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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Studies on the interaction of chemicals with cellular efflux transporter proteins Danio rerio Abcb4 and Homo sapiens ABCB1

Burkhardt-Medicke, Kathleen 06 June 2018 (has links) (PDF)
ABCB1, a member of the ATP binding cassette (ABC) transporter family, hydrolyses ATP as energy source for the translocation of substrate chemicals across the cell membrane. ABCB1-like transporters are found in all studied species. Typically, these transporters are abundant in tissues that separate compartments of the body such as the blood-brain barrier. Among the ABC transporters the ABCB1-like transporter proteins are of particular interest because they accept a broad variety of substrates and are therefore able to confer multidrug resistance (MDR) and multixenobiotic resistance (MXR) in wildlife, respectively. Inhibitors of the ABCB1-like transporter function can cause chemosensitisation, i.e. accumulation and increased sensitivity of organisms towards potentially harmful (natural/man-made) ABCB1-like substrate chemicals. In zebrafish (Danio rerio) Abcb4 was identified as functionally homologous to ABCB1. The aim of this study was to further characterise Danio rerio Abcb4 and to provide a database to approach the question to what extent ABCB1-like transporter related functions/effects are of ecotoxicological relevance. Main objectives are whether and how known ABCB1 ATPase stimulators and inhibitors interact with Abcb4 ATPase activity; to what extent ABCB1 ATPase assay data are transferable to Abcb4 ATPase assay data; and whether and how environmental chemicals interact with Danio rerio Abcb4 ATPase activity. In this study we established a test system – the ATPase assay with recombinant Danio rerio Abcb4 – to study the interaction of chemicals with the ATPase activity of the transporter protein. To relate obtained data to data for the well-known Homo sapiens ABCB1 and because available data for Homo sapiens ABCB1 were not in all cases suitable for a comparison, the ATPase assay with recombinant ABCB1 was adapted accordingly. Chemicals were tested up to concentrations in the range of their water solubilities to modulate basal and stimulator co-treated Abcb4 and/or ABCB1 ATPase activities. ATPase stimulators are often transported substrates. However, lipophilic compounds stimulating the transporter ATPase activity are not or little transported by transporter action. Therefore, experiments revealing whether compounds are translocated by transporters chemical interference with the transporter protein will not be indicated. Chemicals inhibiting the stimulator (here verapamil) co-treated ATPase activity compete with the verapamil to stimulate ATPase activity or are non-competitive inhibitors. When tested individually, these chemicals can be stimulators or inhibitors of basal ATPase activity, or do not interact with basal ATPase activity. ATPase inhibitors mitigate ATPase activity and ABCB1-like transporter mediated translocation of substrate chemicals. Obtained ATPase assay data were analysed with regard to concentrations at half-maximal effects (EC50s) and effect strengths (percent modulation). ATPase assays with recombinant Abcb4 (at 27 °C) are comparable to ABCB1 ATPase assay data obtained at 37 °C. Danio rerio Abcb4 seems less temperature-sensitive than ABCB1. Calculated activation energies for Abcb4 ATPase activities (40.75 kJ/mol for basal ATPase activity) were up to half as high as those for ABCB1 ATPase activities (81.61 kJ/mol for basal ATPase activity). Larger activation energies were previously proposed to be indicative for larger conformational rearrangements and hence possibly smaller rearrangements take place in Abcb4 compared to ABCB1. Known standard modulators of Homo sapiens ABCB1 ATPase activity interacted specifically with Danio rerio Abcb4 ATPase actitiy. The EC50s of the tested chemicals – 16 of 17 tested chemiacals interacted with the ABCB1 and the Abcb4 ATPase activity – ranged from 0.09 to 296 µM for ABCB1 and from 0.14 to 171 µM for Abcb4. Qualitative ATPase assay data for ABCB1, as interaction or not, seems transferable to Danio rerio Abcb4. Furthermore, when aligning amino acid sequences of mammalian ABCB1 transporter proteins and Danio rerio Abcb4 and comparing ABCB1 residues known to bind to (lipophilic) chemicals no obvious hints were found that chemical binding to Abcb4 is certainly different from ABCB1. Twenty-five of 33 studied environmental chemicals modulated the Abcb4 ATPase activity as stimulators and/or inhibitors. Stimulation of basal Abcb4 ATPase activity was lower for environmental chemicals than for known standard modulators. EC50s of environmental chemicals ranged from below 10 to 357 µM. Effects by environmental chemicals on Abcb4 ATPase activity with EC50s close to their water solubilities may be rather unspecific. The results of this work underline that Abcb4 function is of ecotoxicological importance as on the one hand several environmental chemicals were identified to inhibit Abcb4 ATPase activity – likely acting as chemosensitisers, while on the other hand chemicals stimulating basal ATPase activity suggest that these chemicals are possibly transported. A number of environmental chemicals also inhibited the basal Abcb4 ATPase activity. Especially non-transported inhibitors of the basal Abcb4 ATPase activity would be of ecotoxicological relevance as organisms (here Danio rerio) exposed to these chemicals would not be protected by Abcb4 mediated multixenobiotic resistance and were moreover threatened by chemosensitisation. Future studies should systematically elucidate under which circumstances chemicals are apparently net transported by ABCB1-like transporters and relate these findings to concentrations of environmental chemicals and ABCB1-like transporter protein abundance in wildlife.
12

