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  1. Article: E. coli

    Amunugama, Kaushalya / Pike, Daniel P / Ford, David A

    Frontiers in physiology

    2022  Volume 13, Page(s) 980460

    Abstract: Dysregulated lipid metabolism is common in infection and inflammation and is a part of the complex milieu underlying the pathophysiological sequelae of disease. Sepsis is a major cause of mortality and morbidity in the world and is characterized by an ... ...

    Abstract Dysregulated lipid metabolism is common in infection and inflammation and is a part of the complex milieu underlying the pathophysiological sequelae of disease. Sepsis is a major cause of mortality and morbidity in the world and is characterized by an exaggerated host response to an infection. Metabolic changes, including alterations in lipid metabolism, likely are important in sepsis pathophysiology. Here, we designed an
    Language English
    Publishing date 2022-09-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.980460
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Neutrophil Myeloperoxidase Derived Chlorolipid Production During Bacteria Exposure.

    Amunugama, Kaushalya / Kolar, Grant R / Ford, David A

    Frontiers in immunology

    2021  Volume 12, Page(s) 701227

    Abstract: Neutrophils are the most abundant white blood cells recruited to the sites of infection and inflammation. During neutrophil activation, myeloperoxidase (MPO) is released and converts hydrogen peroxide to hypochlorous acid (HOCl). HOCl reacts with ... ...

    Abstract Neutrophils are the most abundant white blood cells recruited to the sites of infection and inflammation. During neutrophil activation, myeloperoxidase (MPO) is released and converts hydrogen peroxide to hypochlorous acid (HOCl). HOCl reacts with plasmalogen phospholipids to liberate 2-chlorofatty aldehyde (2-ClFALD), which is metabolized to 2-chlorofatty acid (2-ClFA). 2-ClFA and 2-ClFALD are linked with inflammatory diseases and induce endothelial dysfunction, neutrophil extracellular trap formation (NETosis) and neutrophil chemotaxis. Here we examine the neutrophil-derived chlorolipid production in the presence of pathogenic
    MeSH term(s) Cells, Cultured ; Escherichia coli/immunology ; Extracellular Traps/immunology ; Fatty Acids/metabolism ; Humans ; Neutrophil Activation/immunology ; Neutrophils/enzymology ; Neutrophils/immunology ; Peroxidase/immunology
    Chemical Substances Fatty Acids ; MPO protein, human (EC 1.11.1.7) ; Peroxidase (EC 1.11.1.7)
    Language English
    Publishing date 2021-08-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.701227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The lipid biology of sepsis.

    Amunugama, Kaushalya / Pike, Daniel P / Ford, David A

    Journal of lipid research

    2021  Volume 62, Page(s) 100090

    Abstract: Sepsis, defined as the dysregulated immune response to an infection leading to organ dysfunction, is one of the leading causes of mortality around the globe. Despite the significant progress in delineating the underlying mechanisms of sepsis pathogenesis, ...

    Abstract Sepsis, defined as the dysregulated immune response to an infection leading to organ dysfunction, is one of the leading causes of mortality around the globe. Despite the significant progress in delineating the underlying mechanisms of sepsis pathogenesis, there are currently no effective treatments or specific diagnostic biomarkers in the clinical setting. The perturbation of cell signaling mechanisms, inadequate inflammation resolution, and energy imbalance, all of which are altered during sepsis, are also known to lead to defective lipid metabolism. The use of lipids as biomarkers with high specificity and sensitivity may aid in early diagnosis and guide clinical decision making. In addition, identifying the link between specific lipid signatures and their role in sepsis pathology may lead to novel therapeutics. In this review, we discuss the recent evidence on dysregulated lipid metabolism both in experimental and human sepsis focused on bioactive lipids, fatty acids, and cholesterol as well as the enzymes regulating their levels during sepsis. We highlight not only their potential roles in sepsis pathogenesis but also the possibility of using these respective lipid compounds as diagnostic and prognostic biomarkers of sepsis.
    MeSH term(s) Biomarkers/chemistry ; Biomarkers/metabolism ; Humans ; Lipids/chemistry ; Sepsis/metabolism ; Sepsis/pathology
    Chemical Substances Biomarkers ; Lipids
    Language English
    Publishing date 2021-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1016/j.jlr.2021.100090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: On the complex relationship between energy expenditure and longevity: Reconciling the contradictory empirical results with a simple theoretical model.

    Hou, Chen / Amunugama, Kaushalya

    Mechanisms of ageing and development

    2015  Volume 149, Page(s) 50–64

    Abstract: The relationship between energy expenditure and longevity has been a central theme in aging studies. Empirical studies have yielded controversial results, which cannot be reconciled by existing theories. In this paper, we present a simple theoretical ... ...

