Relationships among tissues, biofluids, and otolith selenium concentrations in wild female burbot (Lota lota).

In the Lake Koocanusa-Kootenai River system (Montana, USA and British Columbia, Canada), selenium (Se) contamination has become an international concern and is suspected to contribute to the observed burbot (Lota lota) population collapse. Due to our limited ability to sample burbot in Lake Koocanusa for monitoring studies, we used a reference population to develop tools to model tissue Se disposition for a focal species in systems with elevated Se. Total Se concentrations in otoliths, biofluids (blood and endolymph), and tissues (muscle, liver, and ovary) from burbot in reference lakes in northwestern Ontario, Canada, were measured to document tissue-to-tissue Se relationships and evaluate the potential for otoliths to retrace Se exposure in fish. Among burbot tissue, Se concentrations were the highest in the ovary (mean ± SD = 4.55 ± 2.23 µg g-1 dry mass [dm]), followed by the liver (2.69 ± 1.96 µg g-1 dm) and muscle (1.87 ± 1.14 µg g-1 dm), and decreased with body size (p < 0.05). In otoliths, Se was detected at low levels (<1 µg g-1 ). Selenium concentrations in burbot samples were positively correlated among muscle, ovary, liver, and endolymph tissues, but not for the most recent annually averaged or lifetime-averaged Se concentrations in otoliths. We hypothesize that Se concentrations were too low in this study to establish links between otoliths and other fish tissues and to detect significant lifetime variation in individuals, and that further validation using archived otoliths from burbot exposed to elevated Se levels in Lake Koocanusa-Kootenai River is needed to reconstruct exposure histories. However, intercompartmental models proved valuable for estimating Se concentrations in burbot tissues only available by means of lethal sampling (i.e., ovary), although additional work should confirm whether the established models are reliable to predict concentrations in Se-impaired systems as tissue distributions are likely to differ with increasing Se levels. Integr Environ Assess Manag 2023;00:1-11. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Temporal Influences on Selenium Partitioning, Trophic Transfer, and Exposure in a Major U.S. River.

Hydrologic and irrigation regimes mediate the timing of selenium (Se) mobilization to rivers, but the extent to which patterns in Se uptake and trophic transfer through recipient food webs reflect the temporal variation in Se delivery is unknown. We investigated Se mobilization, partitioning, and trophic transfer along approximately 60 river miles of the selenium-impaired segment of the Lower Gunnison River (Colorado, USA) during six sampling trips between June 2015 and October 2016. We found temporal patterns in Se partitioning and trophic transfer to be independent of those in dissolved Se concentrations and that the recipient food web sustained elevated Se concentrations from earlier periods of high Se mobilization. Using an ecosystem-scale Se accumulation model tailored to the Lower Gunnison River, we predicted that the endangered Razorback Sucker (Xyrauchen texanus) and Colorado Pikeminnow (Ptychocheilus lucius) achieve whole-body Se concentrations exceeding aquatic life protection criteria during periods of high runoff and irrigation activity (April-August) that coincide with susceptible phases of reproduction and early-life development. The results of this study challenge assumptions about Se trophodynamics in fast-flowing waters and introduce important considerations for the management of Se risks for biota in river ecosystems.

Do Two Wrongs Make a Right? Persistent Uncertainties Regarding Environmental Selenium-Mercury Interactions.

Mercury (Hg) is a pervasive environmental pollutant and contaminant of concern for both people and wildlife that has been a focus of environmental remediation efforts for decades. A growing body of literature has motivated calls for revising Hg consumption advisories to co-consider selenium (Se) levels in seafood and implies that remediating aquatic ecosystems with ecosystem-scale Se additions could be a robust solution to Hg contamination. Provided that elevated Se concentrations are also known toxicological threats to aquatic animals, we performed a literature search to evaluate the strength of evidence supporting three assertions underpinning the ameliorating benefits of Se: (1) dietary Se reduces MeHg toxicity in consumers; (2) environmental Se reduces Hg bioaccumulation and biomagnification in aquatic food webs; and (3) Se inhibits Hg bioavailability to, and/or methylmercury production by, microbial communities. Limited or ambiguous support for each criterion indicates that many scientific uncertainties and gaps remain regarding Se mediation of Hg behavior and toxicity in abiotic and biotic compartments. Significantly more information is needed to provide a strong scientific basis for modifying current fish consumption advisories on the basis of Se:Hg ratios or for applying Se amendments to remediate Hg-contaminated ecosystems.

Evidence for unmonitored coal ash spills in Sutton Lake, North Carolina: Implications for contamination of lake ecosystems.

