scholarly journals Quantitative modeling of regular retinal microglia distribution

2021 ◽  
Author(s):  
Yoshie Endo ◽  
Daisuke Asanuma ◽  
Shigeyuki Namiki ◽  
Kenzo Hirose ◽  
Akiyoshi Uemura ◽  
...  
Keyword(s):  
Model Simulation ◽  
Cell Movement ◽  
Cell Contact ◽  
Model Parameters ◽  
Regular Distribution ◽  
Cell Spacing ◽  
Process Formation ◽  
Direct Cell ◽  
The Central Nervous System ◽  
Processing Techniques

Microglia are resident immune cells in the central nervous system (CNS), showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglia’s morphology, dynamics, and distribution. However, the mechanism underlying the regular distribution of microglia remains to be elucidated. First, we quantitatively confirmed the regularity of the distribution pattern of microglial soma. Second, we formulated a mathematical model that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). The resulting model simulation from the measured parameters showed that direct cell-cell contact is most important in generating regular cell spacing. Finally, we tried to specify the molecular pathway responsible for the repulsion between neighboring microglia.

scholarly journals Quantitative modeling of regular retinal microglia distribution

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshie Endo ◽  
Daisuke Asanuma ◽  
Shigeyuki Namiki ◽  
Kei Sugihara ◽  
Kenzo Hirose ◽  
...  
Keyword(s):  
Model Simulation ◽  
Cell Movement ◽  
Cell Contact ◽  
Model Parameters ◽  
Regular Distribution ◽  
Cell Spacing ◽  
Process Formation ◽  
Direct Cell ◽  
The Central Nervous System ◽  
Processing Techniques

AbstractMicroglia are resident immune cells in the central nervous system, showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglia’s morphology, dynamics, and distribution. However, the mechanism underlying the regular distribution of microglia remains to be elucidated. First, we quantitatively confirmed the regularity of the distribution pattern of microglial soma in the retina. Second, we formulated a mathematical model that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). The resulting model simulation from the measured parameters showed that direct cell–cell contact is most important in generating regular cell spacing. Finally, we tried to specify the molecular pathway responsible for the repulsion between neighboring microglia.

scholarly journals Computational modelling of cell chain migration reveals mechanisms that sustain follow-the-leader behaviour

2012 ◽  
Vol 9 (72) ◽  
pp. 1576-1588 ◽  
Author(s):  
Michelle L. Wynn ◽  
Paul M. Kulesa ◽  
Santiago Schnell
Keyword(s):  
Cancer Metastasis ◽  
Computational Modelling ◽  
Cell Movement ◽  
Cell Contact ◽  
Model Parameters ◽  
Directional Bias ◽  
Agent Based ◽  
Chain Migration ◽  
A Chain ◽  
Cell Cell

Follow-the-leader chain migration is a striking cell migratory behaviour observed during vertebrate development, adult neurogenesis and cancer metastasis. Although cell–cell contact and extracellular matrix (ECM) cues have been proposed to promote this phenomenon, mechanisms that underlie chain migration persistence remain unclear. Here, we developed a quantitative agent-based modelling framework to test mechanistic hypotheses of chain migration persistence. We defined chain migration and its persistence based on evidence from the highly migratory neural crest model system, where cells within a chain extend and retract filopodia in short-lived cell contacts and move together as a collective. In our agent-based simulations, we began with a set of agents arranged as a chain and systematically probed the influence of model parameters to identify factors critical to the maintenance of the chain migration pattern. We discovered that chain migration persistence requires a high degree of directional bias in both lead and follower cells towards the target. Chain migration persistence was also promoted when lead cells maintained cell contact with followers, but not vice-versa. Finally, providing a path of least resistance in the ECM was not sufficient alone to drive chain persistence. Our results indicate that chain migration persistence depends on the interplay of directional cell movement and biased cell–cell contact.

