Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and bi... more Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and biosolids. Spanning the inner and outer membrane are resistance-nodulation-cell division superfamily (RND) efflux pumps responsible for detoxification of the cell, typically in response to antibiotics and other toxicity inducing substrates. Here, we show that estrogenic endocrine disruptors, common wastewater pollutants, induce genes encoding chemical efflux proteins. Bacteria were exposed to environmental concentrations of the synthetic estrogen 17α-ethynylestradiol, the surfactant nonylphenol, and the plasticizer bisphenol-A, and analyzed for RND gene expression via q-PCR. Results showed that the genes acrB and yhiV were over-expressed in response to the three chemicals in E. coli, and support previous findings that these two transporters export hormones. P. aeruginosa contains 12 RND efflux pumps, which were differentially expressed in response to the three chemicals: 17α-ethynylestradiol, bisphenol-A, and nonylphenol up-regulated mexD and mexF, while nonylphenol and bisphenol-A positively affected transcription of mexK, mexW, and triC. Gene expression via q-PCR of RND genes may be used to predict the interaction of estrogen mimics with RND genes. One bacterial response to estrogen mimic exposure is to induce gene expression of chemical efflux proteins, which leads to the expulsion of the contaminant from the cell.
The effect of bioaerosol size was incorporated into predictive dose‐response models for the effec... more The effect of bioaerosol size was incorporated into predictive dose‐response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol‐size‐dependent models were formulated as modification of the exponential and β‐Poisson dose‐response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose‐response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose‐response data was best fit by an exponential dose‐response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol‐size‐dependence equation and models that better represent the observed dose‐response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.
Bisphenols, anthropogenic pollutants, leach from consumer products and have potential to be inges... more Bisphenols, anthropogenic pollutants, leach from consumer products and have potential to be ingested and are excreted in waste. The endocrine disrupting effects of highly manufactured bisphenols (BPA, BPS, and BPF) are known, however the activities of others are not. Here, the estrogenic and androgenic activities of a series of 4,4'-bisphenols that vary at the inter-connecting bisphenol bridge were determined (BPA, BPB, BPBP, BPC2, BPE, BPF, BPS, and BPZ) and compared to in silico binding to estrogen receptor-alpha and the androgen receptor. Bioassay results showed the order of estrogenicity (BPC2 (strongest) > BPBP > BPB > BPZ > BPE > BPF > BPA > BPS, r2 = 0.995) and anti-androgenicity (BPC2 (strongest) > BPE, BPB, BPA, BPF, and BPS, r2 = 0.996) correlated to nuclear receptor binding affinities. Like testosterone and the anti-androgen hydroxyflutamide, bisphenol fit in the ligand-binding domain through hydrogen-bonding at residues Thr877 and Asn705, bu...
The effect of bioaerosol size was incorporated into predictive dose-response models for the effec... more The effect of bioaerosol size was incorporated into predictive dose-response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol-size-dependent models were formulated as modification of the exponential and β-Poisson dose-response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose-response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose-response data was best fit by an exponential dose-response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol-size-dependence equation and models that better represent the observed dose-response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.
Ecological impacts of natural estrogens and xenoestrogens in treated wastewater include altered s... more Ecological impacts of natural estrogens and xenoestrogens in treated wastewater include altered sexual development and sex ratios among continuously exposed organisms. The primary sources of estrogenic activity in wastewater are natural estrogens such as estrone, 17β-estradiol and estriol and synthetic compounds like 17αethinylestradiol, alkylphenols and alklphenol ethoxylates. Precursors in raw wastewater can yield estrogenic intermediates during wastewater treatment. All these compounds can be destroyed by biochemical processes conventional wastewater treatment processes, suggesting that conventional processes can be optimized for removal of estrogenic activity from wastewater. Sorption to sludges derived from wastewater treatment affects the fates of hydrophobic xenoestrogens such as nonylphenol, in part because the biodegradability of sorbed contaminants is limited. It may also be possible to tailor sludge stabilization processes to remove trace contaminants, including estrogens...
Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and bi... more Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and biosolids. Spanning the inner and outer membrane are resistance-nodulation-cell division superfamily (RND) efflux pumps responsible for detoxification of the cell, typically in response to antibiotics and other toxicity inducing substrates. Here, we show that estrogenic endocrine disruptors, common wastewater pollutants, induce genes encoding chemical efflux proteins. Bacteria were exposed to environmental concentrations of the synthetic estrogen 17α-ethynylestradiol, the surfactant nonylphenol, and the plasticizer bisphenol-A, and analyzed for RND gene expression via q-PCR. Results showed that the genes acrB and yhiV were over-expressed in response to the three chemicals in E. coli, and support previous findings that these two transporters export hormones. P. aeruginosa contains 12 RND efflux pumps, which were differentially expressed in response to the three chemicals: 17α-ethynylestradi...
