Publications by authors named "Oscar Florez-Vargas"

16 Publications

  • Page 1 of 1

Intracellular Accumulation of IFN-λ4 Induces ER Stress and Results in Anti-Cirrhotic but Pro-HCV Effects.

Front Immunol 2021 23;12:692263. Epub 2021 Aug 23.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States.

polymorphisms are inversely associated with the risk of chronic hepatitis C virus (HCV) infection and cirrhosis, two major risk factors for developing hepatocellular carcinoma (HCC). To further explore these inverse associations and their molecular underpinnings, we analyzed polymorphisms represented by the genotype (presence of rs368234815-dG or rs12979860-T alleles) in HCV patients: 2969 from Japan and 2931 from Taiwan. genotype was associated with an increased risk of HCV-related HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058) in the general population of Japanese patients, but not in Taiwanese patients who achieved treatment-induced viral clearance. genotype was also associated with a decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwanese patients). We then engineered HepG2 cells to inducibly express IFN-λ4 in the presence or absence of interferon lambda receptor 1 (IFNLR1). Induction of IFN-λ4 resulted in its intracellular accumulation, mainly in lysosomes and late endosomes, and increased ER stress, leading to apoptosis and reduced proliferation. We identified the very-low-density lipoprotein receptor (), which facilitates HCV entry into hepatocytes, as a transcript induced by IFN-λ4 but not IFN-λ3. Our results suggest that the molecular mechanisms underlying the anti-cirrhotic but pro-HCV associations observed for polymorphisms are, at least in part, contributed by intracellular accumulation of IFN-λ4 causing ER stress in hepatic cells.
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http://dx.doi.org/10.3389/fimmu.2021.692263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419317PMC
August 2021

Genetic regulation of nonsense-mediated decay underlies association with risk of severe COVID-19.

medRxiv 2021 Jul 13. Epub 2021 Jul 13.

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of . We suggest that genetically-regulated loss of expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the risk haplotypes.
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http://dx.doi.org/10.1101/2021.07.09.21260221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288155PMC
July 2021

Glutathione-related genetic polymorphisms are associated with mercury retention and nephrotoxicity in gold-mining settings of a Colombian population.

Sci Rep 2021 Apr 22;11(1):8716. Epub 2021 Apr 22.

Grupo de Inmunología y Epidemiología Molecular, Escuela de Microbiología, Universidad Industrial de Santander, Carrera 32 No. 29-31; Building Roberto Serpa, Floor 5, Office 5, Bucaramanga, Colombia.

Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress. Hg is eliminated from the body as a glutathione conjugate. Thus, single nucleotide polymorphisms (SNPs) in glutathione-related genes might modulate the negative impact of this metal on the kidneys. Glutathione-related SNPs were tested for association with levels of Hg and renal function biomarkers between occupationally exposed (n = 160) and non-exposed subjects (n = 121). SNPs were genotyped by TaqMan assays in genomic DNA samples. Total mercury concentration was measured in blood, urine and hair samples. Regression analyses were performed to estimate the effects of SNPs on quantitative traits. Alleles GCLM rs41303970-T and GSTP1 rs4147581-C were significantly overrepresented in the exposed compared with the non-exposed group (P < 0.01). We found significant associations for GCLM rs41303970-T with higher urinary clearance rate of Hg (β = 0.062, P = 0.047), whereas GCLC rs1555903-C was associated with lower levels of estimated glomerular filtration rate in the non-exposed group (eGFR, β = - 3.22, P = 0.008) and beta-2-microglobulin in the exposed group (β-2MCG, β = - 19.32, P = 0.02). A SNP-SNP interaction analysis showed significant epistasis between GSTA1 rs3957356-C and GSS rs3761144-G with higher urinary levels of Hg in the exposed (β = 0.13, P = 0.04) but not in the non-exposed group. Our results suggest that SNPs in glutathione-related genes could modulate the pathogenesis of Hg nephrotoxicity in our study population by modulating glutathione concentrations in individuals occupationally exposed to this heavy metal.
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http://dx.doi.org/10.1038/s41598-021-88137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062595PMC
April 2021

IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children.

Genes Immun 2021 05 13;22(1):44-55. Epub 2021 Apr 13.

Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13-2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02-1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.
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http://dx.doi.org/10.1038/s41435-021-00127-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042471PMC
May 2021

Targeting natural splicing plasticity of APOBEC3B restricts its expression and mutagenic activity.

Commun Biol 2021 03 22;4(1):386. Epub 2021 Mar 22.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

APOBEC3A (A3A) and APOBEC3B (A3B) enzymes drive APOBEC-mediated mutagenesis. Identification of factors affecting the activity of these enzymes could help modulate mutagenesis and associated clinical outcomes. Here, we show that canonical and alternatively spliced A3A and A3B isoforms produce corresponding mutagenic and non-mutagenic enzymes. Increased expression of the mutagenic A3B isoform predicted shorter progression-free survival in bladder cancer. We demonstrate that the production of mutagenic vs. non-mutagenic A3B protein isoforms was considerably affected by inclusion/skipping of exon 5 in A3B. Furthermore, exon 5 skipping, resulting in lower levels of mutagenic A3B enzyme, could be increased in vitro. Specifically, we showed the effects of treatment with an SF3B1 inhibitor affecting spliceosome interaction with a branch point site in intron 4, or with splice-switching oligonucleotides targeting exon 5 of A3B. Our results underscore the clinical role of A3B and implicate alternative splicing of A3B as a mechanism that could be targeted to restrict APOBEC-mediated mutagenesis.
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http://dx.doi.org/10.1038/s42003-021-01844-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985488PMC
March 2021

Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor.

Nat Genet 2020 12 19;52(12):1283-1293. Epub 2020 Oct 19.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, transcriptionally independent truncated isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In The Cancer Genome Atlas, the expression of dACE2 was enriched in squamous tumors of the respiratory, gastrointestinal and urogenital tracts. In vitro, dACE2, which lacks 356 amino-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, an inflammatory tumor microenvironment or viral co-infections is unlikely to increase the cellular entry of SARS-CoV-2 and promote infection.
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http://dx.doi.org/10.1038/s41588-020-00731-9DOI Listing
December 2020

Genetic Polymorphisms in Multispecific Transporters Mitigate Mercury Nephrotoxicity in an Artisanal and Small-Scale Gold Mining Community in Colombia.

Toxicol Sci 2020 12;178(2):338-346

Laboratorio de Toxicología Ambiental y Toxicogenética.

In artisanal and small-scale gold mining, occupational exposure to mercury (Hg) vapor is related to harmful effects on several organs, including the kidneys. We previously reported significantly increased levels of Hg in blood and urine despite normal kidney function in individuals from Colombia occupationally exposed to Hg compared with those nonexposed. We evaluated the contribution of 4 genetic variants in key genes encoding the transporters solute carrier (SLC; rs4149170 and rs4149182) and ATP-binding cassette(ABC; rs1202169 and rs1885301) in the pathogenesis of nephrotoxicity due to Hg exposure in these groups. Regression analysis was performed to determine the association between the blood- and urine-Hg concentration with SLC and ABC polymorphisms in 281 Colombian individuals (160 exposed and 121 nonexposed to Hg). We found an enrichment of ABCB1 rs1202169-T allele in the exposed group (p = .011; OR= 2.05; 95% CI = 1.18-3.58) compared with the nonexposure group. We also found that carriers of SLC22A8 rs4149182-G and ABCB1 rs1202169-T alleles had a higher urinary clearance rate of Hg than noncarriers (β = 0.13, p = .04), whereas carriers of SLC22A6 rs4149170-A and ABCB1 rs1202169-C alleles showed abnormal levels of estimated glomerular filtration rate (β = -84.96, p = .040) and beta-2-microglobulin (β = 743.38, p < .001). Our results suggest that ABCB1 rs1202169 and its interaction with SLC22A8 rs4149182 and SLC22A6 rs4149170 could mitigate Hg nephrotoxicity by controlling the renal proximal tubule cell accumulation of inorganic Hg. This will be useful to estimate the risk of kidney toxicity associated to Hg and the genetic selection to aid adaptation to Hg-rich environments.
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http://dx.doi.org/10.1093/toxsci/kfaa142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825076PMC
December 2020

Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2.

bioRxiv 2020 Jul 20. Epub 2020 Jul 20.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of , which we designate as . We demonstrate that , but not , is an ISG. , dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on expression and suggest that the ISG-type induction of in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection.
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http://dx.doi.org/10.1101/2020.07.19.210955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386494PMC
July 2020

A rule-based approach to identify patient eligibility criteria for clinical trials from narrative longitudinal records.