scholarly journals Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 600 ◽  
Author(s):  
Erik Nutma ◽  
Démi van Gent ◽  
Sandra Amor ◽  
Laura A. N. Peferoen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cross Talk ◽  
Critical Role ◽  
Disease Onset ◽  
Cell Contact ◽  
Signalling Molecules ◽  
Direct Cell ◽  
The Central Nervous System ◽  
Health And Disease

Over the last decade knowledge of the role of astrocytes in central nervous system (CNS) neuroinflammatory diseases has changed dramatically. Rather than playing a merely passive role in response to damage it is clear that astrocytes actively maintain CNS homeostasis by influencing pH, ion and water balance, the plasticity of neurotransmitters and synapses, cerebral blood flow, and are important immune cells. During disease astrocytes become reactive and hypertrophic, a response that was long considered to be pathogenic. However, recent studies reveal that astrocytes also have a strong tissue regenerative role. Whilst most astrocyte research focuses on modulating neuronal function and synaptic transmission little is known about the cross-talk between astrocytes and oligodendrocytes, the myelinating cells of the CNS. This communication occurs via direct cell-cell contact as well as via secreted cytokines, chemokines, exosomes, and signalling molecules. Additionally, this cross-talk is important for glial development, triggering disease onset and progression, as well as stimulating regeneration and repair. Its critical role in homeostasis is most evident when this communication fails. Here, we review emerging evidence of astrocyte-oligodendrocyte communication in health and disease. Understanding the pathways involved in this cross-talk will reveal important insights into the pathogenesis and treatment of CNS diseases.

scholarly journals Epigenetics and Communication Mechanisms in Microglia Activation with a View on Technological Approaches

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 306
Author(s):  
Sabrina Petralla ◽  
Francesca De Chirico ◽  
Andrea Miti ◽  
Ottavia Tartagni ◽  
Francesca Massenzio ◽  
...  
Keyword(s):  
3D Culture ◽  
Brain Parenchyma ◽  
Microglial Cells ◽  
Phenotypic Change ◽  
Cell Contact ◽  
Pathological Conditions ◽  
Direct Cell ◽  
The Central Nervous System ◽  
And Function

Microglial cells, the immune cells of the central nervous system (CNS), play a crucial role for the proper brain development and function and in CNS homeostasis. While in physiological conditions, microglia continuously check the state of brain parenchyma, in pathological conditions, microglia can show different activated phenotypes: In the early phases, microglia acquire the M2 phenotype, increasing phagocytosis and releasing neurotrophic and neuroprotective factors. In advanced phases, they acquire the M1 phenotype, becoming neurotoxic and contributing to neurodegeneration. Underlying this phenotypic change, there is a switch in the expression of specific microglial genes, in turn modulated by epigenetic changes, such as DNA methylation, histones post-translational modifications and activity of miRNAs. New roles are attributed to microglial cells, including specific communication with neurons, both through direct cell–cell contact and by release of many different molecules, either directly or indirectly, through extracellular vesicles. In this review, recent findings on the bidirectional interaction between neurons and microglia, in both physiological and pathological conditions, are highlighted, with a focus on the complex field of microglia immunomodulation through epigenetic mechanisms and/or released factors. In addition, advanced technologies used to study these mechanisms, such as microfluidic, 3D culture and in vivo imaging, are presented.

scholarly journals Microparticles: A New Perspective in Central Nervous System Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Stephanie M. Schindler ◽  
Jonathan P. Little ◽  
Andis Klegeris
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Treatment Options ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Diagnostic Tools ◽  
Cell Contact ◽  
Direct Cell ◽  
The Central Nervous System ◽  
New Perspective

Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer’s disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS.

scholarly journals Characterization of Moisture Diffusion in Cured Concrete Slabs at Early Ages

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao Zhang ◽  
Hongduo Zhao
Keyword(s):  
Process Model ◽  
Model Simulation ◽  
Moisture Diffusion ◽  
Experimental Results ◽  
Concrete Slabs ◽  
Model Parameters ◽  
Early Age ◽  
Water Curing ◽  
Early Age Concrete

