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Développement et évaluation de médicaments à usage pédiatrique : masquage de goût du principe actif et fabrication de minigranules à désintégration rapide / Development and evaluation of medicines for paediatric useHoang Thi, Thanh Huong 25 November 2012 (has links)
Face au manque de médicaments spécifiquement conçus et mis au point pour répondre aux besoins thérapeutiques de la population pédiatrique, les autorités nationales et européennes se sont vues dans l’obligation d’établir un cadre réglementaire visant à encourager le développement de médicaments à usage pédiatrique. Un médicament destiné à l’enfant nécessite une présentation galénique spécifique et adaptée à son âge, pour permettre une administration simple et sûre. L’Académie nationale de Pharmacie a également travaillé sur le sujet et élaboré un rapport en juin 2005 avec certaines propositions notamment favoriser les formes orales solides dispersibles ou orodispersibles. Cependant, les formes orales solides posent le problème de l’acceptabilité et de l’évaluation de la palatabilité, condition requise qui représente un véritable défi. L’objectif de ce travail était (i) de développer des techniques de masquage du goût d’un principe actif modèle, l'acétaminophène, (ii) de mettre au point des méthodes d’évaluation du masquage de goût et de caractérisation des particules obtenues et, (iii) d'élaborer un procédé de fabrication d’une forme dispersible : des minigranules à désintégration rapide. Le caséinate de sodium et la lécithine, excipients potentiellement tolérables et sans danger pour un usage pédiatrique, ont été utilisés pour encapsuler le principe actif par atomisation-séchage. Le masquage de goût est évalué in vitro de façon indirecte par des études de libération du principe actif. Nous avons développé une méthode simple avec une pompe à seringues qui utilise de faibles volumes et débits de tampon et simule le flux salivaire. La méthode d’évaluation de masquage de goût développée donne des résultats en accord avec ceux d’autres méthodes existantes comme la langue électronique. La caractérisation des particules obtenues, notamment grâce à la spectroscopie par Rayons X qui permet d’obtenir une cartographie de la composition à la surface des particules enrobées, a montré une différence de composition en fonction du ratio caséinate de sodium/lécithine utilisé lors de l’atomisation. Cette différence a pu être mise en relation avec l'efficacité de masquage de goût. Une étude a ensuite été menée pour évaluer l'effet des paramètres du procédé et de la formulation sur l'efficacité de masquage de goût. Un plan factoriel complet a permis de déterminer les variables les plus importantes influant sur la quantité de principe actif libéré durant les premières minutes, soit la quantité de caséinate de sodium et de lécithine. L’optimisation par la méthode du simplex a permis d’obtenir une formulation optimisée pour laquelle la quantité libérée était 7 fois inférieure à celle du principe actif initial durant les deux premières minutes de l’essai de libération. Une autre approche visant à améliorer l'effet de masquage de goût incluait l'utilisation de caséinate de calcium à la place de caséinate de sodium. Le caséinate de calcium a été montré capable de retarder la libération du principe actif de façon plus importante lors de son association avec de la lécithine, ce qui améliore le masquage de goût. En effet, le masquage de goût est obtenu quand sur une courte période de temps (1 à 2 minutes), soit le principe actif n’est pas détecté, soit la quantité détectée est sous le seuil de perception du patient. Une forme galénique multiparticulaire à base de minigranules à désintégration rapide a ensuite été élaborée par extrusion-sphéronisation suivie d’une lyophilisation. Les minigranules présentent des qualités appropriées à savoir, une bonne sphéricité, une faible friabilité, la capacité d’incorporer une quantité élevée de principe actif et de plus, ces minigranules sont presque immédiatement désintégrés en présence d'eau lors de la mesure du temps de désagrégation avec l'analyseur de texture. Ce type de minigranules promet une forme galénique adaptée à la population pédiatrique grâce à la facilité d’administration et la flexibilité de dosage. / The development of paediatric formulations involves an urgent need but also presents many