    Abstract The relationship between energy expenditure and longevity has been a central theme in aging studies. Empirical studies have yielded controversial results, which cannot be reconciled by existing theories. In this paper, we present a simple theoretical model based on first principles of energy conservation and allometric scaling laws. The model takes into considerations the energy tradeoffs between life history traits and the efficiency of the energy utilization, and offers quantitative and qualitative explanations for a set of seemingly contradictory empirical results. We show that oxidative metabolism can affect cellular damage and longevity in different ways in animals with different life histories and under different experimental conditions. Qualitative data and the linearity between energy expenditure, cellular damage, and lifespan assumed in previous studies are not sufficient to understand the complexity of the relationships. Our model provides a theoretical framework for quantitative analyses and predictions. The model is supported by a variety of empirical studies, including studies on the cellular damage profile during ontogeny; the intra- and inter-specific correlations between body mass, metabolic rate, and lifespan; and the effects on lifespan of (1) diet restriction and genetic modification of growth hormone, (2) the cold and exercise stresses, and (3) manipulations of antioxidant.
    MeSH term(s) Aging ; Animals ; Antioxidants/metabolism ; Caloric Restriction ; Diet ; Energy Metabolism ; Female ; Growth Hormone/metabolism ; Lipid Peroxidation ; Longevity ; Male ; Metabolism ; Mice ; Models, Biological ; Oxidative Stress ; Oxygen/chemistry ; Oxygen Consumption ; Physical Conditioning, Animal ; Rats ; Superoxides/chemistry ; Time Factors
    Chemical Substances Antioxidants ; Superoxides (11062-77-4) ; Growth Hormone (9002-72-6) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2015-07
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 183915-9
    ISSN 1872-6216 ; 0047-6374
    ISSN (online) 1872-6216
    ISSN 0047-6374
    DOI 10.1016/j.mad.2015.06.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Identification of novel neutrophil very long chain plasmalogen molecular species and their myeloperoxidase mediated oxidation products in human sepsis.

    Amunugama, Kaushalya / Jellinek, Matthew J / Kilroy, Megan P / Albert, Carolyn J / Rasi, Valerio / Hoft, Daniel F / Shashaty, Michael G S / Meyer, Nuala J / Ford, David A

    Redox biology

    2021  Volume 48, Page(s) 102208

    Abstract: Plasmalogens are a class of phospholipids containing vinyl ether linked aliphatic groups at the sn-1 position. Plasmalogens are known to contain 16- and 18-carbon aliphatic groups at the sn-1 position. Here, we reveal that the human neutrophil ... ...

    Abstract Plasmalogens are a class of phospholipids containing vinyl ether linked aliphatic groups at the sn-1 position. Plasmalogens are known to contain 16- and 18-carbon aliphatic groups at the sn-1 position. Here, we reveal that the human neutrophil plasmenylethanolamine pool uniquely includes molecular species with very long carbon chain (VLC) aliphatic groups, including 20-, 22- and 24-carbon vinyl ether linked aliphatic groups at the sn-1 position. We identified these novel VLC plasmalogen species by electrospray ionization mass spectrometry methods. VLC plasmalogens were only found in the neutrophil plasmenylethanolamine pool. During neutrophil activation, VLC plasmenylethanolamines undergo myeloperoxidase-dependent oxidation to produce VLC 2-chlorofatty aldehyde and its oxidation product, 2-chlorofatty acid (2-ClFA). Furthermore, plasma concentrations of VLC 2-ClFA are elevated in human sepsis. These studies demonstrate for the first time VLC plasmenylethanolamine molecular species, their myeloperoxidase-mediated chlorolipid products and the presence of these chlorolipids in human sepsis.
    Language English
    Publishing date 2021-12-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2701011-9
    ISSN 2213-2317 ; 2213-2317
    ISSN (online) 2213-2317
    ISSN 2213-2317
    DOI 10.1016/j.redox.2021.102208
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Food restriction alters energy allocation strategy during growth in tobacco hornworms (Manduca sexta larvae).

    Jiao, Lihong / Amunugama, Kaushalya / Hayes, Matthew B / Jennings, Michael / Domingo, Azriel / Hou, Chen

    Die Naturwissenschaften

    2015  Volume 102, Issue 7-8, Page(s) 40

    Abstract: Growing animals must alter their energy budget in the face of environmental changes and prioritize the energy allocation to metabolism for life-sustaining requirements and energy deposition in new biomass growth. We hypothesize that when food ... ...

