ABSTRACT
Poor performance of wet scrubbers in rubber processing plants due to breakthrough of specific volatile organic compounds (VOCs) causes odour impact events. The performance of wet scrubbers in the rubber drying process to remove VOCs was investigated in order to determine the responsible odorants. VOC emissions originating at the inlet and outlet of wet scrubbers were quantified using gas chromatography-mass spectrometry/olfactometry (GC-MS/O). Critical VOCs were identified alongside seasonal and daily variations of those VOCs. Altogether, 80 VOCs were detected in rubber emissions with 16 classified as critical VOCs based on their chemical concentration, high odour activity value (OAV) and unpleasant odour. Volatile fatty acids (VFAs) were the dominant VOCs with seasonal variations affecting emission composition. Results demonstrated the ineffectiveness of the wet scrubbers to mitigate odorous VOCs whereas the removal of some VOCs could be improved based on their polarity and solubility. It was found that there is a correlation between the wet scrubber performance and VFAs concentration in the emissions. The findings demonstrated that combining quantitative and sensory analyses improved accuracy in identifying odorous VOCs, which can cause odour annoyance from rubber processing. A VOC identification framework was proposed using both analyses approaches.
Subject(s)
Air Pollutants , Volatile Organic Compounds , Air Pollutants/analysis , Gas Chromatography-Mass Spectrometry , Odorants/analysis , Rubber , Volatile Organic Compounds/analysisABSTRACT
[This corrects the article DOI: 10.1371/journal.pgen.1006528.].
ABSTRACT
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Subject(s)
Adiposity/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Exercise , Obesity/genetics , Adiposity/physiology , Body Mass Index , Epigenomics , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Humans , Male , Obesity/physiopathology , Waist Circumference , Waist-Hip RatioABSTRACT
Varieties of gas chromatography (GC) combined with chemical detection (CD) and sensory analysis at the odour detection port (ODP) for the evaluation of environmental odorants has steadily increased in application and sophistication; this has given rise to a plethora of techniques that cater to specific tasks. With this diversity of approaches in mind, there is a need to assess the critical points at which these approaches differ, as well as likely risks and factors that may affect them. These critical points explained within this review include sample preparation, GC separation techniques (with associated co-elution risks), how the elute is separated between CD and sensory analysis, the type of CD, the type of sensory analysis (with particular attention paid to its factors and guidelines), integrative data techniques, as well as how that data may be used. Additionally, this review provides commentary on the current state of the research space and makes recommendations based on how these analyses should be reported, the standardisation of nomenclature, as well as the impediments to the future goals of this research area. By careful consideration of the critical points of varying analytical processes and how best to communicate these findings, the quality of output within this area will improve. This review provides a benchmark for how GC-CD/sensory analysis should be undertaken and reported.
ABSTRACT
GWAS have identified numerous SNPs associated with prostate cancer risk. One such SNP is rs10993994. It is located in the ß-microseminoprotein (MSMB) promoter region, mediates MSMB prostate secretion levels, and is linked to mRNA expression changes in both MSMB and the adjacent gene NCOA4. In addition, our previous work showed a second SNP, rs7098889, is in positive linkage disequilibrium with rs10993994 and associated with MSMB expression independent of rs10993994. Here, we generate a series of clones with single alleles removed by double guide RNA (gRNA) mediated CRISPR/Cas9 deletions, through which we demonstrate that each of these SNPs independently and greatly alters MSMB expression in an allele-specific manner. We further show that these SNPs have no substantial effect on the expression of NCOA4. These data demonstrate that a single SNP can have a large effect on gene expression and illustrate the importance of functional validation studies to deconvolute observed correlations. The method we have developed is generally applicable to test any SNP for which a relevant heterozygous cell line is available. AUTHOR SUMMARY: In pursuing the underlying biological mechanism of prostate cancer pathogenesis, scientists utilized the existence of common single nucleotide polymorphisms (SNPs) in the human genome as genetic markers to perform large scale genome wide association studies (GWAS) and have so far identified more than a hundred prostate cancer risk variants. Such variants provide an unbiased and systematic new venue to study the disease mechanism, and the next big challenge is to translate these genetic associations to the causal role of altered gene function in oncogenesis. The majority of these variants are waiting to be studied and lots of them may act in oncogenesis through gene expression regulation. To prove the concept, we took rs10993994 and its linked rs7098889 as an example and engineered single cell clones by allelic-specific CRISPR/Cas9 deletion to separate the effect of each allele. We observed that a single nucleotide difference would lead to surprisingly high level of MSMB gene expression change in a gene specific and cell-type specific manner. Our study strongly supports the notion that differential level of gene expression caused by risk variants and their associated genetic locus play a major role in oncogenesis and also highlights the importance of studying the function of MSMB encoded ß-MSP in prostate cancer pathogenesis.
