Academic literature on the topic 'Substrate localisation'
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Journal articles on the topic "Substrate localisation"
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Li, Yanfang, Ki-Eun Park, and Ryan A. Cabot. "Dynamic changes in nuclear import of a nuclear localisation signal-bearing substrate in 8-cell stage porcine embryos." Reproduction, Fertility and Development 27, no. 2 (2015): 385. http://dx.doi.org/10.1071/rd13205.
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Coordinated intracellular trafficking is critically important for proper timing of major cellular events during embryogenesis. Nuclear import mediated by the karyopherin α/β (importin α/β) heterodimer is perhaps the best characterised nuclear trafficking system in eukaryotic cells. Seven karyopherin α subtypes have been identified in the domestic pig, and although each karyopherin α subtype transports proteins bearing classical nuclear localisation signals (NLSs), individual karyopherin α subtypes have been shown to preferentially transport specific cargoes. The aim of the present study was to determine the mechanism by which BRN2, a transcription factor previously reported to be transported by the karyopherin α/β heterodimer, gains access to the nucleus in porcine oocytes and embryos. Using a combination of in vivo and in vitro assays, we tested the hypothesis that discrete karyopherin α subtypes transport BRN2 into the nuclei of porcine oocytes and cleavage stage embryos. Our results show that ectopically expressed BRN2 adopts a nuclear localisation in all nuclei through the 4-cell stage of development, whereas only a subset of blastomeres in 8-cell stage embryos possess nuclear BRN2. This pattern is unique to BRN2 because another ectopically expressed NLS-containing protein is able to adopt a nuclear localisation in all blastomeres of 8-cell stage embryos.
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Neilson, D., and J. S. Thakur. "Continuous Localisation - Delocalisation Transition at Intermediate Electron Densities." Australian Journal of Physics 52, no. 5 (1999): 779. http://dx.doi.org/10.1071/ph99060.
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We find in 2D electron layers in quantum transistors that the interplay between the electron correlations and their interactions with defects in the semiconductor substrate generates a continuous localisation–delocalisation transition for intermediate electron densities (5 ≲ rs ≲ 9). We distinguish this transition from the discontinuous metal–insulator transition which is observed at lower electron densities (rs ≳ 10). The approach we use is based on the behaviour of electrons at low densities. We take into account the interactions between electrons and also their interactions with disorder. We determine a zero temperature phase diagram of localised and delocalised states as a function of electron and impurity densities. The phase boundary of the continuous transition is determined by the localisation length of the electrons.
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Matsuoka, Ken, and Takuji Kawahara. "Modulational instability and wave localisation in Toda lattice with elastic substrate effect." Wave Motion 38, no. 2 (August 2003): 117–30. http://dx.doi.org/10.1016/s0165-2125(03)00024-6.
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Rozova, Vlada S., Ayad G. Anwer, Anna E. Guller, Hamidreza Aboulkheyr Es, Zahra Khabir, Anastasiya I. Sokolova, Maxim U. Gavrilov, et al. "Machine learning reveals mesenchymal breast carcinoma cell adaptation in response to matrix stiffness." PLOS Computational Biology 17, no. 7 (July 23, 2021): e1009193. http://dx.doi.org/10.1371/journal.pcbi.1009193.
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Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), are believed to play key roles in facilitating the metastatic cascade. Metastatic lesions often exhibit a similar epithelial-like state to that of the primary tumour, in particular, by forming carcinoma cell clusters via E-cadherin-mediated junctional complexes. However, the factors enabling mesenchymal-like micrometastatic cells to resume growth and reacquire an epithelial phenotype in the target organ microenvironment remain elusive. In this study, we developed a workflow using image-based cell profiling and machine learning to examine morphological, contextual and molecular states of individual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and >16kPa substrates, respectively. These observations were accompanied by significant changes in E-cadherin and vimentin expression. Furthermore, we demonstrate that the bone-mimicking substrate (64kPa) induced multicellular cluster formation accompanied by E-cadherin cell surface localisation. MDA-MB-231 cells responded to different substrate stiffness by morphological adaptation, changes in proliferation rate and cytoskeleton markers, and cluster formation on bone-mimicking substrate. Our results suggest that the stiffest microenvironment can induce MET.
