Academic literature on the topic 'Systems biology investigation'

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Journal articles on the topic "Systems biology investigation"

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Fernandes, Marco, and Holger Husi. "Integrative Systems Biology Investigation of Fabry Disease." Diseases 4, no. 4 (November 15, 2016): 35. http://dx.doi.org/10.3390/diseases4040035.

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King, Ross D., Maria Liakata, Chuan Lu, Stephen G. Oliver, and Larisa N. Soldatova. "On the formalization and reuse of scientific research." Journal of The Royal Society Interface 8, no. 63 (April 13, 2011): 1440–48. http://dx.doi.org/10.1098/rsif.2011.0029.

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The reuse of scientific knowledge obtained from one investigation in another investigation is basic to the advance of science. Scientific investigations should therefore be recorded in ways that promote the reuse of the knowledge they generate. The use of logical formalisms to describe scientific knowledge has potential advantages in facilitating such reuse. Here, we propose a formal framework for using logical formalisms to promote reuse. We demonstrate the utility of this framework by using it in a worked example from biology: demonstrating cycles of investigation formalization [ F ] and reuse [ R ] to generate new knowledge. We first used logic to formally describe a Robot scientist investigation into yeast ( Saccharomyces cerevisiae ) functional genomics [ f 1 ]. With Robot scientists, unlike human scientists, the production of comprehensive metadata about their investigations is a natural by-product of the way they work. We then demonstrated how this formalism enabled the reuse of the research in investigating yeast phenotypes [ r 1 = R ( f 1 )]. This investigation found that the removal of non-essential enzymes generally resulted in enhanced growth. The phenotype investigation was then formally described using the same logical formalism as the functional genomics investigation [ f 2 = F ( r 1 )]. We then demonstrated how this formalism enabled the reuse of the phenotype investigation to investigate yeast systems-biology modelling [ r 2 = R ( f 2 )]. This investigation found that yeast flux-balance analysis models fail to predict the observed changes in growth. Finally, the systems biology investigation was formalized for reuse in future investigations [ f 3 = F ( r 2 )]. These cycles of reuse are a model for the general reuse of scientific knowledge.
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Smith, Maren L., and Mark P. Styczynski. "Systems Biology-Based Investigation of Host–Plasmodium Interactions." Trends in Parasitology 34, no. 7 (July 2018): 617–32. http://dx.doi.org/10.1016/j.pt.2018.04.003.

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Zou, Jun, Ming-Wu Zheng, Gen Li, and Zhi-Guang Su. "Advanced Systems Biology Methods in Drug Discovery and Translational Biomedicine." BioMed Research International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/742835.

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Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.
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Hogstrand, C., T. S. Carroll, J. D. Rasinger, V. Reffatto, A. K. Lundebye, M. Haave, R. Tassinari, et al. "Systems biology investigation of the mechanisms of brominated flame retardant neurotoxicity." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 157 (September 2010): S4. http://dx.doi.org/10.1016/j.cbpa.2010.06.009.

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Purohit, Vinee, Allon Wagner, Nir Yosef, and Vijay K. Kuchroo. "Systems-based approaches to study immunometabolism." Cellular & Molecular Immunology 19, no. 3 (February 4, 2022): 409–20. http://dx.doi.org/10.1038/s41423-021-00783-9.

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AbstractTechnical advances at the interface of biology and computation, such as single-cell RNA-sequencing (scRNA-seq), reveal new layers of complexity in cellular systems. An emerging area of investigation using the systems biology approach is the study of the metabolism of immune cells. The diverse spectra of immune cell phenotypes, sparsity of immune cell numbers in vivo, limitations in the number of metabolites identified, dynamic nature of cellular metabolism and metabolic fluxes, tissue specificity, and high dependence on the local milieu make investigations in immunometabolism challenging, especially at the single-cell level. In this review, we define the systemic nature of immunometabolism, summarize cell- and system-based approaches, and introduce mathematical modeling approaches for systems interrogation of metabolic changes in immune cells. We close the review by discussing the applications and shortcomings of metabolic modeling techniques. With systems-oriented studies of metabolism expected to become a mainstay of immunological research, an understanding of current approaches toward systems immunometabolism will help investigators make the best use of current resources and push the boundaries of the discipline.
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Ori, Alessandro, Mark C. Wilkinson, and David G. Fernig. "A Systems Biology Approach for the Investigation of the Heparin/Heparan Sulfate Interactome." Journal of Biological Chemistry 286, no. 22 (March 30, 2011): 19892–904. http://dx.doi.org/10.1074/jbc.m111.228114.

