Дисертації з теми "IP3Rs"
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Nougarede, Adrien. "Molecular basis of BCL2L10/Nrh oncogenic activity in breast cancer." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1192/document.
Повний текст джерелаApoptosis, also called “Programmed Cell Death”, plays a key role in many biological processes and pathologies. The B-cell lymphoma 2 (Bcl-2) proteins, whose expression is often altered in tumor cells, are the main regulators of apoptosis.Among this family, the actual physiological function of the human apoptosis inhibitor Nrh, also referred to as BCL2L10 or Bcl-B, remains elusive. Although in most healthy tissues the Nrh protein is nearly undetectable, clinical studies have shown that Nrh expression is correlated with poor prognosis in breast and prostate carcinomas. We have shed light on a novel mechanism by which Nrz, the zebrafish ortholog of Nrh, was found to interact with the Ligand Binding Domain (LBD) of the Inositol-1,4,5-triphosphate receptor (IP3R) type-I Ca2+ channel. Indeed, the regulation of IP3Rs-mediated Ca2+ signaling by Nrz was shown to be critical during zebrafish embryogenesis. We used the knowledge gained with the zebrafish model to investigate Nrh function in cancer. We showed that Nrh interacts with the LBD of IP3Rs via its BH4 (Bcl-2 Homology 4) domain, which is critical to regulate intracellular Ca2+ trafficking and cell death. Actually, this interaction seems to be unique among the Bcl-2 family, and sets Nrh as the only Bcl-2 homolog to negatively regulate apoptosis by acting exclusively at the Endoplasmic Reticulum. Furthermore, we showed that disruption of the Nrh/IP3Rs complex primes Nrh-dependent cells to apoptotic cell death and enhances chemotherapy efficiency in breast cancer cell lines.Lastly our results bring a new insight to the role of Nrh regarding chemotherapy resistance
Criollo-Cespedes, Alfredo. "Regulation of autophagy by IP3R and IKK complex." Paris 11, 2009. http://www.theses.fr/2009PA11T099.
Повний текст джерелаYang, Xiaofei. "Domestic innovation and joint ventures: IPRs, tariff, and spillovers." Connect to online resource, 2007. 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:3256420.
Повний текст джерелаTorti, Valerio. "IPRs and competition in standard setting : objectives and tensions." Thesis, University of Southampton, 2012. https://eprints.soton.ac.uk/348326/.
Повний текст джерелаCriollo, Céspedes Alfredo. "Regulación de la autofagia por el receptor del inositol trisfosfato (IP3R)." Tesis, Universidad de Chile, 2009. http://repositorio.uchile.cl/handle/2250/105178.
Повний текст джерелаLa macroautofagia, comúnmente referida como “autofagia” es la principal vía de degradación de proteínas, organelos y material citoplasmático, permitiendo de este modo el reciclaje del material intracelular. Este proceso consiste en el englobamiento de fracciones citosólicas por una estructura multimembranar llamada “autofagosoma”, el cual posteriormente se fusiona con el lisosoma para formar el “autofagolisosoma”. Luego el material comprendido en el autofagolisosoma es degradado por enzimas hidrolíticas. Un estudio mostró que la inhibición de la enzima inositolmonofosfatasa (IMPasa) usando litio y L690.330, inducía una disminución de los niveles basales del IP3 y en consecuencia la generación de autofagia. Nuestros resultados confirmaron estos datos previos, demostrando que el pre tratamiento con mio-inositol revierte la autofagia inducida por litio y L-690.330. Además se demuestra que el pre tratamiento con mio-inositol también revertía la autofagia inducida por privación de nutrientes. IP3 es ligando de su receptor de IP3 (IP3R), el cual es el principal canal de Ca2+ a nivel del retículo endoplásmico. El principal objetivo de esta tesis es evaluar el rol del IP3R en la regulación de la autofagia. Los resultados mostraron que la disminución de los niveles proteicos del IP3R usando siRNA específicos, así como el tratamiento con antagonistas químicos del IP3R, tales como xestosponginas B y C, estimulaban significativamente el aumento en los niveles de autofagia. Además, xestospongina B, así como también la privación de nutrientes, indujo una pérdida en la interacción entre Bcl-2 y Beclin-1, los cuales interactúan en condiciones basales. El tratamiento con xestospongina B no perturbó los niveles de Ca2+, tanto en retículo endoplásmico como en el citosol, concluyendo que la autofagia inducida por xestospongina B es independiente de una fluctuación del Ca2+. Los experimentos de inmunoprecipitación mostraron que Beclin-1 (regulador clave en la inducción de la autofagia) interactúa tanto con IP3R así como con Bcl-2 en condiciones basales, y la interacción de este complejo es atenuado bajo condiciones de privación de nutrientes o por tratamiento con ABT737, el cual es un mimetizador de dominios BH3. Este resultado sugiere la presencia de un complejo proteico en la regulación de la autofagia. El papel del retículo endoplásmico en el desarrollo de la autofagia toma gran significancia debido al reclutamiento de proteínas clave (IP3R, Beclin-1 and Bcl-2). La relación entre autofagia y estrés de retículo no es clara y por lo tanto se evaluó el efecto de agentes inductores de estrés de retículo en la inducción de la autofagia. Los resultados mostraron que tunicamicina, tapsigargina y brefeldina-A (agentes inductores de estrés de retículo) activaron el UPR (respuesta a proteínas mal plegadas) e indujeron autofagia. La disminución de los niveles de proteínas claves en el desarrollo de la autofagia (Atg5, Atg10, Atg12, Vps34 y Beclin-1) usando específicos RNAs interferentes atenuaron la autofagia inducida por agentes inductores de estrés de retículo y xestospongina B. Además, la sobreexpresión de Bcl-2 y Bcl-XL con destinación a retículo endoplásmico atenuó la autofagia inducida por xestospongina B e inhibidores de la IMPasa. Esta tesis muestra novedosos resultados, los cuales dan cuenta de un complejo proteico IP3R/Beclin-1/Bcl-2 en la regulación de la autofagia.
