scholarly journals Fluidics system for resolving concentration-dependent effects of dissolved gases on tissue metabolism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Varun Kamat ◽  
Brian M Robbings ◽  
Seung-Ryoung Jung ◽  
John Kelly ◽  
James B Hurley ◽  
...  
Keyword(s):  
Consumption Rate ◽  
Cell Function ◽  
Cell Metabolism ◽  
Secretory Function ◽  
Dissolved Gases ◽  
Disease States ◽  
Wide Range ◽  
And Function ◽  
Insulin Secretion Rate ◽  
Unique Ability

Oxygen (O2) and other dissolved gases such as the gasotransmitters H2S, CO and NO affect cell metabolism and function. To evaluate effects of dissolved gases on processes in tissue, we developed a fluidics system that controls dissolved gases while simultaneously measuring parameters of electron transport, metabolism and secretory function. We use pancreatic islets, retina and liver from rodents to highlight its ability to assess effects of O2 and H2S. Protocols aimed at emulating hypoxia-reperfusion conditions resolved a previously unrecognized transient spike in O2 consumption rate (OCR) following replenishment of O2, and tissue-specific recovery of OCR following hypoxia. The system revealed both inhibitory and stimulatory effects of H2S on insulin secretion rate from isolated islets. The unique ability of this new system to quantify metabolic state and cell function in response to precise changes in dissolved gases provides a powerful platform for cell physiologists to study a wide range of disease states.

scholarly journals Fluidics System for Resolving Concentration-Dependent Effects of Dissolved Gases on Tissue Metabolism

2021 ◽  
Author(s):  
Varun Kamat ◽  
Brian M. Robbings ◽  
Seung-Ryoung Jung ◽  
John Kelly ◽  
James B. Hurley ◽  
...  
Keyword(s):  
Consumption Rate ◽  
Cell Function ◽  
Cell Metabolism ◽  
Secretory Function ◽  
Dissolved Gases ◽  
Disease States ◽  
Wide Range ◽  
And Function ◽  
Insulin Secretion Rate ◽  
Unique Ability

ABSTRACTOxygen (O2) and other dissolved gases such as the gasotransmitters H2S, CO and NO affect cell metabolism and function. To evaluate effects of dissolved gases on processes in tissue, we developed a fluidics system that controls dissolved gases while simultaneously measuring parameters of electron transport, metabolism and secretory function. We use pancreatic islets, retina and liver to highlight its ability to assess effects of O2 and H2S. Protocols aimed at emulating hypoxia-reperfusion conditions resolved a previously unrecognized transient spike in O2 consumption rate (OCR) following replenishment of O2, and tissue-specific recovery of OCR following hypoxia. The system revealed both inhibitory and stimulatory effects of H2S on insulin secretion rate from isolated islets. The unique ability of this new system to quantify metabolic state and cell function in response to precise changes in dissolved gases provides a powerful platform for cell physiologists to study a wide range of disease states.

scholarly journals Transglutaminase Regulation of Cell Function

2014 ◽  
Vol 94 (2) ◽  
pp. 383-417 ◽  
Author(s):  
Richard L. Eckert ◽  
Mari T. Kaartinen ◽  
Maria Nurminskaya ◽  
Alexey M. Belkin ◽  
Gozde Colak ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Mechanism Of Action ◽  
Cell Function ◽  
Cellular Systems ◽  
Cancer Development ◽  
Disease States ◽  
Wide Range ◽  
And Function

Transglutaminases (TGs) are multifunctional proteins having enzymatic and scaffolding functions that participate in regulation of cell fate in a wide range of cellular systems and are implicated to have roles in development of disease. This review highlights the mechanism of action of these proteins with respect to their structure, impact on cell differentiation and survival, role in cancer development and progression, and function in signal transduction. We also discuss the mechanisms whereby TG level is controlled and how TGs control downstream targets. The studies described herein begin to clarify the physiological roles of TGs in both normal biology and disease states.

