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Search Results: 1 - 10 of 208535 matches for " Làszlò Tora "
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GPAT: Retrieval of genomic annotation from large genomic position datasets
Arnaud Krebs, Mattia Frontini, Làszlò Tora
BMC Bioinformatics , 2008, DOI: 10.1186/1471-2105-9-533
Abstract: To address this problem, we have developed a Genomic Position Annotation Tool (GPAT) with a simple web interface that allows the rapid and systematic labelling of thousands of genomic positions with several types of annotations. GPAT automatically extracts gene annotation information around the submitted positions from different public databases (Refseq or ENSEMBL). In addition, GPAT provides access to the expression status of the corresponding genes from either existing transcriptomic databases or from user generated expression data sets. Furthermore, GPAT allows the localisation of the genomic coordinates relative to the chromosome bands and the well characterised ENCODE regions. We successfully used GPAT to analyse ChIP on chip data and to identify genes functionally regulated by the TATA binding protein (TBP).GPAT provides a quick, convenient and flexible way to annotate large sets of genomic positions obtained after pre-analysis of ChIP-chip, ChIP-seq or other high throughput sequencing-based techniques. Through the different annotation data displayed, GPAT facilitates the interpretation of genome wide datasets for molecular biologists.One of the major issues in genomics is the genome wide mapping of transcription factor binding sites in order to study their function at the scale of the genome. The chromatin immunoprecipitation (ChIP) technique uses antibodies that are specific for a transcription factor or a chromatin modification, to isolate the DNA to which this factor or modified histone is bound in a cell at a given time. The recent appearance of several genome wide analysis techniques, where ChIP is either followed by DNA microarray analysis (ChIP on chip) or coupled to high throughput sequencing (ChIP-seq), made the genome wide mapping of DNA bound factors technically possible. However, these analyses generate tremendous amounts of genomic location data in the form of one-dimensional series of signals.Recently, efforts have been made to develop academic
Lessons from genome-wide studies: an integrated definition of the coactivator function of histone acetyl transferases
Krishanpal Anamika, Arnaud R Krebs, Julie Thompson, Olivier Poch, Didier Devys, Làszlò Tora
Epigenetics & Chromatin , 2010, DOI: 10.1186/1756-8935-3-18
Abstract: Histone post-translational modifications have shown to be key regulators among transcription regulation mechanisms [1,2]. Histone acetylation is known to play an important role in the regulation of transcriptional activity in eukaryotic cells [3] by affecting higher-order folding of chromatin fibres, loosening of the contacts between the DNA and the nucleosomes and/or histone-nonhistone protein interactions [4-8]. Histone acetylation on various target lysines is in general positively associated with gene expression. Thus, HATs (also called lysine acetyl transferases or KATs) are thought to increase the decompaction of chromatin, which in turn may increase the accessibility of factors that promote transcription [8-11]. In higher eukaryotes, two enzymatic families (GNAT and MYST), each containing a dozen histone acetyltransferase (HAT) enzymes, have been identified and have often been shown to be subunits of larger transcriptional coactivator complexes.Over the past decade, two approaches were mainly used to better understand the functional specificity of HATs. First, in vitro acetylation assays were carried out to investigate the substrate specificity of distinct HATs. These analyses showed that HATs exert a certain degree of specificity for particular lysine residues on different histone tails. Second, in vivo gene inactivation studies allowed testing the HAT specificity by observing phenotypical effects caused by ablation of a particular HAT. Interestingly, most of these studies argued for a high degree of specificity in the developmental or gene expression phenotypes. More recently, availability of new high-throughput technologies such as chromatin immunoprecipitation sequencing (ChIP-seq) allowed the investigation of the recruitment of HATs and the deposition of acetylation marks at a genome-wide scale [12,13]. Contrary to the biochemical and genetic evidence, when carefully analysed, the genome-wide data suggest a low specificity in the recruitment and activity
