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

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells

Despite the well-established sex-specific differences in the incidence of bronchopulmonary dysplasia (BPD), the molecular mechanism(s) behind these are not completely understood. Pulmonary angiogenesis is critical for alveolarization and arrest in vascular development adversely affects lung development. Human neonatal umbilical vein endothelial cells (HUVECs) provide a robust in vitro model for the study of endothelial cell physiology and function. Male and Female HUVECs were exposed to room air (21% O{sub 2}, 5% CO{sub 2}) or hyperoxia (95% O{sub 2}, 5% CO{sub 2}) for up to 72 h. Cell viability, proliferation, H{sub 2}O{sub 2} production and angiogenesis were analyzed. Sex-specific differences in the expression of VEGFR2 and modulation of NF-kappa B pathway were measured. Male HUVECs have decreased survival, greater oxidative stress and impairment in angiogenesis compared to similarly exposed female cells. There is differential expression of VEGFR2 between male and female HUVECs and greater activation of the NF-kappa B pathway in female HUVECs under hyperoxic conditions. The results indicate that sex differences exist between male and female HUVECs in vitro after hyperoxia exposure. Since endothelial dysfunction has a major role in the pathogenesis of BPD, these differences could explain in part the mechanisms behind sex-specific differences in the incidence of this disease. - Highlights: • Cellular sex effects viability and oxidative stress in HUVECs exposed to hyperoxia. • Male HUVECs show greater impairment in angiogenesis compared to female cells. • Sex-specific modulation of VEGFR2 and the NF-kappaB pathway was noted.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Exhaled breath condensate profiles of U.S. Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures

Prolonged exposure to hyperbaric hyperoxia can lead to pulmonary oxygen toxicity (PO 2 tox). PO 2 tox is a mission limiting factor for special operations forces divers using closed-circuit rebreathing apparatus and a potential side effect for patients undergoing hyperbaric oxygen (HBO) treatment. In this study, we aim to determine if there is a specific breath profile of compounds in exhaled breath condensate (EBC) that is indicative of the early stages of pulmonary hyperoxic stress/PO 2 tox. Using a double-blind, randomized 'sham' controlled, cross-over design 14 U.S. Navy trained diver volunteers breathed two different gas mixtures at an ambient pressure of 2 ATA (33 fsw, 10 msw) for 6.5 h. One test gas consisted of 100% O 2 (HBO) and the other was a gas mixture containing 30.6% O 2 with the balance N 2 (Nitrox). The high O 2 stress dive (HBO) and low O 2 stress dive (Nitrox) were separated by at least seven days and were conducted dry and at rest inside a hyperbaric chamber. EBC samples were taken immediately before and after each dive and subsequently underwent a targeted and untargeted metabolomics analysis using liquid chromatography coupled to mass spectrometry (LC-MS). Following the HBO dive, 10 out of 14 subjects reported symptoms of the early stages of PO 2 tox and one subject terminated the dive early due to severe symptoms of PO 2 tox. No symptoms of PO 2 tox were reported following the nitrox dive. A partial least-squares discriminant analysis of the normalized (relative to pre-dive) untargeted data gave good classification abilities between the HBO and nitrox EBC with an AUC of 0.99 (±2%) and sensitivity and specificity of 0.93 (±10%) and 0.94 (±10%), respectively. Furthermore, the resulting classifications identified specific biomarkers that included human metabolites and lipids and their derivatives from different metabolic pathways that may explain metabolomic changes resulting from prolonged HBO exposure.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Selection-enriched genomic loci (SEGL) reveals genetic loci for environmental adaptation and photosynthetic productivity in Chlamydomonas reinhardtii

