Cheminformatics for genome-scale metabolic reconstructions

Genome-scale metabolic reconstructions are an important resource in the study of metabolism. They provide both a system and component level view of the biochemical transformations of metabolites. As more reconstructions have been created it remains a challenge to integrate and reason about their contents. This thesis focuses on the development of computational methods to allow on-demand comparison and alignment of metabolic reconstructions. A novel method is introduced that utilises chemical structure representations to identify equivalent metabolites between reconstructions. Using a graph theoretic representation allows the identification and reasoning of metabolites that have a non-exact match. A key advantage is that the method uses the contents of reconstructions directly and does not rely on the creation or use of a common reference. To annotate reconstructions with chemical structure representations an interactive desktop application is introduced. The application assists in the creation and curation of metabolic information using manual, semi-auto\-mated, and automated methods. Chemical structure representations can be retrieved, drawn, or generated to allow precise metabolite annotation. In processing chemical information, efficient and optimised algorithms are required. Several areas are addressed and implementations have been contributed to the Chemistry Development Kit. Rings are a fundamental property of chemical structures therefore multiple ring definitions and fast algorithms are explored. Conversion and standardisation between structure representations present a challenge. Efficient algorithms to determine aromaticity, assign a Kekulé form, and generate tautomers are detailed. Many enzymes are selective and specific to stereochemistry. Methods for the identification, depiction, comparison, and description of stereochemistry are described.The project was funded by Unilever, the Biotechnology and Biological Sciences Research Council [BB/I532153/1], and the European Molecular Biology Laboratory

The Wehl family of South Australia and their botanical connections with “Dear Uncle” Baron Ferdinand von Mueller

Dr Eduard Wehl and Clara Wehl (née Mueller) and their children hold a unique position in the history of South Australian botany because of their association with Clara’s brother and the children’s uncle, Baron Ferdinand von Mueller, Australia’s most significant botanist of the nineteenth century. Both Wehl parents and six of their twelve surviving children collected botanical specimens for Mueller and about 1200 herbarium specimens have been located with most being held in the National Herbarium of Victoria. The majority of specimens were collected in the vicinity of Mount Gambier and Lake Bonney, South Australia. As well as collecting botanical specimens, two daughters, Marie Magdalene Wehl and Henrietta Jane Wehl, illustrated plants and fungi. About 300 illustrations have survived. Of these, about 240 are of flowering plants and contained in three sketchbooks, two of which are at the National Herbarium of Victoria and one at the State Herbarium of South Australia. Marie made a speciality of illustrating fungi, and 36 illustrations are included in an album in the Natural History Museum, London, and 25 others are held as either loose illustrations or associated with herbarium specimens in the National Herbarium of Victoria. Specimens collected by the Wehls have been used in the typification of at least 23 species names. The family is commemorated in three taxa: Clara Wehl in the marine alga Gigartina wehliae Sond.; Eduard and Clara Wehl jointly in the plant genus Wehlia F.Muell. [= Homalocalyx F.Muell.]; and Marie Wehl in the fungus Agaricus wehlianus F.Muell. ex Cooke [=Pluteus wehlianus (F.Muell. ex Cooke) Sacc.]. In this paper we provide a brief history of the Wehl family in South Australia. We assess the herbarium specimens collected by them, examine their illustrations and determine the connections between them and their current importance for typification. Underlying this, we consider the contribution made by the Wehl family toward the botanical work of Baron Ferdinand von Mueller

Concentrations of Metals in Aquatic Invertebrates from the Ozark National Scenic Riverways, Missouri

This report summarizes the findings of a study conducted as a pilot for part of a park-wide monitoring program being developed for the Ozark National Scenic Riverways (ONSR) of southeastern Missouri. The objective was to evaluate using crayfish (Orconectes spp.) and Asian clam (Corbicula fluminea) for monitoring concentrations of metals associated with lead-zinc mining. Lead-zinc mining presently (2007) occurs near the ONSR and additional mining has been proposed. Three composite samples of each type (crayfish and Asian clam), each comprising ten animals of approximately the same size, were collected during late summer and early fall of 2005 from five sites on the Current River and Jacks Fork within the ONSR and from one site on the Eleven Point River and the Big River, which are outside the ONSR. The Big River has been contaminated by mine tailings from historical leadzinc mining. Samples were analyzed by inductively coupled plasma mass spectrometry for lead, zinc, cadmium, cobalt, and nickel concentrations. All five metals were detected in all samples; concentrations were greatest in samples of both types from the Big River, and lowest in samples from sites within the ONSR. Concentrations of zinc and cadmium typically were greater in Asian clams than in crayfish, but differences were less evident for the other metals. In addition, differences among sites were small for cobalt in Asian clams and for zinc in crayfish, indicating that these metals are internally regulated to some extent. Consequently, both sample types are recommended for monitoring. Concentrations of metals in crayfish and Asian clams were consistent with those reported by other studies and programs that sampled streams in southeast Missouri