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A large body of evidence supports the involvement of heparan sulfate (HS) proteoglycans in physiological processes such as development and diseases including cancer and neurodegenerative disorders. The role of HS emerges from its ability to interact and regulate the activity of a vast number of extracellular proteins including growth factors and extracellular matrix components. A global view on how protein-HS interactions influence the extracellular proteome and, consequently, cell function is currently lacking. Here, we systematically investigate the functional and structural properties that characterize HS-interacting proteins and the network they form. We collected 435 human proteins interacting with HS or the structurally related heparin by integrating literature-derived and affinity proteomics data. We used this data set to identify the topological features that distinguish the heparin/HS-interacting network from the rest of the extracellular proteome and to analyze the enrichment of gene ontology terms, pathways, and domain families in heparin/HS-binding proteins. Our analysis revealed that heparin/HS-binding proteins form a highly interconnected network, which is functionally linked to physiological and pathological processes that are characteristic of higher organisms. Therefore, we then investigated the existence of a correlation between the expansion of domain families characteristic of the heparin/HS interactome and the increase in biological complexity in the metazoan lineage. A strong positive correlation between the expansion of the heparin/HS interactome and biosynthetic machinery and organism complexity emerged. The evolutionary role of HS was reinforced by the presence of a rudimentary HS biosynthetic machinery in a unicellular organism at the root of the metazoan lineage.
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Asnaashari, Solmaz, Elham Amjad, and Babak Sokouti. "A comprehensive investigation on liver regeneration: a meta-analysis and systems biology approach." Clinical and Experimental Hepatology 7, no. 2 (2021): 183–90. http://dx.doi.org/10.5114/ceh.2021.107564.

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Caberlotto, Laura, and Thanh-Phuong Nguyen. "A systems biology investigation of neurodegenerative dementia reveals a pivotal role of autophagy." BMC Systems Biology 8, no. 1 (2014): 65. http://dx.doi.org/10.1186/1752-0509-8-65.

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Figeac, Nicolas, Malgorzata Daczewska, Christophe Marcelle, and Krzysztof Jagla. "Muscle stem cells and model systems for their investigation." Developmental Dynamics 236, no. 12 (2007): 3332–42. http://dx.doi.org/10.1002/dvdy.21345.

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Dissertations / Theses on the topic "Systems biology investigation"

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Gormley, Padhhraig J. "An investigation of advanced data-driven identification methods for systems biology." Thesis, Queen's University Belfast, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534735.

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Gray, Kurtis N. "A Molecular Phylogeny of the Echeneoidea (Perciformes: Carangoidei) and an Investigation of Population Structuring Within the Echeneidae." W&M ScholarWorks, 2005. https://scholarworks.wm.edu/etd/1539617836.

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Wang, Benjamin X. Ph D. Massachusetts Institute of Technology. "Investigation of two-component signaling systems in Pseudomonas aeruginosa and their roles in the mucus barrier." Thesis, Massachusetts Institute of Technology, 2021. https://hdl.handle.net/1721.1/130821.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, February, 2021
Cataloged from the official PDF of thesis.
Includes bibliographical references.
All living things must be able to sense and respond to signals in their environment in order to grow and survive. For bacteria, a common means through which this occurs is via two-component signaling systems, which are typically comprised of a membrane-bound histidine kinase that senses external cues signals, and a cognate cytoplasmic response regulator that triggers changes in gene expression. The importance of these systems is highlighted by the fact that they have been identified in the vast majority of sequenced bacteria. However, despite their prevalence, much remains to be discovered about these sensory systems. In particular, both the actual processes that these systems control, along with the signals that they sense and respond to, remain poorly characterized in many cases.
In this work, I further characterize two-component signaling systems in the opportunistic pathogen Pseudomonas aeruginosa, which is most well-known for chronically infecting the lungs of patients with cystic fibrosis. I begin by screening a collection of in-frame deletion mutants of each histidine kinase in the PA14 strain against a dozen virulence-associated phenotypes, including different types of motility, biofilm formation, virulence factor production, and antibiotic resistance. Through this approach, I identify nearly two dozen of these proteins as important regulators of virulence. As P. aeruginosa is a human-associated mucosal pathogen, I next search for host-derived signals in mucus that act through these sensory systems in P. aeruginosa. I identify mucins and their associated glycans as signals that act through the RetS histidine kinase and the GacS-GacA two-component signaling system.
One major output of this signaling is the downregulation of the type VI secretion system, which suggests that mucin glycans may serve as host-derived "safety signals" that suppress microbial competition under non-dysbiotic conditions. Finally, I characterize the molecular mechanisms by which RetS inhibits GacS activity to better understand the unusual interactions between these two histidine kinases. Overall, this work underscores the diverse and important roles that two-component signaling systems play in bacteria, and begins to shed light on how microbes like P. aeruginosa utilize these systems to sense and respond to signals in the host.
by Benjamin X. Wang.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
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Dubaj, Vladimir, and n/a. "Novel optical fluorescence imaging probe for the investigation of biological function at the microscopic level." Swinburne University of Technology, 2005. http://adt.lib.swin.edu.au./public/adt-VSWT20060905.084615.

