DEVELOPMENT OF CANVA-BASED INTERACTIVE E-BOOK AND BOOK CREATOR USING THE RADEC LEARNING MODEL TO SUPPORT CREATIVE THINKING SKILLS

The involvement of technology in 21st century learning is indispensable at every level of education. Teachers can involve digital learning media to support the process of teaching and learning activities. Digital-based learning media such as interactive e-books can be used as learning media that can be used in 21st century learning. In addition to digital-based learning media, the learning model that can be applied is an innovative learning model. The RADEC learning model is one of the learning models that can be applied in current learning. This study aims to develop an interactive e-book through the RADEC learning model, and determine the feasibility of an interactive e-book through the RADEC learning model. This research is a research and development or Research and Development ADDIE model. This study obtained the feasibility results from the validation of material experts, validation of linguists, and validation of media experts. The results of the validation of material experts, linguists, and media experts get scores in the very valid category for use. The results of student responses regarding product trials get scores in the very interesting category for students to use in the learning process. The results of the group creativity assessment are very interesting and can increase the creativity of students. Based on these results, it can be concluded that interactive e-books through the RADEC learning model are very valid and feasible to be used in learning and can increase students' creativity

Insights into the Function of the CRM1 Cofactor RanBP3 from the Structure of Its Ran-Binding Domain

Proteins bearing a leucine-rich nuclear export signal (NES) are exported from the nucleus by the transport factor CRM1, which forms a cooperative ternary complex with the NES-bearing cargo and with the small GTPase Ran. CRM1-mediated export is regulated by RanBP3, a Ran-interacting nuclear protein. Unlike the related proteins RanBP1 and RanBP2, which promote disassembly of the export complex in the cytosol, RanBP3 acts as a CRM1 cofactor, enhancing NES export by stabilizing the export complex in the nucleus. RanBP3 also alters the cargo selectivity of CRM1, promoting recognition of the NES of HIV-1 Rev and of other cargos while deterring recognition of the import adaptor protein Snurportin1. Here we report the crystal structure of the Ran-binding domain (RBD) from RanBP3 and compare it to RBD structures from RanBP1 and RanBP2 in complex with Ran and CRM1. Differences among these structures suggest why RanBP3 binds Ran with unusually low affinity, how RanBP3 modulates the cargo selectivity of CRM1, and why RanBP3 promotes assembly rather than disassembly of the export complex. The comparison of RBD structures thus provides an insight into the functional diversity of Ran-binding proteins

Dual lysine and N-terminal acetyltransferases reveal the complexity underpinning protein acetylation

Protein acetylation is a highly frequent protein modification. However, comparatively little is known about its enzymatic machinery. N-alpha-acetylation (NTA) and epsilon-lysine acetylation (KA) are known to be catalyzed by distinct families of enzymes (NATs andKATs, respectively), although the possibility that the sameGCN5-relatedN-acetyltransferase (GNAT) can perform both functions has been debated. Here, we discovered a new family of plastid-localizedGNATs, which possess a dual specificity. All characterizedGNATfamily members display a number of unique features. Quantitative mass spectrometry analyses revealed that these enzymes exhibit both distinctKAand relaxedNTAspecificities. Furthermore, inactivation ofGNAT2 leads to significantNTAorKAdecreases of several plastid proteins, while proteins of other compartments were unaffected. The data indicate that these enzymes have specific protein targets and likely display partly redundant selectivity, increasing the robustness of the acetylation processin vivo. In summary, this study revealed a new layer of complexity in the machinery controlling this prevalent modification and suggests that other eukaryoticGNATs may also possess these previously underappreciated broader enzymatic activities

Aggregated cross-media news visualization and personalization

There is an increasing need for online news aggregation and visualization. Commercial systems, such as Google News and Ask.com, have successfully launched a portal aiming at providing an aggregated view of the top news events at a given time. However, these systems, as well as previous research projects, lack the ability to personalize events according to the user’s need. Furthermore, users increasingly prefer to see multiple types of media to be presented when they follow a particular event of interest. In this paper, we describe a novel framework to allow the aggregation of online sources for text articles, images, videos and TV news into news stories, while the visualization enables the users to browse and select the news events based on semantic information. The experimental results have indicated some promising results

Efficient generation of pleasant video summaries

This paper presents an efficient video summarization technique with the focus of generating video summaries that are pleasant to watch. The validity of the technique was tested in the TRECVID 2008 evaluation event. The results show the effectiveness of this technique to produce pleasant video summaries in a short time

Adaptive Responses by Transcriptional Regulators to small molecules in Prokaryotes : Structural studies of two bacterial one-component signal transduction systems DntR and HpNikR

