemia and chronic inflammation. Several pharmacologic PHD inhibitors (PHIs) are available, but our understanding of their selectivity and its chemical basis is limited. We here report that the PHI JNJ-42041935 (JNJ-1935) is structurally similar to the firefly luciferase substrate D-luciferin. Our results demonstrate that JNJ-1935 is a novel inhibitor of firefly luciferase enzymatic activity. In contrast, the PHIs FG-4592 (roxadustat) and FG-2216 (ICA, BIQ, IOX3, YM 311) did not affect firefly luciferase. The JNJ-1935 mode of inhibition is competitive with a K
    MeSH term(s) Animals ; Benzothiazoles/metabolism ; Binding, Competitive ; Fireflies/enzymology ; Glycine/analogs & derivatives ; Glycine/chemistry ; Glycine/metabolism ; Isoquinolines/chemistry ; Isoquinolines/metabolism ; Kinetics ; Luciferases, Firefly/antagonists & inhibitors ; Luciferases, Firefly/genetics ; Luciferases, Firefly/metabolism ; Prolyl-Hydroxylase Inhibitors/chemistry ; Prolyl-Hydroxylase Inhibitors/metabolism ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/isolation & purification ; Renilla/enzymology
    Chemical Substances Benzothiazoles ; D-luciferin ; Isoquinolines ; Prolyl-Hydroxylase Inhibitors ; Recombinant Proteins ; Luciferases, Firefly (EC 1.13.12.7) ; Glycine (TE7660XO1C) ; roxadustat (X3O30D9YMX)
    Language English
    Publishing date 2020-07-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 623022-2
    ISSN 1873-2682 ; 1011-1344
    ISSN (online) 1873-2682
    ISSN 1011-1344
    DOI 10.1016/j.jphotobiol.2020.111980
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    Zs.A 2347: Show issues Location:
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  7. Article ; Online: S1P Stimulates Erythropoietin Production in Mouse Renal Interstitial Fibroblasts by S1P

    Hafizi, Redona / Imeri, Faik / Wenger, Roland H / Huwiler, Andrea

    International journal of molecular sciences

    2021  Volume 22, Issue 17

    Abstract: Erythropoietin (Epo) is the critical hormone for erythropoiesis. In adults, Epo is mainly produced by a subset of interstitial fibroblasts in the kidney, with minor amounts being produced in the liver and the brain. In this study, we used the ... ...

    Abstract Erythropoietin (Epo) is the critical hormone for erythropoiesis. In adults, Epo is mainly produced by a subset of interstitial fibroblasts in the kidney, with minor amounts being produced in the liver and the brain. In this study, we used the immortalized renal interstitial fibroblast cell line FAIK F3-5 to investigate the ability of the bioactive sphingolipid sphingosine 1-phosphate (S1P) to stimulate Epo production and to reveal the mechanism involved. Stimulation of cells with exogenous S1P under normoxic conditions (21% O
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Cell Line ; Cells, Cultured ; Erythropoiesis ; Erythropoietin/metabolism ; Erythropoietin/physiology ; Fibroblasts/metabolism ; Fingolimod Hydrochloride/metabolism ; Humans ; Hypoxia/metabolism ; Hypoxia/physiopathology ; Kidney/metabolism ; Lysophospholipids/metabolism ; Mice ; Protein Binding ; Receptors, Lysosphingolipid/metabolism ; Renal Insufficiency, Chronic/metabolism ; Signal Transduction ; Sphingosine/analogs & derivatives ; Sphingosine/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism ; Sphingosine-1-Phosphate Receptors/physiology
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Lysophospholipids ; Receptors, Lysosphingolipid ; Sphingosine-1-Phosphate Receptors ; sphingosine-1-phosphate receptor-2, mouse ; Erythropoietin (11096-26-7) ; endothelial PAS domain-containing protein 1 (1B37H0967P) ; sphingosine 1-phosphate (26993-30-6) ; Fingolimod Hydrochloride (G926EC510T) ; Sphingosine (NGZ37HRE42)
    Language English
    Publishing date 2021-08-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22179467
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  8. Article ; Online: Fount, fate, features, and function of renal erythropoietin-producing cells.

    Dahl, Sophie L / Bapst, Andreas M / Khodo, Stellor Nlandu / Scholz, Carsten C / Wenger, Roland H

    Pflugers Archiv : European journal of physiology

    2022  Volume 474, Issue 8, Page(s) 783–797

    Abstract: Renal erythropoietin (Epo)-producing (REP) cells represent a rare and incompletely understood cell type. REP cells are fibroblast-like cells located in close proximity to blood vessels and tubules of the corticomedullary border region. Epo mRNA in REP ... ...

    Abstract Renal erythropoietin (Epo)-producing (REP) cells represent a rare and incompletely understood cell type. REP cells are fibroblast-like cells located in close proximity to blood vessels and tubules of the corticomedullary border region. Epo mRNA in REP cells is produced in a pronounced "on-off" mode, showing transient transcriptional bursts upon exposure to hypoxia. In contrast to "ordinary" fibroblasts, REP cells do not proliferate ex vivo, cease to produce Epo, and lose their identity following immortalization and prolonged in vitro culture, consistent with the loss of Epo production following REP cell proliferation during tissue remodelling in chronic kidney disease. Because Epo protein is usually not detectable in kidney tissue, and Epo mRNA is only transiently induced under hypoxic conditions, transgenic mouse models have been developed to permanently label REP cell precursors, active Epo producers, and inactive descendants. Future single-cell analyses of the renal stromal compartment will identify novel characteristic markers of tagged REP cells, which will provide novel insights into the regulation of Epo expression in this unique cell type.
    MeSH term(s) Animals ; Erythropoietin/metabolism ; Hypoxia/metabolism ; Kidney/metabolism ; Mice ; Mice, Transgenic ; RNA, Messenger/metabolism ; Renal Insufficiency, Chronic/metabolism
    Chemical Substances RNA, Messenger ; Erythropoietin (11096-26-7)
    Language English
    Publishing date 2022-06-24
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-022-02714-7
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    Uc I Zs.35: Show issues Location:
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  9. Article ; Online: Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney.

    Kuo, Willy / Rossinelli, Diego / Schulz, Georg / Wenger, Roland H / Hieber, Simone / Müller, Bert / Kurtcuoglu, Vartan

    Scientific data

    2023  Volume 10, Issue 1, Page(s) 510

    Abstract: The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training ...

    Abstract The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks.
    MeSH term(s) Animals ; Mice ; Algorithms ; Benchmarking ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; Kidney/diagnostic imaging
    Language English
    Publishing date 2023-08-03
    Publishing country England
    Document type Dataset ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2775191-0
    ISSN 2052-4463 ; 2052-4463
    ISSN (online) 2052-4463
    ISSN 2052-4463
    DOI 10.1038/s41597-023-02407-5
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  10. Article: The Three "Musketairs" - Lasker Prize 2016 goes to the protagonists of hypoxia research.

    Wenger, Roland H / Katschinski, Dörthe M

    Hypoxia (Auckland, N.Z.)

    2016  Volume 4, Page(s) 161–162

    Language English
    Publishing date 2016-11-25
    Publishing country New Zealand
    Document type Editorial
    ZDB-ID 2780815-4
    ISSN 2324-1128
    ISSN 2324-1128
    DOI 10.2147/HP.S126290
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