Gary N Cherr

University of North Carolina at Wilmington, Wilmington, North Carolina, United States

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Publications (113)340.41 Total impact

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    ABSTRACT: In many modern teleost fish, chorion (egg envelope) glycoproteins are synthesized in the liver of females, and the expression of those genes is controlled by endogenous estrogen released from the ovary during maturation. However, among the classical teleosts, such as salmonid, carp, and zebrafish, the chorion glycoproteins are synthesized in the oocyte as in higher vertebrates. Sturgeon, classified as Chondrostei, represent an ancient lineage of ray-finned fishes that differ from other teleosts in that their sperm possess acrosomes, their eggs have numerous micropyles, and early embryo development is similar to amphibians. In order to understand the molecular mechanisms of chorion formation and the phylogenetic relationship between sturgeon and other teleosts, we employed specific antibodies directed against the primary components of sturgeon chorion glycoproteins, using immunoblotting and immunocytochemistry approaches. The origin of each chorion glycoprotein was determined through analyses of both liver and ovary, and their localization during ovarian development was investigated. Our data indicate that the origin of the major chorion glycoproteins of sturgeon, ChG1, ChG2, and ChG4, derive not only from the oocyte itself but also from follicle cells in the ovary, as well as from hepatocytes. In the follicle cell layer, granulosa cells were found to be the primary source of ChGs during oogenesis in white sturgeon. The unique origins of chorion glycoproteins in sturgeon suggest that sturgeons are an intermediate form in the evolution of the teleost lineage.
    Biology of Reproduction 05/2014; · 4.03 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate the efficacy of integrating a traditional sediment quality triad approach with selected sublethal chronic indicators in resident species in assessing sediment quality in four salt marshes in northern California, USA. These included the highly contaminated (Stege Marsh) and relatively clean (China Camp) marshes in San Francisco Bay and two reference marshes in Tomales Bay. Toxicity potential of contaminants and benthic macroinvertebrate survey showed significant differences between contaminated and reference marshes. Sublethal responses (e.g., apoptotic DNA fragmentation, lipid accumulation, and glycogen depletion) in livers of longjaw mudsucker (Gillichthys mirabilis) and embryo abnormality in lined shore crab (Pachygrapsus crassipes) also clearly distinguished contaminated and reference marshes, while other responses (e.g., cytochrome P450, metallothionein) did not. This study demonstrates that additional chronic sublethal responses in resident species under field exposure conditions can be readily combined with sediment quality triads for an expanded multiple lines of evidence approach. This confirmatory step may be warranted in environments like salt marshes in which natural variables may affect interpretation of toxicity test data. Qualitative and quantitative integration of the portfolio of responses in resident species and traditional approach can support a more comprehensive and informative sediment quality assessment in salt marshes and possibly other habitat types as well.
    Science of The Total Environment 03/2013; 454-455C:189-198. · 3.26 Impact Factor
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    ABSTRACT: In some animals, such as fish, insects and cephalopods, the thick egg coat has a narrow canal--a micropyle--through which spermatozoa enter the eggs. In fish, there is no indication that spermatozoa are attracted by eggs from a distance, but once spermatozoa come near the outer opening of the micropyle, they exhibit directed movement toward it, suggesting that a substance exists in this defined region to attract spermatozoa. Since Coomassie Blue (CB) binds preferentially to the micropyle region in flounder, herring, steelhead and other fish, it probably stains this sperm guidance substance. This substance--a glycoprotein based on lectin staining--is bound tightly to the surface of the chorion, but can be removed readily by protease treatment. Although fertilization in fish (flounder) is possible after removal of this substance, its absence makes fertilization inefficient as reflected by a drastic reduction in fertilization rate. The sperm "attraction" to the micropyle opening is species-specific and is dependent on extracellular Ca(2+). Eggs of some insects, including Drosophila, have distinct micropyle caps with CB-affinity, which also may prove to assist sperm entry. Our attempts to fertilize fly eggs in vitro were not successful.
    Biology of Reproduction 01/2013; · 4.03 Impact Factor
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    ABSTRACT: Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i.e. sex ratio).
