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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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All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

A Multidisciplinary Modeling Approach of Plant Gas Exchange in Reduced Gravity Environments

In-situ food production is a necessary step for human exploration of the solar system and requires a deep understanding of plant growth in reduced gravity environments. In particular, the lack of buoyancy-driven convection changes the gas exchange at the leaf surface, which decreases photosynthesis and transpiration rates, and ultimately biomass production. To understand the intricate relations between physical, chemical, and biochemical processes, the following methodology combines the development of a mechanistic model of plant growth in reduced gravity environments, computational fluid dynamics (CFD) simulations, and experiments in different time frames.The model presented here is a coupled mass and energy balance using the single round leaf assumption, including gravity as an entry parameter, and the leaf surface temperature as an output variable. Measures of the leaf surface temperature using infra-red cameras allow for a computation of the transpiration rate. This approach was followed to design a parabolic flight experiment, which performed 7 flights, and enabled data collection for model validation in different gravity and ventilation settings on a short time frame. Current measures of carbon assimilation and transpiration rate at the leaf and canopy level using an infra-red gas analyzer (Li-6800) in 1g lab conditions on several species will enable a validation on longer time frames and further calibration of the model. CFD studies both on the parabolic flight and on the lab experimental set-up allow the precise assessment of ventilation above the canopy and plants' leaves.Ultimately, this work will provide recommendations for the design of future plant growth hardware, especially on the lowest adequate ventilation for optimal plant growth in reduced gravity environments, as well as assessing biomass and oxygen production rates on planetary surfaces and space stations. This work was funded by CNES, CNRS, Clermont Auvergne Metropole, and NASA Space Biology through NASA postdoctoral program / USRA.

Poulet, Lucie↗
DOE OSTI2025

Unraveling metabolism underpinning biomass composition shift in Scenedesmus obliquus under simulated outdoor conditions using 13 C-fluxomics

To render the resulting biomass more attractive and amenable for utilization as the basis for low-carbon intensity bioproducts, single-celled algae need to be biochemically and metabolically poised to assimilate and store the delivered carbon in the fastest and most efficient manner. Accelerating biochemical carbon storage, as primarily carbohydrates or lipids, is critical to achieve the high carbon capture potential that is assigned to algae. To guide strain optimization and engineering for maximizing carbon capture and storage, it is essential to elucidate the link between carbon metabolism and biomass composition. Most published metabolomics work in algae remains largely restricted to ideal and simplified environmental conditions in model organisms, thereby limiting their translation to outdoor implementation. In this work, we utilize 13 C isotopic labeling to characterize distinct intracellular metabolic fluxes before, during, and after nitrogen depletion-induced compositional shifts in Scenedesmus obliquus UTEX 393. The results indicate that a transition to carbohydrates is characterized by diverting flux to starch instead of replenishing the Calvin cycle for CO 2 fixation whereas the subsequent transition to lipids is fueled by NADPH produced by upregulating the phosphoenolpyruvate carboxylase (PEPC)–malic enzyme (ME) cycle flux. Our work highlights bottlenecks to carbohydrate- and lipid-rich biomass and can guide implementable strategies to control the fate of fixed carbon in S. obliquus.

