scholarly journals Simulation of calcium signaling in fine astrocytic processes: effect of spatial properties on spontaneous activity

2019 ◽  
Author(s):  
Denizot Audrey ◽  
Arizono Misa ◽  
Nägerl U. Valentin ◽  
Soula Hédi ◽  
Berry Hugues
Keyword(s):  
Calcium Channels ◽  
Calcium Signaling ◽  
Spatial Data ◽  
Spatial Organization ◽  
Spatial Scales ◽  
Cytosolic Calcium ◽  
Calcium Signals ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Transient Variations

AbstractAstrocytes, a glial cell type of the central nervous system, have emerged as detectors and regulators of neuronal information processing. Astrocyte excitability resides in transient variations of free cytosolic calcium concentration over a range of temporal and spatial scales, from sub-microdomains to waves propagating throughout the cell. Despite extensive experimental approaches, it is not clear how these signals are transmitted to and integrated within an astrocyte. The localization of the main molecular actors and the geometry of the system, including calcium channels IP3R spatial organization, are deemed essential. However, as most calcium signals occur in astrocytic ramifications that are too fine to be resolved by conventional light microscopy, most of those spatial data are unknown and computational modeling remains the only methodology to study this issue. Here, we propose an IP3R-mediated calcium signaling model for dynamics in such small sub-cellular volumes. To account for the expected stochasticity and low copy numbers, our model is both spatially explicit and particle-based. Extensive simulations show that spontaneous calcium signals arise in the model via the interplay between excitability and stochasticity. The model reproduces the main forms of calcium signals and indicates that their frequency crucially depends on the spatial organization of the IP3R channels. Importantly, we show that two processes expressing exactly the same calcium channels can display different types of calcium signals depending on channels spatial organization. Our model with realistic process volume and calcium concentrations successfully reproduces spontaneous calcium signals that we measured in calcium micro-domains with confocal microscopy. To our knowledge, this model is the first model suited to investigate calcium dynamics in fine astrocytic processes and to propose plausible mechanisms responsible for their variability.

scholarly journals Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling

2009 ◽  
Vol 186 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Eugen Brailoiu ◽  
Dev Churamani ◽  
Xinjiang Cai ◽  
Michael G. Schrlau ◽  
G. Cristina Brailoiu ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Nicotinic Acid ◽  
Calcium Signaling ◽  
Calcium Release ◽  
Pore Channel ◽  
Pore Region ◽  
Calcium Signals ◽  
Essential Requirement ◽  
Molecular Identity ◽  
Conserved Residue

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a widespread and potent calcium-mobilizing messenger that is highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of the target protein is unclear. In this study, we show that the previously uncharacterized human two-pore channels (TPC1 and TPC2) are endolysosomal proteins, that NAADP-mediated calcium signals are enhanced by overexpression of TPC1 and attenuated after knockdown of TPC1, and that mutation of a single highly conserved residue within a putative pore region abrogated calcium release by NAADP. Thus, TPC1 is critical for NAADP action and is likely the long sought after target channel for NAADP.

scholarly journals High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome

2021 ◽  
Vol 22 (14) ◽  
pp. 7327
Author(s):  
Juan A. Fafián-Labora ◽  
Miriam Morente-López ◽  
Fco. Javier de Toro ◽  
María C. Arufe
Keyword(s):  
Calcium Signaling ◽  
Rare Disease ◽  
Cell Lines ◽  
Healthy Aging ◽  
Accelerated Aging ◽  
Cytosolic Calcium ◽  
Calcium Handling ◽  
Therapeutic Window ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is a deadly childhood disorder, which is considered a very rare disease. It is caused by an autosomal dominant mutation on the LMNA gene, and it is characterized by accelerated aging. Human cell lines from HGPS patients and healthy parental controls were studied in parallel using next-generation sequencing (NGS) to unravel new non-previously altered molecular pathways. Nine hundred and eleven transcripts were differentially expressed when comparing healthy versus HGPS cell lines from a total of 21,872 transcripts; ITPR1, ITPR3, CACNA2D1, and CAMK2N1 stood out among them due to their links with calcium signaling, and these were validated by Western blot analysis. It was observed that the basal concentration of intracellular Ca2+ was statistically higher in HGPS cell lines compared to healthy ones. The relationship between genes involved in Ca2+ signaling and mitochondria-associated membranes (MAM) was demonstrated through cytosolic calcium handling by means of an automated fluorescent plate reading system (FlexStation 3, Molecular Devices), and apoptosis and mitochondrial ROS production were examined by means of flow cytometry analysis. Altogether, our data suggest that the Ca2+ signaling pathway is altered in HGPS at least in part due to the overproduction of reactive oxygen species (ROS). Our results unravel a new therapeutic window for the treatment of this rare disease and open new strategies to study pathologies involving both accelerated and healthy aging.