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Zhao, Yan, Lilas Dagher, Chao Huang, Peter Miller, and Nassir F. Marrouche. "Cardiac MRI to Manage Atrial Fibrillation." Arrhythmia & Electrophysiology Review 9, no. 4 (December 24, 2020): 189–94. http://dx.doi.org/10.15420/aer.2020.21.
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AF is the most common arrhythmia in clinical practice. In addition to the severe effect on quality of life, patients with AF are at higher risk of stroke and mortality. Recent studies have suggested that atrial and ventricular substrate play a major role in the development and maintenance of AF. Cardiac MRI has emerged as a viable tool for interrogating the underlying substrate in AF patients. Its advantage includes localisation and quantification of structural remodelling. Cardiac MRI of the atrial substrate is not only a tool for management and treatment of arrhythmia, but also to individualise the prevention of stroke and major cardiovascular events. This article provides an overview of atrial imaging using cardiac MRI and its clinical implications in the AF population.
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Land, C. S., and P. W. Hochachka. "COMPARTMENTATION OF LIVER PHOSPHOENOLPYRUVATE CARBOXYKINASE IN THE AQUATIC TURTLE PSEUDEMYS SCRIPTA ELEGANS: A REASSESSMENT." Journal of Experimental Biology 182, no. 1 (September 1, 1993): 271–73. http://dx.doi.org/10.1242/jeb.182.1.271.
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Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the conversion of oxaloacetate to pyruvate in the first step of gluconeogenesis. Since oxaloacetate is impermeable to the inner mitochondrial membrane, the localisation of PEPCK within the cell plays a major role in defining substrate preferences for gluconeogenesis. As a result, the immunochemically distinct isoenzymes of PEPCK found within the mitochondrial and the cytosolic cell fractions vary in their proportion to one another between organs and species and with prandial state.
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Collins, G., T. Mahony, A. M. Enright, A. Gieseke, D. de Beer, and V. O'Flaherty. "Determination and localisation of in situ substrate uptake by anaerobic wastewater treatment granular biofilms." Water Science and Technology 55, no. 8-9 (April 1, 2007): 369–76. http://dx.doi.org/10.2166/wst.2007.279.
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Radiotracer incubation experiments and beta microimaging, along with fluorescent in situ hybridisation (FISH), are proposed as a complementary approach to specific methanogenic activity testing and measurement of in vitro substrate utilisation rates to understand better the ecophysiology of anaerobic granular biofilms from wastewater treatment reactors.
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Herburger, Klaus, Louise M. Ryan, Zoë A. Popper, and Andreas Holzinger. "Localisation and substrate specificities of transglycanases in charophyte algae relate to development and morphology." Journal of Cell Science 131, no. 2 (August 21, 2017): jcs203208. http://dx.doi.org/10.1242/jcs.203208.
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Njeim, Mario, and Frank Bogun. "Selecting the Appropriate Ablation Strategy: the Role of Endocardial and/or Epicardial Access." Arrhythmia & Electrophysiology Review 4, no. 3 (2015): 184. http://dx.doi.org/10.15420/aer.2015.4.3.184.
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Percutaneous catheter ablation has emerged as an effective treatment modality for the management of ventricular tachycardia. Despite years of progress in this field, the role of epicardial mapping and ablation needs to be further refined. In this review, we discuss the relationship between the type of underlying heart disease and the location of the arrythmogenic substrate as it pertains to a procedural approach. We describe the contribution of preprocedural and intraprocedural diagnostic tools for the localisation of the arrhythmogenic substrate, with a special emphasis on cardiac MRI and electrophysiological mapping. In our opinion, the preferred approach to target ventricular tachycardia should depend on the patient’s underlying heart disease and the location of scar tissue, which can be best visualised using cardiac MRI.
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Preťová, A., B. Obert, and H. Y. Wetzstein. "Substrate Infiltration and Histological Fixatives Affect theIn Situ Localisation ofβ-Glucuronidase Activity in Transgenic Tissues." Acta Biotechnologica 23, no. 4 (December 2003): 383–88. http://dx.doi.org/10.1002/abio.200390049.
Full textDissertations / Theses on the topic "Substrate localisation"
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Court, Naomi Wynne. "The subcellular localisation, tissue expression, substrate specificity and binding partners of stress-activated protein kinase-3." University of Western Australia. School of Biomedical and Chemical Sciences, 2004. http://theses.library.uwa.edu.au/adt-WU2004.0084.
