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At least 685 records · Page 38

Distribution, lipid-bilayer affinity and kinetics of the metabolic effects of dinoseb in the liver

Dinoseb is a highly toxic pesticide of the dinitrophenol group. Its use has been restricted, but it can still be found in soils and waters in addition to being a component of related pesticides that, after ingestion by humans or animals, can originate the compound by enzymatic hydrolysis. As most dinitrophenols, dinoseb uncouples oxidative phosphorylation. In this study, distribution, lipid bilayer affinity and kinetics of the metabolic effects of dinoseb were investigated, using mainly the isolated perfused rat liver, but also isolated mitochondria and molecular dynamics simulations. Dinoseb presented high affinity for the hydrophobic region of the lipid bilayers, with a partition coefficient of 3.75 × 10{sup 4} between the hydrophobic and hydrophilic phases. Due to this high affinity for the cellular membranes dinoseb underwent flow-limited distribution in the liver. Transformation was slow but uptake into the liver space was very pronounced. For an extracellular concentration of 10 μM, the equilibrium intracellular concentration was equal to 438.7 μM. In general dinoseb stimulated catabolism and inhibited anabolism. Half-maximal stimulation of oxygen uptake in the whole liver occurred at concentrations (2.8–5.8 μM) at least ten times above those in isolated mitochondria (0.28 μM). Gluconeogenesis and ureagenesis were half-maximally inhibited at concentrations between 3.04 and 5.97 μM. The ATP levels were diminished, but differently in livers from fed and fasted rats. Dinoseb disrupts metabolism in a complex way at concentrations well above its uncoupling action in isolated mitochondria, but still at concentrations that are low enough to be dangerous to animals and humans even at sub-lethal doses. - Highlights: • Dinoseb presents high affinity for the hydrophobic region of the lipid bilayers. • Its cellular concentration may exceed the extracellular one by a factor of 43.9. • One order of magnitude separates the active concentrations in mitochondria and liver. • Hepatic metabolism is disrupted in the concentration range up to 10 μM.

60 APPLIED LIFE SCIENCES↗

Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations

Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of > 99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. - Highlights: • PBPK modeling and Monte Carlo analysis applied to evaluate historic PFOA exposure. • In vitro to in vivo extrapolation informed description of PFOA transport in kidney. • Model predicted large range of serum PFOA concentrations in two communities. • Variation in serum concentrations may be due to historic non-drinking water exposure.

60 APPLIED LIFE SCIENCES↗

Exosomes secreted from mesenchymal stem cells mediate the regeneration of endothelial cells treated with rapamycin by delivering pro-angiogenic microRNAs

Highlights: • MSC-derived exosomes play an important role in promoting endothelial regeneration treated with rapamycin in vitro. • A distinct class of exosomal miRNAs is identified to be tightly related to endothelial regeneration. • The therapeutic effects of MSC-exosomes may be ascribed to the delivery of pro-angiogenic miRNAs to endothelial cells. • MSC-exosomes may serve as a cell-free therapy for clinical treatment of delayed endothelial healing after DES implantation. Delayed endothelial healing after drug eluting stent (DES) implantation is a critical clinical problem in treatment of coronary artery diseases. Exosomes exhibit proangiogenic potential in a variety of ischemic diseases. However, the association of exosomes with endothelial regeneration after DES implantation has been rarely reported. In this study, we aimed to investigate the therapeutic effects of mesenchymal stem cell (MSC)-derived exosomes on endothelial cells treated with rapamycin and explore the potential mechanisms of MSC-derived exosomes in promoting endothelial regeneration. Exosomes were isolated from MSCs by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot assay. The in vitro effects of MSC-derived exosomes on the proliferation and migration of endothelial cells treated with rapamycin were evaluated by integrated experiment, cell counting kit-8, scratch, tube formation, and transwell assays. And the apoptosis of rapamycin-induced endothelial cells loaded with MSC-derived exosomes was detected using TUNEL and Annexin-V FITC and PI double-staining assays. The microRNA (miRNA) cargo of MSC-derived exosomes was identified by high-throughput RNA sequencing. Pro-angiogenic miRNAs and key pathways were further characterized. Our results indicated that MSC-derived exosomes could be ingested into umbilical vein endothelial cells (HUVECs) and significantly enhanced cell proliferation rate, migratory and tube-forming capabilities in vitro. MSC-derived exosomes also inhibited the apoptosis of HUVECs induced by rapamycin. A distinct class of exosomal miRNAs was further identified, including six miRNAs tightly related to neovasculogenesis. Silencing the expression of exosomal miRNA-21–5p and let-7c-5p attenuated the pro-proliferative and pro-migratory capacity of MSC-derived exosomes. Moreover, functional enrichment analysis indicated that metabolic pathways might contribute to reendothelialization. This study highlights a proregenerative effect of MSC-derived exosomes in vitro, which may be partly explained by the delivery of pro-angiogenic miRNAs to endothelial cells.

