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Biolek, Vojtěch. "Stavební objekt a jeho životní cyklus z pohledu BIM." Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2016. http://www.nusl.cz/ntk/nusl-240361.
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The diploma thesis analyzes detached house created in BIM software. In the practical part was modeled BIM model, which was attributed the Information. Of the exported data was created budget and calculated total cost of building. The part of this work is calculate life-cycle cost and analysis of the most costies parts. The main result of this work is the demonstrace private investors and public procurement the advantages of BIM attitute to projects, Also calculate the price of building and life cycle costs in the studies BIM model can help investor to show how much they will cost of building without investor didn´t invest too much project funds and thus could reconsider the rejection or modification project.
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Sovšáková, Radka. "Marketingový plán spoločnosti Ryor." Master's thesis, Vysoká škola ekonomická v Praze, 2010. http://www.nusl.cz/ntk/nusl-74695.
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The goal of the Master's Thesis is to create one year marketing plan for the Ryor company. The theoretical part gives a base for the practical part, which starts with the discription of the company and the situation analysis, encluding Porter's five forces analysis, analysing the results of qualitative reasearch conducted in 2009 and own questionnaire research. Regarding the results the current aim of the company was reviewed, adjusted and new stratety was suggested. This strategy is step by step transformed to concrete partial strategies of marketing mix. Detailed proposal is ilustrated in the chart of the action plan, followed by the budget. The plan is finished with suggestions of measuring and evaluating the effectiveness of all proposed activities.
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Whiteley, Gareth. "Molecular architecture of Caveolin-3 and the investigation of an interaction with the ryanodine receptor." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/molecular-architecture-of-caveolin3-and-the-investigation-of-an-interaction-with-the-ryanodine-receptor(d5d4e1f1-88c5-4619-b208-7742d0cd81f5).html.
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The muscle-specific membrane protein, Caveolin-3, is a building block of caveolae a type of specialised lipid raft. Caveolin-3 is proposed to play a central role in variety of cellular functions both structural and functional, from cell signalling to cholesterol homeostasis. Caveolin-3 has also been implicated in processes involved in targeting membrane proteins to the plasma membrane, as well as mediating a host of cell signalling processes. Initial attempts were made to express full-length Caveolin-3 in E.coli. However, more success was achieved in expressing and purifying domains of Caveolin-3. To produce purified full-length Caveolin-3 the baculovirus expression system was employed and we report here that the expression of Caveolin-3 in insect (Sf9) cells leads to the formation of caveolae comparable in size to those observed in native vesicles. We subsequently purified the recombinant Caveolin-3 and determined, using multi-angle laser light scattering, that the isolated protein forms an oligomer with a molecular mass of ~200-220kDa. Using negative-stain transmission electron microscopy in conjunction with single particle analysis we have determined the first three-dimensional structure for Caveolin-3 with data converging to suggest that it forms a nonamer. The 9-fold symmetric three-dimensional Caveolin-3 volume is toroidal, ~16.5nm in diameter and 5.5nm thick, and is characterised by an outer rim of protein connected to a central 'cone-shaped' domain. Labelling studies revealed that the C-terminal domain of each of the contributing Caveolin-3 monomers associate to form the central cone density. There is also evidence to suggest that Caveolin-3 is associated with a range of proteins involved in excitation-contraction coupling. Having identified multiple potential caveolin-binding motifs within the Ryanodine Receptor, one of the key protein components of excitation-contraction coupling, we have purified the skeletal isoform of the Ryanodine Receptor (Ryanodine Receptor-1) from sheep calf muscle and using several biophysical techniques probed whether there is an interaction between Caveolin-3 and Ryanodine Receptor-1. Co-immunoprecipitation experiments indicated that the two proteins do indeed interact, but functional studies for analysis of binding characteristics were inconclusive. In conclusion, this thesis describes both the successfully purification and structural determination of Caveolin-3, generating the first 3D data for any of the caveolin proteins, as well as work aimed at understanding its functional relationship with Ryanodine Receptor-1.
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King, James Harmsworth. "Arrhythmogenic mechanisms in RYR2-P2328S murine hearts." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648837.
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Wiklund, Anders. "Eduard Brendlers opera Ryno : källkritik, analys, edition /." Göteborg : [A. Wiklund], 1991. http://catalogue.bnf.fr/ark:/12148/cb36955655x.
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Klipp, Robert Carl. "Novel Compound, 84F2, Inhibits Calmodulin Deficient RyR2." PDXScholar, 2017. https://pdxscholar.library.pdx.edu/open_access_etds/3484.
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The cardiac ryanodine receptor (RyR2) plays a key role in excitation-contraction coupling (ECC). Mutations in RyR2 are known to be linked to the arrhythmogenic disorder, catecholaminergic polymorphic ventricular tachycardia (CPVT), a deadly disease which is characterized by a leak of calcium from sarcoplasmic reticulum and a decrease in calmodulin (CaM) binding. A novel drug, 84F2, shown to inhibit arrhythmias in RyR2-R176Q heterozygous CPVT mouse hearts (2.5 µg/kg), decrease spark frequency in cells derived from CPVT mice (IC50 = 35 nM), and inhibit RyR2 single channel activity at low nanomolar concentrations (IC50 = 8 nM). When CaM is added back to RyR2, 84F2's ability to inhibit channel activity is suppressed approximately 250 fold. A metabolite of 84F2, 78F3, is shown to also be active in the inhibition of RyR2. We propose that 84F2 decreases arrhythmias by binding to the CaM deficient RyR2, but does not affect normal ECC when CaM is present. This work characterizes for the first time a class of drugs whose inhibitory affects are dependent upon the removal of CaM from RyR2.
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Gajdová, Lucie. "Studie zásobovací logistiky ve společnosti RYOR a. s." Master's thesis, Vysoké učení technické v Brně. Fakulta podnikatelská, 2016. http://www.nusl.cz/ntk/nusl-241530.
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The master’s thesis deals with Czech cosmetic company RYOR a. s. In the theoretical part is described the supply logistics and associated processes. The practical part analyses the supply process of the company. The goal of this thesis is proposal of efficient solution of supply process and integration of the information system. This proposal will be introduced to the company and in the case of interest the company can take advantage of it.
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Wang, YueYi. "Ca2+ handling in a mice model of CPVT." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS156/document.
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Le canal calcique de libération du Ca2+, appelé récepteur à la ryanodine (RyR) est localisé dans la membrane du réticulum sarcoplasmique des cardiomyocytes, en incluant ceux du pacemaker, et a un rôle important dans le couplage excitation contraction et la génération du rythme cardiaque. Des mutations dans leur gène sont responsables de la tachycardie catécholergique (CPVT), qui est une maladie létale, manifestée par des syncopes ou mort subite lors de stress émotionnel ou physique. Au repos, ces patients ont un électrocardiogramme normal, mais une tendance plus importante à la bradycardie.Nos collaborateurs ont identifié la mutation RyR2R420Q dans une famille espagnole atteinte de CPVT. Nous avons construit une souris portant cette mutation et étudié l’activité du nœud sinoatrial (NSA, pacemaker principale) afin d’élucider les mécanismes.Nous avons trouvé que les cellules du NSA présentent une activité spontanée plus lente que les souris sauvages (WT). Dans la cellule in situ, on peut étudier l’activité des RyRs par l’analyse des « sparks » Ca2+, qui sont des évenements élémentaires produits par l’activation d’un cluster des RyRs. Nos analyses en microscopie confocale sur des NSA disséquées on montré que la fréquence des sparks Ca2+ était légèrement augmentée. Par contre, la longueur de ces sparks est fortement prolongée dans les cellules KI. Ceci produit une libération plus importante de Ca2+ pendant la diastole dans les cellules KI qui réduit l’automatisme, en réduisant la charge en Ca2+ du réticulum sarcoplasmique et en inactivant le courant calcique type L. Donc les thérapies en étude qi favoriseraient la stabilisation du RyR2 en état fermé pourraient ne pas Être efficaces, et il faudra plutôt essayer des thérapies qui faciliteraient la fermeture du canal, une fois il est ouvertThe cardiac type-2 ryanodine receptor (RyR2) encodes a Ca2+ release channel on sarcoplasmic reticulum (SR) membrane in cardiomyocytes, including sinoatrial node (SAN) myocytes, and releases Ca2+ required for contraction and SAN spontaneous rhythm. Its genetic defects are related to catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a lethal heritable disease characterized by exercise/stress-induced syncope and/or sudden cardiac death. Interestingly, CPVT patients frequently present SAN dysfunction as bradycardia at rest.In a previous study, a novel CPVT-related RyR2 mutation (RyR2R420Q) in a Spanish family, associated with SAN dysfunction was reported. R420 is located at the N-terminal portion of the channel and seems to be an important site for maintaining a stable A/B/C domain of N-terminus in RyR2. As N-terminal mutation resultant RyR2 behaviour and SAN function are never analyzed before, we created the KI mice model bearing mutation R420Q to understand the underlying mechanism.In this thesis, we found increased Ca2+ release during diastole, indicating a gain-of-function effect of RyR2 N-terminal mutation R420Q. Interestingly, this defect may not be only an enhanced activity, as the Ca2+ sparks frequency was only slightly increased in KI, but also the closing mechanism, producing longer Ca2+ sparks. That is, the number of Ca2+ sparks is increased by the RyR2R420Q mutation, and meanwhile the amount of Ca2+ released in each Ca2+ spark is also dramatically enhanced. This increased Ca2+ release retards SR Ca2+ replenishment, disrupting the Ca2+ clock and the coupled clock, resulting in the slower SAN function. Thus favouring RyR stabilization in the closing state might not be an adequate therapy but accelerating its closure
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Labinaitė, Aistė. "Pasaulinių žiniasklaidos kaitos tendencijų atspindys Lietuvoje („Lietuvos ryto“ atvejis)." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2010~D_20140625_183037-32846.
