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  1. Article ; Online: Fatty acid oxidation fuels natural killer cell responses against infection and cancer.

    Sheppard, Sam / Srpan, Katja / Lin, Wendy / Lee, Mariah / Delconte, Rebecca B / Owyong, Mark / Carmeliet, Peter / Davis, Daniel M / Xavier, Joao B / Hsu, Katharine C / Sun, Joseph C

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

    2024  Volume 121, Issue 11, Page(s) e2319254121

    Abstract: Natural killer (NK) cells are a vital part of the innate immune system capable of rapidly clearing mutated or infected cells from the body and promoting an immune response. Here, we find that NK cells activated by viral infection or tumor challenge ... ...

    Abstract Natural killer (NK) cells are a vital part of the innate immune system capable of rapidly clearing mutated or infected cells from the body and promoting an immune response. Here, we find that NK cells activated by viral infection or tumor challenge increase uptake of fatty acids and their expression of carnitine palmitoyltransferase I (CPT1A), a critical enzyme for long-chain fatty acid oxidation. Using a mouse model with an NK cell-specific deletion of CPT1A, combined with stable
    MeSH term(s) Humans ; Lipid Metabolism ; Killer Cells, Natural ; Neoplasms ; Fatty Acids ; Virus Diseases
    Chemical Substances Fatty Acids
    Language English
    Publishing date 2024-03-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2319254121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Identifying Function Determining Residues in Neuroimmune Semaphorin 4A.

    Chapoval, Svetlana P / Lee, Mariah / Lemmer, Aaron / Ajayi, Oluwaseyi / Qi, Xiulan / Neuwald, Andrew F / Keegan, Achsah D

    International journal of molecular sciences

    2022  Volume 23, Issue 6

    Abstract: Semaphorin 4A (Sema4A) exerts a stabilizing effect on human Treg cells in PBMC and CD4+ T cell cultures by engaging Plexin B1. Sema4A deficient mice display enhanced allergic airway inflammation accompanied by fewer Treg cells, while Sema4D deficient ... ...

    Abstract Semaphorin 4A (Sema4A) exerts a stabilizing effect on human Treg cells in PBMC and CD4+ T cell cultures by engaging Plexin B1. Sema4A deficient mice display enhanced allergic airway inflammation accompanied by fewer Treg cells, while Sema4D deficient mice displayed reduced inflammation and increased Treg cell numbers even though both Sema4 subfamily members engage Plexin B1. The main objectives of this study were: 1. To compare the in vitro effects of Sema4A and Sema4D proteins on human Treg cells; and 2. To identify function-determining residues in Sema4A critical for binding to Plexin B1 based on Sema4D homology modeling. We report here that Sema4A and Sema4D display opposite effects on human Treg cells in in vitro PBMC cultures; Sema4D inhibited the CD4+CD25+Foxp3+ cell numbers and CD25/Foxp3 expression. Sema4A and Sema4D competitively bind to Plexin B1 in vitro and hence may be doing so in vivo as well. Bayesian Partitioning with Pattern Selection (BPPS) partitioned 4505 Sema domains from diverse organisms into subgroups based on distinguishing sequence patterns that are likely responsible for functional differences. BPPS groups Sema3 and Sema4 into one family and further separates Sema4A and Sema4D into distinct subfamilies. Residues distinctive of the Sema3,4 family and of Sema4A (and by homology of Sema4D) tend to cluster around the Plexin B1 binding site. This suggests that the residues both common to and distinctive of Sema4A and Sema4D may mediate binding to Plexin B1, with subfamily residues mediating functional specificity. We mutated the Sema4A-specific residues M198 and F223 to alanine; notably, F223 in Sema4A corresponds to alanine in Sema4D. Mutant proteins were assayed for Plexin B1-binding and Treg stimulation activities. The F223A mutant was unable to stimulate Treg stability in in vitro PBMC cultures despite binding Plexin B1 with an affinity similar to the WT protein. This research is a first step in generating potent mutant Sema4A molecules with stimulatory function for Treg cells with a view to designing immunotherapeutics for asthma.
    MeSH term(s) Alanine ; Animals ; Bayes Theorem ; Forkhead Transcription Factors/genetics ; Humans ; Inflammation ; Leukocytes, Mononuclear/metabolism ; Mice ; Nerve Tissue Proteins/metabolism ; Semaphorins/metabolism
    Chemical Substances Forkhead Transcription Factors ; Nerve Tissue Proteins ; SEMA4A protein, human ; Semaphorins ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2022-03-11
    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/ijms23063024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock.