09 BIOMASS FUELS↗
NASA NTRS1998

Taxane recovery from cells of Taxus in micro- and hypergravity

Cell suspension cultures of Taxus cuspidata produce taxanes that are released from the outer surface of cells into the culture medium as free and bound alkaloids. Paclitaxel (Taxol (TM)), is an anti-cancer drug in short supply. It has a taxane ring derived from baccatin III and a C-13 phenylisoserine side-chain. This drug is produced over a wide range of gravitational forces. Monoclonal and polyclonal antibodies to paclitaxel, baccatin III, and the C-13 phenylisoserine side chain were combined in multiple-labeling studies to localize taxanes and paclitaxel on cell surfaces or on particles released into the culture medium. Bioreactor vessel design altered the composition of taxanes recovered from cells in simulated microgravity. At 10(-2) and 2x10(-4)g, taxane recovery was reduced but biomass growth and percent paclitaxel was significantly increased. At 1 to 24g, growth was reduced with a significant recovery of total taxanes with low percent paclitaxel. Bound paclitaxel was also localized in endonuclease-rich fragmenting nuclei of individual apoptotic cells. A model is presented comprising TCH (touch) genes encoding enzymes that modify taxane-bearing xylan residues in cell walls, the calcium-sensing of gravitational forces by the cytoplasm, and the predisposition of nuclei to apoptosis. This integrates the adaptive physiological and biochemical responses of drug-producing genomes with gravitational forces.

Plants, Medicinal/chemistry/cytology↗
NASA NTRS1996

Physiological adaptations and countermeasures associated with long-duration spaceflights

Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.

NASA Center ARC↗
DOE OSTI2022

Enzymatic Nitrogen Insertion into Unactivated C–H Bonds

Selective functionalization of aliphatic C–H bonds, ubiquitous in molecular structures, could allow ready access to diverse chemical products. While enzymatic oxygenation of C–H bonds is well established, the analogous enzymatic nitrogen functionalization is still unknown; nature is reliant on pre-oxidized compounds for nitrogen incorporation. Likewise, synthetic methods for selective nitrogen derivatization of unbiased C–H bonds remain elusive. In this work, new-to-nature heme-containing nitrene transferases were used as starting points for the directed evolution of enzymes to selectively aminate and amidate unactivated C(sp3)–H sites. The desymmetrization of methyl- and ethylcyclohexane with divergent site selectivity is offered as demonstration. The evolved enzymes in these lineages are highly promiscuous and show activity towards a wide array of substrates, providing a foundation for further evolution of nitrene transferase function. Computational studies and kinetic isotope effects (KIEs) are consistent with a stepwise radical pathway involving an irreversible, enantiodetermining hydrogen atom transfer (HAT), followed by a lower-barrier diastereoselectivity determining radical rebound step. In-enzyme molecular dynamics (MD) simulations reveal a predominantly hydrophobic pocket with favorable dispersion interactions with the substrate. Here, by offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Visualizing group II intron dynamics between the first and second steps of splicing

Group II introns are ubiquitous self-splicing ribozymes and retrotransposable elements evolutionarily and chemically related to the eukaryotic spliceosome, with potential applications as gene-editing tools. Recent biochemical and structural data have captured the intron in multiple conformations at different stages of catalysis. Here, we employ enzymatic assays, X-ray crystallography, and molecular simulations to resolve the spatiotemporal location and function of conformational changes occurring between the first and the second step of splicing. We show that the first residue of the highly-conserved catalytic triad is protonated upon 5’-splice-site scission, promoting a reversible structural rearrangement of the active site (toggling). Protonation and active site dynamics induced by the first step of splicing facilitate the progression to the second step. Our insights into the mechanism of group II intron splicing parallels functional data on the spliceosome, thus reinforcing the notion that these evolutionarily-related molecular machines share the same enzymatic strategy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1975

Prevention of decompression sickness during a simulated space docking mission

This study has shown that repetitive exchanges between the Apollo space vehicle atmosphere of 100% oxygen at 5 psia (258 torr) and the Soyuz spacecraft atmosphere of 30% oxygen-70% nitrogen at 10 psia (533 torr), as simulated in altitude chambers, will not likely result in any form of decompression sickness. This conclusion is based upon the absence of any form of bends in seven crewmen who participated in 11 tests distributed over three 24-h periods. During each period, three transfers from the 5 to the 10 psia environments were performed by simulating passage through a docking module which served as an airlock where astronauts and cosmonauts first adapted to each other's cabin gases and pressures before transfer. Biochemical tests, subjective fatigue scores, and the complete absence of any form of pain were also indicative that decompression sickness should not be expected if this spacecraft transfer schedule is followed.