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Šiandieninėje visuomenėje nė vienas žmogus jau nebegali įsivaizduoti savo gyvenimo be televizijos, interneto, spaudos ar radijo. Visuomenės informavimo priemonės suteikia individui galimybę reikšti savo nuomonę ir tuo pačiu gauti norimą informaciją, apie jį supantį pasaulį. Žiniasklaida atlieka svarbų vaidmenį formuodama informuotą individą ir paveikdama visuomenės gyvenimą. Įsigalėjus skaitmeninėms technologijoms ir pasikeitus informacijos perdavimo būdams, pasikeičia ir komunikacija, žiniasklaida. Internetas ir skaitmeninės technologijos buvo veiksniai dėl kurių atsirado elektroninės medijos, kuriose susitelkia ir tekstas, ir vaizdas, ir garsas. Žmogus, ieškodamas informacijos, viską randa viename. Pasikeičia santykis su vartotoju, atsiranda interaktyvumas, dingsta vienpusiškas bendravimas. Šio magistro darbo objektas – žiniasklaidos priemonių konvergencija. Siekiama ištirti, kaip konvergencijos sąlygomis pasikeičia/nepasikeičia visuomenės informavimo priemonės, jų turinys ir jo pateikimas auditorijai. Darbo tikslas – atskleisti pasaulinių žiniasklaidos kaitos tendencijų raišką Lietuvoje, konvergencijos reikšmę žiniasklaidos plėtrai. Darbe formuluojamą problemą galima išreikšti klausimu: ar konvergencija (žiniasklaidos priemonių susiliejimas) palietė ir Lietuvos žiniasklaidos priemones (šiuo atveju konkrečiai Lietuvos ryto visuomenės informavimo priemones)? Darbo uždaviniai: aptarti pasaulio ir Lietuvos žiniasklaidos raidos ypatumus, išryškinti naujosios ir tradicinės... [toliau žr. visą tekstą]In today's society, no man can longer imagine his life without television, internet, press and radio. The media gives the individual the opportunity to express his views and thereby get the desired information about the world around him. The media plays an important role in shaping the individual by informing him and influencing the informed society. Entrenched digital technologies and changes in methods of communication change and the communication and the media itself. The Internet and digital technology were factors resulting the rise of electronic media which focus on text, image and sound. A man searching for information finds everything in one place. The relationship with the consumer changes as the interactivity occurs and one-sided communication disappears. The object of this Master‘s thesis is the convergence of the media. The aim is to investigate how media changes or does not change the content and presentation of an audience under the convergence conditions. The aim of this work is to highlight the resolution of the global trends in the media change and the meaning of the media convergence development in Lithuania. The problem, formulated in this work, can be expressed as a question: does convergence (interflow of media measures) touched the Lithuanian media (in this case, specifically the Lietuvos Rytas mass media)? Job tasks are as follow: to discuss the media development features both globally and in Lithuanian; to highlight the differences between new and... [to full text]
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Yin, Liheng. "Impact of the catecholaminergic polymorphic ventricular tachycardia (CPVT) mutation RyR2R420Q in cell function." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS068.
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La tachycardie ventriculaire polymorphe catécholergique (CPVT) est une arythmie génétique létale qui se manifeste par une syncope ou une mort subite chez les enfants et les jeunes adultes dans des conditions de stress sans anomalie structurelle cardiaque évidente. Plusieurs mécanismes ont été proposés pour expliquer les altérations fonctionnelles sous-jacentes de la libération de Ca2+ dues aux mutations de RyR2 ou de ses protéines accessoires. Une nouvelle mutation CPVT située sur la partie N terminale de RyR2 a été identifiée dans une famille espagnole (RyR2R420Q). Ici, nous avons utilisé un modèle de souris KI exprimant le canal RyR2R420Q et des cardiomyocytes différenciés de cellules souches pluripotentes induites (hiPS-CM) générées à partir de deux patients frères (l'un avec mutation, l'autre sans mutation utilisé comme témoin). L’analyse des cardiomyocytes ventriculaires exprimant le RyR2R420Q humain et de souris étudiées par imagerie Ca2+confocale montre une augmentation des libérations de Ca2+spontanée durant la diastole (visualisé par les Sparks Ca2+), une libération fractionnelle plus élevée et une fréquence de vagues Ca2+ proarythmogènes augmentée après stimulation à l'isoprotérénol. L’analyse électrophysiologique, étudiée en enregistrant les potentiels d'action (AP) en utilisant les techniques de micro-électrodes sur les hiPSC-CM et de patch-clamp sur les cellules ventriculaires de souris KI, a montré des post-dépolarisations retardées dépendants du Ca2+ (DAD). L’amplitude des transitoires [Ca2+]i des cellules stimulées à 1 Hz étaient plus faible chez le groupe muté. La charge en Ca2+ du réticulum sarcoplasmique (SR), estimée par application rapide de caféine (10 mM), était aussi plus réduite dans les hiPS-CM exprimant RyR2R420Q, avant et après l'application ISO (1 μM). Cependant, le RyR2R420Q semble plus enclin à libérer du Ca2+, car le transitoire [Ca2+]i normalisé par la quantité de Ca2+ stockée dans le SR, la libération fractionnaire, était plus élevée dans les cellules mutées. Même si la charge Ca2+ du SR était plus petite dans les cellules RyR2R420Q, elles présentaient souvent un comportement pro-arythmogène tel que les vagues Ca2+ pendant les périodes diastoliques. Ce comportement est encore augmentée lors de la stimulation -adrénergique. Des résultats similaires ont été observés chez les souris KI, montrant ce modèle comme un outil précieux pour étudier la maladie CPVT. Nous avons ensuite étudié l'effet antiarythmique potentiel de la venlafaxine et de la prégabaline dans les cardiomyocytes de souris KI et le hiPS-CM, deux médicaments parmi d'autres prescrits à un membre porteur de la famille et qui a montré une réversion des symptômes du CPVT après le traitement. Nous avons constaté que ces deux médicaments atténuaient les événements arythmogènes de libération du Ca2+ induits par l'ISO dans les cardiomyocytes de souris KI. La venlafaxine a montré un effet antiarythmique dans hiPS-CM à la fois en traitements aigus et chroniques.Ainsi 1) le RyR2R420Q montre une augmentation de la libération diastolique du Ca2+ , encore plus augmentée par la stimulation à l ’isoproterénol, induisant des évènements proarythmogènes. 2) les effets sont retrouvés chez des cardiomyocytes ventriculaires des souris KI et chez des cellules hiPSC-CM, montrant que ces dernières sont un outil valable pour étudier les mécanismes pathologiques ; et 3) que la Venlafaxine peut protéger des arythmies chez les patients CPVT, bien que d’avantage d’expériences sont nécessaires afin de conclure quant à son utilité antiarythmiqueCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests by syncope or sudden death in children and young adults under stress conditions without obvious cardiac structural abnormality. Several mechanisms have been proposed to explain the underlying Ca2+ release functional alterations due to mutations of RyR2 or of its accessory proteins. A novel CPVT mutation located on RyR2 N terminal portion has been identified in a Spanish family (RyR2R420Q). Here we used a KI mice model expressing the RyR2R420Q channel, and differentiated cardiomyocytes from induced pluripotent stem cells (hiPS-CM) generated from two brother patients (one with mutation, the other without mutation used as control). Confocal Ca2+ imaging analysis showed that human and mouse RyR2R420Q expressing ventricular cardiomyocytes have higher occurrence of Ca2+ sparks, enhanced fractional release, and significantly more proarrhythmogenic Ca2+ waves after isoproterenol stimulation. The action potential (AP) analysis, recorded using the micro-electrode technique in hiPSC-CMs and patch-clamp in KI mouse ventricular cells, showed Ca2+ -dependent delayed after depolarizations (DADs). The [Ca2+]i transient amplitudes of 1-Hz paced CPVT hiPSC-CMs was similar to control hiPSC-CMs. Whereas sarcoplasmic reticulum (SR) Ca2+ load, estimated by rapid caffeine (10 mM) application, was smaller in hiPS-CM from the RyR2R420Q carrier, both before and after 1 microM ISO application. However, the RyR2R420Q seems more prone to release Ca2+, as the [Ca2+]i transient normalized by the amount of Ca2+ stored in the SR, the fractional release, was higher in CPVT hiPSC-CMs. Even if SR Ca2+ load was smaller in CPVT hiPSC-CMs, they often presented proarrythmogenic behavior such as Ca2+ waves during diastolic periods. This behavior was further enhanced during β-adrenergic stimulation. Similar results were observed in KI mice, pointing to this model as a valuable tool to study the CPVT disease. We then studied the potential antiarrhythmic effect of venlafaxine and pregabalin in KI mouse cardiomyocytes and hiPS-CMs, two drugs among other medications that have been prescribed to one family carrier member and devoted of CPVT symptoms. We found that both of those drugs blunted ISO induced arrhythmogenic events in KI mouse cardiomyocytes. Venlafaxine showed antiarrhythmic effect in hiPS-CMs both by acute and chronic treatments.On overall, 1) the RyR2R420Q mutation shows enhanced diastolic Ca2+ release, which is further enhanced by isoproterenol inducing proarrhythmogenic events. 2) The effects were similar in hiPSC-CM and RyR2R420Q KI mice cardiomyocytes, pointing to hiPSC-CM as a valuable model to analyze pathological mechanisms; and 3) Venlafaxine may protect from arrhythmic CPVT patients, although more experiments are needed for in vivo test and to determine the mechanism of this antiarrhythmic effect
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Klemiato, Beata. "Dalyvių, pusdalyvių ir padalyvių vartojimas „Respublikos“ ir „Lietuvos ryto“ dienraščiuose." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2007. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2007~D_20070816_170442-18789.
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Šis darbas skirtas didžiausių Lietuvos dienraščių – „Lietuvos ryto“ ir „Respublikos“ – dalyvių, pusdalyvių ir padalyvių vartojimo analizei. Norėta išsiaiškinti, ar dalyviai iki šiol yra dažnai tebevartojami, koks jų santykis minėtuose dienraščiuose. Dalyvių vartojimo polinkiai publicistikoje anksčiau beveik nebuvo tirti, tad darbas galėtų būti tolimesnių bei išsamesnių tyrimų pradžia.
Pagrindinis darbo tikslas buvo nustatyti visų minėtų dalyvinių formų dažnumą, aptarti rašytinės kalbos dalyvinių konstrukcijų vartojimo ypatumus minėtuose dienraščiuose ir palyginti abiejų laikraščių kalbą. Analizuojant tiriamąją medžiagą buvo keliami šie uždaviniai: 1) apžvelgti lingvistinę literatūrą, susijusią su nagrinėjimo objektu; 2) išrinkti iš minėtų dienraščių analizuojamųjų straipsnių dalyvius, pusdalyvius ir padalyvius, sugrupuoti juos; 3) nustatyti ir aptarti dalyvių vartojimo dėsningumus (ypatumus); 4) palyginti dalyvių, pusdalyvių ir padalyvių vartojimą, t. y. nustatyti jų vartojimo santykį dviejuose populiariausiuose Lietuvos dienraščiuose; 5) statistiškai pateikti gautus rezultatus, analizuoti, apibendrinti.
Išanalizavus didžiausių Lietuvos dienraščių „Respublika“ ir „Lietuvos rytas“ 50 straipsnių ir ištyrus juose rastus dalyvius, pusdalyvius bei padalyvius, buvo prieita tam tikrų išvadų. Tyrimas parodė, kad dažniausiai „Respublikos“ ir „Lietuvos ryto“ dienraščiuose vartojami būtojo kartinio laiko veikiamieji ir neveikiamieji dalyviai. Būtojo kartinio laiko neveikiamasis dalyvis... [toliau žr. visą tekstą]This work is aimed at the analysis of usage of participles, half-participles, verbal adverbs in “Lietuvos rytas“ and “Respublika“ newspapers. The purpose was to find out if participles are still often used and what is the frequency of this usage in the magazines. The usage of participles has not been examined yet that is why this work could be the beginning of the further examinations. The main purpose of the work was to assume the frequency of the participles and their forms, discuss the peculiarities of their spelling in the above-mentioned magazines and compare their language. While analyzing the newspapers I set the main goals: 1) examine linguistic literature related to the object of analysis; 2) choose the participles, half-participles and verbal adverbs from the above mentioned newspapers and group them; 3) ascertain and discuss the rules (peculiarities) of the usage of participles; 4) compare the usage of participles, half-participles and verbal adverbs and ascertain the frequency of their usage in the above mentioned magazines; 5) establish the statistics of the results, discuss them and sum up. The results have been made after the analysis and examination of participles, half-participles and verbal adverbs found in 50 articles in the daily newspapers “Respublika“ ir “Lietuvos rytas“. The examination showed that the most frequently used participles are past participles and passive participles. Past passive participles are a little more frequently used in... [to full text]
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Nicoll, Baines Katie Mhairi. "Muscle energetics and ageing in the context of RYR1 variants." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/17288/.
