The nuclear envelope is a highly organised double membrane system that separates the activities of the nuclear and cytoplasmic compartments in eukaryotic systems. The wide range of functions recently associated with the NE and the identification of hundreds of proteins associated with this cellular structure indicates that it is a major signalling node for the cell. Recent work indicates NE functions in signalling innate immune responses to herpesviruses. The viruses, on the other hand, often target or usurp NE functions in different ways. The NE is also a physical barrier that must be overcome for viruses like the herpesviridae that assemble capsids in the nucleus. This thesis addresses two important questions: 1) How do herpesviruses cross the NE after new viral particles are produced in the nucleus? and 2) What is the nuclear envelope role of NET23/STING in the activation of immune factors upon herpesvirus infection? To address the first question, I followed two different approaches. The first used the isolation of microsomes from HSV-1 infected cells to identify possible host factors involved during herpesvirus exit through the NE on the prediction that such proteins would disperse into the ER during infection. I identified a group of vesicle fusion proteins that play a role in this herpesvirus exit through the NE. Depletion of three identified vesicle fusion proteins decreased the growth of HSV-1 in host cells, yielding accumulation of viral particles in the nucleus. The second approach was to follow the fate of nuclear envelope transmembrane proteins (NETs) during HSV-1 infection. To address the question of how NET23/STING is involved in innate immunity I tested the hypothesis that this NET acts as a transport receptor to carry signals through the peripheral channels of the NPC when central channel transport is blocked by pathogens. FRAP was used to quantify the mobility of NET23/STING upon the induction of the innate immune response, finding an increase of the mobility for this protein in the NE. To further elucidate its role within the NE I tested whether some NE-NET23/STING binding partners were being redistributed between the nucleus and cytoplasm during innate immune responses. This revealed two of these binding partners normally redistribute upon innate immune response activation and this is blocked in cells knocked down for NET23/STING. Finally, I confirmed that NET23/STING contributes to chromatin remodelling during infection involving an increase in the H3K9Me3 epigenetic mark. Collectively, these data argue the identification of novel host proteins involved in herpesvirus nuclear egress and the finding of a new role for NET23/STING within the NE.

Eigenmannia virescens is a gymnotiform weakly electric fish which uses a quasi-sinusoidal electric organ discharge (EOD) to sense their environment. EOD frequency (EODF) is individual-specific. In conspecific interactions, each fish perceives the EODF of the conspecific as a periodic amplitude modulation (AM) of their own discharge. When both fish are stationary, the depth of this AM is constant, but it varies when fish are swimming. We hypothesized that AM variations during swimming act as a noise source that could have no effect on, hinder, or enhance EODF identification. To test this, we quantified the jamming avoidance response (JAR) (a natural behaviour wherein fish are required to accurately determine one another’s EODF) in response to stimuli of varying depths of noise. These experiments demonstrated that swimming noise does not impair the ability of E. virescens to identify conspecific EODF, and actually improves its ability to detect the presence of a neighbouring fish.

