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Functional effects of the MICA-129 dimorphism on NK cell activity and association with the outcome of hematopoietic stem cell transplantationIsernhagen, Antje 01 April 2014 (has links)
No description available.
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Caracterização por microscopia de força atômica de camadas lipídicas imobilizadas em superfíciesOliveira, Cristian Schweitzer de January 2007 (has links)
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-graduação em Física. / Made available in DSpace on 2012-10-23T03:51:31Z (GMT). No. of bitstreams: 0Bitstream added on 2013-07-16T20:02:35Z : No. of bitstreams: 1
243265.pdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Neste trabalho foram preparados filmes lipídicos de DMPC (1,2-dimiristilfosfatidilcolina) em substratos de mica, silício hidrofóbico e silício hidrofílico, com a finalidade de sintetizar estruturas que mimetizem membranas biológicas. As técnicas empregadas na preparação dos filmes foram fusão de vesículas lipídicas, espalhamento de solução orgânica por centrifugação (#spin-coating#), e automontagem por evaporação de solvente (#casting#), sendo que somente a última foi realizada nos três tipos de substratos. Os solventes utilizados para dissolver os lipídios foram isopropanol e clorofórmio. A caracterização estrutural e morfológica dos filmes foi realizada por análise topográfica de imagens obtidas por microscopia de força atômica (AFM). As amostras com e sem hidratação por vapor de água foram investigadas em ambiente controlado por fluxo constante de gás nitrogênio (ex-situ). Também foram realizadas imagens com hidratação total dos filmes por completa imersão das amostras em solução fisiológica (in-situ). Superfícies com degraus da ordem de 5 nm, característicos de bicamadas lipídicas, foram observadas principalmente em substratos hidrofílicos, com a formação ou não de estruturas multilamelares.
In this work it has been prepared lipid films of DMPC 1,2-dimyristoyl-snglycero-3-phosphocholine) were prepared on mica, hydrophobic silicon, and hydrophilic silicon substrates, with the purpose of fabricating structures that mimic the biological membranes. The techniques used for the preparation of the lipid layers were vesicle fusion, spin-coating and casting. The solvents used for the dissolution of the lipids were isopropanol and chloroform. The morphologic characterization of the
deposits was performed by acquiring atomic force microscopy (AFM) images of the surfaces. The images of samples with and without hydration in water vapor were taken in a chamber with controlled atmosphere and constant flux of nitrogen gas. This measuring condition is named ex-situ. In-situ experiments were also carried out by imaging the lipid films immersed in a physiologic solution. As a general result, surfaces with step heights of 5 nm, typical of lipid bilayers, were observed on samples prepared on hydrophilic substrates, being observed also the formation of multilayer structures.
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Potassium-argon age determinations on biotites and amphiboles, Bethlehem Copper Property, B.C.Dirom, Gavin Ewan January 1965 (has links)
Potassium-argon apparent ages obtained on biotite and amphibole from various phases of the Guichon Creek batholith present on the Bethlehem Copper property are reported and their geological significances are discussed in this thesis. Although the individual phases were found to be essentially indistinguishable in terms of their potassium-argon apparent ages, the results obtained indicated with considerable certainty that these phases were emplaced during an interval not greater than 10 m.y. centered around 200 m.y. ago and that no major metamorphic event has occurred in this area since this time. It is also believed that this average apparent age of 200 m.y. may represent a better approximation to the maximum age of the Triassic-Jurassic boundary than that previously reported in the literature.
