171 research outputs found
Short Term Effects of Hurricane Irma and Cyanobacterial Blooms On Ammonium Cycling Along a Freshwater-Estuarine Continuum In South Florida
Lacustrine and coastal systems are vulnerable to the increasing number and intensity of tropical storms driven by climate change. Strong winds associated with tropical storms can mobilize nutrients in sediments and alter nitrogen and phosphorus cycling, leading to amplification of preexisting conditions, such as eutrophication and cyanobacterial blooms (cyanoHABs). In 2016, Florida declared a State of Emergency within and downstream of Lake Okeechobee (LO) due to toxic cyanobacterial blooms (primarily Microcystis). The blooms originated in LO, but flood control measures released water from LO to the brackish St. Lucie Estuary (SLE). In September 2017, Hurricane Irma traversed the Florida peninsula with sustained winds exceeding 160 km h–1, generating torrential rains over the watershed. We quantified ammonium (NH4+) regeneration and potential uptake rates, and Microcystis toxin gene (mcyD) abundance in LO and SLE during the massive bloom in July 2016, the bloom in August 2017 (2 weeks before Irma), and 10 days after Hurricane Irma landfall. In 2016, cyanoHABs were present in both LO and SLE, and potential NH4+ uptake rates were high in both systems. In 2017, the bloom was constrained to LO, potential NH4+ uptake rates in LO exceeded those in SLE, and mcyD gene abundance was greater in LO than SLE. Post Hurricane Irma, potential NH4+ uptake rates decreased significantly in LO and SLE, while mcyD gene abundance decreased in LO and increased slightly in SLE. Average NH4+ regeneration rates could support 25–40% of water column potential NH4+ demand in the lake and, when extrapolated to the entire LO water column, exceeded external nitrogen loading. These results emphasize the importance of internal NH4+ recycling for bloom expansion and toxicity in the lake and downstream estuaries. In 2018, the cyanobacterial bloom in the Okeechobee region was one of the largest recorded and is presumed to be driven by the aftermath of Hurricane Irma. Large-scale blooms have also been observed in SLE, likely due to LO flushing and decreased salinity post-hurricane. Thus, results from this study support predictions that increased frequency and strength of tropical storms will lead to more intense blooms in aquatic systems
Mathematical analysis of the regulation of competing methyltransferases
Background
Methyltransferase (MT) reactions, in which methyl groups are attached to substrates, are fundamental to many aspects of cell biology and human physiology. The universal methyl donor for these reactions is S-adenosylmethionine (SAM) and this presents the cell with an important regulatory problem. If the flux along one pathway is changed then the SAM concentration will change affecting all the other MT pathways, so it is difficult for the cell to regulate the pathways independently.
Methods
We created a mathematical model, based on the known biochemistry of the folate and methionine cycles, to study the regulatory mechanisms that enable the cell to overcome this difficulty. Some of the primary mechanisms are long-range allosteric interactions by which substrates in one part of the biochemical network affect the activity of enzymes at distant locations in the network (not distant in the cell). Because of these long-range allosteric interactions, the dynamic behavior of the network is very complicated, and so mathematical modeling is a useful tool for investigating the effects of the regulatory mechanisms and understanding the complicated underlying biochemistry and cell biology.
Results
We study the allosteric binding of 5-methyltetrahydrofolate (5mTHF) to glycine-N-methyltransferase (GNMT) and explain why data in the literature implies that when one molecule binds, GNMT retains half its activity. Using the model, we quantify the effects of different regulatory mechanisms and show how cell processes would be different if the regulatory mechanisms were eliminated. In addition, we use the model to interpret and understand data from studies in the literature. Finally, we explain why a full understanding of how competing MTs are regulated is important for designing intervention strategies to improve human health.
