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Effect of different grouping strategies in developing estimates of personal exposures: specificity versus precision.

There has been increasing interest in recent years in developing strategies in epidemiology for the summarization of occupational exposures, strategies that serve to clarify observed relationships between occupational exposure and health outcomes. Where source occupational exposure data are scarce, it is common to assemble exposure groups with the goal of increasing the extent to which data-based exposure estimates are available for an entire cohort. There has been little guidance, however, on the effect of different grouping strategies on the observed fit between exposure and health outcome. This investigation examined the effect of the use of different exposure summarization strategies on observed relationships between dust exposure and lung function decline among coal mine workers. The dust exposure and spirometry data employed were gathered in the National Study of Coalworkers' Pneumoconiosis. An analysis of variance procedure was carried out to characterize the variability of the dust exposure data, employing single variables relating to mine identity, occupation, and year, as well as two- and three-way multivariate combinations of these variables. The resulting combinations were ranked according to the standard deviation of the observed exposure range to reflect the relative specificity of the various approaches. Sequential arrangements of single- and multiple-variable combinations were constructed, alternately employing highly specific codes or broad categories for mine, occupation, and year. Annual exposure estimates were constructed on the basis of these sequences and used in tandem with longitudinal change in forced expiratory volume (FEV1) in linear multiple regression procedures. Height, age, smoking status, and dust exposure were employed as predictor variables. The results show that the use of broad categorization approaches had a substantial impact on observed regression coefficients. The largest change was observed for categorization according to occupation, which resulted in two- to three-fold increases in the magnitude of observed regression coefficients. These results suggest that the use of highly specific exposure summarization approaches may result in regression outcomes which are marked by a high degree of attenuation, and that consideration of the precision of summarized exposure estimates is an important component of an effective exposure assessment strategy.

Adult↗

Effects of oral exposure to mining waste on in vivo dopamine release from rat striatum.

Several single components of mining waste (arsenic, manganese, lead, cadmium) to which humans are exposed at the mining area of Villa de la Paz, Mexico, are known to provoke alterations of striatal dopaminergic parameters. In this study we used an animal model to examine neurochemical changes resulting from exposure to a metal mixture. We used microdialysis to compare in vivo dopamine release from adult rats subchronically exposed to a mining waste by oral route with those from a control group and from a sodium arsenite group (25 mg/kg/day). We found that arsenic and manganese do accumulate in rat brain after 2 weeks of oral exposure. The mining waste group showed significantly decreased basal levels of dihydroxyphenylacetic acid (DOPAC; 66.7 +/- 7.53 pg/ microl) when compared to a control group (113.7 +/- 14.3 pg/ microl). Although basal dopamine release rates were comparable among groups, when the system was challenged with a long-standing depolarization through high-potassium perfusion, animals exposed to mining waste were not able to sustain an increased dopamine release in response to depolarization (mining waste group 5.5 +/- 0.5 pg/ microl versus control group 21.7 +/- 5.8 pg/ microl). Also, DOPAC and homovanillic acid levels were significantly lower in exposed animals than in controls during stimulation with high potassium. The arsenite group showed a similar tendency to that from the mining waste group. In vivo microdialysis provides relevant data about the effects of a chemical mixture. Our results indicate that this mining waste may represent a health risk for the exposed population.

Administration, Oral↗

Exposures to Legionella pneumophila and Chlamydia pneumoniae in South African Mine Workers.

Exposures of South African mine workers to Legionella pneumophila and Chlamydia pneumoniae were studied over a period of six months. Seroprevalence data were compared with data from a group of factory workers. Antibodies to L. pneumophila serogroups 1-4 were demonstrated in 36% of the mine workers and 10% of the factory workers (p < 0.0001). Seroconversion occurred in 18% of the mine workers during the study period. Antibodies to C. pneumoniae were present in 66% of the mine workers and 22% of the factory workers (p < 0.0001). Seroconversion was demonstrated in 17% of the mine workers during the six months of follow-up. A significant association between the presence of respiratory symptoms and seroconversion was demonstrated (p < 0.025). The data suggest that mine workers are at increased risk for infections with L. pneumophila and C. pneumoniae. Legionella pneumophila; Chlamydia pneumoniae; mine workers; factory workers; risk factors; seroprevalence; seroconversion

Journal Article↗

Derivation and use of sediment quality guidelines for ecological risk assessment of metals and radionuclides released to the environment from uranium mining and milling activities in Canada.

