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  1. Article ; Online: Canonical transient receptor potential channels and hypothalamic control of homeostatic functions.

    Kelly, Martin J / Wagner, Edward J

    Journal of neuroendocrinology

    2024  , Page(s) e13392

    Abstract: Recent molecular biological and electrophysiological studies have identified multiple transient receptor potential (TRP) channels in hypothalamic neurons as critical modulators of homeostatic functions. In particular, the canonical transient receptor ... ...

    Abstract Recent molecular biological and electrophysiological studies have identified multiple transient receptor potential (TRP) channels in hypothalamic neurons as critical modulators of homeostatic functions. In particular, the canonical transient receptor potential channels (TRPCs) are expressed in hypothalamic neurons that are vital for the control of fertility and energy homeostasis. Classical neurotransmitters such as serotonin and glutamate and peptide neurotransmitters such as kisspeptin, neurokinin B and pituitary adenylyl cyclase-activating polypeptide signal through their cognate G protein-coupled receptors to activate TPRC 4, 5 channels, which are essentially ligand-gated calcium channels. In addition to neurotransmitters, circulating hormones like insulin and leptin signal through insulin receptor (InsR) and leptin receptor (LRb), respectively, to activate TRPC 5 channels in hypothalamic arcuate nucleus pro-opiomelanocortin (POMC) and kisspeptin (arcuate Kiss1 [Kiss1
    Language English
    Publishing date 2024-04-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1007517-3
    ISSN 1365-2826 ; 0953-8194
    ISSN (online) 1365-2826
    ISSN 0953-8194
    DOI 10.1111/jne.13392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2634: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  2. Article: Dysregulation of the mRNA Expression of Human Renal Drug Transporters by Proinflammatory Cytokines in Primary Human Proximal Tubular Epithelial Cells.

    Tsang, Yik Pui / Hao, Tianran / Mao, Qingcheng / Kelly, Edward J / Unadkat, Jashvant D

    Pharmaceutics

    2024  Volume 16, Issue 2

    Abstract: Proinflammatory cytokines, which are elevated during inflammation or infections, can affect drug pharmacokinetics (PK) due to the altered expression or activity of drug transporters and/or metabolizing enzymes. To date, such studies have focused on the ... ...

    Abstract Proinflammatory cytokines, which are elevated during inflammation or infections, can affect drug pharmacokinetics (PK) due to the altered expression or activity of drug transporters and/or metabolizing enzymes. To date, such studies have focused on the effect of cytokines on the activity and/or mRNA expression of hepatic transporters and drug-metabolizing enzymes. However, many antibiotics and antivirals used to treat infections are cleared by renal transporters, including the basal organic cation transporter 2 (OCT2), organic anion transporters 1 and 3 (OAT1 and 3), the apical multidrug and toxin extrusion proteins 1 and 2-K (MATE1/2-K), and multidrug resistance-associated protein 2 and 4 (MRP2/4). Here, we determined the concentration-dependent effect of interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF)-α, and interferon-γ (IFN-γ) on the mRNA expression of human renal transporters in freshly isolated primary human renal proximal tubular epithelial cells (PTECs,
    Language English
    Publishing date 2024-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics16020285
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  3. Article ; Online: Molecular Mechanisms of Organic Anion Transporting Polypeptide-Mediated Organic Anion Clearance at the Blood-Cerebrospinal Fluid Barrier.

    Sun, Austin / Hagenbuch, Bruno / Kelly, Edward J / Wang, Joanne

    Molecular pharmacology

    2023  Volume 104, Issue 6, Page(s) 255–265

    Abstract: The blood-cerebrospinal fluid barrier (BCSFB), formed by the choroid plexus epithelial (CPE) cells, plays an active role in removing drugs and metabolic wastes from the brain. Recent functional studies in isolated mouse choroid plexus (CP) tissues ... ...