60 APPLIED LIFE SCIENCES↗

Protein Data Bank (PDB): Fifty-three years young and having a transformative impact on science and society

This review article describes the co-evolution of structural biology as a discipline and the Protein Data Bank (PDB), established in 1971 as the first open-access data resource in biology by like-minded structural scientists. As the PDB archive grew in size and scope to encompass macromolecular crystallography, NMR spectroscopy, and cryo-electron microscopy, new technologies were developed to ingest, validate, curate, store, and distribute the information. Community engagement ensured that the needs of structural biologists (data depositors) and data consumers were met. Today, the archive houses more than 230,000 experimentally determined structures of proteins, nucleic acids, and macromolecular machines and their complexes with one another and small-molecule ligands. Aggregate costs of PDB data preservation are ~1% of the cost of structure determination. The enormous impact of PDB data on basic and applied research and education across the natural and medical sciences is presented and highlighted with illustrative examples. Enablement of de novo protein structure prediction (AlphaFold2, RoseTTAfold, OpenFold, etc.) is the most widely appreciated benefit of having a corpus of rigorously validated, expertly curated 3D biostructure data.

bioinformatics↗

Correlated SEM, FIB-SEM, TEM, and NanoSIMS Imaging of Microbes from the Hindgut of a Lower Termite: Methods for In Situ Functional and Ecological Studies of Uncultivable Microbes

The hindguts of lower termites harbor highly diverse, endemic communities of symbiotic protists, bacteria, and archaea essential to the termite's ability to digest wood. Despite over a century of experimental studies, ecological roles of many of these microbes are unknown, partly because almost none can be cultivated. Many of the protists associate with bacterial symbionts, but hypotheses for their respective roles in nutrient exchange are based on genomes of only two such bacteria. To show how the ecological roles of protists and nutrient transfer with symbiotic bacteria can be elucidated by direct imaging, we combined stable isotope labeling ( 13 C-cellulose) of live termites with analysis of fixed hindgut microbes using correlated scanning electron microscopy, focused ion beam-scanning electron microscopy (FIB-SEM), transmission electron microscopy, and high resolution imaging mass spectrometry (NanoSIMS). We developed methods to prepare whole labeled cells on solid substrates, whole labeled cells milled with a FIB-SEM instrument to reveal cell interiors, and ultramicrotome sections of labeled cells for NanoSIMS imaging of 13 C enrichment in protists and associated bacteria. Our results show these methods have the potential to provide direct evidence for nutrient flow and suggest the oxymonad protist Oxymonas dimorpha phagocytoses and enzymatically degrades ingested wood fragments, and may transfer carbon derived from this to its surface bacterial symbionts.

59 BASIC BIOLOGICAL SCIENCES↗

Polydiketoenamines for a Circular Plastics Economy

The mismanagement and leakage of plastic waste into the environment are failures of modern society. Once in the environment, plastic waste degrades into microplastics on a time scale dependent on the resin chemistry and the associated biotic or abiotic process. Here, the high surface area of microplastics results in the contamination of ecosystems through the leaching of toxic chemicals compounded with plastics during manufacturing. In addition, the small size of microplastics increases the likelihood that they will be inhaled or ingested, which has led to the bioaccumulation of microplastics with documented harm. Furthermore, microplastics are more readily aerosolized and distributed by weather systems to areas remote from locations where plastic waste has been mismanaged. Consequently, the carbon cycle must now account for plastic waste discharge, degradation, and dispersal in the environment after the end of useful life on a global scale.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Naphthalene-DNA Adduct Formation in a Lung Airway Explant Model: The Role of Bioactivation and Naphthalene Metabolites