Studies on the interaction of chemicals with cellular efflux transporter proteins Danio rerio Abcb4 and Homo sapiens ABCB1

Burkhardt-Medicke, Kathleen 27 February 2018 (has links)
ABCB1, a member of the ATP binding cassette (ABC) transporter family, hydrolyses ATP as energy source for the translocation of substrate chemicals across the cell membrane. ABCB1-like transporters are found in all studied species. Typically, these transporters are abundant in tissues that separate compartments of the body such as the blood-brain barrier. Among the ABC transporters the ABCB1-like transporter proteins are of particular interest because they accept a broad variety of substrates and are therefore able to confer multidrug resistance (MDR) and multixenobiotic resistance (MXR) in wildlife, respectively. Inhibitors of the ABCB1-like transporter function can cause chemosensitisation, i.e. accumulation and increased sensitivity of organisms towards potentially harmful (natural/man-made) ABCB1-like substrate chemicals. In zebrafish (Danio rerio) Abcb4 was identified as functionally homologous to ABCB1. The aim of this study was to further characterise Danio rerio Abcb4 and to provide a database to approach the question to what extent ABCB1-like transporter related functions/effects are of ecotoxicological relevance. Main objectives are whether and how known ABCB1 ATPase stimulators and inhibitors interact with Abcb4 ATPase activity; to what extent ABCB1 ATPase assay data are transferable to Abcb4 ATPase assay data; and whether and how environmental chemicals interact with Danio rerio Abcb4 ATPase activity. In this study we established a test system – the ATPase assay with recombinant Danio rerio Abcb4 – to study the interaction of chemicals with the ATPase activity of the transporter protein. To relate obtained data to data for the well-known Homo sapiens ABCB1 and because available data for Homo sapiens ABCB1 were not in all cases suitable for a comparison, the ATPase assay with recombinant ABCB1 was adapted accordingly. Chemicals were tested up to concentrations in the range of their water solubilities to modulate basal and stimulator co-treated Abcb4 and/or ABCB1 ATPase activities. ATPase stimulators are often transported substrates. However, lipophilic compounds stimulating the transporter ATPase activity are not or little transported by transporter action. Therefore, experiments revealing whether compounds are translocated by transporters chemical interference with the transporter protein will not be indicated. Chemicals inhibiting the stimulator (here verapamil) co-treated ATPase activity compete with the verapamil to stimulate ATPase activity or are non-competitive inhibitors. When tested individually, these chemicals can be stimulators or inhibitors of basal ATPase activity, or do not interact with basal ATPase activity. ATPase inhibitors mitigate ATPase activity and ABCB1-like transporter mediated translocation of substrate chemicals. Obtained ATPase assay data were analysed with regard to concentrations at half-maximal effects (EC50s) and effect strengths (percent modulation). ATPase assays with recombinant Abcb4 (at 27 °C) are comparable to ABCB1 ATPase assay data obtained at 37 °C. Danio rerio Abcb4 seems less temperature-sensitive than ABCB1. Calculated activation energies for Abcb4 ATPase activities (40.75 kJ/mol for basal ATPase activity) were up to half as high as those for ABCB1 ATPase activities (81.61 kJ/mol for basal ATPase activity). Larger activation energies were previously proposed to be indicative for larger