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  1. Book: Measuring biological responses with automated microscopy

    Inglese, James

    (Methods in enzymology ; 414)

    2006  

    Author's details ed. by James Inglese
    Series title Methods in enzymology ; 414
    Collection
    Language English
    Size XLIV, 691 S. : Ill., graph. Darst.
    Publisher Elsevier
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book
    HBZ-ID HT014911865
    ISBN 978-0-12-182819-6 ; 0-12-182819-0
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    Se 222 -414- verfügbar in Königswinter Königswinter

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  2. Article: qHTSWaterfall: 3-dimensional visualization software for quantitative high-throughput screening (qHTS) data.

    Queme, Bryan / Braisted, John C / Dranchak, Patricia / Inglese, James

    Journal of cheminformatics

    2023  Volume 15, Issue 1, Page(s) 39

    Abstract: High throughput screening (HTS) is widely used in drug discovery and chemical biology to identify and characterize agents having pharmacologic properties often by evaluation of large chemical libraries. Standard HTS data can be simply plotted as an x-y ... ...

    Abstract High throughput screening (HTS) is widely used in drug discovery and chemical biology to identify and characterize agents having pharmacologic properties often by evaluation of large chemical libraries. Standard HTS data can be simply plotted as an x-y graph usually represented as % activity of a compound tested at a single concentration vs compound ID, whereas quantitative HTS (qHTS) data incorporates a third axis represented by concentration. By virtue of the additional data points arising from the compound titration and the incorporation of logistic fit parameters that define the concentration-response curve, such as EC50 and Hill slope, qHTS data has been challenging to display on a single graph. Here we provide a flexible solution to the rapid plotting of complete qHTS data sets to produce a 3-axis plot we call qHTS Waterfall Plots. The software described here can be generally applied to any 3-axis dataset and is available as both an R package and an R shiny application.
    Language English
    Publishing date 2023-03-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 2486539-4
    ISSN 1758-2946
    ISSN 1758-2946
    DOI 10.1186/s13321-023-00717-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.

    Kinder, Travis B / Dranchak, Patricia K / Inglese, James

    ACS chemical biology

    2020  Volume 15, Issue 7, Page(s) 1974–1986

    Abstract: Immunosuppressants used to treat autoimmunity are often not curative and have many side effects. Our purpose was to identify therapeutics for autoimmunity of the skeletal muscle termed idiopathic inflammatory myopathies (myositis). Recent evidence shows ... ...

    Abstract Immunosuppressants used to treat autoimmunity are often not curative and have many side effects. Our purpose was to identify therapeutics for autoimmunity of the skeletal muscle termed idiopathic inflammatory myopathies (myositis). Recent evidence shows that the pro-inflammatory type I interferons (IFN) and a downstream product major histocompatibility complex (MHC) class I are pathogenic in myositis. We conducted quantitative high-throughput screening on >4500 compounds, including all approved drugs, through a series of cell-based assays to identify those that inhibit the type I IFN-MHC class I pathway in muscle precursor cells (myoblasts). The primary screen utilized CRISPR/Cas9 genome-engineered human myoblasts containing a pro-luminescent reporter HiBit fused to the C-terminus of endogenous MHC class I. Active compounds were counter-screened for cytotoxicity and validated by MHC class I immunofluorescence, Western blot, and RT-qPCR. Actives included Janus kinase inhibitors, with the most potent being ruxolitinib, and epigenetic/transcriptional modulators like histone deacetylase inhibitors and the hypoxia-inducible factor 1 inhibitor echinomycin. Testing in animal models and clinical trials is necessary to translate these therapies to myositis patients. These robust assay technologies can be further utilized to interrogate the basic mechanisms of the type I IFN-MHC class I pathway, identify novel molecular probes, and elucidate possible environmental triggers that may lead to myositis.
    MeSH term(s) Cell Line ; HLA-B Antigens/drug effects ; HLA-B Antigens/metabolism ; High-Throughput Screening Assays ; Humans ; Immunologic Factors/pharmacology ; Interferon Type I/drug effects ; Interferon Type I/metabolism ; Myoblasts/drug effects ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/pharmacology ; STAT1 Transcription Factor/metabolism ; Small Molecule Libraries/pharmacology
    Chemical Substances HLA-B Antigens ; Immunologic Factors ; Interferon Type I ; Protein Kinase Inhibitors ; STAT1 Transcription Factor ; STAT1 protein, human ; Small Molecule Libraries
    Language English
    Publishing date 2020-06-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.0c00343
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.