    PLoS ONE 01/2013; 8(9):e74251. · 3.53 Impact Factor
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    ABSTRACT: Research into the health and environmental safety of nanotechnology has seriouslylagged behind its emergence in industry. While humans have often adopted synthetic chemicals without considering ancillary consequences, the lessons learned from worldwide pollution should motivate making nanotechnology compatible with environmental concerns. Researchers and policymakers need to understand exposure and harm of engineered nanomaterials (ENMs), currently nanotechnology's main products, to influence the ENM industry toward sustainable growth. Yet, how should research proceed? Standard toxicity testing anchored in single-organism, dose-response characterizations does not adequately represent real-world exposure and receptor scenarios and their complexities. Our approach is different: it derives from ecology, the study of organisms' interactions with each other and their environments. Our approach involves the characterization of ENMs and the mechanistic assessment of their property-based effects. Using high throughput/content screening (HTS/HCS) with cells or environmentally-relevant organisms, we measure the effects of ENMs on a subcellular or population level. We then relate those effects to mechanisms within dynamic energy budget (DEB) models of growth and reproduction. We reconcile DEB model predictions with experimental data on organism and population responses. Finally, we use microcosm studies to measure the potential for community- or ecosystem-level effects by ENMs that are likely to be produced in large quantities and for which either HTS/HCS or DEB modeling suggest their potential to harm populations and ecosystems. Our approach accounts for ecological interactions across scales, from within organisms to whole ecosystems. Organismal ENM effects, if propagated through populations, can alter communities comprising multiple populations (e.g., plant, fish, bacteria) within food webs. Altered communities can change ecosystem services: processes that cycle carbon, nutrients, and energy, and regulate Earth's waters and atmosphere. We have shown ENM effects on populations, communities, and ecosystems, including transfer and concentration of ENMs through food chains, for a range of exposure scenarios; in many cases, we have identified subcellular ENM effects mechanisms. To keep pace with ENM development, rapid assessment of the mechanisms of ENM effects and modeling are needed. DEB models provide a method for mathematically representing effects such as the generation of reactive oxygen species and their associated damage. These models account for organism-level effects on metabolism and reproduction and can predict outcomes of ENM-organism combinations on populations; those predictions can then suggest ENM characteristics to be avoided. HTS/HCS provides a rapid assessment tool of the ENM chemical characteristics that affect biological systems; such results guide and expand DEB model expressions of hazard. Our approach addresses ecological processes in both natural and managed ecosystems (agriculture) and has the potential to deliver timely and meaningful understanding towards environmentally sustainable nanotechnology.
    Accounts of Chemical Research 10/2012; · 20.83 Impact Factor
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    ABSTRACT: Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. The authors evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid-contaminated aquatic habitats. The authors then compared the in vivo response with an in vitro assay-chemical activated luciferase gene expression (CALUX). Juvenile M. beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. Though Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. Whereas the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. The results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells. Environ. Toxicol. Chem. © 2012 SETAC.
    Environmental Toxicology and Chemistry 09/2012; · 2.62 Impact Factor
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    ABSTRACT: The canonical Wnt/β-catenin signaling pathway is critical during early teleost development for establishing the dorsal-ventral axis. Within this pathway, GSK-3β, a key regulatory kinase in the Wnt pathway, regulates β-catenin degradation and thus the ability of β-catenin to enter nuclei, where it can activate expression of genes that have been linked to the specification of the dorsal-ventral axis. In this study, we describe the morphological abnormalities that resulted in zebrafish embryos when axis determination was disrupted by environmental contaminants. These abnormalities were linked to abnormal nuclear accumulation of β-catenin. Furthermore, we demonstrated that the developmental abnormalities and altered nuclear β-catenin accumulation occurred when embryos were exposed to commercial GSK-3β inhibitors. Zebrafish embryos were exposed to commercially available GSK-3 inhibitors (GSK-3 Inhibitor IX and 1-azakenpaullone), or common environmental contaminants (dibutyl phthalate or the polycyclic aromatic hydrocarbons phenanthrene and fluorene) from the 2 to 8-cell stage through the mid-blastula transition (MBT). These embryos displayed morphological abnormalities at 12.5h post-fertilization (hpf) that were comparable to embryos exposed to lithium chloride (LiCl) (300mM LiCl for 10min, prior to the MBT), a classic disruptor of embryonic axis determination. Whole-mount immunolabeling and laser scanning confocal microscopy were used to localize β-catenin. The commercial GSK-3 Inhibitors as well as LiCl, dibutyl phthalate, fluorene and phenanthrene all induced an increase in the levels of nuclear β-catenin throughout the embryo, indicating that the morphological abnormalities were a result of disruption of Wnt/β-catenin signaling during dorsal-ventral axis specification. The ability of environmental chemicals to directly or indirectly target GSK-3β was assessed. Using Western blot analysis, the ability of these chemicals to affect enzymatic inhibitory phosphorylation at serine 9 on GSK-3β was examined, but no change in the serine phosphorylation state of GSK-3β was detected in exposed embryos. Furthermore, polycyclic aromatic hydrocarbons and dibutyl phthalate had no direct effect on the in vitro kinase activity of GSK-3β. While developmental abnormalities resulting from these axis-disrupting contaminants were linked to β-catenin accumulation in nuclei, the details of the disruption of this signaling pathway remain unknown. Since phenanthrene and fluorene as well as other hydrocarbons have been shown to disrupt axial development in sea urchin embryos, and since axis determination and the Wnt/β-catenin signaling pathway are highly conserved, we propose that these environmental contaminants may impact embryo development through a similar mechanism across phyla.