conformational rearrangements and hence possibly smaller rearrangements take place in Abcb4 compared to ABCB1. Known standard modulators of Homo sapiens ABCB1 ATPase activity interacted specifically with Danio rerio Abcb4 ATPase actitiy. The EC50s of the tested chemicals – 16 of 17 tested chemiacals interacted with the ABCB1 and the Abcb4 ATPase activity – ranged from 0.09 to 296 µM for ABCB1 and from 0.14 to 171 µM for Abcb4. Qualitative ATPase assay data for ABCB1, as interaction or not, seems transferable to Danio rerio Abcb4. Furthermore, when aligning amino acid sequences of mammalian ABCB1 transporter proteins and Danio rerio Abcb4 and comparing ABCB1 residues known to bind to (lipophilic) chemicals no obvious hints were found that chemical binding to Abcb4 is certainly different from ABCB1. Twenty-five of 33 studied environmental chemicals modulated the Abcb4 ATPase activity as stimulators and/or inhibitors. Stimulation of basal Abcb4 ATPase activity was lower for environmental chemicals than for known standard modulators. EC50s of environmental chemicals ranged from below 10 to 357 µM. Effects by environmental chemicals on Abcb4 ATPase activity with EC50s close to their water solubilities may be rather unspecific. The results of this work underline that Abcb4 function is of ecotoxicological importance as on the one hand several environmental chemicals were identified to inhibit Abcb4 ATPase activity – likely acting as chemosensitisers, while on the other hand chemicals stimulating basal ATPase activity suggest that these chemicals are possibly transported. A number of environmental chemicals also inhibited the basal Abcb4 ATPase activity. Especially non-transported inhibitors of the basal Abcb4 ATPase activity would be of ecotoxicological relevance as organisms (here Danio rerio) exposed to these chemicals would not be protected by Abcb4 mediated multixenobiotic resistance and were moreover threatened by chemosensitisation. Future studies should systematically elucidate under which circumstances chemicals are apparently net transported by ABCB1-like transporters and relate these findings to concentrations of environmental chemicals and ABCB1-like transporter protein abundance in wildlife.
13

A Survey of Functional Retroposed Genes: H. sapiens, M. musculus, D. melanogaster, and C. elegans

Mahmood, Sanaa 27 July 2010 (has links)
Retrogenes are functional genes that are created through retroposition, whereby mature mRNA is reverse-transcribed and re-integrated into the genome. In this study, the following objectives were accomplished: (i) intrachromosomal- and interchromosomal-retroposed genes were located in H. sapiens, (ii) interchromosomal-retroposed genes were located in M. musculus, D. melanogaster, and C. elegans. To date, this is the first assay for intrachromosomal-retroposed genes in H. sapiens and interchromosomal-retroposed genes in C. elegans. Biases discovered include excess interchromosomal generation of retrogenes by chromosome X in H. sapiens, M. musculus, and D. melanogaster. Selection pressure created by the inactivation of the X chromosome during male meiosis appears to be at least partially responsible for this phenomenon. In addition, excess interchromosomal recruitment of retrogenes by chromosome X was observed in H. sapiens. The driving force appears to be an interplay between selection for female-beneficial genes and selection for male-beneficial genes. No other chromosome biases were discovered.
14

A Survey of Functional Retroposed Genes: H. sapiens, M. musculus, D. melanogaster, and C. elegans

