Dissertations / Theses: 'Megality'

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Inoue, Bruna Hitomi. "Bases moleculares da microalbuminúria associada à hipertensão arterial essencial: papel da reabsorção tubular de albumina." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5166/tde-13122012-161119/.

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Evidências epidemiológicas indicam que a presença de microalbuminúria prediz maior freqüência de eventos cardiovasculares e mortalidade em hipertensos essenciais. A microalbuminúria pode ser decorrente do aumento da permeabilidade glomerular e/ou da diminuição da reabsorção desta macromolécula no túbulo proximal. Todavia não é sabido se os mecanismos que regulam a reabsorção de albumina em túbulo proximal renal encontram-se alterados na hipertensão essencial. Este trabalho teve como objetivo investigar as bases moleculares da microalbuminúria associada à hipertensão arterial essencial, focando na reabsorção tubular de albumina. Para tanto, avaliamos a evolução temporal da excreção urinária de albumina em ratos espontaneamente hipertensos (SHR) com 6 semanas de idade (pressão arterial sistólica, PAS, = 105 ± 4 mmHg), 14 semanas de idade (PAS = 180 ± 2 mmHg) e 21 semanas de idade (PAS = 202 ± 2 mmHg). Ratos normotensos Wistar da mesma idade serviram de controle. Observou-se que a excreção urinária diária de albumina aumentou progressivamente com o aumento da pressão arterial em SHR (10,5 ± 1,9; 92 ± 7,0 e 154 ± 27 g/dia, em SHR com PAS média igual a 105, 180 e 202 mmHg respectivamente). Este aumento progressivo não foi observado em ratos normotensos com idade correspondente, indicando que este fenômeno é decorrente do aumento da pressão arterial e não pode ser atribuído ao aumento da idade dos animais durante o período estudado. A análise das proteínas urinárias por eletroforese em gel de poliacrilamida (SDS-PAGE) mostrou que SHR excretam proteínas do tamanho da albumina ou menores (< 70kDa), padrão típico de proteinúria tubular. Adicionalmente, verificou-se que os níveis de expressão dos receptores endocíticos megalina e cubilina, bem como do canal para cloreto ClC-5 diminuem progressivamente no córtex renal de SHR com o aumento da pressão arterial. Observou-se também uma diminuição significativa na expressão de uma outra macromolécula importante no processo de endocitose mediada por receptor em túbulo proximal renal, a v-H+-ATPase. Entretanto, a diminuição da expressão protéica da subunidade B2 desta ATPase foi estatisticamente significante apenas em SHR com 21 semanas comparado aos com 6 semanas de idade. Não foram encontradas alterações no padrão de expressão de componentes estruturais da barreira glomerular como a nefrina e podocina. Em suma, o nosso estudo demonstra que o aumento da excreção urinária de proteínas, especialmente de albumina, está associado com uma menor expressão de componentes essenciais do aparelho endocítico do túbulo proximal renal. É tentador especular que a disfunção da via endocítica no túbulo proximal renal possa ser o principal mecanismo subjacente ao desenvolvimento de microalbuminúria na hipertensão
Epidemiological evidences indicate that the presence of microalbuminuria predicts a higher frequency of cardiovascular events and mortality in essential hypertensive patients. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin. However, it remains to be determined whether the mechanisms that regulate the renal proximal tubular reabsorption of albumin are altered in essential hypertension. The purpose of this work was to investigate the molecular basis of microalbuminuria in essential hypertension, focusing on the renal tubular reabsorption of albumin. To this end, we evaluated the temporal evolution of urinary albumin excretion in spontaneously hypertensive rats (SHR) at 6 weeks of age (systolic arterial pressure, SAP, = 105 ± 4 mmHg), 14 weeks of age (SAP = 180 ± 2 mmHg) and 21 weeks of age (SAP = 202 ± 2 mmHg). Age-matched normotensive Wistar rats were used as controls. It was observed that the daily urinary excretion of albumin progressively increased with blood pressure in SHR from 6 to 21 weeks of age (10.5 ± 1.9, 92 ± 7.0 and 154 ± 27 g in SHR with 105, 180 and 202 mmHg of average SAP, respectively). This progressive increase in microalbuminuria has not been observed in age-matched normotensive Wistar rats, indicating that this phenomenon cannot be attributed to age progression over the studied period. SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (< 70kDa), typical of tubular proteinuria. Additionally, it was verified that the protein expression levels of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 weeks of age. Moreover, it was observed reduction of expression of another macromolecule that plays an important role in the process of receptor mediated endocytosis in the renal proximal tubule, the v-H+- ATPase, was reduced. However, reduced cortical expression of the B2 subunit of the v- H+-ATPase, was only statistically significant in 21-wk-old vs. 6-wk-old SHR. Expression levels of structural components of the glomerular barrier such as nephrin and podocin were unchanged. To sum up, our study demonstrates that the increase in urinary protein excretion, especially of albumin, is associated with lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. It is tempting to speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may be the major mechanism underlying development of microalbuminuria in essential hypertension

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Borba, Susan Caroline Pinto. "Pesquisa de anticorpos anti-megalina em pacientes transplantados renais." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-13092010-161121/.

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Introdução: O papel do sistema HLA na evolução do transplante é indiscutível. Dados da literatura internacional e do nosso laboratório têm mostrado que este não é o único sistema envolvido nos processos de RMA (rejeição mediada por anticorpo) Esse fato é comprovado a partir da constatação de que transplantes realizados entre irmãos com total identidade HLA também são alvos da RMA. Entretanto, os alvos antigênicos desses anticorpos permanecem desconhecidos, dificultando assim o diagnostico e tratamento da RMA não-HLA. No transplante renal a presença desses anticorpos têm sido associada com anticorpos anti células endoteliais, células epiteliais tubulares, podocitos, células mesangiais e monócitos. Nosso objetivo neste estudo foi avaliar a presença e a relevância clínica de anticorpos contra a megalina, membro da família de receptores de LDL, expressa na membrana apical dos túbulos proximais, com importante papel na reabsorção de proteínas no rim. Métodos: Soros pré-transplante de 105 pacientes submetidos a transplante renal, realizado no Serviço de Transplante Renal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (UTR-HC-FMUSP) foram testados por ELISA contra 2 peptídeos da megalina estudados e sintetizados em nosso laboratório. (convencionalmente chamados 18 e 19) Resultado: Não foi detectada a presença de anticorpos do isotipo IgG nas amostras prétransplante dos pacientes estudados. Entretanto, foi detectada a presença de anticorpos do isotipo IgM anti-peptídeo 18 em 33 (31,4%) amostras de soro e anti-peptídeo 19 em 23 (21,9%). Para avaliar a significância clinica desses anticorpos dividimos os pacientes em 2 grupos: pacientes com pelo menos 1 episodio de rejeição aguda (Grupo I) e pacientes sem rejeição (Grupo II) e observamos a distribuição dos pacientes positivos nos 2 grupos. O numero de pacientes com anticorpos anti-peptídeo 18 foi igualmente distribuída nos dois grupos. (12/42, 28,5% no Grupo I e 21/63, 33,3% no Grupo II p=ns). A maioria dos pacientes com anticorpos anti-peptídeo 19 pertenciam ao grupo I (17/42, 40,5% ; 6/63, 9,5% p=0,0003). Esta analise demonstrou uma boa correlação entre presença de anticorpos anti-peptídeo 19 no soro pré-transplante e rejeição. Conclusão: Nossos dados sugerem que anticorpos IgM anti-megalina no pré-transplante podem ser um fator de risco na rejeição do aloenxerto renal. É importante salientar que a nosso conhecimento este é o primeiro estudo envolvendo megalina e rejeição no transplante clínico.
Background. Preformed donor-specific human leukocyte antigen (HLA)- antibodies are accountable for the majority of antibody-mediated rejections (AMR). However, recipients of HLA identical kidneys can develop AMR implicating putative pathogenic antibodies that are directed against non-HLA antigens. Unknown immune targets and consecutive lack of detection methods make non-HLA AMR particularly difficult to diagnose and treat. In renal transplant rejection, the presence of antibodies to non-HLA has been associated with antibodies against endothelial cells, tubular epithelial cells, podocytes, mesangial cells and monocytes. The aim of this study was to evaluate the presence and clinical relevance of preformed antibodies against megalin, a member of the LDL receptor family, expressed on the apical membrane of proximal tubules. Megalin performs a central role in renal protein reabsorption. Methods. Pré-transplant sera of 105 recipients of kidney allograft transplanted at Serviço de Transplante Renal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (STRHCFMUSP) were tested by enzyme-linked immunosorbent assay (ELISA) against 2 megalin-peptides (conventionally named 18 and 19) studied and synthetized in our laboratory. Results. Antibodies were not detected in pretranplant sera when tested for IgG isotype. However, in 33 (31,4%) sera we detected the presence of IgM antibodies to megalin-peptide18 and in 23 (21,9%) to megalin-peptide 19. To evaluate the clinical significance of these antibodies we divided the patients in 2 groups: Group I - 42 patients with at least one rejection episode during the first post-transplant year and Group II - 63 patients without any rejection episode and observed the distribution of positive patients in each of the 2 groups. Patients with megalin-peptide18 antibodies had the same distribution in both groups. (12/42, 28, 5% Group I and 21/63, 33,3% no Group II p=ns). However, patients with megalinpeptide19 antibodies were more frequent in group I. (17/42, 40,5% group I and 6/63, 9,5% group II p=0,0003). This analysis demonstrated a good correlation between preformed anti-megalin-peptide19 antibodies and allograft rejection Conclusion. Our data suggest that presence of IgM megalin antibodies before transplantation might be a risk factor for kidney allograft rejection. To our knowledge, this is the first study involving megalin and rejection in clinical transplantation.

