TY - JOUR AU - Kovács, Ákos AU - Sükösd, Farkas AU - Kuthi, Levente AU - Boros, Imre Miklós AU - Vedelek, Balázs TI - Novel method for detecting frequent TERT promoter hot spot mutations in bladder cancer samples. JF - CLINICAL AND EXPERIMENTAL MEDICINE J2 - CLIN EXP MED VL - 24 PY - 2024 IS - 1 SP - 192 SN - 1591-8890 DO - 10.1007/s10238-024-01464-3 UR - https://m2.mtmt.hu/api/publication/35176626 ID - 35176626 N1 - Funding Agency and Grant Number: University of Szeged; National Research, Development and Innovation Office-NKFIH [GINOP-2.3.2-15- 2016-00020]; National Laboratory of Biotechnology [2022-2.1.1-NL-2022-00008]; National Academy of Scientist Education Program of the National Biomedical Foundation under Hungarian Ministry of Culture and Innovation; University of Szeged Open Fund [6646] Funding text: Open access funding provided by University of Szeged. The financial support of the National Research, Development and Innovation Office-NKFIH through grant GINOP-2.3.2-15- 2016-00020 to I.M.B. and B.V. and 2022-2.1.1-NL-2022-00008 to the National Laboratory of Biotechnology is greatly appreciated. A.K. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation. We are also grateful for the open access support of the University of Szeged Open Fund, for the grant 6646. AB - Telomerase reverse transcriptase promoter (TERTp) mutations are frequently targeted tumor markers, however, they reside in regions with high GC content, which poses challenges when examined with simple molecular techniques or even with next-generation sequencing (NGS). In bladder cancer (BC), TERTp mutations are particularly frequent, however, none of the available tools have demonstrated efficacy in detecting TERTp mutations via a simple noninvasive technique. Therefore, we developed a novel PCR-based method for the detection of the two most common TERTp mutations and demonstrated its use for the analysis of BC samples. The developed SHARD-PCR TERTp mutation detection technique requires PCR and restriction digestion steps that are easily implementable even in less well-equipped laboratories. Cell lines with known mutational status were utilized for method development. Matching urine and tumor tissue samples from BC patients were analyzed, and the results were validated by next-generation sequencing. Analysis of eighteen urine and corresponding tumor tissue samples by SHARD-PCR revealed perfect matches in sample pairs, which paralleled the corresponding NGS results: fourteen samples exhibited mutations at the -124 position, two samples showed mutations at the -146 position, and no mutations were detected in two samples. Our study serves as a proof-of-concept and is limited by its small sample size, nonetheless, it demonstrates that SHARD-PCR is a simple, economic and highly reliable method for detecting TERTp mutations, which are common in different cancer types. For bladder cancer, SHARD-PCR can be performed with the use of noninvasive samples and could replace or complement currently used techniques. LA - English DB - MTMT ER - TY - JOUR AU - Inczefi, Orsolya AU - Eutamene, Hélène AU - Placide, Fanny AU - Tondereau, Valérie AU - Pallagi, Petra AU - Bagyánszki, Mária AU - Bódi, Nikolett AU - Gémes, Nikolett AU - Szebeni, Gábor AU - Molnár, Tamás AU - Theodorou, Vassilia AU - Róka, Richárd László TI - Translational evaluation of Gelsectan® effects on gut barrier dysfunction and visceral pain in animal models and irritable bowel syndrome with diarrhoea JF - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL J2 - UEG JOURNAL PY - 2024 PG - 12 SN - 2050-6406 DO - 10.1002/ueg2.12625 UR - https://m2.mtmt.hu/api/publication/35162166 ID - 35162166 N1 - Department of Medicine, Centre for Gastroenterology, University of Szeged, Szeged, Hungary UMR 1331, Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse III, ENVT, Toulouse, France Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary Department of Internal Medicine, Hematology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary Export Date: 15 August 2024 Correspondence Address: Inczefi, O.; Department of Medicine, Hungary; email: inczefi@gmail.com LA - English DB - MTMT ER - TY - JOUR AU - Szlanka, Tamás AU - Lukacsovich, Tamás AU - Bálint, Éva AU - Virágh, Eszter Erika AU - Szabó, Kornélia AU - Hajdú, Ildikó AU - Molnár, Enikő AU - Lin, Yu-Hsien AU - Zvara, Ágnes AU - Kelemen-Valkony, Ildikó AU - Méhi, Orsolya Katinka AU - Török, István AU - Hegedűs, Zoltán AU - Kiss, Brigitta AU - Ramasz, Beáta AU - Magdalena, Laura M AU - Puskás, László AU - Mechler, Bernard M AU - Fónagy, Adrien AU - Asztalos, Zoltán Imre AU - Steinbach, Gábor AU - Žurovec, Michal AU - Boros, Imre Miklós AU - Kiss, István TI - Dominant suppressor genes of p53-induced apoptosis in Drosophila melanogaster JF - G3-GENES GENOMES GENETICS J2 - G3-GENES GENOM GENET VL - 14 PY - 2024 IS - 9 PG - 11 SN - 2160-1836 DO - 10.1093/g3journal/jkae149 UR - https://m2.mtmt.hu/api/publication/35135174 ID - 35135174 N1 - Funding Agency and Grant Number: Hungarian Scientific Research Fund [OTKA K69279]; German Research Foundation (DFG)-Hungarian Academy of Sciences (MTA) Collaboration Program [UNG 436 113/81/0-6]; National Research, Development and Innovation Office [NKFIH 138128]; European Community's Program Interreg Bayern Tschechische Republik [BYCZ01-039] Funding text: This work was supported by the Hungarian Scientific Research Fund (OTKA K69279). BMM and IK were supported by the German Research Foundation (DFG)-Hungarian Academy of Sciences (MTA) Collaboration Program (UNG 436 113/81/0-6). AF was supported by National Research, Development and Innovation Office (NKFIH 138128). M & Zcaron; was supported by the European Community's Program Interreg Bayern Tschechische Republik (BYCZ01-039). DAS:The strains and the DEP transposon are available upon request. All data confirming the conclusions of the article are included in the article, figures, and tables. AB - One of a major function of programmed cell death (apoptosis) is the removal of cells which suffered oncogenic mutations, thereby preventing cancerous transformation. By making use of a Double-Headed-EP (DEP) transposon, a P element derivative made in our laboratory, we made an insertional mutagenesis screen in Drosophila melanogaster to identify genes which, when overexpressed, suppress the p53-activated apoptosis. The DEP element has Gal4-activatable, outward-directed UAS-promoters at both ends which can be deleted separately in vivo. In the DEP insertion mutants, we used the GMR-Gal4 driver to induce transcription from both UAS-promoters and tested the suppression effect on the apoptotic rough eye phenotype generated by an activated UAS-p53 transgene. By DEP insertions, seven genes were identified which suppressed the p53-induced apoptosis. In four mutants, the suppression effect resulted from single genes activated by one UAS-promoter (Pka-R2, Rga, crol, Spt5). In the other three (Orct2, Polr2M, stg), deleting either UAS-promoter eliminated the suppression effect. In qPCR experiments we found that the genes in the vicinity of the DEP insertion also showed an elevated expression level. This suggested an additive effect of the nearby genes on suppressing apoptosis. In the eucaryotic genomes there are co-expressed gene clusters. Three of the DEP insertion mutants are included and two are in close vicinity of separate co-expressed gene clusters. This raises the possibility that the activity of some of the genes in these clusters may help the suppression of the apoptotic cell death. LA - English DB - MTMT ER - TY - JOUR AU - Ruppert, Zsófia AU - Neuperger, Patricia AU - Rákóczi, Bettina AU - Gémes, Nikolett AU - Dukay, Brigitta AU - Hajdu, Petra AU - Péter, Mária AU - Balogh, Gábor AU - Tiszlavicz, László