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  1. Article ; Online: Intraphagosomal Free Ca

    Dewitt, Sharon / Green, Joanna / Laffafian, Iraj / Lewis, Kimberly J / Hallett, Maurice B

    International journal of molecular sciences

    2024  Volume 25, Issue 8

    Abstract: Phagocytosis (and endocytosis) is an unusual cellular process that results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis but also the external medium, creating a ...

    Abstract Phagocytosis (and endocytosis) is an unusual cellular process that results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notably, Ca
    MeSH term(s) Phagocytosis ; Humans ; Calcium/metabolism ; Phagosomes/metabolism ; Neutrophils/metabolism ; Calcium Signaling ; Cytosol/metabolism ; Cell Membrane/metabolism
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2024-04-11
    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/ijms25084254
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  2. Article ; Online: Mesenchymal Transglutaminase 2 Activates Epithelial ADAM17: Link to G-Protein-Coupled Receptor 56 (ADGRG1) Signalling.

    Bauer, Lea / Edwards, Jessica / Heil, Andreas / Dewitt, Sharon / Biebermann, Heike / Aeschlimann, Daniel / Knäuper, Vera

    International journal of molecular sciences

    2024  Volume 25, Issue 4

    Abstract: A wound healing model was developed to elucidate the role of mesenchymal-matrix-associated transglutaminase 2 (TG2) in keratinocyte re-epithelialisation. TG2 drives keratinocyte migratory responses by activation of disintegrin and metalloproteinase 17 ( ... ...

    Abstract A wound healing model was developed to elucidate the role of mesenchymal-matrix-associated transglutaminase 2 (TG2) in keratinocyte re-epithelialisation. TG2 drives keratinocyte migratory responses by activation of disintegrin and metalloproteinase 17 (ADAM17). We demonstrate that epidermal growth factor (EGF) receptor ligand shedding leads to EGFR-transactivation and subsequent rapid keratinocyte migration on TG2-positive ECM. In contrast, keratinocyte migration was impaired in TG2 null conditions. We show that keratinocytes express the adhesion G-protein-coupled receptor, ADGRG1 (GPR56), which has been proposed as a TG2 receptor. Using ADAM17 activation as a readout and luciferase reporter assays, we demonstrate that TG2 activates GPR56. GPR56 activation by TG2 reached the same level as observed with an agonistic N-GPR56 antibody. The N-terminal GPR56 domain is required for TG2-regulated signalling response, as the constitutively active C-GPR56 receptor was not activated by TG2. Signalling required the C-terminal TG2 β-barrel domains and involved RhoA-associated protein kinase (ROCK) and ADAM17 activation, which was blocked by specific inhibitors. Cell surface binding of TG2 to the N-terminal GPR56 domain is rapid and is associated with TG2 and GPR56 endocytosis. TG2 and GPR56 represent a ligand receptor pair causing RhoA and EGFR transactivation. Furthermore, we determined a binding constant for the interaction of human TG2 with N-GPR56 and show for the first time that only the calcium-enabled "open" TG2 conformation associates with N-GPR56.
    MeSH term(s) Humans ; ADAM17 Protein/genetics ; ADAM17 Protein/metabolism ; ErbB Receptors/metabolism ; Ligands ; Protein Glutamine gamma Glutamyltransferase 2/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction
    Chemical Substances ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86) ; ErbB Receptors (EC 2.7.10.1) ; Ligands ; Protein Glutamine gamma Glutamyltransferase 2 (EC 2.3.2.13) ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2024-02-16
    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/ijms25042329
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  3. Article: Calpain Activation by Ca

    Dewitt, Sharon / Hallett, Maurice B

    Advances in experimental medicine and biology

    2020  Volume 1246, Page(s) 129–151

    Abstract: Although the cytosolic ... ...

    Abstract Although the cytosolic Ca
    MeSH term(s) Animals ; Calcium/metabolism ; Calpain/metabolism ; Cell Shape ; Cytosol/metabolism ; Enzyme Activation ; Humans ; Phagocytosis ; Pseudopodia/metabolism
    Chemical Substances Calpain (EC 3.4.22.-) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-05-12
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-40406-2_8
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  4. Article ; Online: Cell surface topography controls phagocytosis and cell spreading: The membrane reservoir in neutrophils.

    Al-Jumaa, Maha / Hallett, Maurice B / Dewitt, Sharon

    Biochimica et biophysica acta. Molecular cell research

    2020  Volume 1867, Issue 12, Page(s) 118832

    Abstract: Neutrophils exhibit rapid cell spreading and phagocytosis, both requiring a large apparent increase in the cell surface area. The wrinkled surface topography of these cells may provide the membrane reservoir for this. Here, the effects of manipulation of ...

