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Förster resonance energy transfer confirms the bacterial-induced conformational transition in highly-branched poly(N-isopropyl acrylamide with vancomycin end groups on binding to Staphylococcus aureusSarker, P., Swindells, K., Douglas, C.W.I., MacNeil, S., Rimmer, Stephen, Swanson, L. 13 June 2014 (has links)
No / We describe a series of experiments designed to investigate the conformational transition that highly-branched polymers with ligands undergo when interacting with bacteria, a process that may provide a new sensing mechanism for bacterial detection. Fluorescent highly-branched poly(N-isopropyl acrylamide)s (HB-PNIPAM) were prepared by sequential self-condensing radical copolymerizations, using anthrylmethyl methacrylate (AMMA) and fluorescein-O-acrylate (FA) as fluorescent comonomers and 4-vinylbenzyl pyrrole carbodithioate as a branch forming monomer. Differences in reactivity necessitated to first copolymerize AMMA then react with FA in a separate sequential monomer feed step. Modifications of the chain ends produced vancomycin-functional derivatives (HB-PNIPAM-Van). The AMMA and FA labels allow probing of the conformational behaviour of the polymers in solution via Forster resonance energy transfer experiments. It was shown that interaction of this polymer's end groups with Staphylococcus aureus induced a macromolecular collapse. The data thus provide conclusive evidence for a conformational transition that is driven by binding to a bacterium.
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Conformations of single polymer chains on surfaces / non-equilibrium, equilibrium and manipulationEcker, Christof 20 July 2005 (has links)
In dieser Arbeit wurden auf Substratoberflächen adsorbierte Polymermoleküle mit Rasterkraftmikroskopie (RKM) untersucht. Dabei war die Form der Moleküle (Konformation) von besonderem Interesse. Sie ist von zentralerer Bedeutung in der Polymerphysik und wird üblicherweise in Lösung und mit Streumethoden untersucht. Polymerkonformationen auf Oberflächen sind heutzutage noch wenig untersucht. Üblicherweise wird das Verhalten nach dem so genannten Wormlike-Chain Modell angenommen. Es basiert auf der Annahme, dass die Kettenbiegung nur aus thermischen Fluktuationen resultiert, so dass sich die Kettenform durch statistische Mechanik beschreiben lässt. Es wurden für verschiedene Modellsystem einzelne Moleküle hochaufgelöst abgebildet und die Konformation aus den Bildern bestimmt. Es hat sich gezeigt, dass die idealisierte Vorstellung des Wormlike-Chain Modells tatsächlich nur für wenige der untersuchten Systeme erfüllt ist. Abweichende Konformationen sind oft auffallend regelmäßig: entweder sinusartig mäandrierte oder spiralförmig gedrehte. Beide Charakteristika lassen sich aus dem Prozess der Adsorption erklären, was zeigt, dass die Moleküle auf dem Substrat immobil sind, so dass eine thermische Relaxation der Konformation verhindert ist. Konformtionen lassen sich mit RKM nicht nur beobachten, sondern auch gezielt verändern (Nanomanipulation). Für dendronisierte Polymere konnte so gezeigt werden, dass es einen glasartigen Zustand für das einzelne Molekül gibt. In diesem Zustand verhält sich das Molekül nicht mehr wie eine bewegliche Kette, sondern formstabil, ähnlich einem makroskopischen festen Körper. / In this work single polymer molecules adsorbed onto substrate surfaces were investigated by scanning force microscopy (SFM). The focus was on the shape (conformation) of the molecules, which is of central importance in polymer physics. It is commonly investigated in solutions and with scattering methods. Conformations on surfaces are only little investigated thus far. Often a behavior according to the so-called worm-like chain model is assumed. It is based on the assumption that chain bending results entirely from thermal fluctuations so that the overall chain shape can be described by statistical mechanics. For several model systems single molecules were imaged and the conformation was determined from the images. It was found that the idealistic wormlike chain behavior is only valid for a few systems. Deviations are often remarkable regular: either sine-like undulated or spiral wound. Both characteristics can be explained from the process of adsorption, indicating that molecules are immobile on the substrate so that thermal relaxation is inhibited. Conformations can not only be imaged using the SFM, but also changed in a defined way (nanomanipulation). Manipulation experiments with dendronized polymers the existence of a glassy state for the single polymer. In this state the molecule no longer behaves as a flexible chain but remains its shape, similar to a macroscopic solid body.