    Subramani, Kumar / Chu, Xiaogang / Warren, Marie / Lee, Mariah / Lu, Sumin / Singh, Nagendra / Raju, Raghavan

    Biochimica et biophysica acta. Molecular basis of disease

    2019  Volume 1865, Issue 3, Page(s) 688–695

    Abstract: Inflammation and cellular energetics play critical roles in organ dysfunction following hemorrhagic shock. Recent studies suggest a putative role for sirtuin 1 (SIRT1) in potentiating mitochondrial function and improving organ function following ... ...

    Abstract Inflammation and cellular energetics play critical roles in organ dysfunction following hemorrhagic shock. Recent studies suggest a putative role for sirtuin 1 (SIRT1) in potentiating mitochondrial function and improving organ function following hemorrhagic shock in animal models. SIRT1 is an NAD
    MeSH term(s) Animals ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/metabolism ; Myocardium/pathology ; NAD/metabolism ; NADP/metabolism ; Niacin/metabolism ; Niacin/therapeutic use ; Permeability/drug effects ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Shock, Hemorrhagic/drug therapy ; Shock, Hemorrhagic/genetics ; Shock, Hemorrhagic/mortality ; Shock, Hemorrhagic/pathology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Survival Analysis
    Chemical Substances Hcar2 protein, mouse ; Receptors, G-Protein-Coupled ; NAD (0U46U6E8UK) ; Niacin (2679MF687A) ; NADP (53-59-8)
    Language English
    Publishing date 2019-01-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 60-7
    ISSN 1879-260X ; 1879-2596 ; 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) 1879-260X ; 1879-2596 ; 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.bbadis.2019.01.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Self-Concept in the Context of Diabetes Prevention: Development of the Lifestyle Health-Related Self-Concept Questionnaire.

    Thomas, Jenifer J / Lutes, Lesley / Smirnova, Ekaterina / Das, Bhibha M / Huzurbazar, Snehalata / Aldrich, Lisa / Lee, Mariah

    American journal of health promotion : AJHP

    2018  Volume 33, Issue 3, Page(s) 452–456

    Abstract: Purpose: Understanding psychosocial factors in the context of lifestyle change is important to recognize distinctions in type 2 diabetes prevention behaviors. A relatively stable psychosocial feature, such as health-related self-concept (HRSC), may ... ...

    Abstract Purpose: Understanding psychosocial factors in the context of lifestyle change is important to recognize distinctions in type 2 diabetes prevention behaviors. A relatively stable psychosocial feature, such as health-related self-concept (HRSC), may indicate factors that promote or repress positive health behaviors. The present study created a questionnaire specific to lifestyle change activities by modifying the Generalized Health-Related Self-Concept Questionnaire (G-HRSC).
    Design: A modified lifestyle health-related self-concept (Lifestyle-HRSC) questionnaire was developed through creation of new items, context expert review of new items, and small and large sample test of new items.
    Participants: 101 college students completed the Lifestyle-HRSC.
    Analysis: Kaiser-Meyer-Olkin (0.64) and Bartlett sphericity tests (χ
    Results: Six factors were revealed: nutrition, social support, avoiding diabetes, physical activity, problem solving, and challenges related to being healthy. Item analysis was conducted to remove correlated and conceptually redundant items and to create the 31-item final questionnaire.
    Conclusion: The Lifestyle-HRSC provides additional knowledge regarding the relationship between self-concept and health as well as insights into the role of psychosocial factors in the context of diabetes prevention.
    MeSH term(s) Diabetes Mellitus, Type 2/prevention & control ; Diet ; Exercise ; Female ; Health Knowledge, Attitudes, Practice ; Healthy Lifestyle ; Humans ; Male ; Problem Solving ; Reproducibility of Results ; Self Concept ; Social Support ; Surveys and Questionnaires/standards
    Language English
    Publishing date 2018-08-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645160-3
    ISSN 2168-6602 ; 0890-1171
    ISSN (online) 2168-6602
    ISSN 0890-1171
    DOI 10.1177/0890117118791721
    Database MEDical Literature Analysis and Retrieval System OnLINE

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