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1.
Immunobiology ; : 152807, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38821752

ABSTRACT

The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-ß1, IFN-γ and TLR3 genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-ß1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-ß1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.

2.
Nature ; 625(7996): 673-678, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38267680

ABSTRACT

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

3.
Opt Express ; 29(17): 27193-27211, 2021 Aug 16.
Article in English | MEDLINE | ID: mdl-34615140

ABSTRACT

The main advantage of wavelength-dispersive spectrometers applied in X-ray study is their high energy resolution. The design and construction of spectrometer, usually dedicated to the specific experimental systems, for example synchrotron based setups, need information about the characteristics of the main elements of the spectrometer such as X-ray optics elements, crystals and detectors. Such information can be obtained using Monte-Carlo simulations. In this paper, the Monte-Carlo simulations of X-ray tracing in parallel-beam wavelength-dispersive spectrometer (PBWDS), equipped with polycapillary optics, are presented and discussed. The study concentrates on the description of the polycapillary model, simulations of the properties of X-ray polycapillary optics and, finally, on the simulations of X-ray track in the spectrometer designed and installed at the ID21 beamline at the European Synchrotron Radiation Facility (ESRF, Grenoble, France). The results of simulations were compared with experimental data obtained for different registered X-ray energies and spectrometer crystals, showing good agreement. The obtained results showed that the X-ray transmission in the tested polycapillary optics is at the level of 15%, while the divergence of the outgoing beam changes from 8 mrad to 3 mrad with an increase of photon energy from 2 keV to 10 keV. The spectrometer provides an energy resolution of 5 eV and 33 eV in the energy range of 1.4 keV - 6.5 keV. The developed simulation program can be successfully used for the construction of spectrometers dedicated to the different experimental conditions.

4.
Rev Sci Instrum ; 90(6): 063106, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31255015

ABSTRACT

The design and performance of a high-resolution transmission-type X-ray spectrometer for use in the 15-26 keV energy range at synchrotron light sources is reported. Monte Carlo X-ray-tracing simulations were performed to optimize the performance of the transmission-type spectrometer, based on the DuMond geometry, for use at the Super X-ray absorption beamline of the Swiss Light Source at the Paul Scherrer Institute. This spectrometer provides an instrumental energy resolution of 3.5 eV for X-ray emission lines around 16 keV and 12.5 eV for emission lines at 26 keV, which is comparable to the natural linewidths of the K and L X-ray transitions in the covered energy range. First experimental data are presented and compared with results of the Monte Carlo X-ray simulations.

5.
Transplant Proc ; 50(7): 2110-2112, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30177119

ABSTRACT

BACKGROUND: Transplant rejection is one of the major problems after heart transplantation (HTx). The aim of the study was to find possible links between chosen single-nucleotide polymorphisms (SNPs) of Toll-like receptor 4 (TLR4) and heart transplant rejection. MATERIAL AND METHODS: Blood samples were taken from 24 patients subjected to HTx between 2010 and 2016 at the Clinic of Cardiac Surgery and Transplantation and under the control of I Clinic of Cardiology. All the patients were permanently controlled and had therapeutic levels of immunosuppressants in their blood. Their DNA was isolated and analyzed using the high-resolution melting method according to the Toll-like receptor 4 SNPs rs10983755 A/G, rs4986791 C/T, rs4986790 A/G, rs10759932 C/T, rs1927911 C/T, rs11536889 C/G, and rs12377632 C/T. The analysis of the clinical data of biopsies according to International Society for Heart and Lung Transplantation classification was derived from the patients' medical history, divided into two groups: 0-1b and 2-4. A statistical analysis was then performed. RESULTS: The results obtained showed no association between analyzed SNPs and rejection. For rs10983755 A/G, P = .85; rs4986791 C/T, rs4986790 A/G, and rs1927911 C/T had P = .35; and rs10759932 C/T, rs11536889 C/G, and rs12377632 C/T had P = 1. CONCLUSIONS: No association between the SNPs rs10983755 A/G, rs4986791 C/T, rs4986790 A/G, rs10759932 C/T, rs1927911 C/T, rs11536889 C/G, and rs12377632 C/T and heart transplant rejection was found, but further investigation is suggested for TLR4 SNPs with P < .5.