Concentrations of Metals in Aquatic Invertebrates from the Ozark National Scenic Riverways, Missouri

This report summarizes the findings of a study conducted as a pilot for part of a park-wide monitoring program being developed for the Ozark National Scenic Riverways (ONSR) of southeastern Missouri. The objective was to evaluate using crayfish (Orconectes spp.) and Asian clam (Corbicula fluminea) for monitoring concentrations of metals associated with lead-zinc mining. Lead-zinc mining presently (2007) occurs near the ONSR and additional mining has been proposed. Three composite samples of each type (crayfish and Asian clam), each comprising ten animals of approximately the same size, were collected during late summer and early fall of 2005 from five sites on the Current River and Jacks Fork within the ONSR and from one site on the Eleven Point River and the Big River, which are outside the ONSR. The Big River has been contaminated by mine tailings from historical leadzinc mining. Samples were analyzed by inductively coupled plasma mass spectrometry for lead, zinc, cadmium, cobalt, and nickel concentrations. All five metals were detected in all samples; concentrations were greatest in samples of both types from the Big River, and lowest in samples from sites within the ONSR. Concentrations of zinc and cadmium typically were greater in Asian clams than in crayfish, but differences were less evident for the other metals. In addition, differences among sites were small for cobalt in Asian clams and for zinc in crayfish, indicating that these metals are internally regulated to some extent. Consequently, both sample types are recommended for monitoring. Concentrations of metals in crayfish and Asian clams were consistent with those reported by other studies and programs that sampled streams in southeast Missouri

Patient compliance with clinical follow-up after total joint arthroplasty

Patient compliance with clinical follow-up after total joint arthroplast

Assessment of Elemental Concentrations in Streams of the New Lead Belt in Southeastern Missouri, 2002–05

Concerns about possible effects of lead-mining activities on the water quality of federally protected streams located in southeastern Missouri prompted a suite of multidisciplinary studies to be conducted by the U.S. Geological Survey. As part of this investigation, a series of biological studies were initiated in 2001 for streams in the current mining region and the prospecting area. In this report, results are examined for trace elements and other selected chemical measurements in sediment, surface water, and sediment interstitial (pore) water sampled between 2002 and 2005 in association with these biological studies. Compared to reference sites, fine sediments collected downstream from mining areas were enriched in metals by factors as large as 75 for cadmium, 62 for cobalt, 171 for nickel, 95 for lead, and 150 for zinc. Greatest metal concentrations in sediments collected in 2002 were from sites downstream from mines on Strother Creek, Courtois Creek, and the West Fork Black River. Sediments from sites on Bee Fork, Logan Creek, and Sweetwater Creek also were noticeably enriched in lead. Sediments in Clearwater Lake, at least 75 kilometers downstream from mining activity, had metal concentrations that were 1.5 to 2.1 times greater than sediments in an area of the lake with no upstream mining activity. Longitudinal sampling along three streams in 2004 indicated that sediment metal concentrations decreased considerably a few kilometers downstream from mining activities; however, in Strother Creek some metals were still enriched by a factor of five or more as far as 13 kilometers downstream from the Buick tailings impoundment. Compared with 2002 samples, metals concentrations were dramatically lower in sediments collected in 2004 at an upper West Fork Black River site, presumably because beneficiation operations at the West Fork mill ceased in 2000. Concentrations of metals and sulfate in sediment interstitial (pore) waters generally tracked closely with metal concentrations in sediments. Metals, including cobalt, nickel, lead, and zinc, were elevated substantially in laboratory-produced pore waters of fine sediments collected near mining operations in 2002 and 2004. Passive diffusion samplers (peepers) buried 4 to 6 centimeters deep in riffle-run stream sediments during 2003 and 2005 had much lower pore-water metal concentrations than the laboratory-produced pore waters of fine sediments collected in 2002 and 2004, but each sampling method produced similar patterns among sites. The combined mean concentration of lead in peeper samples from selected sites located downstream from mining activities for six streams was about 10-fold greater than the mean of the reference sites. In most instances, metals concentrations in surface water and peeper water were not greatly different, indicating considerable exchange between the surface water and pore water at the depths and locations where peepers were situated. Passive sampling probes used to assess metal lability in pore waters of selected samples during 2004 sediment toxicity tests indicated that most of the filterable lead in the laboratory-prepared pore water was relatively non-labile, presumably because lead was complexed by organic matter, or was present as colloidal species. In contrast, large percentages of cobalt and nickel in pore water appeared to be labile. Passive integrative samplers deployed in surface water for up to 3 weeks at three sites in July 2005 confirmed the presence of elevated concentrations of labile metals downstream from mining operations on Strother Creek and, to a lesser extent, Bee Fork. These samplers also indicated a considerable increase in metal loadings occurred for a few days at the Strother Creek site, which coincided with moderate increases in stream discharges in the area

Adult asthma associated with roadway density and housing in rural Appalachia: the Mountain Air Project (MAP).