O principal objetivo desta dissertação é obter um Teorema do Envelope que permita mecanismos não diferenciáveis, preferências arbitrárias e que possa ser aplicado em modelos com múltiplos agentes. Nós alcançamos isto ao expandir a análise de Milgrom e Segal (2002), generalizando seus resultados para espaços de tipos multidimensionais. Dessa forma, continuamos permitindo que a regra de escolha (mecanismo) seja descontínua. Para obter nosso resultado, é necessário o uso do Teorema do Máximo de Berge e, consequentemente, devemos impor compacidade no conjunto de escolha. Inicialmente esta hipótese pode parecer forte, porém argumentamos que em aplicações _e muito improvável termos um conjunto de escolha aberto ou, principalmente, não limitado. Nós também identificamos condições para que a função valor seja absolutamente contínua e mostramos que sua representação integral também é válida para espaços de tipos multidimensionais. Inicialmente propomos uma generalização direta do resultado de Milgrom e Segal (2002), utilizando a hipótese de continuidade absoluta da função de utilidade do agente. Entretanto, esta exigência não possui muito significado econômico e é considerada pouco elegante por parte da literatura. Neste sentido, incorporamos uma hipótese adicional de diferenciabilidade da utilidade em todo o domínio que gera a mesma representação integral e possui uma maior interpretação econômica. Nossos resultados são, em geral, aplicados a modelos com múltiplos agentes, em especial Economia do Setor Público (provisão de bens públicos e taxação ótima) e teoria dos leilões. / The main objective of this dissertation is to obtain an Envelope Theorem that allows non-di erentiable mechanisms, arbitrary preferences, and that can be applied to models with multiple agents. We achieve that by expanding the analysis of Milgrom and Segal (2002) and generalizing their results to multidimensional type spaces. Thus, we continue allowing that the choice rule (mechanism) is discontinuous. For our result, it is necessary to use the Berge's Maximum Theorem and therefore we must impose compactness in the choice set. Initially this assumption may seem strong, but we argue that in applications there is an open or unbounded choice set is very unlikely. We also identify conditions for the value function is absolutely continuous and show that its integral representation is also valid for multidimensional type spaces. Firstly we propose a direct generalization of the Milgrom and Segal (2002)'s result, using the assumption of absolute continuity of the agent's utility function. However, this requirement does not have much economic interpretation and it is considered not very elegant in the literature. In this sense, we incorporate an additional assumption of di erentiability of the utility in all range that generates the same integral representation and it possesses a greater economic interpretation. Our results are generally applied to models with multiple agents, in particular Public Economics (public goods supply and optimal taxation) and auction theory.

MEDEIROS, Melissa Soares. Polimorfismo do RRE e resistência aos antirretrovirais do vírus da imunodeficiência humana e efeito citopático e replicativo in vitro da enfuvirtida no códon 36 do vírus modificado pNL4-3. 2011. 255 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011. / Submitted by denise santos (denise.santos@ufc.br) on 2016-03-28T11:42:34Z No. of bitstreams: 1 2011_tese_msmedeiros.pdf: 18233541 bytes, checksum: 79da766383cb7344f8326013c6aa304c (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2016-03-28T11:45:13Z (GMT) No. of bitstreams: 1 2011_tese_msmedeiros.pdf: 18233541 bytes, checksum: 79da766383cb7344f8326013c6aa304c (MD5) / Made available in DSpace on 2016-03-28T11:45:13Z (GMT). No. of bitstreams: 1 2011_tese_msmedeiros.pdf: 18233541 bytes, checksum: 79da766383cb7344f8326013c6aa304c (MD5) Previous issue date: 2011 / Introduction: Rev Responsive Element (RRE) is a RNA molecule responsible to mRNA from HIV-1 virus nuclear transportation to cytoplasm through RRE-Rev pathway, essential to virus replication. Enfuvirtide resistance mutations are primary located in a perimeter of 10 amino acids of HR1, a corresponded region of RRE. Characterize RRE should provide a new approach for HIV therapy. Objectives: Sequence and characterize RRE from gp41 to evaluate variability and correlate with laboratory parameters in sequences from HIV-1-infected patients, which were receiving regimens including Enfuvirtide, naïve or rescue therapy. Also evaluated mutation G to D at codon 36 in the presence of fusion inhibitor (enfuvirtide). Methods: Sixty-two samples from HIV patients in Ceara/Brazil were collected and Thirty-five RRE sequences and clinical