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1.

001-es BibID:BIBFORM099535
Első szerző:Bartáné Tóth Beáta (molekuláris biológus)
Cím:Regulatory modules of human thermogenic adipocytes : functional genomics of large cohort and Meta-analysis derived marker-genes / B. Tóth Beáta, Barta Zoltán, Barta Ákos Barnabás, Fésüs László
Dátum:2021
ISSN:1471-2164
Megjegyzések:Background Recently, ProFAT and BATLAS studies identified brown and white adipocytes marker genes based on analysis of large databases. They offered scores to determine the thermogenic status of adipocytes using the gene-expression data of these markers. In this work, we investigated the functional context of these genes. Results Gene Set Enrichment Analyses (KEGG, Reactome) of the BATLAS and ProFAT marker-genes identified pathways deterministic in the formation of brown and white adipocytes. The collection of the annotated proteins of the defined pathways resulted in expanded white and brown characteristic protein-sets, which theoretically contain all functional proteins that could be involved in the formation of adipocytes. Based on our previously obtained RNA-seq data, we visualized the expression profile of these proteins coding genes and found patterns consistent with the two adipocyte phenotypes. The trajectory of the regulatory processes could be outlined by the transcriptional profile of progenitor and differentiated adipocytes, highlighting the importance of suppression processes in browning. Protein interaction network-based functional genomics by STRING, Cytoscape and R-Igraph platforms revealed that different biological processes shape the brown and white adipocytes and highlighted key regulatory elements and modules including GAPDH-CS, DECR1, SOD2, IL6, HRAS, MTOR, INS-AKT, ERBB2 and 4-NFKB, and SLIT-ROBO-MAPK. To assess the potential role of a particular protein in shaping adipocytes, we assigned interaction network location-based scores (betweenness centrality, number of bridges) to them and created a freely accessible platform, the AdipoNET (https//adiponet.com), to conveniently use these data. The Eukaryote Promoter Database predicted the response elements in the UCP1 promoter for the identified, potentially important transcription factors (HIF1A, MYC, REL, PPARG, TP53, AR, RUNX, and FoxO1). Conclusion Our integrative approach-based results allowed us to investigate potential regulatory elements of thermogenesis in adipose tissue. The analyses revealed that some unique biological processes form the brown and white adipocyte phenotypes, which presumes the existence of the transitional states. The data also suggests that the two phenotypes are not mutually exclusive, and differentiation of thermogenic adipocyte requires induction of browning as well as repressions of whitening. The recognition of these simultaneous actions and the identified regulatory modules can open new direction in obesity research.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:BMC Genomics. - 22 : 1 (2021), p. 1-21. -
További szerzők:Barta Zoltán (1967-) (biológus, zoológus) Barta Ákos Barnabás Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
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2.

001-es BibID:BIBFORM054512
Első szerző:Brignull, Louise M.
Cím:Reprogramming of lysosomal gene expression by interleukin-4 and Stat6 / Louise M. Brignull, Zsolt Czimmerer, Hafida Saidi, Bence Daniel, Izabel Villela, Nathan W. Bartlett, Sebastian L. Johnston, Lisiane B. Meira, Laszlo Nagy, Axel Nohturfft
Dátum:2013
ISSN:1471-2164
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:BMC Genomics [electronic resource]. - 14 : 1 (2013), p. 1-20. -
További szerzők:Czimmerer Zsolt (1981-) (molekuláris biológus) Saidi, Hafida Dániel Bence (1987-) (molekuláris biológus) Villela, Izabel Bartlett, Nathan W. Johnston, Sebastian L. Meira, Lisiane B. Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Nohturfft, Axel
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3.

