Shaily Mahendra | University of California, Los Angeles (original) (raw)
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Papers by Shaily Mahendra
ACS Nano, 2012
The use of engineered nanomaterials (eNM) in consumer and industrial products is increasing expon... more The use of engineered nanomaterials (eNM) in consumer and industrial products is increasing exponentially. Our ability to rapidly assess their potential effects on human and environmental health is limited by our understanding of nanomediated toxicity. High-throughput screening (HTS) enables the investigation of nanomediated toxicity on a genome-wide level, thus uncovering their novel mechanisms and paradigms. Herein, we investigate the toxicity of zinc-containing nanomaterials (Zn-eNMs) using a time-resolved HTS methodology in an arrayed Escherichia coli genome-wide knockout (KO) library. The library was screened against nanoscale zerovalent zinc (nZn), nanoscale zinc oxide (nZnO), and zinc chloride (ZnCl(2)) salt as reference. Through sequential screening over 24 h, our method identified 173 sensitive clones from diverse biological pathways, which fell into two general groups: early and late responders. The overlap between these groups was small. Our results suggest that bacterial toxicity mechanisms change from pathways related to general metabolic function, transport, signaling, and metal ion homeostasis to membrane synthesis pathways over time. While all zinc sources shared pathways relating to membrane damage and metal ion homeostasis, Zn-eNMs and ZnCl(2) displayed differences in their sensitivity profiles. For example, ZnCl(2) and nZnO elicited unique responses in pathways related to two-component signaling and monosaccharide biosynthesis, respectively. Single isolated measurements, such as MIC or IC(50), are inadequate, and time-resolved approaches utilizing genome-wide assays are therefore needed to capture this crucial dimension and illuminate the dynamic interplay at the nano-bio interface.
C rather than 13 C, the isotopic ratio of the substrates tends to become enriched in 13 C. As a r... more C rather than 13 C, the isotopic ratio of the substrates tends to become enriched in 13 C. As a result, with a good under- standing of the magnitude of the shift in the carbon isotope ratios caused by a specific process, we can determine the degree of degradation that has occurred. The purpose of this research is to quantify
Environmental Toxicology and Chemistry, 2014
Proper characterization of nanoparticle (NP) interactions with environmentally relevant bacteria ... more Proper characterization of nanoparticle (NP) interactions with environmentally relevant bacteria under representative conditions is necessary to enable their sustainable manufacture, use, and disposal. Previous nanotoxicology research based on planktonic growth has not adequately explored biofilms, which serve as the predominant mode of bacterial growth in natural and engineered environments. Copper nanoparticle (Cu-NP) impacts on biofilms were compared with respective planktonic cultures of the ammonium-oxidizing Nitrosomonas europaea, nitrogen-fixing Azotobacter vinelandii, and denitrifying Paracoccus denitrificans using a suite of independent toxicity diagnostics. Median inhibitory concentration (IC50) values derived from adenosine triphosphate (ATP) for Cu-NPs were lower in N. europaea biofilms (19.6 ± 15.3 mg/L) than in planktonic cells (49.0 ± 8.0 mg/L). However, in absorbance-based growth assays, compared with unexposed controls, N. europaea growth rates in biofilms were twice as resilient to inhibition than those in planktonic cultures. Similarly, relative to unexposed controls, growth rates and yields of P. denitrificans in biofilms exposed to Cu-NPs were 40-fold to 50-fold less inhibited than those in planktonic cells. Physiological evaluation of ammonium oxidation and nitrate reduction suggested that biofilms were also less inhibited by Cu-NPs than planktonic cells. Furthermore, functional gene expression for ammonium oxidation (amoA) and nitrite reduction (nirK) showed lower inhibition by NPs in biofilms relative to planktonic-grown cells. These results suggest that biofilms mitigate NP impacts, and that nitrogen-cycling bacteria in wastewater, wetlands, and soils might be more resilient to NPs than planktonic-based assessments suggest. Environ Toxicol Chem 2015;34:887-897. © 2014 SETAC.