The potassium and argon analytical techniques employed are described briefly, and the analytical precision and accuracy obtained are discussed. Descriptions of the samples collected and samples analyzed are given as an appendix. / Science, Faculty of / Earth, Ocean and Atmospheric Sciences, Department of / Graduate
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Reconhecimento de padr?es pela casca de jabuticaba (Myrciaria jabuticaba (Vell) Berg (jabuticaba sabar?)) e de refrigerante do guaran? (Paullinia cupana) usando infravermelho pr?ximo e quimiometriaPedrosa, Nascilaine Osanilha Costa January 2012 (has links)
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Previous issue date: 2013-02-21 / Na primeira parte do trabalho foi proposto o reconhecimento de padr?es de jabuticaba (Myrciaria jabuticaba (vell) berg (jabuticaba sabar?)) pela avalia??o dos elementos boro, nitrog?nio, magn?sio, f?sforo, pot?ssio, c?lcio, mangan?s, ferro, cobre e zinco na casca empregando-se as t?cnicas de titula??o, espectroscopia de absor??o at?mica e molecular. Os dados obtidos pelas an?lises dos elementos foram dispostos em matriz 7 x 10, sendo sete amostras referente ?s sete cidades analisadas (S?o Jo?o da Chapada, Gouveia, Guinda, Couto de Magalh?es, Po?os de Caldas, Belo Horizonte e Serro) e dez vari?veis correspondendo ?s concentra??es dos elementos determinadas em mgk-1. O reconhecimento de padr?es foi feito empregando-se a An?lise das Componentes Principais e An?lise Hier?rquica por Agrupamentos. Desta forma foi poss?vel identificar pela An?lise das Componentes Principais os grupos formados pela semelhan?a, baseados nos pesos correspondentes ?s influ?ncias das vari?veis. Cerca de cinco componentes principais acumularam 97,47% da vari?ncia total dos dados sendo que a componente principal de n?mero um (01) acumulou cerca de 38,21% da vari?ncia e a componente principal de n?mero tr?s (03) cerca de 16,13% da vari?ncia. Os grupos formados na An?lise das Componentes Principais foram confirmados na An?lise Hier?rquica por Agrupamento, sendo formado quatro grupos, denotando a maior semelhan?a nas amostras de Gouveia e Couto Magalh?es. Na segunda etapa do estudo teve por finalidade classificar e caracterizar quimicamente o refrigerante do tipo guaran?, em diferentes estados brasileiros, foram analisadas suas concentra??es de metais e diferentes compostos atrav?s da absor??o at?mica e espectroscopia de infravermelho respectivamente. Para classificar os refrigerantes dos diversos locais, foi utilizada nos resultados obtidos das an?lises a an?lise explorat?ria baseada em An?lise das Componentes Principais (PCA). A melhor separa??o se deu com as vari?ncias acumuladas na CP2 e CP4, onde as amostras de refrigerantes zero formaram um grupo e amostras coletadas no RJ outro grupo e as amostras de Shim tamb?m formaram um grupo diferente dos demais. Como conclus?o pode-se salientar que os m?todos de reconhecimento de padr?es empregados neste trabalho apresentaram resultados que possibilitam a diferencia??o das amostras em locais distintos. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Qu?mica, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2012. / ABSTRACT
In the first part of the proposed pattern recognition Jabuticaba (Myrciaria jabuticaba (vell) berg (jabuticaba sabar?)) for the evaluation of the elements boron, nitrogen, magnesium, phosphorus, potassium, calcium, manganese, iron, copper and zinc on the shell employing the techniques of titration, atomic absorption spectroscopy and molecular. The data obtained by analysis of the elements were arranged in a matrix 10 x 7, seven samples analyzed referring to the seven cities (S?o Jo?o da Chapada, Gouveia, Guinda, Couto de Magalhaes, Wells Caldas, Belo Horizonte and Serro) and ten variables corresponding concentrations of certain elements in MGK-1. Pattern recognition was done using the Analysis of Principal Components Analysis for Hierarchical Groups. This made it possible to identify the Principal Component Analysis groups formed by similarity, based on the weights corresponding to the influences of variables. About five main components accumulated 97.47% of the total variance of the data being the main component of a number (01) accumulated approximately 38.21% of the variance and the principal component number three (03) approximately 16.13% variance. The groups formed in the Principal Component Analysis were confirmed in the Hierarchic Cluster Analysis, formed four groups, indicating a greater similarity in the samples of Gouveia and Couto Magalh?es. In the second stage of the study aimed to classify and characterize chemically the guarana soda type, in different Brazilian states were analyzed in relation to different concentrations of metals and compounds by atomic absorption and infrared spectroscopy respectively. To sort the drinks at different locations, we used the results of the analyzes exploratory analysis based on Principal Component Analysis (PCA). The best separation was accumulated at variance with the CP2 and CP4, where samples of soft drinks have formed a group and zero samples collected at the RJ and the other group samples Shim also formed a different group of demais. Como conclusion can be noted that methods of pattern recognition in this work presented results that allow the differentiation of samples at different locations.
