scholarly journals Activity pulses induce spontaneous flow reversals in viscoelastic environments

2021 ◽  
Author(s):  
Emmanuel L. C. VI M. Plan ◽  
Julia M. Yeomans ◽  
Amin Doostmohammadi
Keyword(s):  
Viscoelastic Medium ◽  
Cellular Systems ◽  
Time Dependent ◽  
Cell Functions ◽  
Complex Interactions ◽  
Active Particles ◽  
Flow Generation ◽  
Active Flow ◽  
Flow Reversals

Complex interactions between cellular systems and their surrounding extracellular matrices are emerging as important mechanical regulators of cell functions such as proliferation, motility, and cell death, and such cellular systems are often characterized by pulsating acto-myosin activities. Here, using an active gel model, we numerically explore the spontaneous flow generation by activity pulses in the presence of a viscoelastic medium. The results show that cross-talk between the activity-induced deformations of the viscoelastic surroundings with the time-dependent response of the active medium to these deformations can lead to the reversal of spontaneously generated active flows. We explain the mechanism behind this phenomenon based on the interaction between the active flow and the viscoelastic medium. We show the importance of relaxation timescales of both the polymers and the active particles and provide a phase-space over which such spontaneous flow reversals can be observed. Our results suggest new experiments investigating the role of controlled pulses of activity in living systems ensnared in complex mircoenvironments.

scholarly journals Activity pulses induce spontaneous flow reversals in viscoelastic environments

2021 ◽  
Vol 18 (177) ◽  
Author(s):  
Emmanuel L. C. VI M. Plan ◽  
Julia M. Yeomans ◽  
Amin Doostmohammadi
Keyword(s):  
Viscoelastic Medium ◽  
Cellular Systems ◽  
Time Dependent ◽  
Cell Functions ◽  
Complex Interactions ◽  
Active Particles ◽  
Flow Generation ◽  
Active Flow ◽  
Flow Reversals

Complex interactions between cellular systems and their surrounding extracellular matrices are emerging as important mechanical regulators of cell functions, such as proliferation, motility and cell death, and such cellular systems are often characterized by pulsating actomyosin activities. Here, using an active gel model, we numerically explore spontaneous flow generation by activity pulses in the presence of a viscoelastic medium. The results show that cross-talk between the activity-induced deformations of the viscoelastic surroundings and the time-dependent response of the active medium to these deformations can lead to the reversal of spontaneously generated active flows. We explain the mechanism behind this phenomenon based on the interaction between the active flow and the viscoelastic medium. We show the importance of relaxation time scales of both the polymers and the active particles and provide a phase space over which such spontaneous flow reversals can be observed. Our results suggest new experiments investigating the role of controlled pulses of activity in living systems ensnared in complex mircoenvironments.

scholarly journals The neovasculature homing motif NGR: more than meets the eye

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2628-2635 ◽  
Author(s):  
Angelo Corti ◽  
Flavio Curnis ◽  
Wadih Arap ◽  
Renata Pasqualini
Keyword(s):  
Tumor Growth ◽  
Targeted Delivery ◽  
Binding Sites ◽  
Potential Role ◽  
Time Dependent ◽  
Binding Properties ◽  
Cell Functions ◽  
Structural And Functional Properties ◽  
Asparagine Deamidation

Abstract A growing body of evidence suggests that peptides containing the Asn-Gly-Arg (NGR) motif can selectively recognize tumor neovasculature and can be used, therefore, for ligand-directed targeted delivery of various drugs and particles to tumors or to other tissues with an angiogenesis component. The neovasculature binding properties of these peptides rely on the interaction with an endothelium-associated form of aminopeptidase N (CD13), an enzyme that has been implicated in angiogenesis and tumor growth. Recent studies have shown that NGR can rapidly convert to isoaspartate-glycine-arginine (isoDGR) by asparagine deamidation, generating αvβ3 ligands capable of affecting endothelial cell functions and tumor growth. This review focuses on structural and functional properties of the NGR motif and its application in drug development for angiogenesis-dependent diseases. Furthermore, we discuss the time-dependent transition of NGR to isoDGR in natural proteins, such as fibronectins, and its potential role of as a “molecular timer” for generating new binding sites for integrins impli-cated in angiogenesis.