follow-up were analyzed, distributed into three groups: N (naïve therapy), T (treated patients with rescue regimens) and F (rescue regimens containing Enfuvirtide). Sequences obtained were aligned with Los Alamos HIV sequence database by using the HIV BLAST Search. Culture Study was performed using two different pNLA-3 (36D and 36G) with increasing amounts of enfuvirtide. Results: A phylogenetic analyses demonstrated higher prevalence of HIV-1 subtypes B (97.2%). An increased immunology response was observed in CD4 count higher on group T (71.5%) compared with F (2.98%). Group N most common mutations and polymorphisms were Q32L (41.6%), N42S (8.3%), R46K (33.3%), L54M (41.6%); group T: Q32R (8.3%), R46K (25%), L54M (33.3%); and group F: Q32L (18.2%), G36D (9.1%), V38A (9.1%), N42S (27.3%), N42T (9.1%), R46K (27.3%), L54M (45.4%), K77R (54.5%). Three samples demonstrated significant resistance mutations to fusion inhibitors. Analysis of RRE nucleotide primary sites observed mutation 28A in 27.2% and 8.3% on groups F and N respectively, and 27S in 8.3% on group T. There was selective pressure on HR1 region from HIV-1 patients using antiretroviral, independent of enfuvirtide exposure. There was no statistical difference between p24 curves of virus 36D compared with 36G, independent of T20 concentrations (p>0.05). It was observed less syncytial formation in 36D virus, with diminished fusogenic activity besides keeping infectivity. Conclusions: This study defined most prevalent RRE polymorphisms in Ceara/Brazil and suggests highly preserved regions primary sites to Rev connection. Observed a low resistance profile to enfuvirtide in failing regimens with this drug. Selective pressure on HR1 region in failed regimens with out fusion inhibitors was detected. A less syncytial formation in 36D virus with diminished fusogenic activity was detected. / Introdução: Rev Responsive Element (RRE) é uma molécula RNA responsável pelo transporte do mRNA viral do HIV-1 do núcleo para o citoplasma da célula CD4, através da via RRE-Rev, essencial para a replicação viral. As mutações de resistência a Enfuvirtida são primariamente localizadas no perímetro de 10 aminoácidos do HR1, região correspondente no RRE. Caracterizar o RRE poderá fornecer uma nova abordagem terapêutica para a terapia do HIV. Objetivos: Sequenciar e caracterizar o RRE da gp41 para avaliar sua variabilidade e correlação com parâmetros laboratoriais em sequências de pacientes infectados pelo HIV-1 que receberam terapia antirretroviral ou virgens. Em estudo in vitro avaliar a mutação 36D na presença de Enfuvirtida. Metodologia: 62 amostras de pacientes com HIV-1 do Ceará foram coletadas e 35 sequências de RRE foram obtidas e distribuídas em três grupos para fins de análise comparativa: N (virgens de terapia), T (uso de antirretroviral sem inibidor de fusão) e F (uso de antirretroviral associados a Enfuvirtida). Sequências obtidas foram alinhadas com o banco de dados de Los Alamos para HIV usando HIV BLAST Search. Estudo in vitro utilizou dois vírus de laboratório pNLA-3 (36D e 36G) observando citopatogenicidade e proliferação na presença de doses crescentes de Enfuvirtida. Resultados: A análise filogenética demonstrou alta prevalência do HIV-1 subtipo B (97,2%). Observou-se aumento da resposta imunológica no grupo T (71,5%) comparado ao F (2,98%). Mutações mais comuns e polimorfismos do Grupo N foram Q32L (41,6%), N42S (8,3%), R46K (33,3%), L54M (41,6%); no grupo T: Q32R (8,3%), R46K (25%), L54M (33,3%); e no grupo F: Q32L (18,2%), G36D (9,1%), V38A (9,1%), N42S (27,3%), N42T (9,1%), R46K (27,3%), L54M (45,4%), K77R (54,5%). Três amostras demonstraram mutações de resistência significativas para os inibidores de fusão. Análise dos sítios primários de ligação do RRE observou presença de mutação 28A em 27,2% e 8,3% nos grupos F e N respectivamente, e 27S em 8,3% no grupo T. Houve pressão seletiva da região HR1 do HIV-1 de pacientes usando antirretroviral, independente da exposição à Enfuvirtida. Não houve diferença estatística significativa nas curvas de p24 do vírus 36D comparado com 36G, independente de concentrações de T20 (p>0.05). Observou-se menor formação de sincício, com diminuição da capacidade fusogênica, sem impacto na infectividade. Conclusão: O estudo definiu as mutações e polimorfismos mais prevalentes no Ceará, sugerindo alta preservação nas regiões de sítio primário de ligação do Rev-RRE. Evidenciou baixo perfil de resistência a Enfuvirtida em regimes com falha utilizando esta medicação. Detectou-se pressão seletiva no HR1 do HIV-1 de pacientes em uso de Antirretroviral, independente de exposição à Enfuvirtida. Evidenciado in vitro menor formação sincicial no vírus 36D, com diminuição na atividade fusogênica, mantendo infectividade.