scholarly journals Cellular Energetics of Mast Cell Development and Activation

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 524
Author(s):  
Ryan P. Mendoza ◽  
Dylan H. Fudge ◽  
Jared M. Brown
Keyword(s):  
Mast Cell ◽  
Energy Metabolism ◽  
Mast Cells ◽  
Cell Function ◽  
Cell Metabolism ◽  
Cell Development ◽  
The Body ◽  
Mast Cell Activation ◽  
Wide Range ◽  
Ige Mediated

Mast cells are essential first responder granulocytes in the innate immune system that are well known for their role in type 1 immune hypersensitivity reactions. Although mostly recognized for their role in allergies, mast cells have a range of influences on other systems throughout the body and can respond to a wide range of agonists to properly prime an appropriate immune response. Mast cells have a dynamic energy metabolism to allow rapid responsiveness to their energetic demands. However, our understanding of mast cell metabolism and its impact on mast cell activation and development is still in its infancy. Mast cell metabolism during stimulation and development shifts between both arms of metabolism: catabolic metabolism—such as glycolysis and oxidative phosphorylation—and anabolic metabolism—such as the pentose phosphate pathway. The potential for metabolic pathway shifts to precede and perhaps even control activation and differentiation provides an exciting opportunity to explore energy metabolism for clues in deciphering mast cell function. In this review, we discuss literature pertaining to metabolic environments and fluctuations during different sources of activation, especially IgE mediated vs. non-IgE mediated, and mast cell development, including progenitor cell types leading to the well-known resident mast cell.

scholarly journals Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome

2018 ◽  
Vol 215 (9) ◽  
pp. 2463-2476 ◽  
Author(s):  
Xiaoyan Yu ◽  
Xiao-Lu Teng ◽  
Feixiang Wang ◽  
Yuhan Zheng ◽  
Guojun Qu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Cell Metabolism ◽  
Signaling Mechanism ◽  
Cell Responses ◽  
Mtorc1 Signaling ◽  
Cell Stability ◽  
Underlying Mechanisms ◽  
And Function ◽  
Metabolic Fitness

Metabolic programs are crucial for regulatory T (T reg) cell stability and function, but the underlying mechanisms that regulate T reg cell metabolism are elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in the maintenance of T reg cell metabolic fitness. T reg–specific deletion of Traf3ip3 impairs T reg cell function, causing the development of inflammatory disorders and stronger antitumor T cell responses in mice. Excessive mechanistic target of rapamycin complex 1 (mTORC1)–mediated hyper-glycolytic metabolism is responsible for the instability of TRAF3IP3-deficient T reg cells. Mechanistically, TRAF3IP3 restricts mTORC1 signaling by recruiting the serine-threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Our results define TRAF3IP3 as a metabolic regulator in T reg cell stability and function and suggest a lysosome-specific mTORC1 signaling mechanism that regulates T reg cell metabolism.

Cellular mechanisms underlying the cardiovascular actions of oestrogens

2006 ◽  
Vol 111 (2) ◽  
pp. 107-118 ◽  
Author(s):  
Shanhong Ling ◽  
Paul Komesaroff ◽  
Krishnankutty Sudhir
Keyword(s):  
Cardiovascular Health ◽  
Cell Function ◽  
Cellular Mechanisms ◽  
Menopausal Women ◽  
Wide Range ◽  
Health And Disease ◽  
Cardiovascular Cells ◽  
Post Menopausal ◽  
And Function ◽  
Cellular Components

Although pre-menopausal women enjoy relative cardiovascular protection, hormone (oestrogen±progestin)-replacement therapy has not shown cardiovascular benefits in post-menopausal women, suggesting that the effects of oestrogens on the cardiovascular system are much more complex than previously expected. Endothelial cells, smooth muscle cells, cardiac myocytes and fibroblasts, the cellular components of blood vessels and the heart, play important roles in cardiovascular health and disease. During the development and progression of cardiovascular disease, changes occur both in the structure and function of these cells, resulting in a wide range of abnormalities, which affect growth, death and physiological function. These cells contain functional oestrogen receptors and are targets for oestrogen action. This review focuses on recent studies on the effects of oestrogen on cardiovascular cell function. Oestrogens, particularly 17β-oestradiol, exert multiple effects on cardiovascular cells, and these effects may contribute to the gender-associated protection against cardiovascular diseases.