    Abstract The blood-cerebrospinal fluid barrier (BCSFB), formed by the choroid plexus epithelial (CPE) cells, plays an active role in removing drugs and metabolic wastes from the brain. Recent functional studies in isolated mouse choroid plexus (CP) tissues suggested the presence of organic anion transporting polypeptides (OATPs, encoded by SLCOs) at the apical membrane of BCSFB, which may clear large organic anions from the cerebrospinal fluid (CSF). However, the specific OATP isoform involved is unclear. Using quantitative fluorescence imaging, we showed that the fluorescent anions sulforhodamine 101 (SR101), fluorescein methotrexate (FL-MTX), and 8-fluorescein-cAMP (fluo-cAMP) are actively transported from the CSF to the subepithelial space in CP tissues isolated from wild-type mice. In contrast, transepithelial transport of these compounds across the CPE cells was abolished in Oatp1a/1b
    MeSH term(s) Mice ; Humans ; Animals ; Kinetics ; Blood-Brain Barrier/metabolism ; Organic Anion Transporters/metabolism ; Biological Transport ; Fluorescein/metabolism ; Anions/metabolism
    Chemical Substances fluorescein-methotrexate ; Organic Anion Transporters ; Fluorescein (TPY09G7XIR) ; Anions
    Language English
    Publishing date 2023-08-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/molpharm.123.000703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 525: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Kidney microphysiological models for nephrotoxicity assessment.

    Mahadeo, Anish / Yeung, Catherine K / Himmelfarb, Jonathan / Kelly, Edward J

    Current opinion in toxicology

    2022  Volume 30

    Abstract: Nephrotoxicity testing is an important step in preclinical development of new molecular entities (NMEs) and has traditionally been performed in 2-D cell culture systems and animal models. However, 2-D culture systems fail to replicate ... ...

    Abstract Nephrotoxicity testing is an important step in preclinical development of new molecular entities (NMEs) and has traditionally been performed in 2-D cell culture systems and animal models. However, 2-D culture systems fail to replicate complex
    Language English
    Publishing date 2022-03-30
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2468-2934
    ISSN 2468-2934
    DOI 10.1016/j.cotox.2022.03.002
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  5. Article ; Online: The lucent yet opaque challenge of regulating artificial intelligence in radiology.

    Hillis, James M / Visser, Jacob J / Cliff, Edward R Scheffer / van der Geest-Aspers, Kelly / Bizzo, Bernardo C / Dreyer, Keith J / Adams-Prassl, Jeremias / Andriole, Katherine P

    NPJ digital medicine

    2024  Volume 7, Issue 1, Page(s) 69

    Language English
    Publishing date 2024-03-15
    Publishing country England
    Document type Journal Article
    ISSN 2398-6352
    ISSN (online) 2398-6352
    DOI 10.1038/s41746-024-01071-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity.

    Kelly, Conor J / Chitko-McKown, Carol G / Chuong, Edward B

    Genome research

    2022  

    Abstract: Cattle are an important livestock species, and mapping the genomic architecture of agriculturally relevant traits such as disease susceptibility is a major challenge in the bovine research community. Lineage-specific transposable elements (TEs) are ... ...

    Abstract Cattle are an important livestock species, and mapping the genomic architecture of agriculturally relevant traits such as disease susceptibility is a major challenge in the bovine research community. Lineage-specific transposable elements (TEs) are increasingly recognized to contribute to gene regulatory evolution and variation, but this possibility has been largely unexplored in ruminant genomes. We conducted epigenomic profiling of the type II interferon (IFN) response in bovine cells and found thousands of ruminant-specific TEs including MER41_BT and Bov-A2 elements predicted to act as IFN-inducible enhancer elements. CRISPR knockout experiments in bovine cells established that critical immune factors including
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.276241.121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3729: Show issues Location:
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    Zs.MG 8: Show issues

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  7. Article ; Online: Mouse B2 SINE elements function as IFN-inducible enhancers.

    Horton, Isabella / Kelly, Conor J / Dziulko, Adam / Simpson, David M / Chuong, Edward B

    eLife

    2023  Volume 12

    Abstract: Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance ... ...