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Islamist, Antisemit eller Humanist? : En kvalitativ textanalys av två kvällstidningars gestaltning av Mehmet Kaplan mellan den 14-18 april 2016Stray, Liselott January 2016 (has links)
Studiens syfte är att utforska hur Aftonbladet och Expressen gestaltade bostadsministern Mehmet Kaplan från den 14 april 2016 fram till 18 april 2016 då han avgick som minister. Syftet är också att se hur förändring av gestaltningen under dessa dagar ter sig. Slutligen kommer studien att jämföra de två tidningarna för att se om och hur de skiljer sig åt i sin gestaltning. De frågeställningar som studien utifrån detta syfte ämnar behandla är följande. - Hur gestaltas Mehmet Kaplan mellan den 14- 18 april? - Hur förändras gestaltningen under dessa dagar? - Hur skiljer sig de olika tidningarnas gestaltning åt? Metoden som tillämpas är en kvalitativ textanalys, som i praktiken innebär att ställa frågor till texten. Frågorna har byggts upp utifrån Strömbäcks och Entmans teori och definition av gestaltningens fyra grundläggande egenskaper. Vidare har resonemanget om den journalistiska dramaturgins grundläggande element och språkliga redskap inom sensationsjournalistik, använts som stöd i utformandet av analysfrågorna. Analysmaterialet är hämtat från Retriever, begränsat på redaktionellt digitalt publicerade artiklar mellan datumen 14 - 18 april. Urvalet resulterade i 23 aktiva analysenheter för studien varav är 11 från Aftonbladet och 12 från Expressen. Studiens resultat är att Mehmet Kaplan gestaltades från Aftonbladet och Expressens håll som otillgänglig, antisemitisk och islamistisk. Samtidigt vidhöll hans politiska kollegor utåt att Kaplan var humanist, demokrat och antirasist. Rapporteringen under de fyra aktuella dagarna var i olika skeenden. En upptrappning, följas av tystnad och sedan explodera i en enorm rapportering, fram tills att Kaplan avgått. Rapporteringen mellan de tidningarna skiljde sig åt, det förklaras i studien på grund av dess olika politiska ideologier. / The study aims to explore how Aftonbladet and Expressen portrayed Housing Minister Mehmet Kaplan from April 142016 until April 18, 2016 when he resigned as minister. The aim is also to see how the change in depiction during these days seems. Finally, the study will compare the two newspapers to see if and how they differ in their interpretation. The issues that the study on the basis that purpose intend to treat is the following. -How portrayed Mehmet Kaplan from 14-18 April? -How to change the design on these days? -How do the various newspaper design at? The method used is a qualitative text analysis, whichin practice means to put questions to the text. The questions have been built up on the basis Strömbäcks and Entmans theory and definition of Gestalt Association four basic characteristics. Furthermore, the reasoning of the journalistic dramaturgy basic elements and linguistic tools in sensational journalism, used to support the design of analytical questions. The analysis material is taken from the Retriever, bounded on digital editorial articles published between the dates of April 14 to 18. The selection resulted in 23 active units of analysis for the study of which 11 are from Aftonbladet and 12 from Expressen. The study's resultis that Mehmet Kaplan figure was from Aftonbladet and Expressen hold as unavailable, anti-Semitic and Islamist. At the sametime maintained his political colleagues out that Kaplan was a humanist, democrat and anti-racist. Reporting during the four days in question were in various stages. An escalation,followed by silence and then explode in a huge reporting, until the Kaplanresigned. The reporting of the newspapers differed, it is explained in the study because of its different political ideologies.
