Reliable signal transmission among cells is important for long-range coordination. While higher organisms have designated structures for signal transmission, such as axons, it remains unclear how simpler communities of cells are organized to relay signals. Furthermore, many biological systems exhibit spatial heterogeneity, which can interrupt signal propagation. In this thesis, we investigate this problem by modeling the spatial organization and dynamics of electrochemical signaling, and we compare our results to experiments from our collaborators on Bacillus subtilis bacterial biofilms. The experiments show that only a fraction of cells participates in signal propagation and that these cells are spatially clustered with a size distribution that follows a power-law decay. These observations suggest that the fraction of participating cells is just at the tipping point between a disconnected and a fully connected conduit for signal transmission. We utilize percolation theory and a minimal FitzHugh-Nagumo-type excitable dynamics model to test this hypothesis, and genetically modified biofilms with altered structure and dynamics to validate our modeling. Our results suggest that the biofilm is organized near the critical percolation point in order to negotiate the benefit and cost of long-range signal transmission. Then, more detailed experiments show that the participation probability is correlated from cell to cell and varies in space. We use these observations to develop an enhanced percolation model, and show using simulations and a renormalization argument that the main conclusions are unaffected by these features. Finally, we use our dynamic model to investigate the effects of heterogeneity beyond the radial wave regime and into the spiral wave regime. We find that spatial correlations in the heterogeneity promote or suppress spiraling depending on the parameters, a surprising feature that we explain by demonstrating that these spirals form by distinct mechanisms. We characterize the dependence of the spiral period on the heterogeneity using techniques from percolation theory. Taken together, our results reveal that the spatial structure of cell-to-cell heterogeneity can have important consequences for signal propagation in cellular communities.<br>

In 1800, Volta, inspired by the electric organs of a genus of electric fish, the Electrophorus, invented the first electric batteries, which were termed "artificial electric organs." Since then, the far-reaching implications of the fishes’ electrogenesis have come under greater attention and interest. In these fishes, the electric organ resembles a series of batteries. The electric organs are formed by electrocytes (the "batteries") with a distinct cytomorphology for discharging and charging. Although the arrangements of electrocytes in the electric organ are well-understood, the mechanisms involved in generating electric discharges within equivalent circuits remain unclear. In this thesis, the first element consists of adapting spatially defined models that we use to investigate the process of electrocyte charging and recharging under the added assumption of ion homeostasis, the process by which a cell restores its internal milieu. The study focuses on Eigenmannia and Electrophorus, two genera of electric fish. Eigenmannia's steady high-frequency dipole oscillator-like electric organ discharges enables electro-sensing and electro-communication, whilst Electrophorus's brief taser-like electric bursts serve as tetanizing predatory assaults. In addition, the second section of this study proposes a one-dimensional charge difference model that focuses on the modification of endogenous electric fields resulting from the uneven distribution of ions in a homeostatic apparatus.

On caractérise les milieux excitables par le fait qu'ils présentent un point d'équilibre linéairement stable et qu'une perturbation finie peut entraîner une longue excursion dans l'espace des phases. Les comportements de tels milieux sont en général bien approchés par des modèles simplifiés de réaction-diffusion a deux variables. Des exemples de milieux excitables sont le coeur, les axones neuronaux et la réaction de Belousov-Zhabotinsky dans les gels. On peut y observer des ondes d'excitation planes et spirales. Ce mémoire est consacré à l'étude numérique de la dynamique des filaments (ondes spirales empilées le long du filament) d'ondes spirales, éventuellement twistés, dans les milieux excitables. Dans un premier temps on calcule les états stationnaires par une méthode de Newton, puis on étudie la stabilité linéaire de ces états vis à vis de perturbations modulées suivant l'axe du filament par une méthode itérative, enfin on détermine les états restabilisés, quand ils existent, à l'aide de simulations numériques directes. L'étude des filaments non twistés met en évidence deux instabilités distinctes. L'une due à la déstabilisation de la branche de méandre (modulation périodique du rayon de rotation de la spirale) aboutit à un état restabilisé que nous caractérisons précisément. Cette instabilité correspond à une bifurcation de Hopf. L'autre correspond à une déstabilisation des modes de translation et aboutit à un état désordonné. L'étude de l'influence du twist sur la dynamique des filaments de spirales montre que le twist induit une déstabilisation des modes de translation à nombre d'onde fini. Cette bifurcation de Hopf correspond à la transformation du twist imposé au filament en Writhe (déformation géométrique). Le filament prend, dans les cas simples, une forme hélicoïdale. Dans des cas plus compliqués il prend une forme invariante dans le temps qui est la somme de plusieurs hélices. Une analogie avec une tige élastique soumise à la torsion est présentée.

