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  1. Article: Krüppel-like Factor (KLF) family members control expression of genes required for serous cavity and alveolar macrophage identities.

    Pestal, Kathleen / Slayden, Leianna C / Barton, Gregory M

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we ... ...

    Abstract Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Kruppel-like Factor 2 (KLF2) in the development of embryonically derived Large Cavity Macrophages (LCM) in the serous cavities. KLF2 not only directly regulates the transcription of genes previously shown to specify LCM identity, such as retinoic acid receptors and GATA6, but also is required for induction of many other transcripts that define the identity of these cells. We identify a similar role for KLF4 in regulating the identity of alveolar macrophages in the lung. These data demonstrate that broadly expressed transcription factors, such as Group 2 KLFs, can play important roles in the specification of distinct identities of tissue-resident macrophages.
    Language English
    Publishing date 2024-03-03
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.28.582578
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Control of adaptive immunity by pattern recognition receptors.

    Carroll, Shaina L / Pasare, Chandrashekhar / Barton, Gregory M

    Immunity

    2024  Volume 57, Issue 4, Page(s) 632–648

    Abstract: One of the most significant conceptual advances in immunology in recent history is the recognition that signals from the innate immune system are required for induction of adaptive immune responses. Two breakthroughs were critical in establishing this ... ...

    Abstract One of the most significant conceptual advances in immunology in recent history is the recognition that signals from the innate immune system are required for induction of adaptive immune responses. Two breakthroughs were critical in establishing this paradigm: the identification of dendritic cells (DCs) as the cellular link between innate and adaptive immunity and the discovery of pattern recognition receptors (PRRs) as a molecular link that controls innate immune activation as well as DC function. Here, we recount the key events leading to these discoveries and discuss our current understanding of how PRRs shape adaptive immune responses, both indirectly through control of DC function and directly through control of lymphocyte function. In this context, we provide a conceptual framework for how variation in the signals generated by PRR activation, in DCs or other cell types, can influence T cell differentiation and shape the ensuing adaptive immune response.
    MeSH term(s) Immunity, Innate ; Dendritic Cells ; Adaptive Immunity ; Receptors, Pattern Recognition/metabolism ; Lymphocyte Activation
    Chemical Substances Receptors, Pattern Recognition
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2024.03.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Toll-like receptors form different complexes with UNC93B1.

    Rael, Victoria E / Barton, Gregory M

    Nature structural & molecular biology

    2021  Volume 28, Issue 2, Page(s) 121–123

    MeSH term(s) Membrane Transport Proteins ; Toll-Like Receptors/metabolism
    Chemical Substances Membrane Transport Proteins ; Toll-Like Receptors
    Language English
    Publishing date 2021-02-02
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-021-00559-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Locally advanced mismatch repair-deficient gastroesophageal junction cancer: Diagnosis, treatment modifications, and monitoring.

    Mehta, Rutika / Sinnamon, Andrew / Dam, Aamir / Walko, Christine / Palm, Russell / Barton, Laura / Lauwers, Gregory / Pimiento, Jose M

    CA: a cancer journal for clinicians

    2023  Volume 74, Issue 2, Page(s) 123–131

    MeSH term(s) Humans ; DNA Mismatch Repair/genetics ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/genetics ; Stomach Neoplasms/therapy ; Esophageal Neoplasms/diagnosis ; Esophageal Neoplasms/genetics ; Esophageal Neoplasms/therapy ; Esophagogastric Junction
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603553-x
    ISSN 1542-4863 ; 0007-9235
    ISSN (online) 1542-4863
    ISSN 0007-9235
    DOI 10.3322/caac.21813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Dysregulation of TLR9 in neonates leads to fatal inflammatory disease driven by IFN-γ.

    Stanbery, Alison G / Newman, Zachary R / Barton, Gregory M

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 6, Page(s) 3074–3082

    Abstract: Recognition of self-nucleic acids by innate immune receptors can lead to the development of autoimmune and/or autoinflammatory diseases. Elucidating mechanisms associated with dysregulated activation of specific receptors may identify new disease ... ...

    Abstract Recognition of self-nucleic acids by innate immune receptors can lead to the development of autoimmune and/or autoinflammatory diseases. Elucidating mechanisms associated with dysregulated activation of specific receptors may identify new disease correlates and enable more effective therapies. Here we describe an aggressive in vivo model of Toll-like receptor (TLR) 9 dysregulation, based on bypassing the compartmentalized activation of TLR9 in endosomes, and use it to uncover unique aspects of TLR9-driven disease. By inducing TLR9 dysregulation at different stages of life, we show that while dysregulation in adult mice causes a mild systemic autoinflammatory disease, dysregulation of TLR9 early in life drives a severe inflammatory disease resulting in neonatal fatality. The neonatal disease includes some hallmarks of macrophage activation syndrome but is much more severe than previously described models. Unlike TLR7-mediated disease, which requires type I interferon (IFN) receptor signaling, TLR9-driven fatality is dependent on IFN-γ receptor signaling. NK cells are likely key sources of IFN-γ in this model. We identify populations of macrophages and Ly6C
    MeSH term(s) Animals ; Animals, Newborn ; Autoimmune Diseases/immunology ; Autoimmune Diseases/metabolism ; Cells, Cultured ; Inflammation/immunology ; Inflammation/metabolism ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Mice, Transgenic ; Monocytes/immunology ; Monocytes/metabolism ; Signal Transduction/immunology ; Toll-Like Receptor 9/genetics ; Toll-Like Receptor 9/immunology ; Toll-Like Receptor 9/metabolism
    Chemical Substances Tlr9 protein, mouse ; Toll-Like Receptor 9 ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2020-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1911579117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Use of isotonic contrast solution in the artificial urinary sphincter does not impact device longevity.