difficulties, e.g. the safety data of existing and new excipients in children stay restrictive; the development of palatable formulations for better compliance is requisite and challenging; the appropriateness of dosage form faces to dysphagia issue and flexibility of dosing for a large range of age. The aim of this work was (i) to develop a taste-masking formulation of a model drug (acetaminophen) on the one hand, and (ii) to elaborate a process for manufacture of fast disintegrating minigranules on the other hand. Sodium caseinate and lecithin, potentially tolerable and safe excipients for paediatric use, were utilized in order to encapsulate the drug through spray-drying. Taste-masking effect was demonstrated by in vitro drug release study and electronic tongue analysis. The characterization of spray-dried particles showed a difference in the surface composition according to the sodium caseinate/lecithin ratio, which related to the taste-masking efficiency. A study was subsequently undertaken to evaluate the effect of process and formulation parameters on the taste-masking efficiency. A full factorial design allowed screening for the most important variables that affect the released amount of drug during the early minutes, i.e. quantity of sodium caseinate and lecithin. An optimized formulation was successfully achieved by simplex design that released the drug 7-fold less than the unmasked drug during the first two minutes. Another approach to improve the taste-masking effect included the use of calcium caseinate rather than sodium caseinate. Calcium caseinate was showed to be more effective in delaying the drug release to a higher extent in association with lecithin. Indeed, the lower the released amount, the better the taste-masking. A multiparticulate dosage form of fast disintegration was developed through extrusion-spheronization followed by freeze-drying. The pellets exhibited suitable quality, e.g. good sphericity, low friability, ability of high drug loading, and moreover, almost immediately disintegrated in contact with water during measurement of disintegration by texture analyzer. This type of pellets promises age-appropriate dosage form for pediatric population thank to facility of administration and flexibility of dosing.
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The Role of the Fatty Acid Signaling Pathway in Dietary-Induced ObesityNelson, Melissa N. 01 May 2017 (has links)
In recent years, dietary fat has been shown to be capable of activing taste receptor cells in the tongue. Fatty acids (FAs), which act as the chemical cue and are found in dietary fat, activate a cellular signaling pathway that results in a unique signal being sent to the brain that is then interpreted as the taste of fat. One important element in this pathway is the ion channel TrpM5. It is responsible for depolarizing the taste cells that are activated by fatty acids; depolarization is an essential step in cellular response, making TrpM5 essential in the functioning of the FA signaling pathway.
To study the potential roles of the FA signaling pathway, a mouse model, in which mice lacked the TrpM5 gene (TrpM5-/-), was used. From this model, I show that TrpM5 is essential for detection of fatty acids in the oral cavity; without TrpM5, mice were not able to detect FAs in the mouth. I also show here that TrpM5-/- mice eat significantly less and gain significantly less weight on a high fat diet than wildtype mice, who have the TrpM5 gene, linking TrpM5 to both fat intake and weight gain. Interestingly, these responses are only seen in male mice. Females lacking TrpM5 show no deficit in calorie intake compared to the wildtype females. Despite taking in the same amount of calories as the wildtype females, TrpM5-/- females still gain significantly less weight than the wildtypes. This posits a sex-specific response in terms of calorie intake on a high fat diet. Additionally, I show that the TrpM5 pathway is specific for a subtype of fatty acids, primarily the long-chain polyunsaturated fatty acids (PUFAs) and does not contribute to saturated fatty acid taste transduction. Lastly, in this study I show that both male and female mice who do not have TrpM5 excrete significantly less lipids in their feces than the wildtype mice; surprisingly not implicating TrpM5 in fat malabsorption. We are currently looking for other roles of TrpM5 in fat metabolism.