AU - Vigh, László AU - Török, Zsolt AU - Puskás, László AU - Szebeni, Gábor AU - Tóth, Erzsébet Melinda TI - Characterization of obesity-related diseases and inflammation using single cell immunophenotyping in two different diet-induced obesity models JF - INTERNATIONAL JOURNAL OF OBESITY J2 - INT J OBES (LOND) PY - 2024 SN - 0307-0565 DO - 10.1038/s41366-024-01584-6 UR - https://m2.mtmt.hu/api/publication/35133023 ID - 35133023 N1 - Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary PhD School in Biology, University of Szeged, Szeged, Hungary Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, Szeged, Hungary Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Department of Internal Medicine, Hematology Centre, Faculty of Medicine, University of Szeged, Szeged, H6725, Hungary Export Date: 2 August 2024 CODEN: IJOBD Correspondence Address: Tóth, M.E.; Laboratory of Molecular Stress Biology, Hungary; email: toth.erzsebetmelinda@brc.hu Correspondence Address: Szebeni, G.J.; Laboratory of Functional Genomics, Hungary; email: szebeni.gabor@brc.hu A közlemény a Bolyai János Kutatási Ösztöndíj (BO/00582/22/8) segítségével jött létre. LA - English DB - MTMT ER - TY - JOUR AU - Montoya, Brian AU - Melo-Silva, Carolina R. AU - Tang, Lingjuan AU - Kafle, Samita AU - Lidskiy, Peter AU - Bajusz, Csaba AU - Vadovics, Mate AU - Muramatsu, Hiromi AU - Ábrahám, Edit AU - Lipinszki, Zoltán AU - Chatterjee, Debotri AU - Scher, Gabrielle AU - Benitez, Juliana AU - Sung, Molly M. H. AU - Tam, Ying K. AU - Catanzaro, Nicholas J. AU - Schaefer, Alexandra AU - Andino, Raul AU - Baric, Ralph S. AU - Martinez, David R. AU - Pardi, Norbert AU - Sigal, Luis J. TI - mRNA-LNP vaccine-induced CD8+T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies JF - MOLECULAR THERAPY J2 - MOL THER VL - 32 PY - 2024 IS - 6 SP - 1790 EP - 1804 PG - 15 SN - 1525-0016 DO - 10.1016/j.ymthe.2024.04.019 UR - https://m2.mtmt.hu/api/publication/35117415 ID - 35117415 N1 - Funding Agency and Grant Number: Sigal laboratory [R56AI110457, R01AI175567, R01AI169460]; Pardi laboratory [R01AI146101, R01AI153064, P01AI158571]; Baric laboratory [P01 AI158571]; Andino laboratory [R01AI169460]; Hungarian Academy of Sciences [LP2017-7/2017]; National Laboratory for Biotechnology [2022-2.1.1-NL-2022-00008]; National Laboratory for Biotechnology, Szeged, Hungary [2022-2.1.1-NL-2022-00008]; NIAID, NIH, USA [T32AI134646] Funding text: R56AI110457, R01AI175567, and R01AI169460 funded the Sigal laboratory. R01AI146101, R01AI153064, and P01AI158571 funded the Pardi laboratory. P01 AI158571 funded the Baric laboratory. R01AI169460 funded the Andino laboratory. The Lipinszki laboratory was funded by the Hungarian Academy of Sciences (Lenduelet Program Grant [LP2017-7/2017] and the National Laboratory for Biotechnology [2022-2.1.1-NL-2022-00008] ) . C.B. was a postdoctoral fellow in the Pardi Laboratory supported by the National Laboratory for Biotechnology (2022-2.1.1-NL-2022-00008) , Szeged, Hungary. B.M. was partly funded by T32AI134646 (NIAID, NIH, USA) to L.J.S. We thank the NIH tetramer core facility for providing spike-speci fi c tetramers for CD8 + T cell detection. We thank the Thomas Jefferson University Laboratory Animal Facility for animal care. We thank the Thomas Jefferson University BSL3/ABSL3 shared resource, the Center for Vaccines and Pandemic Preparedness, Megan Watson, and Holly Ramage for experimental and technical assistance. AB - The role of CD8+ T cells in SARS-CoV-2 pathogenesis or mRNA-LNP vaccine-induced protection from lethal COVID-19 is unclear. Using mouse-adapted SARS-CoV-2 virus (MA30) in C57BL/6 mice, we show that CD8+ T cells are unnecessary for the intrinsic resistance of female or the susceptibility of male mice to lethal SARS-CoV-2 infection. Also, mice immunized with a di-proline prefusion-stabilized full-length SARS-CoV-2 Spike (S-2P) mRNA-LNP