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[Truncated abstract] Cells need to be able to detect changes in their surrounding environment and transduce these signals into the appropriate cellular compartments. One of the major ways that the cell achieves this signal transduction is through the process of phosphorylation. Protein kinases are the enzymes responsible for catalysing this transfer of phosphate groups from ATP to amino acid residues of their specific substrates. A subfamily of serine/threonine kinases known as the Mitogen-Activated Protein Kinases (MAPKs) is essential in a diverse range of cell processes including growth, metabolism, differentiation and death. The first identified MAPKs, the Extracellular Signal-Regulated Kinases (ERKs), were found to be activated in response to mitogenic stimuli such as growth factors. However, since the discovery of the ERKs, other pathways leading to the activation of related kinases have been recognised. These kinases are preferentially activated in response to stress, and are thus termed “Stress-Activated Protein Kinases” or SAPKs. They consist of the c-Jun N-terminal kinase isoforms 1, 2 and 3 (also called SAPK1γ, SAPK1α and SAPKβ respectively) and the p38 MAPKs, p38α, p38β, p38γ and p38δ (also called SAPK2a, SAPK2b, SAPK3 and SAPK4 respectively). A major challenge in this field has been to identify the substrates and functions of the SAPKs. This has been partly achieved by the development of inhibitors for the JNK MAPKs and SAPK2a/b. However, no inhibitors currently exist that specifically inhibit SAPK3 and SAPK4. Therefore, elucidating the function of these SAPKs has proved more difficult. Recent studies suggest that SAPK3 may play a unique role in the cell compared to other members of the p38 MAPK family. For example, several signalling proteins appear to specifically activate SAPK3 in certain circumstances while not activating other members of the p38 MAPK family. In addition, SAPK3 contains a unique sequence motif that allows it to bind to specialised domains known as PDZ domains. The interaction of SAPK3 with proteins containing these domains may regulate its subcellular localisation and interactions with other proteins in the cell. This project was undertaken to expand the knowledge on the expression, localisation, substrate specificity and binding partners of SAPK3. In Chapter 3 of this thesis, a SAPK3 monoclonal antibody was evaluated for its ability to specifically recognise endogenous SAPK3 protein. SAPK3 was found to be expressed in immortalised cell lines and primary cultures of neonatal rat myocytes, and to be colocalised with the mitochondria of these cells. This co-localisation remained unaltered in response to treatment with the nuclear export inhibitor Leptomycin B, and with exposure to osmotic shock, suggesting that SAPK3 substrates may be localised at the mitochondria
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Isacco, Laurie. "Utilisation des substrats énergétiques à l'exercice chez la femme : influence de la contraception orale, de la prise alimentaire et de la localisation des graisses." Thesis, Clermont-Ferrand 2, 2012. http://www.theses.fr/2012CLF20060.
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La production endogène ou la prise exogène d’hormones sexuelles chez la femme génère un climat hormonal qui lui est propre. Ces particularités endocriniennes influent sur la composition corporelle et modifient les sécrétions et/ou la sensibilité de certaines hormones clés du métabolisme énergétique pouvant conduire à une utilisation spécifique des substrats énergétiques à l’exercice. L’objectif de ce travail était d’étudier l’influence d’une contraception orale (CO : mini dosée monophasique), de la prise alimentaire pré-exercice et de la localisation des graisses sur les réponses métaboliques et hormonales de la femme préménopausée et normo-pondérée à l’exercice (45 min à 65% de O2max). Nos résultats ont montré que la prise d’une CO ne modifiait pas les réponses métaboliques et hormonales et l’utilisation des substrats énergétiques à l’exercice quel que soit le statut nutritionnel des sujets (exercice à jeun ou en situation postprandiale). Cependant, à l’exercice, une situation de jeûne a favorisé une augmentation de l’oxydation lipidique et cela quel que soit le statut hormonal des sujets (CO+ ou CO-). En situation postprandiale, l’exercice physique a stimulé l’activité lipolytique chez des femmes CO+ et CO- sans distinction entre les deux groupes. Enfin, quand l’utilisation des substrats énergétiques à l’exercice est appréhendée en fonction du rapport de la masse grasse abdominale/masse grasse des membres inférieurs (A/MI), nos travaux ont montré une augmentation de la mobilisation et de l’oxydation des lipides chez les femmes présentant un plus faible rapport A/MI (malgré des masses corporelles et des tours de taille normaux). Ainsi, au sein d’une population féminine normo-pondérée, les CO minidosées monophasiques ne semblent pas influer sur l’utilisation des substrats énergétiques à l’exercice, alors que la prise alimentaire pré-exercice et la localisation des graisses semblent avoir un impact plus important sur le métabolisme énergétique à l’exerciceIn the female population, sexual hormones (endogen production or exogenous consumption) induce