JAMIA Open 2019 Dec 20;2(4):521-527. Epub 2019 Aug 20.

School of Computer Science, University of Manchester, Manchester, UK.

Objective: Achieving unbiased recognition of eligible patients for clinical trials from their narrative longitudinal clinical records can be time consuming. We describe and evaluate a knowledge-driven method that identifies whether a patient meets a selected set of 13 eligibility clinical trial criteria from their longitudinal clinical records, which was one of the tasks of the 2018 National NLP Clinical Challenges.

Materials And Methods: The approach developed uses rules combined with manually crafted dictionaries that characterize the domain. The rules are based on common syntactical patterns observed in text indicating or describing explicitly a criterion. Certain criteria were classified as "met" only when they occurred within a designated time period prior to the most recent narrative of a patient record and were dealt through their position in text.

Results: The system was applied to an evaluation set of 86 unseen clinical records and achieved a microaverage F1-score of 89.1% (with a micro F1-score of 87.0% and 91.2% for the patients that met and did not meet the criteria, respectively). Most criteria returned reliable results (drug abuse, 92.5%; Hba1c, 91.3%) while few (eg, advanced coronary artery disease, 72.0%; myocardial infarction within 6 months of the most recent narrative, 47.5%) proved challenging enough.

Conclusion: Overall, the results are encouraging and indicate that automated text mining methods can be used to process clinical records to recognize whether a patient meets a set of clinical trial criteria and could be leveraged to reduce the workload of humans screening patients for trials.
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http://dx.doi.org/10.1093/jamiaopen/ooz041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993990PMC
December 2019

Increasing efficiency of preclinical research by group sequential designs.

PLoS Biol 2017 03 10;15(3):e2001307. Epub 2017 Mar 10.

Center for Stroke Research, Charité Universitätsmedizin Berlin, Berlin, Germany.

Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain.
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http://dx.doi.org/10.1371/journal.pbio.2001307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345756PMC
March 2017

No effect of mercury exposure on kidney function during ongoing artisanal gold mining activities in Colombia.

Toxicol Ind Health 2017 Jan 28;33(1):67-78. Epub 2016 Jul 28.

6 School of Medicine, Universidad de Cartagena, Cartagena, Colombia.

This cross-sectional study examined whether people who are exposed to mercury (Hg) vapours in ongoing artisanal gold mining activities have alteration in kidney function monitoring parameters. The study enrolled 164 miners and 127 participant controls. The Hg concentrations for miners and control participants were measured in blood (B-Hg; median 7.0 vs. 2.5 µg/L), urine (U-Hg; median 3.9 vs. 1.5 µg/g creatinine) and hair (H-Hg; median 0.8 vs. 0.4 µg/g hair). The biomarkers of renal function were creatinine, albumin and excretion of β-2 microglobulin. Glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation. Significant statistical differences were found in Hg concentrations and eGFR levels between the two study groups ( p < 0.01) but not with the other biomarkers of renal function. A multiple regression model was applied to explore the relationship of eGFR levels and Hg concentrations. However, no association was found between the prevalence of reduced eGFR (<71.96 mL/min/1.73 m) and the B-Hg or U-Hg levels after adjustment for covariates. Nevertheless, it was observed that having B-Hg levels above 10 µg Hg/L decreased the eGFR by 1.7 mL/min/1.73 m (confidence interval 95% -5.1 to 1.7) compared to having levels below 2.0 µg Hg/L. Our results found no support for kidney damage associated with Hg vapour exposure in ongoing artisanal gold mining, whose population has a level of Hg exposure from low to moderate (B-Hg from 3.4 to 11.0 µg/L and U-Hg from 1.3 to 9.6 µg/g creatinine).
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http://dx.doi.org/10.1177/0748233716659031DOI Listing
January 2017

Bias in the reporting of sex and age in biomedical research on mouse models.

Elife 2016 Mar 3;5. Epub 2016 Mar 3.

Text Mining Group, School of Computer Science, The University of Manchester, Manchester, United Kingdom.

