Au cours de la spermiogenèse, une réorganisation très importante de la chromatine se produit : la quasi-totalité des histones sont progressivement enlevées et remplacées par des protéines de transition puis par des protamines. Mon travail de thèse a alors consister à caractériser l'organisation finale de cette chromatine dans les spermatozoïdes ainsi que les mécanismes mis en jeu. Nos résultats montrent pour la première fois l'existence, dans les spermatides condensées de souris, de structures nucléoprotéiques contenant l'histone testiculaire TH2B ainsi que de nouveaux variants d'histones identifiés au laboratoire. De plus, ces structures organisent de manière préférentielle l'hétérochromatine péricentromérique de ces cellules. Cette réorganisation impliquerait la protéine chaperonne NAP1L4, qui pourrait être ciblée sur la chromatine en interagissant avec les queues N-terminales des histones H3. D'autres régions particulières du génome pourraient être la cible de la réorganisation différentielle de la chromatine par ces structures, permettant de les différencier du reste du génome et constituant ainsi le support d'une information épigénétique mâle transmise lors de la fécondation. L'analyse des protéines présentes dans les cellules germinales nous a également permis d'identifier deux autres protéines, HMGB4 et FYTTD1, qui ne semblent pas impliqués dans le processus de réorganisation de la chromatine dans les stades tardifs de la spermiogénèse. Néanmoins, le rôle potentiel de FYTTD1 dans le phénomène de maturation des ARN, ces derniers pouvant être un autre support de l'information épigénétique, pourrait s'avérer être un nouveau champ d'investigations très intéressant.

Jun and Fos are components of the AP1 family of transcription factors that bind to the promoters of a diverse multitude of genes involved in critical cellular responses such as cell growth and proliferation, cell cycle regulation, embryonic development and cancer. The specific protein-DNA interactions are driven by the binding of basic zipper (bZIP) domains of Jun and Fos to TPA response element (TRE) and cAMP response element (CRE) within the promoters of target genes. Here, using a diverse array of biophysical techniques, including in particular isothermal titration calorimetry in conjunction with molecular modeling and semi-empirical analysis, I characterize AP1-DNA interactions in thermodynamic and structural terms. My data show that the binding of bZIP domains of Jun-Fos heterodimer to TRE and CRE are under enthalpic control accompanied by entropic penalty at physiological temperatures. This is in agreement with the notion that protein-DNA interactions are largely driven by electrostatic interactions and intermolecular hydrogen bonding. A larger than expected heat capacity change suggests that the basic regions within the bZIP domains are unstructured in the absence of DNA and interact in a coupled folding and binding manner. Further analysis demonstrates that Jun-Fos heterodimer can tolerate single nucleotide variants of the TRE consensus sequence and binds in the biologically relevant micromolar to submicromolar range. Of particular interest is the observation that the Jun-Fos heterodimer binds to specific variants in a preferred orientation. 3D atomic models reveal that such preference in orientation results from asymmetric binding and may in part be attributable to chemically distinct but structurally equivalent residues within the basic regions of Jun and Fos. I further demonstrate that binding of the biologically relevant Jun-Jun homodimer to TRE and CRE occurs with favorable enthalpic contributions accompanied by entropic penalty at physiological temperatures in a manner akin to the binding of Jun-Fos heterodimer. However, anomalously large negative heat capacity changes provoke a model whereby Jun loads onto DNA as unfolded monomers coupled with subsequent folding and homodimerization upon association. The data also reveal that the heterodimerization of leucine zippers is modulated by the basic regions and these regions may undergo at least partial folding upon heterodimerization. Large negative heat capacity changes accompanying the heterodimerization of leucine zippers are consistent with the view that leucine zippers do not retain a-helical conformation in isolation and the formation of the native coiled coil a-helical dimer is attained through a coupled folding-dimerization mechanism. Taken together, this dissertation marks the first comprehensive thermodynamic analysis of an otherwise well-studied and vitally important transcription factor. My studies shed new light on the forces driving the AP1-DNA interaction in thermodynamic and structural terms. The implications of these novel findings on the development of novel therapies for the treatment of disease with greater efficacy coupled with low toxicity cannot be overemphasized.

The RSA cryptosystem, named after its inventors, Rivest, Shamir and Adleman, is the most widely known and widely used public-key cryptosystem in the world today. Compared to other public-key cryptosystems, such as elliptic curve cryptography, RSA requires longer keylengths and is computationally more expensive. In order to address these shortcomings, many variants of RSA have been proposed over the years. While the security of RSA has been well studied since it was proposed in 1977, many of these variants have not. In this thesis, we investigate the security of five of these variants of RSA. In particular, we provide detailed analyses of the best known algebraic attacks (including some new attacks) on instances of RSA with certain special private exponents, multiple instances of RSA sharing a common small private exponent, Multi-prime RSA, Common Prime RSA and Dual RSA.

No description available.

How to solve a multivariate quadratic polynomial equation system is believed to be one of the key points to beark AES. But to solve the MQE problem is NP-hard, so it's very important to develop a good algorithm to solve it. In such a situation, the XL algorithm is claimed to be the method to solve the MQE problem, and the cryptographers pay a lot of attetion to it. But the XL algorithm works only when the equation system is overdefined, for this reason cryptographers are looking for some ways, such as BES, to increase the numbers of equations. In practice we know that the process of solving MQE, the system will extend very fast, therefore if we input too many equations and variates, we usually using out of memory before finding out the solution. In the paper we use multiple plaintext-ciphertext to increase the number of equations and try to do some pre-computing work to reduce the size of a problem, and make it work better in pratice.

