40 research outputs found

    О синергетическом феномене наноструктурного композита краситель–цеолит

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    Рассмотрены причины возникновения аномального эффекта люминесценции при создании нанокомпозита краситель–цеолитРозглянуто причини виникнення аномального ефекту люмінесценції при створенні нанокомпозиту барвник–цеоліт.The causes of the origin of an abnormal effect of luminescence at creating dye–zeolite nanocomposite are considered

    A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

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    Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition

    Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases

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    OBJECTIVE: Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies. METHODS: We meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases. RESULTS: Our analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study. CONCLUSIONS: We have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs

    Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy

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    Contains fulltext : 97006.pdf (publisher's version ) (Open Access)The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc

    Biofilm composition and threshold concentration for growth of Legionella pneumophila on surfaces exposed to flowing warm tap water without disinfectant

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    Legionella pneumophila in potable water installations poses a potential health risk, but quantitative information about its replication in biofilms in relation to water quality is scarce. Therefore, biofilm formation on the surfaces of glass and chlorinated polyvinyl chloride (CPVC) in contact with tap water at 34 to 39°C was investigated under controlled hydraulic conditions in a model system inoculated with biofilm-grown L. pneumophila. The biofilm on glass (average steady-state concentration, 23 ± 9 pg ATP cm -2 ) exposed to treated aerobic groundwater (0.3 mg C liter -1 ; 1 μg assimilable organic carbon [AOC] liter -1 ) did not support growth of the organism, which also disappeared from the biofilm on CPVC (49 ± 9 pg ATP cm -2 ) after initial growth. L. pneumophila attained a level of 4.3 log CFU cm -2 in the biofilms on glass (1,055 ± 225 pg ATP cm -2 ) and CPVC (2,755± 460 pg ATP cm -2 ) exposed to treated anaerobic groundwater (7.9 mg C liter -1 ; 10 μg AOC liter -1 ). An elevated biofilm concentration and growth of L. pneumophila were also observed with tap water from the laboratory. The Betaproteobacteria Piscinibacter and Methyloversatilis and amoeba-resisting Alphaproteobacteria predominated in the clones and isolates retrieved from the biofilms. In the biofilms, the Legionella colony count correlated significantly with the total cell count (TCC), heterotrophic plate count, ATP concentration, and presence of Vermamoeba vermiformis. This amoeba was rarely detected at biofilm concentrations of <100 pg ATP cm -2 . A threshold concentration of approximately 50 pg ATP cm -2 (TCC = 1 × 106 to 2 × 106 cells cm -2 ) was derived for growth of L. pneumophila in biofilms

    Biofilm composition and threshold concentration for growth of Legionella pneumophila on surfaces exposed to flowing warm tap water without disinfectant

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    Legionella pneumophila in potable water installations poses a potential health risk, but quantitative information about its replication in biofilms in relation to water quality is scarce. Therefore, biofilm formation on the surfaces of glass and chlorinated polyvinyl chloride (CPVC) in contact with tap water at 34 to 39°C was investigated under controlled hydraulic conditions in a model system inoculated with biofilm-grown L. pneumophila. The biofilm on glass (average steady-state concentration, 23 ± 9 pg ATP cm -2 ) exposed to treated aerobic groundwater (0.3 mg C liter -1 ; 1 μg assimilable organic carbon [AOC] liter -1 ) did not support growth of the organism, which also disappeared from the biofilm on CPVC (49 ± 9 pg ATP cm -2 ) after initial growth. L. pneumophila attained a level of 4.3 log CFU cm -2 in the biofilms on glass (1,055 ± 225 pg ATP cm -2 ) and CPVC (2,755± 460 pg ATP cm -2 ) exposed to treated anaerobic groundwater (7.9 mg C liter -1 ; 10 μg AOC liter -1 ). An elevated biofilm concentration and growth of L. pneumophila were also observed with tap water from the laboratory. The Betaproteobacteria Piscinibacter and Methyloversatilis and amoeba-resisting Alphaproteobacteria predominated in the clones and isolates retrieved from the biofilms. In the biofilms, the Legionella colony count correlated significantly with the total cell count (TCC), heterotrophic plate count, ATP concentration, and presence of Vermamoeba vermiformis. This amoeba was rarely detected at biofilm concentrations of -2 . A threshold concentration of approximately 50 pg ATP cm -2 (TCC = 1 × 106 to 2 × 106 cells cm -2 ) was derived for growth of L. pneumophila in biofilms. </p

    Slowly biodegradable organic compounds impact the biostability of non-chlorinated drinking water produced from surface water

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    It is possible to distribute drinking water without a disinfectant residual when the treated water is biologically stable. The objective of this study was to determine the impact of easily and slowly biodegradable compounds on the biostability of the drinking water at three full-scale production plants which use the same surface water, and on the regrowth conditions in the related distribution systems. Easily biodegradable compounds in the drinking water were determined with AOC-P17/Nox during 2012–2015. Slowly biodegradable organic compounds measured as particulate and/or high-molecular organic carbon (PHMOC), were monitored at the inlet and after the different treatment stages of the three treatments during the same period. The results show that PHMOC (300–470 μg C L−1) was approximately 10% of the TOC in the surface water and was removed to 50–100 μg C L−1. The PHMOC in the water consisted of 40–60% of carbohydrates and 10% of proteins. A significant and strong positive correlation was observed for PHMOC concentrations and two recently introduced bioassay methods for slowly biodegradable compounds (AOC-A3 and biomass production potential, BPC14). Moreover, these three parameters in the biological active carbon effluent (BACF) of the three plants showed a positive correlation with regrowth in the drinking water distribution system, which was assessed with Aeromonas, heterotrophic plate counts, coliforms and large invertebrates. In contrast, the AOC-P17/Nox concentrations did not correlate with these regrowth parameters. We therefore conclude that slowly biodegradable compounds in the treated water from these treatment plants seem to have a greater impact on regrowth in the distribution system than easily biodegradable compounds

    Isolation and Detection of Enterovirus RNA from Large-Volume Water Samples by Using the NucliSens miniMAG System and Real-Time Nucleic Acid Sequence-Based Amplification

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    Concentration of water samples is a prerequisite for the detection of the low virus levels that are present in water and may present a public health hazard. The aim of this study was to develop a rapid, standardized molecular method for the detection of enteroviruses in large-volume surface water samples, using a concentration method suitable for the detection of infectious viruses as well as virus RNA. Concentration of water was achieved by a conventional filter adsorption-elution method and ultrafiltration, resulting in a 10,000-fold concentration of the sample. Isolation of virus RNA by a silica-based RNA extraction method was compared with the nonmagnetic and magnetic NucliSens RNA isolation methods. By using the silica-based RNA extraction method in two out of five samples, enterovirus RNA was detected, whereas four out of five samples were positive following RNA isolation with magnetic silica beads. Moreover, estimated RNA levels increased at least 100 to 500 times. Furthermore, we compared enterovirus detection by an in-house reverse transcription (RT)-PCR with a novel commercially available real-time nucleic acid sequence-based amplification (NASBA) assay. We found that the rapid real-time NASBA assay was slightly less sensitive than our in-house RT-PCR. The advantages, however, of a commercial real-time NASBA assay, like the presence of an internal control RNA, standardization, and enormous decrease in turnaround time, makes it an attractive alternative to RT-PCR
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