This work demonstrates an approach to produce and select hybrid algal strains exhibiting increased photosynthetic productivity under multiple environmental conditions. This simultaneously addresses two major impediments to improving algal bioenergy production: 1) generating new genetic variants with improved performance; and 2) disentangling complex interactions between genetic and physiological factors contributing to these improvements. We pooled progeny generated from mating two environmental isolates of the green alga Chlamydomonas reinhardtii and cultured the pools under multiple environmental conditions. Strains from the outcompeting populations showed substantial (in some cases over 3 fold) increases in productivity over the parental lines under certain environments related to biomass production, including laboratory conditions as well as hyperoxia, fluctuating light, high salinity and high temperature. The results indicate that C. reinhardtii has remarkable, untapped, directed evolution capacity that may be harnessed using breeding and competition approaches. The populations were deep sequenced at multiple time points to identify “Selection-Enriched Genomic Loci” (SEGL) that accumulated in the populations, and thus likely confer increased fitness under the respective environmental conditions. With improved resolution, SEGL mapping can identify allelic combinations used for targeted breeding approaches, generating elite algal lines with multiple desirable traits, as well as to further understand the genetic and mechanistic bases of photosynthetic productivity. Increasing the photosynthetic efficiency of algae during biomass production is perhaps the most critical hurdle for economically sustainable algal based biofuels. This presents unique challenges because modifications designed to increase photosynthesis often result in decreased fitness, due to production of toxic reactive oxygen species when photosynthesis is not adequately regulated. These problems are exacerbated under natural and outdoor production environments because of the complex nature of photosynthesis and the multifaceted interactions between genetic, environmental and physiological factors. Here, we demonstrate a high throughput biotechnological screening approach that simultaneously produces algal strains with highly increased autotrophic productivity and identifies genomic loci contributing to these improvements. Our results demonstrate that Chlamydomonas reinhardtii exhibits high directed evolutionary capacity readily accessed through breeding and selection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

The role of cysteine in tellurate reduction and toxicity

The tellurium oxyanion tellurate is toxic to living organisms even at low concentrations; however, its mechanism of toxicity is poorly understood. Here, we show that exposure of Escherichia coli K-12 to tellurate results in reduction to elemental tellurium (Te[0]) and the formation of intracellular reactive oxygen species (ROS). Toxicity assays performed with E. coli indicated that pre-oxidation of the intracellular thiol pools increases cellular resistance to tellurate-suggesting that intracellular thiols are important in tellurate toxicity. X-ray absorption spectroscopy experiments demonstrated that cysteine reduces tellurate to elemental tellurium. This redox reaction was found to generate superoxide anions. These results indicate that tellurate reduction to Te(0) by cysteine is a source of ROS in the cytoplasm of tellurate-exposed cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease

Mitochondrial dysfunction and ensuing oxidative damage is typically thought to be a primary cause of Huntington's disease, Alzheimer's disease, and Parkinson disease. There is little doubt that mitochondria (MT) become defective as neurons die, yet whether MT defects are the primary cause or a detrimental consequence of toxicity remains unanswered. Oxygen consumption rate (OCR) and glycolysis provide sensitive and informative measures of the functional status MT and the cells metabolic regulation, yet these measures differ depending on the sample source; species, tissue type, age at measurement, and whether MT are measured in purified form or in a cell. The effects of these various parameters are difficult to quantify and not fully understood, but clearly have an impact on interpreting the bioenergetics of MT or their failure in disease states. A major goal of the review is to discuss issues and coalesce detailed information into a reference table to help in assessing mitochondrial dysfunction as a cause or consequence of Huntington's disease.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Functional metal–organic frameworks as effective sensors of gases and volatile compounds

Developing efficient sensor materials with superior performance for selective, fast and sensitive detection of gases and volatile organic compounds (VOCs) is essential for human health and environmental protection, through monitoring indoor and outdoor air pollutions, managing industrial processes, controlling food quality and assisting early diagnosis of diseases. Metal–organic frameworks (MOFs) are a unique type of crystalline and porous solid material constructed from metal nodes (metal ions or clusters) and functional organic ligands. They have been investigated extensively for possible use as high performance sensors for the detection of many different gases and VOCs in recent years, due to their large surface area, tunable pore size, functionalizable sites and intriguing properties, such as electrical conductivity, magnetism, ferroelectricity, luminescence and chromism. The high porosity of MOFs allows them to interact strongly with various analytes, including gases and VOCs, thus resulting in easily measurable responses to different physicochemical parameters. Although much of the recent work on MOF-based luminescent sensors have been summarized in several excellent reviews (up to 2018), a comprehensive overview of these materials for sensing gases and VOCs based on chemiresistive, magnetic, ferroelectric, and colorimertic mechanisms is missing. In this review, we highlight the most recent progress in developing MOF sensing and switching materials with an emphasis on sensing mechanisms based on electricity, magnetism, ferroelectricity and chromism. We provide a comprehensive analysis on the MOF–analyte interactions in these processes, which play a key role in the sensing performance of the MOF-based sensors and switches. We discuss in detail possible applications of MOF-based sensing and switching materials in detecting oxygen, water vapor, toxic industrial gases (such as hydrogen sulfide, ammonia, sulfur dioxide, nitrous oxide, carbon oxides and carbon disulfide) and VOCs (such as aromatic and aliphatic hydrocarbons, ketones, alcohols, aldehydes, chlorinated hydrocarbons and N,N'-dimethylformamide). Altogether, this review serves as a timely source of information and provides insight for the future development of advanced MOF materials as next-generation gas and VOC sensors.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Antioxidant Activity in Supramolecular Carotenoid Complexes Favored by Nonpolar Environment and Disfavored by Hydrogen Bonding