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Integration of Taste and Odor in Agranular Insular CortexVignovich, Martin Nicholas January 2019 (has links)
Our perception of the world is limited by the senses we are endowed with. In the case of taste, its functional fidelity is so critical for our survival that we come into the world with innate preference for sweet and disgust for bitter. These stereotyped behaviors are hardwired at the lowest levels of taste processing and they support the view that taste serves as an arbiter of the chemical world, passing judgement before permitting ingestion. Yet our experience of foods is manifold. This complexity results from distinct contributions from the sights, sounds and smells of the foods we consume. Of these, odors are a co-equal component of flavor and the impairment of olfaction can disrupt enjoyment of eating and alter patterns of consumption. The goal of this thesis is to identify the neural basis of odor-taste perception and to characterize how neural activity is affected by odor-taste integration. In contrast to the discrete and innate categorization performed by the taste system, the sense of smell enables discrimination of thousands of unique odor percepts which have no innate value. At the level of olfactory cortex, odor representations are randomly distributed and have been shown to be conditioned through association with other stimuli. The act of eating produces near simultaneous taste and odor transduction originating from the same source. Yet despite ultimately projecting to neighboring cortical regions, taste and odor pathways are anatomically segregated prior to reaching the cortex. Using viral tracing strategies, we identified Agranular Insular cortex (AIc) as a putative site of odor-taste integration. We then used in vivo two-photon Ca2+ Imaging to characterize odor and taste responsive neurons and identify changes in population activity when these stimuli were simultaneously presented. We next asked whether specific flavor experiences altered activity in AIc compared to naive animals. Finally, we developed a behavioral task to test whether silencing AIc disrupted perception of a flavor compound.
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Behavioral and functional neuroimaging investigations of odor imageryDjordjevic, Jelena January 2004 (has links)
No description available.
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Interactions between plasticised PVC films and citrus juice componentsFayoux, Stéphane C., University of Western Sydney, Centre for Advanced Food Research January 2004 (has links)
The study presented here consists in an original piece of work to better understand complex food packaging interactions. The majority of investigations on food polymer interactions related to orange juice and this provided a good base to our study (Literature reviews: cf. Chapters 1a and b). Additionally a rather remarkable finding in 1994 was that limonin, a trace bitter material found in some varieties of orange juice was rapidly absorbed by highly plasticised polyvinyl chloride (PVC plastisol) (Chapter 2). Several commercial absorbants are available for debittering, relying on limonin absorption on the large surface area of the highly porous absorbant pellets. However, the absorptive properties of the smooth plastisols apparently relied on a different mechanism. Limonin is a very large (470.5 g/mol) compound, but some preliminary experiments with another much smaller orange juice constituent d- of absorbates in plastisols, methods used earlier (Moisan 1980, Holland and Santangelo 1988) to measure solubilities and diffusion constants in packaging films could be advantageously used to survey these properties in a wide range of materials, including model compounds of various types, and a number of compounds which may be found in citrus juices (Chapters 3, 4 and 5). Experimentally, the method found most suitable was to use a ‘test film’ of pure plastisol which was wrapped tightly on both sides by a similar ‘supply film’ blended with 1 Molar test material (also called ‘absorbate’), setting up a concentration gradient. The inner test film was removed at regular intervals (minutes to hours) to measure (mainly by weighing) the uptake of the test reagent with time. Rather unexpectedly, it was found in a number of cases that the test film lost weight, either from the beginning, or after a period of time. Three main types of behaviour were identified: Type A lost weight from the beginning and over a long period of time, Type B gained weight initially and then lost weight, and Type C gained weight until a steady state was reached. Often the maximum, or near maximum, mass increase occurred within around 100 minutes, indicating a very rapid, liquid-like diffusion mechanism, in harmony with the rapid uptake of d-limonene and limonin. The major parameters of interest with these compounds are their diffusion rates and their solubilities, and in the presence of aqueous media (orange juice and other foodstuffs) the partition coefficient between the plastisol and water, which is related to the hydrophobicity function LogP for the compound. The major complicating factor in these measurements is the observation that the plasticiser materials themselves also migrate, in the reverse direction, because of the lower effective concentration in the supply film. This effect tends to be small, but is one explanation for the mass loss observed above, and cannot be ignored over the long term, nor in its practical applications to contamination in foods. There are many possible applications for the techniques described above. The removal or addition of compounds in food packaging itself is one. Upgrading foods, such as orange juice, commercially, is another. In many cases ‘scalping’ off-flavours or other minor components takes place exclusively through solid or liquid contact with the packaging. The removal from the headspace measured by the current gas permeation methods is irrelevant for the vast numbers of involatile, but easily diffusable compounds. For such compounds these novel applications are simple and rapid, require little specialised equipment, and fill a niche in the armoury of food and packaging chemists. / Doctor of Philosophy (PhD)
