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Ihnatova I.,Masaryk University | Budinska E.,Masaryk University | Budinska E.,Central European Institute of Technology
BMC Bioinformatics | Year: 2015

Background: Pathway analysis methods, in which differentially expressed genes are mapped to databases of reference pathways and relative enrichment is assessed, help investigators to propose biologically relevant hypotheses. The last generation of pathway analysis methods takes into account the topological structure of a pathway, which helps to increase both specificity and sensitivity of the findings. Simultaneously, the RNA-Seq technology is gaining popularity and becomes widely used for gene expression profiling. Unfortunately, majority of topological pathway analysis methods remains without implementation and if an implementation exists, it is limited in various factors. Results: We developed a new R/Bioconductor package ToPASeq offering uniform interface to seven distinct topology-based pathway analysis methods, of which three we implemented de-novo and four were adjusted from existing implementations. Apart this, ToPASeq offers a set of tailored visualization functions and functions for importing and manipulating pathways and their topologies, facilitating the application of the methods on different species. The package can be used to compare the differential expression of pathways between two conditions on both gene expression microarray and RNA-Seq data. The package is written in R and is available from Bioconductor 3.2 using AGPL-3 license. Conclusion: ToPASeq is a novel package that offers seven distinct methods for topology-based pathway analysis, which are easily applicable on microarray as well as RNA-Seq data, both in human and other species. At the same time, it provides specific tools for visualization of the results. © 2015 Ihnatova and Budinska.

Novak J.,St Annes University Hospital Brno | Novak J.,Masaryk University | Kruzliak P.,St Annes University Hospital Brno | Bienertova-Vasku J.,Masaryk University | And 3 more authors.
Theranostics | Year: 2014

MicroRNAs (miRs) are small non-coding RNAs that negatively regulate gene expression by binding to the 3' untranslated regions (3'UTR) of their target mRNAs. MiRs were shown to play pivotal roles in tissue development and function and are also involved in the pathogenesis of various diseases including cancer. MicroRNA-206, which belongs to the group of so-called "myomiRs", is one of the most studied miRs thus far. In addition to being involved in skeletal muscle development and pathology, it has also been established that it is involved in the pathogenesis of numerous diseases including heart failure, chronic obstructive pulmonary disease, Alzheimer's disease and various types of cancers. The aim of this review is to provide a complex overview of microRNA-206, including regulating its expression, a brief description of its known functions in skeletal muscle and a complex overview of its roles in the biology and pathology of other tissues, emphasizing its significant diagnostic and therapeutic potential. © Ivyspring International Publisher.

Rehak P.,Brno University of Technology | Cerny M.,Brno University of Technology | Cerny M.,Central European Institute of Technology | Pokluda J.,Brno University of Technology | Pokluda J.,Central European Institute of Technology
Journal of Physics Condensed Matter | Year: 2012

Lattice dynamics and stability of four fcc crystals (Al, Ir, Pt and Au) under isotropic (hydrostatic) tensile loading are studied from first principles using the linear response method and the harmonic approximation. The results reveal that, contrary to former expectations, strengths of all the studied crystals are limited by instabilities related to soft phonons with finite or vanishing wavevectors. The critical strains associated with such instabilities are remarkably lower than those related to the volumetric instability. On the other hand, the corresponding reduction of the tensile strength is by 20% at the most. An analysis of elastic stability conditions is also performed and the results obtained by means of both approaches are compared. © 2012 IOP Publishing Ltd.

Rehak P.,Central European Institute of Technology | Cerny M.,Brno University of Technology
Key Engineering Materials | Year: 2014

Lattice dynamics and stability of fcc crystal of Ni under isotropic (hydrostatic) tensile loading are studied from first principles using supercell method and a harmonic approximation. According to the results, strength of the crystal is determined by occurrence of an instability related to soft phonons with finite wave vector. On the other hand, the critical strains and stresses associated with such instabilities are only slightly lower than those related to the volumetric instability. © (2014) Trans Tech Publications.

Cerny M.,Brno University of Technology | Sestak P.,Brno University of Technology | Pokluda J.,Brno University of Technology | Pokluda J.,Central European Institute of Technology
Computational Materials Science | Year: 2012

Ab initio simulations of uniaxial tensile and compressive loading in 〈1 1 0〉 direction, 〈1 1 1〉{1 1 0} shear and their superposition in six perfect crystals of bcc metals are performed using a plane wave code working within the framework of density functional theory. Under uniaxial compression, the crystal lattice transforms along an orthorhombic path that connects two bcc states and goes through one or two states of tetragonal symmetry. Such structural transformations determine compressive strengths of bcc crystals. On the other hand, reaching the maximum tensile stress coincides with vanishing of the shear strength in lattice planes perpendicular to the loading axis. The theoretical shear strength is found to be a decreasing (increasing) function of the applied tensile (compressive) normal stress in most studied cases. One of potential applications of this particular result is a prediction of shear instabilities in crystal lattices during tensile tests. Estimated critical tensile stresses related to shear instabilities in Mo and W under 〈1 1 0〉 tension are lower than the computed maximum tensile stresses and somewhat higher than experimental values. © 2011 Elsevier B.V. All rights reserved.

Islam B.,Queen's University of Belfast | Sgobba M.,Queen's University of Belfast | Laughton C.,University of Nottingham | Orozco M.,Barcelona Institute for Research in Biomedicine | And 4 more authors.
Nucleic Acids Research | Year: 2013

The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propellertype topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. Although G-quartet stems have been well characterized, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 ks. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology. © The Author(s) 2013.