Cooke, J. P.↗
NASA NTRS2023

Modeling Global Indices for Estimating Non-Photosynthetic Vegetation Cover

Non-photosynthetic vegetation (NPV) includes plant litter, senesced leaves, and crop residues. NPV plays an essential role in terrestrial ecosystem processes, and is an important indicator of drought severity, ecosystem disturbance, agricultural resilience, and wildfire danger. Current moderate spatial resolution multispectral satellite systems (e.g., Landsat and Sentinel-2) have only a single band in the 2000–2500 nm shortwave infrared “SWIR2” range where non-pigment biochemical constituents of NPV, including cellulose and lignin, have important spectral absorption features. Thus, these current systems have suboptimal capabilities for characterizing NPV cover. This research used simulated spectral mixtures accounting for variability among NPV and soils to evaluate globally-appropriate hyperspectral and multispectral indices for estimation of fractional NPV cover. The Continuum Interpolated NPV Depth Index (CINDI), a weighted ratio index measuring lignocellulose absorption near 2100 nm, was found to produce the lowest error in estimating NPV cover. CINDI was less sensitive to variability in soil spectra and green vegetation cover than competing indices. While CINDI was sensitive to the relative water content of soil and NPV, this sensitivity allowed for correcting error in estimated NPV cover as water content increased. CINDI bands were less capable than Dual Absorption NPV Index (DANI) bands for maintaining continuity with the heritage Landsat SWIR2 band, but combining multiple CINDI bands demonstrated adequate continuity. Three SWIR2 bands with band centers at 2038, 2108, and 2211 nm can provide superior capabilities for future moderate resolution multispectral/superspectral systems targeting NPV monitoring, including the next generation Landsat mission (Landsat Next). These bands and the associated CINDI index provide potential for global NPV monitoring using a constellation of future superspectral sensors and imaging spectrometers, with applications including improving soil management, preventing land degradation, evaluating impacts of drought, mapping ecosystem disturbance, and assessing wildfire danger.

Index optimization↗
NASA NTRS1989

Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity

The effects of simulated microgravity (30 days of continuous 6-deg headdown bedrest, BR) on the structural and metabolic characteristics of human skeletal muscle were determined. Percutaneous needle biopsy samples obtained from the vastus lateralis and soleus muscles before and after the headdown BR were analyzed for histochemical, biochemical and ultrastructual changes. It was found that headdown BR led to decreases in both fast-twitch and slow-twitch fiber areas in both muscles, and there was evidence of remodeling of the ultrastructure in both muscles. The activities of beta-hydroxyacyl-CoA dehydrogenase and citrate synthase were reduced during BR, but phosphofructokinase and lactate dehydrogenase activities did not change. The results indicate that 30-d exposure to simulated microgravity decreased the capacity for aerobic energy supply of human skeletal muscle and led to a disorganization of the contractile machinery.

Hikida, Robert S.↗
DOE OSTI2021

TEA Modeling to Quantify Economic Implications for Biorefinery Processing of Isolated Anatomical Fractions of Corn Stover