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Estudo fitoqu?mico e ensaios biol?gicos de Pseudobrickellia brasiliensis (Spreng.) R.M. King & H. Rob (ASTERACEAE)Amorim, M?rcia Letice Lozer de January 2012 (has links)
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Previous issue date: 2013-02-21 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Capes) / Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG) / Pseudobrickellia brasiliensis (Spreng.) R.M. King & H. Rob (Asteraceae) ? uma esp?cie de Asteraceae conhecida popularmente como arnica-do-mato, arnica-do-campo ou simplesmente arnica. E utilizada na medicina popular contra machucados e dores no corpo, porem a literatura carece de informa??es cient?ficas, encontrando-se apenas um artigo sobre estudo fitoqu?mico. Com o objetivo de contribuir para o estudo de P. brasiliensis, esse trabalho relata o estudo fitoqu?mico e ensaios biol?gicos que investigaram a atividade antiinflamat?ria e antioxidante de extratos das folhas da planta. As folhas foram coletadas na cidade de Diamantina, no Campus JK da UFVJM. Uma parte das folhas ainda frescas foi utilizada para extra??o de ?leo essencial, e outra parte do material vegetal foi seco e submetido ? extra??o com solventes de diferentes polaridades ? hexano, acetato de etila, etanol e ?gua ? obtendo-se quatro extratos. Os constituintes do ?leo essencial foram identificados por CG-EM, encontrando-se 25 terpenos, sendo os majorit?rios os monoterpenos ?-tujeno (17,21%) e ?-pineno (32,61%). Os extratos foram submetidos a t?cnicas cromatogr?ficas cl?ssicas e suas fra??es foram analisadas por CG-EM, IV, RMN de 1H e 13C, identificando-se o diterpeno acido cauren?ico; os triterpenos ?-amirina, acetato de ?-amirina, ?-amirina, acetato de ?-amirina, lupeol, acetato de lupeol, pseudotaraxasterol, taraxasterol; e possivelmente uma lactona sesquiterp?nica. Em ensaios de triagem fitoqu?mica realizados com os extratos, foram detectadas as classes de metab?litos secund?rios: cumarinas, flavon?ides, taninos condens?veis, antocianinas, antraquinonas, saponinas, compostos redutores e triterpenos/ester?ides. A esp?cie apresentou um potencial antiinflamat?rio, uma vez que os extratos aquoso e etan?lico modularam a produ??o da citocina IFN-?, envolvida diretamente na inicializa??o e amplifica??o da resposta inflamat?ria. Os extratos apresentaram baixo potencial antioxidante, nas concentra??es avaliadas e nos ensaios de atividade de retirada de radical, e de poder de redu??o do ?on met?lico Fe3+, apesar dos extratos aquoso e etan?lico possu?rem compostos fen?licos. Sendo assim, o presente trabalho foi uma contribui??o para o estudo fitoqu?mico e de atividades biol?gicas desta planta. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Qu?mica, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2012. / ABSTRACT
Pseudobrickellia brasiliensis (Spreng.) R.M. King & H. Rob (Asteraceae) is a species of Asteraceae popularly known as arnica-do-mato, arnica-do-campo or arnica simply. It is used in folk medicine against wounds and body aches, but there lack of scientific literature and found only one article on phytochemical study. Aiming to contribute to the study of P. brasiliensis, this work reports the phytochemical and biological tests that investigated the anti-inflammatory and antioxidant activity of extracts of the leaves. The leaves were collected in the city of Diamantina, in the Campus JK of UFVJM. Part of the leaves still fresh, were used for extraction of essential oil, and another part of the plant material was dried and subjected to extraction with solvents of different polarities - hexane, ethyl acetate, ethanol and water - resulting in four extracts. The constituents of the essential oil were identified by GC-MS and was found 25 terpenes, of which the major was the monoterpenes ?-thujene (17.21%) and ?-pinene (32.61%). The extracts were subjected to classical chromatographic techniques and their fractions were analyzed by GC-MS, IR, 1H and 13C NMR, identifying the diterpene kaurenoic acid, triterpenes ?-amyrin acetate, ?-amyrin, ?-amyrin, ?-amyrin acetate, lupeol acetate, lupeol, pseudotaraxasterol, taraxasterol, and possibly a sesquiterpene lactone. In tests conducted with phytochemical extracts were detected classes of secondary metabolites, coumarins, flavonoids, condensed tannins, anthocyanins, anthraquinones, saponins, reducing compounds and triterpenes/steroids. The species had an anti-inflammatory potential, because the aqueous and ethanol extracts modulate the production of the cytokine IFN-?, directly involved in the startup and amplification of the inflammatory response. The extracts showed lower antioxidant potential, and concentrations evaluated in the trials of withdrawal of radical activity, and power reduction of Fe3+ metal ion, despite the aqueous and ethanol extracts possess phenolic compounds. Thus, the present work was a contribution to the study phytochemical and biological activities of this plant.