Environmental Science & Technology Letters, 2014
ABSTRACT 1,4-Dioxane (dioxane) is an emerging groundwater contaminant that has significant regula... more ABSTRACT 1,4-Dioxane (dioxane) is an emerging groundwater contaminant that has significant regulatory implications and potential remediation costs, but our current understanding of its occurrence and behavior is limited. This study used intensive data mining to identify and evaluate >2000 sites in California where groundwater has been impacted by chlorinated solvents and/or dioxane. Dioxane was detected at 194 of these sites, with 95% containing one or more chlorinated solvents. Dioxane frequently co-occurs with 1,1,1-trichloroethene (1,1,1-TCA) (76% of the study sites), but despite this, no dioxane analyses were conducted at 332 (67%) of the sites where 1,1,1-TCA was detected. At sites where dioxane has been identified, plumes are dilute but not large (median maximal concentration of 365 mu g/L; median plume length of 269 m) and have been delineated to a similar extent as typically co-occurring chlorinated solvents. Furthermore, at sites where dioxane and chlorinated solvents co-occur, dioxane plumes are frequently shorter than the chlorinated solvent plumes (62%). The results suggest that dioxane has not migrated beyond chlorinated solvent plumes and existing monitoring networks at the majority of sites, and that the primary risk is the large number of sites where dioxane is likely to be present but has yet to be identified.
Other uses, including reproduction and distribution, or selling or licensing copies, or posting t... more Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.
Environmental Science & Technology, 2015
There is a critical need to develop appropriate management strategies for 1,4-dioxane (dioxane) d... more There is a critical need to develop appropriate management strategies for 1,4-dioxane (dioxane) due to its widespread occurrence and perceived recalcitrance at groundwater sites where chlorinated solvents are present. A comprehensive evaluation of California state (GeoTracker) and Air Force monitoring records was used to provide significant evidence of dioxane attenuation at field sites. Temporal changes in the site-wide maximum concentrations were used to estimate source attenuation rates at the GeoTracker sites (median length of monitoring period = 6.8 years). While attenuation could not be established at all sites, statistically significant positive attenuation rates were confirmed at 22 sites. At sites where dioxane and chlorinated solvents were present, the median value of all statistically significant dioxane source attenuation rates (equivalent half-life = 31 months; n = 34) was lower than 1,1,1-trichloroethane (TCA) but similar to 1,1-dichloroethene (1,1-DCE) and trichloroethene (TCE). Dioxane attenuation rates were positively correlated with rates for 1,1-DCE and TCE but not TCA. At this set of sites, there was little evidence that chlorinated solvent remedial efforts (e.g., chemical oxidation, enhanced bioremediation) impacted dioxane attenuation. Attenuation rates based on well-specific records from the Air Force data set confirmed significant dioxane attenuation (131 out of 441 wells) at a similar frequency and extent (median equivalent half-life = 48 months) as observed at the California sites. Linear discriminant analysis established a positive correlation between dioxane attenuation and increasing concentrations of dissolved oxygen, while the same analysis found a negative correlation with metals and CVOC concentrations. The magnitude and prevalence of dioxane attenuation documented here suggest that natural attenuation may be used to manage some but not necessarily all dioxane-impacted sites.
Poly(dimethylsiloxane) PDMS is a chemically and biologically inert material which has been used e... more Poly(dimethylsiloxane) PDMS is a chemically and biologically inert material which has been used extensively for micro-fluidic channels, tissue culture and biomedical applications. This polymer is also transparent, non-conductive and flexible. Embedding nanoparticles in PDMS ...
ABSTRACT Compound Specific Isotope Analysis (CSIA) has been successfully used as a monitoring too... more ABSTRACT Compound Specific Isotope Analysis (CSIA) has been successfully used as a monitoring tool to assess the biodegradation of various organic contaminants. In this study, we report the development of CSIA method for 1,4-dioxane, a probable carcinogen and an important emerging contaminant in water supplies. This method was applied to determine kinetic carbon isotopic fractionation factor (ε) during the aerobic biodegradation of dioxane by Pseudonocardia dioxanivorans CB1190, which can grow using dioxane as its only source of carbon and energy. The fraction of 13C increased as biodegradation progressed, resulting in an ε value of −1.73 ± 0.14. Our study will provide a foundation for stable isotope-based monitoring tools for establishing natural attenuation and biodegradation of 1,4-dioxane in contaminated environments.