The Screening Level Concentration (SLC) approach was used to derive Lowest Effect Level (LEL) and Severe Effect Level (SEL) concentrations for nine metals (As, Cr, Cu, Pb, Mo, Ni, Se, U and V) and three radionuclides (226Ra, 210Pb, and 210Po) released to the aquatic environment during the mining and milling of uranium ore. This method was chosen because it allowed for the best use of the considerable historical and current data collected for diverse purposes in the uranium mining and milling regions of Canada (20,606 data points used in the analysis). Except for Cr, all the LELs derived in this study using the weighted method and published sediment quality guidelines (SQGs) were highly reliable (> 85%) in predicting sites unimpacted by uranium mining/milling defined as sites where reductions in the abundance and species richness of benthic invertebrate communities were < 20%. The derived SEL values and corresponding published SQGs (with the exception of Ni) were not reliable predictors (< or = 60%) of severe impacts on benthic invertebrate communities when severe impacts are defined as a reduction in abundance and species richness > or = 40%. Most of the severely impacted sites had sediment contaminant concentrations well below the SEL values. It is concluded that LELs derived using the weighted method can reliably be used in ecological risk assessments as concentrations below which adverse effects on benthic invertebrate communities are not expected. In contrast, it is recommended that SELs not be used in assessments of uranium mining/milling activities as concentrations above which adverse effects are anticipated.

Animals↗

Mining yeast transcriptional regulatory modules from factor DNA-binding sites and gene expression data.

UNLABELLED: In eukaryotes, gene expression is controlled by various transcription factors that bind to the promoter regions. Transcription factors may act positively, negatively or not at all. Different combinations of them may also activate or repress gene expression, and form regulatory networks of transcription. Uncovering such regulatory networks is a central challenge in genomic biology. In this study, we first defined a new kind of motifs in regulatory networks, transcriptional regulatory modules (TRMs), with the form factorset --> geneset, which emphasizes the combinatorial gene control of the group of factors factorset on the group of genes geneset. Second, we developed an efficient method based on a closed itemset mining technique for finding the two most informative kinds of TRMs, closed inf-TRMs and closed sup-TRMs, from factor DNA-binding sites and gene expression profiles data. The set of all closed inf-TRMs and closed sup-TRMs is often orders of magnitude smaller than the set of all TRMs but does not loss any information. When being applied to yeast data, our method produced results that are more compact, concise and comprehensive than those from previous studies to identify and interpret the transcriptional role of regulator combinations on sets of genes. AVAILABILITY: Supplementary files: http://www.jaist.ac.jp/~h-pham/regulation/.

Algorithms↗

An integrated approach to mapping the proteome of the human bone marrow stromal cell.

Bone marrow stromal cells, also known as mesenchymal stem or progenitor cells, are thought to play a critical role in hematopoiesis. Because hematopoiesis is dysregulated in leukemic individuals, expression profiling in leukemic stromal cells might yield valuable insights into mechanisms of normal and dysregulated hematopoiesis. Here, proteomics was used to identify expressed proteins in normal and leukemic bone marrow stromal cells. Isobaric tags for relative and absolute quantification (iTRAQ) technology and MS/MS were used to identify and quantify proteins in bone marrow stromal cells from two normal and two leukemic individuals. Approximately 900 distinct proteins were identified with >95% confidence, 73 of which were differentially expressed in leukemic stromal cells. cDNA microarray analysis on Affymetrix oligonucleotide gene chips showed that transcripts correlated with approximately 90% of the expressed proteins. A novel integrated approach for mining and visualization of iTRAQ data is presented. The results provide an initial assessment of the proteome in human bone marrow stromal cells, laying the groundwork for comprehensive analysis of the proteome in these cells, and ultimately, for improved understanding of normal and dysregulated hematopoiesis.

Adult↗

Molecular analysis of cancer using DNA and protein microarrays.

In conclusion, array-based technologies have emerged that contribute to profiling tissues at the genomic, transcriptomic and proteomic levels. Analytical tools are needed to mine the vast amount of data generated. Ultimately the molecular analysis of cancer at a genome and proteome scale will allow better classification of disease and tailored individualized therapy for individual patients.

Biotechnology↗

Radioactivity concentrations in soils of the Xiazhuang granite area, China.

