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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Hsa{sub c}irc{sub 0}009910 promotes carcinogenesis by promoting the expression of miR-449a target IL6R in osteosarcoma

Highlights: • Hsa{sub c}irc{sub 0}009910 plays oncogenic role in osteosarcoma cells. • Circ{sub 0}009910 acted as a sponge of miR-449a. • Inhibition of miR-449a impairs the tumor suppressor role of circ{sub 0}009910 silencing. • IL6R was a functional target of miR-449a. • JAK1/STAT3 signaling involves in circ{sub 0}009910/miR-449a/IL6R related tumorigenesis. Circular RNAs (circRNAs) have recently shown capabilities as gene regulators in mammals. Some of them interact with microRNAs (miRNAs) and function as sponges to affect related miRNAs' activities. In this study, the molecular function of circRNA{sub 0}009910 and its potential downstream miRNA targets were explored. The expression levels of hsa{sub c}irc{sub 0}009910 were found to be overexpressed in osteosarcoma (OS) cells. Knockdown of circ{sub 0}009910 induced cell proliferation inhibition, cell cycle arrest, and apoptosis in OS cells. The target miRNA was predicted to be miR-449a, whose expression was downregulated in OS cells. Inhibition of miR-449a abolished the effect of circ{sub 0}009910 knockdown on cell growth and apoptosis. The expression of miR-449a were found to be negatively correlated with that of circ{sub 0}009910 in OS tissues. Direct interaction of circ{sub 0}009910 and miR-449a was confirmed through dual-luciferase assays. Moreover, IL6R was predicted as a potential target of miR-449a. Overexpression of miR-449a decreased the mRNA and protein levels of IL6R. Restoration of IL6R impaired the miR-449a induced inhibition of cell proliferation, cell cycle arrest, and apoptosis. The mRNA expression of IL6R was inversely correlated with miR-449a in OS tissues. In addition, JAK1/STAT3 signaling pathway was regulated by circ{sub 0}009910/miR-449a/IL6R axis. Taken together, we suggested that circ{sub 0}009910 acted as a sponge of miR-449a and upregulated miR-449a functional target IL6R, thereby contributed to carcinogenesis of OS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The SCF ubiquitin ligase Slimb controls Nerfin-1 turnover in Drosophila

Highlights: • Slimb associates with Nerfin-1 and promotes Nerfin-1 turnover. • The C-terminal half of Nerfin-1 is required for Slimb-binding and Slimb-mediated degradation by UPS. • Slimb regulates Nerfin-1 activity in vivo. The C2H2 type zinc-finger transcription factor Nerfin-1 expresses dominantly in Drosophila nervous system and plays an important role in early axon guidance decisions and preventing neurons dedifferentiation. Recently, increasing reports indicated that INSM1 (homologue to nerfin-1 in mammals) is a useful marker for prognosis of neuroendocrine tumors. The dynamic expression of Nerfin-1 is regulated post-transcriptionally by multiple microRNAs; however, its post-translational regulation is still unclear. Here we showed that the protein turnover of Nerfin-1 is regulated by Slimb, the substrate adaptor of SCF{sup Slimb} ubiquitin ligase complex. Mechanistically, Slimb associates with Nerfin-1 and promotes it ubiquitination and degradation in Drosophila S2R{sup +} cells. Furthermore, we determined that the C-terminal half of Nerfin-1 (Nerfin-1{sup CT}) is required for its binding to Slimb. Genetic epistasis assays showed that Slimb misexpression antagonizes, while knock-down enhances the activity of Nerfin-1{sup CT} in Drosophila eyes. Our data revealed a new link to understand the underlying mechanism for Nerfin-1 turnover in post-translational level, and provided useful insights in animal development and disease treatment by manipulating the activity of Slimb and Nerfin-1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Overexpression of NRK1 ameliorates diet- and age-induced hepatic steatosis and insulin resistance

NAD{sup +} is a co-enzyme in redox reactions and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Dietary supplementation of NAD{sup +} precursors nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we sought to identify the roles of nicotinamide riboside kinase 1 (NRK1) plays in regulating hepatic NAD{sup +} biosynthesis and lipid metabolism. Using adenovirus mediated gene transduction to overexpress or knockdown NRK1 in mouse liver, we have demonstrated that NRK1 is critical for maintaining hepatic NAD{sup +} levels and triglyceride content. We have further shown that the hepatic expression of Nmrk1 mRNA is significantly decreased either in mice treated with high-fat diet or in aged mice. However, adenoviral delivery of NRK1 in these diet- and age-induced mice elevates hepatic NAD{sup +} levels, reduces hepatic steatosis, and improves glucose tolerance and insulin sensitivity. Our results provide important insights in targeting NRK1 for treating hepatic steatosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Comparative folding analyses of unknotted versus trefoil-knotted ornithine transcarbamylases suggest stabilizing effects of protein knots

