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  1. Article: Metabolite-sensing GPCRs controlling interactions between adipose tissue and inflammation.

    Duncan, Elaine M / Vita, Luca / Dibnah, Bethany / Hudson, Brian D

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1197102

    Abstract: Metabolic disorders including obesity, diabetes and non-alcoholic steatohepatitis are a group of conditions characterised by chronic low-grade inflammation of metabolic tissues. There is now a growing appreciation that various metabolites released from ... ...

    Abstract Metabolic disorders including obesity, diabetes and non-alcoholic steatohepatitis are a group of conditions characterised by chronic low-grade inflammation of metabolic tissues. There is now a growing appreciation that various metabolites released from adipose tissue serve as key signalling mediators, influencing this interaction with inflammation. G protein-coupled receptors (GPCRs) are the largest family of signal transduction proteins and most historically successful drug targets. The signalling pathways for several key adipose metabolites are mediated through GPCRs expressed both on the adipocytes themselves and on infiltrating macrophages. These include three main groups of GPCRs: the FFA4 receptor, which is activated by long chain free fatty acids; the HCA
    MeSH term(s) Humans ; Receptors, G-Protein-Coupled/metabolism ; Adipose Tissue/metabolism ; Inflammation/metabolism ; Adipocytes/metabolism ; Obesity/metabolism ; Metabolic Diseases/metabolism
    Chemical Substances Receptors, G-Protein-Coupled
    Language English
    Publishing date 2023-07-06
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1197102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development and Characterization of Potent Succinate Receptor Fluorescent Tracers.

    Ciba, Marija / Dibnah, Bethany / Hudson, Brian D / Rexen Ulven, Elisabeth

    Journal of medicinal chemistry

    2023  Volume 66, Issue 13, Page(s) 8951–8974

    Abstract: The succinate receptor (SUCNR1) has emerged as a potential target for the treatment of various metabolic and inflammatory diseases, including hypertension, inflammatory bowel disease, and rheumatoid arthritis. While several ligands for this receptor have ...

    Abstract The succinate receptor (SUCNR1) has emerged as a potential target for the treatment of various metabolic and inflammatory diseases, including hypertension, inflammatory bowel disease, and rheumatoid arthritis. While several ligands for this receptor have been reported, species differences in pharmacology between human and rodent orthologs have limited the validation of SUCNR1's therapeutic potential. Here, we describe the development of the first potent fluorescent tool compounds for SUCNR1 and use these to define key differences in ligand binding to human and mouse SUCNR1. Starting from known agonist scaffolds, we developed a potent agonist tracer, TUG-2384 (
    MeSH term(s) Mice ; Humans ; Animals ; Succinic Acid/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Coloring Agents
    Chemical Substances Succinic Acid (AB6MNQ6J6L) ; Receptors, G-Protein-Coupled ; Coloring Agents
    Language English
    Publishing date 2023-06-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00552
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: Show issues Location:
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  3. Article: Using Biosensors to Study Free Fatty Acid Receptor Pharmacology and Function.

    Hudson, Brian D

    Handbook of experimental pharmacology

    2017  Volume 236, Page(s) 79–100

    Abstract: The free fatty acid (FFA) family of G protein coupled receptors (GPCRs) has generated significant interest for exploiting its members as potential drug targets. However, unravelling the complex pharmacology of this family of receptors has proven ... ...

    Abstract The free fatty acid (FFA) family of G protein coupled receptors (GPCRs) has generated significant interest for exploiting its members as potential drug targets. However, unravelling the complex pharmacology of this family of receptors has proven challenging. In recent years the use of biosensor technologies capable of assessing biological functions in living cells, and in real time, has greatly enhanced our ability to study GPCR pharmacology and function. These include genetically encoded sensors that change the intensity or wavelength of light emitted from a bioluminescent or fluorescent protein in response to a stimulus, as well as non-genetically encoded sensors able to measure more global cellular changes, such as mass redistribution within a cell. This chapter will examine how these sensors can be used to study GPCRs, and in particular how they are helping uncover the pharmacology of the FFA family of receptors.
    MeSH term(s) Animals ; Arrestin/analysis ; Biosensing Techniques/methods ; Fatty Acids, Nonesterified/metabolism ; Humans ; Receptors, G-Protein-Coupled/drug effects ; Receptors, G-Protein-Coupled/physiology ; Signal Transduction
    Chemical Substances Arrestin ; Fatty Acids, Nonesterified ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2017
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 0171-2004
    ISSN 0171-2004
    DOI 10.1007/164_2016_58
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Sign. bis Bd. 125 (1997): 1982 A 2146: Show issues
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  4. Article: 3D Bioprinting of Collagen-based Microfluidics for Engineering Fully-biologic Tissue Systems.