ACS Nano, 2012
The use of engineered nanomaterials (eNM) in consumer and industrial products is increasing expon... more The use of engineered nanomaterials (eNM) in consumer and industrial products is increasing exponentially. Our ability to rapidly assess their potential effects on human and environmental health is limited by our understanding of nanomediated toxicity. High-throughput screening (HTS) enables the investigation of nanomediated toxicity on a genome-wide level, thus uncovering their novel mechanisms and paradigms. Herein, we investigate the toxicity of zinc-containing nanomaterials (Zn-eNMs) using a time-resolved HTS methodology in an arrayed Escherichia coli genome-wide knockout (KO) library. The library was screened against nanoscale zerovalent zinc (nZn), nanoscale zinc oxide (nZnO), and zinc chloride (ZnCl(2)) salt as reference. Through sequential screening over 24 h, our method identified 173 sensitive clones from diverse biological pathways, which fell into two general groups: early and late responders. The overlap between these groups was small. Our results suggest that bacterial toxicity mechanisms change from pathways related to general metabolic function, transport, signaling, and metal ion homeostasis to membrane synthesis pathways over time. While all zinc sources shared pathways relating to membrane damage and metal ion homeostasis, Zn-eNMs and ZnCl(2) displayed differences in their sensitivity profiles. For example, ZnCl(2) and nZnO elicited unique responses in pathways related to two-component signaling and monosaccharide biosynthesis, respectively. Single isolated measurements, such as MIC or IC(50), are inadequate, and time-resolved approaches utilizing genome-wide assays are therefore needed to capture this crucial dimension and illuminate the dynamic interplay at the nano-bio interface.
C rather than 13 C, the isotopic ratio of the substrates tends to become enriched in 13 C. As a r... more C rather than 13 C, the isotopic ratio of the substrates tends to become enriched in 13 C. As a result, with a good under- standing of the magnitude of the shift in the carbon isotope ratios caused by a specific process, we can determine the degree of degradation that has occurred. The purpose of this research is to quantify
Environmental Toxicology and Chemistry, 2014
Proper characterization of nanoparticle (NP) interactions with environmentally relevant bacteria ... more Proper characterization of nanoparticle (NP) interactions with environmentally relevant bacteria under representative conditions is necessary to enable their sustainable manufacture, use, and disposal. Previous nanotoxicology research based on planktonic growth has not adequately explored biofilms, which serve as the predominant mode of bacterial growth in natural and engineered environments. Copper nanoparticle (Cu-NP) impacts on biofilms were compared with respective planktonic cultures of the ammonium-oxidizing Nitrosomonas europaea, nitrogen-fixing Azotobacter vinelandii, and denitrifying Paracoccus denitrificans using a suite of independent toxicity diagnostics. Median inhibitory concentration (IC50) values derived from adenosine triphosphate (ATP) for Cu-NPs were lower in N. europaea biofilms (19.6 ± 15.3 mg/L) than in planktonic cells (49.0 ± 8.0 mg/L). However, in absorbance-based growth assays, compared with unexposed controls, N. europaea growth rates in biofilms were twice as resilient to inhibition than those in planktonic cultures. Similarly, relative to unexposed controls, growth rates and yields of P. denitrificans in biofilms exposed to Cu-NPs were 40-fold to 50-fold less inhibited than those in planktonic cells. Physiological evaluation of ammonium oxidation and nitrate reduction suggested that biofilms were also less inhibited by Cu-NPs than planktonic cells. Furthermore, functional gene expression for ammonium oxidation (amoA) and nitrite reduction (nirK) showed lower inhibition by NPs in biofilms relative to planktonic-grown cells. These results suggest that biofilms mitigate NP impacts, and that nitrogen-cycling bacteria in wastewater, wetlands, and soils might be more resilient to NPs than planktonic-based assessments suggest. Environ Toxicol Chem 2015;34:887-897. © 2014 SETAC.
