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Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound

Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p < 0.01). Using a panel of the top three AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, then the sensitivity was 23.3% at 98.3% specificity. AAb to at least one of these top three antigens were also detected in 7/20 sera (35%) of patients with low CA 125 levels and 0/15 controls. AAb to p53, PTPRA, and PTGFR are potential biomarkers for the early detection of ovarian cancer.

ContributorsAnderson, Karen (Author) / Cramer, Daniel W. (Author) / Sibani, Sahar (Author) / Wallstrom, Garrick (Author) / Wong, Jessica (Author) / Park, Jin (Author) / Qiu, Ji (Author) / Vitonis, Allison (Author) / LaBaer, Joshua (Author) / Biodesign Institute (Contributor)
Created2015-01-01
Description

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the simultaneous detection of six chlorinated ethenes and ethene itself, using a liquid sample volume of 1 mL by concentrating the compounds onto an 85-µm carboxen-polydimenthylsiloxane solid-phase microextraction fiber in 5 min and subsequent chromatographic analysis in 9.15 min. Linear increases in signal response were obtained over three orders of magnitude (∼0.05 to ∼50 µM) for simultaneous analysis with coefficient of determination (R2) values of ≥ 0.99. The detection limits of the method (1.3–6 µg/L) were at or below the maximum contaminant levels specified by the EPA. Matrix spike studies with groundwater and mineral medium showed recovery rates between 79–108%. The utility of the method was demonstrated in lab-scale sediment flow-through columns assessing the bioremediation potential of chlorinated ethene-contaminated groundwater. Owing to its low sample volume requirements, good sensitivity and broad target analyte range, the method is suitable for routine compliance monitoring and is particularly attractive for interpreting the bench-scale feasibility studies that are commonly performed during the remedial design stage of groundwater cleanup projects.

ContributorsZiv-El, Michal (Author) / Kalinowski, Tomasz (Author) / Krajmalnik-Brown, Rosa (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2014-02-01
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Description

Aquaculture production has nearly tripled in the last two decades, bringing with it a significant increase in the use of antibiotics. Using liquid chromatography/tandem mass spectrometry (LC–MS/MS), the presence of 47 antibiotics was investigated in U.S. purchased shrimp, salmon, catfish, trout, tilapia, and swai originating from 11 different countries. All

Aquaculture production has nearly tripled in the last two decades, bringing with it a significant increase in the use of antibiotics. Using liquid chromatography/tandem mass spectrometry (LC–MS/MS), the presence of 47 antibiotics was investigated in U.S. purchased shrimp, salmon, catfish, trout, tilapia, and swai originating from 11 different countries. All samples (n = 27) complied with U.S. FDA regulations and five antibiotics were detected above the limits of detection: oxytetracycline (in wild shrimp, 7.7 ng/g of fresh weight; farmed tilapia, 2.7; farmed salmon, 8.6; farmed trout with spinal deformities, 3.9), 4-epioxytetracycline (farmed salmon, 4.1), sulfadimethoxine (farmed shrimp, 0.3), ormetoprim (farmed salmon, 0.5), and virginiamycin (farmed salmon marketed as antibiotic-free, 5.2). A literature review showed that sub-regulatory levels of antibiotics, as found here, can promote resistance development; publications linking aquaculture to this have increased more than 8-fold from 1991 to 2013. Although this study was limited in size and employed sample pooling, it represents the largest reconnaissance of antibiotics in U.S. seafood to date, providing data on previously unmonitored antibiotics and on farmed trout with spinal deformities. Results indicate low levels of antibiotic residues and general compliance with U.S. regulations. The potential for development of microbial drug resistance was identified as a key concern and research priority.

ContributorsDone, Hansa (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2015-01-23
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Description

The land, water, and energy requirements of hydroponics were compared to those of conventional agriculture by example of lettuce production in Yuma, Arizona, USA. Data were obtained from crop budgets and governmental agricultural statistics, and contrasted with theoretical data for hydroponic lettuce production derived by using engineering equations populated with

The land, water, and energy requirements of hydroponics were compared to those of conventional agriculture by example of lettuce production in Yuma, Arizona, USA. Data were obtained from crop budgets and governmental agricultural statistics, and contrasted with theoretical data for hydroponic lettuce production derived by using engineering equations populated with literature values. Yields of lettuce per greenhouse unit (815 m(2)) of 41 +/- 6.1 kg/m(2)/y had water and energy demands of 20 +/- 3.8 L/kg/y and 90,000 +/- 11,000 kJ/kg/y (+/- standard deviation), respectively. In comparison, conventional production yielded 3.9 +/- 0.21 kg/m(2)/y of produce, with water and energy demands of 250 +/- 25 L/kg/y and 1100 +/- 75 kJ/kg/y, respectively. Hydroponics offered 11 +/- 1.7 times higher yields but required 82 +/- 11 times more energy compared to conventionally produced lettuce. To the authors' knowledge, this is the first quantitative comparison of conventional and hydroponic produce production by example of lettuce grown in the southwestern United States. It identified energy availability as a major factor in assessing the sustainability of hydroponics, and it points to water-scarce settings offering an abundance of renewable energy (e.g., from solar, geothermal, or wind power) as particularly attractive regions for hydroponic agriculture.

