Dissertations / Theses on the topic 'Network physiology'
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Degabriele, Robert, University of Western Sydney, and of Informatics Science and Technology Faculty. "Stress and the immune network." THESIS_FIST_XXX_Degabriele_R.xml, 1999. http://handle.uws.edu.au:8081/1959.7/406.
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The clonal selection/defence paradigm appears unable to reconcile immune function with homeostatic activity whereas organismic homeostasis is central to immune function in the network/autopoiesis paradigm. The aim of this investigation, therefore, was to test the proposition that immune function, that is not clonally driven (central immune system activity), contributes to organismic homeostasis in collaboration with psychoneural responses. In one experiment sheep were confined, either in groups or individually, and the time course of changes in cortisol levels, behaviour and T lymphocyte numbers were monitored. In another study, soldiers were monitored during the stressful experience of recruit training. The combined results suggest that, at least when the immune response is not clonally driven, the psychoneural system and the central immune system may not be operating independently of each other but rather as sub-networks of the organismic network. Consequently, homeostasis is properly characterised as a property of the whole organism. In autopoietic terms, then, homeostasis could be defined as the maintenance of network stability.Doctor of Philosophy (PhD)
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Degabriele, Robert. "Stress and the immune network." Thesis, Campbelltown, N.S.W. : University of Western Sydney, Macarthur, Faculty of Informatics, Science and Technology, 1999. http://handle.uws.edu.au:8081/1959.7/406.
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The clonal selection/defence paradigm appears unable to reconcile immune function with homeostatic activity whereas organismic homeostasis is central to immune function in the network/autopoiesis paradigm. The aim of this investigation, therefore, was to test the proposition that immune function, that is not clonally driven (central immune system activity), contributes to organismic homeostasis in collaboration with psychoneural responses. In one experiment sheep were confined, either in groups or individually, and the time course of changes in cortisol levels, behaviour and T lymphocyte numbers were monitored. In another study, soldiers were monitored during the stressful experience of recruit training. The combined results suggest that, at least when the immune response is not clonally driven, the psychoneural system and the central immune system may not be operating independently of each other but rather as sub-networks of the organismic network. Consequently, homeostasis is properly characterised as a property of the whole organism. In autopoietic terms, then, homeostasis could be defined as the maintenance of network stability.
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Degabriele, Robert. "Stress and the immune network /." Campbelltown, N.S.W. : University of Western Sydney, Macarthur, Faculty of Informatics, Science and Technology, 1999. http://library.uws.edu.au/adt-NUWS/public/adt-NUWS20030520.152905/index.html.
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Wikström, Martin. "Dopaminergic and serotonergic modulation of cellular and locomotor network properties in the lamprey spinal cord /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3731-1/.
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Walker, Valerie. "Human «ether-a-go-go» related gene trafficking is dependent on a cytosolic chaperone network." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86804.
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Long QT Syndrome is a cardiac disorder associated with ventricular arrhythmias that can lead to syncope and sudden death. Loss of function mutations in the human ether-a-go-go related gene (hERG/KCNH2) potassium channel underlie type 2 long-QT syndrome (LQT2). Most often this loss of function is a consequence of defective trafficking of hERG mutants to the cell surface, with channel retention and degradation at the endoplasmic reticulum. This study began with a proteomics screen conducted to search for hERG-interacting proteins that were important for its folding, trafficking, and degradation. The resulting list of putative interactors was huge and included several known components of the cytosolic chaperone network which became the focus of this work. Among them were Hsc70 (70 kDa heat shock cognate protein), Hsp90 (90 kDa heat shock protein), DJA1, Hop (Hsp-organizing protein) and Bag-2 (BCL-associated athanogene 2) as well as the membrane-bound FKBP38 (38 kDa FK506-binding protein; FKBP8). We first demonstrate that FKBP38 immunoprecipitates and co-localizes with hERG in our cellular system and that siRNA knockdown of FKBP38 causes a reduction in hERG trafficking. Next, we identify DJA1 (DNAJA1) and DJA2 (DNAJA2) as key modulators of hERG degradation. Overexpression of the DJAs reduces hERG trafficking efficiency; an effect eliminated by the proteasomal inhibitor lactacystin or with DJA mutants lacking their J domains essential for Hsc70/Hsp70 activation. Both DJA1 and DJA2 cause a decrease in the amount of hERG complexed with Hsc70, indicating a preferential degradation of the complex. Similar effects were observed with the E3 ubiquitin ligase CHIP (C terminus of Hsc70 interacting protein). Finally, we investigate the specific role that these chaperones play in hERG folding. Development of a limited proteolysis assay is used to determine the folding state of hERG as well as its chaperone-dependence. Our results suggest that only subtle differencesLe syndrome du long QT est un trouble cardiaque associé à des arythmies ventriculaires qui peuvent conduire à des syncopes et à la mort subite. Les mutations conduisant à la perte de function de la gene de human ether-a-go-go related gene (hERG/KCNH2) cause le syndrome long QT de type 2 (LQT2). Le plus souvent, cette perte de fonction est une conséquence du trafic défectueux des mutants de hERG à la surface de la cellule, que font retenus et dégradé dans le réticulum endoplasmique. Cette étude a commencé par un criblage protéomique à la recherche des protéines que interagissent avec hERG et qui sont importantes pour son pliage, son trafic et sa dégradation. La liste des presumés protéins que interagissent est énorme et comprend plusieurs composants connus du reseau des chaperons citosoliques qui ont fait l'objet de ce travail. Parmi eux, Hsc70 (la protein connexe du choc thermique de 70 kDa), Hsp90 (la protein connexe du choc thermique de 90 kDa), DJA1, Hop (HSP-organisation de protéine) et de sacs-2 (BCL-associés athanogene 2) ainsi que de la FKBP38 membranaire (38 kDa FK506-binding protein; FKBP8). Nous avons d'abord démontré que FKBP38 immunoprecipite et co-localise avec hERG dans notre système cellulaire et que l'inhibition de la synthèse de FKBP38 par siRNA provoque une baisse du trafic du hERG. Ensuite, nous avons identifié DJA1 (DNAJA1) et DJA2 (DNAJA2) en tant que modulateurs clé de la dégradation du hERG. La surexpression de la DJAs réduit l'efficacité du traffic du hERG, un effet éliminé par un inhibiteur des protéosomes (lactacystin) ou avec des mutants dépourvus de leur domaines J Hsc70/Hsp70 essentiels pour l'activation. Les deux DJA1 et DJA2 entraînent une diminution de la quantité du complexe hERG-Hsc70, indiquant une dégradation préférentielle du complexe. Des effets similaires ont été observés avec la ligase E3 de l'ubiquitine CHIP (C terminus de Hsc70 interacting protein). Enfin, nous avons
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Gopal, Priyanka. "Network Analysis Reveals Aberrant Cell Signaling in Murine Diabetic Kidney." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1427997192.
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Yin, Wenzhe. "Arabidopsis MS1 functions as a hub in the transcriptional regulatory network of late tapetum development." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/43214/.
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The development of the pollen grains within the anther locule relies upon the nourishing and secretory properties of a tissue layer termed tapetum. The transition of the post-meiotic phase of tapetum development depends on the MALE STERILITY 1. In the ms1 mutant tapetum development is arrested post-meiosis and lacks subsequent biological processes, such as biosynthesis and secretion of pollen wall/coat components and the tissue programmed cell death process. MS1 exhibits a transient expression pattern, which is tightly regulated and critical for tapetum development and viable pollen formation. Therefore, understanding the genetic control of MS1 is key to uncover the regulation of post-meiotic tapetum development. During this project, three regulation levels of MS1 were studied: (i) transcriptional activation, (ii) auto-repression and (iii) post-translational proteolysis. Phylogenetic footprinting analysis and molecular promoter dissection was used to investigate the transcriptional control of expression and a distal upstream sequence (−2900 to −2066 bp) was found to be essential for the activation of MS1. Three evolutionarily conserved non-coding sequences (CNS), enriched with unusually long consensus motifs, and binding site combinations of MS1 upstream transcription factors (TFs) were found within the −2 kb MS1 upstream sequence. These may serve as essential cis-regulatory elements (CREs) for MS1 expression. ChIP experiments were used to investigate MS1 autorepression; the MS1 protein was shown to bind to the second exon of its genomic locus and to repress its own expression. Post-translational proteolysis was investigated using a triple mutant of the MS1 interacting gene that encodes for an E3 ubiquitin ligase LRB1 and its two paralogs LRB2 and LRB3; which exhibits a novel tapetum phenotype that may be induced by altered removal of MS1 protein in the lrb123 tapetum. The MS1 protein possesses a Plant Homeotic Domain (PHD) finger and belongs to a plant-specific C-terminal PHD contained protein (CPCP) family. Although extensive research has been carried out on the tapetum regulation role of MS1, very little is known about the underlying molecular mechanism. A series in-silico comparative analysis of the CPCP sequences in this thesis found that this family originated from green algae. Besides the PHD, two evolutionarily conserved domains, termed MS1/MMD1 Associated Domain 1 (MAD1) and MAD2, were identified in the protein. Molecular modelling of the MS1 PHD domain predicted a histone reader role with high affinity to H3K4me2/3 histone peptides. Super-resolution STED confocal observation showed that subnuclear localisation of the MS1 protein is distinctive with canonical TFs and aggregates at rounded speckles that resemble Polycomb bodies. A meta-data-analysis of MS1 microarrays found that most MS1 immediately responding genes are repressed by MS1, which is on the contrary to the previously proposed activator role of MS1. MS1 may therefore be a unique plant-specific histone reader family protein that participates in gene repression as a co-repressor. MYB99 has previously been hypothesised to be a direct target of MS1, regulating late tapetum development. Comprehensive phenotyping was carried out on two MYB99 null alleles; however, no defects were identified, probably due to high function redundancy among the MYB family TFs. In addition, no evidence of direct activation by MS1 was observed by yeast one-hybrid and ChIP analysis. Interestingly, a PCD indicator gene was down-regulated in the myb99 mutant, suggesting a tapetal PCD regulatory role for MYB99.
