Computational analysis of base composition pattern and promoter elements in the putative promoter regions in relation to expression profiles of 682 human genes on chromosome 22

The base composition pattern (BCP) in the putative promoter region (PPRs) up to 5 Kb lengths of 682 human genes on Chromosome 22 (Chr22) was examined. Two-dimensional (2D) and three-dimensional (3D) functions were designed to delineate the DNA base composition, with four major patterns identified. It is found that 17.6% genes include TATA box, 28.0% GC box, 18.9% CAAT box and 38.4% CpG islands, and approximately 10% genes have one of four putative initiator (Inr) motifs. The occurrence of the promoter elements is tightly associated with the base composition features in the promoter regions, and the associations of the base composition features with occurrence of the promoter elements in the promoter regions mediate tissue-wide expression of the genes in human. The occurrence of two or more promoter elements in the promoter regions is required for the medium- and wide-range expression profiles of the human genes on Chr22. Thus, the reported data shed light on the characteristics of the PPRs of the human genes on Chr22, which may improve our understanding of regulatory roles of the PPRs with occurrence of the promoter elements in gene expression.

Evolving noisy oscillatory dynamics in genetic regulatory networks

We introduce a genetic programming (GP) approach for evolving genetic networks that demonstrate desired dynamics when simulated as a discrete stochastic process. Our representation of genetic networks is based on a biochemical reaction model including key elements such as transcription, translation and post-translational modifications. The stochastic, reaction-based GP system is similar but not identical with algorithmic chemistries. We evolved genetic networks with noisy oscillatory dynamics. The results show the practicality of evolving particular dynamics in gene regulatory networks when modelled with intrinsic noise.

Multilevel modelling for inference of genetic regulatory networks

Time-course experiments with microarrays are often used to study dynamic biological systems and genetic regulatory networks (GRNs) that model how genes influence each other in cell-level development of organisms. The inference for GRNs provides important insights into the fundamental biological processes such as growth and is useful in disease diagnosis and genomic drug design. Due to the experimental design, multilevel data hierarchies are often present in time-course gene expression data. Most existing methods, however, ignore the dependency of the expression measurements over time and the correlation among gene expression profiles. Such independence assumptions violate regulatory interactions and can result in overlooking certain important subject effects and lead to spurious inference for regulatory networks or mechanisms. In this paper, a multilevel mixed-effects model is adopted to incorporate data hierarchies in the analysis of time-course data, where temporal and subject effects are both assumed to be random. The method starts with the clustering of genes by fitting the mixture model within the multilevel random-effects model framework using the expectation-maximization (EM) algorithm. The network of regulatory interactions is then determined by searching for regulatory control elements (activators and inhibitors) shared by the clusters of co-expressed genes, based on a time-lagged correlation coefficients measurement. The method is applied to two real time-course datasets from the budding yeast (Saccharomyces cerevisiae) genome. It is shown that the proposed method provides clusters of cell-cycle regulated genes that are supported by existing gene function annotations, and hence enables inference on regulatory interactions for the genetic network.

The Future of EU Cohesion Policy. Endogenous Development – Added Value of Intervention – Regulatory Frameworks

The successful operation of the regional development – or cohesion – policy of the European Union has a strategic importance from the point of view of the whole integration process. Strengthening economic, social and territorial cohesion and decreasing disparities between member states and regions are not only one of the main priorities of the integration, but at the same time these are justified expectations of the people living in the member states of the union. The cohesion transfers should be spent on those factors which have the biggest contribution to the improvement of development prospects and competitiveness in the given regions. Theories on regional development have controversial conclusions about the long-term formation of development disparities. However, it has become evident that successful development policies are based on endogenous factors, innovation and well-functioning institutions. After examining theoretical considerations and regional disparities the study analyses the impacts of EU regional policy and evaluates the main elements of the proposed regulatory frameworks for the period 2014-2020.

Recoding: reprogrammed genetic decoding with an emphasis on antizyme regulatory frameshifting

Recoding embraces mechanisms that augment the rules of standard genetic decoding. The deviations from standard decoding are often purposeful and their realisation provides diverse and flexible regulatory mechanisms. Recoding events such as programed ribosomal frameshifting are especially plentiful in viruses. In most organisms only a few cellular genes are known to employ programed ribosomal frameshifting in their expression. By far the most prominent and therefore well-studied case of cellular +1 frameshifting is in expression of antizyme mRNAs. The protein antizyme is a key regulator of polyamine levels in most eukaryotes with some exceptions such as plants. A +1 frameshifting event is required for the full length protein to be synthesized and this requirement is a conserved feature of antizyme mRNAs from yeast to mammals. The efficiency of the frameshifting event is dependent on the free polyamine levels in the cell. cis-acting elements in antizyme mRNAs such as specific RNA structures are required to stimulate the frameshifting efficiency. Here I describe a novel stimulator of antizyme +1 frameshifting in the Agaricomycotina class of Basidiomycete fungi. It is a nascent peptide that acts from within the ribosome exit tunnel to stimulate frameshifting efficiency in response to polyamines. The interactions of the nascent peptide with components of the peptidyl transferase centre and the protein exit tunnel emerge in our understanding as powerful means which the cell employs for monitoring and tuning the translational process. These interactions can modulate the rate of translation, protein cotranslational folding and localization. Some nascent peptides act in concert with small molecules such as polyamines or antibiotics to stall the ribosome. To these known nascent peptide effects we have added that of a stimulatory effect on the +1 frameshifting in antizyme mRNAs. It is becoming evident that nascent peptide involvement in regulation of translation is a much more general phenomenon than previously anticipated.

Self-regulatory behaviours and flow dispositions in musical practice: a survey with advanced performers

Flow experience, a holistic sensation of total involvement in an activity, seems to have positive influences on musical performance activities. Although its main requirements (balance between challenges and skills, clear goals and unequivocal feedback) are inherent elements of musical practice, there is a lack of research about flow occurrences in the context of musical practice and on how specific practice behaviours affect the experience of flow and its particular dimensions. The aims of this thesis were to investigate advanced performersʼ dispositions to flow in musical practice, and to investigate whether the frequency of these experiences of holistic engagement with practice are associated with self-regulatory practice behaviours. 168 advanced classicallytrained performers (male = 50.0%; female = 50.0%), ranging in age from 18 to 74 years (m = 34.41, SD = 12.39), answered a survey that included two measures: the Dispositional Short Flow Scale, assessing performersʼ flow dispositions, and the Self-Regulated Practice Behaviours Questionnaire, developed specifically for the present research. The overall results of the survey suggested that advanced musicians have high dispositions to flow in musical practice, but not associated with the participantsʼ demographic characteristics. Three of the individual flow indicators were less experienced, suggesting that the most intense flow experiences are rare in musical practice. However, the results point to the existence of another relevant experience, named optimal practice experience. Practice engagement levels were positively associated with knowledge of oneʼs own personal resources and a capacity for practice organization, but not with inclusion/use of external resources. A capacity for setting optimal practice goals was related to self-regulation and to immersion aspects of flow. Current findings offer new clues about the assessment of flow dispositions in performers, helping to clarify how daily practice can heighten positive affective responses in musicians who are vulnerable to the requirements and difficulties of deliberate practice, as well as to other negative practice outcomes. The current research questions issues pertaining to the optimization and sustaining of flow in daily practice, suggesting future directions in the study of the affective subjective functioning of engagement with deliberate practice.

Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis

The self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.