In animal-based biomedical research, both the sex and the age of the animals studied affect disease phenotypes by modifying their susceptibility, presentation and response to treatment. The accurate reporting of experimental methods and materials, including the sex and age of animals, is essential so that other researchers can build on the results of such studies. Here we use text mining to study 15,311 research papers in which mice were the focus of the study. We find that the percentage of papers reporting the sex and age of mice has increased over the past two decades: however, only about 50% of the papers published in 2014 reported these two variables. We also compared the quality of reporting in six preclinical research areas and found evidence for different levels of sex-bias in these areas: the strongest male-bias was observed in cardiovascular disease models and the strongest female-bias was found in infectious disease models. These results demonstrate the ability of text mining to contribute to the ongoing debate about the reproducibility of research, and confirm the need to continue efforts to improve the reporting of experimental methods and materials.
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http://dx.doi.org/10.7554/eLife.13615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821800PMC
March 2016

Laboratory genetic-based reference values for cholinesterase activity in a Colombian population: A step forward in personalized diagnostics.

Biomedica 2015 Aug;35 Spec:20-9

Grupo de Inmunología y Epidemiología Molecular, Escuela de Microbiología, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.

Introduction: The determination of cholinesterase (ChE) activity has been commonly applied in the biomonitoring of exposure to organophosphate and carbamate pesticides. However, ChE activity is influenced by genetic factors. Integrating genotype and phenotype information in clinical laboratory tests would increase the accuracy of the reference values in well-defined populations.

Objective: To establish genetic-based reference values for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in a Colombian population.

Materials And Methods: A total of 397 healthy adults from Bucaramanga were included in the study. AChE and BChE activities were measured in blood samples by potentiometry and spectrophotometry, respectively. Genotyping for ACHE rs17880573 and BCHE rs1803274 was performed using the TaqMan allelic discrimination assay. The statistical analyses to obtain the reference values were performed with the MedCalc® software.

Results: Allele frequencies were 10.58% for rs17880573 A and 8.82% for rs1803274 A. People with genotypes rs1803274 AA and AG showed a reduction of 20.69% and 10.92% respectively in mean BChE activity compared to people with genotype GG. No significant differences were identified in AChE activity between rs17880573 alleles or genotypes. In the overall sample, the corresponding reference values were as follows: for AChE activity, 0.62-0.98 D pH/h and for BChE activity, 4796.3-10321.1 U/L for people carrying the allele rs1803274A and 5768.2-11180.4 U/L for people carrying the genotype rs1803274 GG.

Conclusion: We strongly recommend using these genetic-based reference values for ChE enzymes in our well-defined population in daily clinical practice.
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http://dx.doi.org/10.1590/S0120-41572015000500003DOI Listing
August 2015

Quality of methods reporting in animal models of colitis.

Inflamm Bowel Dis 2015 Jun;21(6):1248-59

*Bio-Health Informatics Group, School of Computer Science, University of Manchester, Manchester, United Kingdom; and †Manchester Immunology Group, Faculty of Life Science, University of Manchester, Manchester, United Kingdom.

Background: Current understanding of the onset of inflammatory bowel diseases relies heavily on data derived from animal models of colitis. However, the omission of information concerning the method used makes the interpretation of studies difficult or impossible. We assessed the current quality of methods reporting in 4 animal models of colitis that are used to inform clinical research into inflammatory bowel disease: dextran sulfate sodium, interleukin-10, CD45RB T cell transfer, and 2,4,6-trinitrobenzene sulfonic acid (TNBS).

Methods: We performed a systematic review based on PRISMA guidelines, using a PubMed search (2000-2014) to obtain publications that used a microarray to describe gene expression in colitic tissue. Methods reporting quality was scored against a checklist of essential and desirable criteria.

Results: Fifty-eight articles were identified and included in this review (29 dextran sulfate sodium, 15 interleukin-10, 5 T cell transfer, and 16 TNBS; some articles use more than 1 colitis model). A mean of 81.7% (SD = ±7.038) of criteria were reported across all models. Only 1 of the 58 articles reported all essential criteria on our checklist. Animal age, gender, housing conditions, and mortality/morbidity were all poorly reported.