    Aquatic toxicology (Amsterdam, Netherlands) 08/2012; 124-125:188-96. · 3.12 Impact Factor
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    ABSTRACT: During maturation, the surface of mammalian spermatozoa undergoes dramatic changes leading to the acquisition of properties vital for survival and performance in the female reproductive tract. A prominent change is the addition to the sperm surface of an atypical β-defensin polypeptide. In primates, the β-defensin DEFB126 becomes adsorbed to the entire sperm surface as spermatozoa move through the epididymal duct. DEFB126 has a conserved β-defensin core and a unique long glycosylated peptide tail. The carbohydrates of this domain contribute substantially to the sperm glycocalyx. DEFB126 is critical for efficient transport of sperm in the female reproductive tract, preventing their recognition by the female immune system, and might facilitate the delivery of capacitated sperm to the site of fertilization. A newly discovered dinucleotide deletion in the human DEFB126 gene is unusually common in diverse populations and results in a null allele. Predictably, men who are homozygous for the deletion produce sperm with an altered glycocalyx and impaired function, and have reduced fertility. Insights into the biology of DEFB126 are contributing to a better understanding of reproductive fitness in humans, as well as the development of diagnostics and therapeutics for male infertility.
    Nature Reviews Urology 06/2012; 9(7):365-75. · 4.79 Impact Factor
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    ABSTRACT: A large body of work has established a link between endocrine disrupting compounds (EDCs) and a number of abnormalities in fishes. However, most EDC studies use several standard laboratory denizens to assess impacts, so assumptions about sensitivity are primarily based on these few species. Additionally, existing methods rely on obtaining sufficient plasma to measure EDC biomarkers. Our objectives were (a) to establish a new model species for estuarine fishes, (b) to evaluate endocrine impacts with a highly sensitive and specific biomarker, and (c) to develop a method for the analysis of this biomarker in small fish that do not possess sufficient blood plasma for protein measurement. As such, we created a polyclonal antibody (Ab) to the estrogen-responsive proteins chorion (Ch) and choriogenin (Chg) in Menidia beryllina, found throughout coastal North America and already utilized in EPA Whole Effluent Testing. We then validated the Ab by using it to measure the response to aqueous ethinylestradiol (EE2) through the development an ELISA using Menidia whole body homogenate (WBH). Sensitivity of the Ab to Menidia WBH is greater than that of the commercially available option. ELISA sensitivity, with a detection limit of 5 ng/ml and a working range of 22.6-1370.9 ng/ml, is comparable to ELISAs developed to measure plasma Chg. To our knowledge this is the first ELISA method developed for the detection of Chg using WBH. Including additional model species and methods allowing the evaluation of alternative sample matrices will contribute to an enhanced understanding of inter-species differences in EDC response.
    Ecotoxicology 03/2012; 21(4):1272-80. · 2.77 Impact Factor
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    ABSTRACT: Pacific herring early life stages provide good model systems for studying effects of suspended sediments on estuarine organisms. To investigate effects on the herring larval stage, we used environmentally relevant particle concentrations for San Francisco Bay (200–400 mg/L of particles <50 μm in size) and exposure times of 16 h in a novel two-pump sediment suspension mesocosm. There were no mortalities during the 16-h suspended sediment incubation. Following sediment exposure, larvae were cultured in sediment-free water for up to 10 days during which survival and condition were measured. None were affected by previous sediment treatment. Four criteria for larval condition included growth, heart rate, prey capture, and critical swimming velocity. These results provide a framework for implementing regulatory decisions on anthropogenic activities such as dredging.