    Inouye, Brian M / Boysen, William R / Barton, Gregory J / Peterson, Andrew C

    Neurourology and urodynamics

    2021  Volume 40, Issue 4, Page(s) 1056–1062

    Abstract: Aims: The artificial urinary sphincter (AUS), the gold standard for treatment of male stress urinary incontinence, can be filled with normal saline (NS) or isotonic contrast solution. Surgeons have voiced concerns about the impact on device malfunction ... ...

    Abstract Aims: The artificial urinary sphincter (AUS), the gold standard for treatment of male stress urinary incontinence, can be filled with normal saline (NS) or isotonic contrast solution. Surgeons have voiced concerns about the impact on device malfunction and longevity, but no studies address this issue. We used industry data to identify differences in outcomes between NS and contrast-filled AUS.
    Methods: Our analysis included all men patients in the industry who maintained the AUS database (Boston Scientific) from 2001 to 2016. Patients were divided into two groups: AUS filled with NS or contrast. Patient demographics and device characteristics were compared. Device survival was defined as time to the need for reoperation. We compared device survival between AUS filled with NS versus contrast using a Kaplan-Meier curve adjusted for age, cuff size, and pressure regulating balloon (PRB) size.
    Results: A total of 39,363 patients were included. 34,674 (88.1%) devices were filled with NS. The reoperation rate overall was 24.5%, with no difference between groups. The mean time to reoperation overall was 3 years (±3.0). After adjustment for age, cuff size, and PRB size, Kaplan-Meier analysis demonstrated a similar time to reoperation between the two groups.
    Conclusion: The use of contrast in the AUS does not appear to change rates of the device malfunction, fluid loss, or need for reoperation. Since filling the device with contrast does not appear inferior to saline in terms of longevity, we feel this should be considered a safe tool for the implanting surgeon.
    MeSH term(s) Humans ; Longevity ; Male ; Reoperation ; Retrospective Studies ; Treatment Outcome ; Urinary Incontinence, Stress/surgery ; Urinary Sphincter, Artificial
    Language English
    Publishing date 2021-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604904-7
    ISSN 1520-6777 ; 0733-2467
    ISSN (online) 1520-6777
    ISSN 0733-2467
    DOI 10.1002/nau.24668
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Suicide Screening, Risk Assessment, and Lethal Means Counseling During Zero Suicide Implementation.

    Boggs, Jennifer M / Richards, Julie / Simon, Gregory / Aguirre-Miyamoto, Erika M / Barton, Lee J / Beck, Arne / Beidas, Rinad S / Bruschke, Cambria / Buckingham, Edward T / Buttlaire, Stuart / Clarke, Gregory / Coleman, Karen / Flores, Jean P / Frank, Catherine / Penfold, Robert B / Richardson, Laura / Ryan, Jacqueline M / Schoenbaum, Michael / Sterling, Stacy /
    Stewart, Christine / Yarborough, Bobbi Jo H / Yeh, Hsueh-Han / Ahmedani, Brian

    Psychiatric services (Washington, D.C.)

    2024  , Page(s) appips20230211

    Abstract: Objective: The authors measured implementation of Zero Suicide (ZS) clinical practices that support identification of suicide risk and risk mitigation, including screening, risk assessment, and lethal means counseling, across mental health specialty and ...