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Sanders, Jeffrey R. "Sacral landscapes : narratives of the megalith in north western Europe." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/2671.

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The construction of archaeological narrative is influenced by a number of factors. Some come from within disciplinary boundaries, whilst others are traced from the wider influences of social, cultural or academic contexts. This thesis examines three areas identified as Neolithic ‘landscapes’, all of which have been the subject of archaeological investigation since the 19th century. The history of research of these areas allows an evaluation of how these disparate influences interact. In this way, the three landscapes act as an arena in which to explore aspects of the archaeological approach itself. This leads to a critical examination of the interpretative tools available to the archaeologist. How concepts such as ‘landscape’ are formed and affect discourse is explored. Wider themes of demarcation, typology and the underlying assumptions of research are investigated in relation to the interpretation of the Neolithic and Early Bronze Age of North Western Europe. The large span of time that these periods encompass allows exploration of change from the short to very long term, although this is not always utilised within archaeological accounts. The treatment of time is therefore considered in conjunction with explanations of change in prehistory. A powerful approach to time is suggested by combining aspects of the work of Pierre Bourdieu and Fernand Braudel and the potential for this is evaluated against the archaeological record of the three areas. How the assumptions of the archaeological approach are acted out within the historiography of each area highlights a number of recurring metaphors that are used to interpret the material record. These promote a portrayal of Neolithic life that combines with the range of influences from the history of archaeology itself to promote an idea of the prehistoric mentalité. A very durable and underlying type that constantly resurfaces in these accounts is the idea of the ‘sacral landscape’, which is the central topic of this thesis.

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Vaske, Kristofer. "Megalith Grave Escape : Using escape room game mechanics for cultural heritage sites." Thesis, Högskolan i Skövde, Institutionen för informationsteknologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17025.

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This report documents the development of a concept and prototype for a mobile application with the purpose of making the megalith graves surrounding the town of Falköping more engaging and interactive for visitors. Because of the limitations of working with heritage sites that cannot be altered to support a gaming experience, the usage of escape room game mechanics is explored. Because escape room games depend on the user's observation and exploration of their environment, they serve as a usable inspiration for applications with the purpose of making visitors experience a location in a similar way. The prototype developed for the project contains puzzles designed for four different megalith grave sites which were then tested with groups of children and parents playing together.

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Larsson, Mårten. "Megalin, an Endocytotic Receptor with Signalling Potential." Doctoral thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6585.

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Megalin is an endocytotic receptor belonging to the low-density lipoprotein family. It has often been viewed only as merely a scavenger receptor of absorptive and secretory epithelia. Recent work has revealed that the megalin intracellular domain contains several motifs potentially binding proteins involved in signal transduction.

To find potential intracellular proteins binding to megalin, a yeast two-hybrid screening was initiated with the intracellular tail of megalin as the bait. A partial clone encoding the scaffolding protein postsynaptic protein 95 (PSD-95) was found to bind to megalin with its second PDZ-domain. Co-localization experiments in HEK-293 cells and kidney, placenta and parathyroid tissue confirmed this interaction. The PSD-95 related proteins PSD-93 and SAP102 were also confirmed to bind megalin with their PDZ2-domains, but the corresponding domain from SAP97 did not bind. Mutation analysis revealed that an amino acid residue change Ala to Thr was the cause of this.

Megalin has within the central nervous system (CNS) been shown to be expressed only in the ependymal cells and choroid plexus. Nothing has been known about megalin expression in the spinal cord. To study spatio-temporal expression of megalin in the spinal cord, extensive staining of prenatal and postnatal mouse spinal cord was undertaken. Megalin expression was found in the dorsal part of the embryonic spinal cord. Most of these cells also expressed vimentin, suggesting that megalin has a role in the normal development of astrocytes. In the postnatal mouse, megalin seems to be expressed in oligodendrocytes only in the spinal cord white matter, and co-incident with myelination. This suggests that megalin is involved in the formation and maintenance of myelin along long spinal pathways. Megalin staining was clearly seen in the nucleus of these cells, indicating that megalin works in a notch-like signalling pathway.

Uptake of retinol to the retina pigment epithelium (RPE) has long been thought to be a diffusion process. Staining for megalin in RPE revealed strong expression, and uptake experiments with 3H-retinol bound to retinol-binding protein and blocking with the LDL-receptor family specific antagonist receptor-associated protein (RAP) showed that megalin is a receptor for uptake of retinol to the RPE.

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Wicher, Grzegorz. "Clusterin and Megalin in The Spinal Cord." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7365.

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Andersson, Emelie. "Trattbägarkeramiken och dess ritualer : En studie av keramikhanteringen vid megalitgravar i Sydskandinavien under neolitikum." Thesis, University of Kalmar, University of Kalmar, University of Kalmar, University of Kalmar, School of Human Sciences, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:hik:diva-1019.

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This essay studies the funnel-beaker ceramic in connection with the megalith graves in South Scandinavia. In my work I have described the nature of ceramics and looked on the crockery types and ornamentation and then discussed the use of the material in a ritual perspective. In the first part I have focused on the critical aspects you have to think about when you do a study like this one. In the second part of this essay I have done a case study, with the ceramic material, in three passages graves in the area of Falbygden, Western Sweden and studied the ceramic material and the nature of it in South Scandinavia as well. Then in the third I discussed the potential use, there is two, of the ceramic material in general of South Scandinavia and looked at it in a ritual perspective.

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Sörgard, Ingegerd. "De första Nösundsborna : en studie av hur västra Orust befolkades." Thesis, Uppsala universitet, Institutionen för arkeologi och antik historia, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-385734.

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The purpose of this thesis is to determine whether western Orust was continuously inhabited during the Stone Age and the Bronze Age. Using reports from the archaeological excavations carried out in Nösund in western Orust as a basis, I discuss what conclusions can be drawn, relating, when possible, the findings to what we, thanks to analyzes of fossil DNA made in recent years, now know about ancient peoples’ descent. The results show that there is no basis for claiming that Nösund has been continuously inhabited under the Mesolithic, despite archaeologists having located and dated half a dozen settlements from the Stone Age and the Bronze Age in the village. The findings from the various archaeological surveys do not allow us to determine the descent of the people living in Nösund during different time-periods, nor whether they were mainly fishermen or hunters. The main reason for this is the absence of organic materials, especially bones, in the findings from Nösund. The conclusion therefore is that much more research has to be done, if we are to provide a comprehensive picture of the earliest settlements in western Orust.
Denna uppsats har syftet att visa huruvida västra Orust varit kontinuerligt bebodd under stenålder och bronsålder. Utgångspunkten har varit rapporterna från de arkeologiska grävningar som utförts i Nösund, och resultaten därifrån diskuteras med utgångspunkt från de nya kunskaper om människors härstamning som de senaste årens analyser av fossilt DNA har gett oss. Resultatet av undersökningen visar att vi inte har underlag för att påstå att Nösund har varit kontinuerligt bebodd under mesolitikum, trots att man lokaliserat och daterat ett halvt dussin boplatser i Nösund från stenålder och bronsålder, och att kunskapen om vad som skedde under neolitikum och bronsålder är ännu mer bristfällig. Fynden från de olika arkeologiska undersökningarna är inte heller av en kvalitet som gör att vi kan uttala oss vilken härstamning människor som bott i Nösund under olika perioder har haft, eller om de huvudsakligen varit fiskare eller jägare. Den största bristen är frånvaron av fynd av organiska material, särskilt ben, i Nösund.

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Imchen, Shisachila. "Morungs and megaliths : heritage among the Naga of Nagaland, northeast India." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10047448/.

