Identification of Conserved Splicing Motifs in Mutually Exclusive Exons of 15 Insect Species

Background: During alternative splicing, the inclusion of an exon in the final mRNA molecule is determined by nuclear proteins that bind cis-regulatory sequences in a target pre-mRNA molecule. A recent study suggested that the regulatory codes of individual RNA-binding proteins may be nearly immutable between very diverse species such as mammals and insects. The model system Drosophila melanogaster therefore presents an excellent opportunity for the study of alternative splicing due to the availability of quality EST annotations in FlyBase. Methods: In this paper, we describe an in silico analysis pipeline to extract putative exonic splicing regulatory sequences from a multiple alignment of 15 species of insects. Our method, ESTs-to-ESRs (E2E), uses graph analysis of EST splicing graphs to identify mutually exclusive (ME) exons and combines phylogenetic measures, a sliding window approach along the multiple alignment and the Welch’s t statistic to extract conserved ESR motifs. Results: The most frequent 100% conserved word of length 5 bp in different insect exons was “ATGGA”. We identified 799 statistically significant “spike” hexamers, 218 motifs with either a left or right FDR corrected spike magnitude p-value < 0.05 and 83 with both left and right uncorrected p < 0.01. 11 genes were identified with highly significant motifs in one ME exon but not in the other, suggesting regulation of ME exon splicing through these highly conserved hexamers. The majority of these genes have been shown to have regulated spatiotemporal expression. 10 elements were found to match three mammalian splicing regulator databases. A putative ESR motif, GATGCAG, was identified in the ME-13b but not in the ME-13a of Drosophila N-Cadherin, a gene that has been shown to have a distinct spatiotemporal expression pattern of spliced isoforms in a recent study. Conclusions: Analysis of phylogenetic relationships and variability of sequence conservation as implemented in the E2E spikes method may lead to improved identification of ESRs. We found that approximately half of the putative ESRs in common between insects and mammals have a high statistical support (p < 0.01). Several Drosophila genes with spatiotemporal expression patterns were identified to contain putative ESRs located in one exon of the ME exon pairs but not in the other.

The Caribbean Court of Justice: An investigation of the impact of elites on its creation and present structure as it relates to original jurisdiction

The primary focus of this dissertation is to determine the degree to which political, economic, and socio-cultural elites in Jamaica and Trinidad & Tobago influenced the development of the Caribbean Court of Justice's (CCJ) original jurisdiction. As members of the Caribbean Community (CARICOM), both states replaced their protectionist model with open regionalism at the end of the 1980s. Open regionalism was adopted to make CARICOM member states internationally competitive. Open regionalism was also expected to create a stable regional trade environment. To ensure a stable economic environment, a regional court with original jurisdiction was proposed. A six member Preparatory Committee on the Caribbean Court of Justice (PREPCOM), on which Jamaica and Trinidad & Tobago sat, was formed to draft the Agreement Establishing the Caribbean Court of Justice that would govern how the Court would interpret the Revised Treaty of Chaguaramas (RTC) and enforce judgments. ^ Through the use of qualitative research methods, namely elite interviews, document data, and text analysis, and a focus on three levels of analysis, that is, the international, regional, and domestic, three major conclusions are drawn. First, changes in the international economic environment caused Jamaica and Trinidad & Tobago to support the establishment of a regional court. Second, Jamaica had far greater influence on the final structure of the CCJ than Trinidad & Tobago. Third, it was found that in both states the political elite had the greatest influence on the development and structure of the CCJ. The economic elite followed by the socio-cultural elite were found to have a lesser impact. These findings are significant because they account for the impact of elites and elite behavior on institutions in a much-neglected category of states: the developing world.^

Exclusive electrodisintegration of three-nucleon systems

The purpose of this research was to develop a theory of high-energy exclusive electrodisintegration of three-nucleon systems on the example of 3He(e, e'NN)N reaction with knocked-out nucleon in the final state. The scattering amplitudes and differential cross section of the reaction were calculated in details within the Generalized Eikonal Approximation(GEA). The manifestly covariant nature of Feynman diagrams derived in GEA allowed us to preserve both the relativistic dynamics and kinematics of the scattering while identifying the low momentum nuclear part of the amplitude with a nonrelativistic nuclear wave function. Numerical calculations of the residual system's total and relative momentum distribution were performed which show reasonable agreement with available experimental data. The theoretical framework of GEA, which was applied previously only for the case of two-body (deuteron) high energy break up reactions, has been practically implemented and shown to provide a valid description for more complex A = 3 systems.