scholarly journals Actin Automata: Phenomenology and Localizations

2015 ◽  
Vol 25 (02) ◽  
pp. 1550030 ◽  
Author(s):  
Andrew Adamatzky ◽  
Richard Mayne
Keyword(s):  
Intracellular Signaling ◽  
Cell Function ◽  
Contractile Activity ◽  
Emergent Behavior ◽  
Polymer Chains ◽  
Structural Support ◽  
Rule Space ◽  
Binary State ◽  
Integral Characteristics ◽  
State Transition Rules

Actin is a globular protein which forms long filaments in the eukaryotic cytoskeleton, whose roles in cell function include structural support, contractile activity to intracellular signaling. We model actin filaments as two chains of one-dimensional binary-state semi-totalistic automaton arrays to describe hypothetical signaling events therein. Each node of the actin automaton takes state "0" (resting) or "1" (excited) and updates its state in discrete time depending on its neighbor's states. We analyze the complete rule space of actin automata using integral characteristics of space-time configurations generated by these rules and compute state transition rules that support traveling and mobile localizations. Approaches towards selection of the localization supporting rules using the global characteristics are outlined. We find that some properties of actin automata rules may be predicted using Shannon entropy, activity and incoherence of excitation between the polymer chains. We also show that it is possible to infer whether a given rule supports traveling or stationary localizations by looking at ratios of excited neighbors that are essential for generations of the localizations. We conclude by applying biomolecular hypotheses to this model and discuss the significance of our findings in context with cell signaling and emergent behavior in cellular computation.

scholarly journals Effects of Extra Virgin Olive Oil Polyphenols on Beta-Cell Function and Survival

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 286
Author(s):  
Nicola Marrano ◽  
Rosaria Spagnuolo ◽  
Giuseppina Biondi ◽  
Angelo Cignarelli ◽  
Sebastio Perrini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Olive Oil ◽  
Beta Cells ◽  
Intracellular Signaling ◽  
Beta Cell Function ◽  
Cell Function ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Insulin Biosynthesis

Extra virgin olive oil (EVOO) is a major component of the Mediterranean diet and is appreciated worldwide because of its nutritional benefits in metabolic diseases, including type 2 diabetes (T2D). EVOO contains significant amounts of secondary metabolites, such as phenolic compounds (PCs), that may positively influence the metabolic status. In this study, we investigated for the first time the effects of several PCs on beta-cell function and survival. To this aim, INS-1E cells were exposed to 10 μM of the main EVOO PCs for up to 24 h. Under these conditions, survival, insulin biosynthesis, glucose-stimulated insulin secretion (GSIS), and intracellular signaling activation (protein kinase B (AKT) and cAMP response element-binding protein (CREB)) were evaluated. Hydroxytyrosol, tyrosol, and apigenin augmented beta-cell proliferation and insulin biosynthesis, and apigenin and luteolin enhanced the GSIS. Conversely, vanillic acid and vanillin were pro-apoptotic for beta-cells, even if they increased the GSIS. In addition, oleuropein, p-coumaric, ferulic and sinapic acids significantly worsened the GSIS. Finally, a mixture of hydroxytyrosol, tyrosol, and apigenin promoted the GSIS in human pancreatic islets. Apigenin was the most effective compound and was also able to activate beneficial intracellular signaling. In conclusion, this study shows that hydroxytyrosol, tyrosol, and apigenin foster beta-cells’ health, suggesting that EVOO or supplements enriched with these compounds may improve insulin secretion and promote glycemic control in T2D patients.

scholarly journals Herpes Simplex Virus Remodels T-Cell Receptor Signaling, Resulting in p38-Dependent Selective Synthesis of Interleukin-10

2007 ◽  
Vol 81 (22) ◽  
pp. 12504-12514 ◽  
Author(s):  
Derek D. Sloan ◽  
Keith R. Jerome
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
T Cell Receptor ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Cell Receptor ◽  
Interleukin 10 ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV)-specific T cells are essential for viral clearance. However, T cells do not prevent HSV latent infection or reactivation, suggesting that HSV has the potential to modulate T-cell function. T-cell receptor (TCR) stimulation is a potent and specific means of activating T cells. To investigate how HSV affects T-cell function, we have analyzed how HSV affects TCR-stimulated intracellular signaling and cytokine synthesis in mock-infected and HSV-infected T cells. Mock-infected T cells stimulated through the TCR synthesized a broad range of cytokines that included the proinflammatory cytokines tumor necrosis factor alpha, gamma interferon, and interleukin-2. In contrast, HSV-infected T cells stimulated through the TCR selectively synthesized interleukin-10, a cytokine that suppresses cellular immunity and favors viral replication. To achieve selective interleukin-10 synthesis, HSV differentially affected TCR signaling pathways. HSV inhibited TCR-stimulated formation of the linker for activation of the T-cell signaling complex, and HSV inhibited TCR-stimulated NF-κB activation. At the same time, HSV activated the p38 and JNK mitogen-activated protein kinases as well as the downstream transcription factors ATF-2 and c-Jun. HSV did not inhibit TCR-stimulated activation of STAT3, a transcription factor involved in interleukin-10 synthesis. The activation of p38 was required for interleukin-10 synthesis in HSV-infected T cells. The ability of HSV to differentially target intracellular signaling pathways and transform an activating stimulus into an immunosuppressive response represents a novel strategy for pathogen-mediated immune modulation. Selective, TCR-stimulated interleukin-10 synthesis may play an important role in HSV pathogenesis.