Carotenoids are well-known antioxidants. They have the ability to quench singlet oxygen and scavenge toxic free radicals preventing or reducing damage to living cells. We have found that carotenoids exhibit scavenging ability towards free radicals that increases nearly exponentially with increasing the carotenoid oxidation potential. With the oxidation potential being an important parameter in predicting antioxidant activity, we focus here on the different factors affecting it. This paper examines how the chain length and donor/acceptor substituents of carotenoids affect their oxidation potentials but, most importantly, presents the recent progress on the effect of polarity of the environment and orientation of the carotenoids on the oxidation potential in supramolecular complexes. The oxidation potential of a carotenoid in a nonpolar environment was found to be higher than in a polar environment. Moreover, in order to increase the photostability of the carotenoids in supramolecular complexes, a nonpolar environment is desired and the formation of hydrogen bonds should be avoided.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Harnessing redox proteomics to study metabolic regulation and stress response in lignin-fed Rhodococci

Abstract Background Rhodococci are studied for their bacterial ligninolytic capabilities and proclivity to accumulate lipids. Lignin utilization is a resource intensive process requiring a variety of redox active enzymes and cofactors for degradation as well as defense against the resulting toxic byproducts and oxidative conditions. Studying enzyme expression and regulation between carbon sources will help decode the metabolic rewiring that stymies lignin to lipid conversion in these bacteria. Herein, a redox proteomics approach was applied to investigate a fundamental driver of carbon catabolism and lipid anabolism: redox balance. Results A consortium of Rhodococcus strains was employed in this study given its higher capacity for lignin degradation compared to monocultures. This consortium was grown on glucose vs. lignin under nitrogen limitation to study the importance of redox balance as it relates to nutrient availability. A modified bottom–up proteomics workflow was harnessed to acquire a general relationship between protein abundance and protein redox states. Global proteomics results affirm differential expression of enzymes involved in sugar metabolism vs. those involved in lignin degradation and aromatics metabolism. As reported previously, several enzymes in the lipid biosynthetic pathways were downregulated, whereas many involved in β-oxidation were upregulated. Interestingly, proteins involved in oxidative stress response were also upregulated perhaps in response to lignin degradation and aromatics catabolism, which require oxygen and reactive oxygen species and generate toxic byproducts. Enzymes displaying little-to-no change in abundance but differences in redox state were observed in various pathways for carbon utilization (e.g., β‑ketoadipate pathway), lipid metabolism, as well as nitrogen metabolism (e.g., purine scavenging/synthesis), suggesting potential mechanisms of redox-dependent regulation of metabolism. Conclusions Efficient lipid production requires a steady carbon and energy flux while balancing fundamental requirements for enzyme production and cell maintenance. For lignin, we theorize that this balance is difficult to establish due to resource expenditure for enzyme production and stress response. This is supported by significant changes to protein abundances and protein cysteine oxidation in various metabolic pathways and redox processes.