    Abstract Growing animals must alter their energy budget in the face of environmental changes and prioritize the energy allocation to metabolism for life-sustaining requirements and energy deposition in new biomass growth. We hypothesize that when food availability is low, larvae of holometabolic insects with a short development stage (relative to the low food availability period) prioritize biomass growth at the expense of metabolism. Driven by this hypothesis, we develop a simple theoretical model, based on conservation of energy and allometric scaling laws, for understanding the dynamic energy budget of growing larvae under food restriction. We test the hypothesis by manipulative experiments on fifth instar hornworms at three temperatures. At each temperature, food restriction increases the scaling power of growth rate but decreases that of metabolic rate, as predicted by the hypothesis. During the fifth instar, the energy budgets of larvae change dynamically. The free-feeding larvae slightly decrease the energy allocated to growth as body mass increases and increase the energy allocated to life sustaining. The opposite trends were observed in food restricted larvae, indicating the predicted prioritization in the energy budget under food restriction. We compare the energy budgets of a few endothermic and ectothermic species and discuss how different life histories lead to the differences in the energy budgets under food restriction.
    MeSH term(s) Animals ; Caloric Restriction ; Energy Metabolism ; Larva ; Manduca/growth & development ; Manduca/metabolism ; Models, Biological ; Temperature
    Language English
    Publishing date 2015-08
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 123257-5
    ISSN 1432-1904 ; 0028-1042
    ISSN (online) 1432-1904
    ISSN 0028-1042
    DOI 10.1007/s00114-015-1289-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cellular oxidative damage is more sensitive to biosynthetic rate than to metabolic rate: A test of the theoretical model on hornworms (Manduca sexta larvae).

    Amunugama, Kaushalya / Jiao, Lihong / Olbricht, Gayla R / Walker, Chance / Huang, Yue-Wern / Nam, Paul K / Hou, Chen

    Experimental gerontology

    2016  Volume 82, Page(s) 73–80

    Abstract: We develop a theoretical model from an energetic viewpoint for unraveling the entangled effects of metabolic and biosynthetic rates on oxidative cellular damage accumulation during animal's growth, and test the model by experiments in hornworms. The ... ...

    Abstract We develop a theoretical model from an energetic viewpoint for unraveling the entangled effects of metabolic and biosynthetic rates on oxidative cellular damage accumulation during animal's growth, and test the model by experiments in hornworms. The theoretical consideration suggests that most of the cellular damages caused by the oxidative metabolism can be repaired by the efficient maintenance mechanisms, if the energy required by repair is unlimited. However, during growth a considerable amount of energy is allocated to the biosynthesis, which entails tradeoffs with the requirements of repair. Thus, the model predicts that cellular damage is more influenced by the biosynthetic rate than the metabolic rate. To test the prediction, we induced broad variations in metabolic and biosynthetic rates in hornworms, and assayed the lipid peroxidation and protein carbonyl. We found that the increase in the cellular damage was mainly caused by the increase in biosynthetic rate, and the variations in metabolic rate had negligible effect. The oxidative stress hypothesis of aging suggests that high metabolism leads to high cellular damage and short lifespan. However, some empirical studies showed that varying biosynthetic rate, rather than metabolic rate, changes animal's lifespan. The conflicts between the empirical evidence and the hypothesis are reconciled by this study.
    MeSH term(s) Aging/metabolism ; Animals ; Caloric Restriction ; Larva/physiology ; Linear Models ; Lipid Peroxidation ; Manduca/physiology ; Models, Theoretical ; Oxidative Stress ; Protein Carbonylation
    Language English
    Publishing date 2016-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 390992-x
    ISSN 1873-6815 ; 0531-5565
    ISSN (online) 1873-6815
    ISSN 0531-5565
    DOI 10.1016/j.exger.2016.05.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Food restriction alters energy allocation strategy during growth in tobacco hornworms (Manduca sexta larvae)

    Jiao, Lihong / Amunugama, Kaushalya / Hayes, Matthew B. / Jennings, Michael / Domingo, Azriel / Hou, Chen

    Naturwissenschaften

    Volume v. 102,, Issue no. 7

    Abstract: Growing animals must alter their energy budget in the face of environmental changes and prioritize the energy allocation to metabolism for life-sustaining requirements and energy deposition in new biomass growth. We hypothesize that when food ... ...

    Abstract Growing animals must alter their energy budget in the face of environmental changes and prioritize the energy allocation to metabolism for life-sustaining requirements and energy deposition in new biomass growth. We hypothesize that when food availability is low, larvae of holometabolic insects with a short development stage (relative to the low food availability period) prioritize biomass growth at the expense of metabolism. Driven by this hypothesis, we develop a simple theoretical model, based on conservation of energy and allometric scaling laws, for understanding the dynamic energy budget of growing larvae under food restriction. We test the hypothesis by manipulative experiments on fifth instar hornworms at three temperatures. At each temperature, food restriction increases the scaling power of growth rate but decreases that of metabolic rate, as predicted by the hypothesis. During the fifth instar, the energy budgets of larvae change dynamically. The free-feeding larvae slightly decrease the energy allocated to growth as body mass increases and increase the energy allocated to life sustaining. The opposite trends were observed in food restricted larvae, indicating the predicted prioritization in the energy budget under food restriction. We compare the energy budgets of a few endothermic and ectothermic species and discuss how different life histories lead to the differences in the energy budgets under food restriction.
    Keywords food availability ; animals ; biomass ; metabolism ; Manduca sexta ; life history ; food restriction ; prioritization ; energy conservation ; insects ; temperature ; models ; allometry ; larvae ; energy requirements ; tobacco ; instars ; budgets ; energy
    Language English
    Document type Article
    ISSN 0028-1042
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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