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Existing optic fibre-bundle based imaging probes have been successfully used to image biological signals from tissue in direct contact with the probe tip (Hirano et al. 1996). These fibre-bundle probe systems employed conventional fluorescence microscopy and thus lacked spatial filtering or a scanned light source, two features used by laser scanning confocal microscopes (LSCMs) to improve signal quality. Improving the methods of imaging tissue in its natural state, deep in-vivo and at cellular resolution is an ever-present goal in biological research. Within this study, a novel (580 μm diameter) optic fibre-bundle direct-contact imaging probe, employing a LSCM, was developed to allow for improved imaging of deep biological tissue in-vivo. The new LSCM/probe system possessed a spatial resolution of 10 μm, and a temporal resolution of 1 msec. The LSCM/probe system was compared to a previously used direct-contact probe system that employed a conventional fluorescence microscope. Quantitative and qualitative data indicated that the LSCM/probe system possessed superior image contrast and quality. Furthermore, the LSCM/probe system was approximately 16 times more effective at filtering unwanted contaminating light from regions below the imaging plane (z-axis). The unique LSCM/probe system was applied to an exploratory investigation of calcium activity of both glial and neuronal cells within the whisker portion of the rat primary somatosensory cortex in-vivo. Fluorescence signals of 106 cells were recorded from 12 female Sprague Dawley rats aged between 7-8 weeks. Fluo-3(AM) fluorophore based calcium fluctuations that coincided with 10 - 14 Hz sinusoidal stimulation of rat whiskers for 0.5-1 second were observed in 8.5% of cells (9 of 106). Both increases and decreases in calcium levels that coincided with whisker stimulation were observed. Of the 8.5 % of cells, 2.8% (3 cells) were categorized as glial and 5.7% (6 cells) as neuronal, based on temporal characteristics of the observed activity. The remaining cells (97 of 106) displayed sufficient calcium-based intensity but no fluctuations that coincided with an applied stimulus. This was partially attributed to electronic noise inherent in the prototype system obscuring potential very weak cell signals. The results indicate that the novel LSCM/probe system is an advancement over previously used systems that employed direct-contact imaging probes. The miniature nature of the probe allows for insertion into soft tissue, like a hypodermic needle, and provides access to a range of depths with minimal invasiveness. Furthermore, when combined with selected dyes, the system allows for imaging of numerous forms of activity at cellular resolution.
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Price, Heather Leigh. "Investigation of larval sensory systems in the marine bryozoan, Bugula neritina." DigitalCommons@CalPoly, 2015. https://digitalcommons.calpoly.edu/theses/1410.

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Bugula neritina is a sessile marine bryozoan with a pelagic larval stage. Larvae frequently settle on boat hulls, facilitating the introduction of B. neritina to bays and estuaries worldwide. Adrenergic agonists, such as the vertebrate hormone noradrenaline, inhibit larval settlement in a variety of marine invertebrate species, including B. neritina. Light also inhibits B. neritina larval settlement, yet the underlying mechanisms by which light and adrenergic compounds exert their effects on larvae are not well understood. Octopamine is considered the invertebrate analog of noradrenaline, and may be an endogenous hormone involved in larval settlement pathways. I observed the effects of the adrenergic agonist noradrenaline and the adrenergic antagonist phentolamine on larval settlement, and found that high concentrations of noradrenaline increased larval mortality, inhibited larval attachment, and increased larval swimming behavior. High concentrations of phentolamine also increased larval mortality, but increased larval attachment and decreased larval swimming behavior. I used fluorescent labeling and microscopy to localize sensory system components, and found that larvae possess adrenergic-like receptors, as well as tyrosine hydroxylase-like and octopamine-like immunoreactivity. I also exposed larvae to phentolamine in both dark and light conditions, and found that light significantly inhibited larval attachment, but phentolamine blocked those inhibitory effects. These results suggest that B. neritina larvae possess adrenergic-like receptors, which serve as the binding sites for noradrenaline and phentolamine. These are likely octopamine receptors, and octopamine may be one endogenous compound involved in controlling larval phototaxis and settlement behavior. Light may increase octopamine production, thereby stimulating cilial activity, extending swimming behavior, and preventing larvae from attaching to a substrate. This research sheds light on previously unknown sensory mechanisms in B. neritina larvae, and may aid in the development of new biofouling control strategies.
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Hyder, Jennifer A. "An Investigation of the Effects of Increased Tidal Inundation, Competition, and Facilitation on Salt Marsh Systems." Thesis, University of South Florida, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3700275.

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The low-lying topographic nature of salt marshes makes plants in these communities particularly vulnerable to increased salinity and inundation exposure associated with sea level rise. Both increased salinity and inundation have been cited as major causes of reduced plant performance and survival in marsh and areas fringing marsh. In addition to limitations imposed by physical stress, interspecific interactions have also been shown to mediate the performance and survival of salt marsh and salt marsh fringing species. The Stress Gradient Hypothesis (SGH) postulates that species interactions shift from competitive to facilitative as stress levels increase and predicts that (a) the frequency and intensity of facilitative interactions increase as conditions become more stressful for plants and (b) the strength of competitive interactions increases as abiotic stress levels diminish. The SGH has been rigorously tested to examine how both the frequency and intensity of species interactions change under varying physical stress levels. Studies conducted in salt marsh systems have shown facilitation to be as strong of a driving force as competition in influencing plant performance and survival and have shown that while competition appears to be the pervasive force in the less physically stressful terrestrial zones fringing salt marshes, facilitation influences the performance and survival of species in harsher marsh areas. Under conditions of sea level rise, it remains unclear if the nature of interspecific interactions would shift as stress levels change. This research endeavors to examine the interplay between abiotic stresses and biotic interactions under conditions of increased salinity and inundation exposure.

The first study presented here investigated the effects of increased inundation and soil salinity associated with sea level rise on four salt marsh fringing species, and assesses how competition and facilitation impact survival of salt marsh fringing plant survival under these changing conditions. All plant species experienced reduced growth and photosynthetic inhibition below their current distributional positions, both in the presence and absence of neighboring above ground vegetation. The findings also signal a potential shift in the nature of interspecific interactions from competition to facilitation to neutral as plants begin to experience increased salt and inundation exposure.