    Abstract Neutrophils exhibit rapid cell spreading and phagocytosis, both requiring a large apparent increase in the cell surface area. The wrinkled surface topography of these cells may provide the membrane reservoir for this. Here, the effects of manipulation of the neutrophil cell surface topography on phagocytosis and cell spreading were established. Chemical expansion of the plasma membrane or osmotic swelling had no effects. However, osmotic shrinking of neutrophils inhibited both cell spreading and phagocytosis. Triggering a Ca
    MeSH term(s) Calcium/metabolism ; Calcium Signaling/genetics ; Cell Membrane/genetics ; Cell Shape/genetics ; Humans ; Neutrophils/metabolism ; Osmotic Pressure ; Phagocytes/metabolism ; Phagocytosis/genetics ; Signal Transduction
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-08-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2020.118832
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.247: Show issues Location:
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  5. Article ; Online: COVID-19 Symptoms by Variant Period in the North Carolina COVID-19 Community Research Partnership, North Carolina, USA.

    DeWitt, Michael E / Tjaden, Ashley H / Herrington, David / Schieffelin, John / Gibbs, Michael / Weintraub, William S / Sanders, John W / Edelstein, Sharon L

    Emerging infectious diseases

    2023  Volume 29, Issue 1, Page(s) 207–211

    Abstract: In North Carolina, USA, the SARS-CoV-2 Omicron variant was associated with changing symptomology in daily surveys, including increasing rates of self-reported cough and sore throat and decreased rates of loss of taste and smell. Compared with the pre- ... ...

    Abstract In North Carolina, USA, the SARS-CoV-2 Omicron variant was associated with changing symptomology in daily surveys, including increasing rates of self-reported cough and sore throat and decreased rates of loss of taste and smell. Compared with the pre-Delta period, Delta and Omicron (pre-BA.4/BA.5) variant periods were associated with shorter symptom duration.
    MeSH term(s) Humans ; COVID-19/epidemiology ; North Carolina/epidemiology ; SARS-CoV-2 ; Cough
    Language English
    Publishing date 2023-01-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1380686-5
    ISSN 1080-6059 ; 1080-6040
    ISSN (online) 1080-6059
    ISSN 1080-6040
    DOI 10.3201/eid2901.221111
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4778: Show issues Location:
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  6. Article: Membrane Tension and the Role of Ezrin During Phagocytosis.

    Roberts, Rhiannon E / Dewitt, Sharon / Hallett, Maurice B

    Advances in experimental medicine and biology

    2020  Volume 1246, Page(s) 83–102

    Abstract: During phagocytosis, there is an apparent expansion of the plasma membrane to accommodate the target within a phagosome. This is accompanied (or driven by) a change in membrane tension. It is proposed that the wrinkled topography of the phagocyte surface, ...

    Abstract During phagocytosis, there is an apparent expansion of the plasma membrane to accommodate the target within a phagosome. This is accompanied (or driven by) a change in membrane tension. It is proposed that the wrinkled topography of the phagocyte surface, by un-wrinkling, provides the additional available membrane and that this explains the changes in membrane tension. There is no agreement as to the mechanism by which unfolding of cell surface wrinkles occurs during phagocytosis, but there is a good case building for the involvement of the actin-plasma membrane crosslinking protein ezrin. Not only have direct measurements of membrane tension strongly implicated ezrin as the key component in establishing membrane tension, but the cortical location of ezrin changes at the phagocytic cup, suggesting that it is locally signalled. This chapter therefore attempts to synthesise our current state of knowledge about ezrin and membrane tension with phagocytosis to provide a coherent hypothesis.
    MeSH term(s) Cell Membrane/metabolism ; Cytoskeletal Proteins/metabolism ; Humans ; Phagocytosis
    Chemical Substances Cytoskeletal Proteins ; ezrin
    Language English
    Publishing date 2020-05-12
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-40406-2_6
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  7. Article ; Online: Perceptions of Clinical Experience and Scientific Evidence in Medical Decision Making: A Survey of a Stratified Random Sample of Swedish Health Care Professionals.

    Dewitt, Barry / Persson, Johannes / Wallin, Annika

    Medical decision making : an international journal of the Society for Medical Decision Making

    2024  Volume 44, Issue 3, Page(s) 335–345

    Abstract: ... Health care professions appear to share some attitudes toward professional knowledge, despite the variation in the age ...