International journal of environmental research and public health, 2015
Humans are increasingly exposed to nanoparticles (NPs) in medicine and in industrial settings, wh... more Humans are increasingly exposed to nanoparticles (NPs) in medicine and in industrial settings, where significant concentrations of NPs are common. However, NP interactions with and effects on biomolecules and organisms have only recently been addressed. Within we review the literature regarding proposed modes of action for metal and metal-oxide NPs, two of the most prevalent types manufactured. Iron-oxide NPs, for instance, are used as tracers for magnetic resonance imaging of oncological tumors and as vehicles for therapeutic drug delivery. Factors and theories that determine the physicochemical and biokinetic behaviors of NPs are discussed, along with the observed toxicological effects of NPs on cells. Key thermodynamic and kinetic models that explain the sources of energy transfer from NPs to biological targets are summarized, in addition to quantitative structural activity relationship (QSAR) modeling efforts. Future challenges for nanotoxicological research are discussed. We co...
Proceedings of the Water Environment Federation, 2010
ABSTRACT This paper is based on a project, supported in part by the Water Environment Research Fo... more ABSTRACT This paper is based on a project, supported in part by the Water Environment Research Foundation (WERF) that sought to better understand the fate of estrogenicity (measured with an in vitro biological assay) and estrogenic compounds (measured with GC/MS/MS, LC/MS/MS, LC/MS) in the solids phase of wastewater treatment. Results of this research project were published by WERF: Fate of Estrogenic Compounds during Sludge Stabilization and Dewatering (04-HHE-6) (Furlong et al, 2010).
Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas, and prevalent in b... more Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas, and prevalent in both industrialized and rural settings. Dose-response models were generated from 22 data sets reported in 10 different studies. All of the selected studies used rodent subjects, primarily hamsters, with the predominant endpoint as mortality with the challenge strain administered intraperitoneally. Dose-response models based on a single evaluation postinfection displayed median lethal dose (LD50 ) estimates that ranged between 1 and 10(7) leptospirae depending upon the strain's virulence and the period elapsed since the initial exposure inoculation. Twelve of the 22 data sets measured the number of affected subjects daily over an extended period, so dose-response models with time-dependent parameters were estimated. Pooling between data sets produced seven common dose-response models and one time-dependent model. These pooled common models had data sets with different test subject hosts, and between disparate leptospiral strains tested on identical hosts. Comparative modeling was done with parallel tests to test the effects of a single different variable of either strain or test host and quantify the difference by calculating a dose multiplication factor. Statistical pooling implies that the mechanistic processes of leptospirosis can be represented by the same dose-response model for different experimental infection tests even though they may involve different host species, routes, and leptospiral strains, although the cause of this pathophysiological phenomenon has not yet been identified.
Journal of Exposure Science and Environmental Epidemiology, 2012
Recreational exposure to surface waters during periods of increased pathogen concentration may le... more Recreational exposure to surface waters during periods of increased pathogen concentration may lead to a significantly higher risk of illness. However, estimates of elementary exposure factors necessary to evaluate health risk (i.e., usage distributions and exposure durations) are not available for many non-swimming water-related activities. No prior studies have assessed non-swimming water exposure with respect to factors leading to impaired water quality from increased pathogen concentration, such as weather condition (rain events produce increased runoff and sewer overflows) and type of day (heavy recreational periods). We measured usage patterns and evaluated the effect of weather and type of day at eight water sites located within Philadelphia, by using a novel "time lapse photography" technology during three peak recreational seasons (May-September) 2008-2010. Camera observations validated with simultaneous in-person surveys exhibited a strong correlation (R(2)=0.81 to 0.96) between the two survey techniques, indicating that the application of remote photography in collecting human exposure data was appropriate. Recreational activities usage varied more on a temporal basis than due to inclement weather. Only 14% (6 out of 44) of the site-specific activity combinations showed dry weather preference, whereas 41.5% (17 out of 41) of the combinations indicated greater usage on weekends as compared with weekday. In general, the log normal distribution described the playing and wading duration distribution, while the gamma distribution was the best fit for fishing durations. Remote photography provided unbiased, real-time human exposure data and was less personnel intensive compared with traditional survey methods. However, there are potential limitations associated with remote surveillance data related to its limited view. This is the first study to report that time lapse cameras can be successfully applied to assess water-based human recreational patterns and can provide precise exposure statistics for non-swimming recreational exposures.
Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and bi... more Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and biosolids. Spanning the inner and outer membrane are resistance-nodulation-cell division superfamily (RND) efflux pumps responsible for detoxification of the cell, typically in response to antibiotics and other toxicity inducing substrates. Here, we show that estrogenic endocrine disruptors, common wastewater pollutants, induce genes encoding chemical efflux proteins. Bacteria were exposed to environmental concentrations of the synthetic estrogen 17α-ethynylestradiol, the surfactant nonylphenol, and the plasticizer bisphenol-A, and analyzed for RND gene expression via q-PCR. Results showed that the genes acrB and yhiV were over-expressed in response to the three chemicals in E. coli, and support previous findings that these two transporters export hormones. P. aeruginosa contains 12 RND efflux pumps, which were differentially expressed in response to the three chemicals: 17α-ethynylestradiol, bisphenol-A, and nonylphenol up-regulated mexD and mexF, while nonylphenol and bisphenol-A positively affected transcription of mexK, mexW, and triC. Gene expression via q-PCR of RND genes may be used to predict the interaction of estrogen mimics with RND genes. One bacterial response to estrogen mimic exposure is to induce gene expression of chemical efflux proteins, which leads to the expulsion of the contaminant from the cell.
The effect of bioaerosol size was incorporated into predictive dose‐response models for the effec... more The effect of bioaerosol size was incorporated into predictive dose‐response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol‐size‐dependent models were formulated as modification of the exponential and β‐Poisson dose‐response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose‐response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose‐response data was best fit by an exponential dose‐response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol‐size‐dependence equation and models that better represent the observed dose‐response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.
Bisphenols, anthropogenic pollutants, leach from consumer products and have potential to be inges... more Bisphenols, anthropogenic pollutants, leach from consumer products and have potential to be ingested and are excreted in waste. The endocrine disrupting effects of highly manufactured bisphenols (BPA, BPS, and BPF) are known, however the activities of others are not. Here, the estrogenic and androgenic activities of a series of 4,4'-bisphenols that vary at the inter-connecting bisphenol bridge were determined (BPA, BPB, BPBP, BPC2, BPE, BPF, BPS, and BPZ) and compared to in silico binding to estrogen receptor-alpha and the androgen receptor. Bioassay results showed the order of estrogenicity (BPC2 (strongest) > BPBP > BPB > BPZ > BPE > BPF > BPA > BPS, r2 = 0.995) and anti-androgenicity (BPC2 (strongest) > BPE, BPB, BPA, BPF, and BPS, r2 = 0.996) correlated to nuclear receptor binding affinities. Like testosterone and the anti-androgen hydroxyflutamide, bisphenol fit in the ligand-binding domain through hydrogen-bonding at residues Thr877 and Asn705, bu...
The effect of bioaerosol size was incorporated into predictive dose-response models for the effec... more The effect of bioaerosol size was incorporated into predictive dose-response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol-size-dependent models were formulated as modification of the exponential and β-Poisson dose-response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose-response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose-response data was best fit by an exponential dose-response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol-size-dependence equation and models that better represent the observed dose-response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.
Ecological impacts of natural estrogens and xenoestrogens in treated wastewater include altered s... more Ecological impacts of natural estrogens and xenoestrogens in treated wastewater include altered sexual development and sex ratios among continuously exposed organisms. The primary sources of estrogenic activity in wastewater are natural estrogens such as estrone, 17β-estradiol and estriol and synthetic compounds like 17αethinylestradiol, alkylphenols and alklphenol ethoxylates. Precursors in raw wastewater can yield estrogenic intermediates during wastewater treatment. All these compounds can be destroyed by biochemical processes conventional wastewater treatment processes, suggesting that conventional processes can be optimized for removal of estrogenic activity from wastewater. Sorption to sludges derived from wastewater treatment affects the fates of hydrophobic xenoestrogens such as nonylphenol, in part because the biodegradability of sorbed contaminants is limited. It may also be possible to tailor sludge stabilization processes to remove trace contaminants, including estrogens...
Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and bi... more Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and biosolids. Spanning the inner and outer membrane are resistance-nodulation-cell division superfamily (RND) efflux pumps responsible for detoxification of the cell, typically in response to antibiotics and other toxicity inducing substrates. Here, we show that estrogenic endocrine disruptors, common wastewater pollutants, induce genes encoding chemical efflux proteins. Bacteria were exposed to environmental concentrations of the synthetic estrogen 17α-ethynylestradiol, the surfactant nonylphenol, and the plasticizer bisphenol-A, and analyzed for RND gene expression via q-PCR. Results showed that the genes acrB and yhiV were over-expressed in response to the three chemicals in E. coli, and support previous findings that these two transporters export hormones. P. aeruginosa contains 12 RND efflux pumps, which were differentially expressed in response to the three chemicals: 17α-ethynylestradi...
