Dissertations / Theses on the topic 'Cell autonomy'
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Davis, Elizabeth M. "Common Characteristics of Young People Who Text: The Connection to Autonomy, Identity and Self-Esteem." DigitalCommons@USU, 2010. https://digitalcommons.usu.edu/etd/596.
Full textAndré-Ratsimbazafy, Marie. "Phenotype plasticity and populations’ dynamics : social interactions among cancer cells." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB032/document.
Full textIt is commonly accepted that tumors arise from cells that escape the homeostatic controls which underlie the healthy histological structure and that cell phenotype is not the result of deterministic biochemical and genetic processes, but rather the stochastic and dynamic outcome of multiple intra- and intercellular regulation networks. This PhD aims to quantitatively study the phenotypic homeostasis of the cell populations and to present an approach to the fundamental question, never heretofore studied, regarding the autonomy versus collective control of cell fate. We studied in the long run, using flow cytometry and in 2D and 3D conditions, the level of expression of CD24 and CD44 of two breast cancer cell lines (SUM149-PT and SUM159-PT). Three phenotypes were isolated (CD24-/CD44+, CD24+/CD44+, CD24-/CD44-), the latter had not previously been documented in the literature. The phenotypic behavior of CD44-low and CD44-high subpopulations has been characterized by assessing their proportion and analyzing the fluorescence map. Thereby, we observed both a periodic behavior of appearance and disappearance of pool of cells characteristics of each cell lines and a phenotypic re-diversification for each subpopulation. Only the resulting population derived from CD24-/CD44- provided the same balance as the original unsorted population. 3D re-diversification process was observed in tumorspheres from CD24-/CD44+ and CD24+/CD44+. The cells CD24-/CD44did not have that potential but nonetheless outlived anoikis. These behaviors suggest that there is an inter-cell coordination regulating the balance of phenotypic proportions. To discover the social rules regulating inter-phenotypic spatial organization, we have set up a reporter of the endogenous variations of CD24 and CD44 and developed a theoretical model of cell interactions. This work has confirmed our hypothesis that inter-cellular social rules are determining the phenotypic expression at both the uni- and multicellular scales
Suppa, Michael. "Autonomous robot work cell exploration using multisensory eye-in-hand systems /." Düsseldorf : VDI-Verl, 2008. http://www.gbv.de/dms/bs/toc/571793746.pdf.
Full textHorváth, Martin. "Mobilní autonomní fotovoltaický systém." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2010. http://www.nusl.cz/ntk/nusl-218312.
Full textKalincik, Tomas Medical Sciences Faculty of Medicine UNSW. "Disturbances of autonomic functions in spinal cord injury: autonomic dysreflexia and thermoregulation." Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43516.
Full textJanáč, Stanislav. "Vývoj ovládacího programového prostředí pro autonomní fotovoltaický systém." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2009. http://www.nusl.cz/ntk/nusl-217927.
Full textOvesný, Karel. "Vývoj fukčních bloků pro autonomní fotovoltaický systém." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2011. http://www.nusl.cz/ntk/nusl-218858.
Full textŠćepanović, Danilo (Danilo R. ). "A model of sinoatrial node cell regulation by the autonomic nervous system." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68457.
Full textCataloged from PDF version of thesis.
Includes bibliographical references (p. 243-260).
The primary function of the heart is to pump blood at a sufficient rate to ensure perfusion of all the organs. This vital task is achieved in large part by controlling the rate of cardiac contractions, which are initiated by cells in the sinoatrial node, the "pacemaker" of the heart. The oscillation rate of these spontaneously active cells is tightly regulated by the sympathetic and parasympathetic branches of the autonomic nervous system. Our understanding of sinoatrial node cell function has been greatly advanced by experimental and modeling efforts that quantitatively describe the numerous ionic currents responsible for the cell's spontaneous depolarization and generation of the action potential. Several models have also explored the effect of sympathetic and parasympathetic activity on specific ion channels and have reproduced the classic slowing and acceleration phenomena. However, a complete model of this interaction does not exist: current models lack the ability to simulate simultaneous sympathetic and parasympathetic activation or to reproduce heart rate dynamics in response to time-varying autonomic inputs. We addressed this need by constructing a bottom-up model of sinoatrial node cell regulation by the autonomic nervous system, with a focus on reproducing the full range of heart rates observed under simultaneous sympathetic and parasympathetic nerve stimulation, as well as the dynamic heart rate response to steps in sympathetic or parasympathetic stimulation rate. In constructing our model, we consolidate a large body of experimental data in a consistent mathematical framework. The model comprises 57 nonlinear coupled ordinary differential equations based on first principles and the current mechanistic understanding of the component reactions, fits well all the experimental data used to build the model, and reproduces high-level features of the system that were not explicitly fit when building the model. The detailed nature of the model also allows numerous conclusions to be drawn about the mechanisms of heart rate control. A better understanding of these mechanisms in health and disease may enable the development of better diagnostics for cardiovascular disease and more targeted drug design. We also identified a number of limitations in the present model that can be refined through further experimental and numerical efforts.
by Danilo Šćepanović.
Ph.D.
Vespalec, Arnošt. "Design autonomní sněžné rolby." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2017. http://www.nusl.cz/ntk/nusl-318671.
Full textSuppa, Michael. "Autonomous robot work cell exploration using multisensory eye in hand systems." Düsseldorf VDI-Verl, 2007. http://d-nb.info/989488659/04.
Full textNout, Yvette Stephanie. "Novel method to study autonomic nervous system function and effects of transplantation of precursor cells on recovery following spinal cord contusion injury." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1141954753.
Full textDe, Roubaix J. A. M. (John Addey Malcolm). "Value, utility and autonomy : a moral-critical analysis of utilitarian positions on the value of prenatal life." Thesis, Stellenbosch : Stellenbosch University, 2005. http://hdl.handle.net/10019.1/50542.