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Petrologia do Plut?o Bom Jardim de Goi?s (PBJG): implica??o na evolu??o neoproterozoica da Prov?ncia TocantinsCoimbra, Keyla Thayrinne Oliveira 25 August 2015 (has links)
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Previous issue date: 2015-08-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O plut?o Bom Jardim de Goi?s (PBJG) ? um corpo de geometria semi-circular, situado na por??o central da Prov?ncia Tocantins, intrusivo em ortognaisses e metassupracrustais do Arco Magm?tico Aren?polis. Estas metasupracrustais apresentam um bandamento / xistosidade de ?ngulo baixo a moderado, definido por micas, andalusita, silimanita e cordierita, caracterizando um metamorfismo na f?cies anfibolito. Tal estrutura ? truncada pela coloca??o das rochas do PBJG. O car?ter abrupto dos contatos e a aus?ncia de estruturas d?cteis demonstram que a intrus?o se deu em crosta relativamente fria. Em termos petrogr?ficos, o plut?o comp?e-se de monzodioritos, tonalitos e granodioritos, seguindo a trajet?ria evolutiva c?lcio-alcalina de pot?ssio baixo a intermedi?rio. As rochas do PBJG possuem hornblenda e biotita como fases m?ficas principais, al?m da ocorr?ncia subordinada de clinopirox?nio, titanita, ep?doto e opacos. Diques tardios de leucogranito cont?m apenas biotita como mineral acess?rio relevante. Uma data??o U-Pb em zirc?o do monzodiorito forneceu uma idade de 550?12 Ma (MSWD = 1,06). Dados litogeoqu?micos e de qu?mica mineral sugerem que as rochas em foco s?o c?lcio-alcalinas, tendo evolu?do por cristaliza??o fracionada de minerais c?lcicos e ferro-magnesianos, sob condi??es de alta fugacidade de oxig?nio. Utilizando o geoterm?metro do par anfib?lio-plagiocl?sio e o geobar?metro de Al em anfib?lio, foram determinadas temperaturas e press?es em torno de 692-791 ?C e 2,4 e 5,0 kbar para a intrus?o do PBJG, o que ? corroborado por associa??es metam?rficas pr?-existentes nas encaixantes. As caracter?sticas geol?gicas, geoqu?micas e a geocronologia do PBJG demonstram sua natureza p?s-tect?nica ou p?s-colisional, com coloca??o em crosta j? soerguida e relativamente fria, ao final da orog?nese brasiliana nesta por??o da Prov?ncia Tocantins. / The Bom Jardim de Goi?s Pluton (PBJG) is a semi-circular body, located in the central portion of the Tocantins Province, intrusive into orthogneisses and metassupracrustals of the Aren?polis Magmatic Arc. These metasupracrustals present a low to moderate dipping banding or schistosity, have a low to moderate angle of banding / foliation, defined by mica, andalusite and sillimanite and cordierite, which characterize an amphibolite facies metamorphism. This structure is crosscut by the emplacement of the PBJG rocks. The abrupt nature of the contacts and the absence of ductile structures indicate that the intrusion took place in a relatively cold crust. Under petrographic grounds, the pluton consists mainly of monzodiorites, tonalite and granodiorite, following the low to medium-K calk-alkaline alkaline trend. Rocks of the PBJG have hornblende and biotite as the main mafic phases, besides subordinate clinopyroxene, titanite, epidote and opaque. Late dikes of leucogranite contain only mineral biotite as relevant accessory mineral. One U-Pb zircon dating of a monzodiorite yielded an age of 550 ? 12 Ma (MSWD = 1.06). Whole-rock and mineral chemistry suggest that the studied rocks are calc-alkaline, having evolved by fractional crystallization of Ca- and Fe-Mg minerals under high oxygen fugacity. Using the amphibole-plagioclase geothermometer and the Al-in amphibole geobarometer, we calculate temperatures and pressures of, respectively, 692-791 ?C e 2.4-5.0 kbar for the intrusion of the PBJG, which is corroborated by previous metamorphic assemblages in the country rocks. The geological, geochemical and geochronological features of PBJG demonstrate their post-tectonic or post-collisional nature, with emplacement into an already uplifted and relatively cool crust at the end of brasiliano orogeny in this portion of the Tocantins Province.