Macroautophagy (herein referred to as “autophagy”) is the major catabolic pathway for entire organelles, long-lived/ aberrant proteins and superfluous portions of the cytosol. It consists of the stepwise engulfment of substrate elements into distinctive multimembraned “autophagosomes”, which after fusion with lysosomes form singlemembraned autophagolysosomes. Into the autophagolysosome, the engulfed material is degradated by lisosomal hidrolytic enzymes, leading the recyclage of intracellular material. A study has suggested that myo-inositol-1,4,5-trisphosphate (IP3) could regulate autophagy because inhibition of inositol monophosphatase (IMPasa) by lithium or L-690.330 stimulates autophagy through the depletion of IP3. Our results have confirmed that the reduction of intracellular IP3 levels by IMPasa inhibitors (lithium and L.690.330) stimulates autophagy, whereas the enhancement of IP3 levels by pre treatment whit mio-inositol inhibits the lithium and L.690.330 effect. Moreover we have demostred that autophagy induced by nutrient privation was also inhibited by treatment with mio-inositol, but the effect of nutrient privation in the intracellular IP3 basal levels was not evaluated. IP3 acts on the IP3 receptor (IP3R), an IP3‑activated Ca2+ channel of the endoplasmic reticulum membrane and consequently we wanted to evaluate de roll of IP3R in the regulation of autophagy. The results obtained in this thesis show that knockdown of the IP3 receptor (IP3R) with specifics small interfering RNAs and pharmacological IP3R antagonist (xestospongin B and C) are a strong stimulus for the induction of autophagy, in addition, xestospongin B (like nutrient starvation) induced loss in the interaction between Beclin-1 and Bcl-2. Moreover, the autophagy promoted by xestospongin B not produced alterations in the steady-state Ca2+ levels in the ER or in the cytosol, therefore the autophagy induced by xestospongin B was Ca2+-independent. Immunoprecipitation assays shown that Beclin- 1 (key protein in the regulation of autophagy) interacts with IP3R and Bcl-2 in basal conditions, and this interaction may be attenuated both by nutrient starvation or ABT737 treatment, which is a mimetic compound of BH3. These results suggest the presence of a protein complex in the regulation of autophagy. The treatment whit ER stressors such as tunicamycin, thapsigargin and brepheldine A induced Unfolded Protein Responses (UPR) and autophagy. The autophagy induced by these agents showed to be IRE1α dependent, but the inhibition of autophagy showed an increase in the cell death, indicating a pro survival function of the autophagy upon endoplasmic reticumum stress conditions. The autophagy induced by treatment with xestospongin B and ER stressors was inhibited by knockdown of Atg5, Atg10, Atg12, Vps34 and Beclin-1, which are keys proteins in the autophagic process. We have also evaluated the roll of Bcl-2 and Bcl-XL in the inhibition of autophgy, and the results showed that Autophagy triggered by IMPasa inhibitors and xestospongin B was inhibited by Bcl-2 and Bcl-XL over expression specifically targeted to ER but not Bcl-2 or Bcl-XL proteins targeted to mitocondria. Altogether, these results suggest that IP3R form a regulator complex with Bcl-2 and Beclin-1, which exerts a major role in the physiological control of autophagy
Ikebara, Juliane Midori. "Role of intracellular calcium receptor inositol 1,4,5-trisphosphate type 1 (IP3R1) in rat hippocampus after neonatal anoxia." reponame:Repositório Institucional da UFABC, 2016.
Знайти повний текст джерелаDissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Neurociência e Cognição, 2016.
Anóxia é uma das maiores causas de morbidade e mortalidade neonatal, especialmente em neonatos pré-maturos, constituindo um importante problema de saúde pública devido às sequelas neurológicas permanentes em pacientes. A privação de oxigênio dispara uma série de cascatas, culminando em morte celular em regiões cerebrais mais vulneráveis, como o hipocampo. Neste processo de morte celular causada pela privação de oxigênio, o cálcio citosólico possui um papel crucial. Receptores intracelulares de inositol 1,4,5-trifosfato (IP3Rs) são importantes reguladores de níveis de deste cálcio, no entanto, não se sabe sobre sua função na anóxia. O objetivo deste estudo é analisar se os IP3Rs do tipo 1 (IP3R1) participam no processo de morte no hipocampo de ratos após a anóxia neonatal. A análise quantitativa de real-time PCR revelou uma diminuição da expressão gênica de IP3R1 24 horas após a anóxia neonatal. Na análise da distribuição de células IP3R1-positivas foi observada uma densidade de IP3R1 na região de CA1 em ambos os grupos, porém, não se observou diferença entre os grupos controle e anóxia. Interessantemente os animais anóxia apresentaram uma alta colocalização de IP3R1 e marcador de núcleo (DAPI), sugerindo que a anóxia causa uma translocação de IP3R1 para o núcleo nas células hipocampais. Além disso, o padrão de marcação mostrou diferentes tamanhos de clusters dos receptores, indicando uma organização diferente entre os grupos. Foi injetado 2-APB, um bloqueador de IP3R1, ou veículo, no hipocampo de forma bilateral após a anóxia. Foi utilizado metodologias de marcação de células degeneradas e foi visto que no grupo 2APB houve uma diminuição do número de células FJC-positivas e TUNEL-positivas em comparação ao grupo veículo anóxia. Porém, não foi observado nenhuma diferença de marcação entre os grupos na imunofluorescência de caspase-3 ativada. Não foi detectada nenhuma diferença entre os grupos no teste de labirinto de Barnes. No teste de campo aberto, observou-se que o grupo 2APB apresentam maiores níveis de ansiedade. Desta forma, este estudo pode contribuir com novas perspectivas na investigação de mecanismos de neurodegeneração ativadas pela privação de oxigênio.
Anoxia is one of the most prevalent causes of neonatal morbidity and mortality, especially in preterm neonates, constituting an important public health problem due to permanent neurological sequelae observed in patients. Oxygen deprivation triggers a series of simultaneous cascades, culminating in cell death mainly located in more vulnerable metabolic brain regions, such as the hippocampus. In the process of cell death by oxygen deprivation, cytosolic calcium plays crucial roles. Intracellular inositol 1,4,5-trisphosphate receptors (IP3Rs) are important regulators of cytosolic calcium levels, although the role of these receptors in neonatal anoxia is completely unknown. This study focused on the functional role of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in rat hippocampus after neonatal anoxia. Quantitative real-time PCR analysis revealed a decrease of IP3R1 gene expression 24 hours after neonatal anoxia. Distribution analysis of IP3R-positive cells was performed and we observed higher IP3R1 pixels quantity in CA1 of both groups; however, we were not able to observe alterations between control and anoxia animals. Interestingly, we observed that anoxia animals present a higher colocalization of IP3R1 and nucleus marker (DAPI), suggesting that neonatal anoxia may cause IP3R1 translocation to the nucleus in hippocampal cells. Furthermore, puncta-labelling pattern showed different cluster sizes, larger in control group, indicating different organization between groups. We injected 2-APB, an IP3R1 blocker, or vehicle in hippocampus bilaterally after anoxia. Labelling techniques of degenerate cells was performed and we observed that 2APB group decrease the number of FJC-positive cells compared to vehicle anoxia group. In contrast, TUNEL labelling and active caspase-3 immunofluorescence showed no difference between groups. Barnes maze test showed no differences between 2APB group and anoxia vehicle group. On the other hand, the open field test showed that 2APB group presents higher anxiety levels than vehicle group. In this way, this study may contribute to new perspectives in the investigation of neurodegenerative mechanisms triggered by oxygen deprivation.