Environmental Science & Technology Letters, 2014
ABSTRACT 1,4-Dioxane (dioxane) is an emerging groundwater contaminant that has significant regula... more ABSTRACT 1,4-Dioxane (dioxane) is an emerging groundwater contaminant that has significant regulatory implications and potential remediation costs, but our current understanding of its occurrence and behavior is limited. This study used intensive data mining to identify and evaluate >2000 sites in California where groundwater has been impacted by chlorinated solvents and/or dioxane. Dioxane was detected at 194 of these sites, with 95% containing one or more chlorinated solvents. Dioxane frequently co-occurs with 1,1,1-trichloroethene (1,1,1-TCA) (76% of the study sites), but despite this, no dioxane analyses were conducted at 332 (67%) of the sites where 1,1,1-TCA was detected. At sites where dioxane has been identified, plumes are dilute but not large (median maximal concentration of 365 mu g/L; median plume length of 269 m) and have been delineated to a similar extent as typically co-occurring chlorinated solvents. Furthermore, at sites where dioxane and chlorinated solvents co-occur, dioxane plumes are frequently shorter than the chlorinated solvent plumes (62%). The results suggest that dioxane has not migrated beyond chlorinated solvent plumes and existing monitoring networks at the majority of sites, and that the primary risk is the large number of sites where dioxane is likely to be present but has yet to be identified.
Other uses, including reproduction and distribution, or selling or licensing copies, or posting t... more Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.
Environmental Science & Technology, 2015
There is a critical need to develop appropriate management strategies for 1,4-dioxane (dioxane) d... more There is a critical need to develop appropriate management strategies for 1,4-dioxane (dioxane) due to its widespread occurrence and perceived recalcitrance at groundwater sites where chlorinated solvents are present. A comprehensive evaluation of California state (GeoTracker) and Air Force monitoring records was used to provide significant evidence of dioxane attenuation at field sites. Temporal changes in the site-wide maximum concentrations were used to estimate source attenuation rates at the GeoTracker sites (median length of monitoring period = 6.8 years). While attenuation could not be established at all sites, statistically significant positive attenuation rates were confirmed at 22 sites. At sites where dioxane and chlorinated solvents were present, the median value of all statistically significant dioxane source attenuation rates (equivalent half-life = 31 months; n = 34) was lower than 1,1,1-trichloroethane (TCA) but similar to 1,1-dichloroethene (1,1-DCE) and trichloroethene (TCE). Dioxane attenuation rates were positively correlated with rates for 1,1-DCE and TCE but not TCA. At this set of sites, there was little evidence that chlorinated solvent remedial efforts (e.g., chemical oxidation, enhanced bioremediation) impacted dioxane attenuation. Attenuation rates based on well-specific records from the Air Force data set confirmed significant dioxane attenuation (131 out of 441 wells) at a similar frequency and extent (median equivalent half-life = 48 months) as observed at the California sites. Linear discriminant analysis established a positive correlation between dioxane attenuation and increasing concentrations of dissolved oxygen, while the same analysis found a negative correlation with metals and CVOC concentrations. The magnitude and prevalence of dioxane attenuation documented here suggest that natural attenuation may be used to manage some but not necessarily all dioxane-impacted sites.
Poly(dimethylsiloxane) PDMS is a chemically and biologically inert material which has been used e... more Poly(dimethylsiloxane) PDMS is a chemically and biologically inert material which has been used extensively for micro-fluidic channels, tissue culture and biomedical applications. This polymer is also transparent, non-conductive and flexible. Embedding nanoparticles in PDMS ...
ABSTRACT Compound Specific Isotope Analysis (CSIA) has been successfully used as a monitoring too... more ABSTRACT Compound Specific Isotope Analysis (CSIA) has been successfully used as a monitoring tool to assess the biodegradation of various organic contaminants. In this study, we report the development of CSIA method for 1,4-dioxane, a probable carcinogen and an important emerging contaminant in water supplies. This method was applied to determine kinetic carbon isotopic fractionation factor (ε) during the aerobic biodegradation of dioxane by Pseudonocardia dioxanivorans CB1190, which can grow using dioxane as its only source of carbon and energy. The fraction of 13C increased as biodegradation progressed, resulting in an ε value of −1.73 ± 0.14. Our study will provide a foundation for stable isotope-based monitoring tools for establishing natural attenuation and biodegradation of 1,4-dioxane in contaminated environments.