The natural radioactivity of soils at the Xiazhuang granite massif of Southern China has been studied. The radioactivities of 55 samples have been measured with a low-background HPGe detector. The radioactivity concentrations of (238)U and (40)K ranged from 40.2 to 442 and from 442 to 913 Bq/kg, respectively, while the radioactivity concentration of (232)Th varied only slightly. In order to evaluate the radiological hazard of the natural radioactivity, the radium equivalent activity (Ra(eq)), the absorbed dose rate (D ), the annual effective dose rate and the external hazard index (H(ex)) have been calculated and compared with the internationally approved values. The study provides background radioactivity concentrations in a granite area, specifically, the area in the vicinity of a uranium mine in Southern China. The data can be used in exploring granite-type uranium deposits.

Algorithms↗

Analysis of the plant proteome.

For many years the analysis of plant proteomes has been restricted to the construction of descriptive catalogues or the search for markers. The analysis of plant proteomes is now gaining a functional dimension, however, because the focus has shifted onto well-defined plant-specific tissues and organelles, the simultaneous mining of proteomic and physiological data and specific methodological efforts.

Biotechnology↗

Patterns of diversifying selection in the phytotoxin-like scr74 gene family of Phytophthora infestans.

Phytophthora infestans, the organism responsible for the Irish famine, causes late blight, a re-emerging disease of potato and tomato. Little is known about the molecular evolution of P. infestans genes. To identify candidate effector genes (virulence or avirulence genes) that may have co-evolved with the host, we mined expressed sequence tag (EST) data from infection stages of P. infestans for secreted and potentially polymorphic genes. This led to the identification of scr74, a gene that encodes a predicted 74-amino acid secreted cysteine-rich protein with similarity to the Phytophthora cactorum phytotoxin PcF. The expression of scr74 was upregulated approximately 60-fold 2 to 4 days after inoculation of tomato and was also significantly induced during early stages of colonization of potato. The scr74 gene was found to belong to a highly polymorphic gene family within P. infestans with 21 different sequences identified. Using the approximate and maximum likelihood (ML) methods, we found that diversifying selection likely caused the extensive polymorphism observed within the scr74 gene family. Pairwise comparisons of 17 scr74 sequences revealed elevated ratios of nonsynonymous to synonymous nucleotide-substitution rates, particularly in the mature region of the proteins. Using ML, all 21 polymorphic amino acid sites were identified to be under diversifying selection. Of these 21 amino acids, 19 are located in the mature protein region, suggesting that selection may have acted on the functional portions of the proteins. Further investigation of gene copy number and organization revealed that the scr74 gene family comprises at least three copies located in a region of no more than 300 kb of the P. infestans genome. We found evidence that recombination contributed to sequence divergence within at least one gene locus. These results led us to propose an evolutionary model that involves gene duplication and recombination, followed by functional divergence of scr74 genes. This study provides support for using diversifying selection as a criterion for identifying candidate effector genes from sequence databases.

Algal Proteins↗

Water stress-responsive genes in loblolly pine (Pinus taeda) roots identified by analyses of expressed sequence tag libraries.

Drought stress is the principal cause of seedling mortality in pine forests of the southeastern United States and in many other forested regions around the globe. As part of a larger effort to discover loblolly pine genes, this study subjected rooted cuttings of three unrelated pine genotypes to three watering regimens. Expressed sequence tags (ESTs) were obtained from both the 3' and 5' ends of 12,918 randomly selected cDNAs generated from root tissues. These ESTs were clustered to identify 6,765 unique transcripts (UniScripts) derived from 6,202 putative unique genes (UniGenes-S). Tentative annotations were assigned on the basis of BLASTX comparisons to the Protein Information Resource Nonredundant Reference (PIR-NREF) database. Expression levels of 42 UniScripts varied with high statistical significance with respect to treatment. Many of them resembled gene products shown to be important for drought tolerance in other species, including dehydrins, endochitinases, cytochrome P450 enzymes, pathogenesis-related proteins and various late-embryogenesis abundant (LEA) gene products. Similarly, expression levels of 110 UniScripts varied with high statistical significance among genotypes, indicating that gene expression patterns in this species are much more dependent on genotype than on treatment. Most of the water stress-induced pine UniScripts that appeared to encode products resembling drought tolerance factors in other species were most highly induced in a single genotype, suggesting that particularly useful adaptive alleles for drought tolerance might exist within the collection of cDNAs characterized from this genotype. Mining and visualizing the complete data set, as well as downloading of both EST and UniScript contig sequences, are possible using MAGIC Gene Discovery at http://fungen.org/genediscovery/.