particular hormonal status leading to specific body composition and metabolic and hormonal responses at rest and during exercise. The aim of this work was to determine the influence of oral contraception (low dose monophasic combined OC), pre-exercise food intake and body fat mass localization on metabolic and hormonal responses during exercise (45 min at 65% of O2max) in normal weight premenopausal women. Our results showed that OC did not alter substrate mobilization and oxidation during exercise (in fast and postprandial conditions). However, during exercise performed in fast condition, women exhibited greater lipid oxidation rates whatever their hormonal status (OC+ vs OC-). In postprandial condition, exercise increased lipolytic activity in OC+ and OC- women without differences between both groups. Finally, it has been observed that abdominal to lower body (A/LB) fat mass ratio influenced substrate mobilization and oxidation in premenopausal women with normal weights and waist circumferences. Subjects with a lower ratio exhibited greater lipid mobilization and oxidation than those with a higher ratio. Therefore, in normal weight women, low dose monophasic combined OC do not appear to influence substrate oxidation whereas pre-exercise food intake and body fat mass localization may have an important impact on substrate metabolism during exercise
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Kanaan, Hussein. "Système de sécrétion de type 1 chez Legionella pneumophila : localisation de son substrat et rôle lors du cycle d'infection." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1090.
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Legionella pneumophila est responsable d'une forme de pneumonie, la legionellose ou de maladie du légionnaire. Entre 2012 et 2015, les cas annuels ont grimpé de 5848 à 7069 en Europe, la France, l’Allemagne, l’Italie et l’Espagne correspondant à 69% du total. De façon inquiétante, la mortalité était de 8,2% faisant de cette maladie un réel enjeu de santé publique. Un facteur de virulence produit par cette bactérie est la protéine RtxA (~700 kDa) de la famille des protéines RTX (Repeats in ToXin) sécrétée via un système de sécrétion de type 1. Dans ce travail, in vitro, la protéase périplasmique LapG clive la partie N-terminale de RtxA au sein d'un motif di-alanine (position 108-109). La construction de mutants déficients dans l’expression de LapG et LapD a révélé une localisation de RtxA sous le contrôle de ces deux protéines, mécanisme semblable au modèle LapA décrit chez P. fluorescens. Un mutant lapG maintient RtxA à la surface de cellules, à l’opposé d’un mutant ?lapD. Nous avons identifié des systèmes homologues T1SS/LapDG dans de nombreuses espèces Legionella ainsi que d’autres gammaproteobactéries. Concernant la virulence de L. pneumophila, les mutants déficients pour le T1SS (lssBD/tolC) étaient plus altérés dans leur virulence que des mutants du système LapDG. Nous avons également montré, grâce à des expériences de compétition, que L. pneumophila semble cibler les cellules hôtes via la protéine RtxA. L’utilisation d’anticorps spécifiques anti-RtxA nous a permis de détecter RtxA à la surface des cellules hôtes, mais aussi de réduire de la virulence de L. pneumophila, suggérant un rôle important de RtxA lors du processus d’infection, bien que non limitantLegionella pneumophila is the causative agent of a form of pneumonia called legionellosis or Legionnaires’ disease. Between 2012 and 2015, the reported European cases of legionellosis increased from 5,848 to 7,069 cases per year where France, Germany, Italy and Spain accounted for 69% of the reported cases. Worryingly, the case fatality of incidents was 8.2% making this disease a considerable health concern. One virulence factor produced by this bacterium is a large protein (~700 kDa) belonging to the RTX (Repeats in ToXin) family called RtxA secreted by the type 1 secretion system. The hereby work reveals that, in vitro, LapG periplasmic protease cleaves RtxA N-terminus in the middle of a di-alanine motif (a.a. 108-109). We also show using lapG and lapD mutant strains, that RtxA release is controlled by these two proteins similar to Pseudomonas fluorescenes LapA. We observed that a strain lacking LapG protease maintains RtxA on the cell surface, while a strain lacking LapD does not exhibit cell surface RtxA. Interestingly, we identified the presence of homologous potential T1SS/LapDG systems in many Legionella species and other Gammaproteobacteria. Regarding L. pneumophila virulence, our work showed that mutants for L. pneumophila T1SS (lssBD/tolC) were more disruptive to its virulence than lapG/lapD mutants. We also hypothesize, by challenging infection, that L. pneumophila might be actively targeting its host via RtxA. Additionally, by observing rtxA mutants as well as detecting RtxA on host surface briefly after inoculation and attenuating virulence by using anti RtxA antibodies, we assume an important but not limiting role for this protein in the infection process
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Duquenne, Philippe. "Influence de la localisation et de la spécificité d'un substrat carbone sur la dynamique d'une population bactérienne introduite dans un sol." Dijon, 1998. http://www.theses.fr/1998DIJOS024.