O principal objetivo desta dissertação é obter um Teorema do Envelope que permita mecanismos não diferenciáveis, preferências arbitrárias e que possa ser aplicado em modelos com múltiplos agentes. Nós alcançamos isto ao expandir a análise de Milgrom e Segal (2002), generalizando seus resultados para espaços de tipos multidimensionais. Dessa forma, continuamos permitindo que a regra de escolha (mecanismo) seja descontínua. Para obter nosso resultado, é necessário o uso do Teorema do Máximo de Berge e, consequentemente, devemos impor compacidade no conjunto de escolha. Inicialmente esta hipótese pode parecer forte, porém argumentamos que em aplicações _e muito improvável termos um conjunto de escolha aberto ou, principalmente, não limitado. Nós também identificamos condições para que a função valor seja absolutamente contínua e mostramos que sua representação integral também é válida para espaços de tipos multidimensionais. Inicialmente propomos uma generalização direta do resultado de Milgrom e Segal (2002), utilizando a hipótese de continuidade absoluta da função de utilidade do agente. Entretanto, esta exigência não possui muito significado econômico e é considerada pouco elegante por parte da literatura. Neste sentido, incorporamos uma hipótese adicional de diferenciabilidade da utilidade em todo o domínio que gera a mesma representação integral e possui uma maior interpretação econômica. Nossos resultados são, em geral, aplicados a modelos com múltiplos agentes, em especial Economia do Setor Público (provisão de bens públicos e taxação ótima) e teoria dos leilões. / The main objective of this dissertation is to obtain an Envelope Theorem that allows non-di erentiable mechanisms, arbitrary preferences, and that can be applied to models with multiple agents. We achieve that by expanding the analysis of Milgrom and Segal (2002) and generalizing their results to multidimensional type spaces. Thus, we continue allowing that the choice rule (mechanism) is discontinuous. For our result, it is necessary to use the Berge's Maximum Theorem and therefore we must impose compactness in the choice set. Initially this assumption may seem strong, but we argue that in applications there is an open or unbounded choice set is very unlikely. We also identify conditions for the value function is absolutely continuous and show that its integral representation is also valid for multidimensional type spaces. Firstly we propose a direct generalization of the Milgrom and Segal (2002)'s result, using the assumption of absolute continuity of the agent's utility function. However, this requirement does not have much economic interpretation and it is considered not very elegant in the literature. In this sense, we incorporate an additional assumption of di erentiability of the utility in all range that generates the same integral representation and it possesses a greater economic interpretation. Our results are generally applied to models with multiple agents, in particular Public Economics (public goods supply and optimal taxation) and auction theory.