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Gustatory effects of dietary fatSong, Hae-Jin, Chemical Sciences & Engineering, Faculty of Engineering, UNSW January 2007 (has links)
This thesis investigates whether fats, akin to other taste stimuli, exhibit sensory properties such as mixture interactions. In order to determine gustatory, rather than tactile or olfactory effects, viscosity-controlled emulsions of deodorised oils were used as the base to which taste stimuli were incorporated and presented to a panel of trained assessors. In preliminary qualitative assessments, panellists described the 10% olive oil emulsion as saltier, stronger, fattier and having a more lingering aftertaste than the non-oil control, suggesting that oil modulates taste duration as well influencing taste intensity and/or perceived quality. Panellists were unable to rate the oil/fat taste per se with any degree of certainty hence further experiments examined the effect of oil on the perception of taste mixtures. In mixture interaction experiments, the addition of oil did not result in mixture suppression or enhancement for sweet, salty, sour or bitter while it significantly enhanced umami. To determine the locus of interaction, when MSG and oil were presented to each side of the tongue separately, the enhancement effect disappeared indicating a peripheral mechanism of interaction, similar to the attenuation of chilli burn by oil. In contrast, suprathreshold sucrose sweetness was enhanced by the contralateral presentation of oil, indicating sensory processing at a higher locus. Furthermore, the addition of oil significantly reduced bitterness in a caffeine-MSG mixture. Since earlier experiments did not indicate any interaction between oil and bitterness, the decrease in the perceived bitterness of this binary mixture is attributed to an increase in umami which is likely to have suppressed bitterness, the perceptually dominant component in this mixture. These findings suggest a gustatory role for fats in modulating the taste profile of mixtures, in particular, enhancing total taste intensity, prolonging taste duration, and enhancing umami. A taste receptor-based model of fat perception provides for an orosensory mechanism capable of signalling the arrival of the most energy-dense nutrient, essential fatty acids and fat-soluble vitamins. The chemosensory signal may also be the basis for hedonic responses with subsequent implications for intake.
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Sensory and instrumental characterisation of consumers perceptions of fresh baked flavour to provide direction for new product developmentHeenan, Samuel Peter, n/a January 2009 (has links)
Freshness is a holistic attribute of a food product, with a meaning that most often includes how recently produced or harvested a food currently is and to what extent it has been preserved. Without knowledge of production date, consumers will judge perceived freshness by the sensory properties of foods. However, these properties are not easily identified and described, as they vary considerably between different product types. The objective of this thesis, was to determine the sensory properties that consumers most associate with baked product freshness, and to determine the volatile composition responsible for "fresh-baked" flavour. In addition, relationships were determined and modelled between volatile composition, sensory properties and perceived freshness, in order to predict perceived freshness without the need for further consumer testing.
Two consumer studies were carried, where perceived freshness of 10 breads, 5 cakes and 5 biscuits was measured based on appearance, flavour and texture, and by product odour only. Individual differences in perceived freshness were represented on two-dimensional Freshness Maps generated using Principal Component Analysis (PCA). Consumers used similar terms to describe product freshness, but different terms were associated with specific product types. An understanding of the sensory characteristics associated with perceived freshness was determined by examining relationships between perceived freshness and descriptive analysis (DA). Sensory characteristics perceived to convey freshness in one product type did not necessarily convey freshness in another.
Further relationships between perceived freshness and sensory characteristics were determined for 20 bread types. Descriptive analysis was carried out with all breads, whereas perceived freshness was measured for 10 of these. Three consumer clusters were identified that were homogenous in their freshness perceptions, indicating that perceived bread freshness varied among consumers. Perceived freshness of breads not evaluated by consumers, but assessed by descriptive sensory analysis, were predicted for each consumer cluster using Partial Least Squares Regression (PLSR). Most fresh breads were described as having "porous" appearance, "floury", "toasted" and "malty" odour, "sweet", "buttery", and "oily" flavour, and "sweet" aftertaste. Least fresh breads were described as "musty" odour, "sour" flavour and "sour" aftertaste. In addition, Proton Transfer Reaction Mass Spectrometry (PTR-MS) measured the volatile composition of all 20 bread types. Thirty-three mass ions significantly discriminated between bread types. Relationships were determined between odour and flavour sensory attributes, and mass spectral data using 15 of the 20 breads. PLSR models predicted the sensory properties and perceived freshness of all breads including five types not included in the construction of models. Bread perceived to be most fresh shared a similar combination of positively correlated mass ions, m/z 87, 97 and 117, also represented by "dairy" odour and "buttery" flavour, whilst the masses m/z 63, 69 and 91 were negatively associated with bread freshness, represented by the sensory attributes "grain", and "musty" odour, and "sour" flavour.