The Feedstock-Conversion Interface Consortium (FCIC; https://www.energy.gov/sites/prod/files/2020/01/f70/beto-fcic-overview-web.pdf), a collaboration of nine national laboratory partners, seeks to understand impacts of feedstock attributes on biorefinery performance. It is hypothesized that different individual anatomical fractions of corn stover vary in composition and recalcitrance, such that processing each fraction on its own through dedicated campaigns may enable better biorefinery economics overall relative to processing the whole stover material. This presentation focuses on techno-economic analysis (TEA) modeling to quantify the yield and cost ramifications for processing isolated anatomical fractions of corn stover through a low-temperature conversion biorefinery, reflecting a biochemical processing pathway consisting of biomass deconstruction through pretreatment and enzymatic hydrolysis, sugar fermentation and upgrading to hydrocarbon fuels, and lignin upgrading to value-added coproducts. Commercial-scale process simulation and economic evaluation leveraged experimental and analytical data from FCIC researchers for conversion of whole corn stover plus three individual anatomical fractions (cobs, husks, and stalks) across key steps of the conversion process. Our assessment found encouraging potential for biorefinery economic gains that may be achieved through this approach. TEA results indicated fuel yields varying from 29-44 gallons gasoline equivalent (GGE)/dry ton for the individual anatomical fractions compared to whole stover at 34 GGE/ton, equating to minimum fuel selling prices (MFSPs) between $6.37-$10.18/GGE for the fractions versus $8.76/GGE for whole stover (when lignin is burned), or $9.15-$15.19/GGE for the fractions versus $13.11/GGE for whole stover (when lignin is upgraded to coproducts, based on current experimental performance levels). Cobs and husks demonstrated the ability to achieve the highest fuel yields and lowest MFSPs, outperforming whole stover, while stalks led to the opposite result, as a composite reflection of compositional differences and process convertibility. Notably, even when taking the weighted average of the results reflecting each anatomical fraction weighted by its corresponding makeup of corn stover, this feasibility TEA screening supports feedstock cost allowances on the order of roughly $22-$29/ton as may reflect accommodating additional biomass fractionation equipment during feedstock pre-processing upstream of the conversion biorefinery gate to separate corn stover into such constituent fractions. Or viewed differently, the weighted average MFSP for the fractions was found to be $0.31-$0.32/GGE lower than the MFSP for the whole stover basis across either lignin scenario, when maintaining a fixed biomass feedstock cost. These findings highlight favorable implications for biorefinery economics as may be achieved by moving to a staged campaign approach for processing different corn stover fractions sequentially. Further opportunities exist for future work to fill in data gaps for remaining anatomical constituents (e.g. leaves) that were not included in the initial experimental studies, though are expected to maintain similar trends.

biochemical processing pathway↗
DOE OSTI2024

Neutrons in Structural Biology: Challenges and Opportunities (Workshop Report)

Gaining a thorough understanding of biological systems requires building our knowledge about biological processes from the level of atoms and electrons, and up to whole organisms. Such comprehensive knowledge will allow for a predictive understanding of complex biological systems behavior. It will guide us in the design and development of novel therapeutics and vaccines to tackle existing health threats and to prepare for future pandemics, and it will provide information necessary to create new biomaterials and bio-inspired technologies through manipulation of biological macromolecules, their assemblies, single cells and even microorganisms. Reaching these goals will require a synergistic combination of multiple experimental techniques with molecular calculations and predictive simulations, and the design and development of new techniques and capabilities that bridge current knowledge and technology gaps. Neutron scattering provides unique information about the biomacromolecular structure and function and can play a major role in achieving these goals. A workshop was held to engage the scientific community in identifying pressing challenges in biochemistry, structural biology, enzymology and structure-guided drug design not solved with the current neutron scattering technologies or utilizing other structural biology techniques such as X-ray crystallography, NMR, and cryo-EM. The workshop brought together structural biology, biochemistry and computational experts, as well as early career researchers and students, creating a forum for discussing scientific advancement and collaboration. The workshop included a one-day satellite training workshop where graduate students and postdoctoral researchers were educated in the application of neutron crystallography and small-angle scattering in structural biology. Furthermore, the Instrument Scientific Advisory Board (ISAB) for the development of a macromolecular neutron diffractometer at ORNL’s Second Target Station was introduced at the workshop. The major outcome was that neutrons can provide atomic-level understanding of biomacromolecular structure, function and dynamics which is of paramount importance for addressing the identified challenges. Neutron crystallography, in particular, can resolve long-standing biochemical issues regarding enzyme function by delineating the underlying chemistry and can have a major impact on the design of small-molecule therapeutics, especially in combination with molecular computation (quantum chemistry and molecular dynamics simulations) and the emerging artificial intelligence (AI)-assisted drug design technologies. The unique properties of neutrons, including their high sensitivity to hydrogen and their non-destructive nature, make them ideal probes of biological matter. There is a palpable need in the scientific community to expand and enhance the impact of neutron sciences on biology. Neutron crystallography is the only structural biology method capable of determining positions of all hydrogen atoms in proteins, nucleic acids and their complexes at near-physiological temperatures and of unstable species at cryogenic temperatures. Moreover, neutron analysis is non-ionizing, non-destructive and does not perturb the structure or redox chemistry of active site metal centers and clusters in proteins, which can be invaluable for studying radiation-sensitive metalloprotein complexes. Further, neutron energies used in scattering applications are similar to atomic motions, permitting neutron spectroscopies to characterize the dynamics of biomacromolecules on the picosecond to microsecond timescales. The different sensitivities of neutrons to protium (H) and deuterium (D) isotopes of hydrogen allow enhanced visibility of specific parts of biological complexes through isotopic labeling. The impact of neutrons will be most powerful when neutron scattering is combined with complementary experimental techniques that use photons and electrons, and with high-performance computing. The interconnection and mutuality of the experimental and theoretical capabilities will drive discoveries in biological and health sciences to generate more complete picture of complex biological systems. The major limitation in the field of biological neutron crystallography has been signal-to-noise, demanding large samples that are difficult to produce for the majority of biomacromolecules and limiting the applicability of this technique in biological sciences. A neutron crystallography instrument at the Second Target Station will revolutionize biological science with neutrons by engaging a large scientific community of structural biologists, enabling successful neutron diffraction experiments from radically smaller biomacromolecular crystals, resolving unanswered biochemical questions, and meaningfully contributing to rational drug design. The meeting highlighted 10 grand challenges that will be addressed with this advanced capability over the next decade and beyond, and the recommendations required to help address them are given below.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1989

