New-Onset Gout as an Independent Risk Factor for Returning to Dialysis After Kidney Transplantation.

BACKGROUND: The causal relationship between gout and renal transplant outcomes is difficult to assess due to multiple interacting covariates. This study sought to estimate the independent effect of new-onset gout on renal transplant outcomes using a methodology that accounted for these interactions. METHODS: This study analyzed data on patients in the US Renal Data System (USRDS) who received a primary kidney transplant between 2008 and 2015. The exposure was new-onset gout, and the primary endpoint was returning to dialysis >12 months postindex date (transplant date). A marginal structural model (MSM) was fitted to determine the relative risk of new-onset gout on return to dialysis. RESULTS: 18 525 kidney transplant recipients in the USRDS met study eligibility. One thousand three hundred ninety-nine (7.6%) patients developed new-onset gout, and 1420 (7.7%) returned to dialysis >12 months postindex. Adjusting for baseline and time-varying confounders via the MSM showed new-onset gout was associated with a 51% increased risk of return to (RR, 1.51; 95% CI, 1.03-2.20). CONCLUSIONS: This finding suggests that new onset gout after kidney transplantation could be a harbinger for poor renal outcomes, and to our knowledge is the first study of kidney transplant outcomes using a technique that accounted for the dynamic relationship between renal dysfunction and gout.

A Retrospective Cohort Study of the Effect of Gout on Mortality Among Patients with a History of Kidney Transplantation.

BACKGROUND Kidney transplantation is associated with increased prevalence of gout. However, evidence of the effect of gout on long-term kidney transplantation outcomes is mixed. This study examined mortality risk among patients with a history of kidney transplantation with vs. without gout. MATERIAL AND METHODS A retrospective study was conducted using Medicare Fee-for-Service administrative claims of patients with a history of kidney transplantation. Cox proportional hazards models determined the effect of gout on all-cause mortality, controlling for confounders, including comorbid mortality risk, via the Charlson Comorbidity Index. Because the relationships between gout and components of the Charlson Comorbidity Index are also debated, 3 different model assumptions were used: 1) gout shares a common cause with these comorbidities, 2) gout is upstream of these comorbidities, 3) the effect of gout on mortality is modified by these comorbidities. RESULTS Gout increased the risk of all-cause mortality in the unadjusted model (hazard ratio: 1.44, 95% CI 1.27-1.63) and after adjustment for demographics and transplant vintage (hazard ratio: 1.16, 95% CI 1.02-1.32). Gout was not a significant risk after adjustment for baseline Charlson Comorbidity Index (hazard ratio: 1.03, 95% CI 0.90-1.17). Gout was associated with greater mortality among patients without baseline comorbidities (Charlson Comorbidity Index=0; hazard ratio: 3.48, 95% CI 1.27-9.57) in the stratified model. CONCLUSIONS Among patients with a history of kidney transplantation, gout did not have an independent effect on all-cause mortality. However, gout was a predictor of mortality among patients with no comorbidities, suggesting that gout is an early warning sign of poor health in kidney transplantation patients.

Immunosuppressant Use and Gout in the Prevalent Solid Organ Transplantation Population.

INTRODUCTION: Gout is a common comorbidity among solid organ transplantation patients and is usually attributed to the use of cyclosporine. This study aims to evaluate the prevalence of gout among solid organ transplantation patients to determine the prevalence in the tacrolimus era. RESEARCH QUESTIONS: To what degree is cyclosporine still used among prevalent solid organ transplantation patients? How prevalent is gout in the solid organ transplantation population not being treated by cyclosporine? METHODS: Immunosuppressant regimens and gout prevalence among prevalent solid organ transplantation patients were assessed using retrospective claims data for a representative sample of commercially insured patients. For comparison to the prevalent solid organ transplantation population, immunosuppressant use at time of transplantation was compiled from published reports. RESULTS: Between 2012 and 2016, the use of cyclosporine declined while use of tacrolimus increased, with greater cyclosporine use among prevalent versus incident solid organ transplantation patients. The prevalence of gout was 18.3%, 9.3%, and 9.1% for solid organ transplantation patients on cyclosporine, tacrolimus, and neither, respectively. Among all solid organ transplantation patients with gout, 66.6% and 21.5% were on tacrolimus versus cyclosporine. The prevalence of gout among noncyclosporine solid organ transplantation patients was significantly higher than in the general population without solid organ transplantation. DISCUSSION: Despite declining cyclosporine use, gout prevalence remains high, with the majority of patients with gout receiving tacrolimus rather than cyclosporine. In summary, gout remains a frequent comorbidity of solid organ transplantation.