The influence of sweetener, fat type and time from baking on perceived freshness was determined for cakes. Four sweeteners (sucrose, glucose, xylitol, isomaltose), three fat types (butter, margarine, shortening) and two times from baking (days zero and 15) were investigated. Descriptive analysis was carried out using a trained panel, and volatile composition of measured using PTR-MS. Twelve cake samples with the largest sensory variation were further selected for consumer testing for perceived freshness. Results demonstrated that sweetener type, fat type, time from baking and their interaction significantly influenced the sensory properties, volatile composition, and perceived freshness of cakes. There was no evidence of perceived freshness segmentation among consumers. Perceived freshness of the twelve cakes not evaluated by consumers was predicted using sensory properties, volatile composition, and their combination. The freshest cakes were evaluated on the day of baking, and contained a combination of margarine and sucrose, and butter and sucrose. The least fresh cakes were evaluated after 15 days of storage and contained a combination of shortening and isomaltose, and butter and isomaltose. The most fresh samples were positively correlated with mass ions m/z 124, 74, 97 and 93, and sensory characteristics of "buttery" odour, and "buttery", "eggy" flavour. The least fresh samples were negatively correlated with mass ions m/z 110 and 95, and sensory characteristics of "rancid", "dusty" and "fatty" odour. Best predictions were obtained for cakes evaluated on day zero that contained a combination of shortening and sucrose.
This research established an objective knowledge of consumers' perceived freshness of baked product types in terms of sensory properties and volatile composition. This approach enabled the understanding of ingredients and time from baking influences, as well their interaction on baked product freshness. The predictive models developed that examined relationships between PTR-MS spectra, sensory characteristics and consumer perceived freshness can be applied to predict freshness of baked products not assessed by consumers.
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Förekomst av smak- och/eller luktförändringar vid antitumoral behandling med kemoterapiTroli, Nils-Edvin January 2010 (has links)
<p><strong>Aim: </strong>The aim of present study was to determine the frequency of taste and smell disorders occuring in patients receiving chemotherapy for cancer.<strong> Methods: </strong>The study was of an empirical cross sectional quantitative descriptive design. During one month, consecutive cancer patients at outpatient units in two Swedish hospitals were asked to participate in the study by completing a questionnaire that had been developed previously for a similar study. All participants had undergone at least 1 cycle of intravenous chemotherapy or a minimum of seven days of oral chemotherapy. <strong>Results: </strong>A total of<strong> </strong>102 patients completed the questionnaire. Results show that 55 % experienced taste disorders and 42 % experienced smell disorders. Both disorders are more common in women than in men. Of patients with taste disorders 47 % reported that it impacted on their daily life to some degree and of patients with smell disorders the corresponding number was 33%. Patients with smell disorders reported a smaller degree of impact on their daily life than did patients with taste disorders.<strong> Conclusion: </strong>Both taste and smell disorders are common in cancer patients treated within chemotherapy. More research into factors that might eliminate or dimnish these problems is needed.<strong> </strong></p>
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Elucidation of the epithelial sodium channel as a salt taste receptor candidate and search for novel salt taste receptor candidatesRiedel, Katja January 2011 (has links)