Conclusions
We give strong computational evidence that once bound GNMT retains half its activity. The long-range allosteric interactions enable the cell to regulate the MT reactions somewhat independently. The low K m values of many MTs also play a role because the reactions then run near saturation and changes in SAM have little effect. Finally, the inhibition of the MTs by the product S-adenosylhomocysteine also stabilizes reaction rates against changes in SAM
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Mathematical modeling of the effects of glutathione on arsenic methylation
Background: Arsenic is a major environmental toxin that is detoxified in the liver by biochemical mechanisms that are still under study. In the traditional metabolic pathway, arsenic undergoes two methylation reactions, each followed by a reduction, after which it is exported and released in the urine. Recent experiments show that glutathione plays an important role in arsenic detoxification and an alternative biochemical pathway has been proposed in which arsenic is first conjugated by glutathione after which the conjugates are methylated. In addition, in rats arsenic-glutathione conjugates can be exported into the plasma and removed by the liver in the bile. Methods: We have developed a mathematical model for arsenic biochemistry that includes three mechanisms by which glutathione affects arsenic methylation: glutathione increases the speed of the reduction steps; glutathione affects the activity of arsenic methyltranferase; glutathione sequesters inorganic arsenic and its methylated downstream products. The model is based as much as possible on the known biochemistry of arsenic methylation derived from cellular and experimental studies. Results: We show that the model predicts and helps explain recent experimental data on the effects of glutathione on arsenic methylation. We explain why the experimental data imply that monomethyl arsonic acid inhibits the second methylation step. The model predicts time course data from recent experimental studies. We explain why increasing glutathione when it is low increases arsenic methylation and that at very high concentrations increasing glutathione decreases methylation. We explain why the possible temporal variation of the glutathione concentration affects the interpretation of experimental studies that last hours. Conclusions: The mathematical model aids in the interpretation of data from recent experimental studies and shows that the Challenger pathway of arsenic methylation, supplemented by the glutathione effects described above, is sufficient to understand and predict recent experimental data. More experimental studies are needed to explicate the detailed mechanisms of action of glutathione on arsenic methylation. Recent experimental work on the effects of glutathione on arsenic methylation and our modeling study suggest that supplements that increase hepatic glutathione production should be considered as strategies to reduce adverse health effects in affected populations
Multisector Dynamics: Advancing the Science of Complex Adaptive Human-Earth Systems
The field of MultiSector Dynamics (MSD) explores the dynamics and co-evolutionary pathways of human and Earth systems with a focus on critical goods, services, and amenities delivered to people through interdependent sectors. This commentary lays out core definitions and concepts, identifies MSD science questions in the context of the current state of knowledge, and describes ongoing activities to expand capacities for open science, leverage revolutions in data and computing, and grow and diversify the MSD workforce. Central to our vision is the ambition of advancing the next generation of complex adaptive human-Earth systems science to better address interconnected risks, increase resilience, and improve sustainability. This will require convergent research and the integration of ideas and methods from multiple disciplines. Understanding the tradeoffs, synergies, and complexities that exist in coupled human-Earth systems is particularly important in the context of energy transitions and increased future shocks
Mathematical model insights into arsenic detoxification
<p>Abstract</p> <p>Background</p> <p>Arsenic in drinking water, a major health hazard to millions of people in South and East Asia and in other parts of the world, is ingested primarily as trivalent inorganic arsenic (iAs), which then undergoes hepatic methylation to methylarsonic acid (MMAs) and a second methylation to dimethylarsinic acid (DMAs). Although MMAs and DMAs are also known to be toxic, DMAs is more easily excreted in the urine and therefore methylation has generally been considered a detoxification pathway. A collaborative modeling project between epidemiologists, biologists, and mathematicians has the purpose of explaining existing data on methylation in human studies in Bangladesh and also testing, by mathematical modeling, effects of nutritional supplements that could increase As methylation.</p> <p>Methods</p> <p>We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects.</p> <p>Results</p> <p>We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic methyltransferase has been upregulated by a factor of two in this population. Finally, we also show that a modification of the model gives excellent fits to the data on arsenic metabolism in human cultured hepatocytes.</p> <p>Conclusions</p> <p>The analysis of the Bangladesh data using the model suggests that folate supplementation may be more effective at reducing whole body arsenic than previously expected. There is almost no data on the upregulation of arsenic methyltransferase in populations chronically exposed to arsenic. Our model predicts upregulation by a factor of two in the Bangladesh population studied. This prediction should be verified since it could have important public health consequences both for treatment strategies and for setting appropriate limits on arsenic in drinking water. Our model has compartments for the binding of arsenicals to proteins inside of cells and we show that these comparments are necessary to obtain good fits to data. Protein-binding of arsenicals should be explored in future biochemical studies.</p
Influence of Grain Boundary Character on Creep Void Formation in Alloy 617