scholarly journals Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders

2021 ◽  
Author(s):  
George B. Stefano ◽  
Richard M. Kream
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Specific ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Mitochondrial Dna Heteroplasmy

AbstractMitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

scholarly journals Extraintestinal Spread and Replication of a Homologous EC Rotavirus Strain and a Heterologous Rhesus Rotavirus in BALB/c Mice

2006 ◽  
Vol 80 (11) ◽  
pp. 5219-5232 ◽  
Author(s):  
M. Fenaux ◽  
M. A. Cuadras ◽  
N. Feng ◽  
M. Jaimes ◽  
H. B. Greenberg
Keyword(s):  
Nonstructural Protein ◽  
Natural Infection ◽  
Mesenteric Lymph Nodes ◽  
Newborn Mice ◽  
Rotavirus Infection ◽  
Rotavirus A ◽  
Reverse Transcription Pcr ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Nasal Secretions

ABSTRACT Although rotavirus infection has generally been felt to be restricted to the gastrointestinal tract, over the last two decades there have been sporadic reports of children with acute or fatal cases of rotavirus gastroenteritis testing positive for rotavirus antigen and/or nucleic acid in various extraintestinal locations such as serum, liver, kidney, bladder, testes, nasal secretions, cerebrospinal fluid, and the central nervous system. Recently, studies in animals and people have demonstrated that rotavirus antigenemia is a common event during natural infection. In this study, we extend these observations and compare the intestinal and extraintestinal spread of wild-type homologous murine rotavirus EC and a heterologous strain, rhesus rotavirus (RRV), in newborn mice. A strand-specific quantitative reverse transcription-PCR (ssQRT-PCR) assay was used to quantify the ability of different rotavirus strains to spread and replicate extraintestinally. Both strain EC and RRV were detected extraintestinally in the mesenteric lymph nodes (MLN), livers, lungs, blood, and kidneys. Extraintestinal replication, as measured by ssQRT-PCR, was most prominent in the MLN and occurred to a lesser degree in the livers, kidneys, and lungs. In the MLN, strain EC and RRV had similar (P < 0.05) RNA copy numbers, although EC was present at a 10,000-fold excess over RRV in the small intestine. Rotavirus nonstructural protein 4 (NSP4) and/or assembled triple-layered particles, indicated by immunostaining with the VP7 conformation-dependent monoclonal antibody 159, were detected in the MLN, lungs, and livers of EC- and RRV-inoculated mice, confirming the ssQRT-PCR findings. Infectious RRV was detected in the MLN in quantities exceeding the amount present in the small intestines or blood. The cells in the MLN that supported rotavirus replication included dendritic cells and potentially B cells and macrophages. These data indicate that extraintestinal spread and replication occurs commonly during homologous and some heterologous rotaviral infections; that the substantial host range restrictions for rhesus rotavirus, a heterologous strain present in the intestine, are not necessarily apparent at systemic sites; that the level and location of extraintestinal replication varies between strains; that replication can occur in several leukocytes subsets; and that extraintestinal replication is likely a part of the normal pathogenic sequence of homologous rotavirus infection.