    Estuaries and Coasts 01/2012; 35(5). · 2.56 Impact Factor
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    ABSTRACT: Pacific herring embryos (Clupea pallasi) spawned three months following the Cosco Busan bunker oil spill in San Francisco Bay showed high rates of late embryonic mortality in the intertidal zone at oiled sites. Dead embryos developed to the hatching stage (e.g. fully pigmented eyes) before suffering extensive tissue deterioration. In contrast, embryos incubated subtidally at oiled sites showed evidence of sublethal oil exposure (petroleum-induced cardiac toxicity) with very low rates of mortality. These field findings suggested an enhancement of oil toxicity through an interaction between oil and another environmental stressor in the intertidal zone, such as higher levels of sunlight-derived ultraviolet (UV) radiation. We tested this hypothesis by exposing herring embryos to both trace levels of weathered Cosco Busan bunker oil and sunlight, with and without protection from UV radiation. Cosco Busan oil and UV co-exposure were both necessary and sufficient to induce an acutely lethal necrotic syndrome in hatching stage embryos that closely mimicked the condition of dead embryos sampled from oiled sites. Tissue levels of known phototoxic polycyclic aromatic compounds were too low to explain the observed degree of phototoxicity, indicating the presence of other unidentified or unmeasured phototoxic compounds derived from bunker oil. These findings provide a parsimonious explanation for the unexpectedly high losses of intertidal herring spawn following the Cosco Busan spill. The chemical composition and associated toxicity of bunker oils should be more thoroughly evaluated to better understand and anticipate the ecological impacts of vessel-derived spills associated with an expanding global transportation network.
    PLoS ONE 01/2012; 7(2):e30116. · 3.53 Impact Factor
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    ABSTRACT: In November 2007, the container ship Cosco Busan released 54,000 gallons of bunker fuel oil into San Francisco Bay. The accident oiled shoreline near spawning habitats for the largest population of Pacific herring on the west coast of the continental United States. We assessed the health and viability of herring embryos from oiled and unoiled locations that were either deposited by natural spawning or incubated in subtidal cages. Three months after the spill, caged embryos at oiled sites showed sublethal cardiac toxicity, as expected from exposure to oil-derived polycyclic aromatic compounds (PACs). By contrast, embryos from the adjacent and shallower intertidal zone showed unexpectedly high rates of tissue necrosis and lethality unrelated to cardiotoxicity. No toxicity was observed in embryos from unoiled sites. Patterns of PACs at oiled sites were consistent with oil exposure against a background of urban sources, although tissue concentrations were lower than expected to cause lethality. Embryos sampled 2 y later from oiled sites showed modest sublethal cardiotoxicity but no elevated necrosis or mortality. Bunker oil contains the chemically uncharacterized remains of crude oil refinement, and one or more of these unidentified chemicals likely interacted with natural sunlight in the intertidal zone to kill herring embryos. This reveals an important discrepancy between the resolving power of current forensic analytical chemistry and biological responses of keystone ecological species in oiled habitats. Nevertheless, we successfully delineated the biological impacts of an oil spill in an urbanized coastal estuary with an overlapping backdrop of atmospheric, vessel, and land-based sources of PAC pollution.
    Proceedings of the National Academy of Sciences 12/2011; 109(2):E51-8. · 9.81 Impact Factor
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    ABSTRACT: A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or a wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from del/del carriers exhibited an 84% reduction in the rate of penetration of a hyaluronic acid gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in hyaluronic acid gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. Nevertheless, DEFB126 genotype and lectin binding were correlated with sperm performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent effect of impaired reproductive function, will allow a better understanding, clinical evaluation, and possibly treatment of human infertility.