ContributorsBarbosa, Guilherme Lages (Author) / Gadelha, Francisca Daiane Almeida (Author) / Kublik, Natalya (Author) / Proctor, Alan (Author) / Reichelm, Lucas (Author) / Weissinger, Emily (Author) / Wohlleb, Gregory (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2015-06-01
Description

The World Health Organization recently proposed the inclusion of brominated congeners in addition to chlorinated congeners when computing the toxic equivalency (TEQ) of dioxin-like compounds (DLCs) in assessments of human health risks. In the present study, 12 polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) were analyzed by gas chromatography/high resolution mass spectrometry

The World Health Organization recently proposed the inclusion of brominated congeners in addition to chlorinated congeners when computing the toxic equivalency (TEQ) of dioxin-like compounds (DLCs) in assessments of human health risks. In the present study, 12 polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) were analyzed by gas chromatography/high resolution mass spectrometry in the composited, archived biosolids that were collected in 32 U.S. states and the District of Columbia from 94 wastewater treatment plants by the United States Environmental Protection Agency in its 2001 national sewage sludge survey. Two PBDDs and five PBDFs were detected in the biosolids composites at varying frequencies (40–100%) with a total mean concentration of 10,000 ng/kg dry weight (range: 630–42,800), of which 1,2,3,4,6,7,8-hepta-BDF constituted about 95% by mass. Relative to commercial polybrominated diphenyl ether (PBDE) formulations, the ratio of PBDD/Fs to PBDEs in biosolids was 55-times higher (∼0.002% vs ∼0.11%), which indicates potential PBDE transformation or possibly additional sources of PBDD/Fs in the environment. The TEQ contribution of PBDD/Fs was estimated at 162 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (range: 15–672), which is equivalent to 75% (range: 12–96%) of the total TEQ in biosolids. The TEQ of DLCs released annually to U.S. soils as a result of the land application of biosolids was estimated at 720 g (range: 530–1600 g). Among all known DLCs determined in biosolids, brominated analogs contributed 370% more TEQ than did chlorinated congeners, which indicates the need to include brominated DLCs in the exposure and risk assessment of land-applied biosolids.

ContributorsVenkatesan, Arjunkrishna (Author) / Halden, Rolf (Author) / Center for Environmental Security (Contributor)
Created2014-09-16
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Description

Background: Buffering to achieve pH control is crucial for successful trichloroethene (TCE) anaerobic bioremediation. Bicarbonate (HCO3−) is the natural buffer in groundwater and the buffer of choice in the laboratory and at contaminated sites undergoing biological treatment with organohalide respiring microorganisms. However, HCO3− also serves as the electron acceptor for hydrogenotrophic

Background: Buffering to achieve pH control is crucial for successful trichloroethene (TCE) anaerobic bioremediation. Bicarbonate (HCO3−) is the natural buffer in groundwater and the buffer of choice in the laboratory and at contaminated sites undergoing biological treatment with organohalide respiring microorganisms. However, HCO3− also serves as the electron acceptor for hydrogenotrophic methanogens and hydrogenotrophic homoacetogens, two microbial groups competing with organohalide respirers for hydrogen (H2). We studied the effect of HCO3− as a buffering agent and the effect of HCO3−-consuming reactions in a range of concentrations (2.5-30 mM) with an initial pH of 7.5 in H2-fed TCE reductively dechlorinating communities containing Dehalococcoides, hydrogenotrophic methanogens, and hydrogenotrophic homoacetogens.

Results: Rate differences in TCE dechlorination were observed as a result of added varying HCO3− concentrations due to H2-fed electrons channeled towards methanogenesis and homoacetogenesis and pH increases (up to 8.7) from biological HCO3− consumption. Significantly faster dechlorination rates were noted at all HCO3− concentrations tested when the pH buffering was improved by providing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) as an additional buffer. Electron balances and quantitative PCR revealed that methanogenesis was the main electron sink when the initial HCO3− concentrations were 2.5 and 5 mM, while homoacetogenesis was the dominant process and sink when 10 and 30 mM HCO3− were provided initially.

Conclusions: Our study reveals that HCO3− is an important variable for bioremediation of chloroethenes as it has a prominent role as an electron acceptor for methanogenesis and homoacetogenesis. It also illustrates the changes in rates and extent of reductive dechlorination resulting from the combined effect of electron donor competition stimulated by HCO3− and the changes in pH exerted by methanogens and homoacetogens.

ContributorsDelgado, Anca (Author) / Parameswaran, Prathap (Author) / Fajardo-Williams, Devyn (Author) / Halden, Rolf (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2012-09-13
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Description

Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients.