09 BIOMASS FUELS↗
DOE OSTI2016

β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD

Resistance to anthracycline based chemotherapy is a major limitation in the treatment of breast cancer, particularly of the triple negative sub-type that lacks targeted therapies. Resistance that arises from tumor-stromal interaction facilitated by integrins provides the possibility of targeted disruption. In the present study, we demonstrate that integrin β3 signaling inhibits apoptosis induced by a DNA-damaging chemotherapeutic agent, epirubicin, in MDA-MB-231 breast cancer cells. Drug efflux based mechanisms do not contribute to this effect. We show that integrin β3 employs the PI3K-Akt and the MAPK pathway for enabling cell survival and proliferation. Further, our results indicate that integrin β3 helps inhibit epirubicin induced cytotoxicity by repression of the pro-apoptotic protein BAD, thus promoting an anti-apoptotic response. Myristoylated RGT peptide and a monoclonal antibody against integrin β3 brought about a reversal of this effect and chemosensitized the cells. These results identify β3 integrin signaling via repression of BAD as an important survival pathway used by breast cancer cells to evade chemotherapy induced stress. - Highlights: • Integrin β3 signaling promotes chemoresistance to epirubicin in breast cancer cells. • Integrin β3 promotes cell survival and proliferation in drug treated cells through the PI3K and MAPK pathways. • Integrin signaling helps evade drug induced cytotoxicity by repression of pro-apoptotic molecule; BAD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Life on the Edge: Microbes in Rock Varnish

The newly discovered high concentrations of manganese on Mars open up new possibilities for habitability on that planet [1, 2]. On Earth, there is a close association between Mn deposits and the presence of Mn- and Fe- oxidizing microbes [3-7]; as such, Mn is considered a principal biosignature for Mars [8]. The most common terrestrial Mn-rich surface material on Earth is desert varnish, a dark, shiny coating on rocks in arid locations. Microorganisms occupy various niches within rock varnish, and it is probable that the concentration of Mn in many rock varnishes is mediated by microbial activity [6, 9, 10]; however, the relationship between microbes and varnish remains a source of long-standing controversy [11]. Do microorganisms drive the formation of varnish, oxidizing Mn and Fe to gain energy, or do they instead utilize varnish as a habitat? This long-standing question has important implications for our understanding of how life on Earth has evolved to capture and harness energy from the physical environment. Additionally, it will greatly influence the search on Mars for the signatures of life that may be present in rock varnish cannot be definitively identified on Mars without first being identified on Earth. Here we explored the microbial species and processes involved in the habitation of rock varnish and identified organic biosignatures that, in concert with trace element and mineralogy, could be used to distinguish the biogenic and abiogenic origins of terrestrial Mn-rich surfaces so that we may then apply the knowledge gained in this work to current Martian datasets from ChemCam. Each of these goals has important implications for our understanding of how life on Earth has evolved to capture and harness energy from the physical environment. A combinatorial experimental approach, utilizing microscopy, high-throughput DNA sequencing, culturing and physiological assays, were used to characterize the microbial communities inhabiting varnished rocks across the Western U.S. Microbial communities inhabiting varnish were shaped by both location (larger contribution) and rock type. However, we found that the unique varnish environment selects for a core group of radiation- and desiccation-tolerant microorganisms across landscapes and rock types. The bacteria comprising this core group include a who’s who of radiation resistant organisms including Rubrobacter spp., Deinococcus spp., Hymenobaceter spp., and Chroococcidiopsis spp. Among the fungi, potential lichen-forming members of the Lecanoromycetes and rock-inhabiting Dothideomycetes were common. Importantly, we found that two of the survival mechanisms employed by these microorganisms are likely key drivers of Mn oxide formation and the biogenesis of varnish. First, we showed that the key cyanobacteria inhabiting the varnish accumulate copious amounts of low molecular weight Mn2+-conjugates, that are critical for their ability to withstand the toxic effects of reactive oxygen species generated upon radiation exposure. Secondly, the microbial community inhabiting varnished rocks were found to be particularly adept at producing siderophores, which are high-affinity chelating compounds secreted by bacteria and fungi that serve to sequester Fe2+ (and Mn2+) from oxidizing environments for transport into cells as essential micronutrients for growth and survival. When tightly bound to organic ligands, Mn2+ is susceptible to oxidation to Mn3+-ligand under atmospheric oxygen and at slightly basic pH levels. Further, Mn3+-ligand can be oxidized to MnO2 (manganese oxide) when it comes into contact with reactive oxygen species (e.g., superoxide radical) formed during the photolysis of water during periods of high UV exposure. The data points towards a scenario whereby cyanobacterial biofilms, and associated radiation resistant, heterotrophic bacteria, comprise the central hub of the varnish community. These communities depend on light and water to slowly establish on the rock surface where they accumulate and concentrate Mn for survival. When the biofilms dry out, mineral rinds rich in Mn oxides form which serve as a habitat for the successive rounds of microbial growth and Mn oxide formation. Copious production and excretion of siderophores, which are extremely stable in the environment, coats the rock surface with a longlived catalyst for Mn oxidation. By discovering these two completely novel mechanisms for biogenic varnish formation, we have gained the underlying knowledge necessary to develop a suite of organic and inorganic biosignatures to distinguish biogenic and abiogenic origins of Mnrich surfaces on Earth or Mars.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Toxicology and Biodegradability of Blendstocks for Mixing Controlled Compression Ignition Combustion: Literature Review of Available Data