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Turan, Nil. "A network inference approach to understanding musculoskeletal disorders." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4863/.
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Musculoskeletal disorders are among the most important health problem affecting the quality of life and contributing to a high burden on healthcare systems worldwide. Understanding the molecular mechanisms underlying these disorders is crucial for the development of efficient treatments. In this thesis, musculoskeletal disorders including muscle wasting, bone loss and cartilage deformation have been studied using systems biology approaches. Muscle wasting occurring as a systemic effect in COPD patients has been investigated with an integrative network inference approach. This work has lead to a model describing the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. This model has shown for the first time that oxygen dependent changes in the expression of epigenetic modifiers and not chronic inflammation may be causally linked to muscle dysfunction. Bone and cartilage deformation observed in ageing, arthritis and multiple myeloma (MM) patients have also been investigated by using a novel modularization approach developed within this thesis. This methodology allows integration of multi-level dataset with large interaction networks. It aims to identify sub-networks with genes differentially expressed between experimental conditions that are co-regulated across samples in different biological systems. This study has identified several potential key players such as Myc, DUSP6 and components of Notch that could enhance osteogenic differentiation in MM patients. In conclusion, this thesis present the effectiveness of systems biology approaches in understanding complex diseases and these approaches could be applied for studying other systems and datasets.
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Tegnér, Jesper. "Modulation of cellular mechanisms in a spinal locomotor network : an experimental and computational study in Lamprey /." Stockholm, 1997. http://diss.kibic.ki.se/1997/19970902tegn.
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Krieger, Patrik. "On the role of metabotropic glutamate receptors in motor control : analysis of synaptic, cellular and network properties /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4449-0/.
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Gao, Xiang, and 高翔. "Exploring the regulatory network and physiological significance of the dipeptide transport system during anaerobic adaptation in Escherichia coli." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/211154.
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Cope, Thomas Edmund. "The physiology of dementia : network reorganisation in progressive non-fluent aphasia as a model of neurodegeneration." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275884.
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The dementias are persistent or progressive disorders affecting more than one cognitive domain that interfere with an individual’s ability to function at work or home, and represent a decline from a previous level of function. In this thesis I consider the neurophysiology of dementia at a number of levels. I investigate the ways in which the connectivity and function of the brain predisposes to the specific focal patterns of neurodegeneration seen in the various dementias. I aim to identify the mesoscopic changes that occur in individuals with neurodegeneration and how these relate to their cognitive difficulties. I show how, by assessing patients in whom there is focal disruption of brain networks and observing the outcomes in comparison to controls, I can gain insight into the mechanisms by which the normal brain makes predictions and processes language. In Chapter 1, I set the scene for the focussed experimental investigations of model diseases by beginning with an introductory, clinically-focussed review that sets out the features, aetiology, management, epidemiology and prognosis of the dementias. This places these model diseases in the context of the broader clinical challenge posed by the dementias. In Chapter 2, I turn to ‘prototypical’ model diseases that represent neurodegenerative tauopathies with predominantly cortical (Alzheimer’s disease, AD) and subcortical (Progressive Supranuclear Palsy, PSP) disease burdens. I investigate the neurophysiological causes and consequences of Tau accumulation by combining graph theoretical analyses of resting state functional MR imaging and in vivo ‘Tau’ PET imaging using the ligand AV-1451. By relating Tau distribution to the functional connectome I provide in vivo evidence consistent with ‘prion-like’ trans-neuronal spread of Tau in AD but not PSP. This provides important validation of disease modification strategies that aim to halt or slow down the progression of AD by sequestration of pathological Tau in the synapse. In contrast, I demonstrate associations consistent with regional vulnerability to Tau accumulation due to metabolic demand and a lack of trophic support in PSP but not AD. With a cross-sectional approach, using Tau burden as a surrogate marker of disease severity, I then go on to show how the changes in functional connectivity that occur as disease progresses account for the contrasting cognitive phenotypes in AD and PSP. In advancing AD, functional connectivity across the whole brain becomes increasingly random and disorganised, accounting for symptomatology across multiple cognitive domains. In advancing PSP, by contrast, disrupted cortico-subcortical and cortico-brainstem interactions meant that information transfer passed through a larger number of cortical nodes, reducing closeness centrality and eigenvector centrality, while increasing weighted degree, clustering, betweenness centrality and local efficiency. Together, this resulted in increasingly modular processing with inter-network communication taking less direct paths, accounting for the bradyphrenia characteristic of the ‘subcortical dementias’. From chapter 3 onwards, I turn to the in-depth study of a model disease called non-fluent variant Primary Progressive Aphasia (nfvPPA). This disease has a clear clinical phenotype of speech apraxia and agrammatism, associated with a focal pattern of mild atrophy in frontal lobes. Importantly, general cognition is usually well preserved until late disease. In chapter 3 itself, I relate an experiment in which patients with nfvPPA and matched controls performed a receptive language task while having their brain activity recorded with magnetoencephalography. I manipulated expectations and sensory detail to explore the role of top-down frontal contributions to predictive processes in speech perception. I demonstrate that frontal neurodegeneration led to inflexible and excessively precise predictions, and that fronto-temporal interactions play a causal role in reconciling prior predictions with degraded sensory signals. The discussion here concentrates on the insights provided by neurodegenerative disease into the normal function of the brain in processing language. Overall, I demonstrate that higher level frontal mechanisms for cognitive and behavioural flexibility make a critical functional contribution to the hierarchical generative models underlying speech perception In chapter 4, I precisely define the sequence processing and statistical learning abilities of patients with nfvPPA in comparison to patients with non-fluent aphasia due to stroke and neurological controls. I do this by exposing participants to a novel, mixed-complexity artificial grammar designed to assess processing of increasingly complex sequencing relationships, and then assessing the degree of implicit rule learning. I demonstrate that agrammatic aphasics of two different aetiologies are not disproportionately impaired on complex sequencing relationships, and that the learning of phonological and non-linguistic sequences occurs independently in health and disease. In chapter 5, I summarise the synergies between the experimental chapters, and explain how I have applied a systems identification framework to a diverse set of experimental methods, with the common goal of defining the physiology of dementia. I then return to the results of chapter 3 with a clinical focus to explain how inflexible predictions can account for subjective speech comprehension difficulties, auditory processing abnormalities and (in synthesis with chapter 4) receptive agrammatism in nfvPPA. Overall, this body of work has contributed to knowledge in several ways. It has achieved its tripartite aims by: 1) Providing in vivo evidence consistent with theoretical models of trans-neuronal Tau spread (chapter 2), and a comprehensive clinical account of the previously poorly-understood receptive symptomatology of nfvPPA (chapter 5), thus demonstrating that systems neuroscience can provide a translational bridge between the molecular biology of dementia and clinical trials of therapies and medications. In this way, I begin to disentangle the network-level causes of neurodegeneration from its consequences. 2) Providing evidence for a causal role for fronto-temporal interactions in language processing (chapter 3), and demonstrating domain separation of statistical learning between linguistic and non-linguistic sequences (chapter 4), thus demonstrating that studies of patients with neurodegenerative disease can further our understanding of normative brain function. 3) Successfully integrating neuropsychology, behavioural psychophysics, functional MRI, structural MRI, magnetoencephalography and computational modelling to provide comprehensive research training, as the platform for a future research programme in the physiology of dementia.
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Iordachescu, Alexandra. "An in-vitro model for the development of mature bone containing an osteocyte network." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8064/.
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Bone tissue continuously adapts to changes in mechanical load. This process can also result in a maladaptive ectopic bone response to mechanical insult, known as heterotopic ossification. The pathological differences at the molecular and structural levels are poorly understood. In vivo models exist but can often be too complex to allow isolation of factors which may stimulate disease progression. This thesis presents the development of a biologically self-structuring bone culture system using a fibrin gel which self-organises between two calcium phosphate anchors when seeded with cells. These bioinspired wound analogues are seeded with primary femoral periosteal cells - key players in bone repair and a range of pathologies- and develop longitudinally over time, allowing to study the temporal evolution of bone mineral and microstructure in excess of a year. Raman spectroscopy and XRD revealed that the mineral was hydroxyapatite and associated with collagen, which was organized like the in vivo tissue. The initial stem cell population differentiated to the terminal osteocytic phase, was linked by longitudinal canalicular networks (demonstrated using nanoCT) and remained viable over the year of culture. This work also demonstrated that pharmacological compounds can prevent the progress of ossification, displaying promise for applications in drug screening.
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Hilts, Wade William. "Emulating Balance Control Observed in Human Test Subjects with a Neural Network." PDXScholar, 2018. https://pdxscholar.library.pdx.edu/open_access_etds/4499.
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Human balance control is a complex feedback system that must be adaptable and robust in an infinitely varying external environment. It is probable that there are many concurrent control loops occurring in the central nervous system that achieve stability for a variety of postural perturbations. Though many engineering models of human balance control have been tested, no models of how these controllers might operate within the nervous system have yet been developed. We have focused on building a model of a proprioceptive feedback loop with simulated neurons. The proprioceptive referenced portion of human balance control has been successfully modeled by a PD controller with a time delay and output torque positive feedback. For this model, angular position is measured at the ankle and corrective torque is applied about the joint to maintain a vertical orientation. In this paper, we construct a neural network that performs addition, subtraction, multiplication, differentiation and signal filtering to demonstrate that a simulated biological neural system based off of the engineering control model is capable of matching human test subject dynamics.
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Thomas, Matthew G. "Development of two in vitro methodologies for the study of brain network dynamics and an application to the study of seizure-evoked adenosine release." Thesis, University of Warwick, 2015. http://wrap.warwick.ac.uk/77199/.