    Dranchak, Patricia K / Oliphant, Erin / Queme, Bryan / Lamy, Laurence / Wang, Yuhong / Huang, Ruili / Xia, Menghang / Tao, Dingyin / Inglese, James

    Disease models & mechanisms

    2023  Volume 16, Issue 3

    Abstract: Quantitative high-throughput screening (qHTS) pharmacologically evaluates chemical libraries for therapeutic uses, toxicological risk and, increasingly, for academic probe discovery. Phenotypic high-throughput screening assays interrogate molecular ... ...

    Abstract Quantitative high-throughput screening (qHTS) pharmacologically evaluates chemical libraries for therapeutic uses, toxicological risk and, increasingly, for academic probe discovery. Phenotypic high-throughput screening assays interrogate molecular pathways, often relying on cell culture systems, historically less focused on multicellular organisms. Caenorhabditis elegans has served as a eukaryotic model organism for human biology by virtue of genetic conservation and experimental tractability. Here, a paradigm enabling C. elegans qHTS using 384-well microtiter plate laser-scanning cytometry is described, in which GFP-expressing organisms revealing phenotype-modifying structure-activity relationships guide subsequent life-stage and proteomic analyses, and Escherichia coli bacterial ghosts, a non-replicating nutrient source, allow compound exposures over two life cycles, mitigating bacterial overgrowth complications. We demonstrate the method with libraries of anti-infective agents, or substances of toxicological concern. Each was tested in seven-point titration to assess the feasibility of nematode-based in vivo qHTS, and examples of follow-up strategies were provided to study organism-based chemotype selectivity and subsequent network perturbations with a physiological impact. We anticipate that this qHTS approach will enable analysis of C. elegans orthologous phenotypes of human pathologies to facilitate drug library profiling for a range of therapeutic indications.
    MeSH term(s) Animals ; Humans ; High-Throughput Screening Assays/methods ; Caenorhabditis elegans/genetics ; Proteomics ; Drug Discovery/methods ; Small Molecule Libraries/pharmacology
    Chemical Substances Small Molecule Libraries
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Intramural
    ZDB-ID 2451104-3
    ISSN 1754-8411 ; 1754-8403
    ISSN (online) 1754-8411
    ISSN 1754-8403
    DOI 10.1242/dmm.049863
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: High-throughput screening identifies cell cycle-associated signaling cascades that regulate a multienzyme glucosome assembly in human cells.

    Schmitt, Danielle L / Dranchak, Patricia / Parajuli, Prakash / Blivis, Dvir / Voss, Ty / Kohnhorst, Casey L / Kyoung, Minjoung / Inglese, James / An, Songon

    PloS one

    2023  Volume 18, Issue 8, Page(s) e0289707

    Abstract: We have previously demonstrated that human liver-type phosphofructokinase 1 (PFK1) recruits other rate-determining enzymes in glucose metabolism to organize multienzyme metabolic assemblies, termed glucosomes, in human cells. However, it has remained ... ...

    Abstract We have previously demonstrated that human liver-type phosphofructokinase 1 (PFK1) recruits other rate-determining enzymes in glucose metabolism to organize multienzyme metabolic assemblies, termed glucosomes, in human cells. However, it has remained largely elusive how glucosomes are reversibly assembled and disassembled to functionally regulate glucose metabolism and thus contribute to human cell biology. We developed a high-content quantitative high-throughput screening (qHTS) assay to identify regulatory mechanisms that control PFK1-mediated glucosome assemblies from stably transfected HeLa Tet-On cells. Initial qHTS with a library of pharmacologically active compounds directed following efforts to kinase-inhibitor enriched collections. Consequently, three compounds that were known to inhibit cyclin-dependent kinase 2, ribosomal protein S6 kinase and Aurora kinase A, respectively, were identified and further validated under high-resolution fluorescence single-cell microscopy. Subsequent knockdown studies using small-hairpin RNAs further confirmed an active role of Aurora kinase A on the formation of PFK1 assemblies in HeLa cells. Importantly, all the identified protein kinases here have been investigated as key signaling nodes of one specific cascade that controls cell cycle progression in human cells. Collectively, our qHTS approaches unravel a cell cycle-associated signaling network that regulates the formation of PFK1-mediated glucosome assembly in human cells.
    MeSH term(s) Humans ; HeLa Cells ; Aurora Kinase A ; High-Throughput Screening Assays ; Cell Cycle ; Glucose/metabolism
    Chemical Substances Aurora Kinase A (EC 2.7.11.1) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-08-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0289707
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Paracatalytic induction: Subverting specificity in hedgehog protein autoprocessing with small molecules.