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Caractérisation structurale de la molécule HLA-DORaby, Nicola 02 1900 (has links)
Les molécules classiques du CMH de classe II présentent des peptides antigéniques aux lymphocytes T CD4+. Cette présentation est régulée par deux molécules non classiques : HLA-DM catalyse la relâche de CLIP et le chargement de peptides et HLA-DO module l’activité de DM. Une expression insuffisante en cellules d’insectes empêche les expériences de cristallisation de DO, probablement en raison de sa conformation, rendant DO instable et inapte à sortir du réticulum endoplasmique (RE). DM corrige la conformation de DO et permet sa sortie du RE. Aussi, par ses ponts disulfures uniques, DM adopte une conformation stable et peut sortir du RE sans lier d’autre molécule. Nous avons tenté de corriger la conformation de DO en introduisant des cystéines pour établir des ponts homologues à ceux de DM. La conformation de DO ne fut pas corrigée. Par ailleurs, nous avons augmenté l’expression de DO en introduisant une séquence partielle de Kozak. Nous avons aussi étudié l’effet de DM sur l’expression de DO. DM a favorisé l’expression de DO, probablement en diminuant sa dégradation.
Chaque chaîne du dimère DMαβ est impliquée dans l’oxydation de sa chaîne partenaire. La conformation non-optimale de DO pourrait traduire une incapacité des chaînes α ou β à favoriser l’oxydation de sa partenaire; DM corrigerait ce problème. Notre analyse d’immunobuvardage de type Western a toutefois démontré que DM ne modifie pas l’état d’oxydation de DOα et DOβ.
Finalement, nous avons étudié l’interaction DO-DM. L’acide aminé DOαE41 est impliqué dans cette liaison. Certains des acides aminés entre α80 et α84 pourraient être impliqués. Nous avons muté des acides aminés de cette région de DOα. Les résidus testés ne semblent pas impliqués dans la liaison DO-DM.
L’obtention de la structure tridimensionnelle de DO et la caractérisation de son état oxydatif et de sa liaison à DM permettront de mieux comprendre son rôle. / Classical MHC class II molecules present antigenic peptides to CD4+ T cells. This presentation is regulated by two non-classical molecules: HLA-DM catalyzes CLIP release and peptide loading and HLA-DO mediates the DM activity. An insufficient expression in insect cells did not allow DO crystal production experiments, probably because of its conformation, rendering DO unstable and unable to leave the endoplasmic reticulum (ER). DM corrects the conformation of DO and allows its egress from the ER. Also, because of its unique disulfide bonds, DM has a stable conformation and can egress from the ER without binding another molecule. We tried to correct the conformation of DO by introducing cysteines to create disulfide bonds homologous to those of DM. However, its conformation was not corrected. Also, we increased DO expression by inserting a partial Kozak sequence. We also studied the effect of DM on DO expression. DM favoured DO expression, probably by reducing its degradation.
Each chain of the DMαβ dimer plays a role in the oxidation of its partner chain. The non-optimal conformation of DO might result from an incapacity of its α and β chains to direct each other’s oxidation; DM would correct this problem. Our Western blot analysis showed, however, that DM does not modify the oxidation state of DOα and DOβ.
Finally, we studied the DO-DM interaction. The DOαE41 amino acid is involved in this interaction, as some of the α80 to α84 might be. We mutated amino acids in this region of DO. Tested amino acids did not seem involved in DO-DM binding.
The tridimensional structure of DO and the characterization of its oxidative state and its DM binding will allow a better understanding of its function.