No description available.

Histone H2A.Z is a highly conserved replication-independent histone variant that is essential for survival in diverse organisms including Tetrahymena thermophila, Drosophila melanogaster, Xenopus laevis, and Mus musculus. H2A.Z has been shown to play a role in many cellular processes including, but not limited to, gene expression, chromosome segregation, cell cycle progression, heterochromatin maintenance and epigenetic transcriptional memory. However, the mechanism by which H2A.Z and its post-translationally modified forms participate in these diverse cellular events and their subsequent effects on chromatin structure and function are not entirely clear. A thorough review of H2A.Z is provided in Chapter 1. We have isolated native non-acetylated and acetylated forms of H2A.Z and characterized nucleosome core particles (NCPs) reconstituted with these proteins using the analytical ultracentrifuge (Chapter 2). We report that NCPs reconstituted with native non-acetylated H2A.Z exhibit a slightly more compact conformation compared to those reconstituted with H2A. Furthermore, we show that acetylation of H2A.Z in conjunction with acetylation of the histone complement, results in NCPs that are less compact and less stable than H2A.Z-containing NCPs reconstituted with non-acetylated histones. Acetylated H2A.Z NCPs are nevertheless more compact and stable than acetylated H2A-containing NCPs. We have also identified the presence of two H2A.Z protein isoforms in vertebrates, H2A.Z-1 and H2A.Z-2, and characterized the sites and abundances of their N-terminal peptide acetylation. Further characterization of the human H2A.Z isoforms is presented in Chapter 3 and indicates that they are expressed across a broad range of human tissues, and that they exhibit a similar but non-identical distribution within chromatin. Our results suggest that H2A.Z-2 preferentially associates with H3 trimethylated at lysine 4 compared to H2A.Z-1, and the phylogenetic analysis of the promoter regions of H2A.Z-1 and H2A.Z-2 indicate that they have evolved separately during vertebrate evolution. Overall, these data suggest that the two isoforms of H2A.Z present in vertebrates may have acquired a degree of functional independence. In Chapter 4, we show that H2A.Z and an N-terminally acetylated form of H2A.Z associate with the prostate specific antigen (PSA) gene promoter and the levels of these proteins are reduced upon induction of the gene with androgen. Furthermore, H2A.Z protein levels increase in response to treatment with androgen which correlates with an increase in the mRNA expression levels of the H2A.Z-1 gene. Preliminary Western Blot and quantitative PCR analysis of H2A.Z (-1 and -2) levels in a tumor progression model of prostate cancer indicate that increased H2A.Z expression may be involved in the development of androgen independent prostate cancer. Collectively, our results contribute to our understanding of H2A.Z biology in vertebrates and support a role for this protein and its acetylated forms in poising promoter chromatin for subsequent gene transcription.

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The thesis collects and analyses the very first (2nd-5th century) clear quotations, references and interpretations of Acts 15:20.29 and Acts 21:25. It consists of three parts: Part I, which is introductory in nature, presents and comments upon the textual variants of these biblical verses. Part II catalogues and analyses all the relevant texts referring to and commenting on Acts 15:20.29 and Acts 21:25. The purpose is to discover each ancient author’s understanding of the Jerusalem Council’s prohibitions, enumerated in the above verses of Acts. The writers and their texts are divided into three groups depending on which main textual variant of Acts 15:20.29 and Acts 21:25 they referred or quote. Part III presents in its first two chapters a synthesis of the above analyses, juxtaposing and summarizing early authors’ views on the meaning and normativity of the prohibitions. Then, the last chapter examines the potential influence of a variant of Acts 15:20.29 and 21:25 quoted or referred to (or preferred if more variants were known to a given author) by the writers on their understanding of the prohibitions. The thesis shows that despite different textual variants used by the early writers, their interpretations of the prohibitions, although often superficially different, have in a number of cases and on a deeper level more in common than one would preliminarily surmise.

Antisocial behaviors (AB), which place an enormous burden on society, are committed by a heterogeneous population, including psychopaths (Poythress et al., 2010). Psychopathy denotes a more serious and entrenched pattern of AB (Hare, 1996) and appears to be a heterogeneous construct as well. In fact, Primary and Secondary psychopathic variants are consistently identified in a variety of samples using person-centered analysis (Drislane et al., 2014; Gill & Stickle, 2016). Both Reinforcement Sensitivity Theory (Gray & McNaughton, 2000) and the Triarchic Model of Psychopathy (Patrick, Fowles, & Krueger, 2009) provide useful frameworks to understand the etiology of the psychopathic variants. The current study identified Primary and Secondary Trait groups in a sample of criminally justice involved adults (N = 377), which differed on measures of negative emotionality. However, the Psychopathic trait groups did not differ on the boldness or meanness domains of the Triarchic Model (Patrick, Fowles & Kreuger). The disinhibition domain of the Triarchic model was significantly associated with aggression, and this association was partially mediated by levels of anxiety. Anxiety is an important dimension to assess in research, evaluation, and treatment of individuals with high levels of antisocial behavior. Keywords: Psychopathy, variants, Triarchic, measurement, antisocial behavior