Subject(s)
Genetic Predisposition to Disease/genetics , Graft Rejection/genetics , Heart Transplantation/adverse effects , Polymorphism, Single Nucleotide , Toll-Like Receptor 4/genetics , Adult , Aged , Female , Humans , Male , Middle Aged
6.
Clin Genet ; 93(4): 784-793, 2018 04.
Article in English | MEDLINE | ID: mdl-28926086

ABSTRACT

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend = 9.70E-10 and Ptrend = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Brain/abnormalities , Cleft Lip/genetics , Cleft Palate/genetics , Membrane Proteins/genetics , Brain/pathology , Cleft Lip/pathology , Cleft Palate/pathology , Discs Large Homolog 1 Protein , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Polymorphism, Single Nucleotide/genetics
7.
Oral Dis ; 24(4): 591-599, 2018 May.
Article in English | MEDLINE | ID: mdl-28992378

ABSTRACT

OBJECTIVE: The etiology of tooth agenesis (TA) is multifactorial and still not fully understood. The aim of the study was to test whether variants of GREM2, encoding a bone morphogenetic protein (BMP) antagonist, are associated with the risk of this common dental anomaly in a Polish population. SUBJECTS AND METHODS: Direct sequencing of the GREM2 coding sequence including exon/intron boundaries was performed in 95 patients with both hypodontia and oligodontia. All identified GREM2 variants were then further tested in an independent group of patients (n = 163) and controls (n = 184). RESULTS: The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia. This mutation generating an allele with increased inhibitory activity was not detected in the control group. The second identified GREM2 variant, c.-1-21C > T (rs11806449), was not associated with the risk TA. The polymorphism allele frequency in both patients and controls was 0.21 (OR = 1.0, 95%CI: 0.76-1.46). The rs11806449 did not correlate either with the overall TA phenotype or hypodontia/oligodontia phenotypes. CONCLUSION: Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly.


Subject(s)
Anodontia/genetics , Intercellular Signaling Peptides and Proteins/genetics , Adult , Cytokines , DNA Mutational Analysis , Female , Gene Frequency , Humans , Male , Mutation , Phenotype , Young Adult
8.
J Physiol Pharmacol ; 68(2): 201-207, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28614769

ABSTRACT

Pyrazoles and their derivatives belong to a class of compounds that demonstrate a great potential in design of anticancer, antiangiogenic, and antimetastatic drugs. Our earlier studies showed that pyrazole derivatives TOSPYRQUIN and TOSIND diminished viability of colorectal adenocarcinoma cells HT-29. Here we demonstrated for the first time in human mammary gland adenocarcinoma cell lines MCF7 and MDA-MB-231 cells the cytotoxic effects of four pyrazole derivatives: TOSIND, PYRIND, METPYRIND, and DIPYR. Three pyrazoles: PYRIND, METPYRIND, and one novel unpublished derivative DIPYR were tested for the first time in living cells. Viability of MCF7 did not significantly change in the presence of TOSIND but it decreased after 72 hours of treatment with PYRIND (IC-50 39.7 ± 5.8 µM). In the presence of METPYRIND the viability was also diminished, while DIPYR increased MCF7 viability after 24 hours of incubation. The viability of MDA-MB-231 cells was strongly decreased by TOSIND (IC-50 17.7 ± 2.7 µM 72 h), and was not influenced by PYRIND and METPYRIND, while DIPYR increased the viability and stimulated the growth of MDA-MB-231 cells. PYRIND, METPYRIND and DIPYR caused a gradual decrease of caspase-3 and caspase-7 activities in MDA-MB-231 cells and there was no influence of TOSIND on the activity of both caspases. Our results open the way to search for other compounds with pendant pyrazole residues in order to increase their cytotoxic activity; especially with regard to its anti-breast cancer activity. It appears that the pyrazoles synthesized by us diminish cell viability in a cell-specific manner. This observation might be useful in designing 'off-DNA' anticancer drugs, compounds which are not harmful to the healthy cells.