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The thesis draws on a year-long field study of morungs and megaliths as important components of Naga heritage, and on written sources documenting Naga ethnography and other relevant literature. It examines the ways in which these objects of material culture are used at two levels: the state and the village, in terms of projecting Naga identity. The phenomenological approach to the study of the stated theme brings out the process of embodiment, materialization and memorialisation of the Naga past in the present through megalithic building, interactions of the people with and within the morung, and festivals involving participation of individuals as members of the community at different levels, Khonoma being a case in point. The study has addressed itself to the dynamics of heritage politics, thereby filling in the gap area that had remained in the extant works on the Naga due to various factors, not least Nagaland’s volatile political climate and inaccessibility till recently. It reveals the extent and nature of state involvement in negotiating heritage to sell its idea of constructing a composite Naga identity with particular reference to the state-sponsored Hornbill Festival. The study also works at the level of village-centric identity formation through the process of socialization, a carry-over from their traditional past. Importantly the use of the phenomenological approach complemented by insights drawn from heritage studies on especially non-Western societies has opened up new lines of inquiry into the ways in which identity is built up, reworked and sustained. In this respect the study makes a significant contribution to the understanding of heritage in contemporary Nagaland and in the broader picture of material culture studies.

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Mullane, Elizabeth Brownell. "Megaliths, mounds, and monuments applying self-organizing theory to ancient human systems /." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1997751651&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.

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Kastner, Christian [Verfasser]. "Tubuläre Volumenregulation bei Glomerulonephritis in der Megalin-teildefizienten Maus / Christian Kastner." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1026695155/34.

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Baines, Richard John. "Megalin cytoplasmic tail phosphorylation and function in kidney proximal tubular cells." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/9513.

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Gouézin, Philippe. "Structures funéraires et pierres dressées : analyses architectorales et spaciales : mégalithes du département du Morbihan." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S112/document.

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Le mégalithisme est l'expression architecturale monumentale d'un ensemble de sociétés qui ont édifiées des structures funéraires et des pierres dressées. La genèse du mégalithisme, phénomène humain de la fin de la préhistoire, puise ses origines dans de multiples conjugaisons des différents courants de la néolithisation aux traditions variées, aux influences géographiques parfois lointaines, aux époques différentes. La combinaison de nombreux éléments sociaux de ces sociétés agro-pastorales a généré des générations d’architectes bâtisseurs et contribué à mettre en œuvre une diversité architecturale La volonté de mise œuvre des maisons des morts au même niveau que les maisons des vivants semble répondre à des critères sociaux et culturels. Une perception visuelle actualisée des mégalithismes, adaptée aux récentes thématiques développées amène un fil conducteur original d’étude de plusieurs mondes qui se sont combinés. L’état des connaissances depuis le milieu du XXème siècle a permis une appréhension différente des mégalithismes : - dans les années 1980, une connaissance plus complète des masses tumulaires et leurs liens étroits avec les chambres sépulcrales (Joussaume, 1997, 1999, 2003 ; Joussaume et al. 2006). - dans les années 2000 une prise en compte de l’histoire des monuments (Joussaume et al. 2006 ; Laporte, 2010 ; Laporte et al. 2004, 2011). - de nos jours, une appréhension différente des articulations entre les pierres dressées, les tumulus et les chambres sépulcrales (Laporte, 2015 ; Laporte et al. 2011). Le processus de cette monumentalisation architecturale a souvent fait l’objet d’études distinctes, les espaces sépulcraux et les pierres dressées servant de bases à deux axes de recherches séparées. Seule l’étude des stèles en remploi avait fait l’objet d’une attention particulière (L’Helgouac’h, 1983 ; Cassen, 2009b) et d’un rapprochement des deux dispositifs. Ce n’est que récemment que la complémentarité entre les espaces sépulcraux et les pierres dressées a réellement été proposée (Laporte, 2015b). Disposant d’un important corpus actualisé des mégalithes du département du Morbihan, il a donc été proposé de développer dans cette thèse cette notion de complémentarité entre les différents dispositifs qui constituent les mégalithismes. Les hypothèses formulées sont de démontrer que les processus de monumentalisation sont issus d’un croisement architectural entre les pierres dressées, les espaces sépulcraux et les masses tumulaires. Nous tenterons également de montrer les liens étroits qui semblent se dessiner entre trois mondes très différents mais intimement liés (le monde des vivants, le monde des morts et le monde naturel)
Megalithism is the monumental architectural expression of a group of societies that have built funerary structures and erected stones. The genesis of megalithism, the human phenomenon of the end of prehistory, draws its origins from multiple conjugations of the different currents of neolithization with varied traditions, geographical influences sometimes distant, at different times. The combination of many social elements of these agro-pastoral societies has generated generations of architects and contributed to the implementation of architectural diversity The desire to put the houses of the dead to the same level as the houses of the living seems to meet social and cultural criteria. An updated visual perception of megalithisms, adapted to the recent themes developed, brings an original thread of study of several worlds that have combined. The state of knowledge since the middle of the 20th century allowed a different apprehension of megalithisms: - in the 1980s, a more complete knowledge of the tumular masses and their close links with the sepulchral chambers (Joussaume, 1997, 1999, 2003, Joussaume et al., 2006). - in the 2000s, taking into account the history of monuments (Joussaume et al., 2006, Laporte, 2010, Laporte et al., 2004, 2011). - today, a different apprehension of the articulations between the erected stones, the tumuli and the sepulchral chambers (Laporte, 2015, Laporte et al., 2011). The process of this architectural monumentalization has often been the subject of separate studies, sepulchral spaces and erected stones serving as bases for two separate lines of research. Only the study of stelae in reuse had been the object of particular attention (L'Helgouac'h, 1983, Cassen, 2009b) and a comparison of the two devices. It is only recently that the complementarity between sepulchral spaces and erected stones has actually been proposed (Laporte, 2015b). It has therefore been proposed to develop in this thesis the notion of complementarity between the different mechanisms that constitute megalithisms. The hypotheses formulated are to demonstrate that the processes of monumentalisation are the result of an architectural crossing between the erected stones, the sepulchral spaces and the tumular masses. We will also try to show the close ties that seem to be taking shape between three very different but intimately linked worlds (the world of the living, the world of the dead and the natural world)

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Burmeister, Regina. "Untersuchungen zur Rolle des Endozytoserezeptors Megalin in der zellulären Aufnahme von Steroidcarrierproteinen." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=967999014.

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Burmeister, Regina. "Untersuchungen zur Rolle des Endozytoserezeptors Megalin in der zellulären Aufnahme von Steroidcarrierproteinen." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2003. http://dx.doi.org/10.18452/14867.

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Der Endozytoserezeptor Megalin gehört zu einer Gruppe von strukturell und funktionell verwandter Rezeptoren, der LDL R Gen Familie. Es sind zwei Arten von Lipidtransportpartikel beschrieben worden, die durch Megalin in Zellen aufgenommen werden. Zum einen werden Lipoproteine über ihre Apoproteine von Megalin erkannt und endozytiert. Zum anderen nimmt Megalin die hydrophoben Vitamine A und D über ihre Carrierproteine in ihre Zielzellen auf. Es handelt sich um Vitamin D bindendes Protein (DBP) und Retinol bindendes Protein (RBP). Zweck dieser Arbeit war es zu untersuchen, ob die Endozytose von Steroidcarriern durch Megalin ein genereller Mechanismus ist oder ob DBP und RBP Ausnahmen darstellen. Hierzu wurden exemplarisch drei Carrierproteine (24p3, Apo D und CCSP) für Steroide ausgesucht, die in Megalin-exprimierende Gewebe aufgenommen werden. Der (rekombinante) Retinolcarrier 23p3 zeigte bei surface plasmon resonance Analysen keine direkte Bindung an Megalin. Der Progesteron-Carrier Apo D hingegen bindet Megalin, ferner konnte in Zellkulturversuchen Endozytose und lysosomale Degradation von Apo D in Megalin-exprimierende Zellen nachgewiesen werden. Auch der Progesteron-Carrier CCSP wird durch Megalin in Zellen aufgenommen, allerdings ist zur Endozytose von CCSP ein Co-Rezeptor notwendig. Mit dieser Arbeit ist die erste in vivo-Beschreibung eines dualen Rezeptorsystems aus Megalin und einem peripheren Membranprotein namens Cubilin gelungen, welches u.a. im proximalen Tubulus der Niere existiert. Abschließend wurde exemplarisch für ein Steroidhormon-abhängiges Gewebe der murine Uterus hinsichtlich seiner Megalin-Expression untersucht. Es konnte ein bereits bekannter Ligand Megalins, das Glykoprotein Laktoferrin, aus der uterinen, luminalen Flüssigkeit aufgereinigt werden. Ferner konnte gezeigt werden, dass die Expression von Laktoferrin im Uterus strenger hormoneller Kontrolle unterliegt.
The endozytic receptor Megalin belongs to a group of structurally and functionally related receptors called LDL R gene family. Two different types of lipid particles are taken up by Megalin into target cells. The first type, lipoproteins are recognized and internalized by Megalin via their apoproteins. In addition, Megalin mediates the endocytosis of the lipophilic vitamins A and D into target cells by means of their carrier proteins. These proteins are the vitamin D binding protein (DBP) and retinal binding protein (RBP). The aim of the investigations was to determine, if the endocytosis of steroid hormone carriers by Megalin is a common occurrence or restricted only to DBP and RBP. Therefore, three carrier proteins for steroids (24p3, Apo D and CCSP) were chosen as an example. All of them are known to be taken up in Megalin expressing tissues. In surface plasmon resonance analysis recombinant 24p3, a carrier of retinol, showed no affinity to Megalin. Whereas the progesterone carrier Apo D bound to Megalin. Furthermore, it was endozytosed and degraded in lysosomes by Megalin expressing cells. The cellular uptake of the progesterone carrier CCSP is mediated by Megalin as well, however a co-receptor is needed. This work demonstrates for the first time the existence of a dual receptor pathway consisting of Megalin and a peripheral membrane protein named Cubilin in vivo. This systems is functional in addition to other tissues in the proximal tubule of the kidney. Finally, the Megalin expression in the murine uterus as an example of a steroid dependent tissue was investigated. Lactoferrin a known Megalin ligand was purified from the luminal uterine fluid. Furthermore, Lactoferrin expression in the uterus was shown to be under tight hormonal control.