Subject(s)
Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Nuclear Receptor Coactivators/biosynthesis , Prostatic Neoplasms/genetics , Prostatic Secretory Proteins/genetics , CRISPR-Cas Systems/genetics , Gene Deletion , Gene Editing/methods , Histone Code/genetics , Humans , Linkage Disequilibrium/genetics , Male , Nuclear Receptor Coactivators/genetics , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , RNA, Messenger/biosynthesisABSTRACT
BACKGROUND: The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. RESULTS: JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. CONCLUSIONS: JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda.
Subject(s)
Evolution, Molecular , Genomics/methods , Software , Codon/genetics , Databases, Genetic , Databases, Protein , Sequence AlignmentABSTRACT
Research into industry-community relationships have focused almost exclusively on the ways in which communities responds to actions from industries. This has led to a paucity of understanding with regards to how community engagement and malodour amelioration practices have been adopted by industry personnel, as well as the attitudes and beliefs of non-community stakeholders in general. In this study, a survey to water industry personnel was distributed to three Australian water utilities in South-Eastern Australia and a semi-structured interview process was carried out with plant managers at six wastewater treatment plants. It was observed that best practice has not yet been established with regards to community engagement and odour amelioration, and that water industry personnel in general had a poor understanding of these concepts. Recommendations for how this situation could be improved, and how non-community stakeholders investigated, are discussed.
Subject(s)
Attitude , Community-Institutional Relations , Industry , Odorants/analysis , Wastewater/analysis , Humans , New South WalesABSTRACT
Odorous emissions from wastewater biosolids processing can cause nuisance impacts to the surrounding community. Odour Wheels are an effective tool for environmental odour management, but have yet to be provided for wastewater biosolids processing. Emissions throughout the biosolids processing from eight wastewater treatment plants, each with different unit operation configurations, were surveyed to identify odorants present and their olfactory properties. Chemical and olfactory methods identified a range of odorants and odours emitted throughout biosolids processing. Within the biosolids processing locations studied Sulfur type odours, described as rotten eggs or cabbage, were typically encountered. However, there was also a varying presence of Rancid/putrid and Faecal/manure type odours. Odour Wheels were generated to communicate both the olfactory and chemical components of emissions which were measured throughout biosolids processing. Examples based on the operation of the eight wastewater treatment plants were used to demonstrate how the Odour Wheels can be used as an onsite odour management aid. The paper demonstrates how Odour Wheels can be prepared using chemical and olfactory measurements and then used to communicate olfactory properties, as well as identify the causes of nuisance emissions throughout biosolids processing at wastewater treatment plants. The linking of odours and odorants to process conditions throughout biosolids processing facilitates effective abatement and management practices.
ABSTRACT
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Subject(s)
Gene Expression Regulation/physiology , Genome-Wide Association Study , Leptin/blood , Leptin/metabolism , Adipose Tissue/metabolism , Animals , Gene Knockdown Techniques , Leptin/genetics , Male , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tissue Culture TechniquesABSTRACT
Though numerous polymorphisms have been associated with risk of developing lymphoma, how these variants function to promote tumorigenesis is poorly understood. Here, we report that lymphoma risk SNPs, especially in the non-Hodgkin's lymphoma subtype chronic lymphocytic leukemia, are significantly enriched for co-localization with epigenetic marks of active gene regulation. These enrichments were seen in a lymphoid-specific manner for numerous ENCODE datasets, including DNase-hypersensitivity as well as multiple segmentation-defined enhancer regions. Furthermore, we identify putatively functional SNPs that are both in regulatory elements in lymphocytes and are associated with gene expression changes in blood. We developed an algorithm, UES, that uses a Monte Carlo simulation approach to calculate the enrichment of previously identified risk SNPs in various functional elements. This multiscale approach integrating multiple datasets helps disentangle the underlying biology of lymphoma, and more broadly, is generally applicable to GWAS results from other diseases as well.