Subject(s)
Antineoplastic Agents/pharmacology , Pyrazoles/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Caspase 3/metabolism , Caspase 7/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Humans
9.
Biomed Pharmacother ; 83: 314-322, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27399808

ABSTRACT

In most populations, gastric cancer (GC) is approximately two times more prevalent in men than in women, which may suggest the protective role of sex steroid hormones in gastric carcinogenesis. Steroid hormones such as androgens and estrogens can be synthesized not only in the gonads but also in peripheral tissues. Many researchers have conducted studies examining the expression profile of enzymes involved in steroid synthesis, the occurrence of estrogen receptors (ERs) and the influence of ERs in the development, proliferation and progression of gastric cancer. Some studies have also evaluated the relationship between the presence of ERs and survival prognosis. However, the results of these studies are often controversial and divergent. In a recent study, it was indicated that sex steroid hormones and estrogen receptors are partly involved in gastric cancer but their clinicopathological significance still needs further investigation.


Subject(s)
Receptors, Estrogen/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Carcinogenesis/metabolism , Carcinogenesis/pathology , Humans , Models, Biological , Risk Factors , Signal Transduction , Stomach Neoplasms/epidemiology
10.
Scand J Immunol ; 84(1): 49-60, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27059274

ABSTRACT

To investigate the potential association between IL-12B and IL-27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case-control study based on the Polish population. Patients with SLE and healthy individuals were examined for -6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL-12B and -924A/G (rs153109) and 4730T/C (rs181206) in IL-27 gene polymorphisms using the high-resolution melting method, PCR-RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL-12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL-12B rs3212227 and IL-27 rs153109 and rs181206 variants between patients with SLE and controls. IL-27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL-12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL-12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL-12B rs17860508 and IL-27 haplotype CG are genetic risk factors for SLE and that both IL-12B rs17860508 and rs3212227 predict disease phenotype.


Subject(s)
Blood Platelets/immunology , Interleukin-12 Subunit p40/genetics , Interleukins/genetics , Lupus Erythematosus, Systemic/genetics , Adult , Aged , Aged, 80 and over , Alkaline Phosphatase/metabolism , Case-Control Studies , Complement C3/metabolism , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Phenotype , Poland , Polymorphism, Single Nucleotide , Prothrombin/metabolism , Young Adult
11.
Clin Exp Obstet Gynecol ; 43(4): 495-499, 2016.
Article in English | MEDLINE | ID: mdl-29734534

ABSTRACT

The subject of the study is the evaluation of the correlation between the polymorphism of candidate genes in the etiology of depression and the occurrence of the symptoms of the climacteric syndrome in women during menopause. The group subjected to the study comprised of 203 women aged between 42-65 years: 71 of them still menstruated (premenopausal group) and 132 at least one year after the last period (postmenopausal group), admitted to the Department of Gynecological Endocrinology at the University of Medical Sciences in Poznan with symptoms of the climacteric syndrome All the examined women were evaluated according to the degree of severity of the climacteric syndrome symptoms using the Kupperman index and the concentration of FSH, LH hormones, 17ß-estradiol, PRL, total testosterone, and DHEAS in peripheral blood serum. Among the candidate genes in the aetiology of depression the following were selected for the research: the serotonergic system receptor genes: 5HTR2A, 5HTR1B, 5HTR2C, TPH 1, TPH2, and MAO-A; the genes of noradrenergic and dopaminergic systems (COMT, NET), the genes of the GABAergic (GABRBl) system, a gene of the estrogen receptor (ESR1), and the genes of the enzymes crucial in the methyl cycle (MTHRF, MTR, and MTHFD1). With regards to the correlation between the examined polymorphisms and the occurrence of the symptoms of the climacteric syndrome, the associations analysis indicated a connection between GABRBl.TaqI polymorphism and the occurrence of vertigo in premenopausal women (0.0198; after correction: 0.0497 CC to CA). The correlation was also found regarding the examined polymorphisms and the concentration of the examined hormones in blood serum: TPH1.MaeI polymorphism and the LH concentration in the postmenopausal group (0.004; after correction: 0.014 CC to CA), NET.Eco1471 polymorphism, and the 17ß-estradiol concentration in the postmenopausal group (0.0208; after correction: 0.048 GG to GA) and HTR2AMspI polymorphism and PRL concentration in all examined women (0.03; after correction: 0.038 TT to CT).