Ritaine, Abigaël. "On the mechanisms of regulation of the IP3R activity by its interaction with Bcl-2." Thesis, Lille, 2018. http://www.theses.fr/2018LIL1S101.
Повний текст джерелаCalcium homeostasis is regulated by various ion channels, among which intracellular Ca2+-permeable channels, such as IP3R. Lately, Bcl-2 protein have been shown to regulate this ion channel activity. However, the study of the functional properties of IP3R in interaction with Bcl-2 is not a straightforward procedure and the molecular players implicated in that interaction are still not well established. Here, we show with the use of a new electrophysiological method, that the IP3R is inhibited by Bcl-2 via its BH4 domain and that the BH4 domain of Bcl-2 can inhibit by itself the single channel activity of the IP3R. Moreover, the binding of the ABT-199 in the hydrophobic groove of Bcl-2 leads to a tail-flip structural change in BH4 domain. We also studied the expression level of different IP3R isoforms as well as Bcl-2 and Bcl-xL protein in different prostate cancer cell lines. Interestingly, IP3R type 3 (IP3R3) expression is increased according the aggressiveness of prostate cancer cell lines. Indeed, IP3R3 was expressed preferentially in highly aggressive prostate cancer cell lines. Moreover, we can observe an significantly important effect of the IP3R3 on migration and invasion properties of human prostate cancer cell lines. Our study also revealed that IP3R3 was not involved in viability, proliferation. Overall, these data provide evidence on IP3R3 contribution to the increased metastatic potential of human prostate cancer cells. Therefore, IP3R3 could provide new perspective molecular target for the disease suppression, in particular at its advances stages
Georgeon, Chartier Carole. "Evaluation des effets du vieillissement sur la signalisation calcique des cellules musculaires lisses des artères cérébrales dans les modèles murins C57BL6/J, SAMR1 et SAMP8 dans des conditions normales et sous restriction calorique." Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14692/document.
Повний текст джерелаDuring aging, cerebral arteries undergo structural and functional changes, particularly in smooth muscle cells (SMC). SMC is responsible for maintaining vascular reactivity via calcium signaling involving different actors and can regulate two phenomena: contraction and relaxation. These actors regroup channels (CCVD, RYR, IP3R) calcium pumps (SERCA, PMCA, NCX, STIM / ORAI) and their regulators (PLB, FKBP12.6, TRPP2, SARAF, TRIC). Caloric restriction (CR) appears as a factor in delaying aging and its pathologies. Our work is strongly involved in the study of calcium signaling in SMC, focusing on genomic and functional alterations during aging of cerebral arteries in mice C57BL6/J. We were able to demonstrate an altered calcium signaling, which is partly through modulation of gene and protein expression levels of calcium channels and pumps involved in this phenomenon, and a functional change in terms of calcium signals and contraction. After 5 months under RC, it was highlighted a slow calcium signaling alterations associated with aging and a decrease of SMC oxidation by SAMP8
Mataragka, Stefania. "High-resolution optical analyses of IP3-evoked Ca2+ signals." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289124.
Повний текст джерела陶, 晟辰. "循環器における小胞体タンパク質TRICに関する研究". 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188726.
Повний текст джерелаBonneau, Benjamin. "Implication des protéines de la famille Bcl-2 dans la régulation des flux calciques au cours du développement embryonnaire précoce du poisson zèbre." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10155/document.
Повний текст джерелаApoptosis is a key cellular process for tissue homeostasis. Apoptotic cell death is under control of Bcl-2 family proteins which regulate outer mitochondrial membrane permeability. However, beyond their role in apoptosis, Bcl-2 family proteins are also involved in other cellular processes such as cell cycle or metabolism. In our laboratory we are interested in non-apoptotic functions of Bcl-2 family proteins in embryonic development. Using zebrafish model we have shown that Bcl-2 proteins control different processes during early development thanks to their ability to regulate calcium homeostasis. Indeed, we have shown that the anti-apoptotic protein Nrz participates in actin cytoskeleton remodeling during epiboly by regulating cytosolic calcium concentration via an interaction with the IP3 receptor (IP3R). We have also demonstrated that Nrz decreases calcium release from the endoplasmic reticulum by inhibiting IP3 fixation on its receptor. We have furthermore identified a new pro-apoptotic member of Bcl-2 family, Bcl-wav which is expressed only in fish and frogs. This protein regulates mitochondrial calcium homeostasis by interacting with VDAC. We have moreover shown that this activity is essential for convergence and extension movements during early zebrafish development
Demarco, Diogo Joel. "Educação e desenvolvimento: o índice paulista de responsabilidade social nos municípios do noroeste paulista." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/48/48134/tde-19042007-161848/.