Methylmercury-total mercury ratios in predator and primary consumer insects from Adirondack streams (New York, USA).

Mercury (Hg) is a global pollutant that affects biota in remote settings due to atmospheric deposition of inorganic Hg, and its conversion to methylmercury (MeHg), the bioaccumulating and toxic form. Characterizing biotic MeHg is important for evaluating aquatic ecosystem responses to changes in Hg inputs. Aquatic insects possess many qualities desired for MeHg biomonitoring, but are not widely used, largely because of limited information regarding percentages of total mercury (THg) composed of MeHg (i.e., MeHg%) in various taxa. Here, we examine taxonomic, spatial, and seasonal variation in MeHg% of stream-dwelling predator and primary-consumer insects from nine streams in the Adirondack region (NY, USA). Predator MeHg% was high (median 94%) and did not differ significantly among five taxa. MeHg% in selected dragonflies (the most abundant predators, Odonata: Aeshnidae and Libellulidae) exhibited little seasonal and spatial variation, and THg concentration was strongly correlated with aqueous (filtered) MeHg (FMeHg; rs = 0.76). In contrast, MeHg% in primary consumers-shredders (northern caddisflies [Trichoptera: Limnephilidae]) and scrapers (flathead mayflies [Ephemeroptera: Heptageniidae]), were lower (medians 52% and 35%, respectively), and differed significantly between taxa, among sites, and seasonally. Correlations of THg with FMeHg were weak (shredders, rs = 0.45, p = 0.09) or not significant (scrapers, p = 0.89). The higher MeHg% of predators corresponded with their higher trophic positions (indicated by nitrogen stable isotopes). Results suggest obligate predators hold the most promise for the use of THg as a surrogate for MeHg biomonitoring with aquatic insects within the Adirondack region.

Prevalence of Gout in the Surviving United States Solid Organ Transplantation Population.

PURPOSE: Although incidence and survival are frequent topics within the solid organ transplantation (SOT) literature, the size of the surviving SOT population is not well known. Existing studies of gout in patients with SOT have focused on the incident SOT population. This analysis was performed to characterize the prevalent SOT population and the prevalence of gout within it. METHODS: This study includes the 2017 United States (US) population size of recipients of kidney, heart, liver, and lung transplants that was estimated by combining primary transplant recipient cohort sizes (1988-2017) with previously published survival rates for each annual cohort's time since transplantation (0-29 years). Gout among prevalent patients with SOT was assessed using Medicare and commercial claims. RESULTS: A total of 637,231 US patients received a primary kidney (393,953), liver (142,186), heart (66,637), or lung (34,455) transplant between 1988 and 2017. An estimated 356,000 (55.8%) recipients were alive in 2017 (233,000 kidney; 78,700 liver; 29,300 heart; 14,700 lung). Gout was identified in 11% of prevalent patients with SOT in 2016. Higher rates of gout were seen in recipients of kidney (13.1%) and heart (12.7%) compared to recipients of liver (6.7%) and lung (5.6%) (P < .0001 in both datasets). Active diagnosed gout prevalence in the US population without a SOT history was 1.1% in 2016. CONCLUSIONS: Hundreds of thousands of US patients are living with a transplanted organ today and these numbers are likely to increase. In patients with SOT, gout is a frequent comorbidity of which physicians should be aware. This study suggests a markedly higher rate of gout among transplant recipients compared to the general US population.

Gout Severity in Recipients of Kidney Transplant.