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16

Akour, Amal. "The role of megalin in the transport of aminoglycosides across human placenta." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/448.

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Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is also expressed in human term placenta and it is reasonable to speculate that it is similarly involved in the placental transport of AGs. However, the mechanisms responsible for placental AG uptake and transport have not yet been characterized. Objective: To evaluate the role of megalin in the transport of AGs across human placenta. Specific aims: (1) To assess and compare megalin expression in term and preterm placental villous tissue, and (2) assess the functional activity of megalin in in vitro placental models. Methods: (1) Following IRB approval, placental tissue samples were collected from pregnant women undergoing term or preterm deliveries. Placental villous tissueswere used to quantify megalin expression by western blotting and q-PCR (2) The human choriocarcinoma cell line (BeWo cells) were grown on Transwell plates, and then megalin expression and function were assessed. Results: Megalin protein and mRNA expression were confirmed in samples of human placental villous tissues. Megalin mRNA expression declined steeply with gestational age till week 31 of gestation then it plateaued thereafter. Also, the expression in the early preterm (n=2) was six fold higher than that of both late preterm (n=3) and term placenta (n=10) (p<0.05). The uptake of 3H-gentamicin by the BeWo cells was time-dependent, saturable (Vmax=42.9 ± 4.9 nmol/mg protein/min; Km=2.93±0.68mM) and partially inhibited by megalin inhibitors. Conclusion: Megalin is expressed in human placental villous tissues as well as the BeWo cells. When grown on Transwell® plates, the BeWo cells appear to be the most appropriate model to study the in vitro transport of AGs across the apical membrane. Time, temperature and concentration dependence of gentamicin uptake in the BeWo cells indicate protein-mediated transport. The inhibition data are consistent with megalin-mediated endocytosis of AGs.

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Eimers, Meike [Verfasser]. "Die Rolle des Endozytoserezeptors Megalin (GP330) bei der Pathogenese progredienter Nephropathien / Meike Eimers." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023623463/34.

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18

Anzenberger, Uwe. "A new role for LRP2 in forebrain development." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2006. http://dx.doi.org/10.18452/15565.

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LRP2 wird waehrend der fruehen Embryonalentwicklung hauptsaechlich im Dottersack und im Neuroepithel exprimiert. Der funktionelle Verlust dieses 600 kDa grossen Proteins in Maeusen fuehrt zu Fehlbildungen bei der Vorderhirnentwicklung, die als Holoprosenzephalie bezeichnet werden. LRP2 kommt daher eine wichtige Funktion waehrend der Vorderhirnentwicklung zu. Fuer diese Arbeit wurden Maeuse verwendet, bei denen lrp2 im gesamten Tier oder nur in bestimmten Geweben inaktiviert war. Die Expression von LRP2 im Neuroepithel, nicht aber im Dottersack ist wichtig fuer die korrekte Vorderhirnentwicklung. Das Fehlen des Proteins fuehrte am Tag 9.5 der Embryonalentwicklung zu einer UEberaktivierung des Bmp4 Signalweges im rostralen Telencephalon. Am Tag 10.5 war ein Verlust der shh-Expression in der anterioren entopeduncularen Zone (AEP) zu sehen. Das Fehlen von Shh in der AEP fuehrte zum Verlust von ventralen Oligodendrozyten und Interneuronen. AEhnliche Defekte wurden ebenfalls in Maeusen beschrieben, bei denen der Bmp4 Signalweg verstaerkt ist. Bmp4 bindet in vitro an LRP2. Diese Ergebnisse deuten darauf hin, dass LRP2 an der Entwicklung des ventralen Telencephalons beteiligt ist - moeglicherweise indem es die verfuegbare Menge an Bmp4 durch Endozytose reguliert. Die Signalwege, in die LRP2 eingebunden ist, sollten im Zebrafisch weiter untersucht werden. Tiere, denen funktionelles LRP2 fehlte, wurden durch die Injektion von Morpholinos generiert. Injizierte Tiere zeigten Stoerungen bei Resorptionsvorgaengen im Pronephros, was darauf hin deutet, dass die Funktion von LRP2 im Zebrafisch Pronephros und in der Niere der Saeugetiere konserviert ist. Die Expressionsmuster von Markergenen fuer die Vorderhirnentwicklung waren allerdings normal.Vermutlich war die Stoerung der lrp2-mRNA Prozessierung nicht ausreichend, um hier einen Effekt hervorzurufen, da bereits im 1-Zell Stadium genuegend komplett prozessierte maternale lrp2-mRNA fuer die Translation von LRP2 vorhanden war.
LRP2 is mainly expressed in the yolk sac and in the neuroepithelium of the early embryo. Deficiency for this 600 kDa protein in mice results in holoprosencephaly, indicating a role for LRP2 in forebrain development. Mice with a complete or a conditional loss of lrp2 function were used to elucidate the consequences of the lack of LRP2 expression. The presence of LRP2 in the neuroepithelium but not in the yolk sac is crucial for early forebrain development. Lack of the receptor resulted in an increase of Bmp4 signaling in the rostral telencephalon at E9.5. As a consequence, shh expression at E10.5 was lost completely in a ventral region of the telencephalon termed anterior entopeduncular area (AEP). The absence of Shh activity in this area led to the loss of ventrally induced oligodendroglial and interneuronal cell populations in lrp2-deficient mice. Similar dorsalizing effects have also been observed in mice with increased Bmp4 signaling. Taking into account that Bmp4 was found to bind to LRP2 in vitro and in vivo, these results suggest a role for LRP2 in patterning the rostral ventral neural tube, possibly by acting as a clearance receptor for Bmp4. The underlying molecular mechanisms were then further analyzed in the zebrafish. LRP2-deficient animals were generated by injecting Morpholinos that interfered with the splicing of the lrp2-pre-mRNA leading to a deletion of the transmembrane-exon. Injected animals suffered from impaired renal clearance processes, demonstrating the functional conservation of LRP2 in the larval zebrafish pronephros. Brain structures were not affected in these animals and the expression patterns of marker genes for early forebrain development that were changed in the mouse were not changed. Apparently, Morpholino mediated interfering with the splicing of the lrp2-pre-mRNA did not affect the early forebrain formation because properly processed lrp2-mRNA was supplied maternally and sufficient for proper brain formation.

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19

Van, Praet Oliver. "Co-expression and interaction of cubilin and megalin in the adult male rat reproductive system." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29485.

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Cubilin is a peripheral membrane protein that co-operates with the endocytic receptor megalin to mediate the endocytosis of ligands in various polarized epithelia. Megalin is expressed in the male reproductive tract where is has been implicated in the process of sperm membrane remodeling. A potential role for cubilin in the male reproductive tract has not been explored. Using RT-PCR, we found that cubilin and megalin mRNAs are expressed in the efferent ducts, corpus and cauda epididymides, and proximal and distal vas deferens. Immunohistological analysis revealed that cubilin was expressed in non-ciliated cells of the efferent ducts, principal cells of the corpus and cauda epididymides and vas deferens. Electron microscopic immunogold labeling showed cubilin in endocytic pits, endocytic vesicles and endosomes of these cells. The expression profile of cubilin in the male reproductive tract was coincident with that of megalin except in principal cells of the caput epididymidis. Double immunogold labeling showed that cubilin and megalin co-localized with one another within the endocytic apparatus and recycling vesicles of efferent duct cells. Neither protein was found in lysosomes. Injection of RAP, an antagonist of megalin interaction with cubilin, reduced the level of intracellular cubilin in cells of the efferent ducts and vas deferens. In conclusion, cubilin and megalin are co-expressed in cells of the epididymis and vas deferens and the endocytosis of cubilin in these tissues is dependent on megalin. Together, these findings highlight the potential for a joint endocytic role for cubilin and megalin in the male reproductive tract.