The second study aimed to disentangle the effects of increased soil salinity and increased soil moisture on four salt marsh fringing species, and to examine the effects of plant neighbors. The results showed that fringe plants exposed to increased inundation experienced a two-fold reduction in performance and survival over 750 g pure salt addition, suggesting that inundation may be a more important limiting factor than salinity with rising sea levels. Landward transplants at the forest-fringe margin exposed to lower soil salinity and decreased inundation exhibited a three-fold increase in performance and survival when compared to controls. Neighbor manipulation studies, which consisted of trimming neighboring vegetation to ground level, again suggested that interspecific interactions in salt marsh fringing species may shift from competitive to facilitative with climate-induced sea level rise. Overall, our findings suggest that salt marsh fringing species may not be able to tolerate changing conditions associated with sea level rise and their survival may hinge on their ability to migrate towards higher elevations.

The final experiment tested the Stress Gradient Hypothesis and investigated the relative importance of facilitation and competition in a salt marsh system under varying stress levels. This study also ascertained whether salt or inundation exposure is the primary influence on salt marsh plant performance and survival. As in previous studies, our findings suggest that many salt marsh plants don't require, but merely tolerate harsher abiotic conditions. The results showed that plants at higher elevations were depressed by strong competitive pressure from neighboring fringe species while plants at lower elevations benefited from the presence of neighbors. Collectively, the results of these studies indicate that species interactions are an integral driver of plant distribution in salt marsh communities. Furthermore, our findings indicate that changing stress levels may not always result in a shift in the nature of interspecific interactions. These studies have endeavored to show that the interplay between competition and facilitation interacts with physical processes to determine the growth and performance of both fringe and marsh plant species. The paucity of studies examining the roles of species interactions and changing abiotic stress levels on multiple salt marsh and salt marsh fringing species warrants the need for additional research. The responses of salt marsh and salt marsh fringing species to sea level rise can not only serve as very valuable and sensitive indictors of climate change, but will also aid in predicting the future location of the marsh-fringe-forest ecotone, which is predicted to shift inland as sea levels continue to rise.

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Britton, Oliver Jonathan. "Combined experimental and computational investigation into inter-subject variability in cardiac electrophysiology." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:6299240d-0528-4662-8e1f-5025f39e730f.

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The underlying causes of variability in the electrical activity of hearts from individuals of the same species are not well understood. Understanding this variability is important to enable prediction of the response of individual hearts to diseases and therapies. Current experimental and computational methods for investigating the behaviour of the heart do not incorporate biological variation between individuals. In experimental studies, experimental results are averaged together to control errors and determine the average behaviour of the studied organism. In computational studies, averaged experimental data is usually used to develop models, and these models therefore represent a 'typical' organism, with all information on variability within the species having been lost. In this thesis we develop a methodology for modelling variability between individuals of the same species in cardiac cellular electrophysiology, motivated by the inability of traditional computational modelling approaches to capture experimental variability. A first study is conducted using traditional modelling approaches to investigate potentially pro-arrhythmic abnormalities in rabbit Purkinje fibres. A comparison with experimental recordings highlights their wide variability and the inability of existing computer modelling approaches to capture it. This leads to the development of a novel methodology that integrates the variability observed in experimental data with computational modelling and simulation, by building experimentally-calibrated populations of computational models, that collectively span the variability seen in experimental data. We apply this methodology to construct a population of rabbit Purkinje cell models. We show that our population of models can quantitatively predict the range of responses, not just the average response, to application of the potassium channel blocking drug dofetilide. This demonstrates an important potential application of our methodology, for predicting pro-arrhythmic drug effects in safety pharmacology. We then analyse a data set of experimental recordings from human ventricular tissue preparations, and use this data to develop a population of human ventricular cell models. We apply this population to study how variability between individuals alters the susceptibility of cardiac cells to developing drug-induced repolarisation abnormalities. These abnormalities can increase the chance of fatal arrhythmias, but the mechanisms that determine individual susceptibility are not well-understood.
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Parikh, Jaimit B. "Theoretical Investigation of Intra- and Inter-cellular Spatiotemporal Calcium Patterns in Microcirculation." FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/1927.

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Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca2+) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC and SMC, coupled EC-SMC and a multi-cellular vessel segment with deterministic and stochastic descriptions of the cellular components were developed, and the intra- and inter-cellular spatiotemporal Ca2+ mobilization was examined. Coupled EC-SMC model simulations captured the experimentally observed localized subcellular EC Ca2+ events arising from the opening of EC transient receptor vanilloid 4 (TRPV4) channels and inositol triphosphate receptors (IP3Rs). These localized EC Ca2+ events result in endothelium-derived hyperpolarization (EDH) and Nitric Oxide (NO) production which transmit to the adjacent SMCs to ultimately result in vasodilation. The model examined the effect of heterogeneous distribution of cellular components and channel gating kinetics in determination of the amplitude and spread of the Ca2+ events. The simulations suggested the necessity of co-localization of certain cellular components for modulation of EDH and NO responses. Isolated EC and SMC models captured intracellular Ca2+ wave like activity and predicted the necessity of non-uniform distribution of cellular components for the generation of Ca2+ waves. The simulations also suggested the role of membrane potential dynamics in regulating Ca2+ wave velocity. The multi-cellular vessel segment model examined the underlying mechanisms for the intercellular synchronization of spontaneous oscillatory Ca2+ waves in individual SMC. From local subcellular events to integrated macro-scale behavior at the vessel level, the developed multi-scale models captured basic features of vascular Ca2+ signaling and provide insights for their physiological relevance. The models provide a theoretical framework for assisting investigations on the regulation of vascular tone in health and disease.
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Chee, Meng May. "Investigations into telomere biology in systemic sclerosis." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3615/.