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In aged muscle, from humans and mice, the ryanodine receptor (RyR1) is leaky, leading to increased levels of resting Ca2+ in the myoplasm. This is also a feature of skeletal muscle disorders caused by variants in RyR1 such as malignant hyperthermia (MH), central core disease (CCD), exertional heat illness (EHI) and late-onset axial myopathy (LOAM). Elevated Ca2+ is damaging to mitochondria, leading to production of reactive oxygen and nitrogen species associated with MH susceptibility to inhalational anaesthetics. Mice with Ryr1 variants show premature muscle ageing and highlight the cycle of inefficient calcium handling and oxidative damage to mitochondria that impairs skeletal muscle energetics. Caenorhabditis elegans models of MH CCD EHI and LOAM variants, both homozygous and heterozygous forms, showed increased sensitivity to halothane. Altered caffeine sensitivity was evident in MH and CCD models, and at very high concentrations in EHI models. Strains with RyR1 variants exhibit age-related accelerated myosin disorganisation. Whole genome Affymetrix arrays revealed genes and pathways correlated with skeletal muscle ageing and MH. Of additional genes of interest investigated UNC13, CASQ1, ORAI1, MCU and MICU1 showed altered expression with age. Array data from blood has been used to identify a signature for MH susceptibility. There is loss of mitochondrial membrane integrity and alteration in mitochondrial number in MH. New apparatus, capable of quantifying heat produced during muscle contraction, has enabled calculation of skeletal muscle efficiency. Preliminary data indicates that there was loss of skeletal muscle efficiency in aged muscle from wild type mice. This work provides new information on the role of RYR1 variants in skeletal muscle ageing and the importance of calcium handling in muscle energetics.
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Kathirvel, Paramasivam. "Mapping and manipulation of the murine ryanodine receptor gene (Ryr1)." Thesis, University of Edinburgh, 2000. http://hdl.handle.net/1842/12330.
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In this present study, experiments were carried out a) to characterise the mouse skeletal muscle ryanodine receptor (Ryr1) gene cDNA, b) to construct a contiguous map of the murine Ryr1 gene and c) to evaluate the phenotype of the Ryr1 knockout transgenic mice and to develop a mouse model, which carries a homologue of the C1843T mutation, associated with MH in pigs and some humans. The murine Ryrl cDNA has been characterised by cDNA cloning and sequence analysis. Murine Ryrl exon-specific RT-PCR primers were designed and used to generate Ryrl cDNA fragments from skeletal muscle total RNA of the mouse strain 129. The cloned RT-PCR products are overlapping and yield about 15 kb cDNA sequence. The cDNA sequence has higher sequence similarity with mammalian sequences than other vertebrate and invertebrate ryanodine receptor gene(s). A contiguous map of the Ryr1 gene has been constructed by DNA fingerprint analysis and STS mapping. Large fragment genomic clones containing murine Ryr1 sequences have been isolated from two libraries - a Bacterial Artificial Chromosome (BAC) library and P1-derived artificial chromosome (PAC) library. Of the 33 clones isolated, 4 were from the BAC and 29 were from the PAC library. The BACs form tow contiguous fragments separated by a gap. The relationships among the BACs were confirmed by DNA fingerprinting using human RYR1 cDNA fragments. This experiment also confirms the isolated clones are skeletal muscle ryanodine receptor isoform (Ryr1) specific. Sequence information from these BAC genomic clones and cDNA sequence information from this study has been used to develop STS markers. A contiguous map of the clones and flanking sequences has been established by STS analysis in BAC/PAC clones, which together span about 495 kb. The presence of all tested STS markers in two single PACs indicates that the murine Ryr1 gene is about 150 kb.
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Duchková, Veronika. "Internetový obchod v rodinném podnikání." Master's thesis, Vysoká škola ekonomická v Praze, 2013. http://www.nusl.cz/ntk/nusl-197846.
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This thesis focuses on the Internet shop in family business. In the first part the terms Internet shop and family business are specified. Its formation, development, advantages and disadvantages are defined, as well as the usage of Internet in marketing and the factors of success and problems connected with family business. The second part describes in detail chosen areas of the company Ryor -- the environment of its e-shop, advertising and distribution of products. This part gives a description of functioning mentioned areas. The real state is confronted with technical literature. On the basis of that, shortcomings are got. Moreover, suggestions for better functioning of chosen areas are formed. The second part of thesis also includes SWOT analysis of e-shop, analysis of competitors and questionnaire survey about customer's satisfaction with areas that the thesis explores.
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Bunte, James. "A Player’s Guide to the Music of Ryo Noda: Performance and Preparation of Improvisation I and Mai." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1282578051.
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Bround, Michael J. "The effects of RYR2 gene deletion on cardiac function and metabolism." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57589.
Full textAbstract:
The cardiac ryanodine receptor 2 (RYR2) is a sarcoplasmic reticulum Ca²⁺ release channel central to cardiomyocyte biology. RYR2 Ca²⁺ release has a well-established role in activating cardiomyocyte motor proteins during excitation-contraction coupling and is therefore critical for heart function. RYR2 is also poised to have other important cardiac functions such as setting heart rate, stimulating ATP metabolism, regulating cardiac hypertrophy, and controlling cardiomyocyte survival. In addition, there is evidence that RYR2 dysfunction occurs during heart disease, suggesting that RYR2 may be a driver of cardiac pathology. The research in this thesis seeks to test which aspects of cardiomyocyte biology are regulated by RYR2 signaling and whether RYR2 loss-of-function is pathogenic. Using a heart-specific, inducible gene deletion system in mice we were able to show that loss of Ryr2 caused heart failure and reduced cardiac contraction. In addition, we saw that Ryr2 deletion lead to reduced heart rate, tachycardic arrhythmia, diminished oxidative metabolism, increased cardiac hypertrophy, and increased cell death via a novel mechanism. To test whether the metabolic and heart rate effects persist in the absence of heart failure, we used an inducible, heart-specific 50% Ryr2 deletion model. In this context we did not see heart failure or decreased cardiac function, but still observed a decrease in heart rate and altered oxidative metabolism. Unlike complete Ryr2 knockout, the 50% Ryr2 ablation model did not display a general decrease in oxidative ATP metabolism, but instead a specific decrease in glucose oxidation. This was associated with reduced mitochondrial Ca²⁺ uptake and decreased activation of the pyruvate dehydrogenase complex, a Ca²⁺ sensitive gatekeeper of glucose oxidation. Collectively, these results provide compelling evidence that RYR2 is an essential component of excitation-contraction coupling and a critical driver of cardiac pacemaking. These results also demonstrate that RYR2 is critical for mitochondrial Ca²⁺ uptake and stimulating oxidative metabolism and strongly suggest that RYR2 has a specific role in activating glucose oxidation. This research also shows that loss of Ryr2 recapitulates heart failure and suggests RYR2 may be involved in hypertrophy and cell death. This suggests a model where RYR2 simultaneously regulates a several facets of cardiomyocyte biology.Medicine, Faculty of
Graduate
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Kjellberg, Jenni. "Rya : ett studieområde inom designpedagogiken." Thesis, Konstfack, Institutionen för Bildpedagogik (BI), 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:konstfack:diva-505.
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Anthony, Diana Francesca. "CaMK118 interaction with the RyR2 complex in normal and failing rabbit hearts." Thesis, University of Strathclyde, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488532.
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Cardiac Ca2+ cycling consist of a series of tightly controlled events, regulated by a number of key proteins that release and sequester Ca2+ both at the cell surface and via intracellular stores. RyR2 is the main SR Ca2+ release channel. Direct regulation of RyR2 by CaMKIId, an important Ca -dependent enzyme, has previously been demonstrated.
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Matačinskaitė, Jurgita. "Periodikos ir interneto konvergencija: "Lietuvos ryto" ir "The New York Times" atvejai." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2008~D_20140623_175831-12207.
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Darbo objektas – periodikos ir interneto konvergencijos samprata bei šios proceso taikymas viename solidžiausių ir didžiausių Lietuvos dienraščių „Lietuvos rytas“ bei viename iš įtakingiausių ir didžiausių Jungtinių Amerikos Valstijų dienraščių „The New York Times“. Darbo tikslas – išnagrinėti periodikos ir interneto konvergencijos ypatumus. Darbo uždaviniai: išsiaiškinti konvergencijos sampratą žiniasklaidos teorijoje; nustatyti priežastis, verčiančias periodiką konverguoti su internetu; įvardinti, kaip naujosios technologijos leidžia tobulinti ir kurti papildomą pridėtinę vertę periodikai; išskirti esminius konvergencijos proceso bruožus; aptarti pagrindinius periodinės spaudos – laikraščių ir žurnalų – interneto versijų bruožus; išnagrinėti žiniasklaidos teorijoje apibrėžto konvergencijos proceso esminių bruožų taikymą dienraščiuose „Lietuvos rytas“ bei „The New York Times“. Naudojantis lyginamąja analize prieita prie išvados, kad dienraščio „Lietuvos rytas“ ir „The New York Times“ interneto versijos geriau nei šių leidinių spausdintos versijos tenkina skaitytojų poreikį greitai ir operatyviai sužinoti esminę tos dienos leidiniuose pateikiamą informaciją. Dienraščių interneto versijose skaitytojui visos svarbiausios tos dienos naujienos pateikiamos iš karto. Remiantis žurnalistikos teorijoje apibrėžtais turinio, vaizdinių priemonių bei interaktyvumo kriterijais prieita prie išvados, kad dienraščio „The New York Times“ konvergencija su internetu yra didesnė nei dienraščio... [toliau žr. visą tekstą]The society is changing its habits to use the computers and the internet both in Lithuania and in the worldwide. The print newspapers and magazines do not want to lose their readers which are more and more tended to search the information on the internet. It is one of the reasons why the print media – the print newspapers and magazines converges with the internet. The print media has to search and to find the new ways to reach the audience. The second reason of the print newspapers and magazines convergence with the internet is the hyper competition in the mass media market. The purpose of this paper is to understand how the periodic press – the print newspapers and the magazines in this case – converge with the internet. The practical background is to check how the process of the convergence is working on the one of the biggest and influential Lithuanian print newspaper “Lietuvos rytas” and on the one of the biggest and most influential print newspaper of the United States of America – „The New York Times“. The statistical data, public surveys in Lithuania and in the United States of America, content analysis, comparison of the documents, the books and the articles from the newspapers, scientific journals and other internet resources has proven, the most distinctive today‘s interaction between the traditional print media instruments and the internet – the majority of Lithuanian and world periodical press, such as the print newspapers and magazines, have their own internet... [to full text]
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Lobo, Joshua J. "3D RECONSTRUCTION OF RyR1 AND STRUCTURAL VALIDATION UNDER DIFFERENT LEVELS OF NOISE." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3633.