Highlights: • The OTC superfamily contains both knotted and unknotted members that can be used to explore the advantages of being knotted. • SAXS confirms that homotrimeric quaternary structures of the unknotted EcOTC and trefoil knotted BfSOTC and XcAOTC. • Knotted BfSOTC and XcAOTC are more resistant to chemical denaturation than does the unknotted EcOTC. • HDX-MS revealed attenuated local fluctuations within the knotted BfSOTC and XcAOTC whereas the unknotted EcOTC exhibited more abundant local unfolding events. • Our results suggest a stabilizing role of folding dynamics for protein knots. Ornithine transcarbamylases (OTCs) are conserved enzymes involved in arginine biosynthesis in microbes and the urea cycle in mammals. Recent bioinformatics analyses identified two unique OTC variants, N-succinyl-l-ornithine transcarbamylase from Bacteroides fragilis (BfSOTC) and N-acetyl-l-ornithine transcarbamylase from Xanthomonas campestris (XcAOTC). These two variants diverged from other OTCs during evolution despite sharing the common tertiary and quaternary structures, with the exception that the substrate recognition motifs are topologically knotted. The OTC family therefore offers a unique opportunity for investigating the importance of protein knots in biological functions and folding stabilities. Using hydrogen-deuterium exchange-coupled mass spectrometry, we compared the native dynamics of BfSOTC and XcAOTC with respect to the unknotted ornithine transcarbamylase from Escherichia coli (EcOTC). Our results suggest that, in addition to substrate specificity, the knotted structures in XcAOTC and BfSOTC may play an important role in stabilizing the folding dynamics, particularly around the knotted structural elements.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Protein hypoacylation induced by Sirt5 overexpression has minimal metabolic effect in mice

Highlights: • Sirt5 overexpression in mice causes protein hyposuccinylation and hypomalonylation in different tissues. • High-fat feeding alters hepatic protein acylation levels. • Protein hypoacylation induced by Sirt5 overexpression has limited effect on the metabolic phenotype of mice. Sirtuins are a family of evolutionary conserved enzymes that dynamically regulate cellular physiology. Mammals have 7 sirtuins, which are located in different cellular compartments. Sirt5, a sirtuin isoform located in multiple subcellular sites, is involved in regulating a diverse range of cellular and metabolic processes through the removal of a range of acyl-lysine modifications on target proteins. Loss of Sirt5 leads to hyper-malonylation and hyper-succinylation of both mitochondrial and extra-mitochondrial proteins, influencing oxidative phosphorylation, the TCA cycle and glycolysis. However despite these findings, the effect of Sirt5 overexpression on metabolism remains poorly investigated. Here we report that overexpression of Sirt5 has minimal effect on mitochondrial metabolism and overall physiology in mice, despite inducing widespread decreases in protein acylation. Our data confirms the role of Sirt5 as an important demalonylase and desuccinylase enzyme in vivo, but questions the relevance of physiological changes in protein acylation levels in the regulation of cellular metabolism.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Presence of calpain-5 in mitochondria

Highlights: • Calpain-5 is present in the inner and outer segments of photoreceptor cells. • Calpain-5 is present in the mitochondria of photoreceptor cells. • Calpain-5 is localized in each mitochondrial subfraction of the retina. • The molecular weight of mitochondrial calpain-5 is smaller than cytosolic one. Calpains are Ca{sup 2+}-dependent cysteine proteases that are widely distributed in animal tissues and modulate a variety of cellular processes. There are 15 members of the calpain family in mammals. In animal cells, there are three types of calpains, viz., calpain-1, calpain-2, and calpain-10 in the mitochondria. The three types of calpains have been shown to play significant roles in pathophysiological conditions, including in apoptosis- and necrosis-like cell death. One of the severe retinal diseases, autosomal dominant neovascular inflammatory vitreoretinopathy, is known to be induced by mutations of the calpain-5 gene. However, the distribution of calpain-5 in the retina has not been elucidated. Therefore, in the present study, we determined the localization of calpain-5 in the porcine retina. We detected calpain-5 in the inner segment of photoreceptor cells using immunohistochemistry. With immunoelectron microscopy, calpain-5 was localized in the mitochondria of photoreceptor cells. Western blot analyses showed that calpain-5 was present in each mitochondrial subfraction. Furthermore, we showed that the molecular weight of mitochondrial calpain-5 was slightly smaller than cytosolic one. Our results demonstrated that a novel mitochondrial calpian, calpain-5, was localized in the mitochondria of retinal photoreceptor cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Decreased expression of LATS1 correlates with astrogliosis after spinal cord injury