The objective of this paper is to investigate the characterization of moisture diffusion inside early-age concrete slabs subjected to curing. Time-dependent relative humidity (RH) distributions of three mixture proportions subjected to three different curing methods (i.e., air curing, water curing, and membrane-forming compounds curing) and sealed condition were measured for 28 days. A one-dimensional nonlinear moisture diffusion partial differential equation (PDE) based on Fick’s second law, which incorporates the effect of curing in the Dirichlet boundary condition using a concept of curing factor, is developed to simulate the diffusion process. Model parameters are calibrated by a genetic algorithm (GA). Experimental results show that the RH reducing rate inside concrete under air curing is greater than the rates under membrane-forming compound curing and water curing. It is shown that the effect of water-to-cement (w/c) ratio on self-desiccation is significant. Lower w/c ratio tends to result in larger RH reduction. RH reduction considering both effect of diffusion and self-desiccation in early-age concrete is not sensitive to w/c ratio, but to curing method. Comparison between model simulation and experimental results indicates that the improved model is able to reflect the effect of curing on moisture diffusion in early-age concrete slabs.

Abstract 15392: Inflammation and Ischemic Heart Failure: Monocyte-Mediated Cardiac Fibroblast Activation and Matrix Remodeling Through a Direct Cell-Cell Contact Mechanism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Holly E Mewhort ◽  
Brodie D Lipon ◽  
Daniyil A Svystonyuk ◽  
David G Guzzardi ◽  
Paul W Fedak
Keyword(s):  
Peripheral Blood ◽  
Cardiac Fibroblast ◽  
Cell Contact ◽  
Β1 Integrin ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Fibroblast Activation ◽  
Direct Cell ◽  
Tgf Β1 ◽  
Cell Cell

BACKGROUND: Following myocardial infarction (MI), activated cardiac myofibroblasts facilitate extracellular matrix (ECM) remodeling to prevent mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity, however, the mechanisms are unclear. In this study, we explored the effects of peripheral blood monocytes on human cardiac fibroblast activation in a 3D ECM microenvironment. METHODS/RESULTS: Human cardiac fibroblasts isolated from surgical human heart biopsies were seeded into 3D collagen matrices. Peripheral blood monocytes isolated from healthy human donors were co-cultured with fibroblasts. Monocytes increased fibroblast activation measured by collagen ECM contraction (17.9±11.1% increase; p<0.01) and resulted in local ECM remodeling observed by confocal microscopy. Under co-culture conditions that prevent cell-cell contact but allow interaction via paracrine factors, monocytes had minimal effects on fibroblast activation (6.4±7.0 vs.17.9±11.1% increase, respectively; p<0.01). Multiplex analysis of the co-culture media revealed an increase in the paracrine factors Transforming Growth Factor-beta 1 (TGF-β1) and Matrix Metalloproteinase 9 when monocytes and fibroblasts were cultured under cell-cell contact conditions (162.2±11.7pg/mL and 17.5±0.5ng/mL, respectively, vs. 21.8±5.7pg/mL and 4.9 ±0.4ng/mL; p<0.001). TGF-β1 blockade abolished monocyte induced cardiac fibroblast activation, as did β1-integrin. These data suggest direct cell-cell interaction between monocytes and cardiac fibroblasts through β1-integrin results in TGF-β1 release facilitating fibroblast activation and matrix remodeling. CONCLUSION: For the first time, we demonstrate that peripheral blood monocytes stimulate human cardiac fibroblast activation through a mechanism involving TGF-β1 release as a consequence of direct cell-cell interaction through β1-integrin. These data implicate inflammation as a driver of cardiac fibrosis post-MI, highlighting potential novel therapeutic targets for the treatment of ischemic HF.

scholarly journals Implications of sea-ice biogeochemistry for oceanic production and emissions of dimethyl sulfide in the Arctic