001-es BibID:BIBFORM072517
035-os BibID:(cikkazonosító)158 (WoS)000426305200003 (Scopus)85042425048
Első szerző:Ivády Gergely (laboratóriumi szakorvos)
Cím:Analytical parameters and validation of homopolymer detection in a pyrosequencing-based next generation sequencing system / Ivády Gergely, Madar László, Dzsudzsák Erika, Koczok Katalin, Kappelmayer János, Krulisova Veronika, Macek Milan, Horváth Attila, Balogh István
Dátum:2018
ISSN:1471-2164
Megjegyzések:BackgroundCurrent technologies in next-generation sequencing are offering high throughput reads at low costs, but still suffer from various sequencing errors. Although pyro- and ion semiconductor sequencing both have the advantage of delivering long and high quality reads, problems might occur when sequencing homopolymer-containing regions, since the repeating identical bases are going to incorporate during the same synthesis cycle, which leads to uncertainty in base calling. The aim of this study was to evaluate the analytical performance of a pyrosequencing-based next-generation sequencing system in detecting homopolymer sequences using homopolymer-preintegrated plasmid constructs and human DNA samples originating from patients with cystic fibrosis.ResultsIn the plasmid system average correct genotyping was 95.8% in 4-mers, 87.4% in 5-mers and 72.1% in 6-mers. Despite the experienced low genotyping accuracy in 5- and 6-mers, it was possible to generate amplicons with more than a 90% adequate detection rate in every homopolymer tract. When homopolymers in the CFTR gene were sequenced average accuracy was 89.3%, but varied in a wide range (52.2 ? 99.1%). In all but one case, an optimal amplicon-sequencing primer combination could be identified. In that single case (7A tract in exon 14 (c.2046_2052)), none of the tested primer sets produced the required analytical performance.ConclusionsOur results show that pyrosequencing is the most reliable in case of 4-mers and as homopolymer length gradually increases, accuracy deteriorates. With careful primer selection, the NGS system was able to correctly genotype all but one of the homopolymers in the CFTR gene. In conclusion, we configured a plasmid test system that can be used to assess genotyping accuracy of NGS devices and developed an accurate NGS assay for the molecular diagnosis of CF using self-designed primers for amplification and sequencing.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Pyrosequencing
Homopolymer detection
Cystic fibrosis
Megjelenés:BMC Genomics. - 19 (2018), p. 1-8. -
További szerzők:Madar László (1972-) (klinikai laboratóriumi kutató) Dzsudzsák Erika Koczok Katalin (1979-) (labororvos) Kappelmayer János (1960-) (laboratóriumi szakorvos) Krulisova, Veronika Macek Jr., Milan Horváth Attila (1988-) (programtervező informatikus) Balogh István (1972-) (molekuláris biológus, genetikus)
Pályázati támogatás:K109076
OTKA
GINOP-2.3.2-15-2016-00039
GINOP
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4.

001-es BibID:BIBFORM065115
Első szerző:Nagy Gergely (molekuláris biológus)
Cím:Motif oriented high-resolution analysis of ChIP-seq data reveals the topological order of CTCF and cohesin proteins on DNA / Gergely Nagy, Erik Czipa, László Steiner, Tibor Nagy, Sándor Pongor, László Nagy, Endre Barta
Dátum:2016
ISSN:1471-2164
Megjegyzések:BACKGROUND:ChIP-seq provides a wealth of information on the approximate location of DNA-binding proteins genome-wide. It is known that the targeted motifs in most cases can be found at the peak centers. A high resolution mapping of ChIP-seq peaks could in principle allow the fine mapping of the protein constituents within protein complexes, but the current ChIP-seq analysis pipelines do not target the basepair resolution strand specific mapping of peak summits.RESULTS:The approach proposed here is based on i) locating regions that are bound by a sufficient number of proteins constituting a complex; ii) determining the position of the underlying motif using either a direct or a de novo motif search approach; and iii) determining the exact location of the peak summits with respect to the binding motif in a strand specific manner. We applied this method for analyzing the CTCF/cohesin complex, which holds together DNA loops. The relative positions of the constituents of the complex were determined with one-basepair estimated accuracy. Mapping the positions on a 3D model of DNA made it possible to deduce the approximate local topology of the complex that allowed us to predict how the CTCF/cohesin complex locks the DNA loops. As the positioning of the proteins was not compatible with previous models of loop closure, we proposed a plausible "double embrace" model in which the DNA loop is held together by two adjacent cohesin rings in such a way that the ring anchored by CTCF to one DNA duplex encircles the other DNA double helix and vice versa.CONCLUSIONS:A motif-centered, strand specific analysis of ChIP-seq data improves the accuracy of determining peak positions. If a genome contains a large number of binding sites for a given protein complex, such as transcription factor heterodimers or transcription factor/cofactor complexes, the relative position of the constituent proteins on the DNA can be established with an accuracy that allow one to deduce the local topology of the protein complex. The proposed high resolution mapping approach of ChIP-seq data is applicable for detecting the contact topology of DNA-binding protein complexes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
CTCF
DNA loop
cohesin
ChIP-seq
Megjelenés:BMC Genomics. - 17 : 637 (2016), p. 1-9. -
További szerzők:Czipa Erik (1990-) (molekuláris biológus, bioinformatikus) Steiner László Nagy Tibor (Gödöllő) Pongor Sándor Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Barta Endre (1963-) (molekuláris biológus)
Pályázati támogatás:TÁMOP-4.2.2.C-11/1/KONV-2012-0010
TÁMOP
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5.