Humans are widely exposed to naphthalene. Once inhaled or ingested, naphthalene is metabolized by cytochrome P450 and other enzymes to form toxic metabolites known to harm lung epithelial cells. Naphthalene metabolites circulate in the blood. Chronic naphthalene inhalation promotes lesions in the epithelium of the mouse lung and rat nose. Oral naphthalene exposure leads to DNA adduct formation in mouse lung, but the contributions of different enzymatic pathways and the metabolites they generate are not fully understood. This study explores the influence of naphthalene metabolites on DNA adduct formation in the lungs of two species (mice and primates). To isolate the lung response, conducting airway explants containing Club cells, a target for pulmonary naphthalene toxicity, were microdissected from live lung tissue and incubated with 14 C-naphthalene or its metabolites: 14 C-1,2-naphthoquinone or 14 C-naphthalene-1,2-dihydrodiol. Explants were incubated for 1 h, then processed immediately (T1), or were transferred to clean media for the remainder of the 24 h (T24), to monitor 14 C in DNA over time. Accelerator mass spectrometry analysis revealed the formation of DNA adducts by all three radiolabeled compounds by T24. Our results support the notion that P450 enzymes of the Cyp2abfgs subfamily contribute to naphthalene-induced DNA adduct formation (approximately 4-fold reduction in male mice lacking the Cyp2abfgs genes, P < 0.01). The finding that naphthalene-1,2-dihydrodiol, a stable metabolite, formed DNA adducts (102–117 adducts/10 8 nucleotides) at 24 h following addition to the culture media validates the concern that circulating naphthalene metabolites can contribute to DNA adduct formation in the lung. DNA adducts persisted to 24 h after exposure in both mouse and primate airways and at comparable levels between species (77.8 vs 129 adducts/10 8 nucleotides, respectively). Together, these results support the importance of a potential genotoxic mechanism of naphthalene and its metabolites in vivo in both mice and nonhuman primates, and possibly also in humans.

Biological and medical sciences↗

Benzo[a]pyrene Induction of Glutathione S-transferases: An activity-based protein profiling investigation

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated from combustion of carbon-based matter. Upon ingestion, these molecules can be bioactivated by cytochrome P450 monooxygenases to oxidized toxic metabolites. Some of these metabolites are potent carcinogens that can form irreversible adducts with DNA and other biological macromolecules. Conjugative enzymes, such as glutathione S-transferases or UDP-glucuronosyltransferases, are responsible for the detoxification and/or facilitate the elimination of these carcinogens. While responses to PAH exposures have been extensively studied for the bioactivating cytochrome P450 enzymes, much less is known regarding the response of glutathione S-transferases in mammalian systems. In this study, we investigated the expression and activity responses of murine hepatic glutathione S-transferases to benzo[a]pyrene exposure using global proteomics and activity-based protein profiling for chemoproteomics, respectively. Using this approach, we identified several enzymes exhibiting increased activity including GSTA2, M1, M2, M4, M6, and P1. One enzyme, GSTA4, was found to be highly enzymatically repressed with increasing B[a]P dose. Activity responses of several of these enzymes were identified as being expression-independent when comparing global and activity-based datasets, possibly alluding to as of yet unknown regulatory post-translational mechanisms.

Stoddard, Ethan G.↗

Elevated concentrations of U and co-occurring metals in abandoned mine wastes in a northeastern Arizona Native American community