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Le succès d'une inoculation est fortement conditionné par le nombre de micro-organismes actifs et survivants présents dans le sol. L'apport d'un substrat carbone dans le sol peut améliorer l'efficacité de l'inoculation en favorisant la survie et la croissance des bactéries introduites. Le travail réalisé visait à favoriser l'utilisation de ces substrats par l'inoculum en tentant de limiter les effets de la compétition nutritionnelle avec la microflore indigène du sol par un apport localisé du substrat ou par l'utilisation d'un substrat spécifique de la souche inoculée. Les travaux ont été conduits sur deux modèles bactériens : B. Japonicum et P. Fluorescens. Nous avons comparé la croissance de l'inoculum dans un sol en fonction de l'apport d'une source de carbone dans le sol (localisée ou non) et de la méthode d'introduction de cellules et des substrats. Dans un sol non stérile, la croissance de l'inoculum est dépendante de la souche inoculée, des techniques d'inoculation et de l'apport des substrats. Seule l'utilisation de microgranules poreux contenant le glycérol, comme support d'inoculation de B. Japonicum, permet la croissance de cette souche et une meilleure efficacité au champ lorsque le substrat est introduit à la dose de 0. 07%. En revanche, dans les mêmes conditions, l'introduction conjointe de l'inoculum et du glycérol dans le sol provoque systématiquement la croissance d'une souche à croissance rapide telle P. Fluorescens pour les deux techniques. Dans tous les cas la localisation des cellules et du substrat dans les microgranules conduit à une croissance plus importante. Pour prendre en considération l'effet de la compétition nutritionnelle sur la part de substrat utilise par l'inoculum pour sa croissance, nous avons développé des études de compétition entre deux microflores bactériennes en système simplifié. Ce système est constitué d'une base d'agrégats stérilisés precolonisés par une souche bactérienne figurant la microflore du sol, et dans lesquels est inoculée une seconde souche. Cette approche a permis de montrer que l'utilisation d'un substrat spécifique à l'inoculum était favorable à la croissance de ce dernier. Cet intérêt semble d'autant plus marqué lorsque la bactérie dégradant ce substrat spécifique a une croissance lente. L'association microgranules/inoculum/substrat spécifique peut donc conduire à une meilleure croissance de l'inoculum. La même approche a également permis d'inoculer une bactérie résistante à des antibiotiques dans un sol precolonisé par la souche sauvage. Ces études montrent que la localisation des cellules et du substrat donne un avantage compétitif a l'inoculum pour une partie de l'enrichissement. Dans un sol non stérile, l'étude de l'effet d'un substrat spécifique sur la croissance de B. Japonicum se heurte à la difficulté de trouver de telles substances.
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Bouslama, Mohamed. "Approche duale de modélisation TCAD et de caractérisations électriques approfondies pour la détermination de la signature et de la localisation des pièges dans les HEMT GaN sur substrat SiC." Thesis, Limoges, 2020. http://www.theses.fr/2020LIMO0076.
