A Dramatic Interpretation of Plato's Phaedo

published or submitted for publicatio

New insights into the biological role of mammalian ADARs; the RNA editing proteins

The ADAR proteins deaminate adenosine to inosine in double-stranded RNA which is one of the most abundant modifications present in mammalian RNA. Inosine can have a profound effect on the RNAs that are edited, not only changing the base-pairing properties, but can also result in recoding, as inosine behaves as if it were guanosine. In mammals there are three ADAR proteins and two ADAR-related proteins (ADAD) expressed. All have a very similar modular structure; however, both their expression and biological function differ significantly. Only two of the ADAR proteins have enzymatic activity. However, both ADAR and ADAD proteins possess the ability to bind double-strand RNA. Mutations in ADARs have been associated with many diseases ranging from cancer, innate immunity to neurological disorders. Here, we will discuss in detail the domain structure of mammalian ADARs, the effects of RNA editing, and the role of ADARs in human diseases

The crystal structure of the Split End protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs

The Split Ends (SPEN) protein was originally discovered in Drosophila in the late 1990s. Since then, homologous proteins have been identified in eukaryotic species ranging from plants to humans. Every family member contains three predicted RNA recognition motifs (RRMs) in the N-terminal region of the protein. We have determined the crystal structure of the region of the human SPEN homolog that contains these RRMs—the SMRT/HDAC1 Associated Repressor Protein (SHARP), at 2.0 Å resolution. SHARP is a co-regulator of the nuclear receptors. We demonstrate that two of the three RRMs, namely RRM3 and RRM4, interact via a highly conserved interface. Furthermore, we show that the RRM3-RRM4 block is the main platform mediating the stable association with the H12-H13 substructure found in the steroid receptor RNA activator (SRA), a long, non-coding RNA previously shown to play a crucial role in nuclear receptor transcriptional regulation. We determine that SHARP association with SRA relies on both single- and double-stranded RNA sequences. The crystal structure of the SHARP-RRM fragment, together with the associated RNA-binding studies, extend the repertoire of nucleic acid binding properties of RRM domains suggesting a new hypothesis for a better understanding of SPEN protein function

The Role of MERCOSUR as a Vehicle for Latin American Integration

This Development examines the scope of MERCOSUR\u27s expansion and analyzes the extent to which Decision 18/04 of the CMC represents meaningful change in MERCOSUR\u27s procedures for incorporating new members. Section 1I will address the history of MERCOSUR\u27s growth leading up to the CMC\u27s summits in July and December 2004, at Puerto Iguazu, Argentina, and at Ouro Preto, Brazil. Section III will evaluate the substance of Decision 18/04 and what effect it is likely to have for current associate states and for other nations seeking membership. Section IV will briefly discuss the Decision 18/04 in terms of the direction of the integration process in Latin America

Differential exposure and reactivity to interpersonal stress predict sex differences in adolescent depression

This study tested the hypothesis that higher rates of depression in adolescent girls are explained by their greater exposure and reactivity to stress in the interpersonal domain in a large sample of 15-year-olds. Findings indicate that adolescent girls experienced higher levels of total and interpersonal episodic stress, whereas boys experienced higher levels of chronic stress (academic and close friendship domains). Higher rates of depression in girls were explained by their greater exposure to total stress, particularly interpersonal episodic stress. Adolescent girls were also more reactive (more likely to become depressed) to both total and interpersonal episodic stress. The findings suggest that girls experience higher levels of episodic stress and are more reactive to these stressors, increasing their likelihood of becoming depressed compared to boys. Results were discussed in terms of girls' greater interpersonal focus and implications for understanding sex differences in depression

Еволюція податкового контролю

Досліджено генезис податкового контролю на території України з часів Київської Русі до створення незалежної держави. Ключові слова: податковий контроль, адміністративно-правове регулювання.Исследован генезис налогового контроля на территории Украины со времен Киевской Руси до создания независимого государства. Ключевые слова: налоговый контроль, административно-правовое регулирование.Genesis of tax control on territory of Ukraine from times of Kiev Rus to creation of the independent state is explored in the article. Key words: the tax control, administrative-legal regulation

COOLAIR Antisense RNAs Form Evolutionarily Conserved Elaborate Secondary Structures

SummaryThere is considerable debate about the functionality of long non-coding RNAs (lncRNAs). Lack of sequence conservation has been used to argue against functional relevance. We investigated antisense lncRNAs, called COOLAIR, at the A. thaliana FLC locus and experimentally determined their secondary structure. The major COOLAIR variants are highly structured, organized by exon. The distally polyadenylated transcript has a complex multi-domain structure, altered by a single non-coding SNP defining a functionally distinct A. thaliana FLC haplotype. The A. thaliana COOLAIR secondary structure was used to predict COOLAIR exons in evolutionarily divergent Brassicaceae species. These predictions were validated through chemical probing and cloning. Despite the relatively low nucleotide sequence identity, the structures, including multi-helix junctions, show remarkable evolutionary conservation. In a number of places, the structure is conserved through covariation of a non-contiguous DNA sequence. This structural conservation supports a functional role for COOLAIR transcripts rather than, or in addition to, antisense transcription