    Shiwarski, Daniel J / Hudson, Andrew R / Tashman, Joshua W / Bakirci, Ezgi / Moss, Samuel / Coffin, Brian D / Feinberg, Adam W

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Microfluidic and organ-on-a-chip devices have improved the physiologic and translational relevance of in vitro systems in applications ranging from disease modeling to drug discovery and pharmacology. However, current manufacturing approaches have ... ...

    Abstract Microfluidic and organ-on-a-chip devices have improved the physiologic and translational relevance of in vitro systems in applications ranging from disease modeling to drug discovery and pharmacology. However, current manufacturing approaches have limitations in terms of materials used, non-native mechanical properties, patterning of extracellular matrix (ECM) and cells in 3D, and remodeling by cells into more complex tissues. We present a method to 3D bioprint ECM and cells into microfluidic collagen-based high-resolution internally perfusable scaffolds (CHIPS) that address these limitations, expand design complexity, and simplify fabrication. Additionally, CHIPS enable size-dependent diffusion of molecules out of perfusable channels into the surrounding device to support cell migration and remodeling, formation of capillary-like networks, and integration of secretory cell types to form a glucose-responsive, insulin-secreting pancreatic-like microphysiological system.
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.26.577422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: FRESH 3D Bioprinting a Ventricle-like Cardiac Construct Using Human Stem Cell-Derived Cardiomyocytes.

    Coffin, Brian D / Hudson, Andrew R / Lee, Andrew / Feinberg, Adam W

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2485, Page(s) 71–85

    Abstract: Here we describe a method to engineer a contractile ventricle-like chamber composed of human stem cell-derived cardiomyocytes using freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting. To do this, we print a support structure ... ...

    Abstract Here we describe a method to engineer a contractile ventricle-like chamber composed of human stem cell-derived cardiomyocytes using freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting. To do this, we print a support structure using a collagen type I ink and a cellular component using a high-density cell ink supplemented with fibrinogen. The gelation of the collagen and the fibrinogen into fibrin is initiated by pH change and enzymatic crosslinking, respectively. Fabrication of the ventricle-like chamber is completed in three distinct phases: (i) materials preparation, (ii) bioprinting, and (iii) tissue maturation. In this protocol, we describe the method to print the construct from a high-density cell ink composed of human stem cell-derived cardiomyocytes and primary fibroblasts (~300 × 10
    MeSH term(s) Bioprinting/methods ; Fibrinogen ; Humans ; Hydrogels/chemistry ; Myocytes, Cardiac ; Printing, Three-Dimensional ; Stem Cells
    Chemical Substances Hydrogels ; Fibrinogen (9001-32-5)
    Language English
    Publishing date 2022-05-26
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2261-2_5
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  6. Article: Predicting neutralization susceptibility to combination HIV-1 monoclonal broadly neutralizing antibody regimens.

    Williamson, Brian D / Wu, Liana / Huang, Yunda / Hudson, Aaron / Gilbert, Peter B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 infection. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against ... ...

    Abstract Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 infection. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratory's Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory concentration < 1 μg/mL. For continuous outcomes, the CP approach performs at least as well as the PC approach, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.
    Language English
    Publishing date 2023-12-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.14.571616
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  7. Article ; Online: Plasma C-reactive protein is lower among marijuana using HIV-negative individuals but not among persons living with HIV

    Ethan Morgan / Hannah Hudson / Richard D’Aquila / Brian Mustanski

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Abstract The use of marijuana is highly prevalent among young men who have sex with men (YMSM). Past work has also shown that inflammation is elevated among YMSM, independent of HIV status. Here, we aim to examine the relationship between marijuana use ... ...