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Understanding the brain in both health and disease is of critical practical importance as well as fundamental scientific interest. The acute neural tissue slice is a widely used experimental preparation, it facilitates treatments and measurements not practical in vivo while preserving a largely connected network representative of the true in vivo structure. This thesis presents the development of two techniques for the study of the acute neural tissue slice, both particularly well suited to the study of epilepsy, followed by an application of one of these techniques. A slice chamber is presented that allows extended regions of a tissue slice to be exposed, in isolation, to changes in ionic environment or pharmacological manipulation, readily providing an entirely in vitro model of focal epilepsy. Secondly, a transformation is derived that converts the slow dynamics of the intrinsic optical signal (IOS) associated with neuronal activity both in vivo and in vitro to the form of the associated local field potential, allowing the advantages of the IOS to be exploited while mitigating the primary disadvantage - the lack of direct correspondence between the IOS and the associated network dynamics. Finally a study is presented that employs the transformation of the IOS to facilitate a quantitative characterisation of the spatio-temporal dynamics of adenosine release in response to electrographic seizure activity.
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Hunt, Robert F. III. "LOCAL SYNAPTIC NETWORK INTERACTIONS IN THE DENTATE GYRUS OF A CORTICAL CONTUSION MODEL OF POSTTRAUMATIC EPILEPSY." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/94.
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Posttraumatic epilepsy is a common consequence of brain trauma. However, little is known about how long-term changes in local excitatory and inhibitory synaptic networks contribute to epilepsy after closed-head brain injury. This study adapted a widely used model of experimental brain injury as a mouse model of posttraumatic epilepsy. Behavioral seizure activity and alterations in synaptic circuitry in the dentate gyrus were examined in mice after experimental cortical contusion brain injury. Spontaneous behavioral seizures were observed in 20% of mice after moderate injury and 36-40% of mice weeks after severe injury. In the dentate gyrus, most mice displayed regionally localized mossy fiber reorganization ipsilateral to the injury that was absent in control mice or sections contralateral to the injury. Extracellular field and whole-cell patch clamp recordings were performed in acute brain slice preparations of the dentate gyrus. Dentate granule cells displayed spontaneous and evoked activity that was consistent with network synchronization and the formation of recurrent excitatory network only in slices that had posttraumatic mossy fiber sprouting. The excitability of surviving hilar GABAergic interneurons, which provide important feedback inhibition to granule cells, was examined at similar time points. Cell-attached and whole-cell voltage-clamp recordings revealed increased spontaneous and glutamate photostimulation-evoked excitatory input to hilar GABA neurons ipsilateral to the injury, versus control and contralateral slices. Despite increased excitatory synaptic input to interneurons, whole-cell voltage-clamp recordings revealed a reduction in inhibitory synaptic input to granule cells. These findings suggest that there are alterations in excitatory and inhibitory circuits in mice with posttraumatic mossy fiber sprouting and seizures after cortical contusion head injury.
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Balasubramanian, Deepak. "Pseudomonas Aeruginosa AmpR Transcriptional Regulatory Network." FIU Digital Commons, 2013. http://digitalcommons.fiu.edu/etd/863.
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In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAO∆ampR were analyzed. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought influencing the differential expression of over 500 genes. In addition to regulating resistance to β-lactam antibiotics via AmpC, AmpR also regulates non-β-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Virulence mechanisms including biofilm formation, QS-regulated acute virulence, and diverse physiological processes such as oxidative stress response, heat-shock response and iron uptake are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the transcriptome data. Further, Caenorhabditis elegans model demonstrates that a functional AmpR is required for full pathogenicity of P. aeruginosa. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. The extensive AmpR regulon included other transcriptional regulators and sigma factors, accounting for the extensive AmpR regulon. Gene expression studies demonstrate AmpR-dependent expression of the QS master regulator LasR that controls expression of many virulence factors. Using a chromosomally tagged AmpR, ChIP-Seq studies show direct AmpR binding to the lasR promoter. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating chronic infection phenotypes. In summary, my dissertation sheds light on the complex regulatory circuit in P. aeruginosa to provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors.
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Tkaczynski, Patrick. "The behavioural ecology of personality in wild Barbary macaques." Thesis, University of Roehampton, 2016. https://pure.roehampton.ac.uk/portal/en/studentthesis/the-behavioural-ecology-of-personality-in-wild-barbary-macaques(023582d2-2214-448c-bf12-c1bef7d5549e).html.
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Personality, that is intra-individual consistency and inter-individual variation in behaviour, is widespread throughout the animal kingdom. This challenges traditional evolutionary assumptions that selection should favour behavioural flexibility, and that variation in behavioural strategies reflects stochastic variation around a single optimal behavioural strategy. Adaptive models to explain personality within the framework of evolutionary and behavioural ecology exist, and are typically empirically explored by identifying proximate associations to, and the functional consequences of, personality expression. To date, such studies have typically quantified a narrow range of personality traits within a species, and focused on captive populations or species with relatively limited behavioural or social repertoires. In this thesis, personality is studied in wild Barbary macaques (Macaca sylvanus). Quantification of personality structure in the species was conducted using a multi-method approach, and subsequently, it was examined whether physiological stress response (a proximate association) was related to personality expression, and whether personality expression affected social (functional) outcomes for individuals. Seven personality constructs were identified in Barbary macaques. Three personality constructs were related to physiological stress responses (Excitability, Tactility and Exploration), with the relationship between stress and personality expression dependent on sex, and in some cases rank or age. Two personality constructs (Excitability and Exploration) were associated with measures of social integration. Subjects generally socially assorted themselves according to personality, tending to be in proximity to individuals with a similar personality to themselves. This study contributes methodologically by demonstrating the plausibility of multi-method approaches to measuring personality in wild primates, and empirically, by generating evidence supporting adaptive models for the evolution of personality, namely that intra-individual consistency in behaviour may be mediated by physiology and that inter-individual variation in behaviour has functional benefits in the formation of social relationships and social structures.
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Gupta, Sneha. "Understanding Regulation of the Cytoskeleton during Cell Cycle Transitions through Examination of Crosstalk between Homologous Fission Yeast Pathways, Septation Initiation Network and Morphogenesis ORB6 Network: A Dissertation." eScholarship@UMMS, 2013. http://escholarship.umassmed.edu/gsbs_diss/693.
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The fission yeast Schizosaccharomyces pombe has become a powerful model system for studying cytokinesis, a process of cytoplasmic division by which one cell divides into two identical daughter cells. Like mammalian cells, S. pombe divides through the use of an actomyosin contractile ring, which is composed of a set of highly conserved cytoskeletal proteins. Cytokinesis in S. pombe is primarily regulated by the SIN pathway, which is activated in late mitosis and is required for actomyosin contractile ring and septum assembly, and also plays a role in spindle checkpoint inactivation, and telophase nuclear positioning. The various functions of the SIN are carried out by the terminal kinase in the pathway called Sid2. The lack of information in the downstream targets of Sid2 has limited our understanding of the different functions of the SIN. We recently showed that, in addition to its other functions, the SIN promotes cytokinesis through inhibition the MOR signaling pathway, which normally drives cell separation and initiation of polarized growth following completion of cytokinesis (Ray et al, 2010). The molecular details of this inhibition and the physiological significance of inhibiting MOR during cytokinesis was unclear. The results presented in Chapter II describe our approach to identify Sid2 substrates, particularly focusing on Nak1 and Sog2 that function in the MOR signaling cascade. We identified and characterized Sid2 phosphorylation sites on the Nak1 and Sog2 proteins. Chapter III explores how post translational modification of MOR proteins by Sid2 regulates polarized growth during cytokinesis. This includes delineating the effect of Sid2 mediated phosphorylation of Nak1 and Sog2 on protein-protein interactions in the MOR pathway as well as on the regulation of their localization during late mitosis. Finally, results in Chapter IV demonstrate that failure to inhibit MOR signaling is lethal because cells initiate septum degradation/cell separation before completing cytokinesis thereby emphasizing the importance of cross-regulation between the two pathways to prevent initiation of the interphase polarity program during cytokinesis.
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Draper, Christiana S. I. "ALS-induced Excitability Changes in Individual Motorneurons and the Spinal Motorneuron Network in SOD1-G93A Mice at Symptom Onset." Wright State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1621064515386592.
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Morcos, Karim M. "Genetic network parameter estimation using single and multi-objective particle swarm optimization." Thesis, Kansas State University, 2011. http://hdl.handle.net/2097/9207.
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Master of ScienceDepartment of Electrical and Computer Engineering
Sanjoy Das
Stephen M. Welch
Multi-objective optimization problems deal with finding a set of candidate optimal solutions to be presented to the decision maker. In industry, this could be the problem of finding alternative car designs given the usually conflicting objectives of performance, safety, environmental friendliness, ease of maintenance, price among others. Despite the significance of this problem, most of the non-evolutionary algorithms which are widely used cannot find a set of diverse and nearly optimal solutions due to the huge size of the search space. At the same time, the solution set produced by most of the currently used evolutionary algorithms lacks diversity. The present study investigates a new optimization method to solve multi-objective problems based on the widely used swarm-intelligence approach, Particle Swarm Optimization (PSO). Compared to other approaches, the proposed algorithm converges relatively fast while maintaining a diverse set of solutions. The investigated algorithm, Partially Informed Fuzzy-Dominance (PIFD) based PSO uses a dynamic network topology and fuzzy dominance to guide the swarm of dominated solutions. The proposed algorithm in this study has been tested on four benchmark problems and other real-world applications to ensure proper functionality and assess overall performance. The multi-objective gene regulatory network (GRN) problem entails the minimization of the coefficient of variation of modified photothermal units (MPTUs) across multiple sites along with the total sum of similarity background between ecotypes. The results throughout the current research study show that the investigated algorithm attains outstanding performance regarding optimization aspects, and exhibits rapid convergence and diversity.