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Ryanodine receptors (RyR) are intracellular channels that are intricately involved in Ca2+ release. These channels large membrane proteins~2.26MDa in size. In this multi-goal project firstly we successfully studied the gating mechanics of the RyR1 in the presence of Mg2+. We used single particle reconstruction and image processing techniques to obtain the 3D structure of the RyR1 with Mg2+. The 3D structure in the presence of Mg2+ and an ATP analog is the closest representation of human physiological conditions. The open and closed state structures of RyR1 are known. However, the physiologically closed state has not been studied before. Understanding this structure will help in the understanding of protein interactions. Our second goal was the validation of this 3D structure under different levels of noise. Validation under different noise levels analyzed the problem of noise bias is present in the field of cryo-EM and single particle reconstruction in select cases.
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Strazdienė, Vaidutė. "Ankstyvoji vaikų ir paauglių nusikalstamumo prevencija; Vilniaus m. „Ryto" vidurinės mokyklos mokinių požiūris." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2005~D_20050615_132122-49328.
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The principal aim of the presented Paper is an analysis of the system of prevention of delinquency of the under-age persons, the attitude of pupils towards the early prevention of children and teenagers and offering versions of its optimization. The hypothesis: measures of early prevention of delinquency, taken by qualified pedagogues upon application active methods, that conform to the needs and age of pupils, should be assessed positively. Unoccupancy is one of the factors affecting delinquency of the under-age. The scope of the investigation: 274 pupils of the 6-12th grades of a secondary school. The methods of the investigation: theoretical analysis of the references related to the subject, questioning of pupils, statistical analysis of the data of quantitative analysis and the method of generalization. On the base of the investigation, the following assumptions may be formulated: · A majority of crimes is committed by unoccupied children and teenagers. Their unoccupancy is an increased risk factor. · Failure to investigate the needs of children and teenagers as well as failure to take them into account form preconditions for their delinquency. The activities organized by qualified pedagogues, taking into account the age and needs of pupils, prevent children and teenagers from delinquency.
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Bertan, Fabio [Verfasser]. "Ryanodine Receptor 2 (RyR2) underlies maintenance and remodeling of dendritic spines / Fabio Bertan." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1229989161/34.
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Milbradt, Anita [Verfasser], and Andreas [Akademischer Betreuer] Ludwig. "Konditionelle Gendeletion des Ryanodinrezeptors RyR2 im Herzen der Maus / Anita Milbradt. Betreuer: Andreas Ludwig." Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2011. http://d-nb.info/1018309039/34.
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Fry, Debra L. "Modulating intracellular Ca2+ signalling using recombinant fragments of the human cardiac ryanodine receptor (RyR2)." Thesis, Cardiff University, 2008. http://orca.cf.ac.uk/54780/.
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Interaction between discrete domains of the cardiac ryanodine receptor (RyR2) has emerged as a pivotal mechanism regulating channel function. RyR2 mutations perturb conformational intra-molecular constraints that are linked to dysregulated Ca2+ release. Previous work from this laboratory identified an interacting- or I-domain of human RyR2 that mediates interaction between the large cytoplasmic assembly and the transmembrane (TM) domain of RyR2. Bioinformatic approaches revealed striking structural homology between sub-fragments of the RyR2 I-domain and I-domain-like regions of inositol 1,4,5-trisphosphate receptors (IP3R). Acute expression of I-domain sub-fragments in human embryonic kidney (HEK) cells (where the rank order of expression is IP3R2 > IP3RI) was associated with profound loss of cell viability predominantly via apoptosis. This increase in apoptosis was linked to altered Ca2+ cycling (measured using a novel index of Ca2+ signal variability) and a remarkable loss of carbachol-evoked Ca2+ release. Intriguingly, increased apoptosis and perturbed Ca2+ handling was also observed in neighbouring cells that did not express recombinant I-domain proteins - a phenomenon termed the bystander effect. The bystander effect is likely mediated by transfer of signalling molecules via direct cell-to-cell coupling (gap junctions) and via diffusible mediators (extracellular route). This thesis supports the novel concept that IP3R-mediated Ca2+ handling and cellular phenotype can be exquisitely tuned by recombinant fragments of RyR2.
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Dornan, Thomas J. "Antioxidant Anthocyanidins and Calcium Transport Modulation of the Ryanodine Receptor of Skeletal Muscle (RyR1)." PDXScholar, 2011. https://pdxscholar.library.pdx.edu/open_access_etds/319.
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Cardiovascular disease (CVD) claims more lives than any other disease in the world. Although numerous biological pathways share the blame, ventricular tachyarrhythmia (VT) is estimated to account for ~25% of all CVD deaths. A complete understanding of the molecular mechanisms underlying VT is unknown but recent studies have linked VT to improper calcium handling in the heart (canine). The principle calcium regulator in the muscle cell is the calcium ion release channel (aka RyR). Numerous endogenous and exogenous compounds can affect the way the RyR regulates calcium. In particular, abnormal levels of oxidants (reactive oxygen species) can oxidize critical thiol groups on the RyR and modulate its activity. Interestingly, high levels of oxidants are also associated with numerous bodily disease states including cancers, muscle fatigue/failure, and CVD. In this thesis, two important dietary antioxidant compounds, the anthocyanidins pelargonidin and delphinidin, are evaluated for their effects on regulating the transport of calcium through the calcium release channel (RyR1) of the sarcoplasmic reticulum of skeletal muscle. Pelargonidin and delphinidin are structurally similar with delphinidin only differing from pelargonidin by the addition of two hydroxyl groups. Both compounds undergo time dependent structural changes in aqueous solutions at physiological pH and a mixture of more than four structures of each compound can be present in solution simultaneously. Pelargonidin and delphinidin show distinct differences in their calcium flux regulating effect on the RyR1. Delphinidin stimulates calcium flux and RyR1 activity where as pelargonidin can cause both inhibition and stimulation of the RyR1. The strength of stimulation and inhibition of calcium transport through the RyR by delphinidin and pelargonidin may be attributed to the structural and chemical changes in those compounds that occur in solutions near physiological pH and the subsequent chemical characteristics of the diverse set of structures that are simultaneously present in solution.
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Caldwell, Patricia Theresa. "Investigations into the Molecular Mechanisms of Trichloroethylene Cardiotoxicity in vivo and in vitro." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/195364.
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Trichloroethylene (TCE) is among the most common water contaminant in the United States and around the world. It is estimated that between 9% and 34% of all drinking water sources contain some TCE. The EPA set a drinking water standard for TCE at 5 parts per billion (ppb) in 1989, however since this date, many studies have shown TCE is dangerous to the health of adults and unborn children, even at low-level exposures. These studies reveal exposure to TCE can cause multi-organ damage, especially for the kidney, liver, reproductive and development systems. We investigated how TCE can effect embryonic heart development by identifing possible target mechanisms changing after exposure. Acute and chronic exposure to rat cardiomyocytes produced altered calcium flow and significant changes with TCE doses as low as 10ppb. Embryonic carcinoma cells, rat cardiomyocytes and fetal heart tissue all showed global changes in gene expression after low-dose TCE exposure, including critical ion channels that drive calcium flux. High levels of folic acid supplementation in combination with 10ppb TCE exposure in maternal diets caused significant genetic modifications in mRNA expression levels of Day 10 embryonic mouse cardiac tissue. We also found both high and low folate maternal diets leads to similar phenotypic outcomes in embryo development.
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Zhou, Xinyu. "Modulation of Ca2+ Signaling by Trimeric Intracellular Cation Channels in the Heart." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1546600975458309.
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Brulé, Cédric. "Vieillissement musculaire : impact de la protéolyse intracellulaire calcium-dépendante." Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13899/document.
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La sarcopénie ou perte involontaire progressive de la masse musculaire chez le sujet âgé s’accompagne de l’altération de nombreux phénomènes physiologiques comparables à ceux observés chez les myopathes. Le processus de régénération musculaire est très ralenti, les activités protéolytiques intracellulaires sont modifiées et de nombreuses fonctions cellulaires sont perturbées en raison d’un stress oxydatif incontrôlé. L’intervention des calpaïnes, protéases neutres calcium-dépendantes, dans les processus associés au développement, à la régénération et à l’intégrité du tissu musculaire est incontestable. Les calpaïnes apparaissent, en effet, comme des acteurs clefs des voies de transductions liées à la myogenèse, la prolifération et la survie cellulaire. Toutefois aucune étude permettant d’établir la relation vieillissement du tissu musculaire- activité calpaïne n’a été entreprise à ce jour. Le projet a donc pour but principal d’inventorier les signaux pro-sarcopéniques interagissant avec les calpaïnes et d’établir leurs relations avec la fonctionnalité des cellules satellites, le stress oxydant et l’apoptose. Nous avons mis en évidence une augmentation de l’expression/activité des calpaïnes durant le vieillissement musculaire chez le rat et identifié des partenaires des calpaïnes impliqués dans des fonctions physiologiques altérées durant la sarcopénie: homéostasie calcique, activité contractile, production d’ATP, régénération musculaire. Nous avons également montré que l’induction d’un stress oxydant entraîne l’activation des calpaïnes au cours de la prolifération des cellules satellites de façon corrélée à une augmentation de l’apoptose. D’une manière intéressante, un traitement préventif par un antioxydant naturel d’écorce de pin (Oligopin®) est capable de prévenir à la fois l’apoptose et l’activation des calpaïnes. L’ensemble de ces résultats suggère que le stress oxydant associé au vieillissement induirait des mécanismes calpaïno-dépendants responsables de l’altération de processus essentiels à la fonction musculaireAging is associated with a progressive and involuntary loss of muscle mass also known as sarcopenia. This condition represents a major public health concern. Although sarcopenia is well documented, the molecular mechanisms of this condition still remain unclear. The calcium-dependent proteolytic system is composed of calcium dependent cystein-proteases named calpains. Calpains are involved in a large number of physiological processes such as muscle growth and differentiation, and pathological conditions such as muscular dystrophies. The aim of this study was to determine the involvement of the proteolytic system in the phenotype associated with sarcopenia by identify the key proteins (substrates or regulators) interacting with calpains during muscle aging and identify pro-sarcopenic signals after oxidative stress induction in satellite cells. Muscle aging was correlated with the up-regulation of calpain activity. Ryanodine receptor 1, ATP synthase subunit alpha and alpha actinin 3 appear as key partners of calpains during muscle aging. Such interactions suggest an implication of calpains in many processes altered during aging including cytoskeletal disorganisation, regulation of calcium homeostasis and mitochondrial dysfunction. Furthermore, oxidative stress induction led to an increase in the activity of calpains correlated to an increase in apoptosis of proliferating satellite cells. In a very interesting way, a preventive treatment with a commercial antioxidant (Oligopin®) prevented these effects. All these data suggest that oxidative stress coupled observed during muscle aging could lead to calpaïno-dependent mechanisms responsible for apoptosis and muscle dysorganisation
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Bosson, Caroline. "Caractérisation génétique des hyperthermies déclenchées." Thesis, Université Grenoble Alpes, 2020. https://thares.univ-grenoble-alpes.fr/2020GRALV015.pdf.
