Bay Paul Center for Comparative Molecular Biology and Evolution

East Falmouth, MA, United States

Bay Paul Center for Comparative Molecular Biology and Evolution

East Falmouth, MA, United States
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Gosse J.A.,University of Maine, United States | Taylor V.F.,Dartmouth College | Jackson B.P.,Dartmouth College | Hamilton J.W.,Bay Paul Center for Comparative Molecular Biology and Evolution | Hamilton J.W.,Brown University
Journal of Applied Toxicology | Year: 2014

Arsenic (As) is considered a top environmental chemical of human health because it has been linked to adverse health effects including cancer, diabetes, cardiovascular disease, and reproductive and developmental problems. In several cell culture and animal models, As acts as an endocrine disruptor, which may underlie many of its health effects. Previous work showed that steroid receptor (SR)-driven gene expression is disrupted in cells treated with inorganic As (arsenite, iAs+3). In those studies, low iAs+3 concentrations (0.1-0.7 μM) stimulated hormone-inducible transcription, whereas somewhat higher but still non-cytotoxic levels (1-3 μM) inhibited transcription. This investigation focuses on the mechanisms underlying these inhibitory effects and evaluates the role of methylated trivalent As metabolites on SR function. Recent evidence suggests that, compared with iAs, methylated forms may have distinct biochemical effects. Here, fluorescence polarization (FP) experiments utilizing purified, hormone-bound human glucocorticoid (GR) and progesterone receptor (PR) have demonstrated that neither inorganic (iAs+3) nor dimethylated (DMA+3) species of trivalent As affect receptor interactions with glucocorticoid DNA response elements (GREs). However, monomethylated forms (monomethylarsenite, MMA+3 and monomethylarsonic diglutathione, MADG) strongly inhibit GR-GRE and PR-GRE binding. Additionally, speciation studies of iAs+3-treated H4IIE rat hepatoma cells show that, under treatment conditions that cause inhibition of hormone-inducible gene transcription, the intracellular concentration of MADG is sufficient to inhibit GR-GRE and PR-GRE interactions in vivo. These results indicate that arsenic's inhibitory endocrine disruption effects are probably caused in part by methylated metabolites' disruption of SR ability to bind DNA response elements that are crucial to hormone-driven gene transcription. © 2013 John Wiley & Sons, Ltd.


Zandbergen F.,Bay Paul Center for Comparative Molecular Biology and Evolution | Jackson B.P.,Dartmouth College | Hamilton J.W.,Bay Paul Center for Comparative Molecular Biology and Evolution
PLoS ONE | Year: 2012

Background: Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). Methodology and Findings: C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Conclusions/Significance: Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations. © 2012 Kozul-Horvath et al.


Mackey K.R.M.,Woods Hole Oceanographic Institution | Mackey K.R.M.,Bay Paul Center for Comparative Molecular Biology and Evolution | Mackey K.R.M.,University of California at Irvine | Post A.F.,Bay Paul Center for Comparative Molecular Biology and Evolution | And 5 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Marine Synechococcus are some of the most diverse and ubiquitous phytoplankton, and iron (Fe) is an essential micronutrient that limits productivity in many parts of the ocean. To investigate how coastal and oceanic Atlantic Synechococcus strains acclimate to Fe availability, we compared the growth, photophysiology, and quantitative proteomics of two Synechococcus strains from different Fe regimes. Synechococcus strain WH8102, from a region in the southern Sargasso Sea that receives substantial dust deposition, showed impaired growth and photophysiology as Fe declined, yet used few acclimation responses. Coastal WH8020, from the dynamic, seasonally variable New England shelf, displayed a multitiered, hierarchical cascade of acclimation responses with different Fe thresholds. The multitiered response included changes in Fe acquisition, storage, and photosynthetic proteins, substitution of flavodoxin for ferredoxin, and modified photophysiology, all while maintaining remarkably stable growth rates over a range of Fe concentrations. Modulation of two distinct ferric uptake regulator (Fur) proteins that coincided with the multitiered proteome response was found, implying the coastal strain has different regulatory threshold responses to low Fe availability. Low nitrogen (N) and phosphorus (P) availability in the open ocean may favor the loss of Fe response genes when Fe availability is consistent over time, whereas these genes are retained in dynamic environments where Fe availability fluctuates and N and P are more abundant.