Повний текст джерелаThe following study is an empirical research, having as its object the indicators of the Índice Paulista de Responsabilidade Social (São Paulo Index of Social Responsibility, here referred as IPRS). Having this Index as reference, we analyze education and development of the cities located in the Northwest of São Paulo State, aiming to understand which factors lead to the good results in schooling indicators obtained by a group of low income cities, rated in group 3 in the IPRS. The study?s purpose is to analyze (through a detailed and critical look at the variables that compose the IPRS) its capacity of expressing the reality of the educational environment in the cities as well as being useful in the definition of policies that would aim to strengthen its development actions. Considering this, we intend to contribute to the debate on the creation of educational indicators that would be more adequate to the analysis of development nowadays. We take as a premise the relevance of education in the current development actions, not seen as a synonym to economical growth anymore, stressing the inclusion of the educational dimension in the measuring instruments of human development. We address the concepts of development seen as freedom and social capital as a guideline to understand the advent of a new generation of development indicators among which is the São Paulo index. These concepts are approached based on the references of theories given by Sen, Putnam, Bourdieu and Coleman, purposing to analyze the capacity of IPRS to encompass all these concepts within its boundaries. Concurrently, we present and examine the IPRS indicators in São Paulo State and in the cities of the Northwestern region, attempting to understand what leads to the appearance of an expressive number of low income cities with satisfactory social indicators. In order to do that we use the secondary data of the IPRS database from Fundação Seade. Considering this, two aspects are evidenced: the relevance of the schooling dimension in the good social results obtained by these cities and the inadequacy of the educational indicators in the São Paulo index, especially in taking into consideration other quantitative variables related to the educational environment available and to the quality of the educational processes developed. The following final points are then presented: the IPRS is an indicator that moves towards to its organization and capacity of depicting the reality of the cities development, distancing itself from the standardization of synthetic indicators, though still presenting some limitation regarding the ability to analyze the educational environment and the education quality offered, and thus effectively collaborate as an instrument of monitoring and assessment of the policies that aim the strengthening of the development actions for São Paulo cities.
Vautrin-Glabik, Alexia. "Implication du récepteur de l'inositol 1,4,5-trisphosphate de type 3 (IP3R3) dans les processus migratoires des cellules cancéreuses mammaires humaines." Thesis, Amiens, 2017. http://www.theses.fr/2017AMIE0039/document.
Повний текст джерелаBreast cancer is the most common lethal cancer in women in worldwide. In spite of screening improvement in early stages of tumor development, it remains difficult to cure late stages when metastases are begun. Metastatic development depends on migratory capacities acquisition by epithelial cells, involving a cytoskeleton remodeling, highly depending of intracellular calcium concentration. While plasma membrane calcium channels have been highly studied in migration processes, the role of IP₃Rs remains misunderstood. Firstly, we highlighted a correlation between IP₃R3 expression level and migratory potential of three human breast cancer cell lines with different migratory potential. Indeed, the more the migratory profile increases, the more is the expression of IP₃R3. Moreover, IP₃R3 expression modulation regulates their migratory capacities. The migratory capacities decreased when silencing IP₃R3, whereas they increased by overexpressing IP₃R3 in the low migratory breast cancer cell line (MCF-7). Furthermore, IP₃R3 silencing reveals an oscillating calcium profile, while its overexpression induces a sustained calcium profile. Secondly, we demonstrated a reverse correlation between IP₃R3 expression level and rounded shape of these three cell lines. Indeed, the longer the cell has an elongated morphology, the greater the IP₃R3 expression is important. Moreover, IP₃R3 silencing induced a rounded shape of migrating cells and decreased of protrusions and adhesion. Our results suggest IP₃R3 implication in modulation of cytoskeleton actors. Indeed, knockdown of IP₃R3 induced a decrease of ARHGAP18 and Cdc42 expression, RhoA and FAK_⁸⁶¹ activity, and a reorganization of profilactin cytoskeleton. Furthermore, in a migratory model, oscillating profile is revealed at wound realization and predominates 3 h amer in cells of the front wound whereas it sets up in cells of back only amer 3 h. The spatio-temporal gap of this oscillating calcium signal reflects an intracellular calcium dynamic essential to migratory processes and cytoskeleton remodelling in breast cancer. In conclusion, our results reveal a key role of IP₃R3 in migratory processes by profilactin cytoskeleton remodeling through ARHGAP18/ RhoA/ FAK pathway thanks to intracellular calcium profile modulation
Neuhäusler, Peter [Verfasser], and Knut [Akademischer Betreuer] Blind. "IPRs, Economic Performance and the Value of Patents – Five Essays from Different Perspectives / Peter Neuhäusler. Betreuer: Knut Blind." Berlin : Universitätsbibliothek der Technischen Universität Berlin, 2012. http://d-nb.info/1027798152/34.
Повний текст джерелаUsui, Ryota. "GPR40 activation initiates store-operated Ca²⁺ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells". Kyoto University, 2020. http://hdl.handle.net/2433/253196.
Повний текст джерелаMakhani, Kiran, and Kiran Makhani. "Mechanism of Action of ERBB Decoy Cancer Therapeutic Peptide SAH5." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/626139.
Повний текст джерелаQuezada, Cornejo Esteban Roque. "Papel del IP3R en los cambios de la expresión del complejo MCU inducida por estímulo eléctrico en músculo esquelético adulto." Tesis, Universidad de Chile, 2018. http://repositorio.uchile.cl/handle/2250/167784.
Повний текст джерелаLa plasticidad muscular es la capacidad que presentan las células musculares esqueléticas de adaptarse a diferentes estímulos externos, modificando su fenotipo. La frecuencia de estimulación eléctrica (EE) (in vitro como in vivo) induce la transición fenotípica de un músculo. De modo interesante, el EE de baja frecuencia induce marcadores de transición fenotípica rápido/lenta por una vía dependiente de la activación del IP3R. Además, se ha establecido al uniportador de Ca2+ mitocondrial como un regulador del trofismo muscular. Hipotetizamos que la regulación de los niveles de RNAm del uniportador de Ca2+ mitocondrial y de sus proteínas reguladoras en respuesta a EE de baja frecuencia es dependiente de la activación del IP3R. Fibras musculares adultas aisladas desde el músculo flexor digitorium brevis (fdb) de ratones C57BL/6J de 8 a 10 semanas de edad fueron expuestas a EE de baja frecuencia en presencia o ausencia de inhibidores de la vía propuesta. Se observó que el estímulo eléctrico de baja frecuencia resulta en una disminución de los niveles de RNAm de MCU, MICU1, MICU2 y EMRE, mientras que el EE de alta frecuencia no genera modificaciones. Las fibras musculares esqueléticas pre-incubadas con apirasa (enzima que degrada ATP) y xestospongina B (inhibidor de los receptores de IP3) previenen la disminución de los niveles de RNAm de MCU, MICU1, MICU2 y EMRE mediada por un EE de baja frecuencia. El ATP extracelular exógeno (agregado al medio de incubación) resulta en una disminución de los niveles de RNAm de MCU, MICU1, MICU2 y EMRE). Además, este efecto de EE no es prevenido por actinomicina D (inhibidor de la transcripción). Este trabajo contribuye a la comprensión de los mecanismos moleculares involucrados en la plasticidad muscular en respuesta a ejercicio físico y en particular, al rol de la mitocondria en estos mecanismos.
Muscular plasticity is the ability of the skeletal muscle cells of different external stimuli, modifying their phenotype. The frequency of electrical stimulation (ES) (in vitro as in vivo) induces the phenotypic transition of a muscle. Interestingly, low frequency ES induces rapid / slow phenotypic transition markers by a pathway dependent on the activation of IP3R. In addition, the mitochondrial Ca2 + uniporter has been established as a regulator of muscle trophism. We hypothesized that the regulation of mRNA levels of the mitochondrial Ca2 + uniporter and its regulatory proteins in response to low frequency EE is dependent on the activation of IP3R. Adult muscle fibers isolated from the flexor digitorium brevis muscle (fdb) of C57BL / 6J mice from 8 to 10 weeks of age were exposed to low frequency ES in the presence or absence of inhibitors of the proposed pathway. It was observed that the low frequency electrical stimulus results in a decrease in mRNA levels of MCU, MICU1, MICU2 and EMRE, while high frequency ES does not generate modifications. Skeletal muscle fibers pre-incubated with apirasa (enzyme that degrades ATP) and xestospongin B (inhibitor of IP3 receptors) prevent the decrease of mRNA levels of MCU, MICU1, MICU2 and EMRE mediated by a low frequency ES. Exogenous extracellular ATP (added to the incubation medium) results in a decrease in mRNA levels of MCU, MICU1, MICU2 and EMRE). In addition, this effect of ES is not prevented by actinomycin D (transcription inhibitor). This work contributes to the understanding of the molecular mechanisms involved in muscle plasticity in response to physical exercise and, in particular, to the role of mitochondria in these mechanisms.
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Al-Mawali, Nasser, and n/a. "Country-specific determinants of vertical and horizontal intra-industry trade: an empirical analysis of South Africa." University of Canberra. Business & Government, 2006. http://erl.canberra.edu.au./public/adt-AUC20060526.120413.
Повний текст джерелаGuillemette, Joelle. "Expression d'une forme tronquée du récepteur de l'Inositol 1,4,5-trisphosphate (IP3R) dans les cellules DT40 dont les gènes des différents isoformes d'IP3R ont été interrompus." Sherbrooke : Université de Sherbrooke, 2003.
Знайти повний текст джерелаAtakpa, Peace. "Ca2+ signalling between the endoplasmic reticulum and lysosomes." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/288002.
Повний текст джерелаSPITALERI, GAETANO. "La tutela delle innovazioni in campo vegetale." Doctoral thesis, Università Cattolica del Sacro Cuore, 2012. http://hdl.handle.net/10280/1303.
Повний текст джерелаIntellectual property rights on plant-related inventions are the subject matter of this thesis. In the first part of this work, the author analyzes the evolution of the specific means of protection for new plant varieties first introduced in the United States of America and then in the member States of the UPOV Convention. The author makes a comparison between these ad hoc means of protection and the patent protection, by pointing out the differences in respect to the conditions for protection and the scope of protection. After that, an assessment of the impact of modern biotechnology on the existent European and American plant-related invention systems of protection is made. The author investigates the approaches which were chosen in Europe and in the United States of America in order to address the issues related to the biotechnological revolution, with particular focus on the interface problems between plant variety protection and patent protection, by means of a study of the principal case law and regulatory interventions adopted during the last years. The author believes that American and European approaches are not so different in substance and, de jure condendo, suggests redefining the relationship between plant variety protection and patent protection in Europe through the elimination of the ban on patent protection for plant varieties, which is the real differential factor between European and American normative contexts.
Rong, Yiping. "Bcl-2 Regulates Proapoptotic Calcium Signals by Interacting with the Inositol 1, 4, 5-Trisphosphate Receptor." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1228322705.
Повний текст джерелаBanzatto, Sofia. "Perfil de mortalidade no estado de São Paulo no período de 2003 a 2013: o indicador Anos Potenciais de Vida Perdidos (APVP) e causas básicas de óbito." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17139/tde-06012017-162347/.
Повний текст джерелаAlthough limited as an expression of health-related events and despite problems concerning the coverage and quality of available data, mortality estimates are among the most important foundations for the planning and evaluation of health services. Traditionally, mortality has been estimated according to the gross and specific mortality rates in a given population. However, these indicators consider the impact of death causes alone, without qualifying the burden resulting from deaths to society. The importance of premature mortality as a social expression of the burden of death has therefore received increasing attention, as it occurs at an age range of high creativity and productivity and affects not only the individual and his direct social group, but society as a whole, whose economic and intellectual potential is affected (REICHENHEIM; WERNECK, 1994). The estimate of potential years of life lost (PYLL) provides a more detailed assessment of mortality by combining death rates and the age when death occurs (KERR-PONTES; ROUQUAYROL, 1999 apud SAUER; WAGNER, 2003, p. 1520). Our study was aimed at assessing the evolution of PYLL rates in the total population of cities and health districts in the State of São Paulo, Brazil, between 2003 and 2013. We also assessed the retrospective evolution of the 15 death causes with the greatest PYLL rates in 2013 for the total population of the State of São Paulo. In order to achieve this, we created a database with information on deaths occurred in the state between 2003 and 2013 which were processed by the Mortality Information System (MIS), with death causes classified according to the 10th revision of the International Classification of Diseases (ICD-10). PYLL rates were calculated according to the method proposed by Romeder and McWhinnie (1988) and data charts 9 were created in TabWin to display the evolution of PYLL rates in the health districts of the state. Line graphs were created to display the evolution of the 15 death causes with the highest PYLL rates between 2003 and 2013. We further assessed the general mortality rate (GMR), child mortality rates (CMR), and mother mortality rates (MMR). Finally, we assessed the education, longevity, and wealth dimensions of the São Paulo Index of Social Responsibility (SPISR) in each of its groups; absolute and relative frequency of the SPISR in each of its groups; relationship of the SPISR according to the Regional Health Care Networks (RHCN); SPISR relationship according to population groups; PYLL rates by SPISR group; PYLL rates by population groups; PYLL rates by RHCN; SPISR dimension \'wealth\' by PYLL rates; SPISR dimension \'longevity\' by PYLL rates; SPISR dimension \'education\' by PYLL rates; and correlations between SPISR dimensions and PYLL rates. All the analyses are valid for the State of São Paulo in the year of 2012 and were made using the Stata 9.0 software. The GMR in the State of São Paulo for the period of 2003-2013 was worse compared to Brazil, and so was the CMR, with a predominance of the post-neonatal component in the State. The MMR indicated the availability of adequate prenatal, delivery, and postpartum assistance in the State during the period. The data charts displaying the evolution of PYLL rates in the State of São Paulo show that the RHCNs with the highest PYLL rates were 6, 7, 9, 10, 11, 12, 13, and 17. From the main 15 death causes according to PYLL rates in the period, 9 can be prevented in primary care. Under-recording and the triple load of diseases were also detected. The SPISR of most of the 645 municipalities in the State of São Paulo in the year 2012 was 4. The probability that the highest PYLL rate was associated with a SPISR of 4 was 95%, with a confidence interval between 17325.04 and 18424.20. An ANOVA with 4 degrees of freedom showed significant differences (p<0.05) in PYLL rates by SPISR group. With 5 degrees of freedom, the test of Kruskal-Wallis provided significant results (p<0.05), indicating the existence of differences between population groups in respect to PYLL rates. With 16 degrees of freedom, the Kruskal-Wallis test indicated the existence of significant differences between the RHCNs in terms of PYLL rates. PYLL rates decreased, although subtly, with the increase of wealth in the SPISR. Longevity and PYLL rates remained stable. As education increased, PYLL rates also increased. Since there was a positive correlation between wealth, longevity, and education, increased wealth was associated 10 with increased longevity and education as well. Concerning the relationship between PYLL rates and wealth and longevity, we found a negative correlation coefficient, indicating that as wealth and longevity increased, PYLL rates decreased. In respect to education, however, the correlation with PYLL rates was positive, indicating that increases in education were associated with increases in PYLL rates. Finally, this dissertation could be presented to the health authorities of the State of São Paulo as a project to reduce early mortality, focused on improvements in basic education, expansion of high-quality health services, and improvements in public security
Butr-Indr, Bhumindr. "La contrefaçon des droits de propriété intellectuelle : étude comparative en droits français et thaïlandais." Thesis, Paris 2, 2012. http://www.theses.fr/2012PA020031/document.
Повний текст джерелаCounterfeiting is an international problem. It appears that the main countries of origin of counterfeit goods seized in the European Union are the Asian countries, including Thailand. The research explains concisely the entire key factors to this whole problem. The research is divided into two parts; in the first place, I will outline pointly the definition of Intellectual Property Rights law (IPRs law) infringement between French and Thailand. Firstly, we focus on the structure of IPRs infringement. The term "counterfeit" in himself both in France and Thailand indicating different forms of an intellectual property rights liability conception. To identify violations constitute infringements, including the material element, we focus on four points, the existence of the creation, dissemination of the creation, use of creation, participation in the infringing action . With regard to the intentional element of infringement, iconcerned the intention of counterfeiter by the civil and criminal aspects as well as the objectives of my research would analysis on two components. First, the application of substantive issues embodies in the civil action. The second is the criminal action. The intention of counterfeiter are also intersect into two parts of action. The secondly,, we research to the proof of infringement. There provides two measures of proof in civil matters and evidence incriminal matters. In addition, there are a customs procedures as an alternative measure of proof . In the second place, we mainly concerned the IPRs law enforcement: Firstly we concerns the penalties imposed by criminal courts. We have already studied the criminal proceedings. In addition, we studied the penaltiesfor counterfeiting. We find that the criminal proceedings in Thailand is totally different from the criminal proceedings in France. In addition, we studied the penalization of IPRs law. We find that the situation in Thailand is totally different from a France, especially in criminal jurisprudence. It seems that the majority of decisions are the penalties imposed by criminal courts. Secondly were search about categories of damages and criteria for proof of damages. We find that the damages, in France as well as in Thailand, is the recovery of profit. Also the difficulty of assessing the damage, in France as well as in Thailand, are the damage of Trademark law, moral right damage and punitive damage
Chi-Yau, Lin. "IPARS: Intelligent Portable Activity Recognition System." 2006. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2407200621442900.
Повний текст джерелаLin, Chi-Yau, and 林琦耀. "IPARS: Intelligent Portable Activity Recognition System." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/16355496028120386644.
Повний текст джерела國立臺灣大學
資訊工程學研究所
94
The things we normally do in daily living including any daily activity we perform for self-care (such as feeding ourselves, bathing, dressing, grooming), work, homemaking, and leisure. The ability or inability to perform activities of daily living (ADLs) can be used as a very practical measure of ability/disability in many disorders. Modeling human ADLs via contextual information is gaining increasing interest in the artificial intelligent and ubiquitous communities. There are several studies on tracking ADLs, such as using video cameras, or microphones. Many people are uncomfortable living with cameras and microphones. Furthermore, video cameras, especially in non-public place spaces, provoke strong privacy concerns. Those approaches sometimes cannot process sensor data with minimal computational resources (e.g., a personal digital assistant (PDA)). Our developed system: Intelligent Portable Activity Recognition System (IPARS) performs activity recognition online with minimal computational resources. Sensors should be low-maintenance, easy to replace and maintain. Tagging objects with a remotely readable identification tag is adopted in our system. In addition, we develop a wearable wrist, based on Radio Frequency Identification (RFID) reader to detect everyday objects. In addition, we use WiFi positioning system to capture a person’s current position. IPARS is equipped with an RFID reader, which connects to a PDA. The way to obtain contexts to infer the current activity of a person is by detecting person-object interactions, and movement. Our approach uses a general framework for activity recognition by building upon and extending multiway tree structure (trie) to model ADLs via contextual information. There are two steps for IPARS to achieve activity recognition. First, by using the interface provided by IPARS, the person can train his activities easily. Therefore, while the person performs activities, IPARS models sequential sensor readings involved in these activities. Second, after modeling human activities, IPARS makes inferences for activity recognition by collecting current contexts and extracting features to map trained activity models. There are two phases in our experiments. In the first phase, we conducted our experiments in the Computer Science and Information Engineering at National Taiwan University. The first goal is using IPARS to test object recognition and location tracking. In the second phase, the experiment is run in a real home. The second goal is to evaluate the proposed solution of the activity recognition problem. We found that a discriminative relational approach for activity recognition based on the framework of multi-tries models to be well-suited to model sequence of contexts for activity recognition. IPARS detected 80 percent correctly for activity recognition. The results are promising. In the future, we focus on how to detect activities about healthcare. We plan to extend our model in a number of ways. First, by collecting data from more subjects, we can learn a set of generic models by clustering the subjects based on their similarities; then we can use a mixture of these models to better recognize activities of a new person.