Full textENGLISH ABSTRACT: Problem statement For utilitarians, human beings have intrinsic moral significance based on only two acquired characteristics: sentience, or the ability to suffer, and psychological personhood. Sentience is the entrance-requirement for moral significance, but does not justify a "right to life" claim; at most a "right" not to suffer. Personhood, described as some sort of self-conscious awareness with a concept of the future, may justify a "right to life" claim. However, since personhood is absent in prenatal beings, and only develops some time after birth, the implication is that such beings have little moral significance and may, for instance, be killed "at will". The moral problem that I address in this dissertation is to investigate, assess and evaluate the utilitarian position on the moral status or value of prenatal life. Methodology and results I firstly, on the basis of an extensive literature study, make a detailed analysis of the utilitarian position with reference to a number of themes that I have identified in their argument. This is followed by a critical philosophical evaluation of the utilitarian position, based on six particular arguments: • Utilitarianism is philosophically incoherent. It over-simplifies the moral argument in claiming that consequences are all that matter morally. Its underlying moral theory is at odds with moral claims contained in contemporary notions of human rights and individual justice. It ignores the moral significance of special obligations to special groups. • Utilitarianism potentially has unacceptable consequences. It IS inherently discriminatory and may lead to legitimate "slippery slope" fears. • Utilitarianism clashes with our fundamental moral intuitions on the value of prenatal life. These intuitions are cherished in most world religions. • Contrary to the utilitarian position, speciesism is inevitable to the human condition, especially argued from a position of existential phenomenology. Self- constitution, simultaneous constitution of the world as we know it, and the very possibility of morality are possible only within a particular notion of speciesism. • The potentiality of pre-persons to develop into persons cannot be as convincingly ignored as is done by the utilitarian. • There is a basic and underlying need and intuition to protect vulnerable human beings, of which pre-persons are exemplars. These notions clash with utilitarian theory. As an alternative, I introduce, set out and evaluate a two-phased position on the moral significance of pre-personal human life, a position of respectfulness of prenatal and pre-personal human life based upon its humanity, potentiality and separation-viability. This leads, firstly, to the conclusion of a graded, sliding scale conception of human prepersonal moral significance in line with the level of development and with the actuation of potentiality. Secondly, it leads to the conclusion that the advent of separationsurvivability (viability) is a morally significant cut-off point beyond which the human fetus may "normally" have a justifiable right to the continuation of its life. In as far as the application of my argument is concerned, I develop a "moderate" position with reference to the abortion debate. Whilst I recognize that all human prenatal beings of which it can be argued that they have a reasonable chance to develop their intrinsic potentiality, i.e., to become full-fledged persons, should have the opportunity to do so, I also recognize that neither this position, nor the complexities of life make it possible to hold "absolute" positions on the justifiability of abortion. I explore this extremely problematic notion in the text. That having been said, the advent of separation-survivability may imply a "moral cut-off point", beyond which termination is only rarely justified. I argue that I find no moral hindrance to wellmotivated research on human pre-embryos and stem cells.
AFRIKAANSE OPSOMMING: Probleemstelling Utilitariste huldig sterk omlynde standpunte oor die waarde van lewe. Hulle redeneer dat menslike (inderwaarheid, alle lewende) wesens slegs op grond van twee eienskappe intrinsieke morele waarde kan verwerf: sentiëntisme, d.i. die vermoë om lyding te ervaar, en persoonstatus. Sentiëntisme is 'n bepalende vereiste vir morele status, maar regverdig nie 'n "reg op lewe"-aanspraak nie. Persoonsyn, verstaan as 'n vorm van selfbewustheid tesame met 'n bewuste belang by die voortsetting van eie bestaan, mag wel so 'n aanspraak regverdig. Voorgeboortelike (en "voorpersoonlike") wesens is egter nie persone nie; hulle word eers (aansienlik) ná geboorte volwaardige persone. Die implikasie is dat sulke wesens weinig morele status het, en byvoorbeeld, na willekeur gedood mag word. Die morele probleem wat ek in hierdie dissertasie aanspreek is om die utilitaristiese beskouing ten opsigte van die morale status of waarde van voorgeboortelike lewe krities-filosofies te ondersoek en te evalueer. Metodologie en gevolgtrekkings Eerstens maak ek na aanleiding van 'n gedetaileerde literatuurstudie 'n in-diepte analise van van die utilitaristiese posisie aan die hand van 'n aantal temas wat ek in hul argument geïdentifiseer het. Daarna volg 'n krities-filosofiese evaluasie van die utilitaristiese posisie, aan die hand van ses argumente: • Utilitarisme is filosofies onsamehangend. Dit oorvereenvoudig die morele argument deur voor te gee dat gevolge al is wat moreel saakmaak. Die onderliggende utilitaristiese teorie bots met die morele eise vervat in kontemporêre sienings van menseregte en geregtigheid. Dit negeer die morele belangrikheid van spesiale verpligtinge teenoor spesiale belangegroepe. • Utilitarisme het potensieelonaanvaarbare gevolge. Dit IS inherent diskriminerend en kan lei tot onkeerbare glybaan ("slippery slope")-argumente. Utilitarisme bots met ons fundamentele morele intuïsies betreffende die waarde van voorgeboortelike lewe. Hierdie intuïsies word onder meer ondersteun deur die meeste hoofstroom godsdienste. • Spesiësisme is, in kontras met die utilitaristiese beskouing, onafwendbaar vir ons selfverstaan as mense, soos aangetoon kan word met 'n beroep op die eksistensiële fenomenologie. Self-konstituering, gelyktydige konstituering van die wêreld van die mens, en selfs die moontlikheid van moraliteit is slegs moontlik vanuit' n bepaalde spesiësistiese beskouing. • Die potensialiteit van "pre-persone" om tot volwaardige persone te ontwikkel kan nie, soos die utilitaris doen, sonder meer geïgnoreer word nie. • Daar is 'n basiese en onderliggende morele eis om swak en weerlose menslike wesens te beskerm. Hierdie idees bots lynreg met utilitaristiese teorie. As 'n alternatief tot die utilitaristiese beskouing, ontwikkel ek 'n twee-fase posisie betreffende die morele waarde van voorgeboortelike menslike lewe. Ek noem hierdie posisie agting vir voorgeboortelike en voor-persoonlike menslike lewe gebaseer op die menslikheid, potensialiteit en oorleefbaarheid van prenatale mense. Dit lei, eerstens, tot die gevolgtrekking van 'n gegradeerde glyskaal konsepsie van voor-persoonlike menslike morele waarde, min of meer parallel aan die vlak van ontwikkeling en die ontwikkeling van potensialiteit. Tweedens lei dit tot die gevolgtrekking dat die ontwikkeling van lewensvatbaarheid 'n moreel-beduidende afsnypunt is waarna die menslike fetus "normaalweg" aanspraak kan maak op 'n reg dat sy lewe voortgesit moet word. In soverre dit die toepassing van my argument betref, ontwikkel ek 'n "gematigde" posisie vis-á-vis aborsie. Ek redeneer dat alle menslike voorgeboortelike wesens wat 'n redelike kans het dat hul intrinsieke potensialiteit verder sal ontwikkel, die geleentheid daartoe gegun behoort te word. Ek aanvaar ook dat nog hierdie beskouing, nog die kompleksiteit van die menslike bestaan "absolute" posisies moreel regverdig. Die problematiek en inherente spanning tussen hierdie oënskynlik-opponerende posisies word in die teks bespreek. Nogtans beskou ek die ontwikkeling van lewensvatbaarheid as 'n moreel insiggewende afsnypunt waarna terminasie net in buitengewone omstandighede moreel regverdigbaar is.