Mapping wildlife: integrating stakeholder knowledge with modelled patterns of deer abundance by using participatory GIS

2009 ◽  
Vol 36 (7) ◽  
pp. 553 ◽  
Author(s):  
Z. Austin ◽  
S. Cinderby ◽  
J. C. R. Smart ◽  
D. Raffaelli ◽  
P. C. L. White
Keyword(s):  
Community Involvement ◽  
Spatial Data ◽  
Spatial Scales ◽  
Stakeholder Participation ◽  
Landscape Scale ◽  
Scientific Data ◽  
Future Research ◽  
Economic Damage ◽  
Participatory Gis ◽  
Wild Deer

Context. Some species that are perceived by certain stakeholders as a valuable resource can also cause ecological or economic damage, leading to contrasting management objectives and subsequent conflict between stakeholder groups. There is increasing recognition that the integration of stakeholder knowledge with formal scientific data can enhance the information available for use in management. This is especially true where scientific understanding is incomplete, as is frequently the case for wide-ranging species, which can be difficult to monitor directly at the landscape scale. Aims. The aim of the research was to incorporate stakeholder knowledge with data derived from formal quantitative models to modify predictions of wildlife distribution and abundance, using wild deer in the UK as an example. Methods. We use selected predictor variables from a deer–vehicle collision model to estimate deer densities at the 10-km square level throughout the East of England. With these predictions as a baseline, we illustrate the use of participatory GIS as a methodological framework for enabling stakeholder participation in the refinement of landscape-scale deer abundance maps. Key results. Stakeholder participation resulted in modifications to modelled abundance patterns for all wild deer species present in the East of England, although the modifications were minor and there was a high degree of consistency among stakeholders in the adjustments made. For muntjac, roe and fallow deer, the majority of stakeholder changes represented an increase in density, suggesting that populations of these species are increasing in the region. Conclusions. Our results show that participatory GIS is a useful technique for enabling stakeholders to contribute to incomplete scientific knowledge, especially where up-to-date species distribution and abundance data are needed to inform wildlife research and management. Implications. The results of the present study will serve as a valuable information base for future research on deer management in the region. The flexibility of the approach makes it applicable to a range of species at different spatial scales and other wildlife conflict issues. These may include the management of invasive species or the conservation of threatened species, where accurate spatial data and enhanced community involvement are necessary in order to facilitate effective management.

scholarly journals A Comprehensive Review of Low Impact Development Models for Research, Conceptual, Preliminary and Detailed Design Applications

Water ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1541 ◽  
Author(s):  
Sahereh Kaykhosravi ◽  
Usman Khan ◽  
Amaneh Jadidi
Keyword(s):  
Spatial Data ◽  
Spatial Scales ◽  
Low Impact Development ◽  
Model Development ◽  
Point Of View ◽  
Tree Canopy ◽  
Balance Model ◽  
Runoff Generation ◽  
Development Models ◽  
Model Features

This review compares and evaluates eleven Low Impact Development (LID) models on the basis of: (i) general model features including the model application, the temporal resolution, the spatial data visualization, the method of placing LID within catchments; (ii) hydrological modelling aspects including: the type of inbuilt LIDs, water balance model, runoff generation and infiltration; and (iii) hydraulic modelling methods with a focus on the flow routing method. Results show that despite the recent updates of existing LID models, several important features are still missing and need improvement. These features include the ability to model: multi-layer subsurface media, tree canopy and processes associated with vegetation, different spatial scales, snowmelt and runoff calculations. This review provides in-depth insight into existing LID models from a hydrological and hydraulic point of view, which will facilitate in selecting the best-suited model. Recommendations on further studies and LID model development are also presented.

scholarly journals Modulation of calcium signaling depends on the oligosaccharide of GM1 in Neuro2a mouse neuroblastoma cells

2020 ◽  
Vol 37 (6) ◽  
pp. 713-727
Author(s):  
Giulia Lunghi ◽  
Maria Fazzari ◽  
Erika Di Biase ◽  
Laura Mauri ◽  
Sandro Sonnino ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Calcium Channels ◽  
Calcium Signaling ◽  
Intracellular Calcium ◽  
Calcium Imaging ◽  
Neuroblastoma Cells ◽  
Ganglioside Gm1 ◽  
Mouse Neuroblastoma ◽  
Neuro2a Cells ◽  
Neuronal Functions