Vahdatihassani, Faezeh. "Regulation of the inositol 1,4,5-trisphosphate receptor 1 (IP3R1) by microRNA-26a in atrial fibrillation." Thesis, 2020. http://hdl.handle.net/1866/24707.
Повний текст джерелаBackground: The pathophysiology of atrial fibrillation (AF) has been characterized by changes in the cellular concentration of Ca2+ and related processes leading to the initiation and maintenance of the condition. Inositol trisphosphate-receptors (IP3Rs) are ligand-gated calcium channels for which overexpression in AF has been linked to cardiac remodeling. microRNA (miR, miRNA)s, small non-coding RNAs, are around 22 nucleotides in length and regulate gene expression by mRNA destabilization or inhibition of its translation. A growing body of evidence has emerged about miRNA's role in the pathophysiology of cardiac disorders, including AF-induced adverse remodeling. Objective: Our laboratory has shown that nuclear IP3R1 level is upregulated in the dog AF model, producing increased nuclear calcium loading. Hence, this study aims to investigate the role of miRNAs in the regulation of IP3R1 initiating and/or perpetuating AF in atrial cardiomyocytes of the dog AF model. Methods: We used AF dog model established by atrial-tachypacing for 600 bpm × one week; Langendorff-perfused hearts to isolate atrial cardiomyocytes for molecular experiments; screening miRs that target ITPR1 gene, encoding IP3R1, using online databases; RT-qPCR to measure ITPR1 mRNA expression and confirm the expression level of the screened miRNAs; western blot analysis to evaluate the protein level of IP3R1; dual-luciferase reporter assay, overexpression and knockdown of miRNAs in primary culture of isolated cardiomyocytes or appropriate cell lines; and Fluo-4 AM calcium fluorescence imaging to assess the potential role of the miRNA on Ca2+ handling. For miRNA manipulation experiments, cells were transfected with 1) non-coding miRNA (miR-NC, control group), 2) miRNA mimic, and 3) inhibitor of the miRNA (AMO). Statistical significance is calculated with Student's t-test or one-way analysis of variance (ANOVA) followed by Tukey's multiple comparisons test using GraphPad Prism software version 6.00. Results: Our data indicated a rise in IP3R1 protein level with no apparent change in ITPR1 gene expression in left atrial cardiomyocytes from our dog AF model. Based on the computational analysis, miR-26a was predicted to target the ITPR1 mRNA. AF significantly downregulated miR-26a in left atrial cardiomyocytes. The dual-luciferase reporter assay in H9C2 cells showed that miR-26a directly acted on the 3′ untranslated region (3′UTR) of ITPR1 mRNA. In addition, miR-26a overexpression reduced the IP3R1 protein level and decreased the diastolic [Ca2+] in both nucleus and cytosol of the electrically-stimulated Ca2+ -transients, dog cardiomyocytes, while miR-26a knockdown reversed these effects. ITPR1 mRNA expression remained unaltered in isolated dog cardiomyocytes after transfection with the miRNA mimic and inhibitor. Conclusion: IP3R1 upregulation in AF is due to translation inhibition by miR-26a, which is downregulated in the atrial cardiomyocytes of the dog AF model. This change is associated with altered Ca2+ handling, reflected as enhanced nuclear diastolic Ca2+ levels. Our results suggest that miR-26a downregulation enhances the IP3R1 expression, contributing to pro-arrhythmic remodeling in AF.
YUAN, CHEN CHIH, and 陳志遠. "Patent Analysis of Various IPRs Relationships Among Smartphone Firms in the North America Region." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/88135704103092917728.
Повний текст джерела國立臺灣大學
商學研究所
101
This thesis examined the relationships between corporation patent assets and four patent strategies - patent infringement lawsuit, patent unilateral licensing, patent cross license and patent purchase - in the North America region. Utilizing 4-digit IPC code of the patent is to extract the core technology areas of the smartphone firm. The comparison of the patent counts with average patent citations in the both smartphone firms’ core technology fields can determine which smartphone firm has competitive advantage in these core technology areas. The results showed that smartphone firms with abundant patent asset in quantity and quality usually take patent infringement lawsuit strategy to block rivals outside the market and to obtain more market share. On the contrary, smartphone firms with scarce patent asset usually need to acquire external patents for the purpose of protecting their products. Patent unilateral licensing strategy, in the case of smartphone firms with huge R&D investments, plays a significant role in activating intangible intellectual asset, since smartphone firms can earn loyalty via unilateral patent license activity. On the other hand, in cases where one of any two smartphone firms possesses predominant patents, whatever in quantity or quality, in the other’s core technology fields, the thesis reveals empirical outcome that it would take patent cross license strategy so as to obtain a win-win situation.
Rud, Jonathan George. "Notch 1 Mediated Inhibition of Nur77-induced apoptosis: Implications for T-cell Leukemia." 2010. https://scholarworks.umass.edu/open_access_dissertations/253.
Повний текст джерела梅嘉玲. "The Application of the EU Exhaustion Doctrine on IPRs and It Comparison with the US Exhaustion Doctrine." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/00321056540615895272.
Повний текст джерелаTing, Lung-Lu, and 丁榮儒. "Essays on parallel imports,the government policies on IPRs,anti-dumping duty and quality-related R&D." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/7n7t44.
Повний текст джерелаKang, Chi, and 康琦. "A Study on the Exploitation of Science R&D Results and IPRs in Universities—Focusing on Patent Management." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/72615068063909737589.
Повний текст джерелаFENG, JUN-YAO, and 馮俊堯. "A Study of Key factors for the Intangible Assets Financing –Focusing on the Valuation of IPRs and the Insurance." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/69a55c.
Повний текст джерела東吳大學
法律學系
106
According to the survey, for the time being these enterprises obtain needed capital mainly from government or guaranteed by the Small and Medium Enterprise Credit Guarantee Fund of Taiwan. They can hardly make it through project finance or syndication loan. As a result, these knowledge-intensive enterprises are unable to take advantage of their Intellectual Property Right to acquire the loan to reinvest and thrive and go to international market. Based on the analysis of the theory of intangible assets value and related evaluation theory, this paper combines the development status of foreign intellectual property rights financing business, and illustrates the research framework of the scope of intellectual property rights and the value evaluation of intellectual property rights. Firstly, this paper analyzes the background and significance of the research on the value of intellectual property financing, and introduces the status quo of foreign related research.Secondly, it expounds the relevant theories of intellectual property financing research; then, analyzes the special value of the value evaluation of intellectual property rights financing; Finally, in order to realize the purpose of intellectual property financing, this paper proposes and expounds the foreign value realization system for intellectual property rights financing, and hopes to provide positive reference for China's intellectual property rights financing business.
