Caruso2020 - Alternative Complement Pathway model
Ontology highlight
ABSTRACT:
SUBMITTER: 
Robin Denhardt-Eriksson
PROVIDER: MODEL2206230002 | BioModels | 2022-06-27
REPOSITORIES: BioModels
Similar Datasets
Project description:This model is based on the publication:
Caruso A, Vollmer J, Machacek M, Kortvely E. "Modeling the activation of the alternative complement pathway and its effects on hemolysis in health and disease." PLoS Comput Biol. 2020 Oct 2;16(10):e1008139.
doi: 10.1371/journal.pcbi.1008139
Curation Comment:
Figure 4 has not been able to be reproduced, however authors are in the process of appending the model code to the publication.
2021-09-11 | MODEL2109110001 | BioModels
Project description:Ultraviolet (UV) wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, while higher doses protect from UVB immunosuppression in mice. We have previously shown that these responses to UVA are genetically restricted as they occur in C57BL/6 but not Balb/c mice. We used gene set enrichment analysis of microarray data and real-time RT-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found up-regulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from down regulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting previous identification of IL-12 and IL-10 in high dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin.
2009-06-29 | GSE15618 | GEO
Project description:Ultraviolet (UV) wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, while higher doses protect from UVB immunosuppression in mice. We have previously shown that these responses to UVA are genetically restricted as they occur in C57BL/6 but not Balb/c mice. We used gene set enrichment analysis of microarray data and real-time RT-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found up-regulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from down regulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting previous identification of IL-12 and IL-10 in high dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin. 24 hours after UVA, UVB and ssUV irradiation, a 1 cm2 uniform section of skin was excised from the dorsal surface of irradiated and control mice. Total RNA was then extracted from the whole skin using TRIzol reagent (Gibco Invitrogen Life Technologies, Carlsbad, CA, USA) according to the manufacturerâ??s instructions, purified, DNase treated and reverse transcribed into cDNA. For the microarray study a direct incorporation of Cyanine 3-dCTP and Cyanine 5-dCTP fluorescent dyes (Perkin Elmer Life Sciences, Inc. Boston, MA, USA) was used for cDNA synthesis. For each UV dose, a reference design was used to compare an unirradiated control against an irradiated sample. Microarray experiments used compugen 22k mouse oligonucleotide microarray slides (The Clive and Vera Ramaciotti Centre for Gene Function Analysis, Sydney Australia (http://www.ramaciotti.unsw.edu.au). Lower and higher UVA doses were used. C57BL/6 mice were irradiated with lower UVA, higher UVA, UVB, or ssUV; Balb/C mice were irradiated with lower or higher UVA. Experiments were replicated 6 times for each UV dose. A fluorescent dye swap was done for each alternate hybridisation to reduce systematic dye bias of incorporated fluorescent dyes.
2010-05-16 | E-GEOD-15618 | biostudies-arrayexpress
Project description:This model is based on the publication:
"Mathematical Modelling of Alternative Pathway of Complement System".
Suruchi Bakshi, Fraser Cunningham, Eva-Maria Nichols, Marta Biedzka-Sarek, Jessica Neisen, Sebastien Petit-Frere, Christina Bessant, Loveleena Bansal, Lambertus A Peletier, Stefano Zamuner, Piet H van der Graaf
DOI: 10.1007/s11538-020-00708-z
Comment:
Correction to the original manuscript is accessible here
Model schematics in Figure 3 and parameter d4 were corrected.
Abstract:
The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation -of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.
2021-07-20 | BIOMD0000001018 | BioModels
Project description:This model is based on the publication:
"Mathematical Modelling of Alternative Pathway of Complement System".
Suruchi Bakshi, Fraser Cunningham, Eva-Maria Nichols, Marta Biedzka-Sarek, Jessica Neisen, Sebastien Petit-Frere, Christina Bessant, Loveleena Bansal, Lambertus A Peletier, Stefano Zamuner, Piet H van der Graaf
DOI: 10.1007/s11538-020-00708-z
Comment:
This model is based on the truncated minimal model equations (Eq. B.1) from the manuscript, which simulate depletion of factor H.