Methods: A pilot study was

Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients.

Methods: A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs.

Results: Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis.

Conclusion: The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

ContributorsGibson, David S. (Author) / Qiu, Ji (Author) / Mendoza, D. Eliseo A. (Author) / Barker, Kristi (Author) / Rooney, Madeleine E. (Author) / LaBaer, Joshua (Author)
Created2012-04-17
Description

Important antibiotics in human medicine have been used for many decades in animal agriculture for growth promotion and disease treatment. Several publications have linked antibiotic resistance development and spread with animal production. Aquaculture, the newest and fastest growing food production sector, may promote similar or new resistance mechanisms. This review

Important antibiotics in human medicine have been used for many decades in animal agriculture for growth promotion and disease treatment. Several publications have linked antibiotic resistance development and spread with animal production. Aquaculture, the newest and fastest growing food production sector, may promote similar or new resistance mechanisms. This review of 650+ papers from diverse sources examines parallels and differences between land-based agriculture of swine, beef, and poultry and aquaculture. Among three key findings was, first, that of 51 antibiotics commonly used in aquaculture and agriculture, 39 (or 76%) are also of importance in human medicine; furthermore, six classes of antibiotics commonly used in both agriculture and aquaculture are also included on the World Health Organization’s (WHO) list of critically important/highly important/important antimicrobials. Second, various zoonotic pathogens isolated from meat and seafood were observed to feature resistance to multiple antibiotics on the WHO list, irrespective of their origin in either agriculture or aquaculture. Third, the data show that resistant bacteria isolated from both aquaculture and agriculture share the same resistance mechanisms, indicating that aquaculture is contributing to the same resistance issues established by terrestrial agriculture. More transparency in data collection and reporting is needed so the risks and benefits of antibiotic usage can be adequately assessed.

ContributorsDone, Hansa (Author) / Venkatesan, Arjunkrishna (Author) / Halden, Rolf (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-05-01
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Description

A significant challenge of our time is conserving biological diversity while maintaining economic development and cultural values. The United Nations Educational, Scientific and Cultural Organization has established biosphere reserves within its Man and the Biosphere program as a model means for accomplishing this very challenge. The East Carpathians Biosphere Reserve

A significant challenge of our time is conserving biological diversity while maintaining economic development and cultural values. The United Nations Educational, Scientific and Cultural Organization has established biosphere reserves within its Man and the Biosphere program as a model means for accomplishing this very challenge. The East Carpathians Biosphere Reserve (ECBR), spreading across Poland, Slovakia, and Ukraine, represents a large social-ecological system (SES) that has been protected under the biosphere reserve designation since 1998. We have explored its successes and failures in improving human livelihoods while safeguarding its ecosystems. The SES framework, which includes governance system, actors, resources, and external influences, was used as a frame of analysis. The outcomes of this protected area have been mixed; its creation led to national and international collaboration, yet some actor groups remain excluded. Implementation of protocols arising from the Carpathian Convention has been slow, while deforestation, hunting, erosion, temperature extremes, and changes in species behavior remain significant threats but have also been factors in ecological adaptation. The loss of cultural links and traditional knowledge has also been significant. Nevertheless, this remains a highly biodiverse area. Political barriers and institutional blockages will have to be removed to ensure this reserve fulfills its role as a model region for international collaboration and capacity building. These insights drawn from the ECBR demonstrate that biosphere reserves are indeed learning sites for sustainable development and that this case is exemplary in illustrating the challenges, but more importantly, the opportunities that arise when ensuring parallel care and respect for people and ecosystems through the model of transboundary protected areas around the world.

Created2016
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Thousands of chemicals have been identified as contaminants of emerging concern (CECs), but prioritizing them concerning ecological and human health risks is challenging. We explored the use of sewage treatment plants as chemical observatories to conveniently identify persistent and bioaccumulative CECs, including toxic organohalides. Nationally representative samples of sewage sludge

Thousands of chemicals have been identified as contaminants of emerging concern (CECs), but prioritizing them concerning ecological and human health risks is challenging. We explored the use of sewage treatment plants as chemical observatories to conveniently identify persistent and bioaccumulative CECs, including toxic organohalides. Nationally representative samples of sewage sludge (biosolids) were analyzed for 231 CECs, of which 123 were detected. Ten of the top 11 most abundant CECs in biosolids were found to be high-production volume chemicals, eight of which representing priority chemicals, including three flame retardants, three surfactants and two antimicrobials. A comparison of chemicals detected in nationally representative biological specimens from humans and municipal biosolids revealed 70% overlap. This observed co-occurrence of contaminants in both matrices suggests that the analysis of sewage sludge can inform human health risk assessments by providing current information on toxic exposures in human populations and associated body burdens of harmful environmental pollutants.

ContributorsVenkatesan, Arjunkrishna (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2014-01-16