Excellence in Research and Innovation for Humanity

International Science Index

Commenced in January 1999 Frequency: Monthly Edition: International Paper Count: 2

2
9998537
Systematic Identification and Quantification of Substrate Specificity Determinants in Human Protein Kinases
Abstract:

Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase–pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed-specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.

1
7998
Component Based Framework for Authoring and Multimedia Training in Mathematics
Abstract:
The new programming technologies allow for the creation of components which can be automatically or manually assembled to reach a new experience in knowledge understanding and mastering or in getting skills for a specific knowledge area. The project proposes an interactive framework that permits the creation, combination and utilization of components that are specific to mathematical training in high schools. The main framework-s objectives are: • authoring lessons by the teacher or the students; all they need are simple operating skills for Equation Editor (or something similar, or Latex); the rest are just drag & drop operations, inserting data into a grid, or navigating through menus • allowing sonorous presentations of mathematical texts and solving hints (easier understood by the students) • offering graphical representations of a mathematical function edited in Equation • storing of learning objects in a database • storing of predefined lessons (efficient for expressions and commands, the rest being calculations; allows a high compression) • viewing and/or modifying predefined lessons, according to the curricula The whole thing is focused on a mathematical expressions minicompiler, storing the code that will be later used for different purposes (tables, graphics, and optimisations). Programming technologies used. A Visual C# .NET implementation is proposed. New and innovative digital learning objects for mathematics will be developed; they are capable to interpret, contextualize and react depending on the architecture where they are assembled.
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