RNA Polymerase II Pausing Downstream of Core Histone Genes Is Different from Genes Producing Polyadenylated Transcripts
Krishanpal Anamika, àkos Gyenis, Laetitia Poidevin, Olivier Poch, Làszlò Tora
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038769
Abstract: Recent genome-wide chromatin immunoprecipitation coupled high throughput sequencing (ChIP-seq) analyses performed in various eukaryotic organisms, analysed RNA Polymerase II (Pol II) pausing around the transcription start sites of genes. In this study we have further investigated genome-wide binding of Pol II downstream of the 3′ end of the annotated genes (EAGs) by ChIP-seq in human cells. At almost all expressed genes we observed Pol II occupancy downstream of the EAGs suggesting that Pol II pausing 3′ from the transcription units is a rather common phenomenon. Downstream of EAGs Pol II transcripts can also be detected by global run-on and sequencing, suggesting the presence of functionally active Pol II. Based on Pol II occupancy downstream of EAGs we could distinguish distinct clusters of Pol II pause patterns. On core histone genes, coding for non-polyadenylated transcripts, Pol II occupancy is quickly dropping after the EAG. In contrast, on genes, whose transcripts undergo polyA tail addition [poly(A)+], Pol II occupancy downstream of the EAGs can be detected up to 4–6 kb. Inhibition of polyadenylation significantly increased Pol II occupancy downstream of EAGs at poly(A)+ genes, but not at the EAGs of core histone genes. The differential genome-wide Pol II occupancy profiles 3′ of the EAGs have also been confirmed in mouse embryonic stem (mES) cells, indicating that Pol II pauses genome-wide downstream of the EAGs in mammalian cells. Moreover, in mES cells the sharp drop of Pol II signal at the EAG of core histone genes seems to be independent of the phosphorylation status of the C-terminal domain of the large subunit of Pol II. Thus, our study uncovers a potential link between different mRNA 3′ end processing mechanisms and consequent Pol II transcription termination processes.
UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells
ákos Gyenis,David Umlauf,Zsuzsanna újfaludi,Imre Boros,Tao Ye,Làszlò Tora
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004483
Abstract: Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2–4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5–6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation.
Glutamine-Expanded Ataxin-7 Alters TFTC/STAGA Recruitment and Chromatin Structure Leading to Photoreceptor Dysfunction
Dominique Helmlinger,Sara Hardy,Gretta Abou-Sleymane,Adrien Eberlin,Aaron B. Bowman,Anne Gansmüller,Serge Picaud,Huda Y. Zoghbi,Yvon Trottier,Làszlò Tora,Didier Devys
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0040067
Abstract: Spinocerebellar ataxia type 7 (SCA7) is one of several inherited neurodegenerative disorders caused by a polyglutamine (polyQ) expansion, but it is the only one in which the retina is affected. Increasing evidence suggests that transcriptional alterations contribute to polyQ pathogenesis, although the mechanism is unclear. We previously demonstrated that theSCA7 gene product, ataxin-7 (ATXN7), is a subunit of the GCN5 histone acetyltransferase–containing coactivator complexes TFTC/STAGA. We show here that TFTC/STAGA complexes purified from SCA7 mice have normal TRRAP, GCN5, TAF12, and SPT3 levels and that their histone or nucleosomal acetylation activities are unaffected. However, rod photoreceptors from SCA7 mouse models showed severe chromatin decondensation. In agreement, polyQ-expanded ataxin-7 induced histone H3 hyperacetylation, resulting from an increased recruitment of TFTC/STAGA to specific promoters. Surprisingly, hyperacetylated genes were transcriptionally down-regulated, and expression analysis revealed that nearly all rod-specific genes were affected, leading to visual impairment in SCA7 mice. In conclusion, we describe here a set of events accounting for SCA7 pathogenesis in the retina, in which polyQ-expanded ATXN7 deregulated TFTC/STAGA recruitment to a subset of genes specifically expressed in rod photoreceptors, leading to chromatin alterations and consequent progressive loss of rod photoreceptor function.