    Abstract Background: Evidence-based medicine recognizes that clinical expertise gained through experience is essential to good medical practice. However, it is not known what beliefs clinicians hold about how personal clinical experience and scientific knowledge contribute to their clinical decision making and how those beliefs vary between professions, which themselves vary along relevant characteristics, such as their evidence base.
    Design: We investigate how years in the profession influence health care professionals' beliefs about science and their clinical experience through surveys administered to random samples of Swedish physicians, nurses, occupational therapists, dentists, and dental hygienists. The sampling frame was each profession's most recent occupational registry.
    Results: Participants (
    Conclusions: Health care professions appear to share some attitudes toward professional knowledge, despite the variation in the age of the professions and the scientific knowledge base available to practitioners. Training and policy making about clinical decision making might improve by accounting for the ways in which knowledge is understood across the professions.
    Highlights: Study participants, representing 5 health care professions-medicine, nursing, occupational therapy, dentistry, and dental hygiene-viewed science as more important for decision making, more certain, and more systematic than their personal clinical experience.Of all the professions represented in the study, physicians saw the greatest differences between the 2 types of knowledge.The effect of years of professional experience varied but tended to be small, attenuating the differences seen between science and clinical experience.
    MeSH term(s) Humans ; Sweden ; Health Personnel ; Physicians ; Research Design ; Clinical Decision-Making
    Language English
    Publishing date 2024-03-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604497-9
    ISSN 1552-681X ; 0272-989X
    ISSN (online) 1552-681X
    ISSN 0272-989X
    DOI 10.1177/0272989X241234318
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1665: Show issues Location:
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  8. Article ; Online: Optical Methods for the Measurement and Manipulation of Cytosolic Calcium Signals in Neutrophils.

    Hallett, Maurice B / Roberts, Rhiannon E / Dewitt, Sharon

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

    2019  Volume 2087, Page(s) 191–205

    Abstract: The measurement and manipulation of cytosolic free ... ...

    Abstract The measurement and manipulation of cytosolic free Ca
    MeSH term(s) Calcium/metabolism ; Calcium Signaling ; Cytosol/metabolism ; Humans ; Microscopy, Confocal ; Microscopy, Fluorescence ; Molecular Imaging/methods ; Neutrophils/immunology ; Neutrophils/metabolism ; Optical Imaging/methods ; Photochemical Processes
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2019-11-14
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0154-9_14
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  9. Article ; Online: Microinjection and Micropipette-Controlled Phagocytosis Methods for Neutrophils.

    Hallett, Maurice B / Campbell, Jennie S / Laffafian, Iraj / Dewitt, Sharon

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

    2019  Volume 2087, Page(s) 117–125

    Abstract: The ability to microinject substances into the cytosol of living neutrophils opens the possibility of manipulating the chemistry within the cell and also of monitoring changes using indicators which otherwise cannot be introduced into the cell. However, ... ...

    Abstract The ability to microinject substances into the cytosol of living neutrophils opens the possibility of manipulating the chemistry within the cell and also of monitoring changes using indicators which otherwise cannot be introduced into the cell. However, neutrophils cannot be microinjected by the conventional glass pipette insertion method. Here we outline two techniques which work well with neutrophils, namely, SLAM (Simple Lipid-Assisted Microinjection) and electromicroinjection. As these methods utilize micropipettes, we also include a simple method which uses a micropipette to deliver a phagocytic stimulus to a specific cell at a defined time, enable detailed study of the phagocytic process from particle contact to particle internalization.
    MeSH term(s) Cell Culture Techniques ; Humans ; Microinjections/methods ; Neutrophils/cytology ; Neutrophils/physiology ; Phagocytosis/genetics ; Phagocytosis/immunology ; Signal Transduction
    Language English
    Publishing date 2019-11-14
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0154-9_9
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  10. Article ; Online: Axial muscle weakness.

    Waheed, Waqar / Allison, James Brian / Dewitt, John / Hallman, Sharon / Tandan, Rup

    Practical neurology

    2020  

    Abstract: Axial myopathy is a rare neuromuscular disorder characterised by selective involvement of the paraspinal muscles, and presenting either as a bent spine and/or dropped head syndrome. The axial muscles can be involved in various conditions, including ... ...

    Abstract Axial myopathy is a rare neuromuscular disorder characterised by selective involvement of the paraspinal muscles, and presenting either as a bent spine and/or dropped head syndrome. The axial muscles can be involved in various conditions, including neuromuscular disease, movement disorders, spinal disease and metabolic disorders. There have been recent descriptions of disorders with selective axial muscle involvement, but overall axial myopathy remains under-recognised. Here, we review disorders of axial muscle function, provide guidance on interpreting axial muscles imaging and suggest a diagnostic algorithm to evaluate patients with axial muscles weakness.
    Language English
    Publishing date 2020-12-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2170881-2
    ISSN 1474-7766 ; 1474-7758
    ISSN (online) 1474-7766
    ISSN 1474-7758
    DOI 10.1136/practneurol-2020-002736
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    Zs.A 6001: Show issues Location:
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