International journal of environmental research and public health, 2015
Humans are increasingly exposed to nanoparticles (NPs) in medicine and in industrial settings, wh... more Humans are increasingly exposed to nanoparticles (NPs) in medicine and in industrial settings, where significant concentrations of NPs are common. However, NP interactions with and effects on biomolecules and organisms have only recently been addressed. Within we review the literature regarding proposed modes of action for metal and metal-oxide NPs, two of the most prevalent types manufactured. Iron-oxide NPs, for instance, are used as tracers for magnetic resonance imaging of oncological tumors and as vehicles for therapeutic drug delivery. Factors and theories that determine the physicochemical and biokinetic behaviors of NPs are discussed, along with the observed toxicological effects of NPs on cells. Key thermodynamic and kinetic models that explain the sources of energy transfer from NPs to biological targets are summarized, in addition to quantitative structural activity relationship (QSAR) modeling efforts. Future challenges for nanotoxicological research are discussed. We co...
Proceedings of the Water Environment Federation, 2010
ABSTRACT This paper is based on a project, supported in part by the Water Environment Research Fo... more ABSTRACT This paper is based on a project, supported in part by the Water Environment Research Foundation (WERF) that sought to better understand the fate of estrogenicity (measured with an in vitro biological assay) and estrogenic compounds (measured with GC/MS/MS, LC/MS/MS, LC/MS) in the solids phase of wastewater treatment. Results of this research project were published by WERF: Fate of Estrogenic Compounds during Sludge Stabilization and Dewatering (04-HHE-6) (Furlong et al, 2010).
Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas, and prevalent in b... more Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas, and prevalent in both industrialized and rural settings. Dose-response models were generated from 22 data sets reported in 10 different studies. All of the selected studies used rodent subjects, primarily hamsters, with the predominant endpoint as mortality with the challenge strain administered intraperitoneally. Dose-response models based on a single evaluation postinfection displayed median lethal dose (LD50 ) estimates that ranged between 1 and 10(7) leptospirae depending upon the strain's virulence and the period elapsed since the initial exposure inoculation. Twelve of the 22 data sets measured the number of affected subjects daily over an extended period, so dose-response models with time-dependent parameters were estimated. Pooling between data sets produced seven common dose-response models and one time-dependent model. These pooled common models had data sets with different test subject hosts, and between disparate leptospiral strains tested on identical hosts. Comparative modeling was done with parallel tests to test the effects of a single different variable of either strain or test host and quantify the difference by calculating a dose multiplication factor. Statistical pooling implies that the mechanistic processes of leptospirosis can be represented by the same dose-response model for different experimental infection tests even though they may involve different host species, routes, and leptospiral strains, although the cause of this pathophysiological phenomenon has not yet been identified.
Journal of Exposure Science and Environmental Epidemiology, 2012
Recreational exposure to surface waters during periods of increased pathogen concentration may le... more Recreational exposure to surface waters during periods of increased pathogen concentration may lead to a significantly higher risk of illness. However, estimates of elementary exposure factors necessary to evaluate health risk (i.e., usage distributions and exposure durations) are not available for many non-swimming water-related activities. No prior studies have assessed non-swimming water exposure with respect to factors leading to impaired water quality from increased pathogen concentration, such as weather condition (rain events produce increased runoff and sewer overflows) and type of day (heavy recreational periods). We measured usage patterns and evaluated the effect of weather and type of day at eight water sites located within Philadelphia, by using a novel "time lapse photography" technology during three peak recreational seasons (May-September) 2008-2010. Camera observations validated with simultaneous in-person surveys exhibited a strong correlation (R(2)=0.81 to 0.96) between the two survey techniques, indicating that the application of remote photography in collecting human exposure data was appropriate. Recreational activities usage varied more on a temporal basis than due to inclement weather. Only 14% (6 out of 44) of the site-specific activity combinations showed dry weather preference, whereas 41.5% (17 out of 41) of the combinations indicated greater usage on weekends as compared with weekday. In general, the log normal distribution described the playing and wading duration distribution, while the gamma distribution was the best fit for fishing durations. Remote photography provided unbiased, real-time human exposure data and was less personnel intensive compared with traditional survey methods. However, there are potential limitations associated with remote surveillance data related to its limited view. This is the first study to report that time lapse cameras can be successfully applied to assess water-based human recreational patterns and can provide precise exposure statistics for non-swimming recreational exposures.
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