No description available.

No description available.

Inwardly rectifying potassium (Kir) channels are essential for controlling the excitability of eukaryotic cells, forming a key part of the inter-cellular signalling system in multi-cellular organisms. However, as prokaryotic (KirBac) channels are less technically challenging to study in vitro and have been shown to be directly homologous to eukaryotic channels, they are often studied in lieu of their mammalian counterparts. A vital feature of Kir and KirBac channels is their mechanism for opening and closing, or their gating: this study predominantly features observations of open and/or closed channel populations. A well-characterised member of the KirBac family, KirBac1.1, has been successfully expressed, purified into detergent micelles, and doubly labelled with fluorescent maleimide dyes in order to enable observation of confocal-in-solution Förster Resonance Energy Transfer (FRET) at the single molecule level. Results demonstrate single-molecule FRET signals from KirBac1.1 and therefore represent the first single-molecule FRET observations from a KirBac channel. Perturbation of the open-closed dynamic equilibrium was performed via activatory point mutations, changes in pH, and ligand binding. A protocol for reconstitution into nanodiscs was optimised in order to more closely approximate native conditions, and the single-molecule FRET observations repeated. This thesis presents a comparison between measurements made using the detergent solubilisation system and those made using nanodiscs.

Embora muitos avanços tenham ocorrido no entendimento dos fatores que afetam a maciez, a incidência de carne dura ainda é significativa. Animais mais reativos apresentam carnes mais duras, porém o mecanismo que determina este efeito ainda não foi estabelecido. Presume-se que o maior estresse nos animais reativos aumente a atividade de calpastatina afetando o amaciamento post mortem. Com objetivo de testar esta hipótese, foram avaliadas correlações da força de cisalhamento (FC), temperamento e temperatura corporal obtida de noventa e seis novilhos Nelore castrados, com cerca de 20 meses de idade. O temperamento foi baseado nas variáveis velocidade de fuga (VF) e escore de tronco (ET) avaliadas 3 - 4 semanas antes do abate (Manejo 1) e 2 dias pré-abate (Manejo 2). A análise de componentes principais com as variáveis de temperamento obtidas em ambos os manejos resultou em dois índices: índice de temperamento (IT) e índice de habituação (IH). Estes índices apresentaram maior correlação com a FC do que a VF. O IH apresentou correlação negativa e positiva com FC e pH (P < 0,05), respectivamente. A temperatura retal foi positivamente correlacionada com IT e negativamente com FC. A termografia infravermelho de várias regiões corporais apresentou correlações baixas com IT ou FC. Dois grupos divergentes quanto à FC (extremos da população para FC), cada qual com 6 novilhos, foram comparados para variáveis de temperamento, expressão dos genes CAPN1, CAST, CAST1 e CAST2, e características de carne. O grupo de alta FC (AFC) apresentou maior (P< 0,05) VF, ET, IT e índice de temperamento com base na média da VF e ET (ITM). Os grupos de AFC e baixa FC (BFC) não diferiram (P > 0,05) para comprimento de sarcômero e pH final, mas tiveram diferenças no amaciamento post mortem, com diferenças em maciez que persistiram em todos os tempos de maturação (2, 16 e 30 dias post mortem; P < 0,05). O grupo AFC apresentou maior atividade inibitória de calpastatina total 48 h post mortem medida no M. triceps brachii (P < 0,05), embora diferenças não tenham sido observadas no M. longissimus lumborum (P > 0,05). No entanto, o grupo AFC teve no M. longissimus maior expressão de CAST do que o grupo de BFC (P < 0,05). Em conclusão, temperamentos divergentes têm impacto na atividade de calpastatina que influência o amaciamento post mortem. / Despite significant advancements in the knowledge of factors affecting beef tenderness, incidence of tough beef continues to be elevated. Animals more excitable have tougher meat, but the mechanism that determines this effect has not been established. It is presumed that more stress in excitable animals increases calpastatin activity with effects on tenderization post mortem. With the aim of test this hypothesis, correlations were measured for shear force (SF), temperament and body surface temperature obtained from ninety-six Nellore with about 20 months of age. Temperament was based on the exit velocity variables (EV) and crush score (CS) measured 3-4 weeks (handling 1) and two days (handling 2) before slaughter. The principal component analysis with the temperament variables obtained in both handlings resulted in two index: temperament index (TI) and habituation index (HI). These indexes had higher correlation with the SF than the VF. The HI had negative and positive correlation with SF and pH (P < 0.05), respectively. Rectal temperature was positively correlated with TI and negatively with SF. Infrared thermography of different body sites had low correlations with TI or SF. Two divergent groups to SF (extremes of the population to FC), each with 6 steers, were compared to temperament variables, expression of genes CAPN1, CAST, CAST1 and CAST2, and meat traits. The high SF group (HSF) had higher EV, CS, TI and temperament index based on the average of EV and CS (ATI) (P < 0.05). The HSF groups and low SF (LSF) did not differ for sarcomere length and final pH (P < 0.05), but it had differences in post mortem tenderization, with differences in tenderness that persisted in all aging times (2, 16 and 30 days post mortem; P < 0.05). The HSF group had higher calpastatin inhibitory activity 48 h post mortem measured in M. triceps brachii (P < 0.05), although no differences were observed in the M. longissimus lumborum (P > 0.05). However, the HSF group had in the M. longissimus greater CAST expression than the LSF group (P < 0.05). In conclusion, divergent temperaments affect the calpastatin activity that influence the tenderization post mortem.