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Systemic sclerosis (SSc) is a complex multisystem autoimmune connective tissue disease of yet unknown aetiology. It is characterised by vascular damage, autoimmunity and progressive fibrosis in the skin and internal organs, with 2 main subsets of disease: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), classified mainly according to skin involvement. Although there has been tremendous progress in the understanding and treatment of autoimmune diseases in the last 20 years, SSc remains a disease with high morbidity and mortality, with no proven treatments that improve long-term outcome. There is therefore a need to improve the understanding of such a devastating disease to facilitate the development of future treatments and improve the prognosis for patients with SSc. Telomeres are nucleo-protein complexes, comprising tandem TTAGGG repeats at the ends of eukaryotic chromosomes, which protect the chromosomes from end-to-end fusion, recombination and degradation. There are a variety of telomere binding proteins which maintain telomere stability and function in sensing, signalling and repairing DNA damage. Telomere lengths have been used as a marker of biological aging for over a decade, and the technologies for measuring telomere lengths have also advanced in recent years. Quantitative real time PCR (QPCR) has now superseded Southern Blotting (SB) for telomere length measurements. Telomere erosion has been implicated in a wide range of diseases and its impact on autoimmune diseases remains unclear. As SSc is associated with particular autoantibodies which have been linked to telomeres, this thesis sought to explore telomere biology in SSc. Initial work measuring telomere lengths in SSc patients using the SB method revealed surprising results, with a lack of age-related telomere erosion in patients with lcSSc, which was in contrast to published literature at the time. The aim of this research was to measure telomere lengths of peripheral blood mononuclear cells (PBMC) in patients with SSc and related connective tissue diseases using QPCR, with the hypothesis that telomere lengths would be shorter in disease, and to explore telomere binding protein genes, with a view to gaining insight into any mechanistic differences in telomere biology in the different subsets of disease. Measurement of telomere lengths of PBMC from healthy controls and patients using QPCR showed that telomere lengths were significantly shorter in disease compared to controls, but when adjusted for age, there was no statistically significant difference in telomere lengths of patients with lcSSc compared to controls. Taking into account the complexity of telomere biology, it is possible that mediators of the inflammatory reaction at the systemic level or autoantibodies against nucleoprotein complexes directly or indirectly interfere with the homeostasis of telomere length in blood. This could occur through disrupting the proteins of the shelterin complex or associated factors relating to DNA repair. Hence, the gene expression of telomere binding proteins and other genes associated with inflammation and DNA repair were explored in patients with SSc using Taqman Low Density Arrays. The majority of these genes were under expressed in disease compared to controls, but when samples were age-matched, only 4 genes were under-expressed in patients with dcSSc: BCL2, POT1, SIRT6 and WRN, and 4 genes were under-expressed in lcSSc: ATM, BCL2, STAU1 and WRN. There was no correlation between telomere lengths and gene expression. These observations are intriguing, and the role of BCL2 and WRN merit further investigation in patients with SSc. This work has confirmed that telomeres shorten with age and disease, in keeping with the original hypothesis and published literature. However, there was no significant difference in age-related telomere erosion in patients with lcSSc. Gene expression analysis of telomere associated genes in SSc revealed lower expression in disease compared with controls. Whether this observation is a cause or effect of disease remains to be proven, but suggests that telomeres may be implicated in the pathophysiology of SSc and there are mechanistic differences between the subsets of disease.
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Wilcock, Paul. "A systems biology approach for investigating oral squamous cell carcinoma (OSCC)." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/a-systems-biology-approach-for-investigating-oral-squamous-cell-carcinoma-oscc(8ec3728b-1928-450f-b467-76996fa970fb).html.