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Masakapalli, Shyam Kumar. "Network flux analysis of central metabolism in plants." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:ac8b3836-9ab7-4060-b50a-df8aaa0e4ba5.
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The aim of this thesis was to develop stable-isotope steady-state metabolic flux analysis (MFA) based on 13C labeling to quantify intracellular fluxes of central carbon metabolism in plants. The experiments focus on the analysis of a heterotrophic cell suspension culture of Arabidopsis thaliana (L) Heynh. (ecotype Landsberg erecta). The first objective was to develop a robust methodology based on combining high quality steady-state stable labeling data, metabolic modeling and computational analysis. A comprehensive analysis of the factors that influence the outcome of MFA was undertaken and best practice established. This allowed a critical analysis of the subcellular compartmentation of carbohydrate oxidation in the cell culture. The second objective was to apply the methodology to nutritional perturbations of the cell suspension. A comparison of growth on different nitrogen sources revealed that transfer to an ammonium-free medium: (i) increased flux through the oxidative pentose phosphate pathway (oxPPP) by 10% relative to glucose utilisation; (ii) caused a substantial decrease in entry of carbon into the tricarboxylic acid cycle (TCA); and (iii) increased the carbon conversion efficiency from 55% to 69%. Although growth on nitrate alone might be expected to increase the demand for reductant, the cells responded by decreasing the assimilation of inorganic N. Cells were also grown in media containing different levels of inorganic phosphate (Pi). Comparison of the flux maps showed that decreasing Pi availability: (i) decreased flux through the oxPPP; (ii) increased the proportion of substrate fully oxidised by the TCA cycle; and (iii) decreased carbon conversion efficiency. These changes are consistent with redirection of metabolism away from biosynthesis towards cell maintenance as Pi is depleted. Although published genome-wide transcriptomic and metabolomic studies suggest that Pi starvation leads to the restructuring of carbon and nitrogen metabolism, the current analysis suggests that the impact on metabolic organisation is much less extreme.
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Chang, Christine Chi-Chen. "Mechanisms and genes controlling the signalling network for biotic and abiotic stress defences in Arabidopsis thaliana (L.) Heyhn : Functional cross-talk between photo-produced reactive oxygen species, photosynthesis and plant disease defence responses." Doctoral thesis, Stockholm : Department of Botany, Stockholm University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-418.
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Tukker, Jan Johan. "Determinants of neuronal firing patterns in the hippocampus." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:0c0c8f92-e146-4e2a-b7f3-6d27a9b12387.
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The activity of networks subserving memory and learning in the hippocampus is under the control of GABAergic interneurons. In order to test the contribution of distinct cell types, I have recorded extracellularly, labelled, and identified different types of interneuron in area CA3 of the hippocampus, a region implicated in the generation of gamma and theta oscillations, and the initiation of sharp-waves. I present here a detailed analysis of the spike timing of parvalbumin-positive (PV) basket and physiologically identified pyramidal cells in area CA3, relative to various network states recorded in area CA3 and CA1 simultaneously. Additionally, I have shown by detailed analysis that five classes of previously recorded and identified CA1 interneuron fired with cell type specific firing patterns relative to local gamma oscillations. In CA3, PV basket cells fired phase locked to theta and gamma oscillations recorded in CA1 as well as in CA3, and increased their firing rates during CA1 sharp-waves. Pyramidal cells in CA3 were also phase-locked, but fired at phases different from basket cells. During theta oscillations, CA3 pyramidal and PV basket cells were phase locked to both CA1 and CA3 theta equally, suggesting a wide coherence of these oscillations; in contrast, cells fired more strongly phase-locked to gamma oscillations in CA3 than in CA1, suggesting a specific role for CA3 in the generation of this rhythm. In contrast to theta and gamma oscillations, CA3 basket cells were phase-locked to ripples in area CA3 but not in CA1. Overall, my results show that the spike timing of several types of interneuron in CA1, and PV basket cells in CA3, is correlated in a cell- and area-specific manner with the generation of particular states of synchronous activity.
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Eichner, Alexander. "The role of branched actin networks in dendritic cell physiology." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-178859.
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Johnson, Joseph S. "Foraging and Roosting Behaviors of Rafinesque's Big-eared Bat (Corynorhinus rafinesquii) at the Northern Edge of the Species Range." UKnowledge, 2012. http://uknowledge.uky.edu/animalsci_etds/5.
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Bat populations in the eastern United States are currently declining at unprecedented rates as a result of habitat loss, commercial wind energy development, and white-nose syndrome. Effective conservation of these declining populations requires knowledge of several aspects of summer and winter ecology, including daytime habitat use (day-roost selection and social behaviors), nocturnal habitat use (foraging habitat selection, prey selection, and prey abundance), and winter hibernation (torpor) patterns. This dissertation addresses these questions for Rafinesque’s big-eared bat (Corynorhinus rafinesquii), a species of conservation concern in the southeastern United States. Kentucky represents the northern edge of the range of Rafinesque’s big-eared bat, and summer and winter behaviors in Kentucky are likely to differ from what has been observed in southern portion of the range, where available habitats and climate are different. My research occurred in two study areas in Kentucky, Mammoth Cave National Park in central Kentucky, and the Ballard Wildlife Management areas in western Kentucky. This dissertation includes all of the work done in western Kentucky, where I radio-tagged 48 adult big-eared bats and documented daytime and nighttime habitat use. Also included is a portion of the work done in central Kentucky, focusing on hibernation patterns of 14 adult big-eared bats radio-tagged during the winter at Mammoth Cave. Data disseminated in this dissertation provide insights into the summer and winter ecology of Rafinesque’s big-eared bat in Kentucky, and can be used to manage populations threatened by habitat loss and white-nose syndrome.
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Beattie, Allison Jane. "Organised neural networks in culture." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/1921/.
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The aim of my research was to recreate simple, spatially organised neural networks in culture for the study of neural network behaviour. Spinal cord neurons were chosen as the biological model, as much is already known about spinal cord tissue circuitry in-vivo. These simple networks of cells were created by chemical patterning techniques (micro-contact printing (mCP)), and topographical guidance mechanisms. mCP was used to test the hypothesis that alterations in network architecture could affect network behaviour. Changes in network structures were identified, using immunocytochemical staining and scanning electron microscopy (SEM). Of the six patterns tested it was concluded that the Jude pattern did not satisfy the criteria required for a neural network. Cells failed to comply to the extreme angles of this design and so a hexagonal pattern was introduced. Dendritic architecture, of varying designs, was incorporated into these hexagonal networks with the aim of determining if variation in dendritic arborisation could affect network activity. An analysis of the result showed that cell morphology and connectivity was visibly altered, suggesting network characteristics were affected. An attempt was made to create organised nerve cultures using micro-metric grooved patterns in poly-dimethylsiloxane (PDMS). The cellular response was determined by immunocytochemical staining and SEM imaging. Cells grown on micrometric topographical patterns did not align within the grooves as predicted. Therefore the effect of nano-metric pillared topography, created in poly-caprolactone, on nerve cell guidance was investigated. In comparison to the flat material, this nanotopography reduced cell adhesion, although it was not completely non-adhesive. After 1 week cells were visibly aligning to the topography, at the micro-and nanometric level, and appeared to be growing longer processes compared to the cells grown on flat structures. This result suggests nanopillared topography has a promising future in nerve guidance studies.
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Ollivier, Julien. "Scalable methods for modelling complex biochemical networks." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104586.