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L’Hyperthermie d’Effort (HE) et l’Hyperthermie Maligne (HM) sont deux pathologies potentiellement fatales déclenchées par un exercice physique intense pour la première, et par l’administration d’anesthésiques halogénés pour la seconde. A ce jour, seule l’HM est bien caractérisée sur le plan génétique car elle est causée en majorité par des mutations dans le gène RYR1, responsables d’une anomalie de l’homéostasie calcique dans le muscle squelettique. L’HM et l’HE partageant de nombreuses similarités cliniques et physiopathologiques, une origine génétique commune a été suggérée. Dans ce contexte, l’objectif de ce travail était d’étudier les causes génétiques de l’HE. Tout d’abord, ce travail a consisté à rechercher l’implication des gènes classiquement associés à l’HM, en particulier RYR1, chez des patients adressés au laboratoire de diagnostic pour suspicion d’HE. Nous avons ainsi montré que le taux de variations dans le gène RYR1 est de 66% chez les patients dont la susceptibilité à l’HM est avérée, mais que ce taux est de 14% chez les patients HE, chez qui nous n’avons d’ailleurs pas identifié de mutation formellement pathogène. Cette faible prévalence des mutations du gène RYR1 dans l’HE a ensuite été confirmée par l’étude d’une seconde cohorte bien caractérisée de militaires atteints d’HE. Cette prévalence étant nettement plus faible que celle observée dans l’HM, une analyse d’exomes a permis d’identifier d’autres gènes candidats dans l’HE comme le gène TRPV1 (prévalence de 3,3%), dont l’effet fonctionnel des mutations identifiées a été validé in vitro. Un troisième gène a également été identifié, avec une prévalence de 10%. Ces résultats permettent de mieux caractériser l’HE sur le plan génétique, afin d’identifier les sujets à risque et prévenir les récidivesExertional Heat Stroke (EHS) and Malignant Hyperthermia (MH) are life-threatening diseases triggered by strenuous activity for the former, and halogenated anesthetics for the latter. Only MH is genetically well-characterized today: it is mainly caused by mutations in the RyR1 channel, triggering an anomaly in calcium homeostasis in the skeletal muscle. As MH and EHS share many common clinical and pathophysiological features, they could also share common genetic causes. In this context, the purpose of this work was to study the genetic causes of EHS. First, we searched for mutations in genes classically associated with MH, especially the RYR1 gene, among patients tested in the laboratory for EHS suspicion. We demonstrated that variations in the RYR1 gene are identified in 66% of recognized MH cases, while they concern only 14% of EHS patients. Moreover, no pathogenic mutation has been identified in EHS patients. This low prevalence of RYR1 variations was next confirmed by studying a second cohort of soldiers suffering from EHS. This prevalence, relatively low when compared to MH cases, suggested the involvement of other gene. The whole exome sequencing confirmed the involvement of the TRPV1 gene in 3.3% of cases. The in vitro analysis of TRPV1 variations demonstrated that they affect the protein function. A third gene was identified, with a prevalence of 10%. These results should help to better characterize EHS at a genetic level and to identify patients at-risk for EHS in order to prevent recurrences
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Krempler, Andrea. "Analyse der RyREF2-Bindungsstelle im Promotor des porcinen RyR1-Gens und Charakterisierung des porcinen FHL1-Gens." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=963553518.
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Clack, Aaron Ian. "Investigating the functional consequences of cardiac ryanodine receptor (RyR2) polymorphisms on arrhythmia-linked Ca2+ release dysfunction." Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/54155/.
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This data provides compelling evidence that mutation-linked RyR2 channel dysfunction is modulated by common sequence polymorphisms and predicts that a more severe clinical phenotype results from the in cis inheritance of G1885E / L433P. Our studies also show that co-expression of L433P and G1885E subunits partially restores the functionality of the resultant heterotetrameric channels. The potential therapeutic benefits of positively modulating RyR2 mutant channel dysfunction via such a trans-complementation approach remain to be explored.
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Nel, Ryno. "Thermal fluid analysis of combined power and desalination concepts for a high temperature reactor / Ryno Nel." Thesis, North-West University, 2011. http://hdl.handle.net/10394/8416.
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South Africa is on a path of dramatically increasing its energy supplying capabilties.
Eskom (the main utility supplying electricity to the national grid) recently announced
that future power station technologies will focus on renewable energy and nuclear
power. This is done in an effort to reduce South Africa’s dependance on burning
fossil-fuels and thereby decreasing CO2 emissions and other harmful gases. This,
together with the fact that there are a lot of fresh water scarce areas especially along the
Eastern Cape coast of South Africa, is what inspired this study. This study investigates
the use of a 200 MWth High Temperature Reactor (HTR) for cogeneration purposes.
Heat from the reactor is utilised for electricity generation (Rankine cycle) and process
heat (desalination). Two desalination concepts were evaluated thermodynamically and
economically, namely Multi-Effect Distillation (MED) and Reverse Osmosis (RO).
Computer software, Engineering Equation Solver (EES), was used to simulate different
cycle configurations, where the heat available in the condenser was increased
successively.
The coupling of the two desalination technologies with a HTR was compared and it was
found that a RO plant produces nearly twice as much water while sending the same
amount of electricity to the grid (compared to coupling with MED). Coupling options
were investigated and each simulation model was optimised to deliver maximum output
(power and water).
The best configuration was found to be the coupling of a HTR with a RO plant
producing 86.56 MW generator power. This is equal to 2077 MWh/day. Using
332 MWh/day for desalination through RO, delivers 73 833 m3/day fresh water and
results in 1745 MWh/day sent to the grid. This scenario is the best option from a
thermodynamic and economic point of view. From an investment point of view, it will
produce an Internal Rate of Return (IRR) of 10.9 percent and the Net Present Value
(NPV) is calculated to be R 2,486,958,689.
The results and analysis for the different cycle configurations are presented in such a
way that an easy comparison can be made.Thesis (M.Ing. (Nuclear Engineering))--North-West University, Potchefstroom Campus, 2011
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Dabertrand, Fabrice. "Identification et rôle fonctionnels de variants d'épissage du récepteur de la ryanodine de type 3 (RyR3)." Bordeaux 2, 2006. http://www.theses.fr/2006BOR21351.
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La fonction du sous-type RYR 3 du récepteur de la ryanodine ne peut se comprendre qu'à travers l'étude de ses différents variants d'épissage. Dans les muscles lisses de souris, nous avons mis en évidence l'existence d'un variant court dominant négatif. En effet, dans le duodenum, celui-ci inhibe le sous-type RYR 2 responsable de la libération du calcium stocké dans le reticulum. L'isoforme complète de RYR3 n'interagit pas avec l'isoforme courte et code des oscillations calciques spontanées lors d'une surharge du contenu en calcium du reticulum. Enfin, cet épissage alternatif est modulé dans le myomètre lors de la gestation. A l'approche de la parturition, l'expression de l'isoforme complète domine ce qui permet aux voies de transduction aboutissant à la production d'ADP-ribose cyclique de produire la libération du calcium stocké, phénomène participant à la contraction utérineThe understanding of the function of ryanodine receptor subtype RYR3 needs the study of RYR3 alternative splicing. In mouse smooth muscles, we have shown the expression of short dominant negative variant. In fact, in duodenum, the short isoform inhibits the RYR2 subtype responsible for the release of stored calcium in reticulum. The complete isoform of RYR3 cannot interact with the short isoform but encodes spontaneous calcium oscillations only when the reticulum is calcium overloaded. This alternative splicing is also modulated in myometrium during pregnancy. Near the term, the expression of complete RYR3 isoform is dominant whch allows cyclic ADP-ribose-dependent transduction pathways to release stored calcium that participates to uterine contraction
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Anttila, K. (Katja). "Swimming muscles of wild, trained and reared fish:aspects of contraction machinery and energy metabolism." Doctoral thesis, University of Oulu, 2009. http://urn.fi/urn:isbn:9789514290770.
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Abstract Billions of reared fish are released to the wild to compensate e.g. for the loss of natural populations. However, the efficiency of the releases is low. It has been proposed that one of the factors affecting the low survival rate of reared fish is their low swimming capacity. The molecular, metabolic and structural characters of muscle fiber define the swimming capacity of fish. Swimming capacity is related to the ecological competence of the fish, including the ability to complete long migrations and catch pray. One of the aims of the current study is to compare the properties of muscles of reared and wild salmon. The second aim of the study is to alter the muscular parameters of reared fish closer to those of wild fish by means of training. The muscular differences between wild, reared and trained fish are analyzed with immunological, histochemical and electron microscopic methods. The main focus is on the dihydropyridine and ryanodine receptors. These receptors are involved for example in the initiation, force and velocity of muscle contraction. According to the results, the level of receptors is higher in the muscles of wild as compared to reared fish. The aerobic ATP production capacity is also higher in the wild fish. However, with training both the level of receptors and oxidative capacity of reared fish increase. Moreover, the swimming capacity is enhanced in trained fish, and there is a connection between the level of receptors and swimming capacity of fish. Training also affects the migration pattern of fish which starts to resemble more that of wild fish. In conclusion, the results of the current study show that the performance of fish as a whole depends on functional parameters at cellular level. For the first time, it is shown that the level of receptors involved in muscular contraction is low in muscles of reared fish. However, the muscular properties are not definite. It is now shown that with training, both the muscular and migration parameters of reared fish approach those of wild fish. This will most probably increase the survival probability of trained, reared fish in the futureTiivistelmä Kalojen kasvatus ja istutus takaisin luontoon on yksi tärkeimmistä keinoista säädellä ja palauttaa kalakantoja vesistöihin. Maailmanlaajuisesti puhutaan miljardien kalojen istutusmääristä vuosittain. On kuitenkin hyvin tunnettu tosiasia, että kasvatetut kalat eivät selviä luonnossa yhtä hyvin kuin villit lajikumppaninsa. On arvioitu, että vain alle 5 % istutetuista kaloista selviää lisääntymisikään asti hengissä. Eräs tekijä, joka voi vaikuttaa kalojen selviytymiseen, on kalojen lihaskunto. Kasvatettujen kalojen uintikyvyn on todettu olevan heikko villeihin lajikumppaneihin verrattuna. Luonnossa kaloilta kuitenkin vaaditaan suurta uintikykyä esim. saalistukseen, pedoilta pakenemiseen ja vaellukseen. Eräs tämän työn päätavoitteista on määrittää, miten kasvatettujen ja villien kalojen lihasten molekulaariset, aineenvaihdunnalliset ja rakenteelliset ominaisuudet poikkeavat toisistaan, jotta voidaan arvioida mitkä solutason tekijät vaikuttavat kalojen uintikykyyn ja sitä kautta selviytymiseen. Toisaalta kasvatettujen kalojen lihasten toiminnallisten tekijöiden tasoja pyritään nostamaan harjoittelun avulla lähemmäksi villien vastaavaa ja täten vaikuttamaan kasvatettujen kalojen uintikykyyn ja sitä kautta lopulta selviytymiseen. Työssä lihasten ominaisuuksia analysoidaan immunologisin, histokemiallisin ja elektronimikroskooppisin menetelmin. Tutkimuksissa keskitytään erityisesti dihydropyridiini- ja ryanodiinireseptorien suhteellisiin määriin. Nämä reseptorit osallistuvat lihasten supistumisen aikaansaatiin ja niiden määrä korreloi positiivisesti lihasten voiman ja supistumisnopeuden kanssa. Tulosten mukaan villien kalojen lihaksissa on huomattavasti enemmän reseptoreita verrattuna kasvatettujen kalojen lihaksiin. Myös aerobinen ATP:n tuottokapasiteetti on villeillä kaloilla huomattavasti tehokkaampaa. Harjoittelun jälkeen kasvatettujen kalojen lihasten reseptorimäärät ja aerobinen kapasiteetti kuitenkin kasvavat lähemmäksi villien vastaavaa. Lisäksi lihasten reseptorimäärä ja uintikapasiteetti näyttävät korreloivan keskenään. Harjoittelun seurauksena kasvatettujen kalojen vaellusnopeus, eräs kalojen selviytymiseen vaikuttavista tekijöistä, muistuttaa myös enemmän villien vastaavaa. Yhteenvetona voidaan sanoa, että kalojen koko suorituskyky riippuu lihasten solutason mekanismien tehokkuudesta. Tässä työssä todettiin ensimmäistä kertaa, että kasvatettujen kalojen lihaksissa niiden reseptoreiden määrät, jotka liittyvät itse lihassupistuksen tehokkuuteen, ovat huomattavasti alemmat kuin villeillä. Lihasten toiminnalliset ominaisuudet eivät kuitenkaan ole muuttumattomia vakioita. Tulosten perusteella harjoitettujen kalojen sekä lihas- että vaellusominaisuudet lähestyvät villien vastaavaa. Tämä harjoittelun jälkeinen muutos lisää todennäköisesti kasvatettujen kalojen selviytymismahdollisuuksia
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Krieger, Thorsten. "Pathophysiologie der malignen Hyperthermie und des Human-Stress-Syndroms Nachweis von drei neuen Mutationen im Ryanodinrezeptorgen (RYR1)." Saarbrücken VDM Verlag Dr. Müller, 2007. http://d-nb.info/989322130/04.