The chemical interactions of U and co-occurring metals in abandoned mine wastes in a Native American community in northeastern Arizona were investigated using spectroscopy, microscopy and aqueous chemistry. The concentrations of U (67–169 μg L –1 ) in spring water samples exceed the EPA maximum contaminant limit of 30 μg L –1 . Elevated U (6,614 mg kg –1 ), V (15,814 mg kg –1 ), and As (40 mg kg –1 ) concentrations were detected in mine waste solids. Spectroscopy (XPS and XANES) solid analyses identified U (VI), As (-I and III) and Fe (II, III). Linear correlations for the release of U vs V and As vs Fe were observed for batch experiments when reacting mine waste solids with 10 mM ascorbic acid (~pH 3.8) after 264 h. The release of U, V, As, and Fe was at least 4-fold lower after reaction with 10 mM bicarbonate (~pH 8.3). These results suggest that U–V mineral phases similar to carnotite [K 2 (UO 2 ) 2 V 2 O 8 ] and As–Fe-bearing phases control the availability of U and As in these abandoned mine wastes. Elevated concentrations of metals are of concern due to human exposure pathways and exposure of livestock currently ingesting water in the area. This study contributes to understanding the occurrence and mobility of metals in communities located close to abandoned mine waste sites.

54 ENVIRONMENTAL SCIENCES↗

Implications of Bioremediation of Polycyclic Aromatic Hydrocarbon-Contaminated Soils for Human Health and Cancer Risk

Background: Bioremediation uses microorganisms to degrade polycyclic aromatic hydrocarbons (PAHs) in contaminated soils. Its success is largely evaluated through targeted analysis of PAH concentrations in soil and cancer risk (exposure) estimates. However, bioremediation often fails to significantly degrade the most carcinogenic PAHs and can initiate formation of more polar metabolites, some of which may be more toxic. Objectives: We aimed to investigate whether the cancer risk associated with PAH-contaminated soils was reduced post-bioremediation and to identify the most effective bioremediation strategies for degrading the carcinogenic and high molecular weight (≥MW302) PAHs. Methods: Pre- and post-bioremediation concentrations of eight B2 group carcinogenic PAHs in soils were collated from the literature and used to calculate excess lifetime cancer risks (ELCR) for adult populations exposed via non-dietary ingestion, per current U.S. Environmental Protection Agency (USEPA) recommendations. Due to the nature of the collated data (reported as mean concentrations ± standard deviations pre- and post-bioremediation), we used simulation methods to reconstruct the datasets and enable statistical comparison of ELCR values pre- and post-bioremediation. Additionally, we measured MW302 PAHs in a contaminated soil prior to and following treatment in an aerobic bioreactor and examined their contributions to cancer risk. Results: 120 of 158 treated soils (76%) exhibited a statistically significant reduction in cancer risk following bioremediation; however, 67% (106/158) of soils had post-bioremediation ELCR values over 10 fold higher than the USEPA health-based ‘acceptable’ risk level. Composting treatments were most effective at biodegrading PAHs in soils and reducing the ELCR. MW302 PAHs were not significantly degraded during bioremediation and dibenzo(a,l)pyrene, alone, contributed an additional 35% to the cancer risk associated with the eight B2 group PAHs in the same bioremediated soil. Conclusions: Bioremediation strategies often fail to reduce carcinogenic PAH concentrations in contaminated soils below USEPA acceptable cancer risk levels. Additionally, MW302 PAHs and ‘unknown’ metabolites (compounds not routinely measured) are not included in current cancer risk assessments and could significantly contribute to soil carcinogenicity.

bioremediation↗

Long-Term in Situ Reduction in Soil Lead Bioavailability Measured in a Mouse Model

In this study, effects of different treatments on the bioavailability of lead (Pb) in soil from a smelter emission contaminated site in Joplin, Missouri, were evaluated in a mouse model. Similar estimates of relative bioavailability for Pb in untreated or treated soil were obtained in mice and in the well-established juvenile swine model. In the mouse model, treatments that used phosphate (phosphoric acid or triple superphosphate) combined with iron oxide or biosolids compost significantly reduced soil Pb bioavailability. Notably, effects of these remediation procedures were persistent, given that up to 16 years had elapsed between soil treatment and sample collection. Remediation of soils was associated with changes in Pb species present in soil. Differences in Pb species in ingested soil and in feces from treated mice indicated that changes in Pb speciation occurred during transit through the gastrointestinal tract. Use of the mouse model facilitates evaluation of remediation procedures and allows monitoring of the performance of procedures under laboratory and field conditions.