001-es BibID:BIBFORM097910
035-os BibID:(cikkazonosító)310
Első szerző:Nagy Nikoletta Andrea (biológus)
Cím:Draft genome of a biparental beetle species, Lethrus apterus / Nagy Nikoletta A., Rácz Rita, Rimington Oliver, Póliska Szilárd, Orozco-terWengel Pablo, Bruford Michael W., Barta Zoltán
Dátum:2021
ISSN:1471-2164
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:BMC Genomics. - 22 : 1 (2021). -
További szerzők:Rácz Rita (1989-) (biológus) Rimington, Oliver Póliska Szilárd (1978-) (biológus) Orozco-terWengel, Pablo Bruford, Michael W. Barta Zoltán (1967-) (biológus, zoológus)
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6.

001-es BibID:BIBFORM018108
Első szerző:Pócsi István (vegyész)
Cím:Comparison of gene expression signatures of diamide, H2O2 and menadione exposed Aspergillus nidulans cultures - linking genome-wide transcriptional changes to cellular physiology / István Pócsi, Márton Miskei, Zsolt Karányi, Tamás Emri, Patricia Ayoubi, Tünde Pusztahelyi, György Balla, Rolf A. Prade
Dátum:2005
ISSN:1471-2164
Megjegyzések:Background In addition to their cytotoxic nature, reactive oxygen species (ROS) are also signal molecules in diverse cellular processes in eukaryotic organisms. Linking genome-wide transcriptional changes to cellular physiology in oxidative stress-exposed Aspergillus nidulans cultures provides the opportunity to estimate the sizes of peroxide (O22-), superoxide (O2?-) and glutathione/glutathione disulphide (GSH/GSSG) redox imbalance responses. Results Genome-wide transcriptional changes triggered by diamide, H2O2 and menadione in A. nidulans vegetative tissues were recorded using DNA microarrays containing 3533 unique PCR-amplified probes. Evaluation of LOESS-normalized data indicated that 2499 gene probes were affected by at least one stress-inducing agent. The stress induced by diamide and H2O2 were pulse-like, with recovery after 1 h exposure time while no recovery was observed with menadione. The distribution of stress-responsive gene probes among major physiological functional categories was approximately the same for each agent. The gene group sizes solely responsive to changes in intracellular O22-, O2?- concentrations or to GSH/GSSG redox imbalance were estimated at 7.7, 32.6 and 13.0 %, respectively. Gene groups responsive to diamide, H2O2 and menadione treatments and gene groups influenced by GSH/GSSG, O22- and O2?- were only partly overlapping with distinct enrichment profiles within functional categories. Changes in the GSH/GSSG redox state influenced expression of genes coding for PBS2 like MAPK kinase homologue, PSK2 kinase homologue, AtfA transcription factor, and many elements of ubiquitin tagging, cell division cycle regulators, translation machinery proteins, defense and stress proteins, transport proteins as well as many enzymes of the primary and secondary metabolisms. Meanwhile, a separate set of genes encoding transport proteins, CpcA and JlbA amino acid starvation-responsive transcription factors, and some elements of sexual development and sporulation was ROS responsive. Conclusion The existence of separate O22-, O2?- and GSH/GSSG responsive gene groups in a eukaryotic genome has been demonstrated. Oxidant-triggered, genome-wide transcriptional changes should be analyzed considering changes in oxidative stress-responsive physiological conditions and not correlating them directly to the chemistry and concentrations of the oxidative stress-inducing agent.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:BMC Genomics. - 6 : 182 (2005), p. 1-18 . -
További szerzők:Miskei Márton (1978-) (molekuláris biológus, genetikus) Karányi Zsolt (1961-) (biostatisztikus, bioinformatikus) Emri Tamás (1969-) (biológus) Ayoubi, Patricia Pusztahelyi Tünde (1969-) (biológus, angol-magyar szakfordító) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Prade, Rolf A.
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7.