BACKGROUND: Appalachian Kentucky is a rural area with a high prevalence of asthma among adults. The relative contribution of environmental exposures in the etiology of adult asthma in these populations has been understudied. OBJECTIVE: This manuscript describes the aims, study design, methods, and characteristics of participants for the Mountain Air Project (MAP), and focuses on associations between small area environmental exposures, including roadways and mining operations, and lifetime and current asthma in adults. METHODS: A cohort of residents, aged 21 and older, in two Kentucky counties, was enrolled in a community-based, cross-sectional study. Stratified cluster sampling was used to select small geographic areas denoted as 14-digit USGS hydrologic units (HUCs). Households were enumerated within selected HUCs. Community health workers collected in-person interviews. The proximity of nearby active and inactive coal mining operations, density of oil and gas operations, and density of roadways were characterized for all HUCs. Poisson regression analyses were used to estimate adjusted prevalence ratios. RESULTS: From 1,459 eligible households contacted, 1,190 individuals were recruited, and 972 persons completed the interviews. The prevalence of lifetime asthma was 22.8%; current asthma was 16.3%. Adjusting for covariates, roadway density was positively associated with current asthma in the second (aPR = 1.61; 95% CI 1.04-2.48) and third tertiles (aPR = 2.00; 95% CI 1.32-3.03). Increased risk of current asthma was associated with residence in public, multi-unit housing (aPR = 2.01; 95% CI 1.27-3.18) compared to a residence in a single-family home. There were no notable associations between proximity to coal mining and oil and gas operations and asthma prevalence. CONCLUSIONS: This study suggests that residents in rural areas with higher roadway density and those residing in public housing units may be at increased risk for current asthma after accounting for other known risk factors. Confirming the role of traffic-related particulates in producing high asthma risk among adults in this study contributes to the understanding of the multiple environmental exposures that influence respiratory health in the Appalachia region

Sensitivity of Snowmelt Hydrology on Mountain Slopes to Forest Cover Disturbance

Alberta Sustainable Resource Development, IP3 Network, NSERC Discovery Grants and Research Tool Instrument Grants and the University of Calgary Biogeoscience Institute.Non-Peer ReviewedMarmot Creek Research Basin was the subject of intense studies of snowmelt, water balance and streamflow generation in order to generate a five year database of precipitation inputs, snowpack dynamics and streamflow that could be used in hydrological model testing. A physically based hydrological model of the basin was constructed using the Cold Regions Hydrological Model and tested over four years of simulation. The model was found to accurately simulate snowpacks in forested and cleared landscapes and the timing and quantity of streamflow over the basin. The model was manipulated to simulate the impacts of forest disturbance on basin snow dynamics, snowmelt, streamflow and groundwater recharge. A total of 40 forest disturbance scenarios were compared to the current land use over the four simulation years. Disturbance scenarios ranged from the impact of pine beetle kill of lodgepole pine to clearing of north or south facing slopes, forest fire and salvage logging impacts. Pine beetle impacts were small in all cases with increases in snowmelt of less than 10% and of streamflow and groundwater recharge of less than 2%. This is due to only 15% of the basin area being covered with lodgepole pine and this pine being at lower elevations which received much lower snowfall and rainfall than did higher elevations and so generated much less streamflow and groundwater recharge. Forest disturbance due to fire and clearing affected much large areas of the basin and higher elevations and were generally more than twice as effective in increasing snowmelt or streamflow. For complete forest cover removal with salvage logging a 45% increase in snowmelt was simulated, however this only translated into a 5% increase in spring and summer streamflow and a 7% increase in groundwater recharge. Forest fire with retention of standing burned trunks was the most effect forest cover treatment for increasing streamflow (up to 8%) due to minimizing both sublimation of winter snow and summer evaporation rates. Peak daily streamflow discharges responded more strongly to forest cover decrease than did seasonal streamflow with increases of over 20% in peak streamflow with removal of forest cover. It is suggested that the dysynchronization of snowmelt timing with forest cover removal resulted in an ineffective translation of changes in snowmelt quantity to streamflow. This resulted in a complementary increase in groundwater recharge as well as streamflow as forest cover was reduced. Presumably, a basin with differing soil characteristics, groundwater regime or topographic orientation would provide a differing hydrological response to forest cover change and the sensitivity of these changes to basin characterisation needs further examination