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  1. Article: The mitochondrial thiolase ACAT1 regulates monocyte/macrophage type I interferon

    Wu, Jing / Singh, Komudi / Shing, Vivian / Gupta, Anand K / Huffstutler, Rebecca D / Lee, Duck-Yeon / Sack, Michael N

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Lipid-derived acetyl-CoA is shown to be the major carbon source for histone acetylation. However, there is no direct evidence demonstrating lipid metabolic pathway contribututions to this process. Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) ... ...

    Abstract Lipid-derived acetyl-CoA is shown to be the major carbon source for histone acetylation. However, there is no direct evidence demonstrating lipid metabolic pathway contribututions to this process. Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes the final step of ß-oxidation, the aerobic process catabolizing fatty acids (FA) into acetyl-CoA. To investigate this in the context of immunometabolism, we generated macrophage cell line lacking ACAT1.
    Language English
    Publishing date 2024-01-31
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.29.577773
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.

    Lee, Byung-Chul / Gin, Ashley / Wu, Chuanfeng / Singh, Komudi / Grice, Max / Mortlock, Ryland / Abraham, Diana / Fan, Xing / Zhou, Yifan / AlJanahi, Aisha / Choi, Uimook / DeRavin, Suk See / Shin, Taehoon / Hong, Sogun / Dunbar, Cynthia E

    Cell stem cell

    2024  

    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2024.04.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.

    Han, Kim / Singh, Komudi / Meadows, Allison M / Sharma, Rahul / Hassanzadeh, Shahin / Wu, Jing / Goss-Holmes, Haley / Huffstutler, Rebecca D / Teague, Heather L / Mehta, Nehal N / Griffin, Julian L / Tian, Rong / Traba, Javier / Sack, Michael N

    Cell reports. Medicine

    2023  Volume 4, Issue 9, Page(s) 101157

    Abstract: To evaluate whether nicotinamide adenine dinucleotide-positive ( ... ...

    Abstract To evaluate whether nicotinamide adenine dinucleotide-positive (NAD
    MeSH term(s) Humans ; NAD/metabolism ; Sequestosome-1 Protein/metabolism ; Antioxidants/metabolism ; NF-E2-Related Factor 2/genetics ; Oxidation-Reduction ; Inflammation/drug therapy
    Chemical Substances NAD (0U46U6E8UK) ; Sequestosome-1 Protein ; Antioxidants ; NF-E2-Related Factor 2
    Language English
    Publishing date 2023-08-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2023.101157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.

    Lee, Byung-Chul / Gin, Ashley / Wu, Chuanfeng / Singh, Komudi / Grice, Max / Mortlock, Ryland / Abraham, Diana / Fan, Xing / Zhou, Yifan / AlJanahi, Aisha / Choi, Uimook / DeRavin, Suk See / Shin, Taehoon / Hong, Sogun / Dunbar, Cynthia E

    Cell stem cell

    2024  Volume 31, Issue 4, Page(s) 455–466.e4

    Abstract: For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has ...

    Abstract For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.
    MeSH term(s) Animals ; Macaca mulatta/genetics ; Hematopoietic Stem Cell Transplantation/methods ; Lentivirus/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; Hematopoietic Stem Cells ; Gene Editing/methods ; CRISPR-Cas Systems/genetics
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2024.02.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6589: Show issues Location:
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  5. Article ; Online: N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4

    Meadows, Allison M / Han, Kim / Singh, Komudi / Murgia, Antonio / McNally, Ben D / West, James A / Huffstutler, Rebecca D / Powell-Wiley, Tiffany M / Baumer, Yvonne / Griffin, Julian L / Sack, Michael N

    iScience

    2023  Volume 26, Issue 5, Page(s) 106578

    Abstract: Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to ... ...

    Abstract Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers these same immunomodulatory effects on transformed cell lines. To identify serum mediators orchestrating this, metabolomic and lipidomic analysis was performed on serum extracted after a 24-h fast and re-feeding. Bioinformatic integration with concurrent peripheral blood mononuclear cells RNA-seq analysis implicated key metabolite-sensing GPCRs in fasting-mediated immunomodulation. The putative GPR18 ligand N-arachidonylglycine (NAGly) was elevated during fasting and attenuated CD4
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106578
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Measuring

    Huang, Huiyan / Singh, Komudi / Hart, Anne C

    Bio-protocol

    2017  Volume 7, Issue 6

    Abstract: ... conserved across the animal kingdom (Singh et al., 2014; Trojanowski & Raizen, 2016). ...

    Abstract C. elegans sleep during development is regulated by genes and cellular mechanisms that are conserved across the animal kingdom (Singh et al., 2014; Trojanowski & Raizen, 2016).
    Language English
    Publishing date 2017-09-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.2174
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Propionate functions as a feeding state-dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity.

    Han, Kim / Meadows, Allison M / Rodman, Matthew J / Russo, Anna Chiara / Sharma, Rahul / Singh, Komudi / Hassanzadeh, Shahin / Dagur, Pradeep K / Huffstutler, Rebecca D / Krause, Fynn N / Griffin, Julian L / Baumer, Yvonne / Powell-Wiley, Tiffany M / Sack, Michael N

    Journal of leukocyte biology

    2024  Volume 115, Issue 4, Page(s) 738–749

    Abstract: Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain ... ...