Habif, Guillaume. "Identification des évènements de signalisation associés à la prolifération autonome induite par le récepteur mutant FLT3-ITD dans les cellules myéloïdes." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10327.
Full textThe FLT3 receptor is involved in stem cells and myeloid progenitors self renewal processes. In about 30% of the acute myeloid leukemia cases, this receptor is mutated and constitutively active, the most common mutation being duplication of sequences in the juxtamembrane domain (Internal Tandem Duplication, ITD). Many chemical inhibitors of FLT3 have been developed for anti-cancer therapies but the clinical trials were a bit disappointing, showing mainly transient effect on blast reduction. Several studies have shown that FLT3-ITD triggers a different signaling from the wild-type receptor, like the specific activation of STAT5a. These data show the necessity of the exhaustive and detailed study of the intracellular signaling induced by FLT3 and its oncogenic mutants, to identify new therapeutic targets. We have overexpressed wild-type and ITD mutant forms of FLT3 in the murine myeloid progenitors cell line FDCP-1/Fms. This model proved it-self representative of the in vivo processes described in the literature in terms of survival, proliferation and monocytic differentiation. Consequently, we have used it for a proteomic approach to identify differentially expressed and/or phosphorylated proteins depending on FLT3 status. Using RAN interference and overexpression of these identified candidate proteins, we have demonstrated the functional involvement of several of them in FLT3 signaling, including Hcls1, Ezrin, and PAK1, which all regulate the cytoskeleton
Hedreville, Mona. "Effet de l'exercice physique sur l'activité du système nerveux autonome des porteurs du trait drépanocytaire et des patients atteints de la drépanocytose homozygotte." Antilles-Guyane, 2010. http://www.theses.fr/2010AGUY0390.
Full textSanchez, Samuel, Alexander A. Solovev, Sabine Schulze, and Oliver G. Schmidt. "Controlled manipulation of multiple cells using catalytic microbots." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-138608.
Full textDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
Merighi, Adalberto. "Light and electron microscopical studies on the distribution of peptides and 'classical' neurotransmitters in dorsal root ganglion cells and in the dorsal horn of the spinal cord." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46446.
Full textGheno, Alexandre. "Printable and printed perovskites photovoltaic solar cells for autonomous sensors network." Thesis, Limoges, 2017. http://www.theses.fr/2017LIMO0108/document.
Full textThis thesis is about the design of photovoltaic solar cells based on hybrid perovskite using inkjet printing technology. The first two chapters present the context of the thesis, namely the powering of an autonomous sensor network, and review the scientific aspects of inkjet and photovoltaic technologies. The third chapter presents the development of a state-of-the-art photovoltaic cell and its evolution towards a printable architecture at low annealing temperatures. The problem of the stability of photovoltaic cells with perovskite is also discussed. The last part presents the different aspects and problems of the inkjet printing of the three inner layers of a perovskite solar cell. At the end of this work the possibility of printing perovskite solar cells with efficiencies higher than 10% has been demonstrated, all in ambient conditions and at low temperature
Xue, Zhi-Gang. "Recherches sur la différenciation du système nerveux periphérique chez les oiseaux : mise en évidence et propriétés des précurseurs de type autonome présents dans les ganglions sensoriels." Paris 13, 1987. http://www.theses.fr/1987PA132008.
Full textSanchez, Samuel, Alexander A. Solovev, Sabine Schulze, and Oliver G. Schmidt. "Controlled manipulation of multiple cells using catalytic microbots." Royal Society of Chemistry, 2011. https://tud.qucosa.de/id/qucosa%3A27763.
Full textDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
Ramond, Adrien. "Conception et réalisation d'une nouvelle architecture multi-entrées multi-sorties pour la gestion de micro puissance dans les systèmes autonomes." Phd thesis, INSA de Toulouse, 2011. http://tel.archives-ouvertes.fr/tel-00660368.
Full textMorel, Élodie. "Étude pathophysiologique de la fibrillation atriale : approche multifacette." Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00729075.
Full textChen, Zetao. "Biologically-inspired place recognition with neural networks." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/98550/1/Zetao_Chen_Thesis.pdf.
Full textLarsen, Hege Ekeberg. "Neuronal control of cardiac excitability in pro-hypertensive states." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:04d38eb6-ea66-4283-91ab-dd75bca246e9.
Full textTesta, Damien. "Contrôler la plasticité du cortex cérébral adulte à travers l'action non-autonome de l'homéoprotéine Otx2 A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor Non-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b/g." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS234.
Full textDuring postnatal development, extracellular Otx2 homeoprotein is preferentially internalized by parvalbumin (PV) interneurons of the visual cortex and regulates the critical period for ocular dominance plasticity. The specificity of Otx2 internalization is mediated by chondroitin sulfate type E (CS-E) which is a component of the extracellular matrix enriched in glycosaminoglycans that condenses around PV cells during the critical period. The continuous supply of Otx2 in adults is necessary to maintain a non-plastic state of the cerebral cortex. Thus, a reopening of plasticity is possible by disrupting Otx2 transfer. We developed a transgenic mouse line with inducible secretion of single chain antibodies directed against Otx2 to separate the autonomous and non-autonomous activity in order to study its role in the maturation of cortical PV cells. We found that this maturation involves direct regulation of Gadd45b/g genes by Otx2 and that Gadd45b may control plasticity by influencing the methylation state of DNA and thus the epigenetic status of PV cells. We have also developed easily synthesizable peptides that mimic CS-E and are able to interact in vivo with Otx2 to block its transfer. Tools for neutralizing extracellular Otx2 have significant therapeutic potential for critical period pathologies
Svoboda, Luděk. "Systém včasné výstrahy před lokální povodní." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219710.
