المؤلفون: Tomasz Budlewski, Joanna Sarnik, Grzegorz Galita, Grzegorz Dragan, Olga Brzezińska, Marta Popławska, Tomasz Popławski, Joanna Makowska

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 8, p 7586 (2023)

مصطلحات موضوعية: rheumatoid arthritis, PADI4, STAT4, PTPN22, single nucleotide polymorphisms, rs2240340, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Single nucleotide polymorphisms in non-HLA genes are involved in the development of rheumatoid arthritis (RA). SNPS in genes: PADI4 (rs2240340), STAT4 (rs7574865), CD40 (rs4810485), PTPN22 (rs2476601), and TRAF1 (rs3761847) have been described as risk factors for the development of autoimmune diseases, including RA. This study aimed to assess the prevalence of polymorphisms of these genes in the Polish population of patients with rheumatoid arthritis as compared to healthy controls. 324 subjects were included in the study: 153 healthy subjects and 181 patients from the Department of Rheumatology, Medical University of Lodz who fulfilled the criteria of rheumatoid arthritis diagnosis. Genotypes were determined by Taqman SNP Genotyping Assay. rs2476601 (G/A, OR = 2.16, CI = 1.27–3.66; A/A, OR = 10.35, CI = 1.27–84.21), rs2240340 (C/T, OR = 4.35, CI = 2.55–7.42; T/T, OR = 2.80, CI = 1.43–4.10) and rs7574865 (G/T, OR = 1.97, CI = 1.21–3.21; T/T, OR = 3.33, CI = 1.01–11.02) were associated with RA in the Polish population. Rs4810485 was also associated with RA, however after Bonferroni’s correction was statistically insignificant. We also found an association between minor alleles of rs2476601, rs2240340, and rs7574865 and RA (OR = 2.32, CI = 1.47–3.66; OR = 2.335, CI = 1.64–3.31; OR = 1.88, CI = 1.27–2.79, respectively). Multilocus analysis revealed an association between CGGGT and rare (below 0.02 frequency) haplotypes (OR = 12.28, CI = 2.65–56.91; OR = 3.23, CI = 1.63–6.39). In the Polish population, polymorphisms of the PADI4, PTPN22, and STAT4 genes have been detected, which are also known risk factors for RA in various other populations.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/8/7586Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/92df57bca73d4db38a7ffb26bc1c76f5Test

المؤلفون: Grzegorz Galita, Joanna Sarnik, Olga Brzezinska, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Ireneusz Majsterek, Tomasz Poplawski, Joanna S. Makowska

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 4; Pages: 3804

مصطلحات موضوعية: rheumatoid arthritis, DNA repair genes, DNA damage response, polymorphisms, SNP

جغرافية الموضوع: agris

الوصف: Rheumatoid arthritis (RA) is a chronic, multifactorial autoimmune disease characterized by chronic arthritis, a tendency to develop joint deformities, and involvement of extra-articular tissues. The risk of malignant neoplasms among patients with RA is the subject of ongoing research due to the autoimmune pathogenesis that underlies RA, the common etiology of rheumatic disease and malignancies, and the use of immunomodulatory therapy, which can alter immune system function and thus increase the risk of malignant neoplasms. This risk can also be increased by impaired DNA repair efficiency in individuals with RA, as reported in our recent study. Impaired DNA repair may reflect the variability in the genes that encode DNA repair proteins. The aim of our study was to evaluate the genetic variation in RA within the genes of the DNA damage repair system through base excision repair (BER), nucleotide excision repair (NER), and the double strand break repair system by homologous recombination (HR) and non-homologous end joining (NHEJ). We genotyped a total of 28 polymorphisms in 19 genes encoding DNA repair-related proteins in 100 age- and sex-matched RA patients and healthy subjects from Central Europe (Poland). Polymorphism genotypes were determined using the Taq-man SNP Genotyping Assay. We found an association between the RA occurrence and rs25487/XRCC1, rs7180135/RAD51, rs1801321/RAD51, rs963917/RAD51B, rs963918/RAD51B, rs2735383/NBS1, rs132774/XRCC6, rs207906/XRCC5, and rs861539/XRCC3 polymorphisms. Our results suggest that polymorphisms of DNA damage repair genes may play a role in RA pathogenesis and may be considered as potential markers of RA.

