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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 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Adaptive laboratory evolution and metabolic engineering of Cupriavidus necator for improved catabolism of volatile fatty acids

Bioconversion of high-volume waste streams into value-added products will be an integral component of the growing bioeconomy. Volatile fatty acids (VFAs) (e.g., butyrate, valerate, and hexanoate) are an emerging and promising waste-derived feedstock for microbial carbon upcycling. Cupriavidus necator H16 is a favorable host for conversion of VFAs into various bioproducts due to its diverse carbon metabolism, ease of metabolic engineering, and use at industrial scales. Here, in this study, we report that a common strategy to improve product titers in C. necator, deletion of the polyhydroxybutyrate (PHB) biosynthetic operon, results in a significant growth defect on VFA substrates. Using adaptive laboratory evolution, we identify mutations to the regulator gene phaR, the two-component response regulator-histidine kinase pair encoded by H16_A1372/H16_A1373, and the tripartite transporter assembly encoded by H16_A2296-A2298 as causative for improved growth on VFA substrates. Deletion of phaR and H16_A1373 led to significantly reduced NADH abundance accompanied by large changes to expression of genes involved in carbon metabolism, balance of electron carriers, and oxidative stress tolerance that may be responsible for improved growth of these engineered strains. These results provide insight into the role of PHB biosynthesis in carbon and energy metabolism and highlight a key role for the regulator PhaR in global regulatory networks. By combining mutations, we generated platform strains with significant growth improvements on VFAs, which can enable improved conversion of waste-derived VFA substrates to target bioproducts.

09 BIOMASS FUELS↗
DOE OSTI2021

Environmental Tuning of Homologs of the Orange Carotenoid Protein-Encoding Gene in the Cyanobacterium Fremyella diplosiphon

The orange carotenoid protein (OCP) family of proteins are light-activated proteins that function in dissipating excess energy absorbed by accessory light-harvesting complexes, i.e., phycobilisomes (PBSs), in cyanobacteria. Some cyanobacteria contain multiple homologs of the OCP-encoding gene ( ocp ). Fremyella diplosiphon , a cyanobacterium studied for light-dependent regulation of PBSs during complementary chromatic acclimation (CCA), contains several OCP homologs – two full-length OCPs, three Helical Carotenoid Proteins (HCPs) with homology to the N-terminus of OCP, and one C-terminal domain-like carotenoid protein (CCP) with homology to the C-terminus of OCP. We examined whether these homologs are distinctly regulated in response to different environmental factors, which could indicate distinct functions. We observed distinct patterns of expression for some OCP, HCP, and CCP encoding genes, and have evidence that light-dependent aspects of ocp homolog expression are regulated by photoreceptor RcaE which controls CCA. RcaE-dependent transcriptional regulator RcaC is also involved in the photoregulation of some hcp genes. Apart from light, additional environmental factors associated with cellular redox regulation impact the mRNA levels of ocp homologs, including salt, cold, and disruption of electron transport. Analyses of conserved sequences in the promoters of ocp homologs were conducted to gain additional insight into regulation of these genes. Several conserved regulatory elements were found across multiple ocp homolog promoters that potentially control differential transcriptional regulation in response to a range of environmental cues. The impact of distinct environmental cues on differential accumulation of ocp homolog transcripts indicates potential functional diversification of this gene family in cyanobacteria. These genes likely enable dynamic cellular protection in response to diverse environmental stress conditions in F . diplosiphon .

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2006

Submicrosecond Power-Switching Test Circuit

A circuit that changes an electrical load in a switching time shorter than 0.3 microsecond has been devised. This circuit can be used in testing the regulation characteristics of power-supply circuits . especially switching power-converter circuits that are supposed to be able to provide acceptably high degrees of regulation in response to rapid load transients. The combination of this power-switching circuit and a known passive constant load could be an attractive alternative to a typical commercially available load-bank circuit that can be made to operate in nominal constant-voltage, constant-current, and constant-resistance modes. The switching provided by a typical commercial load-bank circuit in the constant-resistance mode is not fast enough for testing of regulation in response to load transients. Moreover, some test engineers do not trust the test results obtained when using commercial load-bank circuits because the dynamic responses of those circuits are, variously, partly unknown and/or excessively complex. In contrast, the combination of this circuit and a passive constant load offers both rapid switching and known (or at least better known) load dynamics. The power-switching circuit (see figure) includes a signal-input section, a wide-hysteresis Schmitt trigger that prevents false triggering in the event of switch-contact bounce, a dual-bipolar-transistor power stage that drives the gate of a metal oxide semiconductor field-effect transistor (MOSFET), and the MOSFET, which is the output device that performs the switching of the load. The MOSFET in the specific version of the circuit shown in the figure is rated to stand off a potential of 100 V in the "off" state and to pass a current of 20 A in the "on" state. The switching time of this circuit (the characteristic time of rise or fall of the potential at the drain of the MOSFET) is .300 ns. The circuit can accept any of three control inputs . which one depending on the test that one seeks to perform: a repetitive waveform from a signal generator, momentary closure of a push-button switch, or closure or opening of a manually operated on/off switch. In the case of a signal generator, one can adjust the frequency and duty cycle as needed to obtain the desired AC power-supply response, which one could display on an oscilloscope. Momentary switch closure could be useful for obtaining (and, if desired, displaying on an oscilloscope set to trigger on an event) the response of a power supply to a single load transient. The on/off switch can be used to switch between load states in which static-load regulation measurements are performed.