Large tumor suppressor kinase 1 (LATS1) is a serine/threonine kinase of the AGC kinase family in mammals and involved in various biological processes, it is a key regulator of cell cycle progression. However, the role of LATS1 in central nervous system trauma is still unknown. In present study, we performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of LATS1 expression in the spinal cord. We found that LATS1 protein levels were significantly decreased at day 1 after injury. Meanwhile, double immunofluorescence staining showed these changes were striking in astrocytes, which were largely proliferated after SCI. In vitro, LATS1 overexpression inhibited astrocyte proliferation. Conversely, LATS1 depletion by siRNA promoted cell proliferation in primary astrocyte. Moreover, LATS1 overexpression reduced cyclin D1 expression and increased the expression of p27{sup kip1}. In addition, LATS1 overexpression also promoted yes-associated protein 1 (YAP) phosphorylation. Our data suggested that LATS1 might play an important role in spinal cord injury and suppress astrogliosis through regulating the expression of cyclin D1, p27{sup kip1} and p-YAP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Visualization of specific collagen-producing cells by Col1-GFP transgenic mice revealed novel type I collagen-producing cells other than fibroblasts in systemic organs/tissues

Highlights: • A new reporter mouse was generated to label type I collagen-producing cells. • Type I collagen-producing cells were specifically labeled in this reporter mouse. • Podocytes and Leydig cells showed the ability to produce type I collagen. Type I collagen is one of the most abundant proteins in mammals and plays important roles in maintaining the integrity of many tissues. Although fibroblasts are the main source of type I collagen, other cells also produce it; however, these cells are not well-defined owing to the lack of a specific marker. A transgenic (Tg) mouse line has been generated in which type I collagen-producing cells are labeled with enhanced green fluorescent protein (EGFP), which enables the monitoring of these cells without requiring an additional cell marker. This Tg mouse line has since been widely used to study type I collagen-producing cells and fibrosis; one study revealed that podocytes, which were not previously considered to produce type I collagen, expressed EGFP. This raises a question regarding the specificity of EGFP expression in this Tg mouse line. To exclude the possibility of non-specific EGFP expression in the existing Tg mouse line and specifically monitor type I collagen-producing cells, we generated a new Tg mouse line and histologically confirmed the specificity of EGFP expression throughout the body. Moreover, we explored type I collagen-producing cells other than fibroblasts and revealed for the first time that Leydig cells have the ability to produce type I collagen. Because of its highly specific and physiologically accurate expression, our new Tg mouse line will help to accurately elucidate not only type I collagen-producing cells in normal tissues but also the potential cells in fibrotic tissues, providing new insights into the pathology of fibrosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Conversion of dietary trans-vaccenic acid to trans11,cis13-conjugated linoleic acid in the rat lactating mammary gland by Fatty Acid Desaturase 3-catalyzed methyl-end Δ13-desaturation

Highlights: • FADS3 was shown in vitro to catalyze the Δ13-desaturation of trans-vaccenic acid. • The product is the trans11,cis13-18:2 conjugated linoleic acid isomer. • The proof of this concept is so far lacking in vivo. • Lactating female rats fed with trans-vaccenic acid produced the trans11,cis13-18:2. • This study demonstrates this new pathway in the lactating mammary gland. In vitro, the rat Fatty Acid Desaturase 3 (FADS3) gene was shown to code for an enzyme able to catalyze the unexpected Δ13-desaturation of trans-vaccenic acid, producing the trans11,cis13-conjugated linoleic acid (CLA) isomer. FADS3 may therefore be the first methyl-end trans-vaccenate Δ13-desaturase functionally characterized in mammals, but the proof of this concept is so far lacking in vivo. The present study therefore aimed at investigating further the putative in vivo synthesis of trans11,cis13-CLA from dietary trans-vaccenic acid in rodents. During one week of pregnancy and two weeks post-partum, Sprague-Dawley female rats were fed two diets either high (10.0% of fatty acids and 3.8% of energy intake) or low (0.4% of fatty acids and 0.2% of energy intake) in trans-vaccenic acid. The trans11,cis13-CLA was specifically detected, formally identified and reproducibly quantified (0.06% of total fatty acids) in the mammary gland phospholipids of lactating female rats fed the high trans-vaccenic acid-enriched diet. This result was consistent with FADS3 mRNA expression being significantly higher in the lactating mammary gland than in the liver. Although the apparent metabolic conversion is low, this physiological evidence demonstrates the existence of this new pathway described in the lactating mammary gland and establishes the FADS3 enzyme as a reliable mammalian trans-vaccenate Δ13-desaturase in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ferricrocin, the intracellular siderophore of Trichoderma virens, is involved in growth, conidiation, gliotoxin biosynthesis and induction of systemic resistance in maize

