The Master's Thesis focuses on the impact of the Ukraine political crisis of 2013 - 2014 on Russia's relations with the CIS countries. The crisis was triggered by Ukrainian government when it suspended plans of closer ties with the European Union, and has since spurred escalating tensions between Russia and Western powers. The tense situation in Ukraine and Russia's policies is one of the central affairs in international relations today and this makes this topic especially actual. The Thesis examines impact of Ukrainian events of 2013-2014 on the Eurasian integration led by Russia. Integration projects in the post-Soviet space are a high priority for Russia and a tool, how the country articulates its interests in the region. The work provides a look at the development of Russia's foreign policy since the dissolution of the Soviet Union and considers factors and ideological aspects that affected it. Selected integration projects and Russia's policies towards the Eurasian integration are described. The final part is devoted to the origins of Ukrainian crisis and Russia's attitude to it. Current, as well as potential impact of Ukrainian crisis on Russia's relations with the CIS states is derived from the analysis. KEYWORDS Russian Federation, Russian Foreign Policy, Ukraine, Commonwealth of...

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<p> The ultraviolet absorption spectrum of oxalyl chloride-fluoride has been recorded under high resolution, and has been attributed to a superposition of the spectra of the cis isomer (which appears weakly) and the trans isomer. The ultraviolet spectra of the cis isomers of oxalyl bromide, oxalyl chloride and oxalyl fluoride have also been identified. With the help of theoretical calculations, discrete absorption in the ultraviolet spectrum of trans oxalyl chloride-fluoride has been attributed to the superposition of four systems: (a) the singlet-singlet and singlet-triplet transitions which involve promotion of an electron from the highest energy non-bonding orbital (n₁) to the lowest energy antibonding orbital (π₁*) and (b) the singlet-singlet and singlet-triplet transitions which involve promotion from n₁ to the second lowest energy antibonding π orbital (π₂*). The S-S and S-T, n₁ → π₁* transitions have been analyzed in detail. </p> <p> Theoretical calculations have been carried out which indicate that α,β diketones, promotion of an electron to the lowest energy antibonding skeletal orbital (σ₁*) produces states which have a tendency towards dissociation along the C-C bond. It has been postulated that the diffuseness of the high energy absorption spectrum results from such a molecular dissociation, the Aᵤ(π₁,π₁*) state being strongly predissociated by the Aᵤ(n₁,σ₁*) state while the Aᵤ(n₁,π₁*) state is strongly predissociated by the Aᵤ(π₁,σ₁*) state. </p> <p> It has been postulated that the fluid phases of glyoxal and biacetyl consist of an equilibrium mixture of these molecules in various degrees of aggregation (e.g., monomeric, dimeric, trimeric,...). An ultraviolet band system previously assigned to a second n → π* transitions of these molecules has been reassigned to the first n → π* transition of a polymeric species. Some evidence has been assembled which supports this hypothesis. </p> / Thesis / Doctor of Philosophy (PhD)

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Early mammalian development before the oocyte-to-embryo transition is under 'maternal control' from factors deposited in the cytoplasm during oocyte growth, synthesized independent of de novo transcription. Maternal mRNAs encode proteins necessary for early embryo development. Two elements in the mRNA 3’untranslated region (UTR), the cytoplasmic polyadenylation element (CPE) and the hexanucleotide (AAUAAA) are involved in the control of translation of specific mRNAs during meiotic maturation. Despite advances in understanding the translational regulation during meiotic maturation, regulation at the 1-cell stage has not been explained. More studies are required to explain this complex mechanism of temporal mRNA recruitment after fertilization. Maternal mRNAs translated at different stages were examined to understand how specific maternal mRNAs are synthesized and stored, what are these maternal mRNAs, which maternal mRNAs are translated, and how these maternal mRNAs are temporally regulated. Polysomal mRNAs from eggs and 1-cell embryos were analyzed by microarray analysis and this indicated that temporally significant biological activities were encoded by mRNAs recruited at different stages of development. The mRNAs recruited in eggs were involved in homeostasis and transport mechanisms and those recruited in zygotes were involved in biosynthesis and metabolic activities. These data indicated that there is a temporal regulation of maternal mRNAs to meet the different biological requirements of the embryos. After the identification of temporally translated mRNAs, experiments were performed to understand the mechanism underlying temporal translation. The prevalence of the CPE differed between the two mRNA populations translated i.e., egg and 1-cell stage polysomal mRNAs. CPEs were present in ~53% of transcripts at the 1-cell stage compared to ~86% at the MII stage. This indicated that novel motifs other than CPEs regulate translation of mRNAs at the 1-cell stage. Truncation and deletion experiments were conducted using chimeric mRNAs based on one mRNA that was enriched in the 1- cell polysomes (Bag4). These experiments led to the identification of two regulatory regions that control translation at the 1-cell stage, an 80 nt region and a 43 nt region with different regulatory motifs. The 80 nt region is involved in activation of translation and the 43 nt region has an inhibitory effect on translation at the MII and early 1-cell stage. These results provide a detailed picture of how specific maternal mRNAs are prevented from undergoing translation at the MII stage and how the effect of inhibition is eliminated by the late 1-cell stage. / Biochemistry