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Mécanismes moléculaires d’activation du récepteur A des peptides natriurétiquesParat, Marie 08 1900 (has links)
Le récepteur A des peptides natriurétiques (NPRA) fait partie de la famille des guanylates cyclases membranaires. L’activation du NPRA par ses agonistes naturels, ANP et BNP, induit une production de GMPc qui est responsable de leur rôle dans l’homéostasie cardiovasculaire, l’inhibition de l’hypertrophie et de la fibrose cardiaques et la régulation de la lipolyse. Le NPRA est un homodimère non covalent composé d’un domaine extracellulaire de liaison du ligand (ECD), d’un unique domaine transmembranaire (TM), d’un domaine d’homologie aux kinases et d’un domaine guanylate cyclase. Bien que le NPRA ait un rôle physiologique important, les mécanismes moléculaires régissant son processus d’activation restent inconnus. Nous avons donc analysé les premières étapes du processus d’activation du NPRA. Nous avons d'abord étudié le rôle de la dimérisation des ECD dans l’activation du récepteur. Nous avons utilisé les techniques de liaison de radioligand, de FRET et de modélisation moléculaire, pour caractériser la liaison à l’ECD des agonistes naturels, d’un superagoniste et d’un antagoniste. L’ANP se lie à un dimère d’ECD préformé et la dimérisation spontanée est l’étape limitante du processus de liaison. De plus, comme le démontrent nos études de FRET, tous les peptides, incluant l’antagoniste, stabilisent le récepteur sous sa forme dimérique. Cependant, l’antagoniste A71915 stabilise le dimère d’ECD dans une conformation différente de celle induite par l’ANP. La dimérisation du NPRA semble donc nécessaire, mais non suffisante à l’activation du récepteur. L’état d’activation du NPRA dépend plutôt de l’orientation des sous unités dans le dimère. Nous avons ensuite étudié le mécanisme moléculaire de transduction du signal à travers la membrane. Plusieurs études ont suggéré que l’activation du NPRA implique un changement de conformation du domaine juxtamembranaire (JM). Cependant, les études de cristallographie de l’ECD soluble de NPRA n’ont pas permis de documenter la structure du JM et le changement de conformation impliqué dans la transduction du signal reste inconnu. Pour analyser ce changement de conformation, nous avons d’abord séquentiellement substitué les neuf acides aminés du JM par une cystéine. En étudiant la capacité des mutants à former des dimères covalents de façon constitutive ou induite par l’ANP, nous avons pu évaluer la proximité relative des résidus du JM, avant et après activation du NPRA. Ces résultats ont démontré la proximité élevée de certains résidus spécifiques et sont en contradiction avec les données cristallographiques. Nous avons également démontré que le domaine intracellulaire impose une contrainte conformationnelle au JM à l’état de base, qui est levée après liaison de l’ANP. En introduisant de 1 à 5 alanines dans l’hélice-α transmembranaire, nous avons montré qu’une rotation des TM de 40° induit une activation constitutive du NPRA. Le signal d’activation pourrait donc être transmis à travers la membrane par un mécanisme de rotation des TM. En utilisant nos données expérimentales, nous avons généré le premier modèle moléculaire illustrant la conformation active du NPRA, où les domaines JM et TM sont représentés. Dans son ensemble, cette étude apporte une meilleure compréhension des mécanismes