    Abstract Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography-mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein-coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+ T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ TH cell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA-G protein-coupled receptor linked pathway to regulate CD4+ TH cell immune responsiveness.
    MeSH term(s) Humans ; Propionates/pharmacology ; Fatty Acids, Nonesterified ; Leukocytes, Mononuclear ; Receptors, G-Protein-Coupled/genetics ; Obesity
    Chemical Substances Propionates ; Fatty Acids, Nonesterified ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2024-01-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1093/jleuko/qiae006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 603: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  8. Article: Impact of CRISPR/HDR-editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.

    Lee, Byung-Chul / Gin, Ashley / Wu, Chuanfeng / Singh, Komudi / Grice, Max / Mortlock, Ryland / Abraham, Diana / Fan, Xing / Zhou, Yifan / AlJanahi, Aisha / Choi, Uimook / de Ravin, Suk See / Shin, Taehoon / Hong, Sogun / Dunbar, Cynthia E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) requires both sufficient HDR efficiency and protection of LT-HSC function and number. The impact ... ...

    Abstract For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) requires both sufficient HDR efficiency and protection of LT-HSC function and number. The impact of HDR on true LT-HSCs clonal dynamics in a relevant large animal model has not previously been studied. To track the HDR-edited cells, autologous rhesus macaque (RM) CD34
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.13.571396
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+T cell responsiveness

    Allison M. Meadows / Kim Han / Komudi Singh / Antonio Murgia / Ben D. McNally / James A. West / Rebecca D. Huffstutler / Tiffany M. Powell-Wiley / Yvonne Baumer / Julian L. Griffin / Michael N. Sack

    iScience, Vol 26, Iss 5, Pp 106578- (2023)

    2023  

    Abstract: Summary: Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness ... ...

    Abstract Summary: Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers these same immunomodulatory effects on transformed cell lines. To identify serum mediators orchestrating this, metabolomic and lipidomic analysis was performed on serum extracted after a 24-h fast and re-feeding. Bioinformatic integration with concurrent peripheral blood mononuclear cells RNA-seq analysis implicated key metabolite-sensing GPCRs in fasting-mediated immunomodulation. The putative GPR18 ligand N-arachidonylglycine (NAGly) was elevated during fasting and attenuated CD4+T cell responsiveness via GPR18 MTORC1 signaling. In parallel, NAGly reduced inflammatory Th1 and Th17 cytokines levels in CD4+T cells isolated from obese subjects, identifying a fasting-responsive metabolic intermediate that may contribute to the regulation of nutrient-level dependent inflammation associated with metabolic disease.
    Keywords Human metabolism ; Immunology ; Lipidomics ; Metabolomics ; Transcriptomics ; Science ; Q
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: MAVS Positively Regulates Mitochondrial Integrity and Metabolic Fitness in B Cells.

    Wang, Hongsheng / Sun, Wenxiang / Traba, Javier / Wu, Juan / Qi, Chen-Feng / Amo, Laura / Kole, Hemanta K / Scott, Bethany / Singh, Komudi / Sack, Michael N / Bolland, Silvia

    ImmunoHorizons

    2023  Volume 7, Issue 8, Page(s) 587–599

    Abstract: Activated B cells experience metabolic changes that require mitochondrial remodeling, in a process incompletely defined. In this study, we report that mitochondrial antiviral signaling protein (MAVS) is involved in BCR-initiated cellular proliferation ... ...

    Abstract Activated B cells experience metabolic changes that require mitochondrial remodeling, in a process incompletely defined. In this study, we report that mitochondrial antiviral signaling protein (MAVS) is involved in BCR-initiated cellular proliferation and prolonged survival. MAVS is well known as a mitochondrial-tethered signaling adaptor with a central role in viral RNA-sensing pathways that induce type I IFN. The role of MAVS downstream of BCR stimulation was recognized in absence of IFN, indicative of a path for MAVS activation that is independent of viral infection. Mitochondria of BCR-activated MAVS-deficient mouse B cells exhibited a damaged phenotype including disrupted mitochondrial morphology, excess mitophagy, and the temporal progressive blunting of mitochondrial oxidative capacity with mitochondrial hyperpolarization and cell death. Costimulation of MAVS-deficient B cells with anti-CD40, in addition to BCR stimulation, partially corrected the mitochondrial structural defects and functionality. Our data reveal a (to our knowledge) previously unrecognized role of MAVS in controlling the metabolic fitness of B cells, most noticeable in the absence of costimulatory help.
    MeSH term(s) Animals ; Mice ; B-Lymphocytes ; CD40 Antigens ; Cell Proliferation ; Mitochondria ; Signal Transduction
    Chemical Substances CD40 Antigens ; IPS-1 protein, mouse
    Language English
    Publishing date 2023-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2573-7732
    ISSN (online) 2573-7732
    DOI 10.4049/immunohorizons.2300038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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