No description available.

Cette thèse étudie l'origine de l'activité spontanée dans l'utérus. Cet organe n'a aucune activité jusqu'à la délivrance, où les contractions rapides et efficaces sont générés. Le but de ce travail est de fournir un aperçu de l'origine des oscillations spontanées et de la transition de l'activité asynchrone à synchronisé dans l'utérus gravide. Un aspect intéressant de l'utérus est l'absence de pacemaker. L'organe est composé de cellules musculaires, qui sont excitables, et conjonctives, dont le comportement est purement passif, aucune de ces cellules, pris isolément, oscillent spontanément. Nous développons une hypothèse basée sur l'augmentation grande du couplage électrique entre les cellules observée pendant la grossesse. L'étude est basée sur deux modèles des cellules excitables, couplé à l'autre sur un réseau régulier, et un nombre variable de cellules passives, en accord avec la structure connue de l'utérus. Les deux paramètres du modèle, le couplage entre les cellules excitables, et entre les cellules excitables et passive, croissent pendant la grossesse. En utilisant les deux modèles, nous démontrons que les oscillations peuvent apparaître spontanément lorsque l'on augmente les coefficients de couplage, conduisant finalement à des oscillations cohérentes sur l'ensemble du tissu. Nous étudions la transition vers un régime cohérent, à la fois numériquement et semi-analytique, en utilisant le modèle simple des cellules excitables. Enfin, nous montrons que le modèle réaliste reproduit irréguliers modes de la propagation d'action potentiels ainsi que le comportement de bursting, observé dans les expériences in vitro. / This thesis investigates the origin of spontaneous activity in the uterus. This organ does not show any activity until shortly before delivery, where fast and efficient contractions are generated. The aim of this work is to provide insight into the origin of spontaneous oscillations and into the transition from asynchronous to synchronized activity in the pregnant uterus. One intriguing aspect in the uterus is the absence of any pacemaker cell. The organ is composed of muscular cells, which are excitable, and connective cells, whose behavior is purely passive; None of these cells, taken in isolation, spontaneously oscillates. We develop an hypothesis based on the observed strong increase in the electrical coupling between cells in the last days of pregnancy. The study is based on a mathematical model of excitable cells, coupled to each other on a regular lattice, and to a fluctuating number of passive cells, consistent with the known structure of the uterus. The two parameters of the model, the coupling between excitable cells, and between excitable and passive cells, grow during pregnancy.Using both a model based on measured electrophysiological properties, and a generic model of excitable cell, we demonstrate that spontaneous oscillations can appear when increasing the coupling coefficients, ultimately leading to coherent oscillations over the entire tissue. We study the transition towards a coherent regime, both numerically and semi-analytically, using the simple model of excitable cells. Last, we demonstrate that, the realistic model reproduces irregular action potential propagation patterns as well as the bursting behavior, observed in the in-vitro experiments.