Acclimatization↗

Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease.

BACKGROUND: We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. Here, we examined peritoneal inflammatory cell patterns to determine their concordance with selected enhanced genes. METHODS: Expression patterns of selected inflammatory genes were mined from our previously published data base. Bilateral pelvic peritoneal and subjacent stromal specimens were obtained from 20 women with EOC and 7 women with benign pelvic conditions. Sections were first stained by indirect immunoperoxidase and numbers of monocytes/macrophages (MO/MA), T cells, B cells, and NK cells counted. Proportions of CD68+ cells and CD3+ cells that coexpressed MO/MA differentiation factors (CD163, CCR1, CXCR8, VCAM1, and phosphorylated cytosolic phospholipase A2 [pcPLA2]), which had demonstrated expression in EOC peritoneal samples, were determined by multicolor immunofluorescence. RESULTS: MO/MA were present on both sides of the pelvic peritoneum in EOC patients, with infiltration of the subjacent stroma and mesothelium. CD68+ MO/MA, the most commonly represented population, and CD3+ T cells were present more often in EOC than in benign pelvic tumors. NK cells, B cells, and granulocytes were rare. CXCL8 (IL-8) and the chemokine receptor CCR1 were coexpressed more frequently on MO/MA than on CD3+ cells contrasting with CD68+/CD163+ cells that coexpressed CXCL8 less often. An important activated enzyme in the eicosanoid pathway, pcPLA2, was highly expressed on both CD68+ and CD163+ cells. The adherence molecule Vascular Cell Adhesion Molecule-1 (VCAM1) was expressed on CD31+ endothelial cells and on a proportion of CD68+ MO/MA but rarely on CD3+ cells. CONCLUSION: The pelvic peritoneum in EOC exhibits a general pattern of chronic inflammation, represented primarily by differentiated MO/MA, and distinct from that in benign conditions concordant with previous profiling results.

Journal Article↗

ProteinChip clinical proteomics: computational challenges and solutions.

ProteinChip technology, a suite of analytical tools that includes retentate chromatography, on-chip protein characterization, and multivariate analysis, allows researchers to examine patterns ofprotein expression and modification. Based on the surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) approach, ProteinChip technology has been pioneered by researchers at Ciphergen Biosystems (Fremont, CA, USA), as well as by users of Ciphergen's commercial embodiment of this technology the ProteinChip Biomarker System. This report will begin with a background of the technology and describe its applications in clinical proteomics and will then conclude with a discussion of tools and strategies to mine the large amounts of data generated during the course of a typical clinical proteomics study.

Biomarkers↗

MILANO--custom annotation of microarray results using automatic literature searches.

BACKGROUND: High-throughput genomic research tools are becoming standard in the biologist's toolbox. After processing the genomic data with one of the many available statistical algorithms to identify statistically significant genes, these genes need to be further analyzed for biological significance in light of all the existing knowledge. Literature mining--the process of representing literature data in a fashion that is easy to relate to genomic data--is one solution to this problem. RESULTS: We present a web-based tool, MILANO (Microarray Literature-based Annotation), that allows annotation of lists of genes derived from microarray results by user defined terms. Our annotation strategy is based on counting the number of literature co-occurrences of each gene on the list with a user defined term. This strategy allows the customization of the annotation procedure and thus overcomes one of the major limitations of the functional annotations usually provided with microarray results. MILANO expands the gene names to include all their informative synonyms while filtering out gene symbols that are likely to be less informative as literature searching terms. MILANO supports searching two literature databases: GeneRIF and Medline (through PubMed), allowing retrieval of both quick and comprehensive results. We demonstrate MILANO's ability to improve microarray analysis by analyzing a list of 150 genes that were affected by p53 overproduction. This analysis reveals that MILANO enables immediate identification of known p53 target genes on this list and assists in sorting the list into genes known to be involved in p53 related pathways, apoptosis and cell cycle arrest. CONCLUSIONS: MILANO provides a useful tool for the automatic custom annotation of microarray results which is based on all the available literature. MILANO has two major advances over similar tools: the ability to expand gene names to include all their informative synonyms while removing synonyms that are not informative and access to the GeneRIF database which provides short summaries of curated articles relevant to known genes. MILANO is available at http://milano.md.huji.ac.il.