Subject(s)
Menopause/genetics , Menopause/psychology , Polymorphism, Genetic/genetics , Adult , Aged , Aminohydrolases/genetics , Dehydroepiandrosterone Sulfate/blood , Depression/etiology , Estradiol/blood , Female , Formate-Tetrahydrofolate Ligase/genetics , Genetic Background , Humans , Menopause/blood , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Middle Aged , Minor Histocompatibility Antigens/genetics , Monoamine Oxidase , Multienzyme Complexes/genetics , Premenopause , Tryptophan Hydroxylase/genetics
12.
Z Rheumatol ; 74(10): 902-10, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26347123

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens and by chronic inflammation. The etiology of SLE is the result of interactions between genetic, epigenetic, hormonal, and environmental factors. Changes in histone acetylation and methylation contribute to structural chromatin modifications. OBJECTIVE: We studied the histone demethylase JHDM1D and histone deacetylases HDAC1, HDAC2, and HDAC3 transcript levels in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with systemic lupus erythematosus (SLE). Furthermore, the association of JHDM1D, HDAC1, HDAC2, and HDAC3 transcript levels with gender, age, and major clinical manifestations were analyzed. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) analysis was used to determine JHDM1D, HDAC1, HDAC2, and HDAC3 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 30 patients with SLE and 36 healthy controls. RESULTS: Significantly lower HDAC2 transcript levels (p = 0.006785) and significantly higher JHDM1D (p = 0.0000002) and HDAC1 (p = 0.010581) transcript levels in SLE patients were observed compared with healthy controls. Higher JHDM1D mRNA expression was detected in active SLE patients when compared with inactive patients (p = 0.005). Furthermore, the JHDM1D transcript levels were positively correlated with disease activity (r(s) = 0.368, p = 0.045), while HDAC2 mRNA expression was positively correlated with disease duration (r(s) = 0.502, p = 0.0047). CONCLUSION: Our analyses confirmed the importance of epigenetic alterations (histone demethylation and acetylation) in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, like hematological disease and anti-Ro antibody, might be associated with the dysregulation of histone demethylase and deacetylases mRNA expression levels.


Subject(s)
Histone Deacetylases/blood , Jumonji Domain-Containing Histone Demethylases/blood , Leukocytes, Mononuclear/metabolism , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , RNA, Messenger/blood , Adult , Biomarkers/blood , Female , Genetic Predisposition to Disease/genetics , Histone Deacetylases/genetics , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Lupus Erythematosus, Systemic/genetics , Male , Reproducibility of Results , Sensitivity and Specificity
13.
Exp Parasitol ; 135(2): 437-45, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23994484

ABSTRACT

Toll-like receptors in the gastrointestinal tract can influence intestinal homeostasis and play a role in the repair and restitution of intestinal epithelium following tissue damage. In our previous study a statistically significant increase in the level of TLR4 and TLR2 gene expression was observed in rats in early stages of hymenolepidosis. Moreover, the immunopositive cell number and the intensity of immunohistochemical staining (indicating the presence of TLRs within intestinal epithelial cells) increased over the infection period. In this paper, we determined changes in the expression of TLR2 and TLR4 and the number of anaerobic intestinal commensal bacteria in Hymenolepis diminuta infected rats. In the isolated jejunum of infected rats at 16 days post infection (dpi), the expression of TLR4 and TLR2 was significantly higher than uninfected rats. In the colon, a statistically significantly increased expression of TLR2 was observed from 16 to 40 dpi, and TLR4 from 16 to 60 dpi. The jejunum and colon of infected rats contained Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Enterococcus, Streptococcus, Staphylococcus, Bacillus, Lactobacillus) and Candida. The total number of intestinal bacteria was higher in H. diminuta infected rats, but the observed microbiota had only minor effects on the expression of TLR2 and TLR4. Toll-like receptors play a role in maintaining epithelial barrier function in response to enteric pathogens and parasites. In our study, the alteration of TLR2 and TLR4 expression in the infected rats indicates the potential role of the innate immune system in the pathomechanism of this infection.