moléculaires régissant les premières étapes du processus complexe d’activation du NPRA. / Natriuretic peptide receptor-A (NPRA) is a member of the particulate guanylate cyclase family. NPRA activation by natural agonists, ANP and BNP, leads to cGMP production, which is responsible for their role in cardiovascular homeostasis, cardiac hypertrophy and fibrosis inhibition and lipolysis regulation. NPRA is a non covalent dimer composed of an extracellular domain (ECD) with a ligand binding site, a single transmembrane region (TM), a kinase homology domain, and a guanylyl cyclase domain. Although NPRA plays an important physiologic role, molecular mecanisms driving its activation process are yet unknown. We thus analysed the first steps of NPRA’s activation process. First, we studied the role of ECD dimerization in receptor activation and determined the sequential steps of this dimerization process. We used radioligand binding, FRET and molecular modeling to characterize the interaction of ECD with natural agonists, a superagonist and an antagonist. ANP binds to preformed ECD dimers and spontaneous dimerization is the rate-limiting step of the ligand binding process. Furthermore, like demonstrated with fluorescence homoquenching, all the studied peptides, including A71915 antagonist, stabilize a dimeric form of the receptor. However, A71915 stabilizes the ECD dimer in a conformation distinct from those induced by ANP. Thus, ECD dimerization is necessary but not sufficient for NPRA activation. The activation state of NPRA seems to depend on the orientation of the receptor subunits within the dimer. Then, we tried to identify the molecular mechanism of signal transduction through the plasma membrane. Previous studies have shown that activation of NPRA involves a conformational change of the juxtamembrane domain (JM). However, crystallographic study of the soluble ECD of NPRA has failed to document JM structure, and the conformational change involved in transmembrane signal transduction is still unknown. To analyse this conformational change, we first sequentially substituted nine amino acids of JM by a cysteine residue. By studying the mutant’s capacity to form ANP-induced or constitutive covalent disulfide dimers, we evaluated the relative proximity of JM residues, before and after NPRA activation. These results demonstrate a high proximity of specific JM residues and are in disagreement with crystallography data. We also demonstrated that intracellular domain imposes a conformational constraint on JM at basal state, which becomes relaxed upon ANP binding. We finally confirmed, with a full-length receptor, that A71915 stabilizes NPRA in a dimeric form where JM are in a conformation distinct from the basal state. By introducing 1 to 5 alanine residues in the transmembrane α-helix, we showed that a TM rotation of 40° leads to constitutive NPRA activation. Activation signal could thus be transmitted through the membrane by a TM rotation mechanism. We finally studied the role of the TM in NPRA dimerization. By using the ToxR system, we demonstrated that the last JM residues are required to stabilize the TM dimer. Using these experimental data, we generated the first molecular model illustrating the active conformation of NPRA, where JM and TM are depicted. In summary, this study allows a better understanding of molecular mecanisms driving the first steps of NPRA’s complex activation process.