The goal of the U.S. Department of Energy’s Co-Optima project is to develop an understanding of potential biomass-derived blendstocks for use in the transportation sector. This report documents the estimated environmental and toxicological impact of potential bioblendstocks for mixing controlled compression ignition (MCCI) engines. The candidate molecules were: 2-nonanol; n-undecane; 2,6,10-trimethyldodecane; 5-ethyl-4-propylnonane; hexylhexanoate; methyldecanoate; dibutoxymethane; 4-butoxyheptane; dipentylether; renewable diesel; and soy biodiesel. To provide a robust comparison, diesel surrogate molecules were also considered: α-methylnaphthalene; decahydronaphthalene; 2,2,4,4,6,8,8-heptamethylnonane; n-butylcyclohexane; n-hexadecane; tetralin; and n-dodecylbenzene. The intent of this work was not to provide absolute answers and remove any molecules from consideration, but to provide more robust data for each molecule that can be used in subsequent evaluations. Little literature data was available for many of the molecules, both potential blendstocks and diesel surrogates, so a quantitative structural activity relationship (QSAR) approach was used to provide input into the relevant models. This assessment included an evaluation of compartment partitioning in the event of an accidental chemical spill, fate and transport indicators, estimated biodegradability, and human and environmental toxicology. The higher molecular weight and longer hydrocarbon chain lengths of these MCCI molecules reduce water solubility and mobility. Generally, the oxygenated molecules improved biodegradability metrics. The hydrocarbons farnesane and 5-Et-4-PrNonane are not predicted to be biodegradable. Human acute toxicity was found to be slightly to non-toxic for the MCCI blendstocks and the diesel surrogates. 2-Nonanol, undecane, MeDecanoate, dibutoxymethane, and dipentylether were likely developmental toxicants. Although poorly water soluble, all the compounds, whether Co-Optima blendstocks or diesel surrogates, showed significant toxicity to D. magna. The oxygenated blendstocks were less likely to bioaccumulate than the non-oxygenated blendstocks, which behaved similar to the diesel surrogates. Overall, this predicted analysis showed that the MCCI blendstocks are very similar to their diesel counterparts. No significant showstoppers were found that would indicate concern moving forward with additional research into these potential fuels. The results presented were based solely on predictive models and serve to provide information going forward for continued evaluation of these molecules.

09 BIOMASS FUELS↗
DOE OSTI2020

Diversity in Photoprotection and Energy Balancing in Terrestrial and Aquatic Phototrophs

