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  1. Article ; Online: Aza Analogs of the TRPML1 Inhibitor Estradiol Methyl Ether (EDME).

    Rühl, Philipp / Bracher, Franz

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 21

    Abstract: Estradiol methyl ether ( ...

    Abstract Estradiol methyl ether (
    MeSH term(s) Transient Receptor Potential Channels ; Estradiol/pharmacology ; Nandrolone ; Lysosomes
    Chemical Substances Transient Receptor Potential Channels ; Estradiol (4TI98Z838E) ; Nandrolone (6PG9VR430D)
    Language English
    Publishing date 2023-11-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28217428
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An Ultrasensitive Genetically Encoded Voltage Indicator Uncovers the Electrical Activity of Non-Excitable Cells.

    Rühl, Philipp / Nair, Anagha G / Gawande, Namrata / Dehiwalage, Sassrika N C W / Münster, Lukas / Schönherr, Roland / Heinemann, Stefan H

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2024  , Page(s) e2307938

    Abstract: Most animal cell types are classified as non-excitable because they do not generate action potentials observed in excitable cells, such as neurons and muscle cells. Thus, resolving voltage signals in non-excitable cells demands sensors with exceptionally ...

    Abstract Most animal cell types are classified as non-excitable because they do not generate action potentials observed in excitable cells, such as neurons and muscle cells. Thus, resolving voltage signals in non-excitable cells demands sensors with exceptionally high voltage sensitivity. In this study, the ultrabright, ultrasensitive, and calibratable genetically encoded voltage sensor rEstus is developed using structure-guided engineering. rEstus is most sensitive in the resting voltage range of non-excitable cells and offers a 3.6-fold improvement in brightness change for fast voltage spikes over its precursor ASAP3. Using rEstus, it is uncovered that the membrane voltage in several non-excitable cell lines (A375, HEK293T, MCF7) undergoes spontaneous endogenous alterations on a second to millisecond timescale. Correlation analysis of these optically recorded voltage alterations provides a direct, real-time readout of electrical cell-cell coupling, showing that visually connected A375 and HEK293T cells are also largely electrically connected, while MCF7 cells are only weakly coupled. The presented work provides enhanced tools and methods for non-invasive voltage imaging in living cells and demonstrates that spontaneous endogenous membrane voltage alterations are not limited to excitable cells but also occur in a variety of non-excitable cell types.
    Language English
    Publishing date 2024-03-25
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202307938
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Monitoring of compound resting membrane potentials of cell cultures with ratiometric genetically encoded voltage indicators.

    Rühl, Philipp / Langner, Johanna M / Reidel, Jasmin / Schönherr, Roland / Hoshi, Toshinori / Heinemann, Stefan H

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 1164

    Abstract: The cellular resting membrane potential ( ... ...

    Abstract The cellular resting membrane potential (V
    MeSH term(s) Andersen Syndrome/genetics ; Ectopic Gene Expression/physiology ; HEK293 Cells ; Hallux/abnormalities ; Humans ; Intellectual Disability/genetics ; Membrane Potentials ; Nails, Malformed/genetics ; Potassium Channels, Inwardly Rectifying/genetics ; Potassium Channels, Inwardly Rectifying/metabolism ; Thumb/abnormalities
    Chemical Substances KCNJ2 protein, human ; Potassium Channels, Inwardly Rectifying
    Language English
    Publishing date 2021-10-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02675-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Online ; Thesis: Messung und Modulation membrannaher Prozesse in menschlichen Zellen mit optischen Methoden

    Rühl, Philipp [Verfasser] / Heinemann, Stefan H. [Gutachter] / Pospiech, Helmut [Gutachter] / Wischmeyer, Erhard [Gutachter]

    2022  

    Author's details Philipp Rühl ; Gutachter: Stefan H. Heinemann, Helmut Pospiech, Erhard Wischmeyer
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language Multiple languages
    Publisher Friedrich-Schiller-Universität Jena
    Publishing place Jena
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  5. Article ; Online: Fe

    Gessner, Guido / Rühl, Philipp / Westerhausen, Matthias / Hoshi, Toshinori / Heinemann, Stefan H

    ACS chemical biology

    2020  Volume 15, Issue 8, Page(s) 2098–2106

    Abstract: Heme catabolism by heme oxygenase (HO) with a decrease in intracellular heme concentration and a concomitant local release of CO and ... ...