وصف الملف: application/pdf

العلاقة: Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms24043804Test

الإتاحة: https://doi.org/10.3390/ijms24043804Test

المؤلفون: Grzegorz Galita, Olga Brzezińska, Izabela Gulbas, Joanna Sarnik, Marta Poplawska, Joanna Makowska, Tomasz Poplawski

المصدر: Journal of Clinical Medicine; Volume 9; Issue 4; Pages: 988

مصطلحات موضوعية: DNA damage and repair, rheumatoid arthritis, oxidative DNA lesions, DNA double-strand breaks, comet assay

الوصف: Rheumatoid arthritis (RA) is a systemic, inflammatory disease of the joints and surrounding tissues. RA manifests itself with severe joint pain, articular inflammation, and oxidative stress. RA is associated with certain types of cancer. We have assumed that RA patients’ increased susceptibility to cancer may be linked with genomic instability induced by impaired DNA repair and sensitivity to DNA damaging agents. The aim of this work was to analyze the sensitivity of peripheral blood mononuclear cells (PBMCs) isolated from RA patients to DNA damaging agents: tert-butyl hydroperoxide (TBH), bleomycin, ultraviolet (UV) radiation, and methyl methanesulfonate (MMS) and calculate the repair efficiency. TBH induce oxidative DNA lesions repaired mainly by base excision repair (BER). Bleomycin induced mainly DNA double-strand breaks repaired by non-homologous end joining (NHEJ) and homologous recombination repair (HRR). We included 20 rheumatoid arthritis patients and 20 healthy controls and used an alkaline version of the comet assay with modification to measure sensitivity to DNA damaging agents and DNA repair efficiency. We found an increased number of DNA breaks and alkali-labile sites in the RA patients compared to those in the controls. Exposure to DNA damaging agents evoked the same increased damage in both groups, but we observed statistically higher PMBC sensitivity to TBH, MMS, bleomycin as well as UV. Examination of the repair kinetics of both groups revealed that the DNA lesions induced by TBH and bleomycin were more efficiently repaired in the controls than in the patients. These data suggest impaired DNA repair in RA patients, which may accelerate PBMC aging and/or lead to higher cancer incidence among RA patients.

وصف الملف: application/pdf

العلاقة: Immunology; https://dx.doi.org/10.3390/jcm9040988Test

الإتاحة: https://doi.org/10.3390/jcm9040988Test

المؤلفون: Marta Popławska

المصدر: Rozprawy Społeczne. 12:14-19

مصطلحات موضوعية: Instinct, Psychoanalysis, History, media_common.quotation_subject, Intuition, media_common

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::033df28e4a15232ca0fcb83b0454d8afTest
https://doi.org/10.29316/rs.2018.28Test

المؤلفون: Grzegorz Dudek, Sebastian Sakowski, Olga Brzezińska, Joanna Sarnik, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Tomasz Poplawski, Michał Bijak, Joanna Makowska

المصدر: PLoS ONE, Vol 19, Iss 3, p e0300717 (2024)

مصطلحات موضوعية: Medicine, Science

الوصف: Machine learning (ML) algorithms can handle complex genomic data and identify predictive patterns that may not be apparent through traditional statistical methods. They become popular tools for medical applications including prediction, diagnosis or treatment of complex diseases like rheumatoid arthritis (RA). RA is an autoimmune disease in which genetic factors play a major role. Among the most important genetic factors predisposing to the development of this disease and serving as genetic markers are HLA-DRB and non-HLA genes single nucleotide polymorphisms (SNPs). Another marker of RA is the presence of anticitrullinated peptide antibodies (ACPA) which is correlated with severity of RA. We use genetic data of SNPs in four non-HLA genes (PTPN22, STAT4, TRAF1, CD40 and PADI4) to predict the occurrence of ACPA positive RA in the Polish population. This work is a comprehensive comparative analysis, wherein we assess and juxtapose various ML classifiers. Our evaluation encompasses a range of models, including logistic regression, k-nearest neighbors, naïve Bayes, decision tree, boosted trees, multilayer perceptron, and support vector machines. The top-performing models demonstrated closely matched levels of accuracy, each distinguished by its particular strengths. Among these, we highly recommend the use of a decision tree as the foremost choice, given its exceptional performance and interpretability. The sensitivity and specificity of the ML models is about 70% that are satisfying. In addition, we introduce a novel feature importance estimation method characterized by its transparent interpretability and global optimality. This method allows us to thoroughly explore all conceivable combinations of polymorphisms, enabling us to pinpoint those possessing the highest predictive power. Taken together, these findings suggest that non-HLA SNPs allow to determine the group of individuals more prone to develop RA rheumatoid arthritis and further implement more precise preventive approach.