Full textMorineau, Céline. "Caractérisation d'un nouveau membre du complexe d'élongation des acides gras chez Arabidopsis thaliana : intéractions métaboliques et régulation développementale." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112420.
Full textVery long chain fatty acids (VLCFA) are involved in plant development and particularly in several cellular processes such as membrane trafficking, cell division and cell differentiation. However, the precise role of VLCFA in these different cellular processes is still poorly understood in plants. In order to identify new factors associated with the biosynthesis or function of VLCFA, a yeast multicopy suppressor screen was carried out in a yeast mutant strain defective for fatty acid elongation. Loss of function of the elongase dehydratase PHS1 in yeast and PASTICCINO2 in plants prevents growth and induces cytokinesis defects. PROTEIN TYROSIN PHOSPHATASE-LIKE (PTPLA) previously characterized as an inactive dehydratase was able to restore yeast phs1 growth and VLCFA elongation but not the plant pas2 defects. PTPLA interacted with elongase members in the ER and its absence induced the accumulation of 3-hydroxyacyl-CoA as expected from a dehydratase involved in fatty acid (FA) elongation. However, loss of PTPLA function led to increased VLCFA levels, effect that was dependent of the presence of PAS2 indicating that PTPLA activity repressed FA elongation. The two dehydratases have specific expression profiles in the root with PAS2, mostly restricted in the endodermis, while PTPLA was confined in the vascular tissue and pericycle cells. Comparative ectopic expression of PTPLA and PAS2 in their respective domains confirmed the existence of two independent elongase complexes comprising PAS2 or PTPLA that were functionally interacting in a non-cell autonomous manner. A putative regulating signal could involve cytokinins that were described to be regulated by VLCFA. VLCFA were indeed found to repress IPT3 expression in roots like in leaves. Cytokinins were also found to regulate VLCFA levels suggesting the existence of regulatory feedback loops between cytokinins and VLCFA
Morais, Sharon Del Bem Velloso de. "Efeito das células-tronco mesenquimais na modulação autonômica cardíaca e na sensibilidade do barorreflexo em ratos com insuficiência cardíaca." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17134/tde-09012016-114938/.
Full textCardiovascular diseases are among the leading causes of death, especially those resulting from myocardial infarction (MI). Stem cell therapy has shown promising results after MI in both patients and experimental animals, especially those using mesenchymal stem cells (MSC), which present potential pro-angiogenic, anti-fibrotic and immunomodulatory. However, no studies have been conducted on the heart rate variability (HRV), autonomic tone and baroreflex sensitivity, which are considered risk factors and are attenuated in heart failure (HF) induced by MI. Thus, the main of this study was to examine the effect of bone marrow MSC transplantation on autonomic modulation and baroreflex sensitivity in rats with HF, induced by MI. Therefore, it was performed ligation of the left coronary artery of male Wistar rats (220-360g) and after two to three days, assessment was made of the area infarcted by SPECT. MSC were injected intravenously seven days post-MI. Cardiac function was assessed by ventriculography before and one month after transplantation. After reassessing the ventriculography, the animals underwent electrocardiographic recordings after receiving electrodes implanted subcutaneously on the back, and cannula in the left jugular vein for drug determination of autonomic tone. Also, cannula was implanted in the femoral artery for blood pressure recording and analysis of baroreflex sensitivity. Soon after the records, the animals were sacrificed for collection of the heart and histopathological analysis. For infusion, the MSC were characterized according to the criteria of the International Society for Cellular Therapy. The lesion area induced soon after artery ligation was similar among animals. One month after treatment, infarct size was reduced in the group treated with MSC. A reduction was observed in left ventricular ejection fraction (LVEF) after coronary ligation, and prior to treatment in HF animals. One month after the MSC therapy, or saline injection, there was no improvement in LVEF in both groups with HF. The QT and corrected QT intervals were lengthened by IM, while the MSC had no effect on these parameters. HRV showed a reduction in the standard deviation of successive values (SDNN) of the RR interval (RRi), and the root mean square of the successive (RMSSD) RRi after MI, while the MSC prevented this reduction. In spectral analysis, the RRi spectra, after infarction, showed lower power, in absolute units, of the low frequency, LF, and high frequency band, HF, while MSCs promoted an increase in these parameters. Nonlinear methods of HRV showed a reduction in entropy, and increased detrended fluctuation analysis (DFA) of RRi, post-MI. The MSC therapy prevented the change of entropy and also protected DFA. Heart rate was similar in both groups; however, the intrinsic heart rate was reduced in HF group, while treatment with MSC preserved this attenuation. A lower vagal tone was observed in HF untreated group, while treatment with MSC increased vagal tone. The sympathetic tone did not differ between groups. The baroreflex sensitivity to bradycardia was reduced in HF, while the MSC prevented this reduction. The interstitial collagen was increased in HF, but not in the group treated with MSC. Systolic blood pressure (BP), the mean BP and parameters of BP variability: SDNN and LF were reduced in the groups with HF, treated or not with MSC. Together, these data demonstrate that MSC therapy reduced the infarct size and interstitial fibrosis in the remaining myocardium of the left ventricle. In addition, the cells improved cholinergic autonomic modulation of the heart, heart rate variability and baroreflex sensitivity.
Hierso, Régine. "Implication du stress oxydant dans la physiopathologie de la drépanocytose : crises vaso-occlusives, taux d'anticorps anti-bande 3 et oxydation du globule rouge." Thesis, Antilles, 2015. http://www.theses.fr/2015ANTI0045/document.