    Abstract Heme catabolism by heme oxygenase (HO) with a decrease in intracellular heme concentration and a concomitant local release of CO and Fe
    MeSH term(s) Binding Sites ; Calcium/metabolism ; Carbon Monoxide/metabolism ; Ferrous Compounds/metabolism ; Ferrous Compounds/pharmacology ; HEK293 Cells ; Heme/metabolism ; Humans ; Large-Conductance Calcium-Activated Potassium Channels/agonists ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Magnesium/metabolism ; Patch-Clamp Techniques ; Photolysis
    Chemical Substances Ferrous Compounds ; Large-Conductance Calcium-Activated Potassium Channels ; Heme (42VZT0U6YR) ; Carbon Monoxide (7U1EE4V452) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.0c00282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Membrane potential manipulation with visible flash lamp illumination of targeted microbeads

    Ojha, Navin K / Jin, Jialin / Arifin, Jane C / Rühl, Philipp / Heinemann, Stefan H

    Biochemical and biophysical research communications. 2019 Sept. 17, v. 517, no. 2

    2019  

    Abstract: The electrical membrane potential (Vm) is a key dynamical variable of excitable membranes. Despite the tremendous success of optogenetic methods to modulate Vm with light, there are some shortcomings, such as the need of genetic manipulation and limited ... ...

    Abstract The electrical membrane potential (Vm) is a key dynamical variable of excitable membranes. Despite the tremendous success of optogenetic methods to modulate Vm with light, there are some shortcomings, such as the need of genetic manipulation and limited time resolution. Direct optical stimulation of gold nanoparticles targeted to cells is an attractive alternative because the absorbed energy heats the membrane and, thus, generates capacitive current sufficient to trigger action potentials [1, Carvalho-de-Souza et al., 2015]. However, focused laser light is required and precise location and binding of the nanoparticles cannot be assessed with a conventional microscope. We therefore examined a complementary method to manipulate Vm in a spatio-temporal fashion by non-focused visible flashlight stimulation (Xenon discharge lamp, 385-485 nm, ∼500 μs) of superparamagnetic microbeads. Flashlight stimulation of single beads targeted to cells resulted in transient inward currents under whole-cell patch-clamp control. The waveform of the current reflected the first time derivative of the local temperature induced by the absorbed light and subsequent heat dissipation. The maximal peak current as well as the temperature excursion scaled with the proximity to the plasma membrane. Transient illumination of light-absorbing beads, targeted to specific cellular sites via protein-protein interaction or direct micromanipulation, may provide means of rapid and spatially confined heating and electrical cell stimulation.
    Keywords energy ; genetic engineering ; heat transfer ; lighting ; microbeads ; nanogold ; plasma membrane ; protein-protein interactions ; research ; temperature ; xenon
    Language English
    Dates of publication 2019-0917
    Size p. 297-302.
    Publishing place Elsevier Inc.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2019.07.080
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Diffraction-Unlimited Photomanipulation at the Plasma Membrane via Specifically Targeted Upconversion Nanoparticles.

    Drees, Christoph / Rühl, Philipp / Czerny, Jacqueline / Chandra, Gemini / Bajorath, Janosch / Haase, Markus / Heinemann, Stefan H / Piehler, Jacob

    Nano letters

    2021  Volume 21, Issue 19, Page(s) 8025–8034

    Abstract: Engineered UCNP are used to trigger rapid photoconversion of the fluorescent protein Dendra2 with nanoscopic precision and over longer distances in mammalian cells. By exploiting the synergy of high-level thulium doping with core-shell design and ... ...