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Zugl.: Hamburg, Univ., Diss., 2007 u.d.T.: Krieger, Thorsten: Nachweis von drei neuen Mutationen im Ryanodinrezeptorgen (RYR1) bei Patienten mit maligner Hyperthermie und Human-Stress-SyndromHergestellt on demand
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Phillips, Michael Sean. "The structural organization of the human skeletal muscle ryanodine receptor gene (RYR1) and its involvement in malignant hyperthermia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0015/NQ45648.pdf.
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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.
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Au cours du vieillissement, les artères cérébrales subissent des modifications structurelles et fonctionnelles, notamment au niveau des cellules musculaires lisses (CML). La CML a pour rôle de maintenir la réactivité vasculaire via une signalisation calcique qui fait intervenir différents acteurs pouvant ainsi réguler deux phénomènes : la contraction et la relaxation. Ces acteurs rassemblent, au sein d’une même cellule, des canaux (CCVD, RYR, IP3R), des pompes calciques (SERCA, PMCA, NCX, STIM/ORAI) et leurs régulateurs (PLB, FKBP12.6, TRPP2, SARAF, TRIC). La restriction calorique (RC), apparaît comme étant un facteur retardant le vieillissement et ses pathologies. Notre travail s’est donc fortement impliqué dans l’étude de la signalisation calcique de la CML, en se focalisant sur les altérations génomiques et fonctionnelles au cours du vieillissement des artères cérébrales chez la souris C57Bl6/j. Nous avons ainsi pu mettre en évidence une altération de la signalisation calcique qui passe en partie par une modulation des niveaux d’expressions génique et protéique des canaux et pompes calciques impliqués dans ce phénomène, et par une modification fonctionnelle en termes de signaux calciques et de contraction. Après 5 mois de régime RC, il a été mis en évidence un ralentissement des altérations de la signalisation calcique liées au vieillissement et une diminution de l’oxydation des CMLDuring 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
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Robin, Gaëlle. "Caractérisation de l'efflux calcique du réticulum sarcoplasmique du muscle squelettique normal et dystrophique." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10138.
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La contraction du muscle squelettique est initiée par une libération de Ca2+ du réticulum sarcoplasmique (RS) en réponse à une dépolarisation du sarcolemme. Celle-ci induit un changement de conformation du récepteur des dihydropyridines (DHPR) localisé dans les tubules T entraînant l'ouverture du récepteur de la ryanodine de type 1 (RyR1), canal calcique du RS, et la libération du Ca2+ accumulé dans le RS. Au repos, RyR1 serait maintenu fermé par une action répressive du DHPR. Néanmoins, un efflux de Ca2+ continu se développe à travers la membrane du RS, constamment compensé par l'activité des pompes Ca2+-ATPases. Des études suggèrent que cet efflux pourrait être impliqué dans la perturbation de l'homéostasie calcique dans une des pathologies musculaires des plus fréquentes et sévères, la myopathie de Duchenne. Le travail présenté vise à caractériser l'efflux de Ca2+ du RS dans les fibres musculaires squelettiques de souris normales et mdx, modèle murin de la myopathie de Duchenne, en couplant la technique de potentiel imposé et la mesure fluorimétrique du Ca2+ intracellulaire. La mise au point d'une mesure directe des variations de Ca2+ du RS à l'aide du Fluo-5N a permis de révéler dans les fibres mdx une fuite calcique du RS exacerbée. Cette approche a permis de démontrer que l'efflux calcique du RS dans la fibre musculaire squelettique au repos n'est pas un phénomène incontrôlé à travers RyR1 mais un efflux étroitement contrôlé par le DHPR. Enfin, on s'est intéressée à l'efflux de Ca2+ du RS lors d'une stimulation musculaire prolongée. Nos résultats montrent que le déclin du signal calcique cytosolique dans ces conditions résulterait de la déplétion calcique du RSContraction of skeletal muscle is triggered by the release of Ca2+ from the sarcoplasmic reticulum (SR) in response to depolarization of the sarcolemma. Depolarization elicits a conformational change of the dihydropyridine receptor (DHPR) localized in the tubular membrane that controls the opening of the type 1 ryanodine receptor (RyR1), the SR Ca2+ release channel. At rest, RyR1s are kept in a closed state imposed by the repressive action of DHPRs. Yet, a resting Ca2+ efflux occurs across the SR membrane, constantly balanced by the pumping activity of SR Ca2+-ATPases. Several studies suggest that this SR Ca2+ efflux, considered as purely passive, may contribute to the alteration of Ca2+ homeostasis in one of the most common and severe skeletal muscle disease, namely the Duchenne Muscular Dystrophy. The present work aims at characterizing the SR Ca2+ efflux in skeletal muscle fiber from normal and mdx mice, the murine model of Duchenne Muscular Dystrophy, by combining voltage-clamp and intracellular Ca2+ measurements. The development of a methodology allowing direct monitoring of Ca2+ changes in the SR using the Fluo-5N led us to reveal an elevated SR Ca2+ leak in mdx fibers, which may contribute to the alteration of Ca2+ homeostasis. Still using this approach, we demonstrate that the resting SR Ca2+ efflux in normal skeletal muscle fiber is not, an uncontrolled process through RyR1 but is tightly controlled by DHPR. Finally, we investigates the SR Ca2+ efflux during long-lasting stimulation. Our data indicate that the decline of SR Ca2+ release in these conditions results from SR Ca2+depletion and does not involve voltage-dependent inactivation of SR Ca2+ release
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Jiang, Jie. "Tuning Calcium Bindging Affinities with Related Biological Functions of Calmodulin and Designing Protein Based Contrast Agent." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/chemistry_diss/60.
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Calmodulin (CaM) is a ubiquitous intracellular protein that regulates biological activities of numerous enzymes and ion channels. Upon responding Ca2+ concentration change, Ca2+- dependent CaM activates the hydrolyzation of cGMP by PDE and Ca2+ releasing channel activity of ryanodine receptor. In this dissertation, a series of CaM variants were engineered to enhance Ca2+ binding affinities by increasing the number of negative charged residues in individual EF-hand. The capability of shifting the biphasic Ca2+-activation profile of RyR1 is significantly altered by changing Ca2+ binding affinity of CaM at the C-terminal. This indicates that examining Ca2+-CaM affinity is a valid strategy to tune the activation profile of CaM-regulated ion channels. To further understand interactions between CaM and RyR1, NMR was used to determine their binding mode. To dissect roles of structural components of CaM in metal binding and regulation of biological functions of target proteins, we created half-CaMs and Del-CaM. Binding affinities of these variants to Ca2+, Tb3+ and Gd3+ were determined by fluorescence spectroscopy; functional studies were conducted using single channel analysis and PDE function assay.
Another objective of my dissertation is to design a protein based contrast agent for molecular imaging. CaM was selected as the scaffold protein for designing Gd3+ based MRI contrast agent by modifying metal binding sites as well as grafting a biomarker peptide into the linker region to specifically target cancers with efficient and optimized modifications. The physical kinetic properties and animal imaging effects of these designed contrast agents were investigated by various methods.
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Nell, Ryno Willem. "Development of a novel nitriding plant for the pressure vessel of the PBMR core unloading device / Ryno Willem Nell." Thesis, North-West University, 2010. http://hdl.handle.net/10394/4227.
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The Pebble Bed Modular Reactor (PBMR) is one of the most technologically advanced developments in South Africa. In order to build a commercially viable demonstration power plant, all the specifically and uniquely designed equipment must first be qualified. All the prototype equipment is tested at the Helium Test Facility (HTF) at Pelindaba. One of the largest components that are tested is the Core Unloading Device (CUD).
The main function of the CUD is to unload fuel from the bottom of the reactor core to enable circulation of the fuel core. The CUD housing vessel forms part of the reactor pressure boundary. Pebble-directing valves and other moving machinery are installed inside its machined inner surface. It is essential that the interior surfaces of the CUD are case hardened to provide a corrosion- and wear-resistant layer. Cold welding between the moving metal parts and the machined surface must also be prevented. Nitriding is a case hardening process that adds a hardened wear- and corrosion-resistant layer that will also prevent cold welding of the moving parts in the helium atmosphere.
Only a few nitriding furnaces exist that can house a forging as large as the CUD of the PBMR. Commercial nitriding furnaces in South Africa are all too small and have limited flexibility in terms of the nitriding process. The nitriding of a vessel as large as the CUD has not yet been carried out commercially. The aim of this work was to design and develop a custom-made nitriding plant to perform the nitriding of the first PBMR/HTF CUD.
Proper process control is essential to ensure that the required nitrided case has been obtained. A new concept for a gas nitriding plant was developed using the nitrided vessel interior as the nitriding process chamber. Before the commencement of detail design, a laboratory test was performed on a scale model vessel to confirm concept feasibility. The design of the plant included the mechanical design of various components essential to the nitriding process. A special stirring fan with an extended length shaft was designed, taking whirling speed into account. Considerable research was performed on the high temperature use of the various components to ensure the safe operation of the plant at temperatures of up to 600°C. Nitriding requires the use of hazardous gases such as ammonia, oxygen and nitrogen. Hydrogen is produced as a by-product and therefore safety was the most important design parameter. Thermohydraulic analyses, i.e. heat transfer and pressure drop calculations in pipes, were also performed to ensure the successful process design of the nitriding plant.