Blood biochemical and cellular changes during a decompression procedure involving eight hours of oxygen prebreathing

Chemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 8 h of oxygen prebreathing. The exposure was designed to simulate space-flight extravehicular activity (EVA) for 6 h. Several statistically significant changes in blood parameters were observed following the exposure: increases in calcium, magnesium, osmolality, low-density lipoprotein cholesterol, monocytes, and prothrombin time, and decreases in chloride, creatine phosphokinase and eosinophils. The changes, however, were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression profile used in this study is not likely to result in blood changes that would pose a threat to astronauts during EVA.

Oxygen/administration & dosage↗
DOE OSTI2020

Quantitative comparison between sub-millisecond time resolution single-molecule FRET measurements and 10-second molecular simulations of a biosensor protein

Molecular Dynamics (MD) simulations seek to provide atomic-level insights into conformationally dynamic biological systems at experimentally relevant time resolutions, such as those afforded by single-molecule fluorescence measurements. However, limitations in the time scales of MD simulations and the time resolution of single-molecule measurements have challenged efforts to obtain overlapping temporal regimes required for close quantitative comparisons. Achieving such overlap has the potential to provide novel theories, hypotheses, and interpretations that can inform idealized experimental designs that maximize the detection of the desired reaction coordinate. Here, we report MD simulations at time scales overlapping with in vitro single-molecule Förster (fluorescence) resonance energy transfer (smFRET) measurements of the amino acid binding protein LIV-BP SS at sub-millisecond resolution. Computationally efficient all-atom structure-based simulations, calibrated against explicit solvent simulations, were employed for sampling multiple cycles of LIV-BP SS clamshell-like conformational changes on the time scale of seconds, examining the relationship between these events and those observed by smFRET. The MD simulations agree with the smFRET measurements and provide valuable information on local dynamics of fluorophores at their sites of attachment on LIV-BP SS and the correlations between fluorophore motions and large-scale conformational changes between LIV-BP SS domains. We further utilize the MD simulations to inform the interpretation of smFRET data, including Förster radius (R 0 ) and fluorophore orientation factor (κ 2 ) determinations. The approach we describe can be readily extended to distinct biochemical systems, allowing for the interpretation of any FRET system conjugated to protein or ribonucleoprotein complexes, including those with more conformational processes, as well as those implementing multi-color smFRET.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Determinants of photochemical characteristics of the photosynthetic electron transport chain of maize