    Abstract Engineered UCNP are used to trigger rapid photoconversion of the fluorescent protein Dendra2 with nanoscopic precision and over longer distances in mammalian cells. By exploiting the synergy of high-level thulium doping with core-shell design and elevated excitation intensities, intense UCNP emission is achieved, allowing fast photoconversion of Dendra2 with <10 nm resolution. A tailored biocompatible surface coating and functionalization with a derivate of green fluorescent protein (GFP) for recognition of antiGFP nanobodies are developed. Highly specific targeting of UCNP to fusion proteins of antiGFP on the surface of mammalian cells is demonstrated. UCNP bound to extracellular Dendra2 enable rapid photoconversion selectively in molecular proximity and thus unambiguous detection of cytokine receptor dimerization in the plasma membrane and in endosomes. Remarkably, UCNPs are also suited for manipulating intracellular Dendra2 across the plasma membrane. This study thus establishes UCNP-controlled photomanipulation with nanoscale precision, opening exciting opportunities for bioanalytical applications in cell biology.
    MeSH term(s) Animals ; Cell Membrane ; Green Fluorescent Proteins/genetics ; Nanoparticles
    Chemical Substances Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2021-09-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1530-6992
    ISSN (online) 1530-6992
    DOI 10.1021/acs.nanolett.1c02267
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Membrane potential manipulation with visible flash lamp illumination of targeted microbeads.

    Ojha, Navin K / Jin, Jialin / Arifin, Jane C / Rühl, Philipp / Heinemann, Stefan H

    Biochemical and biophysical research communications

    2019  Volume 517, Issue 2, Page(s) 297–302

    Abstract: The electrical membrane potential ( ... ...

    Abstract The electrical membrane potential (V
    MeSH term(s) HEK293 Cells ; Humans ; Light ; Lighting/instrumentation ; Magnets/chemistry ; Membrane Potentials/radiation effects ; Patch-Clamp Techniques ; Temperature
    Language English
    Publishing date 2019-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2019.07.080
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Estradiol analogs attenuate autophagy, cell migration and invasion by direct and selective inhibition of TRPML1, independent of estrogen receptors.

    Rühl, Philipp / Rosato, Anna Scotto / Urban, Nicole / Gerndt, Susanne / Tang, Rachel / Abrahamian, Carla / Leser, Charlotte / Sheng, Jiansong / Jha, Archana / Vollmer, Günter / Schaefer, Michael / Bracher, Franz / Grimm, Christian

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 8313

    Abstract: The cation channel TRPML1 is an important regulator of lysosomal function and autophagy. Loss of TRPML1 is associated with neurodegeneration and lysosomal storage disease, while temporary inhibition of this ion channel has been proposed to be beneficial ... ...

    Abstract The cation channel TRPML1 is an important regulator of lysosomal function and autophagy. Loss of TRPML1 is associated with neurodegeneration and lysosomal storage disease, while temporary inhibition of this ion channel has been proposed to be beneficial in cancer therapy. Currently available TRPML1 channel inhibitors are not TRPML isoform selective and block at least two of the three human isoforms. We have now identified the first highly potent and isoform-selective TRPML1 antagonist, the steroid 17β-estradiol methyl ether (EDME). Two analogs of EDME, PRU-10 and PRU-12, characterized by their reduced activity at the estrogen receptor, have been identified through systematic chemical modification of the lead structure. EDME and its analogs, besides being promising new small molecule tool compounds for the investigation of TRPML1, selectively affect key features of TRPML1 function: autophagy induction and transcription factor EB (TFEB) translocation. In addition, they act as inhibitors of triple-negative breast cancer cell migration and invasion.
    MeSH term(s) Autophagy/drug effects ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Cell Movement/drug effects ; Cells, Cultured ; Estradiol/analogs & derivatives ; Estradiol/pharmacology ; Female ; Humans ; Neoplasm Invasiveness ; Transient Receptor Potential Channels/antagonists & inhibitors ; Transient Receptor Potential Channels/physiology ; Triple Negative Breast Neoplasms/pathology
    Chemical Substances Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; MCOLN1 protein, human ; TFEB protein, human ; Transient Receptor Potential Channels ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2021-04-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-87817-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Book: Türkische Sprachlehre

    Rühl, Philipp

    Grammatik, Einführung, Lesestücke und Wörterverzeichnis

    1960  

    Author's details Ph. Rühl
    Size 242 S, 8
    Edition 4., durchges. Aufl
    Publisher Groos
    Publishing place Heidelberg
    Document type Book
    Note Mit Literaturverz. (S. 3 - 5)
    Database Former special subject collection: coastal and deep sea fishing

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