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Les HEMT à base du GaN ont déjà démontré leur potentialité pour toutes les applications forte puissance et haute fréquence. Cependant, cette technologie souffre de limitations dues notamment à un mécanisme complexe de piégeage/dépiégeage de charges qui se produit dans le composant et reste encore aujourd’hui mal compris. Ce mécanisme de piégeage limite les performances RF et mais également la fiabilité du transistor. Dans ce travail, nous avons étudié les mécanismes issus de ce phénomène à l'aide de plusieurs méthodes de mesures approfondies (Paramètres S en basse fréquence, I-DLTS, densités spectrales de courant de bruit) qui nous ont permis d’extraire la signature des pièges. Grâce à de la simulation TCAD sur le logiciel de simulation Sentaurus, nous avons pu identifier l'emplacement physique de certains pièges dans le composant et comprendre les phénomènes physiques mis-en jeu. Cet apport fournira des informations efficaces pour les améliorations technologiques dans le futurGaN-based HEMTs have already demonstrated their supreme potential for all high power and high frequency applications. However, this technology suffers from limitations due to complex trapping/de-trapping mechanisms that occurs in the device and that are still not well understood. This trapping mechanism limits the RF performances but also undermines the device reliability. In this work, we have investigated the trapping mechanisms using different advanced measurements techniques (LF S-parameter measurements, I-DLTS, noise current spectral density) to identify the signature of traps.Thanks to SentaurusTCAD simulation, we have identified and understood the physical location of several traps in the device. This contribution would provide an efficient feedback for future technological improvements
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Laboudigue, Agnès. "Etat et localisation d'un pesticide (le dinoseb) fixé par l'hectorite et la vermiculite-décylammonium : contribution à l'étude des mécanismes d'adsorption de molécules xénobiotiques peu solubles dans l'eau sur des substrats organo-minéraux." Lille 1, 1994. http://www.theses.fr/1994LIL10095.
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Les substrats argile-alkylammonium sont utilises dans ce travail comme des modeles de sol dans le but d'etudier les interactions entre un pesticide neutre peu soluble dans l'eau, le dinoseb et des substrats dont les surfaces ont ete rendues hydrophobes. La vermiculite- et l'hectorite-decylammonium sont caracterises par diffraction des rx, et par les spectrometries ir et raman; l'arrangement des cations decylammonium est different dans les deux substrats, en raison des differences de densite et de localisation de la charge dans les deux argiles. Par ailleurs, une relation entre les etats electronique et vibrationnel de la molecule de dinoseb et sa structure est etablie, on etudie en particulier les effets de la competition entre liaisons hydrogene intra- et intermoleculaires et de la dissociation du groupement oh, sur la structure du dinoseb. L'etude de la fixation du dinoseb sur les substrats argile-decylammonium est faite parallelement sur un plan macroscopique et sur un plan moleculaire. Les isothermes d'adsorption permettent de determiner les quantites de pesticide fixees et son affinite vis-a-vis des deux substrats, les donnees de diffraction des rx permettent de preciser la localisation des molecules adsorbees sur les surfaces externes ou dans les espaces interfoliaires des substrats. L'etude des interactions entre les molecules de dinoseb fixees et les substrats est realisee a l'aide des spectrometries ir, raman et de reflexion diffuse electronique. Cette recherche met en evidence le role des interactions hydrophobes dans la dynamique de la fixation de molecules peu solubles dans l'eau sur de tels substrats, et la necessite de la formation d'interactions specifiques dans la fixation de grandes quantites de molecules; la liaison hydrogene est une des formes d'interaction possibles. Le caractere hydrophobe de la surface apparait alors comme une condition necessaire mais non suffisante pour l'adsorption de ces molecules.
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Turner, Christopher Travis. "Substrate localisation as a therapeutic option for Pompe disease." Thesis, 2014. http://hdl.handle.net/2440/91780.