Folk, Eric N.↗
NASA NTRSDate not supplied

Neurovascular Responses to Simulated Deep Space Radiation in a Human Organ-on-a-Chip Model

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high-linear energy transfer (LET) particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue analogs. Therefore, we utilized a high-throughput 3D organ-on-a-chip system, seeded with human induced pluripotent stem cell-derived astrocytes and brain endothelial cells, or brain endothelial cells alone, to study human neurovascular responses to simulated deep space radiation. We investigated the permeability and morphology of vascular structures formed by endothelial cells, as well as oxidative stress and secreted cytokines and chemokine levels over 1-7 days after irradiation with 0.25 – 0.5 Gy 5-ion simplified simulated galactic cosmic rays or 0.3 – 0.8 Gy high-LET 600 MeV/n 56Fe particles, and compared the outcomes to low-LET X-ray irradiation. We observed that simulated deep space radiation caused delayed astrocyte activation in a pattern resembling CNS responses to brain injury, caused oxidative stress and the production of inflammatory cytokines, and compromised BBB integrity by damaging tight junctions, thus increasing vascular permeability. Furthermore, our results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability early after irradiation, followed by switching to a more protective scar-like phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion. In a follow-up study using the same platform, we investigated the dose-rate effects of ionizing radiation, by exposing our model to chronic, low dose-rate, gamma radiation. Our model was significantly improved by adding additional cell types composing the BBB, modelling immune cell infiltration into the brain, and studying the effect of an antioxidant, to measure more complex outcomes and model more closely the effect of deep space radiation on the human BBB. In summary, our results present a human neurovascular model for space radiation studies and potential future automated payload adaptation, and suggest astrocyte regulatory mechanisms as targets for countermeasures to mitigate human neurovascular impairments during deep space exploration.

Ionizing radiation↗
NASA NTRSDate not supplied

Circulating miRNA Signature Predicts and Rescues Spaceflight Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated and real spaceflight and regulates vascular damage by simulated deep space radiation. In previous studies, we identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have validated the expression of key spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twin Study. We demonstrate that this circulating miRNA siganture is conserved between these different species and will serve as an ideal biomarker to monitor increase health risk due to exposure to the space environment. Lastly, to demonstrate their physiological relevance, we have utilized antagomirs to target a subset of miRNAs from the spaceflight associated signature to successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs. These results provide strong evidence to further develop a miRNA based countermeasure in astronauts.

Afshin Beheshti↗
DOE OSTI2020

Role of diversity-generating retroelements for regulatory pathway tuning in cyanobacteria

Abstract Background Cyanobacteria maintain extensive repertoires of regulatory genes that are vital for adaptation to environmental stress. Some cyanobacterial genomes have been noted to encode diversity-generating retroelements (DGRs), which promote protein hypervariation through localized retrohoming and codon rewriting in target genes. Past research has shown DGRs to mainly diversify proteins involved in cell-cell attachment or viral-host attachment within viral, bacterial, and archaeal lineages. However, these elements may be critical in driving variation for proteins involved in other core cellular processes. Results Members of 31 cyanobacterial genera encode at least one DGR, and together, their retroelements form a monophyletic clade of closely-related reverse transcriptases. This class of retroelements diversifies target proteins with unique domain architectures: modular ligand-binding domains often paired with a second domain that is linked to signal response or regulation. Comparative analysis indicates recent intragenomic duplication of DGR targets as paralogs, but also apparent intergenomic exchange of DGR components. The prevalence of DGRs and the paralogs of their targets is disproportionately high among colonial and filamentous strains of cyanobacteria. Conclusion We find that colonial and filamentous cyanobacteria have recruited DGRs to optimize a ligand-binding module for apparent function in signal response or regulation. These represent a unique class of hypervariable proteins, which might offer cyanobacteria a form of plasticity to adapt to environmental stress. This analysis supports the hypothesis that DGR-driven mutation modulates signaling and regulatory networks in cyanobacteria, suggestive of a new framework for the utility of localized genetic hypervariation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1992

Light regulation of the growth response in corn root gravitropism

Roots of Merit variety corn (Zea mays L.) require red light for orthogravitropic curvature. Experiments were undertaken to identify the step in the pathway from gravity perception to asymmetric growth on which light may act. Red light was effective in inducing gravitropism whether it was supplied concomitant with or as long as 30 minutes after the gravity stimulus (GS). The presentation time was the same whether the GS was supplied in red light or in darkness. Red light given before the GS slightly enhanced the rate of curvature but had little effect on the lag time or on the final curvature. This enhancement was expanded by a delay between the red light pulse and the GS. These results indicate that gravity perception and at least the initial transduction steps proceed in the dark. Light may regulate the final growth (motor) phase of gravitropism. The time required for full expression of the light enhancement of curvature is consistent with its involvement in some light-stimulated biosynthetic event.