PURPOSE: This retrospective analysis of medical chart data was performed to compare severity and treatment of gout in patients with or without a history of kidney transplantation (KT). METHODS: Via an online survey, a panel of board-certified US nephrologists (N = 104) provided the following deidentified chart data for their 3 most recent patients with gout: age, sex, serum uric acid, numbers of swollen or tender joints, visible tophi, gout flare events (prior 12 months), gout drug treatment history, and KT history. The presence of "severe, uncontrolled gout" was defined as: serum uric acid ≥ 7.0 mg/dL, ≥1 tophi and ≥2 flares in the last 12 months, and history of xanthine oxidase inhibitor treatment. RESULTS: Twenty-five out of 312 (8.0%) gout patients had a history of KT. Univariate analysis found that patients with gout and history of kidney transplants had: greater prevalence of severe uncontrolled gout (27% vs 8%, P = .007) and tophi (36% vs 17%, P = .030), and higher rates of failure or physician perceived contraindication to allopurinol (44% vs 23%, P = .028). CONCLUSION: This study provides preliminary evidence that gout in patients with history of KT is more severe and poses greater challenges to pharmacologic management. Although gout has been linked to worse outcomes among kidney recipients in the literature, there are presently no publications on gout severity among patients with KT in comparison to other patients with gout. Further investigation of disease severity and appropriate, effective treatment options in recipients of kidney transplant with a diagnosis of gout, especially prior to the transplant, is warranted.

Author Correction: Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening.

In the published version of this paper, Step 64 of the Procedure reads, "Refer to Steps 37-39 for NGS analysis of the sgRNA distribution." This step should refer the reader to Steps 35-39. This text has not been corrected in the original paper.

Environmentally relevant chemical mixtures of concern in waters of United States tributaries to the Great Lakes.

The North American Great Lakes are a vital natural resource that provide fish and wildlife habitat, as well as drinking water and waste assimilation services for millions of people. Tributaries to the Great Lakes receive chemical inputs from various point and nonpoint sources, and thus are expected to have complex mixtures of chemicals. However, our understanding of the co-occurrence of specific chemicals in complex mixtures is limited. To better understand the occurrence of specific chemical mixtures in the US Great Lakes Basin, surface water from 24 US tributaries to the Laurentian Great Lakes was collected and analyzed for diverse suites of organic chemicals, primarily focused on chemicals of concern (e.g., pharmaceuticals, personal care products, fragrances). A total of 181 samples and 21 chemical classes were assessed for mixture compositions. Basin wide, 1664 mixtures occurred in at least 25% of sites. The most complex mixtures identified comprised 9 chemical classes and occurred in 58% of sampled tributaries. Pharmaceuticals typically occurred in complex mixtures, reflecting pharmaceutical-use patterns and wastewater facility outfall influences. Fewer mixtures were identified at lake or lake-influenced sites than at riverine sites. As mixture complexity increased, the probability of a specific mixture occurring more often than by chance greatly increased, highlighting the importance of understanding source contributions to the environment. This empirically based analysis of mixture composition and occurrence may be used to focus future sampling efforts or mixture toxicity assessments. Integr Environ Assess Manag 2018;14:509-518. © 2018 SETAC.

Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: I. Patterns of occurrence.

Human activities introduce a variety of chemicals to the Laurentian Great Lakes including pesticides, pharmaceuticals, flame retardants, plasticizers, and solvents (collectively referred to as contaminants of emerging concern or CECs) potentially threatening the vitality of these valuable ecosystems. We conducted a basin-wide study to identify the presence of CECs and other chemicals of interest in 12 U.S. tributaries to the Laurentian Great Lakes during 2013 and 2014. A total of 292 surface-water and 80 sediment samples were collected and analyzed for approximately 200 chemicals. A total of 32 and 28 chemicals were detected in at least 30% of water and sediment samples, respectively. Concentrations ranged from 0.0284 (indole) to 72.2 (cholesterol) µg/L in water and 1.75 (diphenhydramine) to 20,800 µg/kg (fluoranthene) in sediment. Cluster analyses revealed chemicals that frequently co-occurred such as pharmaceuticals and flame retardants at sites receiving similar inputs such as wastewater treatment plant effluent. Comparison of environmental concentrations to water and sediment-quality benchmarks revealed that polycyclic aromatic hydrocarbon concentrations often exceeded benchmarks in both water and sediment. Additionally, bis(2-ethylhexyl) phthalate and dichlorvos concentrations exceeded water-quality benchmarks in several rivers. Results from this study can be used to understand organism exposure, prioritize river basins for future management efforts, and guide detailed assessments of factors influencing transport and fate of CECs in the Great Lakes Basin.

Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: II. Biological consequences of exposure.

The Laurentian Great Lakes contain one fifth of the world's surface freshwater and have been impacted by human activity since the Industrial Revolution. In addition to legacy contaminants, nitrification and invasive species, this aquatic ecosystem is also the recipient of Contaminants of Emerging Concern (CECs) with poorly understood biological consequences. In the current study, we documented the presence, concentrations, and biological effects of CECs across 27 field sites in six Great Lakes tributaries by examining over 2250 resident and caged sunfish (Lepomis ssp.) for a variety of morphological and physiological endpoints and related these results to CEC occurrence. CEC were ubiquitous across studies sites and their presence and concentrations in water and sediment were highest in effluent dominated rivers and downstream of municipal wastewater treatment plant discharges. However, even putative upstream reference sites were not free of CEC presence and fish at these sites exhibited biological effects consistent with CEC exposure. Only the Fox River exhibited consistent adverse biological effects, including increased relative liver size, greater prominence of hepatocyte vacuoles and increased plasma glucose concentrations. Canonical Redundancy Analysis revealed consistent patterns of biological consequences of CEC exposure across all six tributaries. Increasing plasma glucose concentrations, likely as a result of pollutant-induced metabolic stress, were associated with increased relative liver size and greater prominence of hepatocyte vacuoles. These indicators of pollutant exposure were inversely correlated with indicators of reproductive potential including smaller gonad size and less mature gametes. The current study highlights the need for greater integration of chemical and biological studies and suggests that CECs in the Laurentian Great Lakes Basin may adversely affect the reproductive potential of exposed fish populations.

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening.

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified by the screen, we further describe strategies for confirming the screening phenotype, as well as genetic perturbation, through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9-15 weeks, followed by 4-5 weeks of validation.

Trends in mercury wet deposition and mercury air concentrations across the U.S. and Canada.

This study examined the spatial and temporal trends of mercury (Hg) in wet deposition and air concentrations in the United States (U.S.) and Canada between 1997 and 2013. Data were obtained from the National Atmospheric Deposition Program (NADP) and Environment Canada monitoring networks, and other sources. Of the 19 sites with data records from 1997-2013, 53% had significant negative trends in Hg concentration in wet deposition, while no sites had significant positive trends, which is in general agreement with earlier studies that considered NADP data up until about 2010. However, for the time period 2007-2013 (71 sites), 17% and 13% of the sites had significant positive and negative trends, respectively, and for the time period 2008-2013 (81 sites) 30% and 6% of the sites had significant positive and negative trends, respectively. Non-significant positive tendencies were also widespread. Regional trend analyses revealed significant positive trends in Hg concentration in the Rocky Mountains, Plains, and Upper Midwest regions for the recent time periods in addition to significant positive trends in Hg deposition for the continent as a whole. Sulfate concentration trends in wet deposition were negative in all regions, suggesting a lower importance of local Hg sources. The trend in gaseous elemental Hg from short-term datasets merged as one continuous record was broadly consistent with trends in Hg concentration in wet deposition, with the early time period (1998-2007) producing a significantly negative trend (-1.5±0.2%year(-1)) and the recent time period (2008-2013) displaying a flat slope (-0.3±0.1%year(-1), not significant). The observed shift to more positive or less negative trends in Hg wet deposition primarily seen in the Central-Western regions is consistent with the effects of rising Hg emissions from regions outside the U.S. and Canada and the influence of long-range transport in the free troposphere.

Optimizing fish sampling for fish-mercury bioaccumulation factors.