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A Study of Heavy Minerals Found in a Unique Carbonate Assemblage from the Mt. Mica Pegmatite, Oxford County, MaineJohnson, Christopher M. 01 May 2013 (has links)
This thesis focuses on heavy mineral species found in a unique carbonate assemblage in the Mt. Mica pegmatite in order to determine the conditions of their formation and their mineral paragenesis as well as to gain insight on the origin of this very unusual carbonate-rich unit.
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Contribui????es da psicodin??mica do trabalho para a concep????o de par??metros na mensura????o do risco operacionalChagas, Paulo Cesar 24 October 2017 (has links)
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Previous issue date: 2017-10-24 / This research seeks a work experience, a work and its implications in the relationship with the
work organization, thus involving the work. Thus, the general objective of this study is to
identify in the theory of psychodynamics of work contributions to the development of a
company that works. Under a structural logic of the objectives, this study was built under
three cores and methodologically, was structured as a qualitative approach, of an applied
nature and exploratory objectives that were sustained in grounded bibliographic procedures in
the theory of psychodynamics of work to establish a dialogue with the theory of the
operational risk that has its pillars without managerialism to support the pragmatism of the
mechanistic thinking patrons where as demands for result have in the subject that works the
agent of human failure, since the conceptual horizon of operational risk understands the
worker as a variable in the process productive that it must scrupulously respect as
prescriptions and it is this invisibility of the working person that is demonstrated from a study
empirically developed in this study. And in judging that for the theory it leaves the fasting of
work and fasting, adjustment, repair, arranging and that the subjectivity of the working
subject is in constant pressure between a form and form of doing that, in the research, to
imagine a space for incorporate Inventory on Labor and Risks of Adoption - ITRA in the
operational risk mitigation environment. And this is a contribution of the study when
opportunizing for the management of operational risk access to a base of information about
the perception that works in its work context and evaluation that are the occurrences of
experience, pleasure, suffering and damages caused by this work is based on the ITRA that
will allow managers of operational risk as the dimensions of the interrelationship between
work and the process of subjectivation in the work context. And this know-how, the
engagement of the body, a mobilization of intelligence, a capacity for reflection, interpretation
and reacting to different situations without work environment are contributions of work by
psychodynamics of work that also benefit from another contribution of this study by enabling
the subject who works in the search for psychodynamics of work research in the process of
adjusting the operational procedures. / Esta tese busca na teoria da psicodin??mica do trabalho e do risco operacional um espa??o
comum para pensar a sa??de, o trabalho e suas implica????es na rela????o com a organiza????o do
trabalho, envolvendo, desta forma, o trabalhar. Assim, o objetivo geral deste estudo ??