The photosynthetic electron transport chain (ETC) is the bridge that links energy harvesting during the photophysical reactions at one end and energy consumption during the biochemical reactions at the other. Its functioning is thus fundamental for the proper balance between energy supply and demand in photosynthesis. Currently, there is a lack of understanding regarding how the structural properties of the ETC are affected by nutrient availability and plant developmental stages, which is a major roadblock to comprehensive modeling of photosynthesis. Redox parameters reflect the structural controls of ETC on the photochemical reactions and electron transport. We conducted joint measurements of chlorophyll fluorescence (ChlF) and gas exchange under systematically varying environmental conditions and growth stages of maize and sampled foliar nutrient contents. We utilized the recently developed steady-state photochemical model to infer redox parameters of electron transport from these measurements. We found that the inferred values of these photochemical redox parameters varied with leaf macronutrient content. These variations may be caused either directly by these nutrients being components of protein complexes on the ETC or indirectly by their impacts on the structural integrity of the thylakoid and feedback from the biochemical reactions. Also, the redox parameters varied with plant morphology and developmental stage, reflecting seasonal changes in the structural properties of the ETC. Our findings will facilitate the parameterization and simulation of complete models of photosynthesis.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2013

NASA Models of Space Radiation Induced Cancer, Circulatory Disease, and Central Nervous System Effects

The risks of late effects from galactic cosmic rays (GCR) and solar particle events (SPE) are potentially a limitation to long-term space travel. The late effects of highest concern have significant lethality including cancer, effects to the central nervous system (CNS), and circulatory diseases (CD). For cancer and CD the use of age and gender specific models with uncertainty assessments based on human epidemiology data for low LET radiation combined with relative biological effectiveness factors (RBEs) and dose- and dose-rate reduction effectiveness factors (DDREF) to extrapolate these results to space radiation exposures is considered the current "state-of-the-art". The revised NASA Space Risk Model (NSRM-2014) is based on recent radio-epidemiology data for cancer and CD, however a key feature of the NSRM-2014 is the formulation of particle fluence and track structure based radiation quality factors for solid cancer and leukemia risk estimates, which are distinct from the ICRP quality factors, and shown to lead to smaller uncertainties in risk estimates. Many persons exposed to radiation on earth as well as astronauts are life-time never-smokers, which is estimated to significantly modify radiation cancer and CD risk estimates. A key feature of the NASA radiation protection model is the classification of radiation workers by smoking history in setting dose limits. Possible qualitative differences between GCR and low LET radiation increase uncertainties and are not included in previous risk estimates. Two important qualitative differences are emerging from research studies. The first is the increased lethality of tumors observed in animal models compared to low LET radiation or background tumors. The second are Non- Targeted Effects (NTE), which include bystander effects and genomic instability, which has been observed in cell and animal models of cancer risks. NTE's could lead to significant changes in RBE and DDREF estimates for GCR particles, and the potential effectiveness of radiation mitigator's. The NSRM- 2014 approaches to model radiation quality dependent lethality and NTE's will be described. CNS effects include both early changes that may occur during long space missions and late effects such as Alzheimer's disease (AD). AD effects 50% of the population above age 80-yr, is a degenerative disease that worsens with time after initial onset leading to death, and has no known cure. AD is difficult to detect at early stages and the small number of low LET epidemiology studies undertaken have not identified an association with low dose radiation. However experimental studies in mice suggest GCR may lead to early onset AD. We discuss modeling approaches to consider mechanisms whereby radiation would lead to earlier onset of occurrence of AD. Biomarkers of AD include amyloid beta (A(Beta)) plaques, and neurofibrillary tangles (NFT) made up of aggregates of the hyperphosphorylated form of the micro-tubule associated, tau protein. Related markers include synaptic degeneration, dentritic spine loss, and neuronal cell loss through apoptosis. Radiation may affect these processes by causing oxidative stress, aberrant signaling following DNA damage, and chronic neuroinflammation. Cell types to be considered in multi-scale models are neurons, astrocytes, and microglia. We developed biochemical and cell kinetics models of DNA damage signaling related to glycogen synthase kinase-3(Beta) (GSK3(Beta)) and neuroinflammation, and considered multi-scale modeling approaches to develop computer simulations of cell interactions and their relationships to A(Beta) plaques and NFTs. Comparison of model results to experimental data for the age specific development of A(Beta) plaques in transgenic mice will be discussed.

Cucinotta, Francis A.↗
DOE OSTI2025

Covalent Drug Binding in Live Cells Monitored by Mid-Infrared Quantum Cascade Laser Spectroscopy: Photoactive Yellow Protein as a Model System

The detection of drug-target interactions in live cells enables analysis of therapeutic compounds in a native cellular environment. Recent advances in spectroscopy and molecular biology have facilitated the development of genetically encoded vibrational probes like nitriles that can sensitively report on molecular interactions. Nitriles are powerful tools for measuring electrostatic environments within condensed media like proteins, but such measurements in live cells have been hindered by low signal-to-noise ratios. In this study, we design a spectrometer based on a double-beam quantum cascade laser (QCL)-based transmission infrared (IR) source with balanced detection that can significantly enhance sensitivity to nitrile vibrational probes embedded in proteins within cells compared to a conventional FTIR spectrometer. Here, using this approach, we detect small-molecule binding in Escherichia coli, with particular focus on the interaction between para-Coumaric acid (pCA) and nitrile-incorporated photoactive yellow protein (PYP). This system effectively serves as a model for investigating covalent drug binding in a cellular environment. Notably, we observe large spectral shifts of up to 15 cm –1 for nitriles embedded in PYP between the unbound and drug-bound states directly within bacteria, in agreement with observations for purified proteins. Such large spectral shifts are ascribed to the changes in the hydrogen-bonding environment around the local environment of nitriles, accurately modeled through high-level molecular dynamics simulations using the AMOEBA force field. Our findings underscore the QCL spectrometer’s ability to enhance sensitivity for monitoring drug–protein interactions, offering new opportunities for advanced methodologies in drug development and biochemical research.

chromophores↗
NASA NTRS2013

Photosynthesis-dependent Isoprene Emission from Leaf to Planet in a Global Carbon-chemistry-climate Model

We describe the implementation of a biochemical model of isoprene emission that depends on the electron requirement for isoprene synthesis into the FarquharBallBerry leaf model of photosynthesis and stomatal conductance that is embedded within a global chemistry-climate simulation framework. The isoprene production is calculated as a function of electron transport-limited photosynthesis, intercellular and atmospheric carbon dioxide concentration, and canopy temperature. The vegetation biophysics module computes the photosynthetic uptake of carbon dioxide coupled with the transpiration of water vapor and the isoprene emission rate at the 30 min physical integration time step of the global chemistry-climate model. In the model, the rate of carbon assimilation provides the dominant control on isoprene emission variability over canopy temperature. A control simulation representative of the present-day climatic state that uses 8 plant functional types (PFTs), prescribed phenology and generic PFT-specific isoprene emission potentials (fraction of electrons available for isoprene synthesis) reproduces 50 of the variability across different ecosystems and seasons in a global database of 28 measured campaign-average fluxes. Compared to time-varying isoprene flux measurements at 9 select sites, the model authentically captures the observed variability in the 30 min average diurnal cycle (R2 6496) and simulates the flux magnitude to within a factor of 2. The control run yields a global isoprene source strength of 451 TgC yr1 that increases by 30 in the artificial absence of plant water stress and by 55 for potential natural vegetation.

photosynthesis↗