scholarly journals DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions

2021 ◽  
Vol 118 (21) ◽  
pp. e2021309118
Author(s):  
Kazuki Sato ◽  
Yumi Yamashita-Kanemaru ◽  
Fumie Abe ◽  
Rikito Murata ◽  
Yuho Nakamura-Shinya ◽  
...  
Keyword(s):  
Treg Cell ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Mammalian Target Of Rapamycin ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Cell Dysfunction ◽  
Inflammatory Conditions ◽  
Treg Cell Function

Regulatory T (Treg) cells that express forkhead box P3 (Foxp3) are pivotal for immune tolerance. Although inflammatory mediators cause Foxp3 instability and Treg cell dysfunction, their regulatory mechanisms remain incompletely understood. Here, we show that the transfer of Treg cells deficient in the activating immunoreceptor DNAM-1 ameliorated the development of graft-versus-host disease better than did wild-type Treg cells. We found that DNAM-1 competes with T cell immunoreceptor with Ig and ITIM domains (TIGIT) in binding to their common ligand CD155 and therefore regulates TIGIT signaling to down-regulate Treg cell function without DNAM-1–mediated intracellular signaling. DNAM-1 deficiency augments TIGIT signaling; this subsequently inhibits activation of the protein kinase B–mammalian target of rapamycin complex 1 pathway, resulting in the maintenance of Foxp3 expression and Treg cell function under inflammatory conditions. These findings demonstrate that DNAM-1 regulates Treg cell function via TIGIT signaling and thus, it is a potential molecular target for augmenting Treg function in inflammatory diseases.

scholarly journals Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function

2003 ◽  
Vol 198 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Dong-Gyun Lim ◽  
Jacqueline M. Slavik ◽  
Katarzyna Bourcier ◽  
Kathrine J. Smith ◽  
David A. Hafler
Keyword(s):  
T Cell ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Peptide Ligands ◽  
T Cell Clones ◽  
Altered Peptide Ligands ◽  
Mhc Molecules ◽  
Cell Functions ◽  
T Cell Function ◽  
Cell Clones

T cell receptors recognize small changes in peptide ligands leading to different T cell responses. Here, we analyzed a panel of HLA-A2–Tax11-19 reactive T cell clones to examine how small allelic variations of MHC molecules could alter the functional outcome of antigen recognition. Similar to the effects induced by antigenic altered peptide ligands, weak or partial agonistic T cell functions were identified in individual T cell clones with the recognition of MHC-altered peptide ligands (MAPLs). Interestingly, one subtype of HLA-A2 molecules induced an unusual type of partial agonistic function; proliferation without cytotoxicity. Modeling of crystallographic data indicated that polymorphic amino acids in the HLA-A2 peptide binding groove, especially the D-pocket, were responsible for this partial agonism. Reciprocal mutations of the Tax peptide side chain engaging the D-pocket indeed restored the agonist functions of the MHC–peptide complex. Whereas early intracellular signaling events were not efficiently induced by these MAPLs, phosphorylated c-Jun slowly accumulated with sustained long-term expression. These data indicate that MAPLs can induce atypical partial agonistic T cell function through structural and biochemical mechanisms similar to altered peptide ligands.

Hypoxia-induced reactive oxygen species formation in skeletal muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2379-2388 ◽  
Author(s):  
Thomas L. Clanton
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Cell Function ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Hypoxic Exposure ◽  
Ros Production ◽  
Oxygen Species

The existence of hypoxia-induced reactive oxygen species (ROS) production remains controversial. However, numerous observations with a variety of methods and in many cells and tissue types are supportive of this idea. Skeletal muscle appears to behave much like heart in that in the early stages of hypoxia there is a transient elevation in ROS, whereas in chronic exposure to very severe hypoxia there is evidence of ongoing oxidative stress. Important remaining questions that are addressed in this review include the following. Are there levels of Po2 in skeletal muscle, typical of physiological or mildly pathophysiological conditions, that are low enough to induce significant ROS production? Does the ROS associated with muscle contractile activity reflect imbalances in oxygen uptake and demand that drive the cell to a more reduced state? What are the possible molecular mechanisms by which ROS may be elevated in hypoxic skeletal muscle? Is the production of ROS in hypoxia of physiological significance, both with respect to cell signaling pathways promoting cell function and with respect to damaging effects of long-term exposure? Discussion of these and other topics leads to general conclusions that hypoxia-induced ROS may be a normal physiological response to imbalance in oxygen supply and demand or environmental stress and may play a yet undefined role in normal response mechanisms to these stimuli. However, in chronic and extreme hypoxic exposure, muscles may fail to maintain a normal redox homeostasis, resulting in cell injury or dysfunction.