Regulatory features of interleukin-1β-mediated prostaglandin E2 synthesis in airway smooth muscle

2006 ◽  
Vol 290 (3) ◽  
pp. L501-L508 ◽  
Author(s):  
Rodolfo M. Pascual ◽  
Elizabeth M. Carr ◽  
Michael C. Seeds ◽  
Manhong Guo ◽  
Reynold A. Panettieri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Prostaglandin E2 ◽  
Airway Smooth Muscle ◽  
Phospholipase A ◽  
Time Dependent ◽  
Cell Functions ◽  
Numerous Cell ◽  
Cox 2 ◽  
Sb 203580

Exposure of airway smooth muscle (ASM) cells to the cytokine IL-1β results in an induction of PGE2 synthesis that affects numerous cell functions. Current dogma posits induction of COX-2 protein as the critical, obligatory event in cytokine-induced PGE2 production, although PGE2 induction can be inhibited without a concomitant inhibition of COX-2. To explore other putative regulatory features we examined the role of phospholipase A2 (PLA2) and PGE synthase (PGES) enzymes in IL-1β-induced PGE2 production. Treatment of human ASM cultures with IL-1β caused a time-dependent induction of both cytosolic PLA2 (cPLA2) and microsomal PGES (mPGES) similar to that observed for COX-2. Regulation of COX-2 and mPGES induction was similar, being significantly reduced by inhibition of p42/p44 or p38, whereas cPLA2 induction was only minimally reduced by inhibition of p38 or PKC. COX-2 and mPGES induction was subject to feed-forward regulation by PKA, whereas cPLA2 induction was not. SB-202474, an SB-203580 analog lacking the ability to inhibit p38 but capable of inhibiting IL-1β-induced PGE2 production, was effective in inhibiting mPGES but not COX-2 or cPLA2 induction. These data suggest that although COX-2, cPLA2, and mPGES are all induced by IL-β in human ASM cells, regulatory features of cPLA2 are dissociated, whereas those of COX-2 and mPGES are primarily associated, with regulation of PGE2 production. mPGES induction and, possibly, cPLA2 induction appear to cooperate with COX-2 to determine IL-1β-mediated PGE2 production in human ASM cells.

The photoreceptor cytoskeleton visualized

1992 ◽  
Vol 50 (1) ◽  
pp. 480-481
Author(s):  
Beth Burnside
Keyword(s):  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Polarization ◽  
Synaptic Proteins ◽  
Cell Functions ◽  
Vertebrate Photoreceptor ◽  
Numerous Cell ◽  
Turn Over

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

scholarly journals Hydrodynamics can determine the optimal route for microswimmer navigation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Abdallah Daddi-Moussa-Ider ◽  
Hartmut Löwen ◽  
Benno Liebchen
Keyword(s):  
Flow Field ◽  
Hydrodynamic Interactions ◽  
Optimal Trajectories ◽  
Optimal Route ◽  
Active Particles ◽  
Navigation Strategy ◽  
Navigation Strategies

AbstractAs compared to the well explored problem of how to steer a macroscopic agent, like an airplane or a moon lander, to optimally reach a target, optimal navigation strategies for microswimmers experiencing hydrodynamic interactions with walls and obstacles are far-less understood. Here, we systematically explore this problem and show that the characteristic microswimmer-flow-field crucially influences the navigation strategy required to reach a target in the fastest way. The resulting optimal trajectories can have remarkable and non-intuitive shapes, which qualitatively differ from those of dry active particles or motile macroagents. Our results provide insights into the role of hydrodynamics and fluctuations on optimal navigation at the microscale, and suggest that microorganisms might have survival advantages when strategically controlling their distance to remote walls.

scholarly journals Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 204
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Pol Andrés-Benito ◽  
Belén Marín ◽  
Alicia Otero ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Global Approach ◽  
Profile Data ◽  
Dexamethasone Treatment ◽  
New Approach ◽  
Complex Interactions ◽  
Natural Scrapie ◽  
Anti Inflammatory

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.

scholarly journals Richness of Rhizosphere Organisms Affects Plant P Nutrition According to P Source and Mobility

Agriculture ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 157
Author(s):  
Jean Trap ◽  
Patricia Mahafaka Ranoarisoa ◽  
Usman Irshad ◽  
Claude Plassard
Keyword(s):  
Careful Consideration ◽  
Soil Conditions ◽  
Organic P ◽  
P Nutrition ◽  
Soil P ◽  
P Acquisition ◽  
Complex Interactions ◽  
Experimental Trials ◽  
The Relationship