Highlights: • TvTex10 deletion increases fungal growth rate and sensitivity to oxidative stress. • Mutants demonstrate decreased conidiation and gliotoxin production. • Root colonization is increased in mutant treated plants. • Induced systemic resistance in treated plants is reduced compared to the wild type. Fungal siderophores are known to be involved in iron acquisition and storage, as well as pathogenicity of mammals and plants. As avirulent plant symbionts, Trichoderma spp. colonize roots and induce resistance responses both locally and systemically. To study the role of intracellular siderophore(s) in Trichoderma-plant interactions, we have obtained mutants in a non-ribosomal peptide synthetase, TvTex10, that was predicted to be involved in intracellular siderophore(s) biosynthesis. This gene has a detectable basal level of expression and is also upregulated under iron-deplete conditions. This is unlike two other siderophore-encoding genes, which are tightly regulated by iron. Disruption of tex10 gene using homologous recombination resulted in mutants with enhanced growth rate, reduced conidiation and hyper-sensitivity to oxidative stress as compared to wildtype strain. The mutants also produced reduced levels of gliotoxin and dimethyl gliotoxin but have enhanced ability to colonize maize seedling roots. The mutants were also impaired in induction of induced systemic resistance (ISR) in maize against the foliar pathogen Cochliobolus heterostrophus.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Sesaminol diglucoside, a water-soluble lignan from sesame seeds induces brown fat thermogenesis in mice

Highlights: • Aqueous extract of black sesame seeds induces brown fat thermogenesis in mice. • SDG purified from the aqueous sesame extract prevents weight gain in HFD fed mice. • SDG induces brown fat thermogenesis through β3-adrenergic receptors. Brown adipose tissue (BAT) is the site of non-shivering thermogenesis in mammals, wherein energy is dissipated as heat. We observed that aqueous extract of black sesame seed triggers an increase in the expression of Uncoupling Protein 1 (UCP1) in brown adipocytes from mice. The active component from the extract was purified and identified to be sesaminol diglucoside (SDG). SDG treatment decreased mass of white fat pads and serum glucose levels and increased UCP1 levels in BAT thereby protecting mice against high fat induced weight gain. Further in silico and in vitro studies revealed that these effects are due to the agonist like behaviour of SDG towards beta 3 adrenergic receptors (β3-AR). Together, our results suggest that SDG induces BAT mediated thermogenesis through β3-AR and protects mice against diet-induced obesity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

OpenRBC: A Fast Simulator of Red Blood Cells at Protein Resolution

We present OpenRBC, a coarse-grained molecular dynamics code, which is capable of performing an unprecedented in silico experiment—simulating an entire mammal red blood cell lipid bilayer and cytoskeleton as modeled by multiple millions of mesoscopic particles—using a single shared memory commodity workstation. To achieve this, we invented an adaptive spatial-searching algorithm to accelerate the computation of short-range pairwise interactions in an extremely sparse three-dimensional space. The algorithm is based on a Voronoi partitioning of the point cloud of coarse-grained particles, and is continuously updated over the course of the simulation. The algorithm enables the construction of the key spatial searching data structure in our code, i.e., a lattice-free cell list, with a time and space cost linearly proportional to the number of particles in the system. The position and the shape of the cells also adapt automatically to the local density and curvature. The code implements OpenMP parallelization and scales to hundreds of hardware threads. It outperforms a legacy simulator by almost an order of magnitude in time-to-solution and >40 times in problem size, thus providing, to our knowledge, a new platform for probing the biomechanics of red blood cells.