Subject(s)
Hymenolepiasis/immunology , Hymenolepis diminuta/physiology , Intestine, Large/metabolism , Intestine, Small/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Animals , Bacteria/growth & development , Candida/growth & development , Enterobacteriaceae/growth & development , Feces/parasitology , Gene Expression , Hymenolepiasis/genetics , Hymenolepiasis/parasitology , Immunohistochemistry , Intestine, Large/microbiology , Intestine, Large/parasitology , Intestine, Small/microbiology , Intestine, Small/parasitology , Male , RNA, Messenger/isolation & purification , RNA, Messenger/metabolism , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Tribolium
14.
Clin Genet ; 84(5): 429-40, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23167694

ABSTRACT

Tooth agenesis is one of the most common dental anomalies, with a complex and not yet fully elucidated aetiology. Given the crucial role of the Wnt signalling pathway during tooth development, the purpose of this study was to determine whether nucleotide variants of genes encoding components of this signalling pathway might be associated with hypodontia and oligodontia in the Polish population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT-related genes were analyzed in a group of 157 patients with tooth agenesis and a properly matched control group (n = 430). In addition, direct sequencing was performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single-marker and haplotype analyses showed highly significant association between SNPs in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) tested patients. One novel heterozygous mutation was identified in the PAX9 gene. Borderline association with the risk of non-syndromic tooth agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In conclusion, nucleotide variants of genes encoding important components of the Wnt signalling pathway might influence the risk of tooth agenesis.


Subject(s)
Anodontia/genetics , PAX9 Transcription Factor/genetics , Polymorphism, Single Nucleotide , Tooth/metabolism , Wnt Proteins/genetics , Wnt Signaling Pathway , Adolescent , Adult , Anodontia/pathology , Case-Control Studies , Child , DNA Mutational Analysis , Female , Gene Expression , Gene Frequency , Haplotypes , Heterozygote , Humans , Male , Mutation , Poland , Tooth/pathology
15.
Lupus ; 22(3): 233-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23257401

ABSTRACT

There is one study on the association of the CD40 G > T (rs4810485) single nucleotide polymorphism (SNP) as a risk factor of systemic lupus erythematosus (SLE). Therefore, we studied the prevalence of the CD40 G > T SNP in patients with SLE (n = 261) and controls (n = 545) in a Polish population. We did not find significant differences between the CD40 G > T genotype and allele frequency in patients with SLE and healthy individuals. However, the frequency of the CD40 TT and GT genotypes was statistically different between patients with arthritis and neurologic manifestations and patients without these symptoms (OR = 0.2009 (95% CI = 0.07547-0.5348, p = 0.0004, p (corr) = 0.0068) and OR = 0.2876 (95% CI = 0.1371-0.6031, p = 0.0005, p (corr) = 0.0085) respectively). Our observations indicate that the CD40 T variant might be negatively associated with some clinical disease manifestations in patients with SLE.


Subject(s)
CD40 Antigens/genetics , Lupus Erythematosus, Systemic/genetics , Adult , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Lupus Erythematosus, Systemic/diagnosis , Middle Aged , Poland , Polymorphism, Single Nucleotide , Risk Factors
16.
Rev Sci Instrum ; 83(10): 103105, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23126749

ABSTRACT

We report on the design and performance of a wavelength-dispersive type spectrometer based on the von Hamos geometry. The spectrometer is equipped with a segmented-type crystal for x-ray diffraction and provides an energy resolution in the order of 0.25 eV and 1 eV over an energy range of 8000 eV-9600 eV. The use of a segmented crystal results in a simple and straightforward crystal preparation that allows to preserve the spectrometer resolution and spectrometer efficiency. Application of the spectrometer for time-resolved resonant inelastic x-ray scattering and single-shot x-ray emission spectroscopy is demonstrated.