Plants evolve complex interactions with diverse soil mutualist organisms to enhance P mobilization from the soil. These strategies are particularly important when P is poorly available. It is still unclear how the soil P source (e.g., mineral P versus recalcitrant organic P) and its mobility in the soil (high or low) affect soil mutualist biological (ectomycorrhizal fungi, bacteria and bacterial-feeding nematodes) richness—plant P acquisition relationships. Using a set of six microcosm experiments conducted in growth chamber across contrasting P situations, we tested the hypothesis that the relationship between the increasing addition of soil mutualist organisms in the rhizosphere of the plant and plant P acquisition depends on P source and mobility. The highest correlation (R2 = 0.70) between plant P acquisition with soil rhizosphere biological richness was found in a high P-sorbing soil amended with an organic P source. In the five other situations, the relationships became significant either in soil conditions, with or without mineral P addition, or when the P source was supplied as organic P in the absence of soil, although with a low correlation coefficient (0.09 < R2 < 0.15). We thus encourage the systematic and careful consideration of the form and mobility of P in the experimental trials that aim to assess the role of biological complexity on plant P nutrition.

scholarly journals GSK-3α Inhibition in Drug-Resistant CML Cells Promotes Susceptibility to NK Cell-Mediated Lysis in an NKG2D- and NKp30-Dependent Manner

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1802
Author(s):  
Nayoung Kim ◽  
Mi Yeon Kim ◽  
Woo Seon Choi ◽  
Eunbi Yi ◽  
Hyo Jung Lee ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Negative Regulator ◽  
Target Cells ◽  
Dependent Manner ◽  
Cell Functions ◽  
Cell Based Therapy ◽  
Activating Receptors ◽  
Gsk 3Β

Natural killer (NK) cells are innate cytotoxic lymphocytes that provide early protection against cancer. NK cell cytotoxicity against cancer cells is triggered by multiple activating receptors that recognize specific ligands expressed on target cells. We previously demonstrated that glycogen synthase kinase (GSK)-3β, but not GSK-3α, is a negative regulator of NK cell functions via diverse activating receptors, including NKG2D and NKp30. However, the role of GSK-3 isoforms in the regulation of specific ligands on target cells is poorly understood, which remains a challenge limiting GSK-3 targeting for NK cell-based therapy. Here, we demonstrate that GSK-3α rather than GSK-3β is the primary isoform restraining the expression of NKG2D ligands, particularly ULBP2/5/6, on tumor cells, thereby regulating their susceptibility to NK cells. GSK-3α also regulated the expression of the NKp30 ligand B7-H6, but not the DNAM-1 ligands PVR or nectin-2. This regulation occurred independently of BCR-ABL1 mutation that confers tyrosine kinase inhibitor (TKI) resistance. Mechanistically, an increase in PI3K/Akt signaling in concert with c-Myc was required for ligand upregulation in response to GSK-3α inhibition. Importantly, GSK-3α inhibition improved cancer surveillance by human NK cells in vivo. Collectively, our results highlight the distinct role of GSK-3 isoforms in the regulation of NK cell reactivity against target cells and suggest that GSK-3α modulation could be used to enhance tumor cell susceptibility to NK cells in an NKG2D- and NKp30-dependent manner.

scholarly journals Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

2021 ◽  
Author(s):  
Karthick Dharmalingam ◽  
Amandeep Birdi ◽  
Sojit Tomo ◽  
Karli Sreenivasulu ◽  
Jaykaran Charan ◽  
...  
Keyword(s):  
Immune Response ◽  
Trace Elements ◽  
Viral Entry ◽  
Viral Infections ◽  
Inhibitory Effect ◽  
Antioxidants Activity ◽  
Host Immune Responses ◽  
Complex Interactions ◽  
Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

scholarly journals An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1843-1850 ◽  
Author(s):  
E Arnaud ◽  
M Lafay ◽  
P Gaussem ◽  
V Picard ◽  
M Jandrot-Perrus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Receptor Activation ◽  
Anion Binding ◽  
Thrombin Receptor ◽  
Cell Functions ◽  
Human Thrombin

Abstract An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.

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