The evolution of oxygenic photosynthesis enabled organisms to use sunlight as an energy source, allowing them to colonize new niches. At the same time, life (as we know it) places severe constraints on photosynthesis. For example, the initial reactions of photosynthesis involve highly energetic intermediates that, if not controlled, can generate highly toxic side products (especially reactive oxygen species, ROS), that can damage other essential components of the organisms it powers. Photosynthesis must therefore be tightly regulated to balance the need for efficient energy conversion with the necessity of avoiding photodamage (Gust D, Kramer D, Moore A, Moore T, Vermaas W, Mater Res Bull 33:383–389, 2008). A related constraint on photosynthesis is the need to precisely balance how much energy is stored in ATP and NADPH to precisely meet biochemical demands. If this balancing does not occur, the system will fail, leading to photodamage (Kramer DM, Evans JR, Plant Physiol 155:70–78, 2011). Consideration of these requirements is essential for efforts to improve the efficiency of photosynthesis by introducing CO 2 concentrating mechanisms, altering metabolism or biosynthetic pathways to shunt energy to alternative products (Kramer DM, Evans JR, Plant Physiol 155:70–78, 2011). These balancing processes must be extremely robust to contend with the rapid and unpredictable fluctuations in environmental conditions and metabolic demands that occur in nature. A large body of work has come from model systems, especially terrestrial higher plants and the green alga Chlamydomonas reinhardtii, leading to a model for the regulation of light reactions that involves 1) sensing of the pH gradient component of the thylakoid proton motive force (pmf), and 2) the redox state of the plastoquinone- and stromal pools. Over the short term, these sensors trigger regulation of light capture by altering the activity of ATP synthase leading to adjustments in lumen pH, which fine tunes light capture through nonphotochemical quenching (NPQ) and control of electron flow by adjusting the rate of PQH 2 oxidation at the b 6 f complex. Simultaneously, this system controls the balance of ATP/NADPH by adjusting electron flux to linear and cyclic electron flow pathways to balance ATP/NADPH. This integrated “pmf paradigm” model explains much of the existing data on plants and green algae, but may not extend to other diverse organisms. This review considers how advances in our understanding of photosynthesis over the past 7–8 years, particularly in the discoveries of diverse biochemical/biophysical mechanisms in aquatic photosynthetic species, affects the view of energy balance, including the shunting of electrons to O 2 through the flavodiiron proteins (FLV), the plastid terminal oxidase, the dissipation of electric field by ion movements, and the activation of alternative electron sinks. Furthermore, we will introduce the basic model that has been developed for higher plant chloroplasts, then contrast these with selected aquatic systems, focusing on how the differences impact the needs to re-balance both energy input and its partitioning into energy currencies.

Kanazawa, Atsuko↗
DOE OSTI2017

Hemoglobin pretreatment endows rat cortical astrocytes resistance to hemin-induced toxicity via Nrf2/HO-1 pathway

Highlights: • Hb-pretreatment endowed astrocytes the resistance to hemin-induced toxicity. • Hb-pretreatment induced HO-1 expression and prevented hemin-induced ROS production. • Hb-pretreatment induced Nrf2 expression and promoted its nuclear translocation. • Nrf2 knockdown suppressed Hb-induced upregulation of HO-1 expression. • Nrf2 knockdown increased the susceptibility of Hb-pretreated astrocytes to hemin. Oxidative stress mediated secondary injury contributes to neurological deterioration after intracerebral hemorrhage (ICH). Astrocytes, the most dominant cells in the central nervous system (CNS), play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemoglobin (Hb), the primary component released by hemolysis, is an effective activator of astrocytes. Hemin, the product of Hb degradation, is highly toxic due to the induction of reactive oxygen species (ROS). We speculate that Hb-activated astrocytes are resistant to hemin-induced toxicity. To verify our speculation, Hb-pretreated astrocytes were exposed to hemin, intracellular ROS accumulation and cell apoptosis were evaluated. Heme oxygenase 1 (HO-1) and nuclear transcription factor-erythroid 2 related factor (Nrf2) expression were observed to explore the potential mechanism. The results demonstrated that Hb induced upregulation and nuclear translocation of Nrf2 in astrocytes, resulted in HO-1 upregulation, which contributed to reduced ROS accumulation and apoptosis rate. Knocking down Nrf2 expression by siRNA suppressed Hb-induced upregulation of HO-1 expression and increased the susceptibility of Hb-pretreated astrocytes to hemin-induced toxicity. Taken together, Hb-activated astrocytes acquired resistance to hemin-induced toxicity via Nrf2/HO-1 pathway. This phenomenon can be considered as the adaptive self-defense in the pathological process of ICH. Hb pre-warned astrocytes and enhanced their capability of handling the coming hemin “flood”. Nrf2/HO-1 may be employed as a target for neuroprotection after ICH.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Computational Modeling and Evolutionary Implications of Biochemical Reactions in Bacterial Microcompartments

Bacterial microcompartments (BMCs) are protein-encapsulated compartments found across at least 23 bacterial phyla. BMCs contain a variety of metabolic processes that share the commonality of toxic or volatile intermediates, oxygen-sensitive enzymes and cofactors, or increased substrate concentration for magnified reaction rates. These compartmentalized reactions have been computationally modeled to explore the encapsulated dynamics, ask evolutionary-based questions, and develop a more systematic understanding required for the engineering of novel BMCs. Many crucial aspects of these systems remain unknown or unmeasured, such as substrate permeabilities across the protein shell, feasibility of pH gradients, and transport rates of associated substrates into the cell. This review explores existing BMC models, dominated in the literature by cyanobacterial carboxysomes, and highlights potentially important areas for exploration.