abstract: Natural resource depletion and environmental degradation are the stark realities of the times we live in. As awareness about these issues increases globally, industries and businesses are becoming interested in understanding and minimizing the ecological footprints of their activities. Evaluating the environmental impacts of products and processes has become a key issue, and the first step towards addressing and eventually curbing climate change. Additionally, companies are finding it beneficial and are interested in going beyond compliance using pollution prevention strategies and environmental management systems to improve their environmental performance. Life-cycle Assessment (LCA) is an evaluative method to assess the environmental impacts associated with a products' life-cycle from cradle-to-grave (i.e. from raw material extraction through to material processing, manufacturing, distribution, use, repair and maintenance, and finally, disposal or recycling). This study focuses on evaluating building envelopes on the basis of their life-cycle analysis. In order to facilitate this analysis, a small-scale office building, the University Services Building (USB), with a built-up area of 148,101 ft2 situated on ASU campus in Tempe, Arizona was studied. The building's exterior envelope is the highlight of this study. The current exterior envelope is made of tilt-up concrete construction, a type of construction in which the concrete elements are constructed horizontally and tilted up, after they are cured, using cranes and are braced until other structural elements are secured. This building envelope is compared to five other building envelope systems (i.e. concrete block, insulated concrete form, cast-in-place concrete, steel studs and curtain wall constructions) evaluating them on the basis of least environmental impact. The research methodology involved developing energy models, simulating them and generating changes in energy consumption due to the above mentioned envelope types. Energy consumption data, along with various other details, such as building floor area, areas of walls, columns, beams etc. and their material types were imported into Life-Cycle Assessment software called ATHENA impact estimator for buildings. Using this four-stepped LCA methodology, the results showed that the Steel Stud envelope performed the best and less environmental impact compared to other envelope types. This research methodology can be applied to other building typologies. / Dissertation/Thesis / M.S. Architecture 2013

Central star binarity is often invoked as the main driver behind the shaping of aspherical planetary nebulae, however observational support for this hypothesis is lacking. This work presented in this thesis attempts to observationally test this theory by investigating the relationship between central star binarity and nebular morphology for several planetary nebulae. The discovery of six new binary central star systems is also reported. A detailed spatio-kinematical analysis of Abell 41 was performed, showing the nebula to have a bipolar morphology waisted by a toroidal structure, the symmetry axis of which is found to be perpendicular to the plane of the central binary. This alignment is exactly as predicted, indicating that the central binary, MT Ser, has played a significant role in shaping Abell 41. This is only the second planetary nebulae to have had this link, between binary and nebular inclination, explicitly shown. A spatio-kinematic model has been developed for ETHOS 1, indicating that its spectacular polar outflows are kinematically older than the central region of the nebula. This finding is discussed in the context of binary evolution, and it is concluded that the polar outflows in these nebulae are probably formed before their central binaries have entered the common-envelope phase. The central star of ETHOS 1 has yet to be the subject of detailed study, and as such, the orientation of the nebula could not be compared to that of its central binary. A spatio-kinematical analysis of SuWt 2 is presented, proving that the nebular ring is in fact at the waist of a much larger, extended bipolar structure. SuWt 2 is not known to contain a post-main sequence central star, required to eject and ionise the nebular shell, but rather a double A-type binary. The results of the analysis are discussed with relation to possible formation scenarios for SuWt 2. It is concluded that, while neither component of the double A-type binary could be the nebular progenitor, the presence of a third component to the system, which would have been the progenitor, cannot be ruled out. However, as there is no evidence that the central star of SuWt 2 is a binary alone, it is suggested that SuWt 2 should be removed from future lists of planetary nebulae known to host a binary central star. A sample of sixteen central stars of planetary nebulae, displaying morphological traits believed to be typical of central star binarity, were monitored for signs of periodic photometric variability associated with binarity. Six new photometrically variable close-binary stars were discovered, representing a ~15% increase on the previously known figure. The binary detection success rate from this investigation is compared to that of other surveys, and it is concluded that, while the results are promising, a more rigorous test is required to fully assess the extent to which specific morphological traits can be used as indicators of central star binarity.