17.
ScientificWorldJournal ; 2012: 194845, 2012.
Article in English | MEDLINE | ID: mdl-22619623

ABSTRACT

OBJECTIVE: The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women. METHODS: We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17ß-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction-restriction. RESULTS: We found that the 1460T allele of MAO-A c.1460C>T (SNP 1137070) appeared with a significantly higher frequency in depressed female patients than in the control group (P = 0.011) and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (P = 0.0198). Patients with the 1460TT genotype had a significantly higher 17ß-estradiol concentration than patients with the 1460CT genotype (P = 0.0065) and 1460CC genotype (P = 0.0018). CONCLUSIONS: We concluded that depression in postmenopausal women is closely related to the genetic contribution of MAO-A.


Subject(s)
Depression/genetics , Genetic Predisposition to Disease , Monoamine Oxidase/genetics , Polymorphism, Genetic , Postmenopause , Adult , Aged , Female , Humans , Middle Aged
18.
Biomed Pharmacother ; 66(1): 1-5, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22257695

ABSTRACT

It has recently been demonstrated that phospholipase C gamma-1 (PLCγ1) activation may contribute to breast carcinoma cell motility and their metastasis. Employing MCF-7 breast cancer cells, we showed the effect of trichostatin A (TSA) on the cellular contents of the PLCγ1 molecule. Using reverse transcription, real-time quantitative PCR and western blot analysis, we demonstrated that TSA reduced the PLCγ1 transcript and protein levels in MCF-7 cells. We also found that TSA decreased the half-life of the PLCγ1 transcript from approximately 7hours to 5hours. Moreover, we observed that protein synthesis appears to be essential in the TSA reduction of PLCγ1 mRNA stability. Since PLCγ1 activation is considered a key factor in the initiation of events that increase malignant cell motility, our observations may support the validity of TSA in anticancer studies.


Subject(s)
Breast Neoplasms/drug therapy , Hydroxamic Acids/pharmacology , Phospholipase C gamma/metabolism , Protein Synthesis Inhibitors/pharmacology , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Half-Life , Histone Deacetylase Inhibitors/pharmacology , Humans , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction
19.
Exp Parasitol ; 130(3): 261-6, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22209940

ABSTRACT

Toll receptors play a critical role in the rapid activation of innate immune responses to a variety of pathogens. In mammals, Toll-like receptors (TLR) have been found in both immune related cells and other cells. At present little is known about the participation of TLR in host defense mechanisms during parasitic infections. The aim of this study was to determine the expression of TLR2 and TLR4 genes in rat intestines during experimental hymenolepidosis. There is difference in expression of TLR2 and TLR4 genes in the colon and jejunum in uninfected rats: in the colon, mRNA of the examined TLR is present in much higher amounts than the jejunum, while the protein of the TLR also had a segmented specific distribution. In the jejunum isolated rats infected with Hymeolepis diminuta 6 and 8 days post infection (dpi), mRNA for TLR4 and TLR2 were significantly more strongly expressed in comparison with the uninfected controls. In the colon, a statistically significantly increased expression of TLR4 gene was observed only at 6 dpi, and at 8 dpi for the TLR2 gene. Moreover, we observed that during inflammation, the immunopositive cell number and the intensity of immunohistochemical staining (indicating the presence of TLR within intestinal epithelial cells), increased together with the duration of the infection period.


Subject(s)
Colon/metabolism , Hymenolepiasis/metabolism , Hymenolepis diminuta/genetics , Jejunum/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Animals , Colon/parasitology , Gene Expression , Hymenolepiasis/genetics , Hymenolepis diminuta/metabolism , Immunohistochemistry , Jejunum/parasitology , Male , RNA, Messenger/metabolism , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Tribolium , Up-Regulation
20.
Phys Rev Lett ; 107(5): 053001, 2011 Jul 29.
Article in English | MEDLINE | ID: mdl-21867065

ABSTRACT

Experimental evidence for the correlated two-electron one-photon transitions (1s(-2)→2s(-1)2p(-1)) following single-photon K-shell double ionization is reported. The double K-shell vacancy states in solid Mg, Al, and Si were produced by means of monochromatized synchrotron radiation, and the two-electron one-photon radiative transitions were observed by using a wavelength dispersive spectrometer. The two-electron one-photon transition energies and the branching ratios of the radiative one-electron to two-electron transitions were determined and compared to available perturbation theory predictions and configuration interaction calculations.

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