    Abstract Objective: The authors measured implementation of Zero Suicide (ZS) clinical practices that support identification of suicide risk and risk mitigation, including screening, risk assessment, and lethal means counseling, across mental health specialty and primary care settings.
    Methods: Six health care systems in California, Colorado, Michigan, Oregon, and Washington participated. The sample included members ages ≥13 years from 2010 to 2019 (N=7,820,524 patients). The proportions of patients with suicidal ideation screening, suicide risk assessment, and lethal means counseling were estimated.
    Results: In 2019, patients were screened for suicidal ideation in 27.1% (range 5.0%-85.0%) of mental health visits and 2.5% (range 0.1%-35.0%) of primary care visits among a racially and ethnically diverse sample (44.9% White, 27.2% Hispanic, 13.4% Asian, and 7.7% Black). More patients screened positive for suicidal ideation in the mental health setting (10.2%) than in the primary care setting (3.8%). Of the patients screening positive for suicidal ideation in the mental health setting, 76.8% received a risk assessment, and 82.4% of those identified as being at high risk received lethal means counseling, compared with 43.2% and 82.4%, respectively, in primary care.
    Conclusions: Six health systems that implemented ZS showed a high level of variation in the proportions of patients receiving suicide screening and risk assessment and lethal means counseling. Two opportunities emerged for further study to increase frequency of these practices: expanding screening beyond patients with regular health care visits and implementing risk assessment with lethal means counseling in the primary care setting directly after a positive suicidal ideation screening.
    Language English
    Publishing date 2024-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1220173-x
    ISSN 1557-9700 ; 1075-2730
    ISSN (online) 1557-9700
    ISSN 1075-2730
    DOI 10.1176/appi.ps.20230211
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Could an Impairment in Local Translation of mRNAs in Glia be Contributing to Pathogenesis in ALS?

    Barton, Samantha K / Gregory, Jenna M / Chandran, Siddharthan / Turner, Bradley J

    Frontiers in molecular neuroscience

    2019  Volume 12, Page(s) 124

    Abstract: One of the key pathways implicated in amyotrophic lateral sclerosis (ALS) pathogenesis is abnormal RNA processing. Studies to date have focussed on defects in RNA stability, splicing, and translation, but this review article will focus on the largely ... ...

    Abstract One of the key pathways implicated in amyotrophic lateral sclerosis (ALS) pathogenesis is abnormal RNA processing. Studies to date have focussed on defects in RNA stability, splicing, and translation, but this review article will focus on the largely overlooked RNA processing mechanism of RNA trafficking, with particular emphasis on the importance of glia. In the central nervous system (CNS), oligodendrocytes can extend processes to myelinate and metabolically support up to 50 axons and astrocytes can extend processes to cover up to 100,000 synapses, all with differing local functional requirements. Furthermore, many of the proteins required in these processes are large, aggregation-prone proteins which would be difficult to transport in their fully translated, terminally-folded state. This, therefore, highlights a critical requirement in these cells for local control of protein translation, which is achieved through specific trafficking of mRNAs to each process and local translation therein. Given that a large number of RNA-binding proteins have been implicated in ALS, and RNA-binding proteins are essential for trafficking mRNAs from the nucleus to glial processes for local translation, RNA misprocessing in glial cells is a likely source of cellular dysfunction in ALS. To date, neurons have been the focus of ALS research, but an intrinsic deficit in glia, namely astrocytes and oligodendrocytes, could have an additive effect on declining neuronal function in ALS. This review article aims to highlight the key evidence that supports the contention that RNA trafficking deficits in astrocytes and oligodendrocytes may contribute to in ALS.
    Language English
    Publishing date 2019-05-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2019.00124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Improved detection of RNA foci in

    Mehta, Arpan R / Selvaraj, Bhuvaneish T / Barton, Samantha K / McDade, Karina / Abrahams, Sharon / Chandran, Siddharthan / Smith, Colin / Gregory, Jenna M

    Brain communications

    2020  Volume 2, Issue 1, Page(s) fcaa009

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2020-01-06
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcaa009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Regulation of the nucleic acid-sensing Toll-like receptors.

    Lind, Nicholas A / Rael, Victoria E / Pestal, Kathleen / Liu, Bo / Barton, Gregory M

    Nature reviews. Immunology

    2021  Volume 22, Issue 4, Page(s) 224–235

    Abstract: Many of the ligands for Toll-like receptors (TLRs) are unique to microorganisms, such that receptor activation unequivocally indicates the presence of something foreign. However, a subset of TLRs recognizes nucleic acids, which are present in both the ... ...

    Abstract Many of the ligands for Toll-like receptors (TLRs) are unique to microorganisms, such that receptor activation unequivocally indicates the presence of something foreign. However, a subset of TLRs recognizes nucleic acids, which are present in both the host and foreign microorganisms. This specificity enables broad recognition by virtue of the ubiquity of nucleic acids but also introduces the possibility of self-recognition and autoinflammatory or autoimmune disease. Defining the regulatory mechanisms required to ensure proper discrimination between foreign and self-nucleic acids by TLRs is an area of intense research. Progress over the past decade has revealed a complex array of regulatory mechanisms that ensure maintenance of this delicate balance. These regulatory mechanisms can be divided into a conceptual framework with four categories: compartmentalization, ligand availability, receptor expression and signal transduction. In this Review, we discuss our current understanding of each of these layers of regulation.
    MeSH term(s) Autoimmune Diseases ; Humans ; Ligands ; Nucleic Acids ; Signal Transduction ; Toll-Like Receptors
    Chemical Substances Ligands ; Nucleic Acids ; Toll-Like Receptors
    Language English
    Publishing date 2021-07-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-021-00577-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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