scholarly journals Extracellular matrix, regional heterogeneity of the aorta, and aortic aneurysm

2019 ◽  
Vol 51 (12) ◽  
pp. 1-15 ◽  
Author(s):  
Sayantan Jana ◽  
Mei Hu ◽  
Mengcheng Shen ◽  
Zamaneh Kassiri
Keyword(s):  
Extracellular Matrix ◽  
Aortic Aneurysm ◽  
Aortic Wall ◽  
Cell Function ◽  
Experimental Models ◽  
Aneurysm Rupture ◽  
Regional Heterogeneity ◽  
Structural Support ◽  
Aneurysm Formation ◽  
And Behavior

AbstractAortic aneurysm is an asymptomatic disease with dire outcomes if undiagnosed. Aortic aneurysm rupture is a significant cause of death worldwide. To date, surgical repair or endovascular repair (EVAR) is the only effective treatment for aortic aneurysm, as no pharmacological treatment has been found effective. Aortic aneurysm, a focal dilation of the aorta, can be formed in the thoracic (TAA) or the abdominal (AAA) region; however, our understanding as to what determines the site of aneurysm formation remains quite limited. The extracellular matrix (ECM) is the noncellular component of the aortic wall, that in addition to providing structural support, regulates bioavailability of an array of growth factors and cytokines, thereby influencing cell function and behavior that ultimately determine physiological or pathological remodeling of the aortic wall. Here, we provide an overview of the ECM proteins that have been reported to be involved in aortic aneurysm formation in humans or animal models, and the experimental models for TAA and AAA and the link to ECM manipulations. We also provide a comparative analysis, where data available, between TAA and AAA, and how aberrant ECM proteolysis versus disrupted synthesis may determine the site of aneurysm formation.

Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent

2007 ◽  
Vol 103 (1) ◽  
pp. 184-189 ◽  
Author(s):  
Israel Rubinstein
Keyword(s):  
Substance P ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Cell Function ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Endothelial Cell Function ◽  
Protein Tyrosine

The purpose of this study was to determine whether protein tyrosine kinase, a ubiquitous family of intracellular signaling enzymes that regulates endothelial cell function, modulates bradykinin- and substance P-induced increase in macromolecular efflux from the intact hamster cheek pouch microcirculation. Using intravital microscopy, I found that suffusion of bradykinin or substance P (each, 0.5 and 1.0 μM) onto the cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (FITC-dextran; molecular mass, 70 kDa; P < 0.05). These responses were significantly attenuated by suffusion of genistein (1.0 μM) or tyrphostin 25 (10 μM), two structurally unrelated, nonspecific protein tyrosine kinase inhibitors ( P < 0.05). Conceivably, the kinase(s) involved in this process could be agonist specific because genistein was more effective than tyrphostin 25 in attenuating bradykinin-induced responses while the opposite was observed with substance P. Both inhibitors had no significant effects on adenosine (0.5 M)-induced responses ( P > 0.5). Collectively, these data suggest that the protein tyrosine kinase metabolic pathway modulates, in part, the edemagenic effects of bradykinin and substance P in the intact hamster cheek pouch microcirculation in a specific fashion.

Heterodimerization of FGF-receptor 1 and PDGF-receptor-α: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 1896-1902 ◽  
Author(s):  
Debora Faraone ◽  
Maria S. Aguzzi ◽  
Gianluca Ragone ◽  
Katia Russo ◽  
Maurizio C. Capogrossi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Umbilical Vein ◽  
Pdgf Receptor ◽  
Inhibitory Effects ◽  
Fgf Receptor ◽  
Endothelial Cell Function

Previous evidence has shown that platelet-derived growth factor-BB (PDGF-BB) and fibroblast growth factor-2 (FGF-2) directly interact with high affinity, leading to potent reciprocal inhibitory effects on bovine endothelial cells and rat vascular smooth muscle cells. In this study, we report that PDGF-BB inhibits a series of FGF-2–induced events, such as proliferation of human umbilical vein endothelial cells (HUVECs), FGF-2 cellular internalization, phosphorylation of intracellular signaling factors including p38, rac1/cdc42, MKK4, and MKK3/6, and phosphorylation of FGF-receptor 1 (FGF-R1). PDGF-receptor-α (PDGF-Rα) was found to mediate PDGF-BB inhibitory effects because its neutralization fully restored FGF-2 mitogenic activity and internalization. Additional biochemical analyses, coimmunoprecipitation experiments, and FRET analysis showed that FGF-R1 and PDGF-Rα directly interact in vitro and in vivo and that this interaction is somehow increased in the presence of the corresponding ligands FGF-2 and PDGF-BB. These results suggest that FGF-R1/PDGF-Rα heterodimerization may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control endothelial cell function.

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