Full textBesides the primary defect of sickle cell disease, hemoglobin S (HbS) polymerization, other abnormal processes may contribute to the development of an inflammatory response and to an oxidative stress caused by traumatic hypoxia-reperfusion and autoxidation of HbS. The exacerbation of oxidative stress seems to participate actively in the pathophysiology of the disease and play a role in vaso-occlusive crisis (VOC). The aim of this thesis was to document the deleterious effects of oxidative stress on the red blood cell and its impact in the development of VOC. First, we have evaluated the impact of tert-butyl hydroperoxide-induced oxidative stress on blood rheology of SS and SC sickle cell patients. We have shown that sickle red blood cells (SS RBC) produce more free radicals in the presence of tert-butyl hydroperoxide (TBHP) than control subject red blood cells (AA RBC). Furthermore, SS RBC have a decreased anti-oxidant defense system. Induction of oxidative stress increases the rheological alterations already present in sickle cell patients (ie, decreased deformability, reduced aggregation, increased disaggregation threshold). In control subjects, oxidative stress induces an altered hemorheological profile close to that already present in sickle cell patients. These results suggest that oxidative stress by modulating the hemorheological abnormalities associated with sickle cell disease, could be one of the factors promoting the occurrence of sickle cell complications. Then, we have studied the impact of oxidative stress in the development of VOC, analyzing blood samples from SS patients in crisis and at steady state. 1) We have tested the hypothesis that the protein band 3 of RBC, is a major target of reactive oxygen species, which cause the appearance of senescence epitopes of this protein recognized by auto anti-band 3 antibodies; 2) We have evaluated pro- and anti-oxidants molecular and cellular markers; 3) We have studied the evolution of hemorheological parameters; 4) We have explored the activity of the autonomic nervous system, seen as a potential marker of severity. Our results show during VOC: 1) an exacerbation of the oxidative stress; 2) a decrease in anti-band 3 antibodies levels and an increase in the plasma concentration of erythrocyte microparticles, suggesting that these two processes are linked to the clustering phenomenon of band 3 protein triggered by oxidative stress; 3) an exacerbation of hemorheological abnormalities resulting in a reduction of SS RBC deformability, increased aggregation and disaggregation threshold; 4) an impairment of the autonomic nervous system marked by a withdrawal of parasympathetic activity and this imbalance is accentuated during VOC. This work allows a better understanding of the complex pathophysiology of sickle cell disease, highlighting the impact of oxidative stress in the development of VOC, the leading cause of hospitalization of sickle cell subjects. The data obtained, which reveal relevant markers of oxidative stress during VOC, could promote the implementation of new antioxidant therapeutic approaches and help improving sickle cell patients care
Rue, Timothy James. "Modular Vehicle Design Concept." Thesis, Virginia Tech, 2015. http://hdl.handle.net/10919/51219.
Full textMaster of Science
Wixner, Jonas. "Gastrointestinal disturbances in hereditary transthyretin amyloidosis." Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88745.
Full textSun, Jun. "Study of neuronal networks and mechanisms implicated in locomotor reactivity and Parkinson's disease pathogenesis in the Drosophila model." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS434.
Full textParkinson's disease (PD) is a progressive neurodegenerative motor disorder, characterized by the loss of dopaminergic neurons from the substantia nigra and the presence of cytoplasmic inclusions composed mainly of α-synuclein (α-syn), called Lewy bodies. The objectives of my thesis work were to characterize a PD model developed in Drosophila in order to understand how the accumulation of α-syn in DA neurons can progressively disturb locomotion and to search for new neuroprotective proteins. We first identified brain networks involved in modulating locomotor reactivity in Drosophila, which include subsets of DA neurons associated with the mushroom bodies. We then obtained evidence that the expression of α-syn in DA neurons disrupts mitochondrial dynamics both in these neurons themselves and, through a non-cell-autonomous process, in their cholinergic target neurons of the mushroom bodies. Finally, we show that the Argonaute Piwi protein is induced by oxidative stress and has a neuroprotective effect in a sporadic PD model in Drosophila. Our evidence suggests that Piwi could delay neuronal aging and PD progression by reducing deleterious transcription of transposable elements. Overall, these studies highlight pathological and neuroprotective mechanisms that may constitute novel targets for the therapeutic treatment of PD
Oliveira, Dilton Dantas de. "Uma arquitetura baseada na teoria do perigo para predição de ataques de segurança em redes autonômicas." Universidade Federal de Sergipe, 2013. https://ri.ufs.br/handle/riufs/3356.
Full textO crescimento do número de dispositivos conectados, do volume de dados trafegados e das aplicações utilizadas tem evidenciado um aumento importante na complexidade das redes atuais, deixando a atividade de gerência cada vez mais difícil para os administradores de redes e sistemas. Aspectos de gerência, como a segurança desses sistemas tem sido um dos principais desafios enfrentados pelos pesquisadores, principalmente, considerando que, em paralelo, observa-se um também importante aumento no grau de sofisticação das atividades maliciosas. Tal cenário exige o desenvolvimento de sistemas de segurança igualmente sofisticados, com o intuito de impedir ou conter ataques cada vez mais destrutivos aos sistemas, como os ataques de worms. E a inspiração biológica tem sido uma das grandes aliadas nesta empreitada, trazendo diversos conceitos e novas formas de pensar e resolver esses problemas. Este trabalho utilizou os conceitos bio-inspirados das Redes Autonômicas (redes autogerenciáveis inspiradas nos funcionamento do sistema nervoso humano) e dos Sistemas Imunes Artificiais (sistemas de segurança computacional inspirados no funcionamento do sistema imunológico humano), para definir uma arquitetura de gerência para autoproteção de redes, através da predição de ataques de segurança. Tal arquitetura incorpora o modelo imuno-inspirado da Teoria do Perigo e utiliza o seu Algoritmo das Células Dendríticas para correlacionar eventos e detectar anomalias. A análise da arquitetura foi realizada em um Sistema de Alerta Antecipado, que usa notificações recebidas de máquinas já infectadas por worm como informação adicional para identificar a iminência de uma infecção em máquinas ainda vulneráveis. Nos experimentos o ganho de tempo obtido com essa identificação precoce foi utilizado no modelo de propagação do worm Conficker e os resultados apontaram uma redução no número de máquinas infectadas e, consequentemente, na propagação deste worm em uma rede
Ribera, Melissa Chaves Vieira. "Modulação autonômica cardíaca em crianças e adolescentes com anemia falciforme." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/6/6136/tde-17072017-165426/.
Full textIntroduction - Cardiac changes in sickle cell disease (AF) are frequent and begin early. There is evidence that there is also dysfunction in the regulation of the autonomic nervous system, which may contribute to morbidity events. Objectives - To evaluate the autonomic cardiac modulation by heart rate variability in children and adolescents with sickle cell anemia. Method - An analytical study comparing the heart rate variability of 45 children and adolescents, younger than 20 years, with sickle cell anemia, with a control group matched one by one by age and sex. The heart rate was obtained by pulse frequency and analyzed, beat by beat. These patients are attending the pediatric hematology outpatient of the National Health System. Results - We observed a significant difference in the frequency domain indexes (VLF, LF, HF and LF / HF). The results of this study are in agreement with resolution 466/2012 of the Ministry of Health of Brazil. These differences were not observed in patients taking hydroxyurea. Conclusion - There is an autonomic dysfunction in AF that occurs from childhood, and may be related to a lower modulation of the sympathetic and greater modulation of the parasympathetic. This difference was not observed in patients taking hydroxyurea
Júnior, Evilásio Leobino da Silva. "Expressão de receptores adrenérgicos do sistema nervoso autônomo e dos marcadores de células tipo-Cajal na fibrilação atrial permanente humana." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-06112015-155839/.