Mahmood, Sanaa 27 July 2010 (has links)
Retrogenes are functional genes that are created through retroposition, whereby mature mRNA is reverse-transcribed and re-integrated into the genome. In this study, the following objectives were accomplished: (i) intrachromosomal- and interchromosomal-retroposed genes were located in H. sapiens, (ii) interchromosomal-retroposed genes were located in M. musculus, D. melanogaster, and C. elegans. To date, this is the first assay for intrachromosomal-retroposed genes in H. sapiens and interchromosomal-retroposed genes in C. elegans. Biases discovered include excess interchromosomal generation of retrogenes by chromosome X in H. sapiens, M. musculus, and D. melanogaster. Selection pressure created by the inactivation of the X chromosome during male meiosis appears to be at least partially responsible for this phenomenon. In addition, excess interchromosomal recruitment of retrogenes by chromosome X was observed in H. sapiens. The driving force appears to be an interplay between selection for female-beneficial genes and selection for male-beneficial genes. No other chromosome biases were discovered.
15

Épistémocritique des insectes sociaux dans les essais de Michelet et de Maeterlinck suivi de La trilogie Antennes et L’Excès

Légaré, Isabelle 20 September 2019 (has links)
Ce projet de thèse en création littéraire, divisé en trois parties, vise à poursuivre dans la veine entomologique et littéraire présente dans L’Insecte, de l’historien Jules Michelet, et dans La Vie des Abeilles, La Vie des Fourmis et La Vie des Termites, du poète symboliste Maurice Maeterlinck. Dans un premier temps, nous analyserons la teneur du discours scientifique de ces deux écrivains reconnus par l’institution littéraire en adoptant une approche épistémocritique. Nous chercherons à comprendre comment les connaissances entomologiques au sujet de l’abeille, de la fourmi et du termite servent les textes de notre corpus et à quel point elles diffèrent d’un écrivain à l’autre. Nous examinerons également leur utilisation des références scientifiques, de la terminologie, des figures et des représentations abstraites afin de mieux nous outiller pour la création. Dans un deuxième temps, nous présenterons la trilogie de nouvelles Antennes qui traite des mêmes connaissances entomologiques que Michelet et Maeterlinck, mais d’une façon imagée et à une échelle différente, car nous y transposons les qualités animales aux humains. L’ensemble est construit en fonction de la hiérarchie établie par Maeterlinck au sujet des espèces qu’il a étudiées pour déterminer si cet ordre tient toujours, un siècle plus tard. Nous retrouvons ainsi les qualités de l’indestructible fourmi (L’Organe) qui, par son altruisme, serait supérieure à l’abeille asservie et à la santé fragile (L’Extrudeuse), qui elle-même serait supérieure à l’impitoyable termite (La Termitière). En changeant les proportions et les acteurs, nous expérimentons avec la fiction pour tenter de comprendre ce que signifient la nature, l’intelligence, l’altruisme et la mort pour l’être humain au XXIe siècle. Dans la dernière partie, forte de notre analyse et de notre création, nous aborderons dans L’Excès le comportement de l’espèce humaine et la place qu’elle se croit en droit d’occuper au sein de la nature.
16

L'enseignement des origines d'Homo sapiens, hier et aujourd'hui, en France et ailleurs : programmes, manuels scolaires, conceptions des enseignants.