54 ENVIRONMENTAL SCIENCES↗

Earthworms Exposed to Polyethylene and Biodegradable Microplastics in Soil: Microplastic Characterization and Microbial Community Analysis

While much is known about microplastics in aquatic environments, only few studies have focused on how microplastics interact with terrestrial organisms. The objective of our study was to investigate the interactions of earthworms with microplastics in a natural environment with environmentally realistic plastic concentrations. Here we investigated whether earthworms would ingest microplastics and incorporate them into their bodies and cast, and whether microplastics would alter the intestinal and soil microbiome. Lumbricus terrestris was exposed to two types of mi croplastics, biodegradable polybutylene adipate terephthalate (PBAT) and low-density polyethylene (LDPE) in mesocosoms filled with natural soil. Microplastics were mixed with poplar leaves and earthworms were allowed to forage for food for 20 days. Surface and bulk soil, earthworm cast, and earthworms themselves were sampled and analyzed for plastic content and microbial communities. Earthworms did not show macroscopic health deterioration (weight loss, vitality). We observed microplastics particles in earthworm casts and guts. Raman spectroscopy indicated that PBAT in guts and cast had degraded to some extent; however, LDPE remained unchanged among the different samples. Microbial analysis showed that soil and casts has similar microbial communities; however, they were signicantly different from the guts samples. Microplastic treatments did not result in a statistically signicant change in bacterial richness, diversity or community composition compared to controls. Taken together, our results suggest that, at environmentally realistic concentrations and short exposure times, PBAT and LDPE microplastics do not have adverse effects on Lumbricus terrestris earthworms.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Phagocyte-Inspired Smart Microcapsules

According to the article, phagocytes protect the organism by ingesting harmful foreign particles and cells. We use mesoscale computer simulations to design a phagocyte-inspired active microcapsule that is capable of selectively capturing nanoparticles dispersed in solvent. Our fully synthetic microdevice is actuated by a temperature-sensitive microgel enclosed inside a perforated spherical shell. The shell pores are decorated with a copolymer brush that regulates the transport of solutes into the capsule interior. When exposed to an external stimulus, the microgel swells, expanding through the shell pores to make contact with the nanoparticle-rich solution surrounding the capsule. Upon removal of the external stimulus, the gel retracts back into the shell, bringing along with it captured nanoparticles. We probe how periodic application of the stimulus combined with nanoparticle-microgel adhesion enable selectivity and enhance capturing efficiency of our nature-inspired microdevice.

Polymer Science↗

PreMevE: New Predictive Model for Megaelectron-volt Electrons inside Earth's Outer Radiation Belt

Here, this work designs a new model called PreMevE to predict storm–time distributions of relativistic electrons within Earth's outer radiation belt. This model takes advantage of the cross–energy, –L–shell, and –pitch–angle coherence associated with wave–electron resonant interactions, ingests observations from belt boundaries—mainly by NOAA POES in low–Earth–orbits (LEOs), and provides high–fidelity nowcast (multiple–hour prediction) and forecast (> ~1 day) of MeV electron fluxes over L–shells between 2.8–7 through linear prediction filters. PreMevE can not only reliably anticipate incoming enhancements of MeV electrons during storms with at least 1–day forewarning time, but also accurately specify the evolving event–specific electron spatial distributions afterwards. The performance of PreMevE is assessed against long–term in situ data from one Van Allen Probe and a LANL geosynchronous satellite. Furthermore, this new model enhances our preparedness for severe MeV electron events in the future, and further adds new science utility to existing and next–generation LEO space infrastructure.

79 ASTRONOMY AND ASTROPHYSICS↗

Impact of Lateral Flow on Surface Water and Energy Budgets over the Southern Great Plains – A Modeling Study

As we see the horizontal grid spacing decrease, treatment of hydrologic processes in land surface models, such as the lateral flow of surface and subsurface flow, need to be explicitly represented. Unlike previous studies that mainly focused on the mountainous regions, in this study the offline WRF-Hydro model is employed to study the impact of lateral flow on soil moisture and energy fluxes over the relatively flat southern Great Plains (SGP). The vast amount of measurements over the SGP provide an unique opportunity to assess the model behavior. In addition, newly developed land surface properties and input forcing are ingested into the model, in an attempt to reduce uncertainties associated with the initial and boundary forcing and help to identify model deficiencies. Our results show that the more realistic inputs (parameters, soil types, forcing) lead to larger underestimation of latent heat flux and dry bias, indicating the existence of model structural uncertainty (embedded errors) in WRF-Hydro that need to be characterized to inform future model development efforts. Including lateral flow processes partly mitigates the model deficiencies in representing hydrologic processes and alleviates the dry bias. In particular, both surface and subsurface lateral flow increase soil moisture mainly over the lower elevations, except that subsurface flow also affects soil moisture over steeper terrains. Additional simulations are performed to assess the effect of routing resolution on model results. When LSM resolution is high, noticeable differences in soil moisture are produced between different routing resolutions especially over steep terrain. Whereas when LSM resolution is coarse, differences between routing resolutions become negligible, especially over flat terrain.