Gomes, Sónia Isabel Nunes Guerra. "The impact of astrocyte calcium signaling in cortico-limbic function and behavior." Doctoral thesis, 2020. http://hdl.handle.net/1822/76827.
Повний текст джерелаOs astrócitos desempenham múltiplas funções desde a homeostasia cerebral ao controlo e processamento da atividade sináptica. Eles integram sinais neuronais por elevações complexas de cálcio (Ca2+) com impacto na comunicação neurónio-astrócito. As elevações de Ca2+ nos astrócitos podem ser divididas em dois tipos: globais (presentes no soma e principais processos) e/ou focais (presentes nos microdomínios). Apesar de estar descrito que as elevações globais de Ca2+ nos astrócitos podem modular a comunicação sináptica, continuam por esclarecer quais os mecanismos moleculares envolvidos. Desta forma, urge uma caracterização comportamental, estrutural e molecular detalhada para compreender esses mecanismos. Nesta tese, utilizámos o modelo de murganho que apresenta a deleção constitutiva do receptor 2 do inositol 1,4,5-trifosfato (IP3R2 KO), no qual as elevações globais de Ca2+ nos astrócitos estão ausentes. Na primeira parte deste trabalho (Capítulo 2) demonstramos que os murganhos IP3R2 KO têm um desenvolvimento somático e neurológico normal. Em seguida, a caracterização comportamental deste modelo transgénico (Capítulo 3) revelou que os murganhos IP3R2 KO apresentam uma melhoria do desempenho cognitivo em tarefas dependentes do hipocampo. Identificámos o factor de transcrição Foxo1 como modulador da expressão de genes específicos de astrócitos, responsáveis pela regulação do citoesqueleto e de espinhas dendríticas. A sobre-expressão do FOXO1 em astrócitos do hipocampo de murganho C57BL/6J foi suficiente para mimetizar a melhoria cognitiva verificada no modelo IP3R2 KO. Este resultado levou-nos a avaliar o papel da sinalização global de Ca2+ no contexto da depressão, uma doença que afeta comportamento dependente das regiões cortico-límbicas (Capítulo 4). Os murganhos IP3R2 KO apresentam uma surpreendente resiliência ao efeito ansiogénico do stress crónico. Por fim, explorámos o papel da sinalização de Ca2+ nos astrócitos no envelhecimento cognitivo (Capítulo 5). Os nossos resultados demonstram uma preservação do desempenho cognitivo em murganhos IP3R2 KO envelhecidos, caracterizado por alteração do rácio neurónio/astrócito e por refinamento dendrítico dos neurónios da camada V do córtex pré-frontal. Em suma, este trabalho contribuiu para uma melhor compreensão do papel da sinalização global de Ca2+ nos astrócitos desde o desenvolvimento até ao envelhecimento, num contexto de saúde e doença. Os resultados revelaram um alvo terapêutico específico em astrócitos com potencial aplicação em contextos de depressão e envelhecimento cognitivo.
Astrocytes are responsible for distinct functions ranging from brain homeostasis to the modulation of synaptic functioning. They integrate neuronal signals by complex calcium (Ca2+) elevations that control intracellular mechanisms that in turn drive the neuron-astrocyte dialogue, modulating the activity of cells and networks. It is now recognized that Ca2+ elevations in astrocytes appear spatially distributed in global (soma and main processes) and/or focal regions (microdomains). Although it is observed that global astrocytic Ca2+ signaling contributes to synaptic communication, its role in circuit computation and behavioral performance is still poorly understood. A detailed behavioral, structural and molecular characterization should provide us with putative mechanisms underlying the roles of astrocytic Ca2+. In this thesis, we took advantage of the inositol 1,4,5-trisphosphate receptor type 2 knockout (IP3R2 KO) mouse model, which lacks global Ca2+ signaling in astrocytes. In the first part of this work (Chapter 2), we demonstrate that IP3R2 KO mice retain a normal developmental maturation, as compared with WT littermates. Next, a detailed behavioral characterization of this mouse model (Chapter 3) showed that IP3R2 KO mice display enhanced cognitive performance in hippocampal-dependent tasks. We found Foxo1 as the most active transcription factor controlling the increased expression of astrocyte-specific genes related with fine cytoskeleton modulation and spinogenesis, which could underlie the cognitive enhancement observed. Moreover, specific overexpression of FOXO1 in hippocampal astrocytes of C57BL/6J mice was enough to recapitulate the enhanced fear memory observed in IP3R2 KO mice. This striking observation prompted us to test the role of global Ca2+ signaling in the context of depression, which affects cortico-limbic regions (Chapter 4). IP3R2 KO mice present an unexpected resilience to the installation of stress effects, namely translated into an increased self-care and a reduced anxious-like phenotype. Finally, we explored the role of astrocytic Ca2+ signaling in cortico-limbic performance in aged mice that display cognitive decline (Chapter 5). We observed a preserved cognitive performance in aged IP3R2 KO mice, an altered neuron/astrocyte ratio and a dendritic refinement of mPFC neurons. Overall, this work contributed to a better understanding on the role of global astrocytic Ca2+ signaling from development to aging, both in a health and disease context. We found a putative astrocyte-specific therapeutic target that could be used to prevent depression- and aging-related deficits.
The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), at the School of Medicine, University of Minho. Financial support was provided by a PhD grant (SFRH/BD/101298/2014 to SGG), FCT Investigator grants (IF/00328/2015 to JO, IF/01079/2014 to LP) and PTDC/MED-NEU/31417/2017 from the FCT – Foundation for Science and Technology, by BIAL Foundation grants (207/14 to JO and 427/14 to LP), by Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013); FEDER Funds, through the Competitiveness Factors Operational Programme (COMPETE), and The National Fund, through the FCT (POCI-01-0145-FEDER-007038).
Stamboulian, Severine. "Canaux calciques des spermatozoïde de Mammifères Caractérisation des interactions fonctionnelles et moléculaires au cours de la réaction acrosomique." Phd thesis, 2005. http://tel.archives-ouvertes.fr/tel-00011465.
Повний текст джерела