    Abstract Abstract The use of marijuana is highly prevalent among young men who have sex with men (YMSM). Past work has also shown that inflammation is elevated among YMSM, independent of HIV status. Here, we aim to examine the relationship between marijuana use and inflammation among this high-risk cohort, relative to use of other substances. Data were collected among YMSM aged 16–29 in Chicago. Multiplex cytokine and inflammatory biomarker assays were run on plasma from all persons living with HIV (PLWH) (n = 195) and a subset of HIV-negative participants (n = 489). Bivariate analyses and multivariable models assessed relationships between various substances and inflammatory biomarkers. Models were stratified by HIV status and adjusted for demographic characteristics. Most participants reported use of marijuana in the past 30 days (416, 60.8%). Mean blood C-reactive protein (CRP) levels were above the upper limit of normal (3.0 mg/L), indicative of increased risk for cardiovascular disease (mean CRP was 3.9 mg/L; SD = 8.5). In adjusted, stratified analyses, CRP was significantly lower among participants reporting frequent marijuana use (≥ 6 times per month), relative to those reporting never using marijuana, (β = − 0.38; 95% CI: − 0.73, − 0.03). However, this was entirely accounted for by an association among the HIV-negative participants and there was no significant association between marijuana use and blood CRP level among the PLWH. In summary, YMSM had markedly elevated marijuana use and blood CRP levels. Frequent marijuana use was associated with lower inflammation among only those not diagnosed with HIV. Further research is needed to explicate why there are differences between HIV-negative participants and PLWH and to leverage this information to characterize biological mechanisms by which marijuana decreases inflammation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Impact of the Protein Data Bank on antineoplastic approvals.

    Westbrook, John D / Soskind, Rose / Hudson, Brian P / Burley, Stephen K

    Drug discovery today

    2020  Volume 25, Issue 5, Page(s) 837–850

    Abstract: Open access to 3D structure information from the Protein Data Bank (PDB) facilitated discovery and development of >90% of the 79 new antineoplastic agents (54 small molecules, 25 biologics) with known molecular targets approved by the FDA 2010-2018. ... ...

    Abstract Open access to 3D structure information from the Protein Data Bank (PDB) facilitated discovery and development of >90% of the 79 new antineoplastic agents (54 small molecules, 25 biologics) with known molecular targets approved by the FDA 2010-2018. Analyses of PDB holdings, the scientific literature and related documents for each drug-target combination revealed that the impact of public-domain 3D structure data was broad and substantial, ranging from understanding target biology (∼95% of all targets) to identifying a given target as probably druggable (∼95% of all targets) to structure-guided lead optimization (>70% of all small-molecule drugs). In addition to aggregate impact assessments, illustrative case studies are presented for three protein kinase inhibitors, an allosteric enzyme inhibitor and seven advanced-stage melanoma therapeutics.
    MeSH term(s) Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Databases, Protein ; Drug Discovery/methods ; Humans ; Melanoma/drug therapy ; Protein Conformation ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors
    Language English
    Publishing date 2020-02-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2020.02.002
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    Zs.A 4725: Show issues Location:
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  9. Article: Liopropomaincandescens

    Pinheiro, Hudson T / Shepherd, Bart / Greene, Brian D / Rocha, Luiz A

    ZooKeys

    2019  Volume 863, Page(s) 97–106

    Abstract: A new species of the ... ...

    Abstract A new species of the genus
    Language English
    Publishing date 2019-07-11
    Publishing country Bulgaria
    Document type Journal Article
    ZDB-ID 2445640-8
    ISSN 1313-2970 ; 1313-2989
    ISSN (online) 1313-2970
    ISSN 1313-2989
    DOI 10.3897/zookeys.863.33778
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Agonist-induced phosphorylation of orthologues of the orphan receptor GPR35 functions as an activation sensor.

    Divorty, Nina / Jenkins, Laura / Ganguly, Amlan / Butcher, Adrian J / Hudson, Brian D / Schulz, Stefan / Tobin, Andrew B / Nicklin, Stuart A / Milligan, Graeme

    The Journal of biological chemistry

    2022  Volume 298, Issue 3, Page(s) 101655

    Abstract: G protein-coupled receptor 35 (GPR35) is poorly characterized but nevertheless has been revealed to have diverse roles in areas including lower gut inflammation and pain. The development of novel reagents and tools will greatly enhance analysis of GPR35 ... ...

    Abstract G protein-coupled receptor 35 (GPR35) is poorly characterized but nevertheless has been revealed to have diverse roles in areas including lower gut inflammation and pain. The development of novel reagents and tools will greatly enhance analysis of GPR35 functions in health and disease. Here, we used mass spectrometry, mutagenesis, and [
    MeSH term(s) Animals ; Humans ; Immune Sera/pharmacology ; Mice ; Phosphorylation ; Rats ; Receptors, G-Protein-Coupled/metabolism ; Serine/metabolism ; beta-Arrestin 2/metabolism
    Chemical Substances GPR35 protein, human ; GPR35 protein, mouse ; GPR35 protein, rat ; Immune Sera ; Receptors, G-Protein-Coupled ; beta-Arrestin 2 ; Serine (452VLY9402)
    Language English
    Publishing date 2022-01-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.101655
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