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Pompe disease is a progressive form of muscular dystrophy caused by a deficiency in the lysosomal enzyme α-glucosidase (GAA). GAA catabolises glycogen and its deficiency leads to glycogen accumulation in the vesicular network of affected cells. Multiple therapies exist to treat Pompe disease but these are not completely effective (Winkel et al., 2003), necessitating the development of new therapeutic strategies. A number of enzymes that reside outside of the lysosome, either in the cytoplasm (Watanabe et al., 2008) or in circulation (Ugorski et al., 1983), can catabolise glycogen. It was postulated that if vesicular glycogen in Pompe cells was transferred out of these compartments it could then be alternatively degraded. The ability to remove vesicular glycogen from Pompe cells may reduce the onset/progression of the disorder, providing a therapeutic option for patients. Exocytosis is a ubiquitous cellular mechanism where intracellular vesicles fuse with the cell surface and permit vesicle content to be released from the cell. It was postulated that exocytosis may provide a mechanism to release accumulated glycogen from Pompe cells. Approximately 4% of vesicular glycogen was exocytosed from Pompe skin fibroblasts after 2 hrs in culture. Pompe cells exocytosed 2.7-fold more glycogen than unaffected cells. A cellular mechanism was therefore identified that had the capacity to release glycogen from Pompe cells. Culture conditions can alter the amount of exocytosis in fibroblasts (Martinez et al., 2000). In this study the effect of cell confluence and components of the culture media on lysosomal exocytosis was examined in Pompe skin fibroblasts. Increasing the extracellular concentration of Ca²⁺ led to a 1.4-fold increase in glycogen release compared to cells cultured in standard media conditions. Culture confluence had a key influence on glycogen exocytosis, with sub-confluent Pompe cells releasing >80% of glycogen after 2 hrs in culture, 35-fold higher than confluent cells. Exocytic mechanisms therefore exist that allow up-regulation of glycogen exocytosis in Pompe skin fibroblasts. A number of pharmacological compounds induce exocytosis in cultured cells (Amatore et al., 2006). Pompe skin fibroblasts treated with three compounds; calcimycin, lysophosphatidylcholine and α-L-iduronidase, each demonstrated a ≥ 1.5-fold increase in glycogen exocytosis, when compared to untreated Pompe controls. Calcimycin was the most effective compound for inducing glycogen exocytosis, with 12% released after 2 hrs of treatment, but confluent Pompe cells released less than that observed from sub-confluent Pompe cells. This difference in glycogen release may have resulted from the induction of different exocytic mechanisms. Complete exocytosis, where the vesicle completely fuses with the cell surface and releases all vesicle content, is induced in sub-confluent Pompe cells. In contrast, cavicapture, involving only a partial pore opening and limited vesicle content release, is induced in response to calcimycin treatment. The identification of a compound capable of inducing complete exocytosis may therefore improve glycogen release from Pompe cells. Taken together, natural glycogen exocytosis and the ability to induce glycogen exocytosis with pharmacological compounds provided proof-of-concept for exocytic induction as a strategy to re-locate accumulated glycogen from Pompe cells, potentially providing a new therapeutic option for the disorder.Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2014
Book chapters on the topic "Substrate localisation"
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"Vocabulaire roman-andalou, avec étymologies des mots et localisation des témoins." In Le substrat roman et l’adstrat berbère dans le faisceau dialectal andalou, 55–128. De Gruyter, 2020. http://dx.doi.org/10.1515/9783110679373-007.
Full textConference papers on the topic "Substrate localisation"
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Vollmann, Ralf, and Soon Tek Wooi. "The Sociolinguistic Registers of ‘Malaysian English’." In GLOCAL Conference on Asian Linguistic Anthropology 2020. The GLOCAL Unit, SOAS University of London, 2020. http://dx.doi.org/10.47298/cala2020.7-1.
Full textAbstract:
The interplay of four standard languages and a number of spoken languages makes Malaysia an interesting case of societal multilingualism. There is extensive convergence between the spoken varieties. ‘Malaysian English’ (ME) has developed its own structures which can be shown to copy structures of the mother tongues of the speakers at all levels of grammar, thereby being an example for localisation and the creation of a new dialect/sociolect. An analysis of the basilectal register of ME in ethnic Chinese speakers finds that converging patterns of ME and Malaysian (Chinese) languages, with situational lexical borrowing between the various languages. Sociolinguistically, ME plays the same role as any dialect, with covert prestige as an ingroup (identity) marker which is avoided in acrolectal (outgroup) communication. Spoken English in Malaysia can therefore be seen as a localised creoloid dialect of English, based on linguistic substrates. Sociolinguistically, ME is mainly an orate register for basilectal and mesolectal intra-group communication.