PubMed | Bay Paul Center for Comparative Molecular Biology and Evolution, University of Southern California, Woods Hole Oceanographic Institution and Old Dominion University
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Marine Synechococcus are some of the most diverse and ubiquitous phytoplankton, and iron (Fe) is an essential micronutrient that limits productivity in many parts of the ocean. To investigate how coastal and oceanic Atlantic Synechococcus strains acclimate to Fe availability, we compared the growth, photophysiology, and quantitative proteomics of two Synechococcus strains from different Fe regimes. Synechococcus strain WH8102, from a region in the southern Sargasso Sea that receives substantial dust deposition, showed impaired growth and photophysiology as Fe declined, yet used few acclimation responses. Coastal WH8020, from the dynamic, seasonally variable New England shelf, displayed a multitiered, hierarchical cascade of acclimation responses with different Fe thresholds. The multitiered response included changes in Fe acquisition, storage, and photosynthetic proteins, substitution of flavodoxin for ferredoxin, and modified photophysiology, all while maintaining remarkably stable growth rates over a range of Fe concentrations. Modulation of two distinct ferric uptake regulator (Fur) proteins that coincided with the multitiered proteome response was found, implying the coastal strain has different regulatory threshold responses to low Fe availability. Low nitrogen (N) and phosphorus (P) availability in the open ocean may favor the loss of Fe response genes when Fe availability is consistent over time, whereas these genes are retained in dynamic environments where Fe availability fluctuates and N and P are more abundant.


Jebbett N.J.,University of Vermont | Hamilton J.W.,Bay Paul Center for Comparative Molecular Biology and Evolution | Rand M.D.,University of Vermont | Eckenstein F.,University of Vermont
NeuroToxicology | Year: 2013

Although many previous investigations have studied how mercury compounds cause cell death, sub-cytotoxic levels may affect mechanisms essential for the proper development of the nervous system. The present study investigates whether low doses of methylmercury (MeHg) and mercury chloride (HgCl2) can modulate the activity of JAK/STAT signaling, a pathway that promotes gliogenesis. We report that sub-cytotoxic doses of MeHg enhance ciliary neurotrophic factor (CNTF) evoked STAT3 phosphorylation in human SH-SY5Y neuroblastoma and mouse cortical neural progenitor cells (NPCs). This effect is specific for MeHg, since HgCl2 fails to enhance JAK/STAT signaling. Exposing NPCs to these low doses of MeHg (30-300nM) enhances CNTF-induced expression of STAT3-target genes such as glial fibrillary acidic protein (GFAP) and suppressors of cytokine signaling 3 (SOCS3), and increases the proportion of cells expressing GFAP following 2 days of differentiation. Higher, near-cytotoxic concentrations of MeHg and HgCl2 inhibit STAT3 phosphorylation and lead to increased production of superoxide. Lower concentrations of MeHg effective in enhancing JAK/STAT signaling (30nM) do not result in a detectable increase in superoxide nor increased expression of the oxidant-responsive genes, heme oxygenase 1, heat shock protein A5 and sirtuin 1. These findings suggest that low concentrations of MeHg inappropriately enhance STAT3 phosphorylation and glial differentiation, and that the mechanism causing this enhancement is distinct from the reactive oxygen species-associated cell death observed at higher concentrations of MeHg and HgCl2. © 2013.