bacterial microcompartments↗
DOE OSTI2021

Carotenoid biomarkers in Namibian shelf sediments: Anoxygenic photosynthesis during sulfide eruptions in the Benguela Upwelling System

Significance Anoxygenic photosynthesis by phototrophic sulfur bacteria is prevalent in microbial mat ecosystems and in restricted, highly stratified aquatic environments. This limited distribution reflects their simultaneous requirements for an anoxic habitat, reduced sulfur to supply electrons for carbon fixation, and an appropriate light regime. Although these conditions were often satisfied in ancient seas, as shown by the distinctive carotenoid and chlorophyll pigments preserved in geological samples going back as far as 1.65 billion y, we can find no record of these organisms growing in today’s generally well-ventilated oceans. An array of carotenoids in sediments from the Namibian shelf suggests that green sulfur bacteria, despite their sensitivity to oxygen, can proliferate during episodic toxic gas eruptions in the Benguela Upwelling System.

Ma, Jian↗
DOE OSTI2018

Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling

Chemotherapeutic drugs exert systemic toxicity in lung cancer cells and therefore novel treatment strategies are warranted. Epigallocatechin 3-gallate (EGCG), though possessing beneficial effects in alleviating cancer, its effect has been limited due to ineffective systemic delivery, toxicity and bioavailability. To attain the maximum therapeutic response of EGCG, we have synthesized bovine serum albumin (BSA) encapsulated magnetite nanoparticle (MNPs) loaded with EGCG (nano EGCG). The synthesized nano EGCG was characterized using HR-TEM, XRD and FT-IR. Cytotoxicity analysis of BSA-MNP and nano EGCG using flow cytometry was evaluated in lung adenocarcinoma A549 cells. The effect of native and nano EGCG modulating apoptosis and Nrf2/Keap1 signaling was analysed. Nano EGCG exhibited increased ROS/RNS levels and decreased mitochondrial membrane potential, as evaluated by DCFH and JC1 staining, respectively. Expression of pro-apoptotic Bcl-2 family proteins (Bcl-2, Bax, Bak, Bim and Puma) was evaluated. This study demonstrates that native and nano EGCG induces apoptosis through the involvement of ROS leading to loss in mitochondrial membrane potential. EGCG exhibited an increased expression of Nrf2 and Keap1 that could regulate apoptosis in A549 cells. This study, for the first time reveals the potential of BSA-MNPs loaded EGCG as drug target and renders better efficacy against lung cancer cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Effects of selenium exposure on the hematology, innate immunity, and metabolic rate of yellow-bellied sliders ( Trachemys scripta scripta )

Selenium (Se) is a naturally occurring essential element that can be toxic to vertebrates at high concentrations. Despite studies that have documented that wild reptile species can accumulate copious amounts of Se, little is known regarding specific toxicologic effects of Se. In this study, 70 juvenile yellow-bellied sliders (Trachemys scripta scripta) were exposed to one of three seleno-L-methionine (SetMet) treatments (control, n = 24; 15 mg/kg, n = 23; and 30 mg/kg, n = 23) via weekly oral gavage for 5 weeks. At the conclusion of the experiment, kidney, liver, muscle, and blood samples were collected for quantitative Se analysis. Turtles in the SeMet treatment groups accumulated significantly higher amounts of Se in all tissue types relative to controls (all p < 0.001). Turtles in the 30 mg/kg SeMet group also accumulated significantly higher amounts of Se compared to the 15 mg/kg group (all p < 0.001). Although toxicity thresholds for reptiles have not been established, Se concentrations in liver tissue from both SeMet treatment groups exceeded reported avian toxicity thresholds for liver tissue. Neither oxygen consumption nor innate bactericidal capacity were impacted by SeMet exposure. Furthermore, turtles in the 30 mg/kg SeMet group exhibited anemia, which has been reported in other vertebrates exposed to Se. Furthermore, juvenile T. s. scripta in the 30 mg/kg SeMet group experienced 17% mortality compared to 0% in the 15 mg/kg treatment and control groups. To our knowledge, this study is the first to report dose-dependent Se-associated anemia and mortality in a chelonian species.

59 BASIC BIOLOGICAL SCIENCES↗