Fish Bioaccumulation Factors (BAFs; ratios of mercury (Hg) in fish (Hgfish) and water (Hgwater)) are used to develop total maximum daily load and water quality criteria for Hg-impaired waters. Both applications require representative Hgfish estimates and, thus, are sensitive to sampling and data-treatment methods. Data collected by fixed protocol from 11 streams in 5 states distributed across the US were used to assess the effects of Hgfish normalization/standardization methods and fish-sample numbers on BAF estimates. Fish length, followed by weight, was most correlated to adult top-predator Hgfish. Site-specific BAFs based on length-normalized and standardized Hgfish estimates demonstrated up to 50% less variability than those based on non-normalized Hgfish. Permutation analysis indicated that length-normalized and standardized Hgfish estimates based on at least 8 trout or 5 bass resulted in mean Hgfish coefficients of variation less than 20%. These results are intended to support regulatory mercury monitoring and load-reduction program improvements.

Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex.

Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.

Lacustrine responses to decreasing wet mercury deposition rates--results from a case study in northern Minnesota.

We present a case study comparing metrics of methylmercury (MeHg) contamination for four undeveloped lakes in Voyageurs National Park to wet atmospheric deposition of mercury (Hg), sulfate (SO4(-2)), and hydrogen ion (H+) in northern Minnesota. Annual wet Hg, SO4(-2), and H+ deposition rates at two nearby precipitation monitoring sites indicate considerable decreases from 1998 to 2012 (mean decreases of 32, 48, and 66%, respectively). Consistent with decreases in the atmospheric pollutants, epilimnetic aqueous methylmercury (MeHgaq) and mercury in small yellow perch (Hgfish) decreased in two of four lakes (mean decreases of 46.5% and 34.5%, respectively, between 2001 and 2012). Counter to decreases in the atmospheric pollutants, MeHgaq increased by 85% in a third lake, whereas Hgfish increased by 80%. The fourth lake had two disturbances in its watershed during the study period (forest fire; changes in shoreline inundation due to beaver activity); this lake lacked overall trends in MeHgaq and Hgfish. The diverging responses among the study lakes exemplify the complexity of ecosystem responses to decreased loads of atmospheric pollutants.

The diet of Myotis lucifugus across Canada: assessing foraging quality and diet variability.

Variation in prey resources influences the diet and behaviour of predators. When prey become limiting, predators may travel farther to find preferred food or adjust to existing local resources. When predators are habitat limited, local resource abundance impacts foraging success. We analysed the diet of Myotis lucifugus (little brown bats) from Nova Scotia (eastern Canada) to the Northwest Territories (north-western Canada). This distribution includes extremes of season length and temperature and encompasses colonies on rural monoculture farms, and in urban and unmodified areas. We recognized nearly 600 distinct species of prey, of which ≈30% could be identified using reference sequence libraries. We found a higher than expected use of lepidopterans, which comprised a range of dietary richness from ≈35% early in the summer to ≈55% by late summer. Diptera were the second largest prey group consumed, representing ≈45% of dietary diversity early in the summer. We observed extreme local dietary variability and variation among seasons and years. Based on the species of insects that were consumed, we observed that two locations support prey species with extremely low pollution and acidification tolerances, suggesting that these are areas without environmental contamination. We conclude that there is significant local population variability in little brown bat diet that is likely driven by seasonal and geographical changes in insect diversity, and that this prey may be a good indicator of environment quality.

Optical control of mammalian endogenous transcription and epigenetic states.

The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high-precision spatiotemporal control of many cellular functions. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here we describe the development of light-inducible transcriptional effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical cofactors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of freely behaving mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states.

Optimizing stream water mercury sampling for calculation of fish bioaccumulation factors.