Full textAtrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, presenting the highest morbidity, especially with advancing age. The autonomic nervous system, particularly the adrenergic/cholinergic balance, has a profound influence on the occurrence of AF. AF can be generated and maintained through a variety of electrophysiological mechanisms, and a change in autonomic activity may affect each of mechanism differently. In addition to the autonomous, sympathetic, and parasympathetic nervous systems involved in the genesis and maintenance of AF, there are several other factors known to be involved, including the interstitial cells of Cajal (ICCs), similar to the interstitial cells that contribute to the peristaltic motor activity of the gastrointestinal tract. These cells were found in the atrial and ventricular myocardium, and could be the source of the triggering activity of ectopic electrical foci that generate AF. In the present study, we aimed to analyze the possible changes in the myocardial expression of beta-adrenergic receptors and to quantify ICCs in the atria of human hearts, in particular in the left atrium, and its relation with permanent AF (PAF). For the first objective, we studied 19 hearts from autopsies of patients with PAF and defined chronic cardiomyopathy (group I), and 19 paired hearts with the same cardiomyopathy but without evidence of any supraventricular arrhythmia (group II). A tissue sample from the ceiling of the right atrium, two from the left atrium, and one from the nerve ending involved in the adipose tissue in the epicardium of the left atrium (fat pad) were resected. The myocardial expression of beta-adrenergic receptors 1 and 3, and of the G protein-coupled receptor kinase 5 (GRK5) was assessed according to the positive proportion in the myocardium in the mentioned sections. There was no statistically significant difference between the two groups in the expression of adrenergic receptors (beta-1, beta-2, beta-3, and GRK5), regardless of the use or nonuse of beta-blockers. For the second objective, six hearts from autopsied patients with PAF and defined chronic cardiopathy (group I) were studied, along with six paired hearts with the same cardiopathies but without evidence of any supraventricular arrhythmia (group II). The ICCs were evaluated in the middle region of the diaphragmatic wall of the left atrium. There were no statistically significant changes between the groups when we evaluated the number of positive cells in the myocardium by area of the myocardium in mm2, the number of positive cells in the full section by area of the myocardium in mm2, or the number of positive cells in the full section/area of the full section in mm2, be it in relation to each section individually, the left atrium alone, or all sections together. In conclusion, neither changes in the expression of beta-adrenergic receptors nor the presence of ICCs seem to have a large role in the pathogenesis of permanent AF
Souza, Pamella Ramona Moraes de. "Influência da desnervação seletiva dos barorreceptores e quimiorreceptores nas variáveis hemodinâmicas e morfofuncionais dos tecidos cardíaco e músculo-esquelético em ratos espontaneamante hipertensos." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-20052014-104228/.
Full textArterial hypertension (AH) is a multifactorial disease on which there is the interaction of several mechanisms , therefore is related to functional and / or structural changes of the target organ . Functional changes of the regulatory mechanisms of blood pressure (BP) in the short term , as pressoreceptor and chemoreceptors, has been extensively explored in order to understand the possible mechanisms that may be related to the genesis of hypertension. Thus, we used the experimental model of sinoaortic denervation (DSA) and selective denervation of those afferent aortic (DA) and / or carotid (DC) and the ligature of the carotid body artery (LA) to evaluate the relative importance of baroreceptors and chemoreceptors on control of neurogenic circulation mediating cardiac and musculoskeletal responses in HA. There by, we used Wistar rats (CTR) and spontaneously hypertensive rats (SHR) subjected to different denervation (SHRDSA / SHRDA / SHRDC) and the ligature of the carotid body artery (SHRLA). The animals were followed for 10 weeks after the selective denervation it was performed echocardiographic evaluations, blood gas, hemodynamic, autonomic and regional blood flow. Subsequently, the animals were euthanized for tissue collection for genetic and histological evaluations. Results: SHR animals showed hemodynamic, autonomic dysfunction and gas exchange (respiratory alkalosis) compared to CTR group as well as the analysis of hypertrophy, flow and histology of skeletal muscle, such as the transition to a more glycolytic phenotype profile in soleus and increased cross-sectional area of type I fibers and reduction of type IIB fibers in the diaphragm . In hypertensive experimental groups, animals with prejudice chemoreflex (SHRDC, SHRLA and SHRDSA) , showed higher pCO2 compared to SHR and SHRDA group. All groups with different denervation showed autonomic changes in blood flow and capillarization. However, our major findings were compared to SHRDA group, which was significantly higher than the SHR in SBP (212 ± 2 vs 200 ± 3), DBP (156 ± 4 vs 144 ± 3), MAP (185 ± 9 vs 172 ± 3) and HR (377 ± 4 vs 350 ± 7) parameters. Furthermore, we showed an increase in BP variability (BPV) and in the peripheral sympathetic (BFPAS), otherwise showed in the groups SHRDC and SHRLA compared to SHR . Autonomic control of HR, the SHRDA group showed lower sympathetic and higher parasympathetic effect effect in relation to SHR. Already SHRDC and SHRLA groups had a lower parasympathetic effect without changes in sympathetic, although peripheral vascular resistance was increased in SHRLA group. The cardiac morphofunctional adaptations (echocardiography and cardiac hypertrophy markers) were more evident in the group that had total dysfunction of both receptors (SHRDSA). Conclusion: The absence of reflex control exerted by arterial baroreceptors predominantly showed a greater influence of the aortic component of the carotid on BP. In addition, systolic function appears higher in groups SHRDA and SHRDSA, suggesting that aortic denervation is associated with sympathetic activation. No cardiac abnormality was observed in the carotid denervation. Regarding skeletal muscle, all denervations showed an increased of capillarization, while only SHRDSA group showed reduction of intermediate fibers. Increased capillarization may be associated with the release of the peripheral sympathetic denervation, including removal of the aortic baroreceptors, leading to increased VPA and the absence of chemoreceptors in groups with deafferentation of the carotid receptors
Koton, Jaroslav. "Syntéza a analýza obvodů s moderními aktivními prvky." Doctoral thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2009. http://www.nusl.cz/ntk/nusl-233476.