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20

Mori, Keita. "Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225488.

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21

Jenkins, Mary A. "To megali idea - dead or alive?: the domestic determinants of Greek foreign policy." Thesis, Monterey, California. Naval Postgraduate School, 1994. http://hdl.handle.net/10945/42939.

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Approved for public release, distribution unlimited
This thesis provides an algorithm based on marginal analysis to help CLF Supply Officers load ships with Provisions (food), High Usage Load List (HULL), and ship store stock. The algorithm is incorporated into an EXCEL spreadsheet and produces a prioritized list of items in their optimum stocking sequence. The algorithm is compared to both the Atlantic and Pacific Fleet current loading methods using a food item example and shows a 60-70% increase in expected supply effectiveness. Furthermore, the algorithm is generic and can be applied to and inventory problem where a demand distribution is known and space is the limiting factor in determining stocking levels.

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22

Hinders, Johan. "Dödsrikets livshistorier : Benkemiska isotopanalyser på artikulerade och disartikulerade individer i Frälsegårdens gånggrift." Thesis, Stockholms universitet, Arkeologiska forskningslaboratoriet, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-62099.

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The aim in this thesis is to use carbon, nitrogen and sulfur isotope analysis on teeth and bone to track diet and mobility of the population as well as the individual level from the articulated and disarticulated individuals from the passage grave Frälsegården, situated in Gökhem parish in the region of Falbygden, western Sweden. 50 human samples were analyzed from tooth, mandibula and femur, together with 11 faunal samples from different bone elements of local wild and domestic animals. The results fall well in line with earlier stable isotope work done on passage grave individuals from Falbygden in stable isotopes: A homogenous group with a diet which was clearly terrestrial and lived on a pretty high trophic level. It also seems that the analyzed individuals deliberately focused their food intake to the cultural and natural, megalith and limestone landscape of Falbygden, and not to its surroundings, even if the passage grave is situated in the outermost areas of the region. A small study compares the sulfur results to with earlier work done on strontium isotopes. The results show that the different methods might provide a deeper understanding in the interpretation of the methods, and therefore suggesting that further work should be done to compare the methods.

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23

Jerichow, Timo [Verfasser]. "Die Rolle der Proteinendozytose bei der Pathogenese der tubulointerstitiellen Nierenerkrankung in der Megalin-teildefizienten Maus / Timo Jerichow." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2011. http://d-nb.info/1025239687/34.

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24

Fatah, Hiwa Ramadhan. "Reduced proximal tubular expression of megalin and neonatal Fc receptor in proteinuria : the role of matrix metalloproteinases." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/41079.

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Proteinuria is clearly associated with the progression of chronic kidney disease (CKD) but the mechanisms underlying this relationship remain unclear. Recent evidence suggests that altered proximal tubular (PT) handling of filtered proteins may significantly modulate urine protein excretion and progressive renal disease. Megalin and neonatal Fc receptor (FcRn) are endocytic receptors responsible for the PT reabsorption of glomerular ultrafiltered proteins by receptor-mediated endocytosis (RME) and transcytosis, and are expressed on the luminal surface of the PT. This study aimed to investigate the expression and turnover of megalin and FcRn in proteinuria, and the possible mechanisms underlying down-regulation of expression of these receptors. In protein overload proteinuria (POP), the PT expression of megalin and FcRn were both downregulated compared to control animals. In addition, significant amount of both receptor were detected in the urine of proteinuric animals. This reduction in megalin and FcRn protein expression was accompanied by a significant increase in the urinary excretion of plasma proteins including the most abundant albumin. Increased expression and activity of both matrix metalloproteinase (MMP) and gamma secretase (γ-secretase) was evident in proteinuric animals and was paralleled with the urinary excretion of both megalin and FcRn. Megalin was previously identified to undergo regulated intramembrane proteolysis (RIP). RIP includes the MMP-mediated cleavage of the extracellular domain of megalin which in turn excreted into the urine, and the subsequent cleavage of the intracellular domain by γ-secretase. A synthetic inhibitor of MMPs, batimastat (BB-94) significantly reduced urinary excretion and also preserved the PT expression of megalin. In addition, inhibition of MMPs appeared to be antiproteinuric by markedly reducing urinary excretion of albumin and plasma proteins. The urinary excretion of FcRn was also reduced in BB-94 treated animals but the mechanism of this reduction was not clear. Further, BB-94 treatment preserved PT expression of FcRn in proteinuric animals. The POP model was developed to investigate the degree of tubulointerstitial damage in experimental animals. Injury was detected in the interstitium of proteinuric animals with significant increases in inflammatory markers including tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and the transforming growth factor-beta (TGF-β) as well as interstitial collagen deposition and marked interstitial infiltration of macrophages (F4/80). Blockade of MMP in proteinuric animals significantly reduced the expression of these markers in the kidney and abrogated the progression of interstitial inflammation and fibrosis. In summary this is the first study to correlate the reduced expression of megalin and FcRn, and the urinary excretion of these receptors with the increased cellular activity of MMP and the possible occurrence of RIP in vivo. Inhibition of MMP could be of great importance in treating proteinuria and the progression of tubulointerstitial inflammation and fibrosis, the most characteristic features of CKD.

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25

Rader, Katherine A. "Megalin is a clearance receptor for insulin in proximal tubules and interacts with a novel intracellular protein ANKRA /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9970666.

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26

Zelepos, Ioannis. "Die Ethnisierung griechischer Identität 1870-1912 : Staat und private Akteure vor dem Hintergrund der "Megali Idea /." München : R. Oldenbourg, 2002. http://catalogue.bnf.fr/ark:/12148/cb39910376f.

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27

Mazzocchi, Luciana Carla [Verfasser]. "TGF-beta impairs alveolar protein clearance through downregulation of the endocytic receptor megalin in alveolar epithelial cells / Luciana Carla Mazzocchi." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1136268766/34.

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Buchäckert, Yasmin [Verfasser]. "Role of megalin in albumin transport across the alveolar epithelium and its dysregulation by transforming growth factor beta / Yasmin Buchäckert." Gießen : Universitätsbibliothek, 2012. http://d-nb.info/1064990622/34.

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29

Joseph, Antoine. "La mégaline/lrp2 exprimée dans le neuroépithélium antérieur est critique pour la croissance oculaire." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066144/document.

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La mégaline est un récepteur endocytique multiligand essentiellement connu comme récepteur clé pour la réabsorption protéique rénale. Au cours du développement embryonnaire murin la mégaline a été impliquée dans le développement du prosencéphale et de l’œil mais la mortalité périnatale des souris Meg-/- empêche sone étude à des stades ultérieurs. Pour analyser le rôle de la mégaline dans le système visuel nous avons généré dans le laboratoire des souris conditionnelles FoxG1-Cre MegL/L.L’analyse phénotypique des souris mutantes montre que l’absence de la mégaline dans le neuroépithélium antérieur conduit à une augmentation anormale et progressive de la taille de l’œil accompagnée par un amincissement de la rétine et la diminution, entre autres, des cellules ganglionnaires. Ces observations immunomorphologiques suggèrent que les souris mutantes présentent des signes de myopie forte et sont confirmées par l’analyse ophtalmologique. Les analyses biochimiques des souris mutantes montrent que l’absence de mégaline entraine des modification dans la structure et la fonction du corps ciliaire, à l’origine de cet élongation excessive du globe oculaire. Les résultats obtenus montent que les souris Foxg1-Cre MegL/L sont le premier modèle génétique murin qui reproduit les caractéristiques de la myopie forte. L’élucidation des mécanismes physiopathologiques sous-jacents au développement de la myopie est un préalable indispensable à l’élaboration d’en éventuel traitement préventif, espoir pour les 0,5% à 2% de la population touchés par la cécité liée aux complications de la myopie forte
Megalin is a large multiligand endocytic receptor essentially known as the key receptor for protein reabsorption in the renal proximal tubule. Murin megalin appears to be essential for early forebrain and eye development but the perinatal lethality of Meg-/- mice precludes further analysis. To study the implication of megalin in the formation of the eye we generated (in the laboratory ) FoxG1-Cre MegL/L mice lacking megalin specifically in the anterior neuroepithelium.The phenotypic analysis of these mice show that they suffer from an excessive and progressive eye growth associated with retinal thinning and a strong decrease of some retinal cell types including the ganglion cells. The immunomorphological studies suggest that the mutant mice are highly myopic which is confirmed by the ophtalmological analysis data. The biochemical analysis of these mutant mice shows that the absence of megalin causes structural and functional modifications in the ciliary epithelium, leading to the excessive elongation of the eyeball. These results show that the FoxG1-Cre MegL/L mice are the first murine genetic model recapitulating the characteristics of high myopia. The elucidation of underlying physiopathological mechanisms of high myopia development is essential for the elaboration of a preventive treatment, hope for 0,5 to 2% of the population suffering from blindness caused by the complications of high myopia

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30

Gallagher, Hugh. "Megalin, cubilin and the proximal tubular epithelial cell : extracellular and intracellular interactions and their relevance to the progression of chronic renal disease." Thesis, St George's, University of London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416020.