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Identification and characterization of low pH-triggered conformational changes in the herpes simplex virus glycoprotein BDollery, Stephen 02 March 2011 (has links)
Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to 6.0. The antigenic structure of gB functional region I that is critical for fusion is specifically altered by mildly acidic pH both in vitro and during entry into host cells. Point mutations within gB functional region 1 that block membrane fusion still allow conformational changes in region 1. This suggests that specific hydrophobic residues are essential for fusion domain insertion into the host cell membrane but not conformational change. The detected conformational changes were reversible, similar to other class III fusion glycoproteins. Exposure to mildly acidic pH directly triggered the fusion function of HSV glycoproteins and caused gB, but not other glycoproteins, to become more hydrophobic. The oligomeric conformation of gB is altered at a similar pH range. In addition, several approaches were used to monitor gB throughout glycoprotein synthesis and maturation. It is shown that gB may cotranslationally fold and oligomerize as it is synthesized on the ribosome. As gB matures it then alters conformation and/or binding partner to form antigenically distinct populations of gB within the cell and virion. I conclude that intracellular low pH induces changes in gB conformation that, together with additional triggers such as receptor-binding, are essential for virion-cell fusion during herpesviral entry by endocytosis.
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Rôles des interactions entre loci dans l'organisation spatiale fonctionnelle et l'évolution des génomes de mammifèresWürtele, Hugo January 2006 (has links)
Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.
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[en] STABILITY OF VISCOELASTIC FORWARD ROLL COATING FLOWS / [pt] ESTABILIDADE DO ESCOAMENTO VISCOELÁSTICO EM PROCESSO DE REVESTIMENTO POR ROTAÇÃO DIRETAGLADYS AUGUSTA ZEVALLOS NALVARTE 09 February 2004 (has links)
[pt] O processo de revestimento por rotação é caracterizado pelo uso de cilindros girantes para controlar a espessura e aplicar uma fina camada de líquido em um substrato em movimento. A não ser a baixas velocidades dos cilindros, o escoamento bi-dimensional na região de formação dos filmes sobre cada cilindro é instável e o padrão observado experimentalmente consiste em um escoamento tri-dimensional
e periódico na direção transversal ao substrato. Esta instabilidade pode limitar a velocidade máxima do processo se a camada líquida depositada sobre o substrato tem que ser uniforme. Para líquidos Newtonianos, a estabilidade deste escoamento é determinada pela competição de forças viscosas e capilares: a instabilidade ocorre acima de um número de capilaridade máximo. Apesar da maioria dos
líquidos utilizados em processos de revestimento serem não Newtonianos, as análises disponíveis deste escoamento se limitam a estudos de líquidos Newtonianos. O comportamento não Newtoniano do líquido pode alterar completamente a natureza do escoamento perto da superfície livre; quando pequenas quantidades de polímeros flexíveis de alto peso molecular estão presentes, a instabilidade na direção transversal ocorre a velocidades muito mais baixas, quando comparado ao caso Newtoniano. Os mecanismos responsáveis pela instabilidade a baixas velocidades ainda não são completamente compreendidos. Este escoamento viscoelástico com superfície livre é analisado neste trabalho através de
duas equações constitutivas diferenciais, o modelo de Oldroyld-B e o modelo de FENE-P. As equações de conservação de massa, quantidade de movimentos acopladas com os modelos constitutivos, e as equações não-lineares de mapeamento que transformam o problema de superfície livre em um problema de valor de contorno foram resolvidas pelo método de elementos finitos DEVSS-G/SUPG. O sistema de equações
algébricas não linear foi resolvido pelo método de Newton com continuação por pseudo-comprimento de arco. Os resultados mostram como o campo de tensão muda com o aumento do número de Weissenberg (elasticidade do líquido), levando a formação de uma camada limite de tensão elástica na superfície livre e tensões elásticas compressivas na direção transversal, que podem explicar o aparecimento da instabilidade a baixas velocidades. Este trabalho também apresenta a formulação de estabilidade linear para escoamentos viscoelásticos com superfícies livres. O modelo dá origem a um problema de auto-valor generalizado, que foi resolvido pelo método de GMRES (ARPACK). Os auto-valores dominantes da matriz Jacobiana indicam a estabilidade do escoamento. Esta formulação foi testada em três escoamentos
distintos: escoamento em uma cavidade de tampa móvel, piscina de líquido estática e um escoamento de Couette (simples de cisalhamento). / [en] Roll coating is distinguished by the use of one or more gaps between rotating cylinders to meter and apply a liquid layer to a substrate. Except at low speed, the film splitting flow that occurs in forward roll coating is three-dimensional and results in more or less regular stripes in the machine direction. This instability can limit the speed of the process if a smooth film is required as a final product. For Newtonian liquids, the stability of the film-split flow is determined by the competition of capillary forces and viscous forces: the onset of meniscus nonuniformity is market by a critical value of the capillary number. Although most of the liquids coated industrially are polymeric solutions and dispersions, that are not Newtonian, most of previous theoretical analyses of film splitting flows dealt only with Newtonian liquids. Non-Newtonian behavior can drastically change the nature of the flow near the free surface; when minute amounts of flexible polymer are present, the onset of the three-dimensional instability occurs at much lower speeds than in the
Newtonian case. the mechanisms responsible for the early onset of this flow instability is not well understood. This free surface coating flow is analyzed here with differential constitutive models, the Oldroyld-B and the FENE-P equations. The continuity, momentum equations coupled with the constitutive models, and the non-linear mapping equations that transform the free boundary problem into a fixed boundary problem are solved by Newton s method with pseudo-arc-length continuation. The results show how the stress field changes with Weisenberg number, leading to the formation of an elastic boundary layer near the free surface and compressive elastic stresses in the crss-flow direction that may explain the onset of the ribbing instability at the smaller Capillary numbers when viscoelastic liquids are used. This work also presents the formulation for linear stanility analysis of viscoelastic free surface flows. The model leads to a generalized eigenproblem that is solved here using the Arnoldi s method with the software (ARPACK). The leading eigenvalues of the Jacobian Matrix indicate the stability of the flow. The formulation is tested in three different flows: lid-driven cavity, static liquid pool and a couette flow.