Coal combustion residuals (CCRs, also known as "coal ash") contain high concentrations of toxic and carcinogenic elements that can pose ecological and human health risks upon their release into the environment. About half of the CCRs that are generated annually in the U.S. are stored in coal ash impoundments and landfills, in most cases adjacent to coal plants and waterways. Leaking of coal ash ponds and CCR spills are major environmental concerns. One factor which may impact the safety of CCRs stored in impoundments and landfills is the storage area's predisposition to flooding. The southeastern U.S., in particular, has a large number of coal ash impoundments located in areas that are vulnerable to flooding. In order to test for the possible presence of CCR solids in lake sediments following Hurricane Florence, we analyzed the magnetic susceptibility, microscopic screening, trace element composition, and strontium isotope ratios of bottom sediments collected in 2015 and in 2018 from Sutton Lake in eastern North Carolina and compared them to a reference lake. The results suggest multiple, apparently previously unmonitored, CCR spills into Sutton Lake from adjacent CCR storage sites. The enrichment of metals in Sutton Lake sediments, particularly those with known ecological impact such as As, Se, Cu, Sb, Ni, Cd, V, and Tl, was similar to or even higher than those in stream sediments impacted by the Tennessee Valley Authority (TVA) in Kingston, Tennessee, and the Dan River, North Carolina coal ash spills, and exceeded ecological screening standards for sediments. High levels of contaminants were also found in leachates extracted from Sutton Lake sediments and co-occurring pore water, reflecting their mobilization to the ambient environment. These findings highlight the risks of large-scale unmonitored spills of coal ash solids from storage facilities following major storm events and contamination of nearby water resources throughout the southeastern U.S.

Beyond Selenium: Coal Combustion Residuals Lead to Multielement Enrichment in Receiving Lake Food Webs.

Effluents from coal-fired power plant ash ponds are a major source of environmental contamination, annually loading more than a million metric tons of pollutants to aquatic ecosystems in the United States alone. Though this waste stream is characterized by elevated concentrations of numerous inorganic constituents, decades of previous research effort have focused on the ecotoxicological consequences of a single stressor: selenium. In this study, we compared concentrations of 10 trace elements among three North Carolina reservoirs with varying burdens following decades of coal combustion residual (CCR) inputs. Along this pollution gradient, we examined (1) environmental compartment-specific trace element enrichment relative to reference lake levels and (2) differences in CCR accumulation patterns among abiotic and biotic compartments. We report significant multivariate differences between CCR-receiving and reference lakes for surface water, pore water, sediment, and fish tissues as well as differences in CCR accumulation among North Carolina resident fish species. Multiple-element enrichment across receiving lake compartments additionally highlighted that CCR pollution is a mixtures contamination issue. Our results inform the ongoing discussion about effective regulation of impaired water bodies and identify important questions that might guide the monitoring of these systems as they recover.

Selenium Ecotoxicology in Freshwater Lakes Receiving Coal Combustion Residual Effluents: A North Carolina Example.

Anthropogenic activities resulting in releases of selenium-laden waste streams threaten freshwater ecosystems. Lake ecosystems demand special consideration because they are characterized by prolonged retention of selenium and continuous cycling of the element through the food chain, through which it becomes available to toxicologically susceptible egg-laying vertebrates. This study documents the current selenium burden of lakes in North Carolina (NC) with historic selenium inputs from nearby coal-fired power plants. We measured selenium concentrations in surface waters, sediment pore waters, and resident fish species from coal combustion residual (CCR)-impacted lakes and paired reference lakes. The data are related to levels of recent selenium inputs and analyzed in the context of recently updated federal criteria for the protection of aquatic life. We show that the Se content of fish from lakes with the highest selenium inputs regularly exceed these criteria and are comparable to those measured during historic fish extirpation events in the United States. Large legacy depositions of CCRs within reservoir sediments are likely to sustain Se toxicity for many years despite recent laws to limit CCR discharge into surface waters in NC. Importantly, the widespread use of high-selenium coals for electricity generation extends the potential risk for aquatic ecosystem impacts beyond U.S. borders.

Sex differences in Sjögren's syndrome: a comprehensive review of immune mechanisms.

Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women. Sjögren's syndrome (SS) is an AD that occurs predominately in women over men (16:1). The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth. The disease is believed to be mediated by an inflammatory and autoantibody response directed against salivary and lacrimal gland tissues. This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren's syndrome in order to gain a better understanding of disease pathogenesis.

Sex differences in translocator protein 18 kDa (TSPO) in the heart: implications for imaging myocardial inflammation.

Myocarditis is more severe in men than in women and difficult to diagnose due to a lack of imaging modalities that directly detect myocardial inflammation. Translocator protein 18 kDa (TSPO) is used extensively to image brain inflammation due to its presence in CD11b(+) brain microglia. In this study, we examined expression of TSPO and CD11b in mice with coxsackievirus B3 (CVB3) myocarditis and biopsy sections from myocarditis patients in order to determine if it could be used to image myocarditis. We found that male mice with CVB3 myocarditis upregulated more genes associated with TSPO activation than female mice. TSPO expression was increased in the heart of male mice and men with myocarditis compared with female subjects due to testosterone, where it was expressed predominantly in CD11b(+) immune cells. We show that TSPO ligands detect myocardial inflammation using microSPECT, with increased uptake of [(125)I]-IodoDPA-713 in male mice with CVB3 myocarditis compared with undiseased controls.

TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4.