The nitriding plant was subsequently constructed and operated to verify the correct design. A large amount of experimental and operating data was captured during the actual operation of the plant. This data was analysed and the thermohydraulic analyses were verified. Nitrided specimens were subjected to hardness and layer thickness tests.
The measured temperature of the protruding fan shaft was within the limits predicted by Finite Element Analysis (FEA) models. Graphs of gas flow rates and other operation data confirmed the inverse proportionality between ammonia supply flow rate and measured dissociation rate. The design and operation of the nitriding plant were successful as a nitride layer thickness of 400 μm and hardness of 1 200 Vickers hardness (VHN) was achieved.
This research proves that a large pressure vessel can successfully be nitrided using the vessel interior as a process chamber.Thesis (M.Ing. (Mechanical Engineering))--North-West University, Potchefstroom Campus, 2010.
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Chameau, Pascal. "Le recepteur de la ryanodine de type 3 (ryr3) : localisation et role dans l'excitabilite neuronale et la transmission synaptique." Paris 6, 1999. http://www.theses.fr/1999PA066101.
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Le recepteur de la ryanodine de type 3 (ryr3), exprime dans les neurones, est l'isoforme la moins caracterisee de cette famille de recepteurs-canaux ca 2 + du reticulum endoplasmique. J'ai developpe un anticorps polyclonal dirige contre ryr3 qui m'a permis de determiner la localisation de cette isoforme dans la region proximale des dendrites apicaux des neurones pyramidaux de la region ca1 de l'hippocampe de souris. Cet anticorps s'est avere bloquant du mecanisme de calcium-induced calcium release (cicr) dans lequel ryr3 est implique. Dans les neurones ca1, l'injection de l'anticorps anti-ryr3 reduit le courant k+ active par le ca2+ (courant isahp, pour slow after hyperpolarization, sensible a la ryanodine). Ce resultat montre que l'activation du courant isahp est declenchee en partie par le ca2+ libere du reticulum endoplasmique par ryr3. Ce ryr3 joue donc un role essentiel dans la mise en jeu de la phase de post-hyperpolarisation prolongee de la membrane neuronale, phenomene a l'origine du mecanisme d'adaptation de la frequence de decharge des potentiels d'action. L'etude du courant isahp souligne egalement le role des proteines associees a ryr3, cibles de la rapamycine et du cadp-ribose, comme elements determinants de l'activation de ce ryr. Chez l'aplysie un recepteur de type ryr3 est localise principalement dans les axones des neurones du ganglion buccal. L'injection de l'anticorps anti-ryr3, dans le neurone presynaptique d'un couple synaptique cholinergique parfaitement identifie, induit une diminution de la quantite d'acetylcholine liberee par un potentiel d'action presynaptique comparable a celle de la ryanodine. Ce resultat met en evidence le role d'un recepteur de type ryr3 dans la modulation de la transmission synaptique. La sequence peptidique utilisee comme antigene est situee dans une boucle cytoplasmique de ryr3. Ce peptide lie les ions ca2+ et a la capacite d'affecter les phenomenes physiologiques dependants du ca2+ : il reduit l'amplitude des courants isahp dans les neurones pyramidaux ca1 de l'hippocampe de souris et la liberation evoquee d'acetylcholine dans les neurones presynaptiques d'aplysie. Cette sequence peptidique pourrait donc jouer un role essentiel comme tout ou partie du site de liaison du ca2+ sur ryr3.
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飯田, 綱規. "小胞体膜タンパク質TRICチャネルの分子機能解析." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225529.
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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.
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Polster, Alexander [Verfasser]. "FRET reveals substantial reorientation of the cytoplasmic interface of the skeletal muscle DHPR in the presence of RyR1 / Alexander Polster." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover, 2011. http://d-nb.info/1011397404/34.
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Ziober, Iris Lamberti. "Carnes PSE (pale, soft, exudative) de frangos : análise dos transcritos do gene codificador da proteína ?RyR." Universidade Estadual de Londrina. Centro de Ciências Agrárias. Programa de Pós-Graduação em Ciência de Alimentos, 2009. http://www.bibliotecadigital.uel.br/document/?code=vtls000151534.
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Carnes PSE (pálida, flácida e exsudativa) ocorrem por fatores múltiplos, e o estresse e causas genéticas tem papeis cruciais. Em suínos, uma mutação no gene RYR1 (receptor de rianodina tipo 1) leva à PSS (Síndrome do Estresse Suíno) e às carnes PSE. A RyR1 é uma proteína formadora do canal de liberação de Ca2+ no retículo sarcoplasmático de células musculares. Em suínos com a mutação neste gene o estresse desencadeia um acúmulo intracelular de Ca2+, e consequentemente à uma contração muscular permanente, fazendo com que a célula dispenda mais glicogênio tentando relaxar o músculo, produzindo assim mais ácido lático, provocando uma rápida queda do pH enquanto a carcaça ainda está quente, o que leva às carnes PSE. Em frangos, a região N-terminal do RYR a região hotspot para mutações que levam à carnes PSE em suínos ainda não foi sequenciada. O objetivo deste trabalho foi selecionar animais pelo teste do halotano, além de submeter aves ao estresse térmico (ET) e exposição ao halotano pré abate para avaliar alterações nos transcritos do RYR e correlacioná-los com a ocorrência de carnes PSE. Para isso foram realizados quatro experimentos (A, B, C e D) e após o abate, foi coletado um fragmento do músculo Pectoralis major de onde se extraiu RNA total, o qual foi utilizado para obtenção de cDNA; amplificou-se a região a ser estudada, e estes fragmentos foram clonados e sequenciados. Para classificação de carnes PSE utilizou-se o valor de L* em 24h. Em 75 amostras analisadas, foram identificadas 62 variações ao longo das sequências obtidas. A sequência mais conservada apresentou 97% de similaridade com RYR de perus. No experimento A, das 10 amostras que apresentaram proteínas alteradas, sete originaram carnes PSE, e apenas quatro eram de amostras HAL+. Mas amostras HAL- que também tinham alterações nos transcritos também originaram carnes PSE. No experimento B 88,2% das amostras, desenvolveram carnes normais (provavelmente devido ao tempo de jejum pré-abate superior a 24h) e nenhuma das alterações dos transcritos encontradas ocorreram em amostras que produziram carnes PSE. O halotano não foi um bom identificador de amostras com alterações. No Experimento C, quando as aves foram submetidas ao halotano no pré abate e também ao ET, proteínas truncadas (TR) foram prevalentes nas aves expostas ao halotano, mas apenas as que também foram expostas ao ET, originaram carnes PSE. No Experimento D, não houve jejum pré abate nem chiller e 94,5% das amostras foram PSE, enquanto que o teste do halotano, em conjunto com o ET detectou amostras que teriam proteínas TR. Conclui-se então que o teste do halotano não foi eficaz para triar amostras que teriam alterações no mRNA nesta região do RYR. O ET em conjunto com a exposição ao halotano parecem denunciar o aparecimento de códons sem sentido do RYR (proteínas TR) e de carnes PSE. Não houve uma mutação em comum entre os grupos testados que pudesse ser correlacionada com carnes PSE e a resposta ao halotano. O ET pode ter modulado a expressão gênica, o que explicaria o grande número de transcritos alterados encontrados, principalmente quando esta variável foi aplicada. Esses resultados indicam diferenças nos mecanismos de formação de carnes PSE e resposta ao halotano entre aves e mamíferos.Broiler PSE meat is the consequence of multiple factors being the physiological stress the cause most evaluated and recently genetic origin has gained its scientific attention. In pigs, a mutation in the RYR1 gene, receptor for rianodine type 1, leads to the PSS (Pork Stress Syndrome,) and subsequently to PSE (Pale, Soft, Exudative) meat. RyR1 is a protein forming the Ca2+ release channel within muscle cells sarcoplasmic reticulum. In pigs with this mutation, the physiological stress triggers an accumulation of intracellular calcium, and consequently to a continuous muscle contraction, thus accelerating the glycolysis producing more lactic acid subsequently leading to the PSE meat formation. The objective of this work was to sequence broiler chicken N-terminal region of RYR since it is the region most prone to mutations that conducted to the PSS and subsequently to PSE meat. In order to select the genetically sensitive animals, four experiments were conducted in birds that had prior selection by the halothane test (HAL+ and HAL-) and treatments of thermal stress (TS) and halothane exposure before slaughtering. A fragment of Pectoralis major m. was collected from samples previously classified as PSE and non PSE meat by measuring their characteristic colors. The extraction of total RNA was performed, which was used to obtain cDNA and the specific region was amplified and thus these fragments were cloned and sequenced. Among 75 samples analyzed, 62 samples were found to have variations within the sequence of 468 obtained base pairs, which presented 97% of similarity with turkey RyR. The following results were obtained from these four experiments: In Experiment A, from the 10 samples that showed alterations in the protein, seven originated PSE meat and just four of them were HAL+. However samples HAL- that had alterations within the transcripts also originated PSE meat. In Experiment B, the halothane test was not a good genetic identifier of samples with transcript alterations. Non-PSE meat was produced by 88,2% of the animals, presumably because of a long fasting pre slaughtering treatment that the birds were submitted and none of the the found altered transcripts were correlated to PSE meat development. In Experiment C, the truncated proteins were prevalent in birds exposed to halothane test, but only those that were associated to TS were capable to originated PSE meat. Finally, in Experiment D, in birds submitted to non pre slaughter fasting and the meat did not go through the chiller, 94.5% of breast samples presented PSE meat and furthermore truncated proteins were detected in chicken HAL+ associated to TS treatment. Lastly, our results pointed out that the halothane test was not fully efficient to detect samples that presented alterations at that strategic regions of RYR gene. However only the association of the thermal stress, and halothane exposure presented evidence for this role suggesting a modulation of gene expression by the environmental factors. Unfortunately, a common gene mutation was not found and the large number of altered transcripts found was possibly the result of environmental factors particularly heat stress which could somehow modulate the RYR gene expression. Also our results indicated that the avian physiological role related to halothane susceptibility and PSE is different in relation to the mammals.
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Yehya, Mohamad. "Implication des voies du stress oxydant dans le remodelage du récepteur de la Ryanodine au cours de la Dysfonction Diaphragmatique induite par la Ventilation Mécanique." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONT4001.