    Science translational medicine 07/2011; 3(92):92ra65. · 10.76 Impact Factor
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    ABSTRACT: The fate and behavior of nanomaterials (NMs) in environmental media has important consequences for toxicity. The majority of aquatic research to date has focused on NM behavior in freshwater systems. However, pH and salinity differences of seawater affect dissolution and aggregation of NMs. In this study, physical characteristics of metal oxide NMs in seawater were linked with their toxicity to developing sea urchins. The metal oxide NMs TiO(2) and CeO(2) up to 10mg/L were not toxic to the embryos of the white sea urchin (Lytechinus pictus). In contrast, ZnO NM was highly toxic to these embryos (EC(50) = 99.5 μg/L). The toxicity of ZnO NM was not significantly different from bulk ZnO or soluble Zn(2+) (from ZnSO(4) · 7H(2)O), suggesting that the toxicity of ZnO NM can be attributed to soluble Zn(2+). Furthermore, solubility data indicate that at the concentrations used in our sea urchin embryo experiments, ZnO NM was rapidly and completely solubilized in seawater. The present study also demonstrated that Fe-doped NMs were less soluble in seawater compared to pure ZnO NMs, but there was no concomitant reduction in toxicity.
    Journal of hazardous materials 07/2011; 192(3):1565-71. · 4.14 Impact Factor
  • Ecotoxicology 03/2011; 20(5):937-9. · 2.77 Impact Factor
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    ABSTRACT: Previous studies have shown that engineered nanomaterials can be transferred from prey to predator, but the ecological impacts of this are mostly unknown. In particular, it is not known if these materials can be biomagnified-a process in which higher concentrations of materials accumulate in organisms higher up in the food chain. Here, we show that bare CdSe quantum dots that have accumulated in Pseudomonas aeruginosa bacteria can be transferred to and biomagnified in the Tetrahymena thermophila protozoa that prey on the bacteria. Cadmium concentrations in the protozoa predator were approximately five times higher than their bacterial prey. Quantum-dot-treated bacteria were differentially toxic to the protozoa, in that they inhibited their own digestion in the protozoan food vacuoles. Because the protozoa did not lyse, largely intact quantum dots remain available to higher trophic levels. The observed biomagnification from bacterial prey is significant because bacteria are at the base of environmental food webs. Our findings illustrate the potential for biomagnification as an ecological impact of nanomaterials.
    Nature Nanotechnology 01/2011; 6(1):65-71. · 31.17 Impact Factor
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    ABSTRACT: Sperm motility-initiating substance (SMIS), a novel motility inducer from newt egg-jelly, is activated by the release from associated jelly substances at the beginning of internal fertilization and affects female-stored sperm. We examined motility initiation kinetics of newt sperm in response to SMIS by monitoring the changes of sperm intracellular calcium ([Ca²(+)](i)). In quiescent non-motile sperm loaded with the Ca²(+) indicator Fluo-4, intracellular free Ca²(+) was observed around mitochondria using confocal scanning laser microscopy. A slight increase in [Ca²(+)](i) occurred simultaneously and transiently at motility initiation in sperm treated with either heated jelly extract (hJE) containing activated SMIS, or a low osmotic solution, which naturally initiates motility in externally-fertilizing amphibians and can initiate motility in urodele sperm. When the increase of [Ca²(+)](i) at motility-initiation was monitored using spectrofluorometry, large increases in [Ca²(+)](i) occurred immediately in the low osmotic solution and within 1.5 min in the hJE. In the intact jelly extract (no heating), small increases of [Ca²(+)](i) irregularly occurred from around 1 min and for about 4 min, during which motility was differentially initiated among sperm. These results indicate that the SMIS induces differential initiation of sperm motility depending on the activational states of the SMIS and its overall activity. The motility initiation in the jelly extract was delayed in sperm whose intracellular Ca²(+) had been chelated with BAPTA-AM. The relative levels of [Ca²(+)](i) were variable with a mean of 414 ± 256 nmol/L among resting sperm, suggesting that the level of [Ca²(+)](i) in the resting sperm modulates the responsiveness to the SMIS.