Prokaryotes are continually exposed to variations in their environment. Survival in unstable milieu requires a wide range of transcriptional regulators (TRs) that respond to specific environmental and cellular signals by modulating gene expression and provide an appropriate physiological response to external stimuli. These adaptive responses to environmental signals are mostly mediated by TRs from one of two families: the single or the two component signal transduction systems (1CSTS; 2CSTS). In this thesis the structural analysis of two 1CSTS – DntR and NikR − are presented. One study was carried out to try to develop a bacterial biosensor for synthetic dinitrotulenes compounds, the other to characterise the Ni-sensing mechanism that contributes to the acid adaptation of the human pathogen Helicobacter pylori. DntR belongs to the LysR family and the crystal structures obtained have allowed the proposal a model of the interaction of DntR with salicylate inducer as well as giving insights into the signal propagation mechanism in LysR-type transcription factors (paper I). DntR mutant crystal structures combined with the modelling of DntR-2,4-dnt interactions led to the design of a DntR mutant that has a limited response to 2,4-dnt in a whole cell biosensor system (paper 2). Crystal structures of apo-NikR from H. pylori (HpNikR) and of Ni-bound intermediary states of the protein were obtained. The latter have helped in unravelling the Ni incorporation and selectivity mechanisms of NikRs and have shown a strong cooperativity between conformational changes in the Ni binding domain with movements of the DNA binding domain (paper 3). Biochemical studies and comparisons of the HpNikR crystal structures with those of NikR homologues strongly suggest that HpNikR has evolved different surface properties (paper 4) and a new mode of DNA binding

Myristoylation, an ancient protein modification mirroring eukaryogenesis and evolution

International audienceN-myristoylation (MYR) is a crucial fatty acylation catalyzed by N-myristoyltransferases (NMTs) that is likely to have appeared over 2 billion years ago. Proteome-wide approaches have now delivered an exhaustive list of substrates undergoing MYR across approximately 2% of any proteome, with constituents, several unexpected, associated with different membrane compartments. A set of \textless10 proteins conserved in eukaryotes probably represents the original set of N-myristoylated targets, marking major changes occurring throughout eukaryogenesis. Recent findings have revealed unexpected mechanisms and reactivity, suggesting competition with other acylations that are likely to influence cellular homeostasis and the steady state of the modification landscape. Here, we review recent advances in NMT catalysis, substrate specificity, and MYR proteomics, and discuss concepts regarding MYR during evolution

Proteome-wide probing of the dual NMT-dependent myristoylation tradeoff unveils potent, mechanism-based suicide inhibitors

ABSTRACT N-myristoyltransferases (NMTs) catalyze protein myristoylation, a major and ubiquitous lipid modification. Originally thought to modify only N-terminal glycine α-amino groups (G-myristoylation), NMTs are now known to modify lysine ε-amino groups (K-myristoylation), the significance of which is uncertain. Here we exploited systematic structural proteomics analyses and a novel pipeline involving the Shigella IpaJ protease to discriminate K- and G-myristoylation with unprecedented accuracy and identify the specific features driving each modification. NMT-dependent K-myristoylation occurs post-translationally and only on lysines 1, 2, or 3 following G-myristoylation or caspase cleavage. Direct interactions between the substrate’s reactive amino group and the NMT catalytic base slow K-myristoylation catalysis. IpaJ unmasked novel K-myristoylation sites in a dozen human proteins. The unique properties of NMT-driven K-myristoylation allowed us to design potent, mechanism-based suicide NMT inhibitors. These analyses unravel the respective paths towards K-myristoylation, G-myristoylation, or NMT inhibition, which rely on a very subtle tradeoff embracing the chemical landscape around the reactive group. SIGNIFICANCE STATEMENT We report the specific and unique elements guiding N-myristoyltransferase to either alpha or epsilon myristoylation, allowing us to establish the post-translational nature of N-myristoyltransferase-dependent lysine myristoylation and design novel, potent N-myristoyltransferase inhibitors

Structural and large-scale analysis unveil the intertwined paths promoting NMT-catalyzed lysine and glycine myristoylation

International audienceN-myristoyltransferases (NMTs) catalyze protein myristoylation, a lipid modification crucial for cell survival and a range of pathophysiological processes. Originally thought to modify only N-terminal glycine α-amino groups (G-myristoylation), NMTs were recently shown to also modify lysine ε-amino groups (K-myristoylation). However, the clues ruling NMTdependent K-myristoylation and the full range of targets are currently unknown. Here we combine mass spectrometry, kinetic studies, in silico analysis, and crystallography to identify the specific features driving each modification. We show that direct interactions between the substrate's reactive amino group and the NMT catalytic base promote K-myristoylation but with poor efficiency compared to G-myristoylation, which instead uses a water-mediated interaction. We provide evidence of depletion of proteins with NMT-dependent Kmyristoylation motifs in humans, suggesting evolutionary pressure to prevent this modification in favor of G-myristoylation. In turn, we reveal that K-myristoylation may only result from post-translational events. Our studies finally unravel the respective paths towards Kmyristoylation or G-myristoylation, which rely on a very subtle tradeoff embracing the chemical landscape around the reactive group

Biochemical and structural analysis of N-myristoyltransferase mediated protein tagging

International audienceN-terminal myristoylation is an essential eukaryotic modification crucial for cellular homeostasis in the context of many physiological processes. Myristoylation is a lipid modification resulting in a C14 saturated fatty acid addition. This modification is challenging to capture due to its hydrophobicity, low abundance of target substrates, and the recent discovery of unexpected NMT reactivity including myristoylation of lysine side chains and N-acetylation in addition to classical N-terminal Gly-myristoylation. This chapter details the high-end approaches developed to characterize the different features of N-myristoylation and its targets through in vitro and in vivo labeling