identificar na teoria da psicodin??mica do trabalho contribui????es para o desenvolvimento de
par??metros de mensura????o do risco operacional, que focalize a pessoa que trabalha. Sob uma
l??gica estrutural dos objetivos espec??ficos, este estudo foi constru??do sob tr??s n??cleos e
metodologicamente foi estruturado como de abordagem qualitativa, de natureza aplicada e
objetivos explorat??rios, os quais foram sustentados em procedimentos bibliogr??ficos,
alicer??ados na teoria da psicodin??mica do trabalho para estear um di??logo com a teoria do
risco operacional, que tem seus pilares no gerencialismo para sustentar o aprisionamento aos
padr??es do pensamento mecanicista; onde as exig??ncias pelo resultado tem no sujeito que
trabalha o agente da falha humana, a julgar que o horizonte conceitual do risco operacional
entende o trabalhador como uma vari??vel no processo produtivo que deve respeitar
escrupulosamente as prescri????es. Esta invisibilidade da pessoa que trabalha ?? demonstrada a
partir de um estudo emp??rico apresentado nesta tese o qual evidencia a exposi????o do sujeito
que trabalha a necessidade gerencialista de resultado. E ao julgar que para teoria dejouriana
trabalhar ?? constantemente ajustar, adaptar, reparar, arranjar e que a subjetividade do sujeito
que trabalha est?? em constante press??o entre a forma e a f??rma do fazer que possibilitou, nesta
pesquisa, imaginar um espa??o para incorporar o Invent??rio sobre Trabalho e Riscos de
Adoecimento (ITRA) no ambiente de mitiga????o do risco operacional. Esta ?? uma contribui????o
deste estudo ao oportunizar o acesso para o gerenciamento do risco operacional de uma base
dados de informa????es sobre a percep????o que os trabalhadores t??m de seu contexto de trabalho
e da avalia????o que eles fazem das ocorr??ncias de viv??ncia, de prazer, de sofrimento e de
danos provocados por este trabalho, base esta constru??da a partir do ITRA, que possibilitar??
aos gestores do risco operacional conhecer as dimens??es da inter-rela????o trabalho e processo
de subjetiva????o no pr??prio contexto de trabalho. Este saber-fazer, o engajamento do corpo, a
mobiliza????o da intelig??ncia, a capacidade de refletir, de interpretar e de reagir a diferentes
situa????es no ambiente de trabalho s??o contribui????es ofertadas pela psicodin??mica do trabalho
que tamb??m se beneficia com outra contribui????o deste estudo ao possibilitar que o sujeito que
trabalha possa demandar pesquisa da psicodin??mica do trabalho a partir do processo de
ajustamento dos procedimentos operacionais.
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An??lise do impacto estrutural de polimorfismos de base ??nica n??o-sin??nimos (nsSNPs) presentes no gene da uroguanilina mediante simula????es por din??mica molecular de longa dura????oMarcolino, Antonio Carlos Silveira 29 March 2016 (has links)
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Previous issue date: 2016-03-29 / The guanylate cyclase activator 2B, also known as uroguanylin, is part of the guanylin peptide family, which includes peptides such as guanylin and lymphoguanylin. The guanylin peptides are related to sodium absorption inhibition and water secretion induction. Uroguanylin may be related to various pathologies such as chronic renal failure, congestive heart failure and nephrotic syndrome. Uroguanylin mutations have already been associated with essential hypertension. However, there are no studies on the structural changes in the uroguanylin???s protein that used single nucleotide polymorphisms through the use of molecular dynamics simulations. This study used 16 in silico SNP impact prediction tools to evaluate non synonymous SNPs and to select mutations considered as convergent deleterious, which were further analyzed through long time molecular dynamics simulations of 1 microsecond of duration. The results of the molecular dynamics simulations suggest that all SNPs considered as convergent deleterious suffered some kind of structural change, however, four of these nsSNPs have also undergone flexibility changes, possibly resulting in functional changes. / O ativador guanilato ciclase 2B, tamb??m conhecido como uroguanilina, faz parte da fam??lia de pept??deos da guanilina, a qual inclui pept??deos como a guanilina e a linfoguanilina. Os pept??deos da guanilina est??o ligados ?? inibi????o da absor????o de s??dio e indu????o da secre????o de ??gua. A disfun????o da uroguanilina est?? relacionada ao desenvolvimento de v??rias patologias, como insufici??ncia renal cr??nica, insufici??ncia card??aca congestiva e s??ndrome nefr??tica. Muta????es na uroguanilina tamb??m j?? foram associadas ?? hipertens??o essencial. Entretanto, n??o existem estudos sobre a utiliza????o de simula????es por din??mica molecular para avaliar o impacto estrutural causado por nsSNPs presentes no gene codificador da prote??na uroguanilina. Este estudo utilizou 16 ferramentas in silico de predi????o de impacto de nsSNPs para filtrar nsSNPs convergentes delet??rios para posterior an??lise por simula????es por din??mica molecular de longa dura????o (1 microssegundo de dura????o). Os resultados das simula????es por din??mica molecular sugerem que todos os nsSNPs considerados como convergentes delet??rios sofreram algum tipo de altera????o estrutural, por??m, quatro destes SNPs tamb??m sofreram altera????es de flexibilidade, possivelmente resultando em altera????es funcionais.