Salty taste has evolved to maintain electrolyte homeostasis, serving as a detector for salt containing food. In rodents, salty taste involves at least two transduction mechanisms. One is sensitive to the drug amiloride and specific for Na+, involving epithelial sodium channel (ENaC). A second rodent transduction pathway, which is triggered by various cations, is amiloride insensitive and not almost understood to date. Studies in primates showed amiloride-sensitive as well as amiloride-insensitive gustatory responses to NaCl, implying a role of both salt taste transduction pathways in humans. However, sensory studies in humans point to largely amiloride-insensitive sodium taste perception. An involvement of ENaC in human sodium taste perception was not shown, so far. In this study, ENaC subunit protein and mRNA could be localized to human taste bud cells (TBC). Thus, basolateral αβγ-ENaC ion channels are likely in TBC of circumvallate papillae, possibly mediating basolateral sodium entry. Similarly, basolateral βγ-ENaC might play a role in fungiform TBC. Strikingly, δ-ENaC subunit was confined to taste bud pores of both papillae, likely mediating gustatory sodium entry in TBC, either apical or paracellular via tight junctions. However, regional separation of δ-ENaC and βγ-ENaC in fungiform and circumvallate TBC indicate the presence of unknown interaction partner necessary to assemble into functional ion channels. However, screening of a macaque taste tissue cDNA library did neither reveal polypeptides assembling into a functional cation channel by interaction with δ-ENaC or βγ-ENaC nor ENaC independent salt taste receptor candidates. Thus, ENaC subunits are likely involved in human taste transduction, while exact composition and identity of an amiloride (in)sensitive salt taste receptors remain unclear.
Localization of δ-ENaC in human taste pores strongly suggests a role in human taste transduction. In contrast, δ-ENaC is classified as pseudogene Scnn1d in mouse. However, no experimental detected sequences are annotated, while evidences for parts of Scnn1d derived mRNAs exist. In order to elucidate if Scnn1d is possibly involved in rodent salt taste perception, Scnn1d was evaluated in this study to clarify if Scnn1d is a gene or a transcribed pseudogene in mice. Comparative mapping of human SCNN1D to mouse chromosome 4 revealed complete Scnn1d sequence as well as its pseudogenization by Mus specific endogenous retroviruses. Moreover, tissue specific transcription of unitary Scnn1d pseudogene was found in mouse vallate papillae, kidney and testis and led to identification of nine Scnn1d transcripts. In vitro translation experiments showed that Scnn1d transcripts are coding competent for short polypeptides, possibly present in vivo. However, no sodium channel like function or sodium channel modulating activity was evident for Scnn1d transcripts and/or derived polypeptides. Thus, an involvement of mouse δ-ENaC in sodium taste transduction is unlikely and points to species specific differences in salt taste transduction mechanisms. / Der Salzgeschmack ermöglicht elektrolytreiche Nahrungsquellen zu erkennen und ist eine essentielle Komponente für den Erhalt des Elektrolythaushalts. In Nagern sind bisher zwei Mechanismen bekannt, welche an der Vermittlung des Salzgeschmacks beteiligt sind. Ein Natrium-spezifischer, Amilorid-sensitiver Signaltransduktionsweg wird über den epithelialen Natriumkanal (ENaC) vermittelt. Ein weiterer, bisher ungeklärter Transduktionsweg, ist Amilorid-unempfindlich und wird durch verschiedene Kationen vermittelt. Studien in Primaten konnten Amilorid-sensitive als auch -insensitive gustatorische Signaltransduktionswege nachweisen, wohingegen sensorische Studien auf eine Amilorid-Unempfindlichkeit des Natrium-spezifischen humanen Salzgeschmacks hinweisen. Eine Beteiligung des ENaC bei der Vermittlung des menschlichen Salzgeschmacks wurde bislang nicht gezeigt. In dieser Arbeit konnte die mRNA als auch Proteine von ENaC Untereineiten in menschlichen Geschmacksrezeptorzellen (GRZ) lokalisiert werden. Demzufolge, sind αβγ-ENaC Ionenkanäle möglicherweise an einem basolateralen Natriumeinstrom in circumvallaten GRZ beteiligt. Die basolaterale Lokalisation von βγ-ENaC in fungiformen GRZ weißt auf eine gleichartige Funktion hin. Die außergewöhnliche Lokalisation der δ-ENaC Untereineit ausschließlich in der Porenregion von Geschmacksknospen beider Geschmackspapillen, legt eine Beteiligung dieser ENaC Untereinheit bei der Vermittlung geschmacksrelevanter apikaler bzw. transzellulärer Natriumströme nahe. Gleichwohl weist die räumliche Trennung von apikalen δ-ENaC und basolateralen βγ-ENaC auf die Existenz unbekannter Interaktionspartner hin, da beide getrennt voneinander nicht in der Lage sind effektive Natriumkanäle zu assemblieren. Die Durchmusterung einer geschmacksrelevanten cDNA Bibliothek führte weder zur Identifikation von ENaC Interaktionspartnern, noch von ENaC unabhängigen Polypeptiden, welche in der Lage sind einen Kationenkanal zu bilden. Die genaue Zusammensetzung humaner Amilorid- (in)sensitiver Salzrezeptoren bleibt daher unklar und ein spannendes Feld.