    Abstract Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of
    MeSH term(s) Animals ; Mice ; Regulatory Sequences, Nucleic Acid ; Promoter Regions, Genetic ; Interferon-gamma/genetics ; Biological Evolution ; Binding Sites ; DNA Transposable Elements ; Enhancer Elements, Genetic/genetics
    Chemical Substances Interferon-gamma (82115-62-6) ; DNA Transposable Elements
    Language English
    Publishing date 2023-05-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.82617
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  8. Article: Inhibition of glioblastoma cell proliferation and invasion by the choline-kinase inhibitor JAS239 varies with cell type and hypoxia.

    Louise Kelly, Claire / Wydrzynska, Martyna / Phelan, Marie M / Osharovich, Sofya / Delikatny, Edward J / Sée, Violaine / Poptani, Harish

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: Elevated choline kinase alpha (ChoK) is observed in most solid tumours including glioblastomas (GBM), yet until recently, inhibitors of ChoK have demonstrated limited efficacy in GBM models. Given that hypoxia is associated with GBM therapy ... ...

    Abstract Background: Elevated choline kinase alpha (ChoK) is observed in most solid tumours including glioblastomas (GBM), yet until recently, inhibitors of ChoK have demonstrated limited efficacy in GBM models. Given that hypoxia is associated with GBM therapy resistance, we hypothesised that tumour hypoxia could be responsible for such limitations. We therefore evaluated in GBM cells, the effect of hypoxia on the function of JAS239, a potent ChoK inhibitor.
    Methods: Rodent (F98 and 9L) and human (U-87 MG and U-251 MG) GBM cell lines were subjected to 72 hours of hypoxia conditioning and treated with JAS239 for 24 hours. NMR metabolomic measurements and analyses were performed to evaluate the signalling pathways involved. In addition, cell proliferation, cell cycle progression and cell invasion were measured in cell monolayers and 3D spheroids, with or without JAS239 treatment in normoxic or hypoxic cells to assess how hypoxia affects JAS239 function.
    Results: Hypoxia and JAS239 treatment led to significant changes in the cellular metabolic pathways, specifically the phospholipid and glycolytic pathways associated with a reduction in cell proliferation via induced cell cycle arrest. Interestingly, JAS239 also impaired GBM invasion. However, JAS239 effects were variable depending on the cell line, reflecting the inherent heterogeneity observed in GBMs.
    Conclusion: Our findings indicate that JAS239 and hypoxia can deregulate cellular metabolism, inhibit proliferation and alter cell invasion. These results may be useful for the design of new therapeutic strategies based on ChoK inhibition that can act on multiple pro-tumorigenic features.
    Language English
    Publishing date 2024-01-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.17.576078
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Mouse B2 SINE elements function as IFN-inducible enhancers

    Isabella Horton / Conor J Kelly / Adam Dziulko / David M Simpson / Edward B Chuong

    eLife, Vol

    2023  Volume 12

    Abstract: Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance ... ...

    Abstract Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of Dicer1. The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity, and exemplifies how lineage-specific TEs can facilitate evolutionary turnover and divergence of innate immune regulatory networks.
    Keywords interferon ; transposon ; gene regulation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Neutrophil Extracellular Traps Are Induced by Coronavirus 2019 Disease-Positive Patient Plasma and Persist Longitudinally: A Possible Link to Endothelial Dysfunction as Measured by Syndecan-1.

    Kelly, Edward J / Oliver, Mary A / Carney, Bonnie C / Kolachana, Sindhura / Moffatt, Lauren T / Shupp, Jeffrey W

    Surgical infections

    2023  Volume 24, Issue 10, Page(s) 887–896

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) Humans ; COVID-19 ; Extracellular Traps/chemistry ; Extracellular Traps/metabolism ; Histones ; Neutrophils ; Peroxidase/analysis ; Peroxidase/metabolism ; Syndecan-1
    Chemical Substances Histones ; Peroxidase (EC 1.11.1.7) ; Syndecan-1 ; SDC1 protein, human
    Language English
    Publishing date 2023-11-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1440120-4
    ISSN 1557-8674 ; 1096-2964
    ISSN (online) 1557-8674
    ISSN 1096-2964
    DOI 10.1089/sur.2023.156
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    Zs.A 5617: Show issues Location:
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