Quessada, Marie-Pierre 24 November 2008 (has links) (PDF)
À l'heure où l'enseignement de l'évolution biologique, et particulièrement des origines de l'espèce humaine, se heurte à des mouvements anti-évolutionnistes dans plusieurs pays, notre recherche analyse la façon dont ce thème d'une part a été enseigné en France au cours des 19e et 20e siècles, d'autre part est aujourd'hui enseigné dans 19 pays. Les interactions entre science et société, et plus précisément entre connaissances scientifiques, valeurs et pratiques sociales sont étudiées. <br />En préalable, une approche épistémologique de l'avancée des connaissances scientifiques depuis les travaux de Linné au 18e siècle, permet de caractériser les conceptions des scientifiques et d'identifier les principales ruptures épistémologiques successives sur ce thème. <br />L'analyse des programmes et manuels d'enseignement scientifique relatifs à l'origine de l'homme dans le secondaire au cours des 19e et 20e siècles montre que la transposition didactique dans ce domaine est fortement dépendante du contexte social. Pour mesurer cette influence, un nouveau concept est proposé : le DTD (Délai de Transposition Didactique) : l'écart entre la date de publication d'une avancée scientifique et la date de son apparition dans les programmes ou les manuels scolaires. Le grand retard de l'introduction des idées transformistes au 19e siècle ou encore la rapidité de l'entrée à l'école de l'homme préhistorique en 1885, sont mis en lien avec leurs contextes historiques et scolaires.<br />L'analyse synchronique révèle de très grandes différences dans le traitement scolaire de ce thème dans les 19 pays étudiés : de l'absence totale dans 4 pays à une présence sur plusieurs niveaux scolaires dans d'autres pays, d'une conception gradualiste linéaire et finaliste à une conception buissonnante et contingente. Cependant, dans tous les pays qui abordent ce thème, l'image d'Homo sapiens dans les manuels scolaires reste globalement la même : celle d'un mâle blanc occidental.<br />Le dernier chapitre de cette thèse analyse les conceptions d'enseignants de ces 19 pays (7050 enseignants du primaire et du secondaire, de lettres et de biologie). Les conceptions créationnistes des enseignants sont fortement corrélées avec leur degré de croyance en Dieu et de pratique religieuse, ainsi qu'avec le PNB-personne de leur pays. Enfin, plus des enseignants ont des diplômes universitaires élevés, plus ils sont évolutionnistes, qu'ils enseignent au Primaire ou au Secondaire, en Lettres ou en Biologie.
17

L’organisation spatiale : un comportement clé de Néandertal et d’Homo sapiens : analyse spatiale des couches moustériennes (MS1-MS2) et protoaurignaciennes (A1-A2) de Riparo Bombrini (Imperia, Italie)

Vallerand, Amélie 06 1900 (has links)
Le site de Riparo Bombrini (Ligurie, Italie) offre un cadre unique pour comparer l’organisation spatiale des occupations de Néandertal et d’Homo sapiens dans un seul et même site archéologique. La disparition des Néandertaliens est l’un des plus grands débats de la préhistoire puisque la période de leur déclin correspond à l’arrivée d’Homo sapiens en Europe. Il est donc supposé que des différences fondamentales distinguent les deux espèces, et la capacité de structurer l’espace au sein des sites qu’elles occupaient en zones d’activité distinctes est souvent invoquée comme un trait clé de l’humain. Cependant, ce comportement n’a jamais été évalué pour les deux groupes dans un même site, ce qui rend les comparaisons directes impossibles. Ce projet vise ainsi à évaluer objectivement le degré d’organisation spatiale dans les niveaux protoaurignaciens (A1-A2, associés à Homo sapiens) ainsi que les derniers niveaux moustériens (MS1-MS2, associés aux Néandertaliens) à Riparo Bombrini afin d’établir si ces prétendues différences fondamentales entre les deux espèces existent. La combinaison de SIG et de méthodes quantitatives permet d’étudier la distribution spatiale des artéfacts et des caractéristiques à ces niveaux, démontrant que les Néandertaliens ont en effet organisé leurs espaces de vie comme Homo sapiens. Les résultats des analyses indiquent qu’il existe une logique derrière la manière dont les artéfacts sont distribués dans l’espace sous-tendant des capacités cognitives similaires des humains anatomiquement modernes et des Néandertaliens. Cela fournit de nouvelles données au débat en cours sur la « modernité comportementale », suggérant qu’elle ne se limite pas à notre seule espèce. / The site of Riparo Bombrini (Liguria, Italy) offers a unique setting to compare the spatial organization of Neandertal and Homo sapiens occupations in a single archaeological site. The disappearance of the Neandertals is one of the greatest debates in prehistory since the period of their decline corresponds to the arrival of Homo sapiens in Europe. It is thus often assumed that fundamental differences distinguish the two populations, and the ability to structure space within the sites they occupied into distinct activity areas is often invoked as a key distinctive trait of our species. However, this behavior has never been assessed for both groups at a single site, making direct comparisons impossible so far. This project thus aims to objectively evaluate the degree of spatial organization in the earliest Protoaurignacian levels (A1-A2, associated with Homo sapiens) as well as the latest Mousterian levels (MS1-MS2, associated with Neandertals) at Riparo Bombrini in order to establish whether these alleged fundamental differences between the two species do exist. Combining GIS and quantitative methods allow the study of the spatial distribution of artefacts and features in these levels, showing that Neandertals indeed organized their living spaces like Homo sapiens. The results of the analyses indicates that there is a logic behind the distribution of artefacts and the use of the space suggesting similar cognitive capacities for both anatomically modern humans and Neandertals. This contributes new data to the ongoing debates over ‘behavioral modernity,’ suggesting it is not limited to our species alone.
18