Biophysics↗
DOE OSTI2015

Structural Basis for Molecular Discrimination by a 3',3'-cGAMP Sensing Riboswitch

Cyclic dinucleotides are second messengers that target the adaptor STING and stimulate the innate immune response in mammals. Besides protein receptors, there are bacterial riboswitches that selectively recognize cyclic dinucleotides. We recently discovered a natural riboswitch that targets 3',3'-cGAMP, which is distinguished from the endogenous mammalian signal 2',3'-cGAMP by its backbone connectivity. Here, we report on structures of the aptamer domain of the 3',3'-cGAMP riboswitch from Geobacter in the 3',3'-cGAMP and c-di-GMP bound states. The riboswitch adopts a tuning forklike architecture with a junctional ligand-binding pocket and different orientations of the arms are correlated with the identity of the bound cyclic dinucleotide. Subsequent biochemical experiments revealed that specificity of ligand recognition can be affected by point mutations outside of the binding pocket, which has implications for both the assignment and reengineering of riboswitches in this structural class.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Regional Control of Hairless versus Hair-Bearing Skin by Dkk2

Haired skin is a defining characteristic of mammals. Yet, some specialized skin regions, such as human palms, soles and ventral wrist, and mouse plantar foot, are entirely hairless. Using mouse plantar skin as a model system, we show that the endogenous secreted Wnt inhibitor DKK2 suppresses plantar hair follicle development and permits the formation of hairless skin. Plantar skin retains all of the mechanistic components needed for hair follicle development, as genetic deletion of Dkk2 permits formation of fully functional plantar hair follicles that give rise to external hair, contain sebaceous glands and a stem cell compartment, and undergo regenerative growth. In the absence of Dkk2 , Wnt/β-catenin signaling activity is initially broadly elevated in embryonic plantar skin and gradually becomes patterned, mimicking follicular development in normally haired areas. These data reflects a paradigm in which regionally restricted expression of a Wnt inhibitor underlies specification of hairless versus hairy skin.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Protecting honey bees through microbiome engineering

Honey bees are indispensable insects. Their pollination services support modern agriculture and natural ecosystems. Managed honey bee colonies face increasing threats to their survival, ranging from environmental stressors that include agrochemicals to infestations of arthropod pests and infections with microbial pathogens. Like humans, honey bees have a native gut microbiome that supports their health. However, the bee gut microbiome has a simpler composition than the gut microbiome of mammals, and its main constituent bacterial species can be easily cultured outside of the host. Furthermore, this experimental tractability and the need for new methods for protecting hive health have made honey bees a testbed for synthetic microbiomes augmented with probiotic bacteria and engineered DNA. Here, we discuss the natural benefits of bee gut bacteria, recent progress in genetically modifying these bacteria, and how symbiont-mediated RNA interference and other microbiome engineering approaches can boost bee immunity and suppress bee pathogens and parasites. Finally, we discuss how emerging methods for microbiome engineering and biocontainment could be applied to honey bees and used to address challenges in translating these proof-of-principle achievements into safe and effective technologies for field applications at scale.

Biological and medical sciences↗
DOE OSTI2022

Contrasting modes of macro and microsynteny evolution in a eukaryotic subphylum

Examination of the changes in order and arrangement of homologous genes is key for understanding the mechanisms of genome evolution in eukaryotes. Previous comparisons between eukaryotic genomes have revealed considerable conservation across species that diverged hundreds of millions of years ago (e.g., vertebrates, bilaterian animals, and filamentous fungi). However, understanding how genome organization evolves within and between eukaryotic major lineages remains underexplored. We analyzed high-quality genomes of 120 representative budding yeast species (subphylum Saccharomycotina) spanning ~400 million years of eukaryotic evolution to examine how their genome organization evolved and to compare it with the evolution of animal and plant genome organization. We, in this study, found that the decay of both macrosynteny (the conservation of homologous chromosomes) and microsynteny (the conservation of local gene content and order) was strongly associated with evolutionary divergence across budding yeast major clades. However, although macrosynteny decayed very fast, within ~100 million years, the microsynteny of many genes—especially genes in metabolic clusters (e.g., in the GAL gene cluster)—was much more deeply conserved both within major clades and across the subphylum. We further found that when genomes with similar evolutionary divergence times were compared, budding yeasts had lower macrosynteny conservation than animals and filamentous fungi but higher conservation than angiosperms. In contrast, budding yeasts had levels of microsynteny conservation on par with mammals, whereas angiosperms exhibited very low conservation. Our results provide new insight into the tempo and mode of the evolution of gene and genome organization across an entire eukaryotic subphylum.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Sedentary nestlings of Wood Stork as monitors of mercury contamination in the gold mining region of the Brazilian Pantanal