Algorithms↗

Geochemical modeling of gold precipitation conditions in the Bloco do Butiá Mine, Lavras do Sul/Brazil.

A geochemical modeling of gold deposition was performed using the EQ3/EQ6 software package using conditions inferred from geological, petrographic, geochemical and fluid inclusion data from the Bloco do Butiá gold mine, Lavras do Sul, RS. Gold in the mine occurs only in the pyrite structure (invisible gold). The pyrite occurs associated with white mica (phengite) in the zone of phyllic alteration. The process of gold deposition showed to be related to temperature and pH decrease. The pH decrease was fundamental to gold deposition by destabilization of sulfur species [Au(HS)2- , HAu(HS)2(0) and Au(HS)0] dissolved in the aqueous solution, being Au(HS)0 the main gold transporting complex. The addition of KCl is hard to accept as cause of gold precipitation because no Cl- was detected in phengite. However, the geochemical mass balance calculation resulted in the gain of some potassium in the zone of phyllic alteration. The precipitation of pyrite (+/- auriferous) may have been strongly influenced by iron availability resulting from dissolution of ferrous chlorites by the fluids responsible for phengite deposition. The low salinity in quartz grain fluid inclusions from the propylitized wall rock also indicates the little importance of chlorine as gold transporting agent. Sulfur, and not chlorine, compounds must have dominated the gold transporting complexes in the Bloco do Butiá gold area.

Journal Article↗

Pre-operational survey of a U mine near Val Vedello, Italy.

Results obtained from radiometric research carried out from 1980-81 in the region of U mines in the Val Vedello are provided. Data are presented on 222Rn, 226Ra and natural U concentrations in spring and surface waters. Concentrations were found to be relatively low. There is some increase in the vicinity of the exploratory U mine but this is, at least up to the present, only of a local character. Data are presented on external gamma exposure, 210Pb and 210Po in foodstuffs and in the urine of normal and exposed population as well as 226Ra in milk and vegetable samples. The aim of this study is to outline a preliminary map of natural radioactivity on the site before starting the mining activity. This will enable us later to detect changes caused by the U mining, milling and mill-tailing disposal operations.

Air Pollutants, Radioactive↗

Fuzzy versus quantitative association rules: a fair data-driven comparison.

As opposed to quantitative association rule mining, fuzzy association rule mining is said to prevent the overestimation of boundary cases, as can be shown by small examples. Rule mining, however, becomes interesting in large databases, where the problem of boundary cases is less apparent and can be further suppressed by using sensible partitioning methods. A data-driven approach is used to investigate if there is a significant difference between quantitative and fuzzy association rules in large databases. The influence of the choice of a particular triangular norm in this respect is also examined.

Algorithms↗

Exposure to silica and silicosis among tin miners in China: exposure-response analyses and risk assessment.

OBJECTIVES: To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust). METHODS: A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III-similar to an International Labour Organisation (ILO) classification of 1/1 or greater. RESULTS: There were 1015 (33.7%) miners identified with silicosis, who had a mean age of 48.3 years, with a mean of 21.3 years after first exposure (equivalent to 11.0 net years in a dusty job). Among those who had silicosis, 684 miners (67.4%) developed silicosis after exposure ended (a mean of 3.7 years after). The risk of silicosis was strongly related to cumulative exposure to silica dust and was well fitted by the Weibull distribution, with the risk of silicosis less than 0.1% when the Chinese measure of cumulative exposure to total dust (CTD) was under 10 mg/m(3)-years (or 0.36 mg/m(3)-years of respirable crystalline silica), increasing to 68.7% when CTD exposure was 150 mg/m(3)-years (or 5.4 mg/m(3)-years of respirable crystalline silica). Latency period was not correlated to the risk of silicosis or cumulative dose of exposure. This study predicts about a 36% cumulative risk of silicosis for a 45 year lifetime exposure to these tin mine dusts at the CTD exposure standard of 2 mg/m(3), and a 55% risk at 45 years exposure to the current United States Occupational Safety and Health Administration and Mine Safety and Health Administration standards of 0.1 mg/m(3) 100% respirable crystalline silica dust. CONCLUSIONS: A clear exposure-response relation was detected for silicosis in Chinese tin miners. The study results were similar to most, but not all, findings from other large scale exposure-response studies.

Adult↗