وصف الملف: electronic resource

العلاقة: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0300717&type=printableTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/cacca4404d51460ea692419b62c432a3Test

المؤلفون: Joanna Jerzynska, Marta Poplawska, Jaroslaw Dziadek, Tomasz Grzelewski, Pawel Majak, Wlodzimierz Stelmach, Iwona Stelmach, Malgorzata Podsiadlowicz-borzecka, Cellular Immunity In Children

المساهمون: The Pennsylvania State University CiteSeerX Archives

المصدر: http://cvi.asm.org/content/12/10/1246.full.pdfTest.

الوصف: This article cites 23 articles, 4 of which can be accessed free at

وصف الملف: application/pdf

العلاقة: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.602.4914Test; http://cvi.asm.org/content/12/10/1246.full.pdfTest

الإتاحة: http://cvi.asm.org/content/12/10/1246.full.pdfTest

المؤلفون: Grzegorz Galita, Joanna Sarnik, Olga Brzezinska, Tomasz Budlewski, Marta Poplawska, Sebastian Sakowski, Grzegorz Dudek, Ireneusz Majsterek, Joanna Makowska, Tomasz Poplawski

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 5, p 2619 (2024)

مصطلحات موضوعية: rheumatoid arthritis, comet assay, DNA double-strand break, DNA repair, single-nucleotide polymorphism, RAD50, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation affecting up to 2.0% of adults around the world. The molecular background of RA has not yet been fully elucidated, but RA is classified as a disease in which the genetic background is one of the most significant risk factors. One hallmark of RA is impaired DNA repair observed in patient-derived peripheral blood mononuclear cells (PBMCs). The aim of this study was to correlate the phenotype defined as the efficiency of DNA double-strand break (DSB) repair with the genotype limited to a single-nucleotide polymorphism (SNP) of DSB repair genes. We also analyzed the expression level of key DSB repair genes. The study population contained 45 RA patients and 45 healthy controls. We used a comet assay to study DSB repair after in vitro exposure to bleomycin in PBMCs from patients with rheumatoid arthritis. TaqMan SNP Genotyping Assays were used to determine the distribution of SNPs and the Taq Man gene expression assay was used to assess the RNA expression of DSB repair-related genes. PBMCs from patients with RA had significantly lower bleomycin-induced DNA lesion repair efficiency and we identified more subjects with inefficient DNA repair in RA compared with the control (84.5% vs. 24.4%; OR 41.4, 95% CI, 4.8–355.01). Furthermore, SNPs located within the RAD50 gene (rs1801321 and rs1801320) increased the OR to 53.5 (95% CI, 4.7–613.21) while rs963917 and rs3784099 (RAD51B) to 73.4 (95% CI, 5.3–1011.05). These results were confirmed by decision tree (DT) analysis (accuracy 0.84; precision 0.87, and specificity 0.86). We also found elevated expression of RAD51B, BRCA1, and BRCA2 in PBMCs isolated from RA patients. The findings indicated that impaired DSB repair in RA may be related to genetic variations in DSB repair genes as well as their expression levels. However, the mechanism of this relation, and whether it is direct or indirect, needs to be elucidated.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/5/2619Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/a9c9ee6f333f4796b520fc672da98ccdTest

المؤلفون: Marta Popławska, Włodzimierz Stelmach, Tomasz Grzelewski, Paweł Majak, Małgorzata Podsiadłowicz-Borzęcka, Iwona Stelmach, Joanna Jerzyńska, Jarosław Dziadek