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A systems biology approach was adopted in order to assess various aspects of the disease oral squamous cell carcinoma. Three main aims were addressed; assess the ability of CoCl2 to mimic the hypoxic response in a eukaryotic cell line, assess the role of PDE4D in oral squamous cell carcinoma (OSCC) and the construction of a normoxic/hypoxic mathematical model to identify therapeutic targets.Cancer cells often acquire a revised metabolism which aids in initiation, survival and progression of the tumour. This is predominantly due to the transcription factor HIF-1 which is activated under hypoxic conditions. Certain compounds such as cobalt chloride (CoCl2) have been used extensively to inhibit the degradation of HIF-1α and simulate hypoxia. CoCl2 is likely to have off-target effects on metabolism; these effects were examined when exposing human telomerase reverse transcriptase (hTERT) cells to 100μM CoCl2. Gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) based metabolomics were utilised in combination with ELISA assays for HIF-1α and ATP. Central metabolism was accurately mimicked when hTERT cells were subjected to 100μM CoCl2, however; it was apparent that this concentration of CoCl2 does not induce an equal extent of hypoxia as 1% oxygen. A number of off-target effects of CoCl2 were observed in secondary metabolism, specifically in lipids and fatty acids. In conclusion, CoCl2 should be used with caution as a hypoxic mimicker with the caveat that interpretation of results should be restricted to its effects on central metabolism.The transcription factor CREB has the ability to regulate approximately 4000 genes, a number of which are associated with cancer initiation and progression. Cyclic adenosine monophosphate (cAMP) is required to activate CREB and is partially regulated through its degradation via the enzyme phosphodiesterase type 4D (PDE4D). A homozygous deletion of PDE4D has been associated with OSCC; however; the exact consequence of this deletion has not been fully elucidated. PDE4D was knocked down in the OSCC cell line BicR16 and cellular proliferation, migration, resistance to ionising radiation and central metabolism was investigated using MTT, scratch, clonogenic and GC-MS, respectively. The knockdown resulted in an increase in proliferation, migration and radiation resistance suggesting the role of PDE4D as a TSG. Amino acids, cholesterol, fatty acids, carbohydrates and TCA intermediates were found to be altered in concentration.A mathematical model of glycolysis, TCA and glutaminolysis under normoxia and hypoxia was constructed through the amalgamation of two established models from the literature. New reactions, parameters and metabolite concentrations were added and unnecessary entities were deleted. COmplex PAthway SImulator (COPASI) was utilised to construct the model before validating the model using experimental data from the literature and steady state and flux analyses. Sensitivity analysis and a reduction in external glucose and glutamine were mimicked and the alterations in hypoxic and normoxic metabolism analysed. The reactions vCSII, vGS, vPGK and vGII were identified as potential therapeutic targets which may affect metabolism in hypoxia only. However, certain validation methods proved unsuccessful and hence the model requires further work before attempting the analyses again.
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Books on the topic "Systems biology investigation"

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Winthrop University. Department of Biology, ed. Biology 151: Laboratory manual: investigations into living systems. Mason, OH: Cengage Learning, 2008.

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Three-Dimensional Confocal Microscopy: Volume Investigation of Biological Specimens: Volume Investigation of Biological Specimens (Cell Biology). Academic Press, 1994.

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(Editor), John K. Stevens, Linda R. Mills (Editor), Judy E. Trogadis (Editor), Dennis E. Buetow (Series Editor), Ian T. Cameron (Series Editor), G. M. Padilla (Series Editor), and A. M. Zimmerman (Series Editor), eds. Three-Dimensional Confocal Microscopy: Volume Investigation of Biological Specimens: Volume Investigation of Biological Specimens (Cell Biology). Academic Press, 1994.

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Three-dimensional confocal microscopy: Volume investigation of biological specimens. San Diego: Academic Press, 1994.

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Burton, Derek, and Margaret Burton. Essential Fish Biology. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780198785552.001.0001.

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This book summarizes the basic features of living fish. It is introduced by a chapter on the diversity of a group which has over 30,000 species, the largest within the vertebrates, describing the classification systems used for them and the variety of their habitats and morphology. Thereafter the physiology of fish is described and discussed initially by categories such as the outer boundary (the skin), the circulatory system, food processing, reproduction, hormones as integrators and controllers, the nervous system and the very complex set of sensory receptors including the eyes, ears, lateral line and electro-receptors. Unusual structures, adaptations and behaviours reveal the breadth of fish lifestyles from deep-ocean to shallow reef habitats, with both fresh water and marine margins favouring some near-terrestrial forms even emerging to spawn. With enormous ranges of size, shape and lifecycles, fish are capable of extreme longevity and amazing adjustments to their environment, including colour change, light emission by photophores and sporadic hermaphroditism (both sexes in one individual). The use of fish types by scientists is discussed. Referenced throughout, the scope of the book includes reviews of historically important and recent discoveries and some speculation on the future for fish and fish conservation. Appendices are provided to give in-depth information on some topics, including material briefly describing practical procedures, relevant to experimentation and aquaculture, which may prompt further investigation. The glossary with explanations of terms, and the copious illustrations help understanding of this complex subject area.
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Kaskel, Albert, Paul Jr Hummer, Raymond F. Oram, and James E. Kennedy. Laboratory Biology: Investigating Living Systems. Merrill Pub Co, 1999.

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Study, Biological Sciences Curriculum. Investigating Systems and Change. Kendall/Hunt Publishing Company, 1993.

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Kauffman, Stuart A. Investigations. Oxford University Press, USA, 2000.

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Kauffman, Stuart A. Investigations. Oxford University Press, 2000.

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Kauffman, Stuart A. Investigations. Oxford University Press, 2002.

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Book chapters on the topic "Systems biology investigation"

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Thomas-Vaslin, Véronique, Adrien Six, Bertrand Bellier, and David Klatzmann. "Lymphocyte Labeling, Cell Division Investigation." In Encyclopedia of Systems Biology, 1152–54. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-9863-7_708.

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Cong, Xiao, John W. Patrick, Yang Liu, Xiaowen Liang, Wen Liu, and Arthur Laganowsky. "Investigation of Protein–Lipid Interactions Using Native Mass." In Microbial Systems Biology, 41–64. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1585-0_3.

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Ramji, Dipak P., Alaa Ismail, Jing Chen, Fahad Alradi, and Sulaiman Al Alawi. "Survey of Model Systems for Investigation of Key Associated with." In Methods in Molecular Biology, 39–56. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-1924-7_3.