Full textMouafo, Zanguim Idriss. "Dimensionamento del Sistema Propulsivo Elettrico Puro di un Velivolo Cessna 172k." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/18702/.
Full textChaar, Laiali Jurdi El. "Hipertensão arterial e disfunção autonômica induzidas por dieta hiperlipídica: papel do CART e de fatores inflamatórios em núcleos autonômicos do sistema nervoso central." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-05092016-160200/.
Full textObesity is a risk factor for high blood pressure and the mechanisms involved in this disease are not fully clarified. C57BL/6J and transgenic mice with toll-like-NFκB receptor inflammatory- pathway deletion in neurons and glia were fed with high-fat diet (HL) for 8 or 15 weeks and assessed metabolic parameters, blood pressure, heart rate, autonomic nervous system activity, inflammatory factors and neuropeptides in the hypothalamus and brainstem. The HL mice developed hypertension accompanied with autonomic dysfunction and increased CART in DMH. Transgenic animals when submitted to HL diet developed obesity, but not showed high blood pressure and autonomic dysfunction. In addition, HL animals had increased CCL5 mRNA in hypothalamus, CD86 mRNA in brainstem and micróglia density in caudal NTS. The results suggest new mechanisms for hypertension and autonomic dysfunction secondary to intake of high-fat diet by showing CART role in DMH and the involvement of the inflammatory pathway TLR-NFκB in neurons and glia.
Berrebi, Johanna. "Contribution à l'intégration d'une liaison avionique sans fil. L'ingénierie système appliquée à une problématique industrielle." Phd thesis, Ecole Polytechnique X, 2013. http://pastel.archives-ouvertes.fr/pastel-00800141.
Full textPaiva, Rafael Almeida. "Thumus autonomy." Doctoral thesis, 2021. http://hdl.handle.net/10362/130705.
Full textSiechen, Scott A. "Axon guidance autonomy and tensional requirement for synaptic function : is learning a forced response? /." 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3223717.
Full textSource: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3622. Adviser: Akira Chiba. Includes bibliographical references (leaves 39-42) Available on microfilm from Pro Quest Information and Learning.
Vinette, Billy. "Expériences d’apprentissage de jeunes adultes ayant reçu une greffe de cellules souches dans la gestion de leurs symptômes." Thèse, 2019. http://hdl.handle.net/1866/23590.
Full textHematological diseases, such as leukemia and lymphoma, are among the most common forms of cancers that can affect young adults. Hematopoietic stem cell transplantation is a common intervention to treat blood-related cancers such as leukemia and lymphoma. However, an allogeneic stem cell transplant (ASCT) can provoke many acute and chronic symptoms. Young adult cancer survivors are expected to develop expertise to self-manage these symptoms. Yet little is known about their self-management experiences. The purpose of this study was to describe self-management learning experiences of young adults (18-39 years old) following ASCT. An interpretive qualitative descriptive design (Thorne, 2016) was conducted with seven young adults who had undergone an ASCT (n=7, mean 26 years old, mean 14,71 months post-ASCT). The results suggest that learning self-management expertise following ASCT is progressive and was described into a five-level process with distinct characteristics. Certain factors could positively or negatively affect the learning process and hence the development of this self-management expertise. In addition, our results indicate that young adults developed body awareness (interoceptive ability) related to their symptoms. This ability allows young adults to adapt their self-management strategies and promote better control of their symptoms. Finally, various recommendations were made to promote self-management in young adults who have undergone an ASCT, including educational interventions
Weaver, Staci A. "Brain glycogen metabolism during hypoglycemia : role in hypoglycemia associated autonomic failure, memory and neuronal cell death." 2011. http://liblink.bsu.edu/uhtbin/catkey/1657878.
Full textDepartment of Biology
Marques, Ana Luísa Cadilhe. "Técnica da mão esquerda: uma ajuda essencial aos alunos de violoncelo do Ensino Básico." Master's thesis, 2013. http://hdl.handle.net/1822/28932.
Full textO presente projeto intitulado “Técnica da Mão Esquerda: Uma Ajuda Essencial aos Alunos de Violoncelo do Ensino Básico” é o relatório de estágio de Ana Luísa Cadilhe Marques, tendo sido realizado no âmbito do Mestrado em Ensino de Música, da Universidade do Minho. Este projeto teve como base uma tentativa de implementação de uma prática mais saudável do seu estudo diário, complementando-se com exercícios de índole técnica, de modo a dotar os alunos pertencentes ao quarto grau de violoncelo com ideias e soluções para as dificuldades respeitantes à mão esquerda que se lhes apresentam no decorrer do seu dia-a-dia. Embora se encontre já num grau avançado do ensino da música, a grande maioria destes discentes não sabe questionar-se durante o estudo e encontrar soluções para os obstáculos que vão surgindo em cada peça que o professor lhes fornece. Deste modo, desperdiçam muito do seu precioso tempo rodeando o problema ao invés de o solucionar diretamente na raiz. Este relatório é constituído por três partes: uma primeira onde se faz uma contextualização sócio escolar, uma segunda onde se faz uma breve abordagem histórica do violoncelo e da técnica da mão esquerda e se expõe os objetivos e finalidades do projeto em si, e uma terceira onde se efetua a avaliação dos questionários realizados e a sua relevância dentro do processo avaliativo do projeto, considerando-se a sua legitimidade e a sua relevância no contexto do ensino artístico português na atualidade, chegando-se então às considerações finais, em que se avalia todo o processo.
This project entitled "Left Hand Technique: An Essential Aid to Cello Students in Basic Education” is the internship report of Ana Luísa Cadilhe Marques, and was realized under the Master of Music Teaching from the University of Minho. This project was based on the attempt to implement a healthier practice in student´s daily study, providing it with technical exercises, in order to equip students belonging to cello fourth grade with ideas and solutions to problems related to the left hand in the course of their everyday. Although they are already in an advanced degree, the vast majority of these students do not know how to question themselves during the study and find solutions to the obstacles faced in each piece provided by the teacher. Therefore, students waste too much of their precious time circling the problem instead of solving it directly on the source. This report consists of three parts: the first one describes the school context, the second sets out the objectives and purposes of the project itself, as well as a brief historical perspective of the cello and his left hand technique and sets out the objectives and purposes of the project itself, and a third part where it makes the evaluation of the queries made and their relevance in the evaluation process of the project, considering its legitimacy and its relevance in the context of today´s Portuguese art education, completing the final considerations that evaluate the whole process.