Abstract Despite the large amount of research work in condition based maintenance and condition monitoring methods, there is still a need for more reliable and accurate methods. The clear evidence of that need is the continued dependence on time based maintenance, especially for critical applications such as turbomachinery and airplane engines. The lack of accurate condition monitoring systems could lead to not only the unexpected failures as well as the resulting hazards and repair costs, but also a huge waste of material and time because of unnecessary replacement due to false alarms and unnecessary repair and maintenance. Temperature change is a phenomenon that accompanies every dynamic activity in the universe. However, it has not been adequately exploited for mechanical system condition monitoring. The reason is the slow response of current temperature monitoring systems compared to other condition monitoring methods such as vibration analysis. Many references inferred that the change in temperature is not sensible until approaching the end of the monitored component life and even the whole system life (Kurfess, et al., 2006; Randall, 2011; Patrick, et al., March 7-14, 2009). On the other hand, the most commonly used condition monitoring method, i.e., vibration analysis, is not free from pitfalls. Although vibration analysis has shown success in detecting some bearing faults, for other faults like lubrication problems and gradual wear it is much less effective. Also, it does not give a reliable indication of fault severity for many types of bearing faults. The advancement of thermography as a temperature monitoring tool encourages the reconsideration of temperature monitoring for mechanical system fault detection. In addition to the improved accuracy and responsiveness, it has the advantage of non-contact monitoring which eliminates the need for complex sensor mounting and wiring especially for rotating components. Therefore, in current studies the thermography-based monitoring method is often used either as a distinct method or as a complementary tool to vibration analysis in an integrated condition monitoring system. The main objectives of this study are hence to: 1. Define heat sources in the rolling element bearings and overview two of the most famous bearing temperature calculation methods. 2. Setup a bearing test rig that is equipped with both vibration and temperature monitoring systems. 3. Develop a temperature calculation analytical model for rolling element bearing that include both friction calculation and heat transfer models. The friction calculated by the model will be compared to that calculated using the pre-defined empirical methods. The heat transfer model is used for bearing temperature calculation that will be compared to the experimental measurement using different temperature monitoring devices. 4. Propose a new in-band signal enhancement technique, based on the synchronous averaging technique, Autonomous Time Synchronous Averaging (ATSA) that does not need an angular position measuring device. The proposed method, in addition to the Spectral Kurtosis based band selection, will be used to enhance the bearing envelope analysis. 5. Propose a new method for classification of the bearing faults based on the fault severity and the strength of impulsiveness in vibration signals. It will be used for planning different types of tests using both temperature and vibration methods. 6. Develop and experimentally test a new technique to stimulate the bearing temperature transient condition. The technique is supported by the results of finite element modeling and is used for bearing temperature condition monitoring when the bearing is already running at thermal equilibrium condition.

The cell envelope of mycobacteria is critical for the survival and virulence of pathogenic species during infection, and its biosynthesis has been a proven drug target. Therefore, finding new targets in the biosynthetic pathway of cell envelope components is of great interest. Mycobacterium smegmatis is a model organism for the study of the devastating pathogen Mycobacterium tuberculosis. Previously, lipomannan elongation factor A (LmeA) has been identified as a cell envelope protein that is critical for the control of mannan chain length of lipomannan (LM) and lipoarabinomannan (LAM), lipoglycan components of the cell envelope. The deletion mutant, ∆lmeA, accumulates abnormal LM/LAM with fewer mannan residues. To understand the importance of this protein, the antibiotic sensitivity of ∆lmeA was tested using a resazurin-based viability assay. We found that the lmeA deletion leads to increased sensitivities to antibiotics such as vancomycin and erythromycin, and lmeA overexpression leads to increased antibiotic resistance. To directly test if the increased antibiotic sensitivity is due to the defective permeability barrier, we used an ethidium bromide uptake assay and found that ∆lmeA is more efficient in taking up ethidium bromide in the cell. We have also found that LmeA is important for protein stabilization under stress conditions. MptA is an α1,6-mannosyltransferase involved in elongation of LM and LAM mannan chain. During stress conditions in the ΔlmeA mutant, levels of MptA decrease significantly relative to wild-type. This also results in delayed doubling time after stress, a phenotype not seen in this mutant under normal growth conditions. In addition, the ΔlmeA mutant has differential protein expression during stress conditions relative to ΔlmeA in log phase, or to wild-type in either condition. To help elucidate the role of LmeA at the molecular level, binding behavior of this protein to membrane fractions was determined. In a subcellular fractionation analysis, LmeA localizes to fractions containing plasma membrane, which is tightly bound to cell wall layers. To test the binding of LmeA to membrane further, LmeA was heterologously expressed in Escherichia coli, purified, and mixed M. smegmatis cell lysate. LmeA localized to intracellular domain fractions (IMD), indicating that LmeA is capable of localizing to fractions containing only plasma membrane. Consistent with this finding, LmeA is capable of binding to spheroplasts in both an ELISA setting as well as in a sucrose gradient fractionation setting. It has also been determined that ΔlmeA has a defective capsular layer with a unique phenotype relative to other strains. We have concluded that LmeA is important for antibiotic resistance, cell envelope permeability, capsule formation, stress response, and have also determined its binding properties.