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Desoeuvres, Aurélien, Peter Szmolyan, and Ovidiu Radulescu. "Qualitative Dynamics of Chemical Reaction Networks: An Investigation Using Partial Tropical Equilibrations." In Computational Methods in Systems Biology, 61–85. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-15034-0_4.

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Ramanathan, S., A. K. Wright, and G. W. Arbuthnott. "A Physiological Investigation of the Two Corticostriatal Systems in Rat Somatsensory Striatum." In Advances in Behavioral Biology, 389–97. Boston, MA: Springer US, 2002. http://dx.doi.org/10.1007/978-1-4615-0715-4_39.

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Rowden, Stephen J. L., Paolo Bombelli, and Christopher J. Howe. "Biophotovoltaics: Design and Study of Bioelectrochemical Systems for Biotechnological Applications and Metabolic Investigation." In Methods in Molecular Biology, 335–46. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7786-4_20.

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Traynard, Pauline, François Fages, and Sylvain Soliman. "Model-Based Investigation of the Effect of the Cell Cycle on the Circadian Clock Through Transcription Inhibition During Mitosis." In Computational Methods in Systems Biology, 208–21. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-23401-4_18.

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Bersch, Beate, Matthew R. Groves, Johann P. Klare, Andrew E. Torda, and Darío Ortiz de Orué Lucana. "Applications of Structural Biology and Bioinformatics in the Investigation of Oxidative Stress-Related Processes." In Systems Biology of Free Radicals and Antioxidants, 505–34. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-30018-9_196.

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Wang, Yu-Chao, and Bor-Sen Chen. "Network Biomarker Construction for Molecular Investigation and Diagnosis of Lung Cancer via Microarray Data." In A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems, 3–29. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-9047-5_1.

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Krishnan, J., and C. Liu. "An Investigation of Signal Transduction and Irreversible Decision Making Through Monostable and Bistable Switches." In A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems, 219–43. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-9047-5_9.

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Conference papers on the topic "Systems biology investigation"

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"The investigation of Poly(ADP-ribose)polymerase activity in the context of nucleosome." In SYSTEMS BIOLOGY AND BIOINFORMATICS. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 2019. http://dx.doi.org/10.18699/sbb-2019-20.

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Glier, Michael W., Daniel A. McAdams, and Julie S. Linsey. "An Experimental Investigation of Analogy Formation Using the Engineering-to-Biology Thesaurus." In ASME 2013 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/detc2013-13160.

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Identifying applicable biological systems for engineering design remains a persistent challenge for bioinspired design. Previous researchers have proposed an Engineering-to-Biology thesaurus that allows designers to identify biological keywords that are functionally similar to terms in the Functional Basis. This work presents an experimental examination of the effectiveness of the Engineering-to-Biology thesaurus. A group of 100 mechanical engineering students are presented with a simple design problem: to create a device to remove the husk and silk from ears of corn. The participants read passages drawn from a large biology corpus with keywords from the Engineering-to-Biology thesaurus and indicate which passages prompt some idea for solving the design problem. The analysis of student responses indicates that students’ level of design training is not a significant factor in the number of analogies they found in the passages and that some non-random criteria is used to identify passages as useful for idea generation. Passages that rarely offer participants ideas can be reasonably well classified as either being too technical for a lay-reader to understand or lacking information on a biological system. Passages that typically offer ideas cannot be so easily classified. Finally, keywords from the Engineering-to-Biology thesaurus are examined to find that keywords very specific to biology and those that are very common words with multiple meanings are rarely contained in sentences that offer strong design inspiration.
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"Investigation of the role of alternative splicing." In Bioinformatics of Genome Regulation and Structure/ Systems Biology. institute of cytology and genetics siberian branch of the russian academy of science, Novosibirsk State University, 2020. http://dx.doi.org/10.18699/bgrs/sb-2020-288.

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"Detection and investigation of genes with circadian expression pattern in common wheat." In Bioinformatics of Genome Regulation and Structure/ Systems Biology. institute of cytology and genetics siberian branch of the russian academy of science, Novosibirsk State University, 2020. http://dx.doi.org/10.18699/bgrs/sb-2020-201.

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"Investigation of various hemodynamic regimes in elastic vessels." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-132.

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Kozak, Maciej, Carlos Granja, Claude Leroy, and Ivan Stekl. "Small Angle X-ray Scattering in Structural Investigation of Selected Biological Systems." In Nuclear Physics Medthods and Accelerators in Biology and Medicine. AIP, 2007. http://dx.doi.org/10.1063/1.2825775.

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Sehndkar C V, Mahadevappa M., Lenka P K, Kumar Ratnesh, and Biswas A. "Efficacy of FES for restoring hand grasp in hemiplegia: Investigation using biosignals." In 2016 International Conference on Systems in Medicine and Biology (ICSMB). IEEE, 2016. http://dx.doi.org/10.1109/icsmb.2016.7915074.

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Egan, Paul F., Jonathan Cagan, Christian Schunn, and Philip R. LeDuc. "Utilizing Emergent Levels to Facilitate Complex Systems Design: Demonstrated in a Synthetic Biology Domain." In ASME 2013 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/detc2013-12072.