Alloy 617, a high temperature creep-resistant, nickel-based alloy, is being considered for the primary heat exchanger for the Next Generation Nuclear Plant (NGNP) which will operate at temperatures exceeding 760oC. Orientation imaging microscopy (OIM) is used to characterize the grain boundaries in the vicinity of creep voids that develop during high temperature creep tests (800-1000oC at creep stresses ranging from 20-85 MPa) terminated at creep strains ranging from 5-40%. Observations using optical microscopy indicate creep rate does not significantly influence the creep void fraction at a given creep strain. Preliminary analysis of the OIM data indicates voids tend to form on grain boundaries parallel, perpendicular or 45o to the tensile axis, while few voids are found at intermediate inclinations to the tensile axis. Random grain boundaries intersect most voids while CSL-related grain boundaries did not appear to be consistently associated with void development
The Atacama Cosmology Telescope: Cosmological parameters from three seasons of data
We present constraints on cosmological and astrophysical parameters from
high-resolution microwave background maps at 148 GHz and 218 GHz made by the
Atacama Cosmology Telescope (ACT) in three seasons of observations from 2008 to
2010. A model of primary cosmological and secondary foreground parameters is
fit to the map power spectra and lensing deflection power spectrum, including
contributions from both the thermal Sunyaev-Zeldovich (tSZ) effect and the
kinematic Sunyaev-Zeldovich (kSZ) effect, Poisson and correlated anisotropy
from unresolved infrared sources, radio sources, and the correlation between
the tSZ effect and infrared sources. The power ell^2 C_ell/2pi of the thermal
SZ power spectrum at 148 GHz is measured to be 3.4 +\- 1.4 muK^2 at ell=3000,
while the corresponding amplitude of the kinematic SZ power spectrum has a 95%
confidence level upper limit of 8.6 muK^2. Combining ACT power spectra with the
WMAP 7-year temperature and polarization power spectra, we find excellent
consistency with the LCDM model. We constrain the number of effective
relativistic degrees of freedom in the early universe to be Neff=2.79 +\- 0.56,
in agreement with the canonical value of Neff=3.046 for three massless
neutrinos. We constrain the sum of the neutrino masses to be Sigma m_nu < 0.39
eV at 95% confidence when combining ACT and WMAP 7-year data with BAO and
Hubble constant measurements. We constrain the amount of primordial helium to
be Yp = 0.225 +\- 0.034, and measure no variation in the fine structure
constant alpha since recombination, with alpha/alpha0 = 1.004 +/- 0.005. We
also find no evidence for any running of the scalar spectral index, dns/dlnk =
-0.004 +\- 0.012.Comment: 26 pages, 22 figures. This paper is a companion to Das et al. (2013)
and Dunkley et al. (2013). Matches published JCAP versio
The genomes of two key bumblebee species with primitive eusocial organization
Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation
Providing baseline data for conservation–Heart rate monitoring in captive scimitar-horned oryx
Heart rate biologging has been successfully used to study wildlife responses to natural and human-caused stressors (e.g., hunting, landscape of fear). Although rarely deployed to inform conservation, heart rate biologging may be particularly valuable for assessing success in wildlife reintroductions. We conducted a case study for testing and validating the use of subcutaneous heart rate monitors in eight captive scimitar-horned oryx (Oryx dammah), a once-extinct species that is currently being restored to the wild. We evaluated biologger safety and accuracy while collecting long-term baseline data and assessing factors explaining variation in heart rate. None of the biologgers were rejected after implantation, with successful data capture for 16–21 months. Heart rate detection accuracy was high (83%–99%) for six of the individuals with left lateral placement of the biologgers. We excluded data from two individuals with a right lateral placement because accuracies were below 60%. Average heart rate for the six scimitar-horned oryx was 60.3 ± 12.7 bpm, and varied by about 12 bpm between individuals, with a minimum of 31 bpm and a maximum of 188 bpm across individuals. Scimitar-horned oryx displayed distinct circadian rhythms in heart rate and activity. Heart rate and activity were low early in the morning and peaked near dusk. Circadian rhythm in heart rate and activity were relatively unchanged across season, but hourly averages for heart rate and activity were higher in spring and summer, respectively. Variation in hourly heart rate averages was best explained by a combination of activity, hour, astronomical season, ambient temperature, and an interaction term for hour and season. Increases in activity appeared to result in the largest changes in heart rate. We concluded that biologgers are safe and accurate and can be deployed in free-ranging and reintroduced scimitar-horned oryx. In addition to current monitoring practices of reintroduced scimitar-horned oryx, the resulting biologging data could significantly aid in 1) evaluating care and management action prior to release, 2) characterizing different animal personalities and how these might affect reintroduction outcomes for individual animals, and 3) identifying stressors after release to determine their timing, duration, and impact on released animals. Heart rate monitoring in released scimitar-horned oryx may also aid in advancing our knowledge about how desert ungulates adapt to extreme environmental variation in their habitats (e.g., heat, drought)
STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+T cell dysregulation and accumulation
The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co -exist-ing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8+ T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. STAT3 GOF mutations drove the accumulation of effector CD8+ T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. This subset also expressed genes for granzymes, perforin, interferon-y, and Ccl5/Rantes and required NKG2D and the IL-15/IL-2 receptor IL2RB for maximal accumula-tion. Leukocyte-restricted STAT3 GOF was sufficient and CD8+ T cells were essential for lethal pathology in mice. These results demonstrate that STAT3 GOF mutations cause effector CD8+ T cell oligoclonal accumu-lation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.Peer reviewe
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