Scratch2 (Scrt2) é um fator de transcrição (FT) expresso em células neurais recém-pós-mitóticas. O mecanismo de regulação de sua transcrição permanece desconhecido. Nós buscamos por potenciais elementos cis-regulatórios (CR) e sítios de ligação para FT na região genômica de Scrt2. Nós testamos o efeito in vivo da região CR intrônica através de eletroporação em embrião de galinha. Esta CR intrônica levou à expressão de eGFP tubo neural, mas não gerou um padrão semelhante ao Scrt2 endógeno. Estes dados sugerem que esta região CR pode contribuir com o controle da expressão de Scrt2, mas requer regiões regulatórias adicionais. Nós também verificamos o papel de mAsh1, cPax6, cNgn2 e Brn na regulação da expressão de Scrt2 através da superexpressão destes no tubo neural embrionário. As análises foram realizadas por qPCR e hibridação in situ. A superexpressão de mAsh1 e cNgn2 levou a um leve aumento na expressão de cScrt2 visto através da hibridação in situ. Já a superexpressão de cPax6 e mBrn-Eng reduziu os níveis de cScrt2, com Brn apresentando efeitos mais severos. / Scratch2 (Scrt2) is a transcription factor expressed in early post-mitotic neural cells. The mechanisms that control its transcription remain unknown. We searched for potential cis-regulatory elements and putative transcription factors binding sites in the genomic region of cScrt2. Then, we tested the function of a candidate cis-regulatory intronic region through electroporation in chick embryos. This fragment drove eGFP expression in the neural tube of chick embryo, but its expression did not resemble the cScrt2 endogenous pattern. Thus, this cis-regulatory region likely requires the presence of other regulatory regions. We also evaluated the role of mAsh1, cPax6, cNgn2 e Brn in regulating cScrt2 expression through overexpression of these factors in chick neural tubes and subsequent qPCR and in situ hybridization. Overexpression of mAsh1 and cNgn2 increased slightly cScrt2 expression level as seen by in situ hybridization. Overexpression of cPax6 and mBrn-Eng, reduced cScrt2 levels, with more severe effects with Brn.

Populações nativas da América do Sul apresentam diversidade genética reduzida em relação às demais populações do mundo e alta diferenciação interpopulacional dentro do continente. As pressões seletivas sobre a região cis-reguladora do CCR5 geram uma assinatura de diversidade oposta àquela esperada com base na história demográfica, reduzindo a variação interpopulacional e contribuindo para uma elevação das taxas de polimorfismo. No presente estudo investigamos a interação entre esses processos micro-evolutivos, analisando o polimorfismo da região cis-reguladora de ameríndios da América do Sul e comparando os resultados com aqueles obtidos em outras regiões do mundo. Sequenciamos 927 pares de base (pb) da região controladora do CCR5 em 7 tribos indígenas da região amazônica. Em ameríndios, nenhum haplótipo exclusivo foi encontrado em ameríndios e os dois haplogrupos mais comuns foram de diferentes clusters filogenéticos. A diversidade nucleotídica (&#960;) para a amostra total, foi a mais alta dentre todas as regiões do mundo já estudadas (&#960;=0,0027). A estimativa da diversidade genética populacional para ameríndios, baseada no número de sítios polimórficos (&#952;s), foi similar aos valores encontrados para as populações não-africanas, sendo que em africanos o valor foi praticamente o dobro. Conseqüentemente, foi observado um valor de D de Tajima positivo e estatisticamente significativo (D=2,82, p<0,01), maior do que aquele visto para outras regiões do mundo. Através de comparações empíricas e de simulações coalescentes verificamos que o alto valor de D de Tajima encontrado para ameríndios não é explicável por um recente modelo demográfico de evolução humana. O teste Ewens-Watterson indicou para a amostra ameríndia uma taxa de heterozigose maior do que esperada para um população neutra. O valor de Fst observado para comparação envolvendo asiáticos e ameríndios foi mais baixo que 1000 valores de Fst calculados a partir de 783 microssatélites genotipados em amostras de mesmo tamanho de regiões geográficas similares. Essas caraterísticas corroboram a hipótese de seleção balanceadora na região cis-reguladora do CCR5 de ameríndios da região amazônica brasileira. No presente estudo demonstramos também a existência de uma associação estatisticamente significativa (p<0,01) entre os alelos mantidos em freqüências intermediárias na população humana e regiões ativadoras de splicing localizadas em exons (ESEs). Finalmente, nós acreditamos que um modelo demográfico de evolução humana, complementar ao utilizado neste trabalho, deve ser testado para se refutar a hipótese de que a forte assinatura de seleção balanceadora observada em ameríndios não foi causada por seleção natural que atuou em população ancestral à de indígenas americanos / Native american populations show lower genetic diversity and higher interpopulational genetic differences than populations from other continents. Within South America groups from the non-andean geographic region shows extremely high genetic differentiation. The strong signature of balancing selection observed for 5\' cis-regulatory region of the CCR5 gene at the worldwide scale represents an opposite pattern of genetic variation to that expected by demographic process which acted in Amerindians. To evaluate the impact of complex demographic history on the 5\' cis-regulatory region of CCR5 we resequenced 927 bp of this locus in 62 individuals from different native groups located in the Brazilian Amazonian region. No new haplotype was detected and the two most common haplogroups observed were from different phylogenetic clusters, according with the pattern observed for other human populations. The level of heterozigosity of the total sample, measured by nucleotide diversity (&#960;) was the highest yet described for human populations (&#960;=0,0027) while values based on polymorphic sites (&#952;s) were similar among Amerindians and non-Africans populations. Consequently we observed a positive and significant Tajima\'s D value (D=2,82, p <0,01). This value was higher than all D values observed for the other human populations. Observed summary statistics (&#960; and D) were significantly higher than same statistics estimated from 2000 simulated samples assuming a recently proposed demographic model of human evolution. We also found significant deviations in Ewens-Watterson homozygosity test toward an excess of heterozygosity for Amerindian sample. Another striking feature of CCR5 cis-regulatory region was the low Fst value among populations. The Fst among Asians and Amerindians was an outlier among 1000 Fst values estimated by 783 microssatelites of samples from similar geographic regions and with the same sample sizes as those of the CCR5 5\' cis-regulatory data. These features corroborates the strong signature of balancing selection described for CCR5 5\'cis regulatory region. We also contributed to discussion about functional aspects of CCR5 cis-regulatory region demonstrating a significant association between intermediate frequency SNPs and exonic splicing enhancers (ESEs) regions (p<0,01). Finally, we believe that improved models of demographic human evolution must be tested to refute the hypothesis that the strong signature of balancing selection observed in Amerindians was not caused by a selection pressure which occurred in an ancestral population.