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In cells, complex networks of interacting biomolecules process both environmental and endogenous signals to control gene expression and other cellular processes. This poses a challenge to researchers who attempt to develop mathematical and computational models of biochemical networks that reflect this complexity. In this thesis, I propose methods that help manage complexity by exploiting the finding that, as for other biological systems, cellular networks are characterized by a modularity that appears at all levels of organization.The first part of this work focuses on the modular properties of proteins and how their function can be characterized through their structure and allosteric properties. I develop a modular rule-based framework and formal modelling language that describes the computations performed by allosteric proteins and that is rooted in biophysical principles. Rule-based modelling conventionally addresses the problem of combinatorial complexity, whereby protein interactions can generate a combinatorial explosion of protein complex states. However, I explore how these same interactions can potentially require a combinatorial number of parameters to describe them. I demonstrate that my rule-based framework effectively addresses this problem of regulatory complexity, and describes allosteric proteins and networks in a unified, consistent, and modular fashion. I use the framework in three applications. First, I show that allostery can make macromolecular assembly more efficacious when a protein that joins two separable parts of a complex is present in excessively high concentrations. Second, I demonstrate that I can straightforwardly analyze the complex cooperative interactions that arise when competitive ligands bind to a multimeric protein. Third, I analyze a new model of G protein-coupled receptor signalling and demonstrate that it explains the functional selectivity of these receptors while being parsimonious in the number of parameters used. Overall, I find that my rule-based modelling framework, implemented as the Allosteric Network Compiler software tool, can ease of modelling and analysis of complex allosteric interactions.If cellular networks are modular, this implies that small sub-systems can be studied in isolation, provided that external inputs and perturbations to the system can be modelled appropriately. However, cellular networks are subject to both intrinsic noise, which is endogenous to the system, but also extrinsic noise, arising from noisy inputs. Furthermore, many inputs may be dynamic, whether due to experimental protocols or perhaps reflecting the cyclic process of cell division. This motivates my development, in the second part of this work, of efficient stochastic simulation algorithms for biochemical networks that can accommodate time-varying biochemical parameters. Starting from Gillespie's well-known First Reaction Method and Gibson and Bruck's Next Reaction Method, I develop two new algorithms that allow time-varying inputs of arbitrary functional form while scaling well to systems comprising many biochemical reactions. I analyze their scaling properties and find that a modified First Reaction Method may scale better than a modified Next Reaction Method in some applications.The third and last part of this thesis introduces a new software tool, Facile, that eases the creation, update and simulation of biochemical network models. Models created through a simple and intuitive textual language are automatically converted into a form usable by downstream tools, for example ordinary differential equations for simulation by Matlab. Also, Facile conveniently accommodates mathematical and time-varying expressions in rate laws.Au niveau cellulaire, des réseaux complexes d'interaction biomoléculaire traitent les signaux tant environnementaux qu'endogènes dans le but de contrôler l'expression génétique ainsi que d'autres processus cellulaires. Ceci est un défi pour les chercheurs qui veulent concevoir des modèles mathématiques et calculatoires des réseaux biochimiques. Dans cette thèse, je propose des méthodes qui facilitent la gestion de cette complexité en exploitant la constatation que, tout comme d'autres systèmes biologiques, les réseaux cellulaires se caractérisent par une modularité qui transparaît à tous les niveaux d'organisation.Dans la première partie, je mets l'accent sur les propriétés modulaires des protéines et sur la façon de caractériser leur fonction, compte tenu de leur structure et de leurs propriétés allostériques. J'ai mis au point un cadre modulaire à base de règles ainsi qu'un langage formel de modélisation qui permet de décrire les calculs effectués par les protéines allostériques et qui découle de principes biophysiques. La modélisation à base de règles s'adresse conventionnellement au problème de la complexité combinatoire, où les interactions entre les protéines peuvent générer une explosion combinatoire d'états des complexes protéiques. J'examine, cependant, comment il peut s'avérer nécessaire d'utiliser un nombre combinatoire de paramètres pour décrire ces mêmes interactions. Je démontre que notre cadre à base de règles peut régler efficacement ce problème de la complexité régulatoire, et permet de décrire les protéines et les réseaux allostériques de façon unifiée, cohérente et modulaire. J'utilise le cadre développé dans trois applications. Tout d'abord, je montre que l'allostérie peut rendre l'assemblage macromoléculaire plus efficace lorsqu'une protéine qui unit deux parties distinctes d'un complexe protéique est présente en concentration excessive. Deuxièmement, je démontre qu'il est relativement simple d'analyser les interactions coopératives complexes qui surviennent lorsque des ligands compétitifs se lient à une protéine multimérique. En troisième lieu, j'analyse un nouveau modèle de la signalisation des récepteurs couplés aux protéines G qui explique leur sélectivité fonctionnelle tout en limitant le nombre des paramètres utilisés. Globalement, je montre que ce cadre basé sur des règles, qui est implémenté dans le logiciel ‘Allosteric Network Compiler', peut faciliter la modélisation et l'analyse d'interactions allostériques complexes.Si les réseaux cellulaires sont modulaires, il en résulte que des sous-systèmes peuvent être étudiés séparément, à la condition que les entrées et les perturbations externes du système puissent être modélisées adéquatement. Cependant, ces réseaux sont soumis à l'influence du bruit intrinsèque, qui est endogène au système, mais également au bruit extrinsèque, venant des entrées bruyantes. De plus, de nombreuses entrées peuvent être dynamiques. Cela motive, dans la deuxième partie de ce travail, le développement d'algorithmes efficients de simulation stochastique pour les réseaux biochimiques qui peuvent tenir compte de paramètres biochimiques dynamiques. En me fondant sur la méthode maintenant célèbre de Gillespie, d'appellation ‘First Reaction Method', et sur celle de Gibson et Bruck, la ‘Next Reaction Method', j'ai développé deux nouveaux algorithmes qui permettent des entrées dynamiques de forme fonctionnelle arbitraire tout en s'échelonnant bien sur les systèmes qui comportent de nombreuses réactions biochimiques. J'analyse leurs propriétés d'échelonnement et je constate que, pour certaines applications, la ‘First Reaction Method' modifiée s'échelonne mieux que la ‘Next Reaction Method' modifiée.La troisième et dernière partie cette thèse est la présentation d'un nouvel outil informatique, Facile, qui simplifie la création, la mise à jour et la simulation de modèles de réseaux biochimiques.
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Naqib, Faisal. "Spatial and temporal effects on molecular signaling networks." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119609.
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Two areas that are particularly suited to mathematical modeling analysis are how molecular signaling pathways process the timing of stimuli and how spatial structure can influence a signaling pathway's dynamics. These topics are explored through specific examples. The timing of stimuli is known to affect the strength of memory formation. This phenomenon has been studied in the sensory-motor neuron synapse of Aplysia. In this system, training that is separated by rest periods (spaced training) leads to persistent changes in synaptic strength that depend on biochemical pathways that are distinct from those that are engaged when the training lacks rest periods (massed training). Applications of serotonin (5HT), the neurotransmitter implicated in inducing these synaptic changes, causes desensitization of PKC Apl II, in a manner that depends on the timing of 5HT stimulation; spaced applications of 5HT cause more desensitization than massed applications of 5HT. We developed a mathematical model of this response to gain insight into how neurons process the timing difference in stimuli. The model represents the trafficking of the 5HT receptor responsible for activating PKC Apl II. Each component of the model was developed incrementally and was experimentally validated. We discovered two major elements of the signaling pathway mediating PKC Apl II desensitization. First, we discovered that PKA activity leads to an increase in the reversal from desensitization. Second, we propose that the mechanism allowing the signaling pathway to differentiate spaced from massed applications of 5HT is largely driven by the rates of synthesis and degradation of a pair of hypothetical proteins, named AD and D, that regulate receptor activity. We further developed the isolated sensory neuron work by experimentally observing the desensitization of PKC Apl II translocation in co-cultured sensory and motor neurons. We found that the formation of a synapse results in a change in the desensitization of PKC Apl II translocation: spaced applications of 5HT no longer caused greater desensitization than massed applications. This finding implies that the sensory neuron has undergone a change during synapse formation in the signaling network regulating the desensitization of PKC Apl II. To explain these changes, we created two new models: one of the cell body of sensory neurons co-cultured with motor neurons and one of the synapses of these neurons. These new models were able to explain the change in desensitization of PKC translocation by making changes to the expression and activity of regulatory proteins. These models provide a signaling pathway mechanism for neurons to encode the timing of stimuli. The model of PKC Apl II desensitization was able to describe these signaling dynamics without taking into consideration the spatial structure of the system. However, the geometry of a system may have a significant impact on a signaling pathway's output. To examine this issue in more detail, we modeled the general case of a signaling pathway with two signaling molecules, an activating species and an inhibiting species forming a negative feedback, which are synthesized at unique sites and interact with each other through diffusion. The dynamical behaviors in these systems depend on the spatial locations of the synthetic sites. In a negative feedback system with two sites, we find two dynamical modes: fixed point and stable oscillations whose frequency can be tuned by varying the distance between the sites. When there are multiple synthetic sites, we find more diverse dynamics, including chaos, quasiperiodicity, and bistability. These studies propose a mechanism for signaling pathways to encode the timing of stimuli, and demonstrate the effects spatial structure can have on signaling output. Furthermore, they provide examples of the use of mathematical modeling in furthering our understanding of molecular signaling networks.Il est connu que le moment de présentation des stimuli a un effet important sur la force de la mémoire formée. Un excellent modèle pour étudier ce phénomène est la synapse sensori-motrice des neurones de l'aplysie. Dans ce système, une stimulation séparée par des périodes de repos (applications espacées) conduit à des changements persistants au niveau de la force synaptique qui dépend de voies biochimiques différentes de celles qui se produisent lors d'une stimulation sans périodes de repos (applications continues). Récemment, il a été montré que dans les neurones sensoriels isolés, l'application de la sérotonine, qui est le neurotransmetteur impliqué dans l'induction de ces changements synaptiques, entraîne une désensibilisation de la réponse PKC Apl II d'une manière qui dépend du moment précis de la stimulation par la sérotonine. Nous avons développé un modèle mathématique de cette réponse afin de mieux comprendre comment les neurones traitent-ils la différence temporelle entre stimuli. Le modèle représente le trafic du récepteur de la sérotonine responsable de l'activation de PKC. Chaque composante du modèle a été développée progressivement et a été validé expérimentalement. Basée sur ce modèle, nous avons découvert deux éléments majeurs de la voie de signalisation médiatrice de désensibilisation de la PKC. Premièrement, nous avons découvert l'activité PKA conduit également à une augmentation du processus réversible de désensibilisation. Deuxièmement, nous proposons que le mécanisme permettant à la voie de signalisation de différencier l'effet de la sérotonine, dépendamment d'une application espacée ou une application continue, est largement déterminée par les taux de synthèse et de dégradation d'une paire de protéines hypothétiques, que nous nommerons AD et D qui régulent l'activité des récepteurs. Nous avons élargi le travail des neurones sensoriels isolés en observant la désensibilisation de la translocation PKC Apl II dans des co-cultures de neurones sensoriels et moteurs, où le neurone sensoriel forme une connexion synaptique avec le motoneurone. Nous avons constaté que la formation d'une synapse résulte d'un changement de la désensibilisation de la translocation PKC: les applications espacées de 5HT ne sont plus capables de causer une désensibilisation plus importante que celles des applications continues. Ceci peut signifier que, le neurone sensoriel a subi un changement durant la formation de synapses dans le réseau de signalisation régulant l'activation de la PKC. Pour expliquer ces changements, nous avons créé deux nouveaux modèles: l'un dédié aux corps cellulaires des neurones sensoriels co-cultivés avec des neurones moteurs et l'autre aux synapses de ces neurones. Ces nouveaux modèles ont été en mesure d'expliquer le changement dans la désensibilisation de la translocation de la PKC en pratiquant des changements dans les taux de synthèse et de dégradation des proteines AD et D.Le modèle de la translocation PKC Apl II a pu décrire les dynamiques biologiques sans prendre en considération la structure spatiale du système. Néanmoins, la géométrie d'un système peut avoir un impact significatif sur la résultante d'une des voies de signalisation. Ainsi, nous considérons le cas général d'une voie de signalisation ayant deux molécules de signalisation: une espèce activatrice et une espèce inhibitrice avec une rétroactivité négative, qui sont synthétisés dans des sites uniques et qui interagissent les uns avec les autres à travers un processus de diffusion. Les comportements dynamiques de ces systèmes dépendent des localisations spatiales des sites de synthèse. Dans un système de rétroactivité négative à deux sites, on trouve une dynamique à deux modes: point fixe et oscillations stables dont la fréquence peut être ajustée en faisant varier la distance entre les deux sites. Quand il y'a plusieurs sites de synthèse, nous avons constaté une dynamique plutôt diverse, incluant chaos, quasi-périodicité et instabilité.