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31

Wollentz, Gustav. "Att begravas vid gårdagens sida : Återbruket under bronsåldern på Öland samt i Falbygden i relation till det i Mysinge gånggrift." Thesis, Linnéuniversitetet, Institutionen för kulturvetenskaper, KV, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-16819.

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This essay is focused on the re-use during the Bronze Age of the Stone Age passage grave RAÄ 85 in Mysinge, Öland. To increase the knowledge of the phenomena of re-use in general and that which occurred in Mysinge passage grave in particular I’ve looked at other forms of re-use on Öland and the re-use of passage graves in Falbygden. The research has been limited to the Bronze Age. My goal has been to see what this might tell us about the relationship people during the Bronze Age had towards the abstract subject of “non-existence”, in other words death. The research clearly shows that Mysinge passage grave is the oldest grave that were in use during the Bronze Age as a grave, of those known to us, with 1/3 of its dated burials dated to the first half of the Bronze Age and the earliest to early Neolithic. This makes the other three megalithic tombs in the area very interesting since none of them has been excavated. The other forms of re-use of graves that were observed in Öland during the Bronze Age were all later covered by a cairn or a stone packing of some sorts. This most often occurred during the late Bronze Age. However, subsequent burials continued after the construction of the cairn/stone packing throughout the Bronze Age and in most cases into the Iron Age. The cairns/stone packings have a lot in common with the entrance cairn at Mysinge passage grave which also seems to have been constructed during the late Bronze Age. However, while cairns/stone packings mark endings of something they at the same time are monuments of today and are continually being used as a grave (but now according to local burial customs). Entrance cairns on the other hand first and foremost mark endings of something, even though these endings are most likely meant to be remembered. None of the passage graves analysed in this essay in Falbygden indicate the same use of the chamber as Mysinge passage grave. With a few exceptions (Rössberga Rör and Norra Lundby 41) the chamber seems to generally stop being used during Late Neolithic and during the Bronze Age and Iron Age secondary burials in the surrounding mound is instead common. However, it mainly seems to occur during the late Bronze Age and into the Iron Age. Not a single grave in the mound indicate a early Bronze Age date. It is clear that the past often had an important role in the relationship to death and burials during the Bronze Age.

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Alammari, Dalia Muhammed. "Comparative in vitro analyses of the effect of immunoglobulin λ light chain and fatty acid free albumin on proximal tubular epithelial cells-involvement of megalin phosphorylation." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38821.

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Kidney disease is a major challenge for health care systems, and the prevalence is increasing. Proteinuria is a hallmark of progressive renal dysfunction and describes the pathological excess of plasma proteins in urine, mainly albumin. Multiple Myeloma is a cancer of plasma cells that leads to excessive presence of free light chain protein (FLC) in blood. Renal failure due to overproduction of FLC and the associated light chain proteinuria occurs as a result of decreased renal function or as a direct toxic effect on the proximal tubular cells (PTCs) by excessive protein. Proteins are normally reabsorbed by endocytosis via megalin receptor that binds proteins and mediates their uptake. Exceeding the proximal tubular epithelial cells (PTECs) reabsorption capacity might trigger inflammation detrimental to the kidney. In proteinuric nephropathy the cytoplasmic tail of megalin (MegCT) is phosphorylated after interaction between proteins and megalin on the PTECs, which activates signalling cascades that regulate the phosphorylation. An in vitro proteinuric model was established using HK2 cells (a proximal tubular epithelial cell line derived from normal human kidney) treated with high concentrations of essentially fatty acid free human serum albumin (FAF-HSA) or lambda light chain (λ-LC) isolated and purified from the urine of a myeloma patient, to induce cellular damage. The potential pathogenic role for FAF-HSA and λ-LC on HK2 cells was examined. Also, renal toxicity that comes from the intracellular signalling through phosphorylation of MegCT was addressed by utilising antibodies directed against specific phosphorylation site (PPPSP) of the intracellular portion of megalin in HK2 cells stimulated with different concentrations of FAF-HSA and λ-LC, so-called pre-stimulated HK2. In vitro analyses showed (i) a detrimental effect of FAF-HSA and λ-LC on viability of HK2, (ii) phosphorylation of the cytoplasmic tail of megalin in pre-stimulated HK2 cells. (iii) Production of inflammatory cytokines and H2O2 generation, activation of autophagy process and increase in several kidney biomarkers/ injury mediators, which are involved in different pathways in response to protein overload. All these reasons are likely to contribute to direct PTECs injury and kidney failure in patients. Potentially these mechanisms may be attractive for drug development to benefit patients with kidney failure and help to inhibit the progression of proteinuric nephropathy and as such may save lives.

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Komuraiah, Myakala. "Proliferation Signal Inhibitor associated proteinuria in a renal transplant recipient: Dysfunction of proximal tubular epithelial cells is a result of decreased cubilinand/or megalin expression? : Proliferation Signal Inhibitor associated Proteinuria." Thesis, University of Skövde, School of Life Sciences, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-3885.

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Background The proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (ERL) are the potent immunosuppressive drugs using in organ transplantation and has been used successfully in renal transplant recipients (RTX) as well. PSIs are the key factors to overcome the allograft rejections after successful organ transplantation since the immune system starts to react against the graft. SRL and ERL prevents the action of immune system b inhibits the proliferation of T- and B-cells by inhibiting the intracellular signaling of interleukin-2. The presence of excess amount of serum proteins including albumin in the urine is considered as proteinuria, which reflects the loss of kidney function. The occurrence of proteinuria can be the result of abnormal glomerular filtration and/or impaired tubular endocytic function of renal proximal tubular epithelial cells (PTECs). Megalin and cubulin are two scavenger receptors present on epical surface of PTECs and involved in reabsorption of proteins after glomerular ultrafiltration process in the kidney. Proteinuria appears too high in renal transplanted patients during ongoing treatment with PSIs.

Aim Our study aimed to investigate and correlate the expression level of megalin and cubilin and albumin uptake in PTEC of renal transplanted patients before and after conversion to PSI.

Methods To retrieve the maximal expression of our interest molecules in renal PTECs, we optimized antigen retrieval (AR) method and primary antibody dilution for each molecule separately. An optimization experiment was performed on 3 different normal patients renal biopsies were used. Later, human renal biopsy specimens originated from 4 different renal transplanted patients were used in this study. From all the 4 patients biopsy specimens were taken before and ongoing administration of PSIs (SRL, ERL). The expression of megalin, cubilin and albumin uptake in PTEC of renal transplant patients was determined by immunohistochemical staining.

Results Based on the optimization experiments, we selected the AR method and primary antibody dilution for the expression of megalin, cubilin and albumin uptake. In 4 renal transplanted patients following administration of PSIs results in patients 1, 2, 3 expression of megalin, cubilin and albumin uptake during ongoing PSI treatment was not comparable or even more intense than before PSIs introduction. The expression of megalin, cubilin and albumin uptake was reduced in patient 4 during ongoing PSI treatment.

Conclusion Our findings suggest that the renal transplant patient 4 developed proteinuria during PSI medication. The expression of megalin, cubilin and albumin uptake was markedly decreased during ongoing PSI treatment in patient 4. We concluded that there is a direct link between PSI medication and tubular dysfunction, which might cause proteinuria

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34

Phan, Thanh-Hien. "Simulation and Experimental Characterization of the Scintillation Detector for IGOSat." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCC048.