Lajiness, Jacquelyn D. "Shp2 deletion in post-migratory neural crest cells results in impaired cardiac sympathetic innervation." Thesis, 2014. http://hdl.handle.net/1805/5495.
Full textAutonomic innervation of the heart begins in utero and continues during the neonatal phase of life. A balance between the sympathetic and parasympathetic arms of the autonomic nervous system is required to regulate heart rate as well as the force of each contraction. Our lab studies the development of sympathetic innervation of the early postnatal heart in a conditional knockout (cKO) of Src homology protein tyrosine phosphatase 2 (Shp2). Shp2 is a ubiquitously expressed non-receptor phosphatase involved in a variety of cellular functions including survival, proliferation, and differentiation. We targeted Shp2 in post-migratory neural crest (NC) lineages using our novel Periostin-Cre. This resulted in a fully penetrant mouse model of diminished cardiac sympathetic innervation and concomitant bradycardia that progressively worsen. Shp2 is thought to mediate its basic cellular functions through a plethora of signaling cascades including extracellular signal-regulated kinases (ERK) 1 and 2. We hypothesize that abrogation of downstream ERK1/2 signaling in NC lineages is primarily responsible for the failed sympathetic innervation phenotype observed in our mouse model. Shp2 cKOs are indistinguishable from control littermates at birth and exhibit no gross structural cardiac anomalies; however, in vivo electrocardiogram (ECG) characterization revealed sinus bradycardia that develops as the Shp2 cKO ages. Significantly, 100% of Shp2 cKOs die within 3 weeks after birth. Characterization of the expression pattern of the sympathetic nerve marker tyrosine hydroxylase (TH) revealed a loss of functional sympathetic ganglionic neurons and reduction of cardiac sympathetic axon density in Shp2 cKOs. Shp2 cKOs exhibit lineage-specific suppression of activated pERK1/2 signaling, but not of other downstream targets of Shp2 such as pAKT (phosphorylated-Protein kinase B). Interestingly, restoration of pERK signaling via lineage-specific expression of constitutively active MEK1 (Mitogen-activated protein kinase kinase1) rescued TH-positive cardiac innervation as well as heart rate. These data suggest that the diminished sympathetic cardiac innervation and the resulting ECG abnormalities are a result of decreased pERK signaling in post-migratory NC lineages.
VanDusen, Nathan J. "Hand2 function within non-cardiomyocytes regulates cardiac morphogenesis and performance." Thesis, 2014. http://hdl.handle.net/1805/6170.
Full textThe heart is a complex organ that is composed of numerous cell types, which must integrate their programs for proper specification, differentiation, and cardiac morphogenesis. During cardiac development the basic helix-loop-helix transcription factor Hand2 is dynamically expressed within the endocardium and extra-cardiac lineages such as the epicardium, cardiac neural crest cells (cNCCs), and NCC derived components of the autonomic nervous system. To investigate Hand2 function within these populations we utilized multiple murine Hand2 Conditional Knockout (H2CKO) genetic models. These studies establish for the first time a functional requirement for Hand2 within the endocardium, as several distinct phenotypes including hypotrabeculation, tricuspid atresia, aberrant septation, and precocious coronary development are observed in endocardial H2CKOs. Molecular analyses reveal that endocardial Hand2 functions within the Notch signaling pathway to regulate expression of Nrg1, which encodes a crucial secreted growth factor. Furthermore, we demonstrate that Notch signaling regulates coronary angiogenesis via Hand2 mediated modulation of Vegf signaling. Hand2 is strongly expressed within midgestation NCC and endocardium derived cardiac cushion mesenchyme. To ascertain the function of Hand2 within these cells we employed the Periostin Cre (Postn-Cre), which marks cushion mesenchyme, a small subset of the epicardium, and components of the autonomic nervous system, to conditionally ablate Hand2. We find that Postn-Cre H2CKOs die shortly after birth despite a lack of cardiac structural defects. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla, causing downregulation of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit significantly slower heart rates than control littermates. In conjunction with the aforementioned gene expression analyses, these results indicate that loss of Hand2 function within the adrenal medulla results in a catecholamine deficiency and subsequent heart failure.
Boudreau-Béland, Jonathan. "Effets de divers stimuli sur les caractéristiques des cardiomyocytes en culture dans le but de définir les conditions optimisées pour la fabrication de tissu cardiaque de remplacement." Thèse, 2015. http://hdl.handle.net/1866/18365.
Full textIn 2015, there are still a large number of people who die due to diseases of uncontrolled heart rhythm or due to lack of availability of compatible donor organs. Tissue engineering aim to create, repair or improve the function by different techniques. Tissue engineering is a viable option to reduce the mortality associated with many heart conditions. The overall goal of my PhD research was to study the functional impact of different stimuli in cardiac environment (mechanical and electrical stimulation) on cardiac cell cultures. This, in order to define optimized culture conditions for the production of replacement tissue using tissue engineering. This thesis presents the stages of creation and development of a bioreactor; a system that permits the culture of cardiac cells by integrating various stimuli. The optimization of culture conditions by using the bioreactor was confirmed by cell culture experiments that focus on cell proliferation, cell organization, gene and protein expression as well as on spontaneous activity. In the first place, our results show that although mean frequency of spontaneous activity remained unaltered, incidence of reentrant activity was significantly higher in samples cultured on glass compared to PDMS substrates. Higher spatial and temporal instability of the spontaneous rate activation was found when cardiomyocytes were cultured on PDMS, and correlated with decreased connexin-43 (unsignificant) and a significant increased CaV3.1 and HCN2 mRNA levels. Compared to cultures on glass, cultures on PDMS were associated with the strongest response to isoproterenol (β-adrenergic) and acetylcholine (parasympathetic). Secondly, we present the design of our bioreactor with an emphasis on its characteristics and by putting in perspective the relevance of our approach to optimize culture conditions and to improve profitability culture experiences and production stages of replacement heart tissue. Finally, a new approach is proposed to evaluate the characteristics of the contractile cells in culture which allows to validate the functional impact of stimuli, evaluate the heterogeneity in the beating behavior of the cells and to detect localized abnormal activity that could favour arrhythmia.