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Estudio de la expresión de NKG2D y su ligando MICA en el pulmón como factor de susceptibilidad a la Enfermedad Pulmonar Obstructiva CrónicaSánchez Font, Albert 13 June 2012 (has links)
En la presente Tesis Doctoral, Estudio de la expresión de NKG2D y su ligando MICA en el pulmón como factor de susceptibilidad a la Enfermedad Pulmonar Obstructiva Crónica, se demuestra que los ligandos del receptor NK cell group 2D (NKG2D) no se expresan de forma constitutiva en las células epiteliales bronquiales ni alveolares de sujetos sanos sin exposición al humo del tabaco ni en animales (ratones) no tratados previamente. Utilizando muestras de epitelio pulmonar de ratones expuestos al humo del tabaco y cultivos de células epiteliales expuestos a extracto de humo de tabaco in vitro, demostramos que se induce la expresión de RAET1, ligando de NKG2D, activando citotoxicidad. La expresión de MICA (ligando más potente del receptor NKG2D) tiene traducción funcional al precipitar citotoxicidad mediada por células sobre las células epiteliales pulmonares expuestas al humo del tabaco y se traduce en un aumento de la apoptosis en estas células. La expresión de ligandos de NKG2D es independiente de la expresión de receptor NKG2D en los pacientes afectos de EPOC, demostrando que la expresión del ligando es el factor limitante en la activación de los linfocitos T.
En los modelos animales se establece una relación de causa-efecto entre la expresión aberrante de los ligandos de NKG2D y las alteraciones histológicas típicas del enfisema pulmonar y el bloqueo específico de la acción de MICA mediante la utilización de anticuerpos monoclonales contra su receptor NKG2D permitió prevenir la aparición de la enfermedad evaluada en términos de enfisema pulmonar.
La Tesis incluye estudios de asociación en humanos, estudios de causalidad en modelos animales transgénicos condicionales, y estudios de causalidad in vitro. Los resultados tienen una aplicabilida práctica pues representan una descripción original del biomarcador MICA que, eventualmente, podría inclusive representar una nueva diana terapéutica en el futuro. La publicación de los resultados de la Tesis en la revista de amplio impacto Journal of Clinical Investigation significa que existe una aceptación por pares expertos del ámbito científico especializado en inmunología. / In the present thesis, study of the expression of NKG2D and its ligand MICA in the lung as a factor of susceptibility to chronic obstructive pulmonary disease, demonstrates that receptor NK cell group 2D (NKG2D) ligands are not expressed constitutive form in the bronchial and alveolar epithelial cells of healthy subjects without exposure to cigarette smoke or in animals (mice) not previously treated. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early transcript 1 (RAET1) as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. The expression of MICA (most potent ligand NKG2D receptor) has functional translation to precipitate cytotoxicity mediated by cells on lung epithelial cells exposed to the smoke of tobacco and translates into an increase in apoptosis of cells. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies. Our findings that NKG2D mediated CTL activation after exposure to cigarette smoke, that NKG2D ligand expression caused emphysema in transgenic mice, and that NKG2D ligands were aberrantly expressed in the pulmonary epithelium of both animal models and patients with COPD, which coincided with emphysema development, provide mechanistic insight into COPD pathogenesis. Moreover, we demonstrated that anti-NKG2D blocking antibody abrogated emphysema development in the animal model, which suggests the NKG2D pathway maybe a molecular target for complementary treatment and/or prevention of emphysema.
The thesis includes association studies in humans, studies of causality in conditional transgenic animal models, and causality in vitro studies. The results have a practical aplicabilida since they represent an original description of the MICA biomarker which, eventually, could even represent a new therapeutic target in the future. The publication of the results of the thesis in the journal of broad impact Journal of Clinical Investigation means that there is an acceptance by expert pairs of science specializing in immunology.
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