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Cette thèse décrit les travaux effectués pour le développement du détecteur à scintillation du nanosatellite IGOSat. Sur la base des exigences du projet, un concept de détecteur a été validé, concept qui doit également être validé à la fois par la simulation et par l’expérience.IGOSat est un projet de satellite universitaire visant à développer un nanosatellite contenant une charge utile, basée sur un scintillateur, capable de mesurer le fond radiatif dans les zones aurorales et l’Anomalie de l’Atlantique Sud (ASA) en orbite terrestre basse. Le satellite dispose aussi d'une charge utile GPS bi-fréquence permettant de mesurer le contenu électronique total (TEC) de l'ionosphère. Ces deux charges utiles sont hébergées sur une plateforme 3U CubeSat qui sera lancée sur une orbite polaire à une altitude d’environ 650 km.La charge utile du scintillateur comprend un détecteur composé d'un cristal scintillant inorganique entouré de cinq scintillateurs organiques. Le scintillateur inorganique choisi est un cristal de CeBr3, sensible à la fois aux photons gamma et aux électrons. Les cinq scintillateurs plastiques EJ-200, qui sont principalement sensibles aux électrons, ont été choisis pour permettre de distinguer les deux types de particules. En d'autres termes, nous pouvons dire qu'une particule est un photon gamma lorsqu'elle n'interagit que dans le cristal de CeBr3, alors qu'il s'agit d'un électron si au moins une interaction est survenue dans un des scintillateurs plastique.Une simulation Monte-Carlo a été utilisée pour étudier la capacité de détection de ce détecteur. Une matrice de réponse a été élaborée pour la simulation des rayons gamma, qui peut être utilisée pour estimer le spectre en énergie des photons gamma en orbite terrestre basse.Un banc d'essai expérimental a été mis en place pour mesurer le spectre de rayonnement de sources radioactives. Ces mesures servent non seulement à valider le résultat de la simulation, mais également à en déduire la résolution en énergie du détecteur et une méthode d’étalonnage correspondante.Une comparaison entre les simulations de Monte-Carlo et les mesures expérimentales est également fournie dans cette thèse.Sur la base des travaux décrits ci-dessus, la thèse est constituée de 6 chapitres énumérés ci-dessous:- Le chapitre 1 est l'introduction au projet et une revue des études sur le fond radiatif en orbite terrestre basse, ainsi que les activités de développement CubeSat.- Le chapitre 2 décrit la configuration su satellite IGOSat, qui est développé pour remplir les exigences de fonctionnement des charges utiles.- Le chapitre 3 décrit le concept du détecteur à scintillation, son système électronique de lecture et le concept opérationnel de la charge utile.- Le chapitre 4 explique les processus physiques d’interaction d'une particule dans les matériaux à scintillation, la simulation de Monte-Carlo et la matrice de réponse du détecteur IGOSat.- Le chapitre 5 fournit les résultats des mesures expérimentales, issues des bancs de tests spécifiques mis en place. Les comparaisons entre simulation et expérience sont également décrites à la fin de ce chapitre.Le chapitre 6 est la conclusion de ce travail
This dissertation describes the work that has been done for the development of the scintillation detector of the IGOSat nanosatellite. Based on the requirements of the project, a concept of the detector has been proposed which required the validation by both simulations and experiments.IGOSat is a university satellite project aimed at developing a nanosatellite containing a scintillator payload that can measure the radiative background in the aurora zones and the South Atlantic Anomaly (SAA) on Low-Earth Orbit. Beside that, the satellite has a GPS Dual-Frequency Payload for measuring the Total Electronics Content (TEC) in the ionosphere. These two payloads are hosted on a 3U CubeSat platform that will be launched on a polar orbit at an altitude of about 650 km.The scintillator payload included a detector which is composed of an inorganic scintillation crystal and five surrounding organic scintillators. The chosen inorganic scintillator is Cerium Bromide (CeBr3), which is sensitive to both gamma-ray photons and electrons. The five surrounding EJ-200 plastic scintillators, which are mainly sensitive to the electrons, are chosen to discriminate the two types of particles. In other words we can say a particle is a gamma-ray photon when it interacts only in the CeBr3 crystal, while it is an electron if at least one interaction happened in a plastic scintillator.Monte-Carlo simulations have been used to investigate the detection ability of this detector. A response matrix has been made for the gamma-ray simulation, which can be used to estimate the original energy spectrum of the Low-Earth Orbit gamma-ray photons.An experimental test bench has been set up for measuring the detected spectrum of radioactive sources. These measurements are not only used to validate the simulation results, but also to determine the energy resolution of the detector, and a calibration method for it.A comparison between the Monte-Carlo simulations and the experimental measurements is also provided in this dissertation.Based on the topics described above, the dissertation has 6 chapters as listed below:- Chapter 1 is the introduction to the project and a review of the studies on Low-Earth Orbit radiative background, as well as description on the CubeSat development activities.- Chapter 2 describes the IGOSat satellite configuration on the platform, which is developed to support the payload based on their requirements.- Chapter 3 describes the concept of the scintillation detector, its electronics readout system and the operational concept of the payload.- Chapter 4 explains the physical processes of a particle in the scintillation materials, the Monte-Carlo simulations and the response matrix of the IGOSat detector.- Chapter 5 provides the experimental measurement results, based on each test bench that has been set up. The comparisons between simulation and experiment are also described at the end of this chapter.Chapter 6 is the conclusion of the work

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Mania, Foteini. "Contextualizing Atrocity : The Ottoman Greeks' Suffering through the Athenian Newspapers Estia and Empros, May 1919-December 1922." Thesis, Uppsala universitet, Historiska institutionen, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-411093.

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The present thesis offers an innovative perspective analysing the perception of Turkish atrocities against the Ottoman Greek communities during the temporal period May 1919-December 1922 through the Athenian newspapers Estia and Empros, which were committed to the ubiquitous Greek irredentist vision of the Megali Idea. Delving into theories which emphasize on the political nature of nationalism, on national mobilisation and on the exploitation of mass communication by the elite, this thesis attempts to elaborate on the inclusion of the Ottoman Greeks into an expanded Greek nation-state, based on the principle of self-determination. Hence, from the Greek Press' perspective, the presented Turkish atrocities against a part of the Greek nation and potential subjects of a broadened Greek state had been contextualized on the basis of Greek nationalism. The study shows that, despite the widespread and divided Greek communities in the Ottoman Empire/Turkey, Estia and Empros were declaring that their common denominator had been their Greek self-determination and the fact that all these communities were viewing the Greek state and the Greek army as their guarantors for their safety. Adding to the agents of Hellenism also the Ecumenical Patriarchate, Estia and Empros were highlighting the crucial role of these agents towards the endangered Ottoman Greek communities. Thus, the presentation of the respective information in the newspapers was leaning on this theoretical schema.

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Fornander, Elin. "Consuming and communicating identities : Dietary diversity and interaction in Middle Neolithic Sweden." Doctoral thesis, Stockholms universitet, Institutionen för arkeologi och antikens kultur, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-62020.

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Isotope analyses on human and faunal skeletal remains from different Swedish Neolithic archaeological contexts are here applied as a means to reconstruct dietary strategies and mobility patterns. The chronological emphasis is on the Middle Neolithic period, and radiocarbon dating constitutes another central focus. The results reveal a food cultural diversity throughout the period in question, where dietary differences in part correspond to, but also transcend, the traditionally defined archaeological cultures in the Swedish Early to Middle Neolithic. Further, these differences, and the apparent continued utilisation of marine resources in several regions and cultural contexts, can only in part be explained by chronology or availability of resources depending on geographic location. Thus, the sometimes suggested sharp economic shift towards an agricultural way of life at the onset of the Neolithic is refuted. Taking the potential of isotope analyses a step further, aspects of Neolithic social relations and identities are discussed, partly from a food cultural perspective embarking from the obtained results. Relations between people and places, as well as to the past, are discussed. The apparent tenacity in the dietary strategies observed is understood in terms of their rootedness in the practices and social memory of the Neolithic societies in question. Food cultural practices are further argued to have given rise to different notions of identity, some of which can be related to the different archaeological cultures, although these cultures are not to be perceived as bounded entities or the sole basis of self-conceptualisation. Some of these identities have been focused around the dietary strategies of everyday life, whereas others emanate from practices, e.g. of ritualised character, whose dietary importance has been more marginal. Isotope analyses, when combined with other archaeological indices, have the potential to elucidate both these food cultural aspects.
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Submitted. Paper 5: In press. Paper 6: Accepted.

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Wade, Richard Peter. "A systematics for interpreting past structures with possible cosmic references in Sub-Saharan Africa." Diss., Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-05052009-174557/.

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Kordová, Ema. "Megalitická architektura Menorky v rámci talayotské kultury." Master's thesis, 2011. http://www.nusl.cz/ntk/nusl-298872.