Mladek A.,Academy of Sciences of the Czech Republic | Banas P.,Palacky University | Jurecka P.,Palacky University | Otyepka M.,Palacky University | And 3 more authors.
Journal of Chemical Theory and Computation | Year: 2014

Sugar-phosphate backbone is an electronically complex molecular segment imparting RNA molecules high flexibility and architectonic heterogeneity necessary for their biological functions. The structural variability of RNA molecules is amplified by the presence of the 2′-hydroxyl group, capable of forming multitude of intra- and intermolecular interactions. Bioinformatics studies based on X-ray structure database revealed that RNA backbone samples at least 46 substates known as rotameric families. The present study provides a comprehensive analysis of RNA backbone conformational preferences and 2′-hydroxyl group orientations. First, we create a benchmark database of estimated CCSD(T)/CBS relative energies of all rotameric families and test performance of dispersion-corrected DFT-D3 methods and molecular mechanics in vacuum and in continuum solvent. The performance of the DFT-D3 methods is in general quite satisfactory. The B-LYP-D3 method provides the best trade-off between accuracy and computational demands. B3-LYP-D3 slightly outperforms the new PW6B95-D3 and MPW1B95-D3 and is the second most accurate density functional of the study. The best agreement with CCSD(T)/CBS is provided by DSD-B-LYP-D3 double-hybrid functional, although its large-scale applications may be limited by high computational costs. Molecular mechanics does not reproduce the fine energy differences between the RNA backbone substates. We also demonstrate that the differences in the magnitude of the hyperconjugation effect do not correlate with the energy ranking of the backbone conformations. Further, we investigated the 2′-hydroxyl group orientation preferences. For all families, we conducted a QM and MM hydroxyl group rigid scan in gas phase and solvent. We then carried out set of explicit solvent MD simulations of folded RNAs and analyze 2′-hydroxyl group orientations of different backbone families in MD. The solvent energy profiles determined primarily by the sugar pucker match well with the distribution data derived from the simulations. The QM and MM energy profiles predict the same 2′-hydroxyl group orientation preferences. Finally, we demonstrate that the high energy of unfavorable and rarely sampled 2′-hydroxyl group orientations can be attributed to clashes between occupied orbitals. © 2013 American Chemical Society.

Fulcher N.,Austrian Academy of Sciences | Derboven E.,Austrian Academy of Sciences | Valuchova S.,Austrian Academy of Sciences | Riha K.,Austrian Academy of Sciences | Riha K.,Central European Institute of Technology
Cellular and Molecular Life Sciences | Year: 2014

Genome organization into linear chromosomes likely represents an important evolutionary innovation that has permitted the development of the sexual life cycle; this process has consequently advanced nuclear expansion and increased complexity of eukaryotic genomes. Chromosome linearity, however, poses a major challenge to the internal cellular machinery. The need to efficiently recognize and repair DNA double-strand breaks that occur as a consequence of DNA damage presents a constant threat to native chromosome ends known as telomeres. In this review, we present a comparative survey of various solutions to the end protection problem, maintaining an emphasis on DNA structure. This begins with telomeric structures derived from a subset of prokaryotes, mitochondria, and viruses, and will progress into the typical telomere structure exhibited by higher organisms containing TTAGG-like tandem sequences. We next examine non-canonical telomeres from Drosophila melanogaster, which comprise arrays of retrotransposons. Finally, we discuss telomeric structures in evolution and possible switches between canonical and non-canonical solutions to chromosome end protection. © Springer Basel 2013.

Krenkova J.,Academy of Sciences of the Czech Republic | Foret F.,Academy of Sciences of the Czech Republic | Foret F.,Central European Institute of Technology
Proteomics | Year: 2012

After shining as the ultimate separation - sequencing technique used for the successful completion of the Human Genome Project, in the early 2000s CE experienced lowered popularity among separation scientists. The renewed interest in recent years relates to the separation needs, especially in proteomics, metabolomics, and glycomics, where CE complements liquid chromatography techniques. This interest is further boosted by the regulators requiring additional separation techniques for characterization of newly developed pharmaceuticals. This paper gives a short overview of recent developments in the on-line interfacing of CE separation techniques with electrospray ionization/mass spectrometric analysis. Both the instrumentation and selected CE/ESI/MS applications including analyses of peptides, proteins, and glycans are discussed with the stress on research published in the past 3 years. Techniques related to the proteomic and glycomic analyses such as sample preconcentration, on-line protein digestion, and analyte derivatization prior CE/ESI/MS analysis are also included. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Werner K.,Central European Institute of Technology | Oberzaucher J.,Central European Institute of Technology | Werner F.,Central European Institute of Technology
Proceedings - 2012 6th International Conference on Complex, Intelligent, and Software Intensive Systems, CISIS 2012 | Year: 2012

This paper describes the evaluation of human-robot-interaction (HRI) related to the future use of a humanoid robotic system as interface in intelligent home environments. The core motivation was to enhance the user interaction between smart home systems and senior users by introducing a humanoid, mobile socially assistive robot as user interface. To what extend older users accept and use the autonomous robot as interface is the central research topic covered in this paper. To evaluate this question a user evaluation was performed together with 16 older people within the "Living Lab Schwechat" in Austrias [15] and a senior citizen home in Tel Aviv, Israel. Detailed results covering user acceptance, the users' attitude towards the robot, perception of the robot by the users and scores regarding the naturalness, animacy and intelligence of the tested system are presented and recommendations for improvements of the system are given. © 2012 Crown Copyright.

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