Autism-spectrum disorders (ASDs) are a group of neurodevelopmental disorders that are becoming increasingly more prevalent. A diagnostic criterion for autism is the presence of restricted, repetitive behaviours (RRBs), one of which is the intense fascinations for virtually any topic: circumscribed interests (CIs). CIs have the potential to be used for motivational purposes. This study employed semi-structured interviews using Interpretative Phenomenological Analysis (IPA) with individuals with ASDs and their parents. In total, 11 families participated in this study, comprising 33 individuals (16 parents and 17 individuals with ASDs). This study found five themes: He's Very Unique; They Don't Realize that Not Everyone Lives and Thinks the Same Thing All the Time; We Couldn't even Pronounce the Names of These Dinosaurs, and Jason was Telling Us; You Can't Change Them, You Can Only Love Them; and So I Can Do My Job at the Same Time and Observe the Weather at the Same Time.

Pin1 is an enzyme central to cell signaling pathways because it catalyzes the cis–trans isomerization of the peptide ω-bond in phosphorylated serine/threonine-proline motifs in many proteins. This regulatory function makes Pin1 a drug target in the treatment of various diseases. The effects of phosphorylation on Pin1 substrates and the basis for Pin1 recognition are not well understood. The conformational consequences of phosphorylation on Pin1 substrate analogues and the mechanism of recognition by the catalytic domain of Pin1 were determined using molecular dynamics simulations. Phosphorylation perturbs the backbone conformational space of Pin1 substrate analogues. It is also shown that Pin1 recognizes specific conformations of its substrate by conformational selection. Dynamical correlated motions in the free Pin1 enzyme are present in the enzyme of the enzyme–substrate complex when the substrate is in the transition state configuration. This suggests that these motions play a significant role during catalysis. These results provide a detailed mechanistic understanding of Pin1 substrate recognition that can be exploited for drug design purposes and further our understanding of the subtleties of post-translational phosphorylation and cis–trans isomerization. Results from accelerated molecular dynamics simulations indicate that catalysis occurs along a restricted path of the backbone configuration of the substrate, selecting specific subpopulations of the conformational space of the substrate in the active site of Pin1. The simulations show that the enzyme–substrate interactions are coupled to the state of the prolyl peptide bond during catalysis. The transition-state configuration of the substrate binds better than the cis and trans states to the catalytic domain of Pin1. This suggests that Pin1 catalyzes its substrate by noncovalently stabilizing the transition state. These results suggest an atomistic detail understanding of the catalytic mechanism of Pin1 that is necessary for the design of novel inhibitors and the treatment of several diseases. Additionally, a set of constant force biased molecular dynamics simulations are presented to explore the kinetic properties of a Pin1 substrate and its unphosphorylated analogue. The simulations indicate that the phosphorylated Pin1 substrate isomerizes slower than the unphosphorylated analogue. This is due to the lower diffusion constant for the phosphorylated Pin1 substrate.