Embora muitos avanços tenham ocorrido no entendimento dos fatores que afetam a maciez, a incidência de carne dura ainda é significativa. Animais mais reativos apresentam carnes mais duras, porém o mecanismo que determina este efeito ainda não foi estabelecido. Presume-se que o maior estresse nos animais reativos aumente a atividade de calpastatina afetando o amaciamento post mortem. Com objetivo de testar esta hipótese, foram avaliadas correlações da força de cisalhamento (FC), temperamento e temperatura corporal obtida de noventa e seis novilhos Nelore castrados, com cerca de 20 meses de idade. O temperamento foi baseado nas variáveis velocidade de fuga (VF) e escore de tronco (ET) avaliadas 3 - 4 semanas antes do abate (Manejo 1) e 2 dias pré-abate (Manejo 2). A análise de componentes principais com as variáveis de temperamento obtidas em ambos os manejos resultou em dois índices: índice de temperamento (IT) e índice de habituação (IH). Estes índices apresentaram maior correlação com a FC do que a VF. O IH apresentou correlação negativa e positiva com FC e pH (P < 0,05), respectivamente. A temperatura retal foi positivamente correlacionada com IT e negativamente com FC. A termografia infravermelho de várias regiões corporais apresentou correlações baixas com IT ou FC. Dois grupos divergentes quanto à FC (extremos da população para FC), cada qual com 6 novilhos, foram comparados para variáveis de temperamento, expressão dos genes CAPN1, CAST, CAST1 e CAST2, e características de carne. O grupo de alta FC (AFC) apresentou maior (P< 0,05) VF, ET, IT e índice de temperamento com base na média da VF e ET (ITM). Os grupos de AFC e baixa FC (BFC) não diferiram (P > 0,05) para comprimento de sarcômero e pH final, mas tiveram diferenças no amaciamento post mortem, com diferenças em maciez que persistiram em todos os tempos de maturação (2, 16 e 30 dias post mortem; P < 0,05). O grupo AFC apresentou maior atividade inibitória de calpastatina total 48 h post mortem medida no M. triceps brachii (P < 0,05), embora diferenças não tenham sido observadas no M. longissimus lumborum (P > 0,05). No entanto, o grupo AFC teve no M. longissimus maior expressão de CAST do que o grupo de BFC (P < 0,05). Em conclusão, temperamentos divergentes têm impacto na atividade de calpastatina que influência o amaciamento post mortem. / Despite significant advancements in the knowledge of factors affecting beef tenderness, incidence of tough beef continues to be elevated. Animals more excitable have tougher meat, but the mechanism that determines this effect has not been established. It is presumed that more stress in excitable animals increases calpastatin activity with effects on tenderization post mortem. With the aim of test this hypothesis, correlations were measured for shear force (SF), temperament and body surface temperature obtained from ninety-six Nellore with about 20 months of age. Temperament was based on the exit velocity variables (EV) and crush score (CS) measured 3-4 weeks (handling 1) and two days (handling 2) before slaughter. The principal component analysis with the temperament variables obtained in both handlings resulted in two index: temperament index (TI) and habituation index (HI). These indexes had higher correlation with the SF than the VF. The HI had negative and positive correlation with SF and pH (P < 0.05), respectively. Rectal temperature was positively correlated with TI and negatively with SF. Infrared thermography of different body sites had low correlations with TI or SF. Two divergent groups to SF (extremes of the population to FC), each with 6 steers, were compared to temperament variables, expression of genes CAPN1, CAST, CAST1 and CAST2, and meat traits. The high SF group (HSF) had higher EV, CS, TI and temperament index based on the average of EV and CS (ATI) (P < 0.05). The HSF groups and low SF (LSF) did not differ for sarcomere length and final pH (P < 0.05), but it had differences in post mortem tenderization, with differences in tenderness that persisted in all aging times (2, 16 and 30 days post mortem; P < 0.05). The HSF group had higher calpastatin inhibitory activity 48 h post mortem measured in M. triceps brachii (P < 0.05), although no differences were observed in the M. longissimus lumborum (P > 0.05). However, the HSF group had in the M. longissimus greater CAST expression than the LSF group (P < 0.05). In conclusion, divergent temperaments affect the calpastatin activity that influence the tenderization post mortem.