Cusack D.F.,University of California at Los Angeles | Axsen J.,Simon Fraser University | Shwom R.,Rutgers University | Hartzell-Nichols L.,University of Washington | And 3 more authors.
Frontiers in Ecology and the Environment | Year: 2014

Mitigating further anthropogenic changes to the global climate will require reducing greenhouse-gas emissions ("abatement"), or else removing carbon dioxide from the atmosphere and/or diminishing solar input ("climate engineering"). Here, we develop and apply criteria to measure technical, economic, ecological, institutional, and ethical dimensions of, and public acceptance for, climate engineering strategies; provide a relative rating for each dimension; and offer a new interdisciplinary framework for comparing abatement and climate engineering options. While abatement remains the most desirable policy, certain climate engineering strategies, including forest and soil management for carbon sequestration, merit broad-scale application. Other proposed strategies, such as biochar production and geological carbon capture and storage, are rated somewhat lower, but deserve further research and development. Iron fertilization of the oceans and solar radiation management, although cost-effective, received the lowest ratings on most criteria. We conclude that although abatement should remain the central climate-change response, some low-risk, cost-effective climate engineering approaches should be applied as complements. The framework presented here aims to guide and prioritize further research and analysis, leading to improvements in climate engineering strategies. © The Ecological Society of America.


Mackey K.R.M.,Bay Paul Center for Comparative Molecular Biology and Evolution | Mackey K.R.M.,University of California at Santa Cruz | Mackey K.R.M.,Woods Hole Oceanographic Institution | Paytan A.,University of California at Santa Cruz | And 7 more authors.
Plant Physiology | Year: 2013

In this study, we develop a mechanistic understanding of how temperature affects growth and photosynthesis in 10 geographically and physiologically diverse strains of Synechococcus spp. We found that Synechococcus spp. are able to regulate photochemistry over a range of temperatures by using state transitions and altering the abundance of photosynthetic proteins. These strategies minimize photosystem II (PSII) photodamage by keeping the photosynthetic electron transport chain (ETC), and hence PSII reaction centers, more oxidized. At temperatures that approach the optimal growth temperature of each strain when cellular demand for reduced nicotinamide adenine dinucleotide phosphate (NADPH) is greatest, the phycobilisome (PBS) antenna associates with PSII, increasing the flux of electrons into the ETC. By contrast, under low temperature, when slow growth lowers the demand for NADPH and linear ETC declines, the PBS associates with photosystem I. This favors oxidation of PSII and potential increase in cyclic electron flow. For Synechococcus sp. WH8102, growth at higher temperatures led to an increase in the abundance of PBS pigment proteins, as well as higher abundance of subunits of the PSII, photosystem I, and cytochrome b6f complexes. This would allow cells to increase photosynthetic electron flux to meet the metabolic requirement for NADPH during rapid growth. These PBS-based temperature acclimation strategies may underlie the larger geographic range of this group relative to Prochlorococcus spp., which lack a PBS. © 2013 American Society of Plant Biologists. All Rights Reserved.


Mackey K.R.M.,University of California at Santa Cruz | Mackey K.R.M.,Woods Hole Oceanographic Institution | Mackey K.R.M.,Bay Paul Center for Comparative Molecular Biology and Evolution | Buck K.N.,Bermuda Institute of Ocean Sciences | And 6 more authors.
Frontiers in Microbiology | Year: 2012

This study investigated the impact of atmospheric metal deposition on natural phytoplank- ton communities at open-ocean and coastal sites in the Sargasso Sea during the spring bloom. Locally collected aerosols with different metal contents were added to natural phytoplankton assemblages from each site, and changes in nitrate, dissolved metal con- centration, and phytoplankton abundance and carbon content were monitored. Addition of aerosol doubled the concentrations of cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), and nickel (Ni) in the incubation water. Over the 3-day experiments, greater drawdown of dissolved metals occurred in the open ocean water, whereas little metal drawdown occurred in the coastal water. Two populations of picoeukaryotic algae and Synechococcus grew in response to aerosol additions in both experiments. Particulate organic carbon increased and was most sensitive to changes in picoeukaryote abundance. Phytoplankton community composition differed depending on the chemistry of the aerosol added. Enrichment with aerosol that had higher metal content led to a 10-fold increase in Synechococcus abundance in the oceanic experiment but not in the coastal experi- ment. Enrichment of aerosol-derived Co, Mn, and Ni were particularly enhanced in the oceanic experiment, suggesting the Synechococcus population may have been fertilized by these aerosol metals. Cu-binding ligand concentrations were in excess of dissolved Cu2in+ both experiments, and increased with aerosol additions. Bioavailable free hydrated Cu concentrations were below toxicity thresholds throughout both experiments.These experiments show (1) atmospheric deposition contributes biologically important metals to seawater, (2)thesemetalsareconsumedovertimescalescommensuratewithcellgrowth, and (3) growth responses can differ between distinct Synechococcus or eukaryotic algal populations despite their relatively close geographic proximity and taxonomic similarity. © 2012 Mackey, Buck, Casey, Cid, Lomas, Sohrin and Paytan.