Conclusions: Failure to include all essential criteria is a cause for concern; this failure can have large impact on the quality and replicability of published colitis experiments. We recommend adoption of our checklist as a requirement for publication to improve the quality, comparability, and standardization of colitis studies and will make interpretation and translation of data to human disease more reliable.
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http://dx.doi.org/10.1097/MIB.0000000000000369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450905PMC
June 2015

Lack of autoantibody induction by mercury exposure in artisanal gold mining settings in Colombia: Findings and a review of the epidemiology literature.

J Immunotoxicol 2015 5;12(4):368-75. Epub 2014 Dec 5.

Environmental Toxicology and Toxicogenomics Laboratory, Group of Immunology and Molecular Epidemiology, Faculty of Health .

Mercury (Hg) has been implicated as an immunotoxicant in experimental animal models, but its role in the induction of human autoimmunity remains unclear due to contradictory findings. Therefore, it has been claimed that it is important to examine other populations in order to clarify the role of Hg in these diseases. The aim of this study was to investigate whether occupational Hg exposure due to artisanal gold mining is associated with the prevalence of autoimmune biomarkers. A cross-sectional study was conducted comparing Hg-exposed gold miners (n = 164) with a control population (n = 127). Hair, blood, and 24-h urine samples were collected for measures of Hg levels, as well as of anti-nuclear antibodies (ANA) and rheumatoid factor (RF). Participants were clinically evaluated by a general practice physician, a rheumatologist, and a toxicologist. Statistically significant differences (p < 0.001) were found between Hg-exposed and non-exposed groups for all Hg biomarkers tested: blood (7.03 versus 2.46 µg Hg/L), urine (3.96 versus 1.48 µg Hg/g creatinine), and hair (0.79 versus 0.39 µg Hg/g). No difference was observed in ANA (cut-off titre of 1:80; PR = 0.93, 95% CI = 0.45-1.90) and RF (cut-off = 30 IU/mL; PR = 0.062, 95% CI = 0.03-1.08) status between the groups. In conclusion, the findings here do not support the hypothesis that Hg exposure due to artisanal gold mining activities had a significant impact on autoantibodies as biomarkers of autoimmune diseases. In a review context, the epidemiological findings were interpreted in light of the conflicting data in the literature about how Hg exposure was linked to development of autoantibodies. Validation of these findings in prospective studies is needed to firmly establish the role of Hg in development of autoimmunity in human populations.
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http://dx.doi.org/10.3109/1547691X.2014.986591DOI Listing
May 2016

The quality of methods reporting in parasitology experiments.

PLoS One 2014 30;9(7):e101131. Epub 2014 Jul 30.

Bio-health Informatics Group, School of Computer Science, University of Manchester, Manchester, United Kingdom; Manchester Immunology Group, Faculty of Life Science, University of Manchester, Manchester, United Kingdom.

There is a growing concern both inside and outside the scientific community over the lack of reproducibility of experiments. The depth and detail of reported methods are critical to the reproducibility of findings, but also for making it possible to compare and integrate data from different studies. In this study, we evaluated in detail the methods reporting in a comprehensive set of trypanosomiasis experiments that should enable valid reproduction, integration and comparison of research findings. We evaluated a subset of other parasitic (Leishmania, Toxoplasma, Plasmodium, Trichuris and Schistosoma) and non-parasitic (Mycobacterium) experimental infections in order to compare the quality of method reporting more generally. A systematic review using PubMed (2000-2012) of all publications describing gene expression in cells and animals infected with Trypanosoma spp was undertaken based on PRISMA guidelines; 23 papers were identified and included. We defined a checklist of essential parameters that should be reported and have scored the number of those parameters that are reported for each publication. Bibliometric parameters (impact factor, citations and h-index) were used to look for association between Journal and Author status and the quality of method reporting. Trichuriasis experiments achieved the highest scores and included the only paper to score 100% in all criteria. The mean of scores achieved by Trypanosoma articles through the checklist was 65.5% (range 32-90%). Bibliometric parameters were not correlated with the quality of method reporting (Spearman's rank correlation coefficient <-0.5; p>0.05). Our results indicate that the quality of methods reporting in experimental parasitology is a cause for concern and it has not improved over time, despite there being evidence that most of the assessed parameters do influence the results. We propose that our set of parameters be used as guidelines to improve the quality of the reporting of experimental infection models as a pre-requisite for integrating and comparing sets of data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101131PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116335PMC
November 2015
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