vaccine, which induces Spike-specific antibodies and CD8+ T cells specific for the Spike-derived VNFNFNGL peptide, are protected from SARSCoV-2 infection-induced lethality and weight loss, while mice vaccinated with mRNA-LNPs encoding only VNFNFNGL are protected from lethality but not weight loss. CD8+ T cell depletion ablates protection in VNFNFNGL but not in S-2P mRNApresent but essential for survival in their absence. Hence, vacSARS-CoV-2 variants that mutate epitopes targeted by protective antibodies. LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Lili AU - Tóth, Ágnes AU - Harami, Gábor AU - Pálinkás, János AU - Karatayeva, Nargis AU - Sajben-Nagy, Enikő Ilona AU - Bene, Szabolcs AU - Afzali, Sara AU - Kovács, Mihály AU - Juhász, Szilvia AU - Burkovics, Péter TI - Werner helicase interacting protein 1 contributes to G-quadruplex processing in human cells JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-024-66425-y UR - https://m2.mtmt.hu/api/publication/35090013 ID - 35090013 N1 - Funding Agency and Grant Number: HUN-REN Biological Research Centre, Szeged Funding text: Open access funding provided by HUN-REN Biological Research Centre, Szeged. DAS:All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. AB - Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood. Here we show that human WRNIP1 interacts with G4 structures and provide evidence for its contribution to G4 processing. The absence of WRNIP1 results in elevated levels of G4 structures, DNA damage and chromosome aberrations following treatment with PhenDC3, a G4-stabilizing ligand. Additionally, we establish a functional and physical relationship between WRNIP1 and the PIF1 helicase in G4 processing. In summary, our results suggest that WRNIP1 aids genome replication and maintenance by regulating G4 processing and this activity relies on Pif1 DNA helicase. LA - English DB - MTMT ER - TY - JOUR AU - Dukic, Barbara AU - Ruppert, Zsófia AU - Tóth, Erzsébet Melinda AU - Hunya, Ákos AU - Czibula, Ágnes AU - Bíró, Péter AU - Tiszlavicz, Ádám AU - Péter, Mária AU - Balogh, Gábor AU - Erdélyi, Miklós AU - Timinszky, Gyula AU - Vigh, László AU - Gombos, Imre AU - Török, Zsolt TI - Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms JF - CELLS J2 - CELLS-BASEL VL - 13 PY - 2024 IS - 13 PG - 16 SN - 2073-4409 DO - 10.3390/cells13131141 UR - https://m2.mtmt.hu/api/publication/35083838 ID - 35083838 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [OTKA ANN132280, OTKA K135759, OTKA K143248, OTKA FK135699, 2018-1.1.2-KFI-2018-00202, TKP2021-NVA-19]; Hungarian Research Network [SA-72/2021] Funding text: This research was funded by the National Research, Development and Innovation Office(OTKA ANN132280, OTKA K135759, OTKA K143248, OTKA FK135699, 2018-1.1.2-KFI-2018-00202,TKP2021-NVA-19) and the Hungarian Research Network (SA-72/2021). AB - Previous studies reported that a mild, non-protein-denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed that the master regulator of the UPR, the IRE1 (inositol-requiring enzyme 1) protein, is clustered as a result of UPR activation in a human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, a temperature-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we detected significant intracellular thermogenesis in mouse embryonic fibroblast (MEF) cells. Temperatures reached at least 8 °C higher than the external environment (40 °C), resulting in exceptionally high ER temperatures similar to those previously described for mitochondria. Mild heat-induced thermogenesis in the ER of MEF cells was likely due to the uncoupling of the Ca2+/ATPase (SERCA) pump. The high ER temperatures initiated a pronounced cytosolic heat-shock response in MEF cells, which was significantly lower in U2OS cells in which both the ER thermogenesis and SERCA pump uncoupling were absent. Our results suggest that depending on intrinsic