Der Nachweis von ENaC in humanen GRZ und insbesondere die Poren assoziierte Lokalisation der δ-ENaC Untereinheit impliziert eine wichtige Rolle bei der gustatorischen Signaltransduktion. Erstaunlicherweise ist die orthologe δ-ENaC Untereinheit der Maus als Scnn1d Pseudogen klassifiziert. Neben dieser automatischen Annotierung sind keine experimentell ermittelten Sequenzen in Datenbanken hinterlegt obwohl Scnn1d abgeleitete mRNA nachgewiesen werden konnte. Im Rahmen dieser Arbeit wurde untersucht ob Scnn1d ein Gen oder ein transkribiertes Pseudogen ist, um eine mögliche Rolle bei der Transduktion des murinen Salzgeschmacks zu klären. Durch Sequenzabgleich mit humanen SCNN1D konnte das vollständige Scnn1d Gen auf dem Chromosom 4 der Maus identifiziert werden, wobei sich dessen Pseudogenisierung durch Mus spezifische endogene Retroviren zeigte. Darüber hinaus wurden neun gewebsspezifische Scnn1d Transkripte nachgewiesen, welche für kurze Polypeptide kodieren. Eine mögliche Funktion derselben als Ionenkanal bzw. eine modulatorische Funktion konnte nicht gezeigt werden. Eine Beteiligung des pseudogenisierten δ-ENaC an der Vermittlung des Salzgeschmacks der Maus ist daher unwahrscheinlich und deutet auf Speziesunterschiede der Salzgeschmacksvermittlung hin.
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On Cultural Capital: Fine Tuning the Role of Barriers, Timing and Duration of Socialization, and Learning Experiences on Highbrow Musical ParticipationHo, Lok See 21 August 2012 (has links)
Recent research in the sociology of culture has placed significant focus on musical taste and practices. This research agenda has ushered an understanding of the relationship between social class and cultural consumption, and particularly, the implications that patterns of cultural preferences and practices have on social inequality. A frontrunner in this line of work is Bourdieu (1984), who offers a sophisticated and useful theoretical framework—the Cultural Capital Theory—to illuminate the role of culture and its consumption in society. Written as three publishable papers, the chapters use empirical evidence to explore three issues surrounding highbrow musical practices that enrich Bourdieu (1984)’s framework. The first paper (Chapter 2) examines the role of structural and personal barriers in blocking attendance to highbrow concerts. It takes as a starting point Bourdieu (1984)’s argument that upper class individuals are more likely to attend classical music and opera concerts than their lower class counterparts, and questions whether these distinct patterns of participation are attributable to the different barriers that each class faces. The second paper (Chapter 3) offers a sophisticated analysis of the impact of socialization on highbrow concert attendance. By innovatively integrating the concepts of timing and duration, hallmarks the Life Course Perspective, I map out the potentially dynamic nature of the socialization process. In doing so, I illustrate the varying implications that different timing and duration of exposure has on later life highbrow concert participation. The last paper (Chapter 4) investigates the process of socialization to understand what conditions present during this crucial period in time encourage persistence in highbrow musical practices. I find that engaging in interactions that allow one to experience positive emotional resonance, develop a musical identity, and feel a sense of autonomy over musical decisions lead to the propensity to remain engaged in musical activities throughout life.
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