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Designing complex systems often requires consideration of many components interacting across vast scales of space and time, thus producing highly challenging design spaces to search. In particular, nano-based technologies may require considerations of how nanoscale (10−9) embodiments affect macroscale (∼100) systems and typically have multiple layers of emergent behavior. It is frequently cited that counter-intuitive properties of emergence complicates design tasks; however, we investigate whether some multiscale emergent systems have organizational levels that may inform more effective design methods and searches. Investigations are conducted by extending an agent-based simulation that predicts the emergent interactions of myosin motors interacting with a motile actin filament. Both the behaviors of individual motors and an ensemble of motors are stochastic, therefore analytical methods are often unable to form accurate design evaluations and computationally intensive simulations are required for investigation. Our modification of the simulation enables the prediction of the duration of time that motors will carry an actin filament before system dissociation (termed its processive life-time), which is a vital performance metric for future nanotechnology designs such as molecular sorters. Virtual experiments were conducted that determines how perturbations of synthetic myosin design configurations, and the number of myosins present, affects emergent ensemble performance with respect to run-length and energy usage. It is found that all systems have nearly identical average processive life-times for a given input energy regardless of how much energy individual myosins utilize. Such a finding reduces the total information that a designer must consider, since it is a fundamental relationship that holds regardless of lower level component configurations. Such relationships may occur in complex systems in additional domains, and knowledge of these emergent relationships could greatly facilitate the efficiencies of design methods and automated searches for future technologies.
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Qureshi, T. R., C. R. Chatwin, Zhou Zhou, Nan Li, and W. Wang. "Investigation of voltage source design's for electrical impedance mammography (EIM) systems." In 2012 34th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2012. http://dx.doi.org/10.1109/embc.2012.6346246.

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"Investigation of structure differences between archaeal and human translation initiation factor 2." In Systems Biology and Bioinformatics (SBB-2021) : The 13th International Young Scientists School;. ICG SB RAS, 2021. http://dx.doi.org/10.18699/sbb-plantgen-2021-17.

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Reports on the topic "Systems biology investigation"

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Gottlieb, Yuval, Bradley Mullens, and Richard Stouthamer. investigation of the role of bacterial symbionts in regulating the biology and vector competence of Culicoides vectors of animal viruses. United States Department of Agriculture, June 2015. http://dx.doi.org/10.32747/2015.7699865.bard.

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Symbiotic bacteria have been shown to influence host reproduction and defense against biotic and abiotic stressors, and this relates to possible development of a symbiont-based control strategy. This project was based on the hypothesis that symbionts have a significant impact on Culicoides fitness and vector competence for animal viruses. The original objectives in our proposal were: 1. Molecular identification and localization of the newly-discovered symbiotic bacteria within C. imicola and C. schultzei in Israel and C. sonorensis in California. 2. Determination of the prevalence of symbiotic bacteria within different vector Culicoides populations. 3. Documentation of specific symbiont effects on vector reproduction and defense: 3a) test for cytoplasmic incompatibility in Cardinium-infected species; 3b) experimentally evaluate the role of the symbiont on infection or parasitism by key Culicoides natural enemies (iridescent virus and mermithid nematode). 4. Testing the role(s) of the symbionts in possible protection against infection of vector Culicoides by BTV. According to preliminary findings and difficulties in performing experimental procedures performed in other insect symbiosis systems where insect host cultures are easily maintained, we modified the last two objectives as follows: Obj. 3, we tested how symbionts affected general fitness of Israeli Culicoides species, and thoroughly described and evaluated the correlation between American Culicoides and their bacterial communities in the field. We also tried alternative methods to test symbiont-Culicoides interactions and launched studies to characterize low-temperature stress tolerances of the main US vector, which may be related to symbionts. Obj. 4, we tested the correlation between EHDV (instead of BTV) aquisition and Cardinium infection. Culicoides-bornearboviral diseases are emerging or re-emerging worldwide, causing direct and indirect economic losses as well as reduction in animal welfare. One novel strategy to reduce insects’ vectorial capacity is by manipulating specific symbionts to affect vector fitness or performance of the disease agent within. Little was known on the bacterial tenants occupying various Culicoides species, and thus, this project was initiated with the above aims. During this project, we were able to describe the symbiont Cardinium and whole bacterial communities in Israeli and American Culicoides species respectively. We showed that Cardinium infection prevalence is determined by land surface temperature, and this may be important to the larval stage. We also showed no patent significant effect of Cardinium on adult fitness parameters. We showed that the bacterial community in C. sonorensis varies significantly with the host’s developmental stage, but it varies little across multiple wastewater pond environments. This may indicate some specific biological interactions and allowed us to describe a “core microbiome” for C. sonorensis. The final set of analyses that include habitat sample is currently done, in order to separate the more intimately-associated bacteria from those inhabiting the gut contents or cuticle surface (which also could be important). We were also able to carefully study other biological aspects of Culicoides and were able to discriminate two species in C. schultzei group in Israel, and to investigate low temperature tolerances of C. sonorensis that may be related to symbionts. Scientific implications include the establishment of bacterial identification and interactions in Culicoides (our work is cited in other bacteria-Culicoides studies), the development molecular identification of C. schultzei group, and the detailed description of the microbiome of the immature and matched adult stages of C. sonorensis. Agricultural implications include understanding of intrinsic factors that govern Culicoides biology and population regulation, which may be relevant for vector control or reduction in pathogen transmission. Being able to precisely identify Culicoides species is central to understanding Culicoides borne disease epidemiology.
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