001-es BibID:BIBFORM081935
035-os BibID:(WOS)000499182500001 (Scopus)85075277364
Első szerző:Szabó Krisztina (molekuláris biológus)
Cím:Deletion of the fungus specific protein phosphatase Z1 exaggerates the oxidative stress response in Candida albicans / Krisztina Szabó, Ágnes Jakab, Szilárd Póliska, Katalin Petrényi, Katalin Kovács, Lama Hasan Bou Issa, Tamás Emri, István Pócsi, Viktor Dombrádi
Dátum:2019
ISSN:1471-2164
Megjegyzések:Background:Candida albicansis an opportunistic pathogen which is responsible for widespread nosocomialinfections. It encompasses a fungus specific serine/threonine protein phosphatase gene, CaPPZ1 that is involvedin cation transport, cell wall integrity, oxidative stress response, morphological transition, and virulence accordingto the phenotypes of thecappz1deletion mutant.Results:We demonstrated that a short-term treatment with a sublethal concentration oftert-butyl hydroperoxidesuppressed the growth of the fungal cells without affecting their viability, both in thecappz1mutant and in thegenetically matching QMY23 control strains. To reveal the gene expression changes behind the above observationswe carried out a global transcriptome analysis. We used a pilot DNA microarray hybridization together withextensive RNA sequencing, and confirmed our results by quantitative RT-PCR. Novel functions of the CaPpz1enzyme and oxidative stress mechanisms have been unraveled. The numbers of genes affected as well as theamplitudes of the transcript level changes indicated that the deletion of the phosphatase sensitized the responseofC. albicansto oxidative stress conditions in important physiological functions like membrane transport, cellsurface interactions, oxidation-reduction processes, translation and RNA metabolism.Conclusions:We conclude that in the wild typeC. albicansCaPPZ1 has a protective role against oxidative damage.We suggest that the specific inhibition of this phosphatase combined with mild oxidative treatment could be afeasible approach to topical antifungal therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Candida albicans
Protein phosphatase Z1
Deletion mutant
Oxidative stress
tert-butyl hydoperoxide
Transcriptome
DNA microarray
RNA-Seq
Quantitative RT-PCR
Megjelenés:Bmc Genomics. - 20 (2019), p. 1-17. -
További szerzők:Jakab Ágnes (1987-) (biológus) Póliska Szilárd (1978-) (biológus) Petrényi Katalin (1988-) (Ph.D hallgató) Kovács Katalin (1978-) (biokémikus) Issa, Lama Hasan Bou Emri Tamás (1969-) (biológus) Pócsi István (1961-) (vegyész) Dombrádi Viktor (1953-) (biokémikus)
Pályázati támogatás:NKFIH-K108989
NKFIH
EFOP-3.6.1-16-2016-00022
EFOP
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8.

001-es BibID:BIBFORM049100
Első szerző:Veréb Zoltán (immunológus, mikrobiológus, molekuláris biológus)
Cím:Comparison of upstream regulators in human ex vivo cultured cornea limbal epithelial stem cells and differentiated corneal epithelial cells / Zoltán Veréb, Réka Albert, Szilárd Póliska, Ole Kristoffer Olstad, Saeed Akhtar, Morten C. Moe, Goran Petrovski
Dátum:2013
ISSN:1471-2164
Megjegyzések:BACKGROUND:The surface of the human eye is covered by corneal epithelial cells (CECs) which regenerate from a small population of limbal epithelial stem cells (LESCs). Cell therapy with LESCs is a non-penetrating treatment for preventing blindness due to LESC deficiency or dysfunction. Our aim was to identify new putative molecular markers and upstream regulators in the LESCs and associated molecular pathways.RESULTS:Genome-wide microarray transcriptional profiling was used to compare LESCs to differentiated human CECs. Ingenuity-based pathway analysis was applied to identify upstream regulators and pathways specific to LESCs. ELISA and flow cytometry were used to measure secreted and surface expressed proteins, respectively. More than 2 fold increase and decrease in expression could be found in 1830 genes between the two cell types. A number of molecules functioning in cellular movement (381), proliferation (567), development (552), death and survival (520), and cell-to-cell signaling (290) were detected having top biological functions in LESCs and several of these were confirmed by flow cytometric surface protein analysis. Custom-selected gene groups related to stemness, differentiation, cell adhesion, cytokines and growth factors as well as angiogenesis could be analyzed. The results show that LESCs play a key role not only in epithelial differentiation and tissue repair, but also in controlling angiogenesis and extracellular matrix integrity. Some pro-inflammatory cytokines were found to be important in stemness-, differentiation- and angiogenesis-related biological functions: IL-6 and IL-8 participated in most of these biological pathways as validated by their secretion from LESC cultures.CONCLUSIONS:The gene and molecular pathways may provide a more specific understanding of the signaling molecules associated with LESCs, therefore, help better identify and use these cells in the treatment of ocular surface diseases.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Limbal epithelial stem cells
Corneal epithelial cells
Gene array
Upstream regulators
Cytokines
Cell adhesion
IL-6
IL-8
Angiogenesis
Megjelenés:BMC Genomics. - 14 : 1 (2013), p. [1-33]. -
További szerzők:Albert Réka (1986-) Póliska Szilárd (1978-) (biológus) Olstad, Ole Kristoffer Akhtar, Saeed (1949-) (molekuláris biológus) Moe, Morten C. Petrovski, Goran (1975-) (orvos)
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