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Estimação de parâmetros genéticos para características de crescimento, reprodução e categóricas em uma população de bovinos de corte compostos (Bos taurus x Box indicus) sob abordagem bayesiana e modelos lineares generalizados mistos / Estimation of genetic parameters for traits of growth, reproduction and categorical in a population of composite beef cattle (Bos taurus x Bos indicus) in Bayesian approach and generalized linear mixed modelsOliveira, Tiago Almeida de 30 August 2012 (has links)
Os objetivos deste trabalho foram avaliar diferentes modelos de seleção com base nos efeitos aleatórios maternos considerados para características de crescimento e perímetro escrotal, estimar parâmetros genéticos para pesos do nascimento aos 12 meses (pesos ao nascer, a desmama e aos 12 meses de idade); perímetro escrotal aos 12 meses e correlações genéticas entre as características para bovinos compostos Montana Tropical, em análises uni, bicaracterísticas. Estimar parâmetros genéticos para as características categóricas de musculosidade, precocidade e conformação aos 12 meses em modelos uni e bicaracterísticas utilizando diferentes metodologias para análise (modelos mistos, modelos thresholds bayesianos e modelos lineares generalizados mistos) e compará-los. Nas análises feitas para as características de crescimento e perímetro escrotal os efeitos maternos influenciaram os pesos do nascimento aos 12 meses de idade. As estimativas de herdabilidade direta obtidas das análises bicaracterísticas foram superiores àquelas obtidas das análises unicaracterísticas e as estimativas pela análise bicaracterística para as herdabilidades foram 0,27 para peso ao nascer; 0,18 para peso à desmama; 0,20 para peso aos 12 meses; e 0,19 para perímetro escrotal aos 12 meses. As correlações genéticas estimadas entre pesos obtidos em idades jovens com peso ao ano foram moderadas a baixas (< 0,60). A correlação genética obtida entre perímetro escrotal e características de crescimento foram 0,04, e <0,01 com peso a desmama indicando baixa associação entre as características e de 0,38 com peso aos 12 meses o que pode ao longo do tempo gerar animais mais pesados aos 12 meses. A seleção com base em características de crescimento em qualquer idade pode promover ganhos genéticos moderados no peso corporal de animais do composto Montana Tropical. É importante considerar nas análises os pesos prévios à seleção para estimar parâmetros genéticos para pesos após a seleção. Para as características morfológicas as estimativas de herdabilidade foram de baixas a moderadas e houve diferença entre o modelo linear e o de limiar e o modelo linear generalizado misto, na obtenção de estimativas de herdabilidades e correlações genéticas, de características categóricas morfológicas multinomiais. As estimativas dos parâmetros genéticos obtidas por modelo de limiar foram superiores aos demais métodos avaliados, com valores de 0,42; 0,37 e 0,25 para musculosidade, precocidade e conformação aos 12 meses, e as correlações genéticas estimadas em conjunto com peso a desmama para musculosidade, precocidade e conformação aos 12 meses foram 0,89; 0,22 e 0,83 respectivamente. Os escores visuais de conformação, precocidade e musculatura aos 12 meses podem responder rapidamente à seleção individual. / The objectives this study were to evaluate different models of selection based on maternal random effects considered for growth traits and scrotal circumference; to estimate genetic parameters for weights from birth to 12 months (birth weight, weaning and 12 months old), scrotal circumference at 12 months and to estimate genetic correlations between traits for cattle composite Montana Tropical, by univariate and two-trait analysis. To estimate genetic parameters for categorical traits of muscling, precocity and conformation at 12 months in uni-and two-trait models using different methodologies for analysis (mixed models, Bayesian models thresholds and generalized linear mixed models) and compare them. In the analysis made for growth traits and scrotal circumference, maternal effects influenced the weights from birth to 12 months of age. Direct heritability estimates obtained from two-trait analyzes were higher than those obtained using univariate models, and the estimates of heritability for the two traits analysis were 0.27 for birth weight, 0.18 for weaning weight, 0.20 for weight at 12 months , and 0.19 for scrotal circumference at 12 months. The genetic correlation obtained between weights at young ages and yearling weight were moderate to low ( < 0.60). Genetic correlation obtained between scrotal circumference and growth traits were 0.04, and < 0.01 with weaning weight indicating a low correlation between the traits and 0.38 from weight at 12 months which may over time provide heavier animals at 12 months. Selection based on growth traits at any age can provide moderate genetic gains in body weight of animals of the composite Montana Tropical. It is important to consider in the analysis to selecting the prior weights to estimate genetic parameters for weights after selection. For the morphological traits, heritability estimates were low to moderate and there was a difference between the threshold and linear model and generalized linear mixed model, for estimates of heritability and genetic correlations of morphological multinomial categorical traits. Estimates of genetic parameters by the threshold model were higher than the other methods evaluated, with values of 0.42, 0.37 and 0.25 for muscling, precocity, and conformation at 12 months, and the genetic correlations estimated in with weaning weight for muscling, precocity and conformation at 12 months were 0.89, 0.22 and 0.83 respectively. The visual scores of conformation, precocity and muscling at 12 months can respond quickly to individual selection.
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Decoding the Epigenome of Neuronal Networks in Health and DiseaseJain, Gaurav 15 October 2018 (has links)
No description available.
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