    Ciulla, Daniel A / Xu, Zihan / Pezzullo, John L / Dranchak, Patricia / Wang, Chunyu / Giner, José-Luis / Inglese, James / Callahan, Brian P

    Methods in enzymology

    2023  Volume 685, Page(s) 1–41

    Abstract: Paracatalytic inducers are antagonists that shift the specificity of biological catalysts, resulting in non-native transformations. In this Chapter we describe methods to discover paracatalytic inducers of Hedgehog (Hh) protein autoprocessing. Native ... ...

    Abstract Paracatalytic inducers are antagonists that shift the specificity of biological catalysts, resulting in non-native transformations. In this Chapter we describe methods to discover paracatalytic inducers of Hedgehog (Hh) protein autoprocessing. Native autoprocessing uses cholesterol as a substrate nucleophile to assist in cleaving an internal peptide bond within a precursor form of Hh. This unusual reaction is brought about by HhC, an enzymatic domain that resides within the C-terminal region of Hh precursor proteins. Recently, we reported paracatalytic inducers as a novel class of Hh autoprocessing antagonists. These small molecules bind HhC and tilt the substrate specificity away from cholesterol in favor of solvent water. The resulting cholesterol-independent autoproteolysis of the Hh precursor generates a non-native Hh side product with substantially reduced biological signaling activity. Protocols are provided for in vitro FRET-based and in-cell bioluminescence assays to discover and characterize paracatalytic inducers of Drosophila and human hedgehog protein autoprocessing, respectively.
    MeSH term(s) Animals ; Humans ; Hedgehog Proteins/genetics ; Hedgehog Proteins/chemistry ; Hedgehog Proteins/metabolism ; Drosophila Proteins/chemistry ; Drosophila/metabolism ; Cholesterol/metabolism ; Catalysis
    Chemical Substances Hedgehog Proteins ; Drosophila Proteins ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2023-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ISSN 1557-7988
    ISSN (online) 1557-7988
    DOI 10.1016/bs.mie.2023.03.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book: Measuring biological responses with automated microscopy

    Inglese, James

    (Methods in enzymology ; v. 414)

    2006  

    Author's details edited by James Inglese
    Series title Methods in enzymology ; v. 414
    Keywords Microscopy/Technique. ; Enzymology/Equipment and supplies.
    Language English
    Size xliv, 691 p. :, ill. (some col.) ;, 24 cm.
    Publisher Elsevier/Academic Press
    Publishing place Amsterdam ; Boston
    Document type Book
    ISBN 0121828190 ; 9780121828196
    Database NAL-Catalogue (AGRICOLA)

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Book: Measuring biological responses with automated microscopy

    Inglese, James

    (Methods in enzymology ; v. 414)

    2006  

    Author's details edited by James Inglese
    Series title Methods in enzymology ; v. 414
    MeSH term(s) Cell Physiological Phenomena ; Microscopy, Fluorescence/methods ; Automation ; Cells ; Microscopy, Fluorescence/instrumentation
    Language English
    Size xliv, 691 p. :, ill. (some col.) ;, 24 cm.
    Publisher Elsevier/Academic Press
    Publishing place Amsterdam ; Boston
    Document type Book
    ISBN 9780121828196 ; 0121828190
    Database Catalogue of the US National Library of Medicine (NLM)

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    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  9. Book: Measuring biological responses with automated microscopy

    Inglese, James

    (Methods in enzymology ; 414)

    2006  

    Author's details ed. by James Inglese
    Series title Methods in enzymology ; 414
    Keywords Messung ; Biochemische Reaktion ; Mikroskopie
    Language English
    Size XLIV, 691 S., Ill., graph. Darst.
    Publisher Elsevier, Acad. Press
    Publishing place Amsterdam u.a.
    Document type Book
    Note Literaturangaben
    ISBN 0121828190 ; 9780121828196
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  10. Book ; Online: Measuring biological responses with automated microscopy

    Inglese, James

    (Methods in enzymology ; 414)

    2006  

    Abstract: The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and ... ...

    Author's details ed. by James Inglese
    Series title Methods in enzymology ; 414
    Abstract The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today-truly an essential publication for researchers in all fields of life sciences

    The critically acclaimed laboratory standard for more than forty years, Methods in Enzymologyis one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today-truly an essential publication for researchers in all fields of life sciences.
    Keywords Enzymology/Equipment and supplies ; Microscopy/Technique ; Messung ; Biochemische Reaktion ; Mikroskopie ; Technik / Wissen # Biologie ; Technik / Wissen # Sonstiges
    Language English
    Size Online-Ressource (XLIV, 691 S.)
    Publisher Elsevier, Acad. Press
    Publishing place Amsterdam u.a.
    Document type Book ; Online
    Note Literaturangaben
    ISBN 0121828190 ; 9780121828196
    Database Former special subject collection: coastal and deep sea fishing

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