54 ENVIRONMENTAL SCIENCES↗

Influence of Aerosol Embedded in Shallow Cumulus Cloud Fields on the Surface Solar Irradiance

Ubiquitous shallow cumulus clouds are associated with complex variability in surface solar irradiance (SSI). Aerosol embedded in the cloud field typically has a much smaller overall radiative effect, but can significantly perturb the shape of the SSI probability density function (PDF). These perturbations have important implications for several applications that utilize SSI, but are poorly quantified and are the subject of this study. Multiple cases of shallow cumulus cloud fields with embedded aerosol are simulated at the Southern Great Plains Atmospheric Observatory using large eddy simulation (LES). The LES-derived cloud and aerosol fields are then ingested into Monte Carlo three-dimensional (3D) radiative transfer to simulate SSI. We find a variety of perturbations to the SSI PDF that depend on aerosol presence and optical properties. The processes leading to these perturbations include extinction of the direct beam that often increases from the clear-sky region toward cloud edge due to aerosol hygroscopic growth, and scattering of radiation by aerosol into cloud shadows. The ability to predict the SSI PDF in the presence of aerosol is assessed by adding three representative aerosol optical properties into an existing machine learning framework. We show that machine learning accurately predicts the SSI PDF across a wide range of conditions with negligible computational expense. Importance metrics reveal the relatively high influence of aerosol optical properties in making the predictions. These new findings highlight the important role that aerosol plays in SSI variability for highly 3D cloud-aerosol environments and provides a computationally efficient route forward for its simulation.

3D radiative transfer↗

A Performant, Scalable Processing Pipeline for High‐Quality and FAIR Environmental Sensor Data

High-resolution environmental monitoring is necessary to record, understand, and predict biogeochemical and ecological changes particularly in coastal systems but brings significant challenges in processing and making rapidly available the resulting data. The COMPASS-FME project established a network of coastal observational sites across the Chesapeake Bay and western Lake Erie regions extensively instrumented with soil, vegetation, and weather sensors logging data every 15 min. Our data processing framework, written in R and completely open source, prioritizes rapid model-experiment iteration and makes biogeochemical data rapidly available for quality assurance/quality control, analysis, and model ingestion. This pipeline is distinguished by a standardized and modular approach to data curation, extensive metadata and documentation, and its high performance. These attributes combine to make biogeochemical data rapidly accessible across COMPASS-FME and the broader community. Flexible, powerful, and reproducible approaches to handling high-volume environmental data are crucial for accelerating biogeosciences research.

Pennington, Stephanie C. [Pacific Northwest Nation↗

An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.

Plutonium is a toxic synthetic element with no natural biological function, but it is strongly retained by humans when ingested. Using small-angle X-ray scattering, receptor binding assays and synchrotron X-ray fluorescence microscopy, we find that rat adrenal gland (PC12) cells can acquire plutonium in vitro through the major iron acquisition pathway -- receptor-mediated endocytosis of the iron transport protein serum transferrin; however, only one form of the plutonium-transferrin complex is active. Low-resolution solution models of plutonium-loaded transferrins derived from small-angle scattering show that only transferrin with plutonium bound in the protein's C-terminal lobe (C-lobe) and iron bound in the N-terminal lobe (N-lobe) (Pu{sub c}Fe{sub N}Tf) adopts the proper conformation for recognition by the transferrin receptor protein. Although the metal-binding site in each lobe contains the same donors in the same configuration and both lobes are similar, the differences between transferrin's two lobes act to restrict, but not eliminate, cellular Pu uptake.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