cellular properties, mild hyperthermia-induced intracellular thermogenesis defines the cellular response mechanism and determines the outcome of hyperthermic stress. LA - English DB - MTMT ER - TY - JOUR AU - Szebeni, Gábor AU - Balog, Attila TI - Closing Editorial: Immunophenotyping in Autoimmune Diseases and Cancer 3.0 JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 12 PG - 5 SN - 1661-6596 DO - 10.3390/ijms25126311 UR - https://m2.mtmt.hu/api/publication/34959555 ID - 34959555 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFI), Hungary [GINOP-2.3.2-15-2016-00030, 2020-1.1.6-JOVO-2021-00003, 2022-1.2.6-TET-IPARI-TR-2022-00023, 142877 FK22]; SZTE OK-KKA Hetenyi 2020 grant; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00582/22/8]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-23-5-SZTE-694] Funding text: This research was funded by the GINOP-2.3.2-15-2016-00030, 2020-1.1.6-JOVO-2021-00003, 2022-1.2.6-TET-IPARI-TR-2022-00023 and 142877 FK22 grants from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by an SZTE OK-KKA Hetenyi 2020 grant (AB). This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GJS) and the UNKP-23-5-SZTE-694 New National Excellence Program of the Ministry for Innovation and Technology (GJS). AB - The mammalian immune system is a Janus-faced network of well-coordinated highly specialized cells and biomolecules [...] LA - English DB - MTMT ER - TY - JOUR AU - Karkas, Réka AU - Abdullah, Khaldoon Sadiq Ahmed AU - Kaizer, László AU - Ürmös, A AU - Raya, May AU - Tiszlavicz, Lilla Györgyi AU - Pankotai, Tibor AU - Nagy, István AU - Mátés, Lajos AU - Sükösd, Farkas TI - LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment JF - INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY J2 - INT J GYNECOL PATHOL VL - AiP PY - 2024 SN - 0277-1691 DO - 10.1097/PGP.0000000000001035 UR - https://m2.mtmt.hu/api/publication/34883229 ID - 34883229 LA - English DB - MTMT ER - TY - JOUR AU - Moss, Charlotte E. AU - Johnston, Simon A. AU - Kimble, Joshua V. AU - Clements, Martha AU - Codd, Veryan AU - Hamby, Stephen AU - Goodall, Alison H. AU - Deshmukh, Sumeet AU - Sudbery, Ian AU - Coca, Daniel AU - Wilson, Heather L. AU - Kiss-Tóth, Endre TI - Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs JF - CELL REPORTS J2 - CELL REP VL - 43 PY - 2024 IS - 4 PG - 25 SN - 2211-1247 DO - 10.1016/j.celrep.2024.114073 UR - https://m2.mtmt.hu/api/publication/34873163 ID - 34873163 N1 - Funding Agency and Grant Number: Healthy Lifespan Institute, University of Sheffield Funding text: We thank Mark Ariaans, Jonathan Kilby, and Kay Hopkinson for technical assistance. We also thank phlebotomists Salman Almalki and Saffron Foster as well as all of the volunteers who donated blood to this research. Finally, we thank Steve Renshaw, Alison Condliffe, and Colin Bingle for their editorial input. This work was supported by the Healthy Lifespan Institute, University of Sheffield. AB - Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age -related changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration, and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years old) compared with younger (18-30 years old) donors, alongside downregulation of transcription factors MYC and USF1. In MDMs from young donors, knockdown of MYC or USF1 decreases phagocytosis and chemotaxis and alters the expression of associated genes, alongside adhesion and extracellular matrix remodeling. A concordant dysregulation of MYC and USF1 target genes is also seen in MDMs from older donors. Furthermore, older age and loss of either MYC or USF1 in MDMs leads to an increased cell size, altered morphology, and reduced actin content. Together, these results define MYC and USF1 as key drivers of MDM age -related functional decline and identify downstream targets to improve macrophage function in aging. LA - English DB - MTMT ER -