AbstractRecently, we demonstrated that the oligosaccharide portion of ganglioside GM1 is responsible, via direct interaction and activation of the TrkA pathway, for the ability of GM1 to promote neuritogenesis and to confer neuroprotection in Neuro2a mouse neuroblastoma cells. Recalling the knowledge that ganglioside GM1 modulates calcium channels activity, thus regulating the cytosolic calcium concentration necessary for neuronal functions, we investigated if the GM1-oligosaccharide would be able to overlap the GM1 properties in the regulation of calcium signaling, excluding a specific role played by the ceramide moiety inserted into the external layer of plasma membrane. We observed, by calcium imaging, that GM1-oligosaccharide administration to undifferentiated Neuro2a cells resulted in an increased calcium influx, which turned out to be mediated by the activation of TrkA receptor. The biochemical analysis demonstrated that PLCγ and PKC activation follows the TrkA stimulation by GM1-oligosaccharide, leading to the opening of calcium channels both on the plasma membrane and on intracellular storages, as confirmed by calcium imaging experiments performed with IP3 receptor inhibitor. Subsequently, we found that neurite elongation in Neuro2a cells was blocked by subtoxic administration of extracellular and intracellular calcium chelators, suggesting that the increase of intracellular calcium is responsible of GM1-oligosaccharide mediated differentiation. These results suggest that GM1-oligosaccharide is responsible for the regulation of calcium signaling and homeostasis at the base of the neuronal functions mediated by plasma membrane GM1.

scholarly journals Multi-scale data on intertidal macrobenthic biodiversity and environmental features in three New Zealand harbours

2019 ◽  
Author(s):  
Casper Kraan ◽  
Barry L. Greenfield ◽  
Simon F. Thrush
Keyword(s):  
New Zealand ◽  
Environmental Variables ◽  
Spatial Organization ◽  
Spatial Scales ◽  
Species Distributions ◽  
Sediment Grain Size ◽  
High Resolution Data ◽  
Multi Scale ◽  
Grain Size Distributions ◽  
Patterns And Processes

Abstract. Understanding how the plants and animals that live in the seafloor vary in their spatial patterns of diversity and abundance is fundamental to gaining insight in the role of biodiversity in maintaining ecosystem functioning in coastal ecosystems, as well as advancing the modelling of species distributions under realistic assumptions. Yet, it is virtually unknown how the relationships between abundance patterns and different biotic and environmental processes change depending on spatial scales, which is mainly due to a lack of data. Within the project Spatial Organization of Species Distributions: Hierarchical and Scale-Dependent Patterns and Processes in Coastal Seascapes at the National Institute for Water and Atmospheric Research (NIWA) in New Zealand we collected multi-scale and high-resolution data on macrobenthic biodiversity. We found 146 species, i.e. bivalves, polychaetes and crustaceans (> 500 μm) that live hidden in marine sandflats, and collected point measurements of important environmental variables (sediment grain-size distributions, chlorophyll a concentration, and visible sandflat parameters) in three large intertidal Harbours (Kaipara, Tauranga and Manukau). In each Harbour we sampled 400 points for macrobenthic community composition and abundances, as well as the full set of environmental variables. Using an elaborate sampling design, we were able to cover scales from 30 centimetres to a maximal extent of 1 km. All data and extensive metadata are available from the data publisher PANGAEA via the persistent identifier https://doi.org/10.1594/PANGAEA.903448.

Myelin Basic Protein inhibits the calcium response to phytohaemagglutinin in human lymphocytes

1990 ◽  
Vol 10 (1) ◽  
pp. 55-59
Author(s):  
Tiziana Bellini ◽  
Diana Degani ◽  
Maurizio Matteuzzi ◽  
Franco Dallocchio
Keyword(s):  
Myelin Basic Protein ◽  
Protein Concentration ◽  
Basic Protein ◽  
Human Lymphocytes ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Cellular Activation ◽  
The Central Nervous System ◽  
Pre Treatment ◽  
Preincubation Time

Myelin Basic Protein, one of the major membrane protein component of the central nervous system, was used to probe the molecular mechanism of cellular activation by phytohaemagglutinin. Pre-treatment of human lymphocytes with myelin basic protein results in a lower rising of cytosolic concentration of free calcium after stimulation with phytohaemagglutinin. This effect is dependent on myelin basic protein concentration and on the preincubation time of the protein with the cells. It is not due to a interaction between myelin basic protein and phytohaemagglutinin, but appears to be a consequence of the binding of the protein to the cell surface. The reduction of the rise of cytosolic calcium induced by phytohaemagglutinin is specific for the myelin basic protein because other proteins like albumin and protamine have no effect.

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