Conflict inhabitation: an emerging deleuzoguattarian inspired conflict studies reterritorialized assemblage

Opheim, David W. 08 April 2019 (has links)
Utilizing the lexicon of the French experimental thinkers Gilles Deleuze and Felix Guattari, research is engaged which indicates that their insights are compatible with and augmentative to the field of Conflict Studies. Specifically, four recognized conflict management approaches, which include the concepts of negotiation, the transformation of the conflict, narrative, and the transformation of the conflicted parties, are populated via an emerging Deleuze and Guattari inspired modus operandi. This process has resulted in an original new term, Conflict Inhabitation, which proposes that the conflicted parties recognize, to their mutual benefit, the centrality of difference to possibility and the acknowledgement of existence as dynamically becoming. This adventure is contextualized utilizing a Personal Narrative Autoethnographic Methodology which systematically engages the intensity of what it means to reside as a person in midst of the human induced Global Warming Climate Change experience during the Anthropocene Epoch. / Graduate
19

Knuckle-Walking Signatures in Hominoid Scapulae

Kreierhoff, Jennifer Lynn 24 April 2014 (has links)
No description available.
20

Gemensamma Symboliska Beteenden Och Interaktioner Mellan Neanderthalare Och H. Sapiens

Karlsson, Julia January 2022 (has links)
The behaviours that the Neanderthals and Homo sapiens sapiens had in common could have made their interaction more advanced and deeper. Ever since Richard E. Green et al’s discovery in 2010 that a lot of the modern day population have inherited about 1-4 %  of the genome from Neanderthals, the assumption that Neanderthals are primitive beings lacking advanced cognition has changed. For H. Sapiens to interbreed with Neanderthals one could argue that they could not have been that dissimilar. Since the modern day population inherited parts of the Neanderthals it could be very interesting to bring more insight into how their relationship and interaction would have looked in relation to H. Sapiens. In this thesis some behaviours will be analysed and compared that existed among them both. In this remark it will be about behaviors of a symbolic nature, indicating a more advanced thinking. These are the usage of personal ornaments, the burial practice, and lastly language and speech. The personal ornaments they used are in some instances very similar, but there is also variation in what they put value in as personal ornaments, later H. Sapiens put a lot of energy into making beads of different types, and Neanderthals having a focus on birds of prey. The burial practice is in general nothing that is too common among either of them during the middle palaeolithic or African Middle stone age. Before the upper palaeolithic there is not too much evidence indicating that they had a tradition of burying their dead. In cases they did bury their dead there is evidence of places with multiple burials, maybe working as grave centers. The anatomical capacities for speech existed among them both. When it comes to language it is harder to discern, since it does not fossilise, but since language is symbolic it could be argued that evidence of symbolism among them could indicate that they had language as well. In the discussion and conclusions it is argued that these common behaviours could have made it possible for a more advanced interaction and relationship between the two.

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