Plusieurs publications, parues lors de ma thèse, ont révélé que les protéines de la membrane nucléaireinterne (INM) et plus particulièrement l’émerine, la lamine A, SUN1, l’actine et BAF, jouaient un rôleessentiel dans les propriétés mécaniques du noyau et de la cellule. L’assemblage de l’enveloppenucléaire et les interactions de ces protéines entre-elles sont régulées par des évènements dephosphorylation et d’oligomérisation. Mon objectif était de décrire les évènements moléculairesessentiels à l’assemblage de l’enveloppe nucléaire interne, afin de pouvoir par la suite comprendrecomment l’enveloppe nucléaire répond à un stress mécanique.J’ai dans un premier temps caractérisé les évènements d’oligomérisation et de phosphorylation de laprotéine émerine. J’ai montré que cette protéine était capable de former, in vitro et en cellules, de grosoligomères indispensables à son interaction avec la lamine A. J’ai également observé que desmutations dans l’émerine, aboutissant à la dystrophie musculaire d’Emery-Dreifuss, affectaient lespropriétés d’auto-association de cette protéine.En parallèle, j’ai étudié les interactions entre émerine, lamine, SUN1, actine et BAF in vitro. J’ai pumontrer des interactions directes entre le domaine C-terminal de la lamine A et les protéines émerine,actine et SUN1. Ces trois protéines lient la lamine A sur des surfaces différentes suggérant l’existencede complexes à 3 ou 4 protéines dans la cellule. L’analyse des modes de régulation des interactionsentre ces protéines doit être poursuivie afin de comprendre quels sont les évènements moléculairesessentiels au maintien de l'intégrité nucléaire et à la transmission d’un signal mécanique entre lecytosquelette et le nucléosquelette. / During my PhD, several papers revealed that the inner nuclear membrane (INM) proteins, andespecially emerin, lamin A, SUN1, actin and BAF, played an essential role in the mechanicalproperties of the nucleus and the cell. The nuclear envelope assembly and the interactions betweenthese proteins are regulated by phosphorylation and oligomerization events. My aim was to describemolecular events essential for inner nuclear envelope assembly as a first step to understand how thenuclear envelope responds to a mechanical stress.I first characterized the oligomerization and phosphorylation states of the protein emerin. I showedthat this protein is capable of forming, in vitro and in cells, large oligomers essential to its interactionwith lamin A. I also observed that several emerin mutations leading to Emery-Dreifuss musculardystrophy impaired the self-association properties of this protein.In parallel, I studied the interactions between emerin, lamin, SUN1, actin and BAF in vitro. I was ableto demonstrate direct interactions between the C-terminal domain of lamin A and the proteins emerin,actin and SUN1. These three proteins bind lamin A on different surfaces suggesting the existence ofcomplexes of 3 or 4 proteins in the cell. Analysis of the mechanisms regulating interactions betweenthese proteins should be pursued in order to understand what are the molecular events responsible forthe maintenance of nuclear integrity and the transmission of a mechanical signal between thecytoskeleton and the nucleoskeleton.