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Oates, Christopher J. "Bayesian inference for protein signalling networks." Thesis, University of Warwick, 2013. http://wrap.warwick.ac.uk/58325/.
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Cellular response to a changing chemical environment is mediated by a complex system of interactions involving molecules such as genes, proteins and metabolites. In particular, genetic and epigenetic variation ensure that cellular response is often highly specific to individual cell types, or to different patients in the clinical setting. Conceptually, cellular systems may be characterised as networks of interacting components together with biochemical parameters specifying rates of reaction. Taken together, the network and parameters form a predictive model of cellular dynamics which may be used to simulate the effect of hypothetical drug regimens. In practice, however, both network topology and reaction rates remain partially or entirely unknown, depending on individual genetic variation and environmental conditions. Prediction under parameter uncertainty is a classical statistical problem. Yet, doubly uncertain prediction, where both parameters and the underlying network topology are unknown, leads to highly non-trivial probability distributions which currently require gross simplifying assumptions to analyse. Recent advances in molecular assay technology now permit high-throughput data-driven studies of cellular dynamics. This thesis sought to develop novel statistical methods in this context, focussing primarily on the problems of (i) elucidating biochemical network topology from assay data and (ii) prediction of dynamical response to therapy when both network and parameters are uncertain.
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Wheeler, Damian George. "Monitoring CRE-dependent Gene Expression Induced by Synaptic Activity in Live Networks of Neurons." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95597.
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During development, neuronal activity plays an important role in shaping functionalsynaptic networks. Moreover, in adults, neuronal activity is thought to produce long-termchanges during learning and memory. For these changes to persist, however, neuronalactivity must engage signaling pathways that result in alterations in gene expression.Pathways that activate the transcription factor CREB (cAMP-response element-bindingprotein), which binds to CREs (cAMP response elements) in gene promoters, have beenimplicated in this long-term, activity-dependent plasticity. The focus of my research is toinvestigate the mechanisms of CRE-dependent gene expression induced by physiologicalsynaptic activity. Together with my supervisor, I developed a sensitive biosensor tomeasure CRE-dependent gene expression in neurons; this biosensor consists of apromoter-reporter construct derived from the major immediate-early promoter/enhancerof the human cytomegalovirus (hCMV promoter) coupled to Green Fluorescent Protein(GFP). Our studies show that this promoter acts as an activity-dependent switch inneurons. The hCMV promoter functions poorly in unstimulated neurons, but is stronglyinduced by neuronal activity or other stimuli that activate CREB; moreover, site-directedmutagenesis of the five CREs in the promoter eliminated this inducibility. To express thisbiosensor in neurons, we used adenoviral-mediated gene transfer which has an efficiencyof>95%, allowing one to monitor reporter gene expression in individual neurons of afunctional network for several days. Using this system we, discovered that nicotine, atlow-levels in the range that circulates in smokers, acts in a distributed manner throughout a neuronal network to alter CRE-dependent gene expression induced by network activity . Further, exploiting the sensitivity of this biosensor, we found that weak neuronal activity,including spontaneous release of neurotransmitter, is a sufficient stimulus to recruitsignaling pathways that resu
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O'Sullivan, Abigail. "Networks of creativity : a study on scientific achievement in British physiology, c.1881-1945." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249851.
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Lewis, John E. "Dynamics of neural networks and respiratory rhythm generation." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=60568.
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The phase resetting effects of stimulating the superior laryngeal nerve at different phases of the respiratory cycle in cats were measured in terms of the latency of onset of the cycle following stimulation. Fixed-delay stimulation was also used; for certain combinations of delay, stimulus intensity, and cycles between stimuli, it resulted in (1) a variable, rather than consistent, response, and (2) a transient increase in cycle duration during and after stimulation. Phase resetting and fixed-delay stimulation of a simple three-phase model for neural rhythm generation produce responses that are qualitatively similar to those obtained experimentally.We consider the dynamical properties of a class of theoretical models of neural networks that have the same mathematical formulation as the above three-phase model, but consist of a larger number of randomly connected elements. A simple transformation of these models shows correspondence with previous neural network models and enables a theoretical analysis of steady states and cycles. Complex aperiodic dynamics are found in networks consisting of 6 or more elements.
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Eichner, Alexander [Verfasser], and Klaus [Akademischer Betreuer] Förstemann. "The role of branched actin networks in dendritic cell physiology / Alexander Eichner. Betreuer: Klaus Förstemann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1066206597/34.
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Batra, Sanjay. "Geometry of capillary networks during normal and pathological growth of the rat myocardium." Thesis, University of Ottawa (Canada), 1991. http://hdl.handle.net/10393/7907.
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The aim of this dissertation was to provide a thorough description of the coronary microvasculature at different phases of cardiac contraction, during normal postnatal growth, and pathologically accelerated growth due to pressure and volume overloading. The histochemical technique used to visualize capillaries was novel in that it served to distinguish arteriolar and venular capillary regions by colour. Arteriolar capillary (AC) regions stained blue in colour, positive for the presence of Alkaline Phosphatase in the endothelium. Venular capillary (VC) regions stained red in colour, positive for the presence of Dipeptidyl Peptidase IV. The morphometric methods used to assess capillary geometry from cross and longitudinal tissue sections were classified according to AC and VC regions. From tissue cross sections, capillaries were represented as a bivariate (CV, blue; VC, red) point pattern in the tissue plane. Our software program for capillary domains served to divide the plane into polygonal regions of tissue, each polygon enclosing one capillary. The area subtended by each polygon, the capillary domain, was closer to the enclosed capillary than any other. From individual domain areas, the equivalent radius of the Krogh cylinder with the same area was calculated. As the distribution of these radii is log-normal, the variability was best characterized by the logarithmic standard deviation (SDlog). In this manner, SDlog, the heterogeneity of capillary spacing was determined. From longitudinal sections, scale drawings of capillary sets, which consisted of all the capillary pathways that could be clearly followed from the same terminal arteriole to collecting venule served as the basic unit of study. From these capillary sets, we have defined and measured several morphometric parameters, appropriate as indicators of geometrical conditions for oxygen supply. Among these parameters are the minimal capillary length, the shortest contiguous pathway from arteriole to venule; mean capillary length, the average length of all possible capillary paths from arteriole to venule; and capillary segment length, the distance between two successive capillary branch points. To illustrate the effect of changes in capillary geometry on myocardial oxygenation, we have chosen as an illustration, the results obtained from pressure overloaded hearts. (Abstract shortened by UMI.)
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Miraldi, Emily R. (Emily Rae). "Bridging the gap between protein-tyrosine phosphorylation networks, metabolism and physiology in liver-specific PTP1b deletion mice." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72824.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2012.Cataloged from PDF version of thesis.
Includes bibliographical references.
Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) suggests that hepatic PTPlb inhibition would mitigate metabolic syndrome progression through amelioration of hepatic insulin resistance, endoplasmic reticulum stress, and whole-body lipid metabolism. However, the network alterations underlying these phenotypes are poorly understood. Mass spectrometry was used to quantitatively discover protein phosphotyrosine network changes in L-PTP lb-/- mice relative to control mice under both normal and high-fat diet conditions. A phosphosite set enrichment analysis was developed to identify numerous pathways exhibiting PTPlb- and diet-dependent phosphotyrosine regulation. Detection of PTP lb-dependent phosphotyrosine sites on lipid metabolic proteins initiated global lipidomics characterization of corresponding liver samples and revealed altered fatty acid and triglyceride metabolism in L-PTPlb-/- mice. Multivariate modeling techniques were developed to infer molecular dependencies between phosphosites and lipid metabolic changes, resulting in quantitatively predictive phenotypic models.
by Emily R. Miraldi.
Ph.D.
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Gezelius, Henrik. "Studies of Spinal Motor Control Networks in Genetically Modified Mouse Models." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-109889.
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Bendali, Amel. "Brain-Machine Interfaces : from retinal network reconstruction to retinal implants." Paris 6, 2013. http://www.theses.fr/2013PA066050.