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Talayotic architecture arose on The Balearic Islands at the end of 2. millenium as syntesis of local megalitic culture of Bronze Age and cultural influence from central Mediterraen Sea, mainly from Sardinia and Corsica. The core of talayotic buildings was a naveta and megalithic tombs, whose using were abandoned just at the beginning of Iron Age. The talayotic architecture was developing on proper way in the manner of the insular cultures of occidental Mediterraen Sea until the Fenicians arrived ,in the same time the construction of talayots had declined. On the other hand the santuaries and taulas had reached their full using. Approximately in the 6 century in postalayotic period megalitic culture disapeared definitely. Last talayotic site were destroyed during Roman colonization.

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Zavřelová, Barbora. "Keltové a jejich vliv na moderní evropské kultury." Master's thesis, 2015. http://www.nusl.cz/ntk/nusl-353165.

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The diploma thesis Celts and their influence on modern European cultures engages in Celtic nations, describes their history and presents remainders of Celtic culture in modern cultures. The thesis is focused on the influence of the Celts on the French region of Brittany and the Czech Republic. It mainly describes the heritage of the Celtic culture in the contemporary society in the form of Druidism, feasts, perception of nature and other traditions. It aims to create a complex image of the Celtic civilization. The second objective of the thesis is to confirm or refute the original connection of the modern Celtic cultural elements on a historical culture of the Celts. It achieves these aims on the basis of analysis, synthesis and subsequent comparison of obtained information about historical and contemporary Celts. The diploma thesis comes to the conclusion that all studied cultural elements have a real historical basis, but most of them, in their modern form, are created artificially. Nevertheless this fact does not detract from the importance of the cultural heritage of the Celts. KEYWORDS Celts, Brittany, the Czech Republic, megaliths, druids, feasts, traditions, cultural heritage of Celts

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Gomes, Joana dos Santos Peixoto. "Expression of megalin in the central nervous system." Master's thesis, 2017. http://hdl.handle.net/1822/54834.

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Dissertação de mestrado em Bioquímica Aplicada
The incidence of neurodegenerative diseases is increasing today, so there is an increasing interest and need to better understand the mechanisms involved. Transthyretin (TTR) is a protein that has several physiological functions, being highly involved in the homeostasis of the nervous system. Changes in TTR expression levels are associated with several neurodegenerative pathologies. In addition, TTR plays a crucial role in the preservation and survival of neurons since its internalization through the action of megalin, activates several signalling mechanisms. Megalin has been extensively studied over the years; changes in the levels of this protein are also associated with neurodegenerative pathologies, thus functioning as a biomarker. Furthermore, TTR is regulated by heat shock factor 1 (HSF-1). HSF-1 acts in response to thermal shock, as well as to environmental stress (including ROS presence) and in pathological conditions such as protein misfolding, thus being associated with neuronal stress conditions. Thus, one of the aims of this work was to produce an antibody specific for soluble non membranar megalin and to characterize it so that one could quantify the levels of megalin in mice samples. The anti-megalin antibody was characterized by immunohistochemistry (IHC), by enzymelinked immunosorbent assays (ELISA) and Western blot; it was used to study megalin expression in the brain of wild-type (WT), TTR-knockout (TTR-KO) and HSF-1-deficient mice (with and without TTR), with and without an oxidative diet. The results show that megalin is expressed in the brain, especially in the retrosplenial area of the cortex. Additionally, WT animals present higher levels of megalin in this region than other stains, namely TTR-KOs and HSF-1-deficients. Furthermore, untreated animals presented higher levels of megalin expression in comparison to treated animals. The results suggest that i) the oxidative diet has an impact on the expression of megalin and ii) TTR influences the expression of megalin. The implication of megalin expression and its modulation in the retrosplenial area of the cortex deserves further investigation.
A incidência das doenças neurodegenerativas é cada vez mais elevada nos dias de hoje, pelo que cada vez é maior o interesse e a necessidade de se compreender melhor os mecanismos envolventes. A transtirretina (TTR) é uma proteína que apresenta diversas funções fisiológicas, estando altamente envolvida na homeostasia do sistema nervoso. Alterações nos níveis de expressão de TTR estão associadas a diversas patologias neurodegenerativas. Além disso, a TTR desempenha um papel crucial na preservação e sobrevivência dos neurônios uma vez que a sua internalização pela ação da megalina, ativa mecanismos de sinalização. A megalina tem sido um alvo de estudo uma vez que alterações nos níveis desta estão também associadas a patologias neurodegenerativas, funcionando por isso como um biomarcador. A TTR é também regulada pelo fator de transcrição de choque térmico 1 (HSF-1). HSF-1 para além de atuar na resposta ao choque térmico, atua como resposta ao stress (como na presença de espécies reativas de oxigénio) e em condições patológicas como no mau-enrolamento de proteínas, estando associado a condições de stress neuronal. Desta forma, um dos objetivos deste trabalho foi produzir um anticorpo específico para a megalina solúvel e caraterizá-lo para que com ele se pudesse analisar os níveis de megalina em amostras de ratinho. A caraterização do anticorpo foi feita por estudos de imunohistoquímica, por ensaios de imunoabsorção enzimática e Western blot. A expressão da megalina foi estuda em grupos de animais com TTR (WT), sem TTR (TTR-KO) e animais com ausência de HSF-1 (com e sem TTR), na presença e ausência de uma dieta oxidativa. Os resultados obtidos mostram que a megalina é expressa no cérebro nomeadamente na área retrosplenial do córtex. Além disso, verificou-se que os animais WT apresentam níveis mais altos de megalina nesta zona do córtex do que as outras estirpes, nomeadamente em animais com ausência de TTR e com falta de HSF-1 (quer com e sem TTR). Verificou-se também que os animais sujeitos à dieta apresentam menor expressão de megalina que os animais sem sujeitos à dieta. Os resultados sugerem que: i) a dieta oxidativa tem impacto na expressão de megalina e ii) a TTR influencia a expressão de megalina. Estudos sobre a interferência da expressão de megalina e a sua modulação na área retrosplenial do córtex devem ser desenvolvidos.

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Nogueira, Renata Filipa Barbosa Soares. "The role of megalin in the neuroprotective properties of Transthyretin." Dissertação, 2014. https://repositorio-aberto.up.pt/handle/10216/92247.

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Nogueira, Renata Filipa Barbosa Soares. "The role of megalin in the neuroprotective properties of Transthyretin." Master's thesis, 2014. https://repositorio-aberto.up.pt/handle/10216/92247.

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Burmeister, Regina [Verfasser]. "Untersuchungen zur Rolle des Endozytoserezeptors Megalin in der zellulären Aufnahme von Steroidcarrierproteinen / von Regina Burmeister." 2003. http://d-nb.info/967999014/34.

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Li, Jian-Lin, and 李建霖. "Lovastatin increases RhoA level and megalin-mediated endocytosis of serum-derived bovine serum albumin in cultured cortical astrocytes." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/05015140727777750017.

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碩士
國立陽明大學
神經科學研究所
101
Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, reduce both cholesterol and isoprenoid synthesis and have been used to treat patients with diseases associated with hypercholesterolemia. Moreover, previous studies have demonstrated their therapeutical effectiveness in some, but not all, patients suffering Alzheimer’s disease. Previous studies from this laboratory have demonstrated that lovastain increases cellular levels of RhoA and serum-derived bovine serum albumin (BSA) in astrocytes, but not in neurons. This study thus aims to explore the mechanism(s) by which lovastatin modulates RhoA expression and albumin endocytosis in astrocytes. In this study, we found that lovastatin increases the cellular content of serum-derived bovine serum albumin (BSA) in cortical astrocytes. Immunoprecipitation and immunocytochemical studies reveal that lovastatin treatment increases the interaction of BSA with megalin, an endocytic receptor for multiple ligands including albumin. In addition, lovastatin increase the internalization of biotin-labeled surface proteins and the cellular content of BSA after BSA challenge. Interestingly, elevated level of RhoA was observed in astrocytes treated with lovastatin for 24 hr when the cellular BSA content was not affected. The effect of lovastatin on BSA, in fact, became apparent at a later time point, 48 hr. As noted, it was also found that lovastatin caused accumulation of ubiquitin-labeled proteins in a temporal profile similar to the increase in RhoA content. Moreover, mevalonate prevented lovastatin from increasing both RhoA and ubiquitin-labeled proteins. However, lovastatin didn’t decrease chymotrypsin-like proteasome activity. Together, results from this work demonstrate the involvement of ubiquitin and megalin in elevated levels of RhoA and internalized BSA, respectively, in astrocytes exposed to lovasatin.

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Biagioni, Siria. "Long-term dynamics of tropical rainforests, climate, fire, human impact and land-use change in Indonesia." Doctoral thesis, 2015. http://hdl.handle.net/11858/00-1735-0000-0028-8748-3.

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Dissertations / Theses on the topic 'Megality'

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