Glutamine-Expanded Ataxin-7 Alters TFTC/STAGA Recruitment and Chromatin Structure Leading to Photoreceptor Dysfunction
Dominique Helmlinger,Sara Hardy equal contributor,Gretta Abou-Sleymane equal contributor,Adrien Eberlin,Aaron B Bowman,Anne Gansmüller,Serge Picaud,Huda Y Zoghbi,Yvon Trottier,Làszlò Tora ,Didier Devys
PLOS Biology , 2006, DOI: 10.1371/journal.pbio.0040067
Abstract: Spinocerebellar ataxia type 7 (SCA7) is one of several inherited neurodegenerative disorders caused by a polyglutamine (polyQ) expansion, but it is the only one in which the retina is affected. Increasing evidence suggests that transcriptional alterations contribute to polyQ pathogenesis, although the mechanism is unclear. We previously demonstrated that theSCA7 gene product, ataxin-7 (ATXN7), is a subunit of the GCN5 histone acetyltransferase–containing coactivator complexes TFTC/STAGA. We show here that TFTC/STAGA complexes purified from SCA7 mice have normal TRRAP, GCN5, TAF12, and SPT3 levels and that their histone or nucleosomal acetylation activities are unaffected. However, rod photoreceptors from SCA7 mouse models showed severe chromatin decondensation. In agreement, polyQ-expanded ataxin-7 induced histone H3 hyperacetylation, resulting from an increased recruitment of TFTC/STAGA to specific promoters. Surprisingly, hyperacetylated genes were transcriptionally down-regulated, and expression analysis revealed that nearly all rod-specific genes were affected, leading to visual impairment in SCA7 mice. In conclusion, we describe here a set of events accounting for SCA7 pathogenesis in the retina, in which polyQ-expanded ATXN7 deregulated TFTC/STAGA recruitment to a subset of genes specifically expressed in rod photoreceptors, leading to chromatin alterations and consequent progressive loss of rod photoreceptor function.
Ankle-Foot Continuous Passive Motion Device for Mobilization of Acute Stroke Patients  [PDF]
Csilla Vér, Gergely Hofgárt, László Menyhárt, László Kardos, László Csiba
Open Journal of Therapy and Rehabilitation (OJTR) , 2015, DOI: 10.4236/ojtr.2015.32004
Abstract: Purpose: To develop a continuous passive motion (CPM) device for the passive motion of the paretic ankle-foot and investigate the effect of continuous passive motion of bedridden, hemiparetic acute stroke patients. Methods: 49 patients with stroke were investigated. Results in stroke patients (device group) were compared with those of 15 control subjects (manual group) also with stroke but not treated by device. The period of the treatment was 7 days; the duration was 30 minutes per day by CPM device in the device group. The efficacy of the device was evaluated by scales used in the clinical routine (6th item of National Institutes of Health Stroke Scale (NIHSS), Modified Ashworth Scale (MAS), modified Rankin Scale (mRS)). Ankle’s passive range of motion (PROM) and flexible equinovalgus deformitiy were measured every day with a goniometer. Results: 6th item of NIHSS score improved by -0.76 (SD = 0.56) points in the device group (p < 0.001) compared to the baseline values; the mean change in the manual group was -0.33 (SD = 0.62) points (p = 0.055). The mean of MAS decreased significantly by -0.53 (SD = 1.12) point in the device group (p < 0.001). The ankle’s mean plantar flexion PROM increased by 3.41 (SD = 5.19) degrees in the device group (p < 0.001). Significant improvement of the mean dorsiflexion in the PROM of the ankle was also detected (p = 0.019). The equinovalgus improved significantly by -5.12 (SD = 8.02) degrees (p < 0.001) in the device group. The scores of the mRS also improved significantly in the device group (p < 0.001). Conclusion: In the early phase of rehabilitation, ankle-foot continuous passive motion device treatment combined with manual therapy improved the ankle’s PROM better than manual therapy alone; in addition, device treatment decreased the foot’s equinovalgus, improved the 6th item NIHSS score, and decreased the severity of spasticity.