Recent findings indicate that TLR3 polymorphisms increase susceptibility to enteroviral myocarditis and inflammatory dilated cardiomyopathy (iDCM) in patients. TLR3 signaling has been found to inhibit coxsackievirus B3 (CVB3) replication and acute myocarditis in mouse models, but its role in the progression from myocarditis to iDCM has not been previously investigated. In this study we found that TLR3 deficiency increased acute (P = 5.9 × 10(-9)) and chronic (P = 6.0 × 10(-7)) myocarditis compared with WT B6.129, a mouse strain that is resistant to chronic myocarditis and iDCM. Using left ventricular in vivo hemodynamic assessment, we found that TLR3-deficient mice developed progressively worse chronic cardiomyopathy. TLR3 deficiency significantly increased viral replication in the heart during acute myocarditis from day 3 through day 12 after infection, but infectious virus was not detected in the heart during chronic disease. TLR3 deficiency increased cytokines associated with a T helper (Th)2 response, including IL-4 (P = 0.03), IL-10 (P = 0.008), IL-13 (P = 0.002), and TGF-ß(1) (P = 0.005), and induced a shift to an immunoregulatory phenotype in the heart. However, IL-4-deficient mice had improved heart function during acute CVB3 myocarditis by echocardiography and in vivo hemodynamic assessment compared with wild-type mice, indicating that IL-4 impairs cardiac function during myocarditis. IL-4 deficiency increased regulatory T-cell and macrophage populations, including FoxP3(+) T cells (P = 0.005) and Tim-3(+) macrophages (P = 0.004). Thus, TLR3 prevents the progression from myocarditis to iDCM following CVB3 infection by reducing acute viral replication and IL-4 levels in the heart.

IL-33 independently induces eosinophilic pericarditis and cardiac dilation: ST2 improves cardiac function.

BACKGROUND: IL-33 through its receptor ST2 protects the heart from myocardial infarct and hypertrophy in animal models but, paradoxically, increases autoimmune disease. In this study, we examined the effect of IL-33 or ST2 administration on autoimmune heart disease. METHODS AND RESULTS: We used pressure-volume relationships and isoproterenol challenge to assess the effect of recombinant (r) IL-33 or rST2 (eg, soluble ST2) administration on the development of autoimmune coxsackievirus B3 myocarditis and dilated cardiomyopathy in male BALB/c mice. The rIL-33 treatment significantly increased acute perimyocarditis (P=0.006) and eosinophilia (P=1.3×10(-5)), impaired cardiac function (maximum ventricular power, P=0.0002), and increased ventricular dilation (end-diastolic volume, P=0.01). The rST2 treatment prevented eosinophilia and improved heart function compared with rIL-33 treatment (ejection fraction, P=0.009). Neither treatment altered viral replication. The rIL-33 treatment increased IL-4, IL-33, IL-1ß, and IL-6 levels in the heart during acute myocarditis. To determine whether IL-33 altered cardiac function on its own, we administered rIL-33 to undiseased mice and found that rIL-33 induced eosinophilic pericarditis and adversely affected heart function. We used cytokine knockout mice to determine that this effect was due to IL-33-mediated signaling but not to IL-1ß or IL-6. CONCLUSIONS: We show for the first time to our knowledge that IL-33 induces eosinophilic pericarditis, whereas soluble ST2 prevents eosinophilia and improves systolic function, and that IL-33 independently adversely affects heart function through the IL-33 receptor.

Testosterone and interleukin-1ß increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n.

Myocarditis and dilated cardiomyopathy (DCM) are often caused by viral infections and occur more frequently in men than in women, but the reasons for the sex difference remain unclear. The aim of this study was to assess whether gene changes in the heart during coxsackievirus B3 (CVB3) myocarditis in male and female BALB/c mice predicted worse DCM in males. Although myocarditis (P = 4.2 × 10(-5)) and cardiac dilation (P = 0.008) were worse in males, there was no difference in viral replication in the heart. Fibrotic remodeling genes, such as tissue inhibitor of metalloproteinase (TIMP)-1 and serpin A 3n, were upregulated in males during myocarditis rather than during DCM. Using gonadectomy and testosterone replacement, we showed that testosterone increased cardiac TIMP-1 (P = 0.04), serpin A 3n (P = 0.007), and matrix metalloproteinase (MMP)-8 (P = 0.04) during myocarditis. Testosterone increased IL-1ß levels in the heart (P = 0.02), a cytokine known to regulate cardiovascular remodeling, and IL-1ß in turn increased cardiac serpin A 3n mRNA (P = 0.005). We found that 39 of 118 (33%) genes identified in acute DCM patients were significantly altered in the heart during CVB3 myocarditis in mice, including serpin A 3n (3.3-fold change, P = 0.0001). Recombinant serpin A 3n treatment induced cardiac fibrosis during CVB3 myocarditis (P = 0.0008) while decreasing MMP-3 (P = 0.04) and MMP-9 (P = 0.03) levels in the heart. Thus, serpin A 3n was identified as a gene associated with fibrotic cardiac remodeling and progression to DCM in male myocarditis patients and mice.