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Les interfaces cerveau/machine consistent en l’interfaçage direct d’un tissu nerveux avec unsystème électronique. Dans le cas des interfaces in vitro, il s’agit de tirer parti du traitement de l’information parallélisé au sein de ces réseaux neuronaux pour atteindre des performances de calcul supérieures à celles des processeurs classiques. In vivo, les interfaces cerveau/machine ont pour objectif d’introduire de nouvelles informations dans le circuit neuronal par stimulation électrique du tissu afin de compenser ou réhabiliter des fonctions cognitives ou sensori-motrices perdues. Qu’il soit question de recueil de données ou de transfert d’information, le défi majeur de ces interfaces se trouve au niveau des interactions cellules/matériaux. C’est notamment le cas des prothèses rétiniennes pour lesquelles la résolution actuelle est insuffisante pour permettre aux patients de lire des textes complexes, de se mouvoir dans un environnement complexe et de reconnaître des visages. Cependant, les premiers essais cliniques ont apporté des résultats encourageants chez des patients non-voyants, même si l’acuité visuelle retrouvée reste inférieure à la limite légale de cécité. Au cours de ce doctorat, nous avons travaillé sur la biocompatibilité de nouveaux matériaux semi-conducteurs, la fonctionnalisation et la distribution des électrodes pour des interfaces rétine-machine in vitro et in vivo. La première partie de mon travail a porté sur la reconstruction d’un réseau neuronal rétinien sur une matrice de multi-électrodes. Nous proposons une nouvelle technique pour sélectionner spécifiquement des populations neuronales sur des électrodes prédéfinies d’une matrice en utilisant soit un anticorps soit une lectine spécifique. Cette sélection s’opère à partir d’une suspension cellulaire mixte dans laquelle la population d’intérêt peut être faiblement représentée. Cette possibilité de reconstruire un réseau neuronal rétinien ouvre de nouvelles perspectives dans l’étude du fonctionnement et la formation de ce réseau neuronal. La seconde partie de mon travail a porté sur le développement d’approches nouvelles pour augmenter la résolution et la stabilité à long-terme des implants rétiniens. Dans un premier temps, nous avons démontré la biocompatibilité de deux matériaux semi-conducteurs à base de carbone, le graphène et le diamant, pour les neurones rétiniens. Ces derniers peuvent en effet développer de longs prolongements directement sur ces matériaux en l’absence de tout revêtement protéique. Par contre, les cellules gliales montrent une nette préférence pour les surfaces recouvertes de peptides. Intégrant ces matériaux sur des implants in vivo, nous avons d’abord mis en évidence l’avantage d’une structure 3D pour focaliser les courants de stimulation sur des neurones s’intégrant à l’intérieur de cavités ou puits. La présence de diamant à la surface de ces prototypes 3D d’implant souples n’induit pas de réaction majeure dans la rétinede rats aveugles. Ces travaux ouvrent de nouvelles perspectives pour les interfaces cerveau machine et les neuroprothèses, en particulier les implants rétiniens en confirmant l’intérêt du diamant et du graphène et en proposant de nouvelles stratégies d’interfaçage cellule/électrode ou tissu/implantBrain-Machine Interfaces consist in the direct interfacing of a nervous tissue onto an electronic device. In vitro interfaces are expected to outperform computer calculations by achieving parallel information processing within neural networks. Applying electrical stimulations, in vivo brain-machine interfaces aim at assisting, rehabilitating or repairing cognitive or sensory-motor functions. Either for data analysis or information transfer, the main challenge of these interfaces relies in the cell/material interactions. Particularly in the case of retinal prosthetics, the current resolution remains insufficient to allow patients to read complex texts, to perform locomotion tasks in a complex environment and recognize faces. However, the first clinical trials showed encouraging results in blind patients, even though the restored visual acuity is still below legal blindness. During my PhD, we have worked on the biocompatibility of new semi-conducting materials, the functionalization and configuration of electrodes for retina-machine interfaces, both in vitro and in vivo. The first part of my work consisted in reconstructing a retinal neuronal network on a multielectrode array. We propose a novel technique to specifically address neuronal populations on pre-defined electrodes on an array, using either a specific antibody or lectine. This selection is performed from a mixed cell suspension even when selected neurons represent a minor population. This possibility to reconstruct a retinal neuronal network opens new perspectives for studying the formation and physiology of this neuronal network. The second topic of my work concerned the development of new approaches to increase the resolution and long-term stability of retinal implants. First, we demonstrated the biocompatibility of two semi-conducting carbon-based materials, graphene and diamond, with retinal neurons. These neurons could develop long neurites directly on the tested materials without any protein coating. By contrast, glial cells showed a clear preference for peptide-coated surfaces. Prior to integrating these materials on in vivo implants, we have shown the advantage of 3D structures to focalize stimulation currents onto neurons filling the implant cavities or wells. The diamond coating at the surface of these 3D soft implant prototypes does not seem to induce any major inflammation in the retina of blind rats. These works open new perspectives in the field of brain machine interfaces, neuroprostheses, with a specific emphasis on visual rehabilitation confirming the interest of diamond and graphene and proposing new strategies of cell/electrode or tissue/implant interfaces
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Zhao, Yi. "Incorporating contrast invariance into a developmental model of orientation selectivity /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?ECED%202007%20ZHAO.
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Chik, Tai-wai David, and 戚大衛. "Global coherent activities in inhibitory neural systems: Chik Tai Wai David." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31040408.
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Morales, Arroyo Miguel Angel. "The Physiology of Collaboration: An Investigation of Library-Museum-University Partnerships." Thesis, Connect to this title online, 2003. http://www.library.unt.edu/theses/open/20032/morales%5Farroyo%5Fmiguel/index.htm.
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Kanady, John. "Morphogenesis of lymphatic vascular networks| Insights from connexin and Foxc2 knockout mice." Thesis, The University of Arizona, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3671779.
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To maintain human health, the lymphatic system requires a structurally and functionally sound network of lymph vessels to absorb lipid-based nutrients, preserve extracellular fluid homeostasis, and mediate immune responses. Aside from lymphedema, investigations in the past few decades have found that impairment of the lymphatic vasculature is also involved in processes such as inflammation, tumor metastasis, fat metabolism, and obesity. However, despite a long history of study and rekindled vigor in the field of lymphatic vascular research, our knowledge of lymph vessel development and physiology is still quite limited. Recently, mutations in a protein family known as connexins (Cxs) were identified as the cause of lymphatic dysfunction in some cases of inherited lymphedema. This dissertation explores the role of primarily two specific connexins, Cx37 and Cx43, and the transcription factor Foxc2 in the morphogenesis and function of the lymphatic vasculature in mice. To accomplish this, phenotypic characterization of mice with genetic deficiencies (knockout mice) in Cx37, Cx43, and/or Foxc2 was performed principally via necropsy, histological techniques (immuno-fluorescence microscopy and H&E staining), and Evans blue dye (EBD) injections. Developmental abnormalities were found in lymphatic vascular growth, patterning, and remodeling in mice lacking Cx37, Cx43, Foxc2 or a combined deficiency of these proteins. Reductions or complete loss of lymphatic valves were a common finding in mice lacking one or more of these proteins. These valve deficits underlay lymphatic insufficiencies that resulted in lymphedema and chylothorax in some genotypes. Foxc2 was found to be a regulator of Cx37 expression. Moreover, Foxc2 was also dependent on Cx37 function for proper morphogenesis of lymph vessels. These findings pertaining to the expression of connexins in the lymphatic vasculature, their role in lymphatic valvulogenesis, and the interdependence of Cx37 and Foxc2 during lymph-vascular development represent my original contributions to human knowledge.
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Ritter, Ashlyn D. "The Influence of the Insulin-Like Gene Family and Diet-Drug Interactions on Caenorhabditis elegans Physiology: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/872.
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Aging can be defined as the accumulation of changes affecting the maintenance of homeostatic processes over time, leading to functional decline and increased risk for disease and death. In its simplicity, aging is the systemwide deterioration of an organism. Genetic studies have identified many potential molecular mechanisms of aging including DNA damage, telomere shortening, mitochondrial dysfunction, increased oxidative stress, uncontrolled inflammation, and hormone dysregulation (reviewed in [1]). However, in reality, aging is likely to be a combination of some (or potentially all) of these mechanisms.
Interestingly, aging and metabolism are tightly coordinated. Aging is a major contributor to metabolic decline and related diseases, including type 2 diabetes, metabolic syndrome, and cancer. One of the best characterized metabolic pathways implicated in aging is the insulin/IGF-1 signaling (IIS) pathway. Downstream signaling components of the IIS pathway receptor have been well studied and include an interconnected network of signaling events that regulate many physiological outputs. However, less is known about the role of upstream signaling components and how intracellular pathways and physiology are regulated accordingly. In Part I, I present my work towards understanding upstream IIS pathway components using a systems biology approach. The goal of this study is to gain insight into the redundancy and specificity of the insulin gene family responsible for initiating IIS pathway activity in Caenorhabditis elegans. The information gained will serve as a foundation for future studies dissecting the molecular mechanisms of this pathway in efforts to uncouple the downstream signaling and physiological outputs.
The clear impact of metabolism on aging and disease stimulated questions regarding the potential of promoting health and longevity through diet and dietary mimetics. Recent findings indicate reduced food intake, meal timing and nutritional modulation of the gut microbiome can ameliorate signs of aging and age-associated diseases. Aging, therefore, is also the result of dynamic and complex interplay between genes of an organism and its environment. In Part II, I will discuss my efforts to gain insight into how diet influences aging. This preliminary study has demonstrated that diet can affect lifespan in the model organism, C. elegans. Additionally, we observe diet-specific effects on drug efficacy that, in turn, modulates C. elegans lifespan and reproduction. The implications of these experiments, while limited, illustrate a potentially greater role in diet- and drug-mediated effects on lifespan.
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Ritter, Ashlyn D. "The Influence of the Insulin-Like Gene Family and Diet-Drug Interactions on Caenorhabditis elegans Physiology: A Dissertation." eScholarship@UMMS, 2008. http://escholarship.umassmed.edu/gsbs_diss/872.
Full textAbstract:
Aging can be defined as the accumulation of changes affecting the maintenance of homeostatic processes over time, leading to functional decline and increased risk for disease and death. In its simplicity, aging is the systemwide deterioration of an organism. Genetic studies have identified many potential molecular mechanisms of aging including DNA damage, telomere shortening, mitochondrial dysfunction, increased oxidative stress, uncontrolled inflammation, and hormone dysregulation (reviewed in [1]). However, in reality, aging is likely to be a combination of some (or potentially all) of these mechanisms.
Interestingly, aging and metabolism are tightly coordinated. Aging is a major contributor to metabolic decline and related diseases, including type 2 diabetes, metabolic syndrome, and cancer. One of the best characterized metabolic pathways implicated in aging is the insulin/IGF-1 signaling (IIS) pathway. Downstream signaling components of the IIS pathway receptor have been well studied and include an interconnected network of signaling events that regulate many physiological outputs. However, less is known about the role of upstream signaling components and how intracellular pathways and physiology are regulated accordingly. In Part I, I present my work towards understanding upstream IIS pathway components using a systems biology approach. The goal of this study is to gain insight into the redundancy and specificity of the insulin gene family responsible for initiating IIS pathway activity in Caenorhabditis elegans. The information gained will serve as a foundation for future studies dissecting the molecular mechanisms of this pathway in efforts to uncouple the downstream signaling and physiological outputs.