المصدر: Clinical and Vaccine Immunology. 12:1246-1250

مصطلحات موضوعية: Male, Microbiology (medical), Immunoglobulin A, Cellular immunity, Mycoplasma pneumoniae, Time Factors, Clinical Biochemistry, Immunology, Antibodies and Mediators of Immunity, Immunoglobulin E, medicine.disease_cause, Immunoglobulin G, Immunophenotyping, Immune system, Pneumonia, Mycoplasma, medicine, Humans, Immunology and Allergy, Lymphocytes, Prospective Studies, Immunity, Cellular, biology, respiratory tract diseases, Immunoglobulin Isotypes, Child, Preschool, Immune System, Antibody Formation, Humoral immunity, biology.protein, Female, Antibody

الوصف: To determine whether children have persistent abnormalities in cellular and humoral immunity development after acute Mycoplasma pneumoniae infection, serum immunoglobulin G (IgG), IgA, IgM, and IgE levels and lymphocyte phenotypes were determined. There were no changes in the levels of IgG, IgM, IgA, or CD4 or CD19 lymphocytes that were measured in M. pneumoniae-positive patients after 3 months or after 12 months, but there were increases in these in M. pneumoniae-negative patients. Serum IgE increased in M. pneumoniae-positive patients. We have shown alterations in immunity development after M. pneumoniae infection. Mycoplasma pneumoniae is a common pathogen of children’s respiratory tracts (8), and its abilities to act as a polyclonal activator of lymphocytes and autoantibodies to various tissues and immune complexes are well known (2, 16). CD4 T cells, B cells, and plasma cells infiltrate the lungs, which is followed by further amplification of the immune response, namely, proliferation of lymphocytes, production of immunoglobulins, and release of proinflammatory cytokines (3, 14). It has been previously described that the levels of total immunoglobulins, immunoglobulin A (IgA), IgM, and IgG, in serum increase during the convalescent phase of the disease (19) and that there is production of IgE specific to M. pneumoniae during infection (18). The bronchoalveolar lavage cytokine data suggest a predominant Th2-like cytokine response in M. pneumoniae infections, thus representing a favorable condition for IgE production (7), although other results suggest a Th1 cytokine response predominance (5, 21). Previous studies are confined to the acute phase of M. pneumoniae infection and do not answer questions about the possible duration of the humoral and cellular imbalance after M. pneumoniae infection in children. In this study, we hypothesized that children may have persistent abnormalities in cellular and humoral immunity development after acute M. pneumoniae infection. The study participants included 110 patients (52 male and 58 female) aged 1 to 5 years, all suffering from recurrent respiratory tract infections, defined according to Ribeiro (15). The diagnosis of M. pneumoniae infection was based on clinical symptoms (12, 20) and the presence of IgM, determined by enzyme-linked immunosorbent assay (ELISA) and confirmed by PCR. Children diagnosed with M. pneumoniae infection were treated with clarithromycin (4). None of the patients had previously suffered from allergic disease or immunodeficiency syndrome. The characteristics of the patients are presented in Table 1. There were five study visits. At the first visit, patients were informed about the purpose of the study and were told that the second visit would occur after 3 months or earlier (in the case of respiratory tract infection). The patient’s medical history was recorded, a physical examination was done, and blood samples for IgG, IgA, IgM, and IgE serum levels and lymphocyte phenotypes were taken at each visit. During the second visit, a blood sample was taken to determine the presence of M. pneumoniae-specific IgM by ELISA. For patients who had M. pneumoniae IgM, the third visit occurred 1 week after the second, for determination of M. pneumoniae DNA by PCR. For patients without M. pneumoniae IgM, the third visit occurred 3 weeks after the second, when a blood sample was collected for the second determination of M. pneumoniaespecific IgM by ELISA. The fourth visit was 3 months after the second, and the fifth visit was 12 months after the second. Blood samples (5 ml) were collected, serum specimens were stored frozen, and the acute- and convalescent-phase serum specimens from each patient were tested for IgM antibodies in the same run. Upon their receipt, serum samples were serologically investigated for M. pneumoniae-specific IgM antibodies, using a commercial ELISA kit (Viro-Immun Labor-Diagnostica, Germany). We used capillary PCR to diagnose M. pneumoniae infection (6). Two whole-blood samples (3 ml) were obtained from each patient and were collected into sterile sodium heparinized tubes. The presence of Mycoplasma DNA in the clinical samples collected was tested using a nested-PCR assay with primers MPP-11, MPP-12, and MPSW-1 (TGCCATCAACCCGCG

