Water supply assessment and ranking of watershed dams in Georgia

Proceedings of the 2009 Georgia Water Resources Conference, April 27, 28, and 29, 2009 Athens, Georgia.Jordan, Jones & Goulding, Inc. (JJG, teamed with Schnabel Engineering, LLC) was selected by the Georgia Soil and Water Conservation Commission (Commission) to inventory and evaluate the water supply potential for 166 existing Watershed Dams in Georgia. Because of tremendous growth in the past several decades, water supply sources are increasingly in demand in Georgia, particularly in North Georgia. Also, environmental permitting requirements associated with constructing new reservoirs are increasingly stringent. Expansion of existing reservoir structures may be more acceptable to resource agencies, because many of the environmental impacts associated with existing reservoirs have already occurred. The Commission wanted a methodology to assess its existing dams and to rank their relative suitability for water supply; but inventory, assessment and ranking of 166 dams and their potential for expansion is no small task. JJG employed a GIS-based approach to the inventory and evaluation process. Available data resources were accessed and pertinent information on many factors was obtained, including wetlands, streams (including trout streams), protected species, cultural resources, numbers of affected structures and roads, impaired streams [303(d) or 305(b) listed], and distance to existing surface water intakes. Use of these data coverages made the organization of this huge amount of information manageable. The available environmental resource data was compared to potential reservoir yields, potential for pumpedstorage operation, and distance/cost of pumping to existing water systems. This information was assembled into an electronic matrix that enabled ranking of the various economic and non-economic factors according to their perceived importance. By iterations of the matrix, sensitivity analyses of the alternatives were done to look at their robustness under various yields and operating conditions. The top twenty alternatives that emerged from the ranking process were physically surveyed by JJG ecologists and engineers to refine the previously-collected data under “real-world” field conditions. Field data sets were collected using global positioning system (GPS) equipment, enabling the more accurate information to be downloaded directly into the GIS database. This in turn enabled a rapid re-evaluation of the rankings of the 20 most suitable alternatives.Sponsored by: Georgia Environmental Protection Division U.S. Geological Survey, Georgia Water Science Center U.S. Department of Agriculture, Natural Resources Conservation Service Georgia Institute of Technology, Georgia Water Resources Institute The University of Georgia, Water Resources FacultyThis book was published by Warnell School of Forestry and Natural Resources, The University of Georgia, Athens, Georgia 30602-2152. The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of The University of Georgia, the U.S. Geological Survey, the Georgia Water Research Institute as authorized by the Water Research Institutes Authorization Act of 1990 (P.L. 101-307) or the other conference sponsors

Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge

Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4(+) T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 × 10(−7)), but no methylation site reached epigenome-wide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genome-wide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD

\u3cem\u3eCPT1A\u3c/em\u3e Methylation Is Associated with Plasma Adiponectin

Background and Aims—Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood. Methods and Results—We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n= 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression coefficient ± SE= 0.01 ± 0.001, P=3.4x10−13) between plasma adiponectin levels and methylation of a CpG site in CPT1A, a key player in fatty acid metabolism. The association was replicated (n=474, P=0.0009) in whole blood samples from the Amish participants of the Heredity and Phenotype Intervention (HAPI) Heart Study as well as White (n=592, P=0.0005) but not Black (n=243, P=0.18) participants of the Bogalusa Heart Study (BHS). The association remained significant upon adjusting for BMI and smoking in GOLDN and HAPI but not BHS. We also identified associations between methylation loci in RNF145 and UFM1 and plasma adiponectin in GOLDN and White BHS participants, although the association was not robust to adjustment for BMI or smoking. Conclusion—We have identified and replicated associations between several biologically plausible loci and plasma adiponectin. These findings support the importance of epigenetic processes in metabolic traits, laying the groundwork for future translational applications

Menopause accelerates biological aging

Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further

Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity

Background: The putative functional variant -265T\u3eC (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity. Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction. Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (\u3c22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites. Results: In the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar results were observed in the GOLDN Study and the FHS. Additionally, in the FHS, cg04436964 methylation was negatively correlated with APOA2 expression in the blood of participants consuming a high-SFA diet. Furthermore, when consuming a high-SFA diet, CC carriers had lower APOA2 expression than those with the TT genotype. Lastly, metabolomic analysis identified 4 pathways as overrepresented by metabolite differences between CC and TT genotypes with high-SFA intake, including tryptophan and branched-chain amino acid (BCAA) pathways. Interestingly, these pathways were linked to rs5082-specific cg04436964 methylation differences in high-SFA consumers. Conclusions: The epigenetic status of the APOA2 regulatory region is associated with SFA intake and APOA2 -265T\u3eC genotype, promoting an APOA2 expression difference between APOA2 genotypes on a high-SFA diet, and modulating BCAA and tryptophan metabolic pathways. These findings identify potential mechanisms by which this highly reproducible gene-diet interaction influences obesity risk, and contribute new insights to ongoing investigations of the relation between SFA and human health. This study was registered at clinicaltrials.gov as NCT03452787

Epigenomics and Metabolomics Reveal the Mechanism of the \u3cem\u3eAPOA2\u3c/em\u3e-Saturated Fat Intake Interaction Affecting Obesity

Background: The putative functional variant −265T \u3e C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity. Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction. Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (\u3c 22 g/d) or high-SFA diet (≥ 22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites. Results: In the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar results were observed in the GOLDN Study and the FHS. Additionally, in the FHS, cg04436964 methylation was negatively correlated with APOA2 expression in the blood of participants consuming a high-SFA diet. Furthermore, when consuming a high-SFA diet, CC carriers had lower APOA2 expression than those with the TT genotype. Lastly, metabolomic analysis identified 4 pathways as overrepresented by metabolite differences between CC and TT genotypes with high-SFA intake, including tryptophan and branched-chain amino acid (BCAA) pathways. Interestingly, these pathways were linked to rs5082-specific cg04436964 methylation differences in high-SFA consumers. Conclusions: The epigenetic status of the APOA2 regulatory region is associated with SFA intake and APOA2 -265T \u3e C genotype, promoting an APOA2 expression difference between APOA2 genotypes on a high-SFA diet, and modulating BCAA and tryptophan metabolic pathways. These findings identify potential mechanisms by which this highly reproducible gene-diet interaction influences obesity risk, and contribute new insights to ongoing investigations of the relation between SFA and human health. This study was registered at clinicaltrials.gov as NCT03452787

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms