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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 37 records · Page 2

Metal Bioavailability and Ecotoxicity of Bioremediated Oils and Tailings by BioTiger{sup TM}, a Microbial Consortium

Oil Sands and Mature Fine Tailings: Oil sand reserves are a major source of oil for the United States. Oil sands are a mixture of sand, clay, water, and bitumen. The refining process requires large volumes of water and generates hazardous Mature Fine Tailings (MFTs) that are stored in engineered settling ponds. They are of major environmental concern due to their persistence and difficulty to naturally biodegrade. MFT Contaminants of Concern: Naphthenic Acids (NAs), Polycyclic Aromatic Hydrocarbons (PAHs), Benzene, Toluene, Ethylbenzene and Xylene (BTEX), Metals, Residual Bitumen. BioTiger{sup TM} (BT{sup TM}), the SRNL patented 12 component microbial consortia was found to cometabolically degrade some NAs and PAHs. Previous studies performing short term exposure (48 hours and 7 days) to BT{sup TM} have resulted in increased toxicity due to the partial degradation of PAHs forming toxic intermediates. Objective: Evaluate the ecotoxicity of BT{sup TM} remediated MFTs exposed to a 2 week period w/ yeast (Y) extract. This work will determine BT{sup TM}'s remediation of MFTs from Fort McMurray, Alberta. Acute toxicity tests will be performed under section 9 of EPA's Method for Measuring Acute Toxicity using the freshwater organism, Ceriodaphnia dubia. Monitor BT{sup TM} growth through Most Probable Number (MPN) counts, pH, and metal bioavailability will also be evaluated. Preparing tailing solutions for biodegradation: BT{sup TM} components were grown in R2A media and combined. Mother BT{sup TM} was centrifuged at 7000 rpm for 20 minutes and resuspended in Bushnell Haus. 33 g of tailings were added to 1100 mL Bushnell Haus along with yeast extract (11 g) to create a 3% tailing solution. Treatments were performed in triplicate. Preparing solutions for toxicity tests using C. dubia: Supernatant was collected immediately after centrifuging at 7000 rpm for 20 min. Supernatant was filtered via a 0.22 μm sterile system. All treatments except MFT, Y peaked at T=4. This decrease in microbial growth could be associated with toxicity from intermediate byproducts. Treatments containing only MFTs decreased in the initial 11 days before growing significantly. Final solution for MFT, Y treatment had the highest pH. This could potentially be due to increased microbial activity linked with yeast consumption. All treatments except MFT, Y peaked at T=4. This decrease in microbial growth could be associated with toxicity from intermediate byproducts. Treatments containing only MFTs decreased in the initial 11 days before growing significantly. Future Direction: Await results from Acute Toxicity Tests and Metal Bioavailability Quantification of biosurfactant production. Evaluate hydrocarbon degradation byproducts using an analytical chemistry approach. More toxicity experiments with variations in time and conditions.

54 ENVIRONMENTAL SCIENCES↗

From PROTAC to inhibitor: Structure-guided discovery of potent and orally bioavailable BET inhibitors

An X-ray structure of a CLICK chemistry-based BET PROTAC bound to BRD2(BD2) inspired synthesis of JQ1 derived heterocyclic amides. This effort led to the discovery of potent BET inhibitors displaying overall improved profiles when compared to JQ1 and birabresib. A thiadiazole derived 1q (SJ1461) displayed excellent BRD4 and BRD2 affinity and high potency in the panel of acute leukaemia and medulloblastoma cell lines. A structure of 1q co-crystalised with BRD4-BD1 revealed polar interactions with the AZ/BC loops, in particular with Asn140 and Tyr139, rationalising the observed affinity improvements. In addition, exploration of pharmacokinetic properties of this class of compounds suggest that the heterocyclic amide moiety improves drug-like features. Finally, our study led to the discovery of potent and orally bioavailable BET inhibitor 1q (SJ1461) as a promising candidate for further development.

60 APPLIED LIFE SCIENCES↗

Oestrogen regulates SOX9 bioavailability by rapidly activating ERK1/2 and stabilising microtubules in a human testis-derived cell line

Highlights: • Brief oestrogen treatment causes the cytoplasmic retention of the testis factor SOX9. • The cytoplasmic retention of SOX9 by oestrogen is associated with the rapid stabilisation of microtubules. • ERK1/2 is required for the stabilisation of microtubules by activated oestrogen receptors. • Oestrogen can act on both a non-genomic and genomic level to impact gonad somatic cell fate. Nuclear SOX9 is essential for Sertoli cell differentiation and the development of a testis. Exposure of Sertoli cells to exogenous oestrogen causes cytoplasmic retention of SOX9, inhibiting testis development and promoting ovarian development. The cytoplasmic localisation of SOX9 requires a stabilised microtubule network and a key MAPK complex, ERK1/2, is responsive to oestrogen and known to affect the microtubule network. We hypothesised that oestrogen could stabilise microtubules through the activation of ERK1/2 to promote the cytoplasmic retention of SOX9. Treatment of human testis-derived NT2/D1 cells for 30 min with oestrogen rapidly activated ERK1/2, stabilised the microtubule network and increased cytoplasmic localisation of SOX9. The effects of oestrogen on SOX9 and tubulin were blocked by the ERK1/2 inhibitor U0126, demonstrating that ERK1/2 mediates the stabilisation of microtubules and cytoplasmic retention of SOX9 by oestrogen. Together, these data revealed a previously unknown mechanism for oestrogen in impacting MAPK signalling to block SOX9 bioavailability and the differentiation of Sertoli cells.

60 APPLIED LIFE SCIENCES↗

Biogeochemical Controls on Wood Degradation as a Source of Bioavailable Carbon in Denitrifying Bioreactors

Woodchip bioreactors (WBRs) are important tools for the removal of nitrate in agricultural drainage, but their effectiveness is often limited by the slow degradation of lignocellulosic wood residues into bioavailable forms of carbon that fuel denitrifying microorganisms. Here, we examine biogeochemical factors regulating wood degradation in saturated woodchip beds, with a focus on the effects of dissolved oxygen (DO), iron (Fe), and manganese (Mn) in generating oxidative activity that can enhance wood decomposition. Woodchips from a 10-year-old WBR were characterized with bulk techniques and a novel combination of μX-ray scattering, μXRF, and μXANES to visualize the depletion of crystalline cellulose as a proxy for wood degradation. Woodchips from upstream portions of the reactor exhibited the greatest degradation, probably due to greater DO exposure, and degradation was localized to a 100 to 200 μm thick surface layer that was also associated with higher concentrations of Fe and Mn. Greater degradation was associated with faster nitrate removal. μXANES analysis of Fe and Mn in the surface layer indicated the presence of a microenvironment in which oxygenation reactions of Fe(II) and Mn(II) could contribute to the formation of reactive oxidants involved in the degradation of lignocellulose. In conclusion, our results provide new insight into biogeochemical properties that influence wood decomposition in WBRs at both micro- and macroscales and how these wood degradation processes are coupled with denitrification.

36 MATERIALS SCIENCE↗

RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors

Abstract DNA polymerase θ (Polθ) is a polymerase-helicase fusion protein that is synthetically lethal with homologous recombination (HR) factors, such as BRCA1/2, and confers resistance to PARP inhibitors (PARPi) and other genotoxic cancer therapies. Previously developed Polθ polymerase (Polθ-pol) inhibitors (Polθi) exhibited limited pharmacological activity and metabolic stability, warranting the development of a Polθi with improved drug-like properties. Here, we developed RTx-303, a selective allosteric small-molecule Polθ-pol inhibitor that exhibits 5.1 nM IC50, 88% oral bioavailability, and a prolonged half-life along with its equipotent metabolite. X-ray crystallography highlights the development of a solvent-exposed side-chain that is essential for the optimal drug-like properties of RTx-303. Notably, RTx-303 exhibits significantly higher cellular potency than previously developed Polθ-pol inhibitors and strongly potentiates PARPi in BRCA1/2 mutant cells and patient-derived xenograft models. The superior potency, robust pharmacological activity, and high tolerability of RTx-303 warrant further development as a Polθ-pol inhibitor drug candidate.

Chandramouly, Gurushankar [Thomas Jefferson Univer↗

Characterizing Bioavailable Soil Nutrients Across Coastal Systems: Western Lake Erie and Chesapeake Bay

Terrestrial Aquatic Interfaces (TAIs), defined as where land meets water, exhibit important hydrological, biological, and biogeochemical dynamics and play a critical role in the Earth’s carbon cycle. Current Earth System Models improperly represent this role due to the complexity of these systems and the disproportionally large impact TAIs have relative to their area. To improve our predictive capacity of coastal system dynamics, a better understanding of carbon and nutrient cycling across TAI’s is needed. Coastal Observations, Mechanisms, and Predictions Across Systems and Scales (COMPASS) aims to achieve this through field observations and laboratory incubations throughout the Western Lake Erie and Chesapeake Bay regions. Here, we report on preliminary results from a soil characterization experiment across the WLE and CB regions. This experiment was conducted as part of the 2-year field, measurements, and experiments (FME) pilot study portion of COMPASS to provide initial baseline data for the sites and to characterize the spatial variability of our analytes. Soil samples were collected from three locations along the TAI transect (upland forest, transitional forest, and wetland) and analyzed for bioavailable nutrients using three types of extractions: (a) water extractions, (b) 2M KCl extractions, and (c) 1M NH4Cl extractions to analyze (a) water soluble organic carbon (WSOC), (b) ammonium and nitrate, and (c) base cations, including Ca, Mg, Na, K, and Fe. These analyses, in conjunction with other bulk physicochemical analyses, will help establish baseline understanding of these sites to drive future research and design focused experiments that will ultimately improve our predictive understanding of these freshwater and marine coastal TAIs and their response to short and long-term changes.

54 ENVIRONMENTAL SCIENCES↗

Biosensors for detecting and/or neutralizing bioavailable uranium and related U-sensitive genetic molecular components, gene cassettes, vectors, genetic circuits, compositions, methods and systems

UO 2 F 2 biosensors, and related U-sensing and/or F-sensing genetic molecular components, genetic circuits, compositions, methods and systems are described, which in several embodiments can be used to detect and/or neutralize uranium and in particular bioavailable UO 2 F 2 .

Park, Dan Mcfarland↗