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a16d52abfb6d824c075a07fec2aaa59fTest
https://doi.org/10.1128/cdli.12.10.1246-1250.2005Test

المؤلفون: Malini Rajagopalan, Hava Lofton, Jarosław Dziadek, Erin Maloney, Murty V. V. S. Madiraju, Ashwini Chauhan, Marta Popławska

المصدر: FEMS Microbiology Letters. 250:9-17

مصطلحات موضوعية: Cell division, Recombinant Fusion Proteins, Mycobacterium smegmatis, Biological Transport, Active, macromolecular substances, medicine.disease_cause, physiological processes, Microbiology, Plasmid, Bacterial Proteins, Two-Hybrid System Techniques, Escherichia coli, Genetics, medicine, FtsZ, Molecular Biology, Gene, Aspartic Acid, Base Sequence, biology, Membrane Proteins, Colocalization, biology.organism_classification, Cell biology, Cytoskeletal Proteins, Genes, Bacterial, biology.protein, bacteria, biological phenomena, cell phenomena, and immunity, Cell Division, Plasmids, Mycobacterium

الوصف: We provide genetic evidence to show that the Mycobacterium tuberculosis FtsZ and FtsW proteins interact, and that these interactions are biologically relevant. Furthermore, we show by fluorescence microscopy that Mycobacterium smegmatis FtsW is part of its septasomal complex and colocalizes with FtsZ to the midcell sites. Colocalization experiments reveal that approximately 27% of the cells with septal Z-rings contain FtsW whereas 93% of the cells with FtsW bands are associated with FtsZ indicating that FtsW is late recruit to the septum, as in Escherichia coli. Our results suggest that mycobacterial FtsZ can localize to the septum independent of FtsW, and that interactions of FtsW with FtsZ are critical for the formation of productive FtsZ-rings and the cell division process in mycobacteria.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::edff8853475169822f6ac29953a40c5dTest
https://doi.org/10.1016/j.femsle.2005.06.043Test

المؤلفون: Elżbieta Szymańska, Marta Popławska

المصدر: Folia Turistica. 42:125

مصطلحات موضوعية: Psychology

الوصف: Cel. Problemem badawczym podjętym w artykule jest wywieranie wpływu pracowników przedsiębiorstw turystycznych na decyzje zakupowe turystów. Celem badań jest wskazanie najbardziej skutecznych technik wywierania wpływu stosowanych przez pracowników przedsiębiorstw turystycznych. Metoda. Do realizacji celu wykorzystano metodę wywiadu standaryzowanego. Pytania dotyczyły technik wykorzystywanych w procesie sprzedaży, a także działań w zakresie budowania relacji z klientem. Wywiady przeprowadzono z przedstawicielami pięciu przedsiębiorstw sektora turystycznego, reprezentujących typowe rodzaje działalności turystycznej, a mianowicie: biura podróży, hotelu, firmy transportowej, restauracji i punktu informacji turystycznej parku narodowego. Badania prowadzono we wrześniu i październiku 2015 roku. Wyniki. Rezultatem badań jest konkluzja, że wszystkie badane przedsiębiorstwa stosują techniki wywierania wpływu przy obsłudze klientów, jednak ich skuteczność jest zróżnicowana. Wszyscy respondenci stosują politykę stada jako skuteczną metodę wywierania wpływu, natomiast klienci czterech przedsiębiorstw łatwo ulegają sprzedawcom, których uważają za autorytet w dziedzinie turystyki. Ograniczenia badań i wnioskowania. Artykuł prezentuje wyniki badań empirycznych o charakterze jakościowym. Implikacje praktyczne. Wyniki przeprowadzonych badań wnoszą wkład do praktyki gospodarczej i mogą być przydatne w zarządzaniu przedsiębiorstwem turystycznym poprzez wskazanie zróżnicowanych technik wywierania wpływu na klientów oraz ocenę ich skuteczności. Oryginalność. Na rynku wydawniczym brak jest kompleksowego opracowania dotyczącego technik wywierania wpływu na klientów korzystających z usług turystycznych. Rodzaj pracy. Artykuł prezentujący wyniki badań empirycznych.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::26cf6167582b40ca0c7fdbe19b933b17Test
https://doi.org/10.5604/01.3001.0010.4095Test