Sedentary organisms that are at top trophic levels allow inference about the level of local mercury contamination. We evaluated mercury contamination in feather tissue of nestling Wood Storks (Mycteria americana), sampled in different parts of the Brazilian Pantanal that were variably polluted by mercury releases from gold mining activities. Levels of mercury in feathers sampled in seven breeding colonies were determined by atomic absorption spectroscopy, and the mean value of mercury concentration was 0.557 {mu}g/g, dry weight (n=124), range 0.024-4.423 {mu}g/g. From this total sample, 21 feathers that represent 30% of nestlings collected in Porto da Fazenda and Tucum colonies, in the northern region, ranged from 1.0 to 4.43 {mu}g/g, dry weight (median value=1.87 {mu}g/g). We found significant differences among regions (H=57.342; p=0<0.05). Results suggest that permanently flooded areas, or along mainstream rivers are more contaminated by mercury than dry areas, regardless of the distance from the gold mining center, which is located in the northern Pantanal. Highest values found in nestlings feathers were similar to those found in feathers of adult birds and in tissues of adult mammals that are less sedentary and were captured in the same region of Pantanal. These findings indicate that mercury released has been biomagnified and it is present in high concentrations in tissues of top consumers. We suggest a program to monitor mercury availability in this ecosystem using sedentary life forms of top predators like Wood Storks or other piscivorous birds. - Highlights: Black-Right-Pointing-Pointer Sedentary stork nestlings were used for the first time to show local mercury contamination of Pantanal. Black-Right-Pointing-Pointer Differences were found among regions but they are not explained only by distance from the gold mining. Black-Right-Pointing-Pointer Permanently flooded areas and areas along mainstream rivers are more contaminated than dry areas. Black-Right-Pointing-Pointer Mercury has been biomagnified in Pantanal and it is found in high concentrations in top consumers.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

A systematic study of the disposition and metabolism of mercury species in mice after exposure to low levels of thimerosal (ethylmercury)

Thimerosal (TM) is an ethylmercury (etHg)-containing preservative used in some vaccines despite very limited knowledge on the kinetics and direct interaction/effects in mammals' tissues after exposure. Thus, this study aimed to evaluate the kinetics of Hg species in mice in a time course analysis after intramuscular injection of TM, by estimating Hg half-lives in blood and tissues. Mice were exposed to one single intramuscular dose of 20 µg of Hg as TM. Blood, brain, heart, kidney and liver were collected at 0.5 hour (h), 1 h, 8 h, 16 h, 144 h, 720 h and 1980 h after TM exposure (n=4). Hg species in animal tissues were identified and quantified by speciation analysis via liquid chromatography hyphenated with inductively coupled mass spectrometry (LC–ICP-MS). It was found that the transport of etHg from muscle to tissues and its conversion to inorganic Hg (inoHg) occur rapidly. Moreover, the conversion extent is modulated in part by the partitioning between EtHg in plasma and in whole blood, since etHg is rapidly converted in red cells but not in a plasma compartment. Furthermore, the dealkylation mechanism in red cells appears to be mediated by the Fenton reaction (hydroxyl radical formation). Interestingly, after 0.5 h of TM exposure, the highest levels of both etHg and inoHg were found in kidneys (accounting for more than 70% of the total Hg in the animal body), whereas the brain contributed least to the Hg body burden (accounts for <1.0% of total body Hg). Thirty days after TM exposure, most Hg had been excreted while the liver presented the majority of the remaining Hg. Estimated half-lives (in days) were 8.8 for blood, 10.7 for brain, 7.8 for heart, 7.7 for liver and 45.2 for kidney. Taken together, our findings demonstrated that TM (etHg) kinetics more closely approximates Hg{sup 2+} than methylmercury (meHg) while the kidney must be considered a potential target for etHg toxicity. - Highlights: • Ethylmercury is rapidly converted to inorganic mercury. • Hg substantially accumulates in kidney with a terminal half-life of 45.2 d. • The dealkylation of ethylmercury occurs in red blood cells but not in plasma. • Hydroxyl radical is probably the main effector of this dealkylation. • Kidney must be considered a potential target for ethylmercury toxicity.

60 APPLIED LIFE SCIENCES↗