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La ventilation mécanique en réanimation (VM) est une mesure de sauvetage pour les patients qui présentent une incapacité temporaire à assurer par leur fonction ventilatoire une oxygénation tissulaire adéquate. Elle peut pourtant être à l’origine d’une dysfonction diaphragmatique induite par la ventilation (DDIV), augmentant la dépendance du patient à son ventilateur et la durée de son séjour en réanimation. La mise au repos brutale du diaphragme induite par la ventilation peut engendrer un stress énergétique ainsi qu’un stress mécanique participant à l’initiation d’un stress oxydant à la base d’une DDIV. Ainsi, l’objectif de cette thèse est d’évaluer les mécanismes physiopathologiques impliqués précocement dans la genèse de ce stress oxydant et d’en faire le lien mécanistique avec la dysfonction contractile du diaphragme ventilé sur un modèle murin. La compréhension de ces mécanismes nous permettra de proposer des nouvelles pistes thérapeutiques afin de limiter l’impact négatif de cette pathologie sur le devenir des patients pris en charge en réanimation par la ventilation mécanique. Dans notre première étude, nous avons montré pour la première fois, dans le diaphragme de souris ventilées mécaniquement, la présence dès 6 heures de ventilation d’un stress oxydant mitochondrial responsable d’un remodelage biochimique précoce du canal de libération du calcium du réticulum sarcoplasmique RyR1, aboutissant à des troubles de l’homéostasie calcique à la base d’altération du couplage excitation-contraction (CEC), impliqués dans la DDIV. Nous avons également montré qu’avec une période plus longue de VM, cette altération de l'homéostasie calcique contribue à une activation secondaire du système de protéase calcium-dépendant liée au désassemblage des complexes d'actomyosine et à l'atrophie participant à la DDIV. Enfin nous avons montré qu’en ciblant pharmacologiquement le RyR1 afin de réduire les fuites calciques nous pouvions prévenir la DDIV. La mise au repos du diaphragme engendre précocement un phénomène de fission mitochondriale qui a été lié à un stress métabolique. Dans notre deuxième étude, nous montrons que cette fission mitochondriale précoce est responsable d’un stress oxydant mitochondrial et que son inhibition pharmacologique au cours de la VM prévient la production de ROS d’origine mitochondriale ainsi que le remodelage du canal calcique RyR1 avec une bonne efficacité thérapeutique sur la prévention de la DDIV. La ventilation mécanique, par la genèse d’asynchronie entre le patient et son ventilateur peut induire un stress mécanique dont l’implication dans le DDIV est mal connue. Sur un modèle murin dystrophique (souris mdx), dont le diaphragme est plus sensible au stress mécanique du fait d’une déficience en Dystrophine, nous avons modélisé ce stress au cours de la ventilation mécanique par l’application in vitro, après 6 heures de ventilation, de contractions excentriques. Ainsi, dans notre troisième étude, nous avons monté que 6 heures de VM chez la souris mdx augmentent la susceptibilité du diaphragme aux contractions excentriques impliquant un remodelage biochimique des canaux RyR1 et une présence de fuite de Ca2+ intracellulaire. Nous démontrons sur ce modèle murin dystrophique, qu’un stress mécanique appliqué in vitro après 6 heures de VM, pouvait activer les NOX2, à la base d’un stress oxydant venant aggraver le remodelage du diaphragme RyR1 déjà altéré par la VM. Nous avons également montré que l’inhibition pharmacologique de NOX2 gommait les effets délétères de ce stress mécanique imposé in vitro. Enfin, nous montrons également dans ce dernier travail, qu’un entraînement respiratoire préventif des muscles respiratoires chez la souris mdx atténue la DDIV ainsi que la susceptibilité à la contraction excentrique induite par VM. Ce travail préliminaire devra être continué afin d’évaluer les mécanismes de cette amélioration induite par cet entrainementMechanical ventilation in the intensive care unit (MV) is a rescue measure for patients who have a temporary disability to provide adequate tissue oxygenation through their ventilatory function. It may, however, be the cause of a ventilator-induced diaphragmatic dysfunction (VIDD), increasing the patient's dependence on his ventilator and his length of stay in intensive care unit. Sudden resting of the diaphragm induced by ventilation can cause energy stress as well as mechanical stress participating in the initiation of oxidative stress at the base of an VIDD. Thus, the aim of this thesis is to evaluate the physiopathological mechanisms involved in the genesis of this oxidative stress and to make the mechanistic link with the contractile dysfunction of the diaphragm ventilated on a murine model. The understanding of these mechanisms will allow us to propose new therapeutic approaches to limit the negative impact of this pathology on the future of patients treated in intensive care by mechanical ventilation.In our first study, we showed for the first time, in the diaphragm of mechanically ventilated mice, the presence of a mitochondrial oxidative stress at 6 hours of ventilation, responsible for an early biochemical remodeling of the calcium release channel of the sarcoplasmic reticulum RyR1, leading to disorders of calcium homeostasis at the base of alteration of excitation-contraction coupling, involved in the VIDD. We have also shown that with a longer period of MV, this alteration of calcium homeostasis contributes to a secondary activation of the calcium-dependent protease system linked to the disassembly of actomyosin complexes and to atrophy participating in the VIDD. Finally, we have shown that by pharmacologically targeting RyR1, in order to reduce calcium leak, we could prevent VIDD.Resting the diaphragm early results in a mitochondrial fission phenomenon that has been linked to metabolic stress. In our second study, we show that this early mitochondrial fission is responsible for mitochondrial oxidative stress and that its pharmacological inhibition during MV prevents the production of ROS of mitochondrial origin as well as the remodeling of the RyR1 calcium channel with good therapeutic efficacy on the prevention of VIDD.Mechanical ventilation, by the genesis of assynchrony between the patient and his ventilator can induce a mechanical stress whose involvement in the VIDD is poorly known. In a dystrophic murine model (mdx mice), whose diaphragm is more sensitive to mechanical stress due to a deficiency in dystrophin, we modeled this stress during mechanical ventilation by in vitro application, after 6 hours of ventilation, eccentric contractions. Thus, in our third study, we found that 6 hours of MV in mdx mice increase the susceptibility of the diaphragm to eccentric contractions involving biochemical remodeling of RyR1 channels and the presence of intracellular Ca2 + leakage. We demonstrate on this dystrophic murine model, that a mechanical stress applied in vitro after 6 hours of MV, could activate the NOX2, at the base of an oxidative stress coming to aggravate the remodeling of the diaphragm RyR1 already altered by the MV. We have also shown the pharmacological inhibition of NOX2 to erase the deleterious effects of this mechanical stress imposed in vitro.Finally, we also show in this last work, that a respiratory breathing preventive training in the mdx mice attenuates the VIDD as well as the susceptibility to the eccentric contraction induced by MV. This preliminary work should be continued in order to evaluate the mechanisms of this improvement induced by this training.Thus during this thesis we were able to identify the mechanisms involved in
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Filipova, Dilyana [Verfasser], Niels [Gutachter] Gehring, and Stefan [Gutachter] Herzig. "From excitation-contraction coupling to gene expression: Roles of RYR1 and Cav1.1 in myogenesis / Dilyana Filipova ; Gutachter: Niels Gehring, Stefan Herzig." Köln : Universitäts- und Stadtbibliothek Köln, 2018. http://d-nb.info/1165772779/34.
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Dornan, Thomas Joseph. "Calcium Transport Inhibition, Stimulation, and Light Dependent Modulation of the Skeletal Calcium Release Channel (RyR1) by the Prototropic Forms of Pelargonidin." PDXScholar, 2014. https://pdxscholar.library.pdx.edu/open_access_etds/1931.
Full textAbstract:
The principle calcium regulator in the muscle cell is the calcium ion release channel (RyR). Improper calcium homeostasis in the muscle cell is the foundation of many pathological states and has been targeted as a contributing factor to ventricular tachycardia, which is known to precede sudden cardiac arrest.
Numerous endogenous and exogenous compounds can affect the way RyR regulates calcium. In this study the anthocyanidin Pelargonidin (Pg), an important natural colorant and dietary antioxidant, is evaluated for its effect on regulating the transport of calcium through the RyR1 of skeletal muscle sarcoplasmic reticulum. Pelargonidin undergoes time dependent structural changes in aqueous solutions at physiological pH and a mixture of up to seven forms of Pelargonidin are present in solution simultaneously. Pelargonidin is a unique RyR1 modulator. It can both stimulate and inhibit the RyR1 depending on the experimental conditions. In addition, when Pelargonidin is irradiated with white light, its inhibition properties on the RyR1 are essentially nullified. Proposed mechanisms include excited state charge shift within RyR1-Pg complexes.
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Bosch, Calero Cristina. "Determinants moleculars de la mort sobtada cardíaca en una gran família de les Illes Canàries." Doctoral thesis, Universitat de Girona, 2016. http://hdl.handle.net/10803/406951.
Full textAbstract:
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a sudden cardiac
death (SCD) associated disease characterized by the presence of polymorphic or
bidirectional ventricular tachycardia during emotional or physical stress. Most cases of
CPVT are caused by mutations in the RyR2 gene. This thesis starts with the
identification of a large family in the Canary Islands, with a long history of SCD due to
CPVT. The genetic study revealed the presence of a mutation in the RyR2 gene in
affected patients. The functional and proteomic studies of the channel has shown that
the mutation unmasks its pathogenicity behavior only in conditions that mimic
catecholaminergic stress and these functional consequences could be due to the
introduction of a new phosphorylation site in the mutant channel. The evidence
presented in this thesis shed light into the mechanisms by which RyR2 mutations may
promote arrhytmogenic intracellular Ca2+ handling associated with SCD.
2/La taquicàrdia ventricular polimòrfica catecolaminèrgica (CPVT) és una malaltia associada a mort sobtada cardíaca (MSC) que es caracteritza per la presència de taquicàrdies ventriculars polimòrfiques i/o bidireccionals durant estrès emocional o físic. La majoria de casos de CPVT són causats per mutacions al gen RyR2. Aquesta tesi parteix de la identificació d’una gran família de les Illes Canàries, amb una llarga història de MSC a causa de la CPVT. L'estudi genètic realitzat en aquesta tesi ha revelat la presència d'una mutació al gen RyR2 en els individus afectats, l'estudi funcional i proteòmic del canal ha demostrat que la mutació desenmascara la seva patogeneicitat en condicions mimètiques a estrès i que, aquest fet, pot ser degut a la introducció d’un nou lloc de fosforilació en el canal mutant. Aquesta tesis aporta evidències que permeten ampliar el coneixement dels mecanismes moleculars pels quals les mutacions al RyR2 alteren l’homeòstasi del Ca2+ intracel·lular i produeixen MSC. 1/
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Owen, Laura Jean. "Calcium and Redox Control of the Calcium Release Mechanism of Skeletal and Cardiac Muscle Sarcoplasmic Reticulum." PDXScholar, 2011. https://pdxscholar.library.pdx.edu/open_access_etds/430.
Full textAbstract:
The sarcoplasmic reticulum is an internal membrane system that controls the Ca²⁺ concentration inside muscle cells, and hence the contractile state of both skeletal and cardiac muscle. A key protein that that regulates the Ca²⁺ concentration in this membrane is known as the calcium release channel (CRC). The effects on Ca²⁺ dependent activation is of major importance in the study of CRC since other channel modifiers cannot effect the channel in the absence of Ca²⁺, or they require Ca²⁺ for maximum results. In this study of the high-affinity Ca²⁺ binding site, expected increases in total binding and shifts in the sensitivity of the channel to Ca²⁺ were observed when the pH increased or the solution redox status became more oxidative. Ranolazine, a drug used for treating Angina Pectoris (chest pain), desensitized the cardiac CRC activation but had no effect on the skeletal CRC. This selective desensitization may be the cause of Ranolazine's beneficial therapeutic effects. Both Ranolazine, and homocystein thiolactone (HCTL), a naturally occurring derivative of homocysteine, alters Ca²⁺ dependent activation by calcium without changing the number of channels found in the open state. Surprisingly the effect of HCTL was observed only in a reduced redox potential which leads to speculation that the formation of an alpha-carbon radical by HCTL on the cardiac CRC only occurs if select thiols are in a reduced state.