Abstract:
The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.
2021-07-20 | BIOMD0000001017 | BioModels
Project description:This model is based on the publication:
"Mathematical Modelling of Alternative Pathway of Complement System".
Suruchi Bakshi, Fraser Cunningham, Eva-Maria Nichols, Marta Biedzka-Sarek, Jessica Neisen, Sebastien Petit-Frere, Christina Bessant, Loveleena Bansal, Lambertus A Peletier, Stefano Zamuner, Piet H van der Graaf
DOI: 10.1007/s11538-020-00708-z
Comment:
This model is based on the truncated minimal model equations (Eq. B.1) from the manuscript, which simulate depletion of factor H.
Abstract:
The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.
2021-07-20 | BIOMD0000001016 | BioModels
Project description:Lineage tracing of individual cells during directed differentiation human iPSC into alveolospheres was performed using a lentiviral barcode labeling system (Weinreb et al., 2020) as described in Hurley et al., 2020.
2019-09-24 | GSE137805 | GEO
Project description:Complement component 3a receptor 1 (C3ar1) was predicted as a causal gene for abdominal using a novel statistical method named LCMS (Schadt et al., 2005, Nature Genetics). In order to validate this prediction, we profiled the liver tissues of complement component 3a receptor 1 knockout (C3ar1-/-) mice and their littermate wild-type (wt) controls to examine the gene expression signature as well as pathways/networks resulting from the single gene perturbation.
2009-03-08 | GSE11995 | GEO
Project description:VSMCs expressing SCA1 have increased proliferative capacity (Dobnikar et al, 2018; Worssam et al, 2022; Pan et al, 2020). We therefore, mapped chromatin accessibility changes using bulk ATAC-seq for SCA1+ and SCA1- lineage traced VSMCs.
2024-04-09 | GSE246646 | GEO
Project description:While DNA methylation is an important gene regulatory mechanism in mammals (Razin and Riggs 1980; Moore, Le, and Fan 2013), its function in arthropods remains poorly understood. Studies in eusocial insects have argued for its role in caste development by regulating gene expression and splicing (Elango et al. 2009; Lyko et al. 2010; Bonasio et al. 2012; Flores et al. 2012; Foret et al. 2012; Li-Byarlay et al. 2013; Marshall, Lonsdale, and Mallon 2019; Shi et al. 2013)(Alvarado et al. 2015; Kucharski et al. 2008). However, such findings are not always consistent across studies, and have therefore remained controversial (Arsenault, Hunt, and Rehan 2018; Cardoso-Junior et al. 2021; Harris et al. 2019; Herb et al. 2012; Libbrecht et al. 2016; Oldroyd and Yagound 2021b; Patalano et al. 2015). Here we use CRISPR/Cas9 to mutate the maintenance DNA methyltransferase DNMT1 in the clonal raider ant, Ooceraea biroi. Mutants have greatly reduced DNA methylation but no obvious developmental phenotypes, demonstrating that, unlike mammals (Brown and Robertson 2007; En Li, Bestor, and Jaenisch 1992; Jackson-Grusby et al. 2001; Panning and Jaenisch 1996), ants can undergo normal development without DNMT1 or DNA methylation. Additionally, we find no evidence of DNA methylation regulating caste development. However, mutants are sterile, while in wildtypes, DNMT1 is localized to the ovaries and maternally provisioned into nascent oocytes. This supports the idea that DNMT1 plays a crucial but unknown role in the insect germline (Amukamara et al. 2020; Arsala et al. 2021; Bewick et al. 2019; Schulz et al. 2018; Ventós-Alfonso et al. 2020; Washington et al. 2020).
2023-03-23 | GSE182212 | GEO