    Embryologia 01/2011; 53(1):9-17. · 2.21 Impact Factor
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    ABSTRACT: Protein 4.1R (4.1R) has been identified as the major component of the human erythrocyte membrane skeleton. The members of the protein 4.1 gene family are expressed in a tissue-specific alternative splicing manner that increases their functions in each tissue; however, the exact roles of cardiac 4.1R in the developing myocardium are poorly understood. In zebrafish (ZF), we identified two heart-specific 4.1R isoforms, ZF4.1RH2 and ZF4.1RH3, encoding N-terminal 30 kDa (FERM) domain and spectrin-actin binding domain (SABD) and C-terminal domain (CTD), separately. Applying immunohistochemistry using specific antibodies for 30 kDa domain and CTD separately, the gene product of ZF4.1RH2 and ZF4.1RH3 appeared only in the ventricle and in the atrium, respectively, in mature hearts. During embryogenesis, both gene expressions are expressed starting 24 h post-fertilization (hpf). Following whole-mount in situ hybridization, ZF4.1RH3 gene expression was detected in the atrium of 37 hpf embryos. These results indicate that the gene product of ZF4.1RH3 is essential for normal morphological shape of the developing heart and to support the repetitive cycles of its muscle contraction and relaxation.
    Embryologia 09/2010; 52(7):591-602. · 2.21 Impact Factor
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    ABSTRACT: A decrease in zinc (Zn) levels increases the production of cell oxidants, affects the oxidant defense system and triggers oxidant sensitive signals in neuronal cells. However, the underlying mechanisms are still unclear. This work tested the hypothesis that the increase in neuronal oxidants that occurs when cellular Zn decreases is mediated by the activation of the NMDA receptor. Differentiated PC12 cells were cultured in control, Zn-deficient or Zn-repleted media. The incubation in Zn deficient media led to a rapid increase in cellular calcium levels, which was prevented by a NMDA receptor antagonist (MK-801). Cellular calcium accumulation was associated with NADPH oxidase and nitric oxide synthase (NOS) activation, an increase in cell oxidant levels, and an associated activation of a redox-sensitive signal (AP-1). In cells incubated in the Zn deficient medium, NADPH oxidase activation was prevented by MK-801 and by a protein kinase C inhibitor. The rise in cell oxidants was prevented by inhibitors of NADPH oxidase, of the NOS and by MK-801. A similar pattern of inhibitor action was observed for zinc deficiency-induced AP-1 activation. Results demonstrate that a decrease in extracellular Zn leads to an increase in neuronal oxidants through the activation of the NMDAR that leads to calcium influx and to a calcium-mediated activation of protein kinase C/NADPH oxidase and NOS. Changes in extracellular Zn concentrations can be sensed by neurons, which using reactive oxygen and nitrogen species as second messengers, can regulate signaling involved in neuronal development and function.
    Free Radical Biology & Medicine 03/2010; 48(12):1577-87. · 5.27 Impact Factor
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    ABSTRACT: There is a pressing need for information on the mobility of nanoparticles in the complex aqueous matrices found in realistic environmental conditions. We dispersed three different metal oxide nanoparticles (TiO(2), ZnO and CeO(2)) in samples taken from eight different aqueous media associated with seawater, lagoon, river, and groundwater, and measured their electrophoretic mobility, state of aggregation, and rate of sedimentation. The electrophoretic mobility of the particles in a given aqueous media was dominated by the presence of natural organic matter (NOM) and ionic strength, and independent of pH. NOM adsorbed onto these nanoparticles significantly reduces their aggregation, stabilizing them under many conditions. The transition from reaction to diffusion limited aggregation occurs at an electrophoretic mobility from around -2 to -0.8 microm s(-1) V(-1) cm. These results are key for designing and interpreting nanoparticle ecotoxicity studies in various environmental conditions.
    Environmental Science and Technology 02/2010; 44(6):1962-7. · 5.26 Impact Factor

Publication Stats

2k Citations
340.41 Total Impact Points


  • 2013
    • University of North Carolina at Wilmington
      Wilmington, North Carolina, United States
  • 1984–2013
    • University of California, Davis
      • • Bodega Marine Laboratory
      • • Department of Environmental Toxicology
      • • Department of Obstetrics and Gynecology
      • • Department of Animal Science
      Davis, CA, United States
  • 2011
    • Yamagata University
      • Department of Biology
      Ямагата, Yamagata, Japan
  • 1986–2009
    • CSU Mentor
      Long Beach, California, United States
  • 2005
    • University of Washington Seattle
      • Department of Aquatic and Fishery Sciences
      Seattle, WA, United States
  • 1997–2003
    • Sonoma State University
      • Department of Biology
      Rohnert Park, CA, United States
  • 2002
    • St. Marianna University School of Medicine
      • Department of Medicine
      Kawasaki, Kanagawa-ken, Japan
  • 1994
    • University of California, Santa Cruz
      Santa Cruz, California, United States