Mercury (Hg) bioaccumulation factors (BAFs) for game fishes are widely employed for monitoring, assessment, and regulatory purposes. Mercury BAFs are calculated as the fish Hg concentration (Hg(fish)) divided by the water Hg concentration (Hg(water)) and, consequently, are sensitive to sampling and analysis artifacts for fish and water. We evaluated the influence of water sample timing, filtration, and mercury species on the modeled relation between game fish and water mercury concentrations across 11 streams and rivers in five states in order to identify optimum Hg(water) sampling approaches. Each model included fish trophic position, to account for a wide range of species collected among sites, and flow-weighted Hg(water) estimates. Models were evaluated for parsimony, using Akaike's Information Criterion. Better models included filtered water methylmercury (FMeHg) or unfiltered water methylmercury (UMeHg), whereas filtered total mercury did not meet parsimony requirements. Models including mean annual FMeHg were superior to those with mean FMeHg calculated over shorter time periods throughout the year. FMeHg models including metrics of high concentrations (80th percentile and above) observed during the year performed better, in general. These higher concentrations occurred most often during the growing season at all sites. Streamflow was significantly related to the probability of achieving higher concentrations during the growing season at six sites, but the direction of influence varied among sites. These findings indicate that streamwater Hg collection can be optimized by evaluating site-specific FMeHg-UMeHg relations, intra-annual temporal variation in their concentrations, and streamflow-Hg dynamics.

Intra- and inter-basin mercury comparisons: Importance of basin scale and time-weighted methylmercury estimates.

To assess inter-comparability of fluvial mercury (Hg) observations at substantially different scales, Hg concentrations, yields, and bivariate-relations were evaluated at nested-basin locations in the Edisto River, South Carolina and Hudson River, New York. Differences between scales were observed for filtered methylmercury (FMeHg) in the Edisto (attributed to wetland coverage differences) but not in the Hudson. Total mercury (THg) concentrations and bivariate-relationships did not vary substantially with scale in either basin. Combining results of this and a previously published multi-basin study, fish Hg correlated strongly with sampled water FMeHg concentration (ρ = 0.78; p = 0.003) and annual FMeHg basin yield (ρ = 0.66; p = 0.026). Improved correlation (ρ = 0.88; p < 0.0001) was achieved with time-weighted mean annual FMeHg concentrations estimated from basin-specific LOADEST models and daily streamflow. Results suggest reasonable scalability and inter-comparability for different basin sizes if wetland area or related MeHg-source-area metrics are considered.

Influence of dietary carbon on mercury bioaccumulation in streams of the Adirondack Mountains of New York and the Coastal Plain of South Carolina, USA.

We studied lower food webs in streams of two mercury-sensitive regions to determine whether variations in consumer foraging strategy and resultant dietary carbon signatures accounted for observed within-site and among-site variations in consumer mercury concentration. We collected macroinvertebrates (primary consumers and predators) and selected forage fishes from three sites in the Adirondack Mountains of New York, and three sites in the Coastal Plain of South Carolina, for analysis of mercury (Hg) and stable isotopes of carbon (δ(13)C) and nitrogen (δ(15)N). Among primary consumers, scrapers and filterers had higher MeHg and more depleted δ(13)C than shredders from the same site. Variation in δ(13)C accounted for up to 34 % of within-site variation in MeHg among primary consumers, beyond that explained by δ(15)N, an indicator of trophic position. Consumer δ(13)C accounted for 10 % of the variation in Hg among predatory macroinvertebrates and forage fishes across these six sites, after accounting for environmental aqueous methylmercury (MeHg, 5 % of variation) and base-N adjusted consumer trophic position (Δδ(15)N, 22 % of variation). The δ(13)C spatial pattern within consumer taxa groups corresponded to differences in benthic habitat shading among sites. Consumers from relatively more-shaded sites had more enriched δ(13)C that was more similar to typical detrital δ(13)C, while those from the relatively more-open sites had more depleted δ(13)C. Although we could not clearly attribute these differences strictly to differences in assimilation of carbon from terrestrial or in-channel sources, greater potential for benthic primary production at more open sites might play a role. We found significant variation among consumers within and among sites in carbon source; this may be related to within-site differences in diet and foraging habitat, and to among-site differences in environmental conditions that influence primary production. These observations suggest that different foraging strategies and habitats influence MeHg bioaccumulation in streams, even at relatively small spatial scales. Such influence must be considered when selecting lower trophic level consumers as sentinels of MeHg bioaccumulation for comparison within and among sites.