2017 ◽  
Vol 14 (12) ◽  
pp. 3129-3155 ◽  
Author(s):  
Hakase Hayashida ◽  
Nadja Steiner ◽  
Adam Monahan ◽  
Virginie Galindo ◽  
Martine Lizotte ◽  
...  
Keyword(s):  
Sea Ice ◽  
Water Column ◽  
Dimethyl Sulfide ◽  
Phytoplankton Bloom ◽  
Model Simulation ◽  
Field Measurements ◽  
Sulfur Cycle ◽  
The Arctic ◽  
Model Parameters ◽  
Ocean Ecosystem

Abstract. Sea ice represents an additional oceanic source of the climatically active gas dimethyl sulfide (DMS) for the Arctic atmosphere. To what extent this source contributes to the dynamics of summertime Arctic clouds is, however, not known due to scarcity of field measurements. In this study, we developed a coupled sea ice–ocean ecosystem–sulfur cycle model to investigate the potential impact of bottom-ice DMS and its precursor dimethylsulfoniopropionate (DMSP) on the oceanic production and emissions of DMS in the Arctic. The results of the 1-D model simulation were compared with field data collected during May and June of 2010 in Resolute Passage. Our results reproduced the accumulation of DMS and DMSP in the bottom ice during the development of an ice algal bloom. The release of these sulfur species took place predominantly during the earlier phase of the melt period, resulting in an increase of DMS and DMSP in the underlying water column prior to the onset of an under-ice phytoplankton bloom. Production and removal rates of processes considered in the model are analyzed to identify the processes dominating the budgets of DMS and DMSP both in the bottom ice and the underlying water column. When openings in the ice were taken into account, the simulated sea–air DMS flux during the melt period was dominated by episodic spikes of up to 8.1 µmol m−2 d−1. Further model simulations were conducted to assess the effects of the incorporation of sea-ice biogeochemistry on DMS production and emissions, as well as the sensitivity of our results to changes of uncertain model parameters of the sea-ice sulfur cycle. The results highlight the importance of taking into account both the sea-ice sulfur cycle and ecosystem in the flux estimates of oceanic DMS near the ice margins and identify key uncertainties in processes and rates that should be better constrained by new observations.

scholarly journals Estimation of baseflow parameters of variable infiltration capacity model with soil and topography properties for predictions in ungauged basins

2011 ◽  
Vol 8 (4) ◽  
pp. 7017-7053 ◽  
Author(s):  
Z. Bao ◽  
J. Liu ◽  
J. Zhang ◽  
G. Fu ◽  
G. Wang ◽  
...  
Keyword(s):  
Goodness Of Fit ◽  
Model Simulation ◽  
Parameters Estimation ◽  
Model Parameters ◽  
Ungauged Basins ◽  
Variable Infiltration Capacity ◽  
Infiltration Capacity ◽  
Ungauged Catchments ◽  
Vic Model ◽  
Predictions In Ungauged Basins

Abstract. Equifinality is unavoidable when transferring model parameters from gauged catchments to ungauged catchments for predictions in ungauged basins (PUB). A framework for estimating the three baseflow parameters of variable infiltration capacity (VIC) model, directly with soil and topography properties is presented. When the new parameters setting methodology is used, the number of parameters needing to be calibrated is reduced from six to three, that leads to a decrease of equifinality and uncertainty. This is validated by Monte Carlo simulations in 24 hydro-climatic catchments in China. Using the new parameters estimation approach, model parameters become more sensitive and the extent of parameters space will be smaller when a threshold of goodness-of-fit is given. That means the parameters uncertainty is reduced with the new parameters setting methodology. In addition, the uncertainty of model simulation is estimated by the generalised likelihood uncertainty estimation (GLUE) methodology. The results indicate that the uncertainty of streamflow simulations, i.e., confidence interval, is lower with the new parameters estimation methodology compared to that used by original calibration methodology. The new baseflow parameters estimation framework could be applied in VIC model and other appropriate models for PUB.

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