scholarly journals Salmonella Typhimurium infection drives NK cell loss and conversion to ILC1-like cells, and CIS inhibition enhances antibacterial immunity

2021 ◽  
Author(s):  
Fernando Souza-Fonseca-Guimaraes ◽  
Timothy McCulloch ◽  
Gustavo Rossi ◽  
Timothy J Wells
Keyword(s):  
Bacterial Infection ◽  
Nk Cells ◽  
Bacterial Infections ◽  
Cell Function ◽  
Nk Cell ◽  
Therapeutic Option ◽  
Cell Metabolism ◽  
Cell Loss ◽  
Cytotoxic Lymphocytes ◽  
And Function

Immunotherapy has revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes. More recently, immunotherapy has emerged to restore immunity against infectious agents, including bacterial infections. Immunotherapy primarily targets inhibitory pathways in tumor-resident T cells, however interest in other effector populations, such as natural killer (NK) cells, is growing. We have previously discovered that NK cell metabolism, proliferation, and activation can be neutralized through the TGF-β immunosuppressive pathway by inducing plasticity of NK cells and differentiation into ILC1-like subsets. NK cells are also regulated through cytokine-inducible SH2-containing protein (CIS), which is induced by IL-15 and is a potent intracellular checkpoint suppressing NK cell survival and function. Targeting these two distinct pathways to restore NK cell function has shown promise is cancer models, but their application in bacterial infection remains unknown. Here, we investigate whether enhancement of NK cell function can improve anti-bacterial immunity, using Salmonella Typhimurium as a model. We identified conversion of NK cells to ILC1-like for the first time in the context of bacterial infection, however TGF-β signaling was curiously redundant in this plasticity. Future work should focus on identifying drivers of ILC1 plasticity and its functional implication in bacterial infection models. We further describe that CIS-deficient mice displayed enhanced pro-inflammatory function and dramatically enhanced anti-infection immunity. Inhibition of CIS may present as a viable therapeutic option to enhance immunity towards bacterial infection.

scholarly journals Therapeutic blockade of Activin-A improves NK cell function and anti-tumor immunity

2018 ◽  
Author(s):  
Jai Rautela ◽  
Laura F. Dagley ◽  
Iona S. Schuster ◽  
Soroor Hediyeh-Zadeh ◽  
Rebecca B. Delconte ◽  
...  
Keyword(s):  
Nk Cells ◽  
Tumor Immunity ◽  
Cell Function ◽  
Nk Cell ◽  
Cell Metabolism ◽  
Activin A ◽  
Type I ◽  
Tumor Killing ◽  
Β Receptor ◽  
And Function

AbstractNatural killer (NK) cells are innate lymphocytes that play a major role in immunosurveillance against tumor initiation and metastasis spread. Signals and checkpoints that regulate NK cell fitness and function in the tumor microenvironment are not well defined. Transforming grow factor (TGF)-β is a recognized suppressor of NK cells that inhibits IL-15 dependent signaling events and induces cellular transdifferentiation, however the role of other SMAD signaling pathways in NK cells is unknown. In this report, we show that NK cells express the type I Activin receptor, ALK4, which upon binding its ligand Activin-A, phosphorylates SMAD2/3 to efficiently suppress IL-15-mediated NK cell metabolism. Activin-A impairs human and mouse NK cell proliferation and downregulates intracellular granzyme B levels to impair tumor killing. Similar to TGF-β, Activin-A also induced SMAD2/3 phosphorylation and drove NK cells to upregulate several ILC1-like surface markers including CD69, TRAIL and CD49a. Activin-A also induced these changes on TGF-β receptor deficient NK cells, highlighting that Activin-A and TGF-β are independent pathways that drive SMAD2/3-mediated NK cell suppression. Finally, therapeutic inhibition of Activin-A by Follistatin significantly slowed orthotopic melanoma growth in mice. These data highlight independent SMAD2/3 pathways target NK cell fitness and function and identify a novel therapeutic axis to promote tumor immunity.One Sentence Summary:Activin-A can directly inhibit NK cell effector functions, promote NK cells transdifferentiation into ILC1-like cells and suppress anti-melanoma immunity.