Kamennaya N.A.,Hebrew University of Jerusalem | Post A.F.,Bay Paul Center for Comparative Molecular Biology and Evolution
Applied and Environmental Microbiology | Year: 2011

Cyanobacteria of the genera Synechococcus and Prochlorococcus are the most abundant photosynthetic organisms on earth, occupying a key position at the base of marine food webs. The cynS gene that encodes cyanase was identified among bacterial, fungal, and plant sequences in public databases, and the gene was particularly prevalent among cyanobacteria, including numerous Prochlorococcus and Synechococcus strains. Phylogenetic analysis of cynS sequences retrieved from the Global Ocean Survey database identified >60% as belonging to unicellular marine cyanobacteria, suggesting an important role for cyanase in their nitrogen metabolism. We demonstrate here that marine cyanobacteria have a functionally active cyanase, the transcriptional regulation of which varies among strains and reflects the genomic context of cynS. In Prochlorococcus sp. strain MED4, cynS was presumably transcribed as part of the cynABDS operon, implying cyanase involvement in cyanate utilization. In Synechococcus sp. strain WH8102, expression was not related to nitrogen stress responses and here cyanase presumably serves in the detoxification of cyanate resulting from intracellular urea and/or carbamoyl phosphate decomposition. Lastly, we report on a cyanase activity encoded by cynH, a novel gene found in marine cyanobacteria only. The presence of dual cyanase genes in the genomes of seven marine Synechococcus strains and their respective roles in nitrogen metabolism remain to be clarified. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Parfrey L.W.,University of Massachusetts Amherst | Grant J.,Lane College | Tekle Y.I.,Lane College | Tekle Y.I.,Yale University | And 7 more authors.
Systematic Biology | Year: 2010

An accurate reconstruction of the eukaryotic tree of life is essential to identify the innovations underlying the diversity of microbial and macroscopic (e.g., plants and animals) eukaryotes. Previous work has divided eukaryotic diversity into a small number of high-level "supergroups," many of which receive strong support in phylogenomic analyses. However, the abundance of data in phylogenomic analyses can lead to highly supported but incorrect relationships due to systematic phylogenetic error. Furthermore, the paucity of major eukaryotic lineages (19 or fewer) included in these genomic studies may exaggerate systematic error and reduce power to evaluate hypotheses. Here, we use a taxon-rich strategy to assess eukaryotic relationships. We show that analyses emphasizing broad taxonomic sampling (up to 451 taxa representing 72 major lineages) combined with a moderate number of genes yield a well-resolved eukaryotic tree of life. The consistency across analyses with varying numbers of taxa (88-451) and levels of missing data (17-69%) supports the accuracy of the resulting topologies. The resulting stable topology emerges without the removal of rapidly evolving genes or taxa, a practice common to phylogenomic analyses. Several major groups are stable and strongly supported in these analyses (e.g., SAR, Rhizaria, Excavata), whereas the proposed supergroup " Chromalveolata" is rejected. Furthermore, extensive instability among photosynthetic lineages suggests the presence of systematic biases including endosymbiotic gene transfer from symbiont (nucleus or plastid) to host. Our analyses demonstrate that stable topologies of ancient evolutionary relationships can be achieved with broad taxonomic sampling and a moderate number of genes. Finally, taxon-rich analyses such as presented here provide a method for testing the accuracy of relationships that receive high bootstrap support (BS) in phylogenomic analyses and enable placement of the multitude of lineages that lack genome scale data. © 2010 The Author(s).

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