Magnetic anisotropy and chirality of frustrated Cr nanostructures on Au(111)
László Balogh,László Udvardi,László Szunyogh
Physics , 2014, DOI: 10.1088/0953-8984/26/43/436001
Abstract: By using a fully relativistic embedded cluster Green's function technique we investigated the magnetic anisotropy properties of four different compact Cr trimers (equilateral triangles) and Cr mono-layers deposited on Au(111) surface in both fcc and hcp stackings. For all trimers the magnetic ground state was found a frustrated 120$^\circ$ N\'eel configuration. Applying global spin rotations to the magnetic ground state, the predictions of an appropriate second order spin Hamiltonian were reproduced with high accuracy by the first principles calculations. For the Cr trimers with adjacent Au atoms in similar geometry we obtained similar values for the in-plane and out-of-plane anisotropy parameters, however, the Dzyaloshinskii-Moriya (DM) interactions appeared to differ remarkably. For two kinds of trimers we found an unconventional magnetic ground state showing 90$^\circ$ in-the-plane rotation with respect to the high symmetry directions. Due to higher symmetry, the in-plane anisotropy term was missing for the mono-layers and distinctly different DM interactions were obtained for the different stackings. The chiral degeneracy of the N\'eel configurations was lifted by less then 2 meV for the trimers, while this value raised up to about 15 meV per 3 Cr atoms for the hcp packed mono-layer.
Local order and orientational correlations in liquid and crystalline phases of carbon tetrabromide from neutron powder diffraction measurements
László Temleitner,László Pusztai
Physics , 2010, DOI: 10.1103/PhysRevB.81.134101
Abstract: The liquid, plastic crystalline and ordered crystalline phases of CBr$_4$ were studied using neutron powder diffraction. The measured total scattering differential cross-sections were modelled by Reverse Monte Carlo simulation techniques (RMC++ and RMCPOW). Following successful simulations, the single crystal diffraction pattern of the plastic phase, as well as partial radial distribution functions and orientational correlations for all the three phases have been calculated from the atomic coordinates ('particle configurations'). The single crystal pattern, calculated from a configuration that had been obtained from modelling the powder pattern, shows identical behavior to the recent single crystal data of Folmer et al. (Phys. Rev. {\bf B77}, 144205 (2008)). The BrBr partial radial distribution functions of the liquid and plastic crystalline phases are almost the same, while CC correlations clearly display long range ordering in the latter phase. Orientational correlations also suggest strong similarities between liquid and plastic crystalline phases, whereas the monoclinic phase behaves very differently. Orientations of the molecules are distinct in the ordered phase, whereas in the plastic crystal their distribution seems to be isotropic.
V473 Lyrae, a unique second-overtone Cepheid with two modulation cycles
László Molnár,László Szabados
Physics , 2014, DOI: 10.1093/mnras/stu1091
Abstract: V473 Lyrae is the only Galactic Cepheid with confirmed periodic amplitude and phase variations similar to the Blazhko effect observed in RR Lyrae stars. We collected all available photometric data and some radial velocity measurements to investigate the nature of the modulation. The comparison of the photometric and radial velocity amplitudes confirmed that the star pulsates in the second overtone. The extensive data set, spanning more than 40 years, allowed us to detect a secondary modulation cycle with a period of approximately 5300 days or 14.5 years. The secondary variations can be detected in the period of the primary modulation, as well. Phenomenologically, the light variations are analogous to the Blazhko effect. To find a physical link, we calculated linear hydrodynamic models to search for potential mode resonances that could drive the modulation and found two viable half-integer (n:2) and three n:4 resonances between the second overtone and other modes. If any of these resonances will be confirmed by non-linear models, it may confirm the mode resonance model, a common mechanism that can drive modulations both in RR Lyrae and Cepheid stars.
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