Chaperonin as the normal controls and pathological anti-stress response in the human reproductive system

2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  
Keyword(s):  
Reproductive System ◽  
Stress Proteins ◽  
Physiological Stress ◽  
Protein Complexes ◽  
Reproductive Function ◽  
Intercellular Signaling ◽  
Toll Like Receptors ◽  
Wide Range ◽  
Protein Functions ◽  
And Function

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.

Possession and Repetition

2012 ◽  
Vol 6 (1-3) ◽  
pp. 243-259 ◽  
Author(s):  
Yohan Yoo
Keyword(s):  
First Century ◽  
Daily Lives ◽  
Modern Times ◽  
Sacred Texts ◽  
New Methods ◽  
Wide Range ◽  
Lay Buddhists ◽  
Iconic Status ◽  
And Function ◽  
To Receive

This article demonstrates the need for the iconic status and function of Buddhist scripture to receive more attention by illuminating how lay Korean Buddhists try to appropriate the power of sutras. The oral and aural aspects of scripture, explained by Wilfred Cantwell Smith, provide only a limited understanding of the characteristics of scripture. It should be noted that, before modern times, most lay people, not only in Buddhist cultures but also in Christian and other traditions, neither had the chance to recite scriptures nor to listen to their recitations regularly. Several clear examples demonstrate contemporary Korean Buddhists’ acceptance of the iconic status of sutras and their attempt to appropriate the power and status of those sacred texts. In contemporary Korea, lay Buddhists try to claim the power of scriptures in their daily lives by repeating and possessing them. Twenty-first century lay believers who cannot read or recite in a traditional style have found new methods of repetition, such as internet programs for copying sacred texts and for playing recordings of their recitations. In addition, many Korean Buddhists consider the act of having sutras in one’s possession to be an effective way of accessing the sacred status and power of these texts. Hence, various ways of possessing them have been developed in a wide range of products, from fancy gilded sutras to sneakers embroidered with mantras.

The Art of Love Poetry

2018 ◽  
Author(s):  
Erik Gray
Keyword(s):  
Popular Culture ◽  
Cultural History ◽  
Literary Tradition ◽  
Love Poetry ◽  
Erotic Love ◽  
Wide Range ◽  
History Of ◽  
And Function ◽  
Meaning And Function ◽  
Comprehensive History

Love begets poetry; poetry begets love. These two propositions have seemed evident to thinkers and poets across the Western literary tradition. Plato writes that “anyone that love touches instantly becomes a poet.” And even today, when poetry has largely disappeared from the mainstream of popular culture, it retains its romantic associations. But why should this be so—what are the connections between poetry and erotic love that lead us to associate them so strongly with one another? An examination of different theories of both love and poetry across the centuries reveals that the connection between them is not merely an accident of cultural history—the result of our having grown up hearing, or hearing about, love poetry—but something more intrinsic. Even as definitions of them have changed, the two phenomena have consistently been described in parallel terms. Love is characterized by paradox. Above all, it is both necessarily public, because interpersonal, and intensely private; hence it both requires expression and resists it. In poetry, especially lyric poetry, which features its own characteristic paradoxes and silences, love finds a natural outlet. This study considers both the theories and the love poems themselves, bringing together a wide range of examples from different eras in order to examine the major structures that love and poetry share. It does not aim to be a comprehensive history of Western love poetry, but an investigation into the meaning and function of recurrent tropes, forms, and images employed by poets to express and describe erotic love.

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