The clear impact of metabolism on aging and disease stimulated questions regarding the potential of promoting health and longevity through diet and dietary mimetics. Recent findings indicate reduced food intake, meal timing and nutritional modulation of the gut microbiome can ameliorate signs of aging and age-associated diseases. Aging, therefore, is also the result of dynamic and complex interplay between genes of an organism and its environment. In Part II, I will discuss my efforts to gain insight into how diet influences aging. This preliminary study has demonstrated that diet can affect lifespan in the model organism, C. elegans. Additionally, we observe diet-specific effects on drug efficacy that, in turn, modulates C. elegans lifespan and reproduction. The implications of these experiments, while limited, illustrate a potentially greater role in diet- and drug-mediated effects on lifespan.
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Galtier, Mathieu. "A mathematical approach to unsupervised learning in recurrent neural networks." Paris, ENMP, 2011. https://pastel.hal.science/pastel-00667368.
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Dans cette thèse nous tentons de donner un sens mathématique à la proposition : le néocortex se construit un modèle de son environnement. Nous considérons que le néocortex est un réseau de neurones spikants dont la connectivité est soumise à une lente évolution appelée apprentissage. Dans le cas où le nombre de neurones est proche de l'infini, nous proposons une nouvelle méthode de champ-moyen afin de trouver une équation décrivant l'évolution du taux de décharge de populations de neurones. Nous étudions donc la dynamique de ce système moyennisé avec apprentissage. Dans le régime où l'apprentissage est beaucoup plus lent que l'activité du réseau nous pouvons utiliser des outils de moyennisation temporelle pour les systèmes lents/rapides. Dans ce cadre mathématique nous montrons que la connectivité du réseau converge toujours vers une unique valeur d'équilibre que nous pouvons calculer explicitement. Cette connectivité regroupe l'ensemble des connaissances du réseau à propos de son environnement. Nous comparons cette connectivité à l'équilibre avec les stimuli du réseau. Considérant que l'environnement est solution d'un système dynamique quelconque, il est possible de montrer que le réseau encode la totalité de l'information nécessaire à la définition de ce système dynamique. En effet nous montrons que la partie symétrique de la connectivité correspond à la variété sur laquelle est définie le système dynamique de l'environnement, alors que la partie anti-symétrique de la connectivité correspond au champ de vecteur définissant le système dynamique de l'environnement. Dans ce contexte il devient clair que le réseau agit comme un prédicteur de son environnementIn this thesis, we propose to give a mathematical sense to the claim: the neocortex builds itself a model of its environment. We study the neocortex as a network of spiking neurons undergoing slow STDP learning. By considering that the number of neurons is close to infinity, we propose a new mean-field method to find the ''smoother'' equation describing the firing-rate of populations of these neurons. Then, we study the dynamics of this averaged system with learning. By assuming the modification of the synapses' strength is very slow compared the activity of the network, it is possible to use tools from temporal averaging theory. They lead to showing that the connectivity of the network always converges towards a single equilibrium point which can be computed explicitely. This connectivity gathers the knowledge of the network about the world. Finally, we analyze the equilibrium connectivity and compare it to the inputs. By seeing the inputs as the solution of a dynamical system, we are able to show that the connectivity embedded the entire information about this dynamical system. Indeed, we show that the symmetric part of the connectivity leads to finding the manifold over which the inputs dynamical system is defined, and that the anti-symmetric part of the connectivity corresponds to the vector field of the inputs dynamical system. In this context, the network acts as a predictor of the future events in its environment
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Witts, Emily. "Purinergic and cholinergic modulation of spinal motor networks in mice." Thesis, University of St Andrews, 2016. http://hdl.handle.net/10023/8513.
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Neuromodulation allows flexibility within networks of neurons controlling rhythmic motor behaviours. This thesis explores how purinergic and cholinergic neuromodulation contributes to the functioning of spinal motor networks in mice. Purinergic modulation in the spinal cord was investigated using neonatal mouse in vitro spinal cord preparations in which locomotor-related bursts of activity were pharmacologically induced. Ventral root recordings from these preparations showed that glia release ATP, which is broken down to adenosine and binds to A1 adenosine receptors to reduce the frequency of locomotor-related bursts. Whole-cell patch-clamp recordings showed that adenosine opens leak potassium channels in ventral horn interneurons, leading to general network inhibition. Interestingly, although adenosine reduces synaptic inputs in interneurons and motoneurons, interneurons show a reversible hyperpolarisation and reduction of miniature postsynaptic currents (mPSCs) in response to adenosine, while motoneurons show a reversible depolarisation and no change in mPSCs. It was therefore concluded that adenosine opens leak potassium channels in ventral horn interneurons which reduces the speed of locomotor-related output from the whole network. However, motoneuron activity is prevented from falling so far as to cause muscle contraction to cease. Cholinergic modulation of mouse spinal motor networks was also investigated. Pitx2+ cells, known to be the source of cholinergic C-bouton inputs to motoneurons, were selectively transfected with channelrhodopsin and light was used to activate the Pitx2+ cell population. Pitx2+ cell activation was found to reduce rheobase and range of firing in small numbers of spinal motoneurons. The role of Pitx2+ cells in behaviour was also investigated by testing adult mice before and after Pitx2+ cell ablation. No difference in performance was observed in reaching or ladder walking tasks. It therefore seems likely that activation of Pitx2+ cells modulates motoneurons via C bouton synapses, but this modulation is task-dependent and is not critical for goal-directed movements requiring fine motor control.
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Gallagher, Alexis. "Evolvability : a formal approach." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:d3b0511e-bee5-4778-8822-703c514c1c1d.
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This dissertation clarifies the concept of evolvability, the increased capacity of some organisms or systems to support evolution, especially the evolution of life-like complexity. I survey the literature, which is spread over the fields of population genetics, developmental biology, artificial life, and microbial and molecular evolution. Finding that researchers have often used the term vaguely and incompatibly I identify five distinct kinds or senses of evolvability. I also identify five key constituent ideas, which I discuss in the context of organismic evolvability, a sense of evolvability with deep roots in the traditional fields of animal development and macroevolution. In these fields research into evolvability has historically been hampered by an insufficiently detailed knowledge of development. Research in molecular evolution has produced a thorough knowledge of the folding of RNA into secondary structure, which can be regarded as a model of development. This has motivated new approaches to evolvability based on representing development via a single genotype-phenotype mapping function. I build on these approaches to invent new mathematical methods to formalise the traditional ideas. I create an exact model illustrating a classic example of evolvability, the capacity for repeated segmentation and simple modularity. I analyse this with two new formal approaches. First is the genospace algebra, a propositional calculus based on graph theory. It is a formal language for describing genotype-phenotype maps. It provides a system for making calculations, proofs, and diagrams about mutational structures in genotype space, and it is flexible enough to allow description at arbitrary degrees of resolution. Second is a pair of concepts, the genetic leverage and the genetic fulcrum. The leverage provides a crude numerical measure of evolvability, and the fulcrum provides a heuristic for identifying the genomic and developmental causes of evolvability. Besides its specific relevance to diversification and development, evolvability is also crucial to the fundamental question of how evolution produces ordinary biological life. Simulation systems that implement only a conventional textbook model of evolution -– systems possessing only variation, inheritance, and selection –- fail to evolve anything resembling the complexity of the biological world. Research into evolvability is our best bet to illuminate the "missing ingredient" for life-like evolution.
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Arnold, William Kenneth. "INSIGHTS INTO KEY GENE REGULATORY NETWORKS IN BORRELIA BURGDORFERI." UKnowledge, 2018. https://uknowledge.uky.edu/microbio_etds/19.
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Gene regulatory networks are composed of interconnected regulatory nodes created by regulatory factors of multiple types. All organisms finely tune gene expression in order to adapt to and survive within their current niche. Obligate parasitic bacteria are under extreme pressure to quickly and appropriately adapt their gene regulatory programs in order to survive within their given host. Borrelia burgdorferi is one such organism and persists in nature by alternating between two hosts; Ixodes spp. ticks and small vertebrate animals. These two hosts represent drastically different environments; requiring a unique gene regulatory program to survive and transmit between them. Microbiologists have long sought to better understand exactly what stimuli pathogens sense and how that information is relayed in to physiologic adaptation.
In this work I aimed to examine two parts of this interesting field. First, I sought to better understand the stimuli B. burgdorferi sense in order to adapt to their hosts by testing several hypotheses centered on the general notion that B. burgdorferi senses both internal and external metabolic cues as primary signals for adaptation. I demonstrated that a second messenger system immediately downstream of a critical metabolic pathway is important during vertebrate infection and that a key regulator of virulence is itself regulated by a factor involved in DNA replication.
Second, I sought to better define the topology of gene regulatory networks, known and unknown, that are important for the ability of the bacteria to adapt. The work in this section focus on the idea that B. burgdorferi gene regulatory networks are extremely complex and are not currently well defined in the literature. My studies revealed that B. burgdorferi possesses a large number of previously undefined regulatory targets, including extended 5’ and 3’ UTRs of known genes, and encodes several hundred-putative small non-coding RNAs. Furthermore, I demonstrate that two essential regulatory factors share substantial, independent, overlap in their regulons highlighting the still undefined complexity of regulatory networks at play in B. burgdorferi.
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Kuai, Wenming. "Neural networks constructed using families of dense subsets of L[subscript]2(R) functions and their capabilities in efficient and flexible training." Diss., Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/29587.
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Perchiazzi, Gaetano. "Artificial Neural Networks (ANN) in the Assessment of Respiratory Mechanics." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4665.
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