NASA Discipline Number 40-50↗
DOE OSTI2026

OxyR regulates the oxidative stress response in Zymomonas mobilis during oxic growth and anoxic biofuel fermentation

The bacterium Zymomonas mobilis is widely studied for its potential as an industrial biofuel producer. Anoxic fermentation by Z. mobilis in lignocellulosic hydrolysate can generate bioethanol from renewable plant biomass. In this study, we deleted a gene from the Z. mobilis genome encoding a homolog of OxyR, a transcription factor that activates an oxidative stress response in bacteria to reduce reactive oxygen species (ROS). Deletion of this transcription factor inhibited growth of Z. mobilis in oxic, but not anoxic, conditions in laboratory media. RNA-Sequencing was perfromed on wild-type Z. mobilis (ZM4) and ∆oxyR in both oxic and anoxic conditions in rich media (ZRMG). This study reveals the indirect regulon of OxyR in Z. mobilis, which is important for both oxic growth and anoxic biofuel fermentation.

bioenergy↗
DOE OSTI2026

OxyR regulates the oxidative stress response in Zymomonas mobilis during oxic growth and anoxic biofuel fermentation

The bacterium Zymomonas mobilis is widely studied for its potential as an industrial biofuel producer. Anoxic fermentation by Z. mobilis in lignocellulosic hydrolysate can generate bioethanol from renewable plant biomass. In this study, we deleted a gene from the Z. mobilis genome encoding a homolog of OxyR, a transcription factor that activates an oxidative stress response in bacteria to reduce reactive oxygen species (ROS). Deletion of this transcription factor inhibited growth of Z. mobilis in oxic, but not anoxic, conditions in laboratory media. A ROS probe revealed that the oxyR response is required to reduce intracellular ROS during oxic growth. Importantly for biofuel production, the absence of oxyR inhibited growth and delayed ethanol production during anoxic hydrolysate fermentation. To determine the source of oxidative stress in hydrolysates, we grew ΔoxyR in a synthetic hydrolysate containing known inhibitors found in hydrolysates. There was no growth defect in ΔoxyR in the synthetic hydrolysate, indicating that known inhibitory compounds are not the source of anoxic oxidative stress. We determined that ammonia-fiber expansion switchgrass hydrolysate contains significant peroxide concentrations. Addition of catalase to hydrolysate improves growth of both ΔoxyR and wild-type Z. mobilis in hydrolysate. This study uncovers an important source of stress to Z. mobilis during biofuel fermentation.

OxyR↗
NASA NTRS2002

Understanding Fluid Shifts in the Brain: Choroidal Regulation Involved in the Cerebral Fluid Response to Altered Gravity

Fluid balance and regulation of body fluid production are critical aspects of life and survival on Earth. In space, without gravity exerting its usual downward pulling effect, the fluids of the human body shift in an unnatural, headward direction. After awhile, humans and other mammalian species adapt to the microgravity environment which leads to changes in the regulation and distribution of these body fluids. Previous spaceflight experiments have indicated that production of fluid in the brain and spinal cord, cerebrospinal fluid (CSF), might be reduced in rats exposed to microgravity. In this experiment conducted by Dr. Jacqueline Gabrion (University of Pierre and Marie Curie, France), proteins important for CSF production, and several molecules that regulate water and mineral transport, will be investigated in rats flown on the Shuttle. Dr. Gabrion and her team will determine the amounts of these proteins and molecules present in the brain in order to evaluate whether any changes have taken place during the rats' adaptation to microgravity. The levels of different aquaporins (proteins that act as a channel for water transport in and out of cells) will also be investigated in other areas of the brain and body to better understand the regulatory responses affecting these important water channel proteins. In addition to producing essential and basic information about fluid production in the brain and body, this experiment will reveal fundamental information about the mechanisms involved in cerebral adaptation and fluid balance during spaceflight.

Gabrion, Jaqueline↗
DOE OSTI2024

Carbon-phosphorus cycle models overestimate CO 2 enrichment response in a mature Eucalyptus forest

The importance of phosphorus (P) in regulating ecosystem responses to climate change has fostered P-cycle implementation in land surface models, but their CO 2 effects predictions have not been evaluated against measurements. Here, we perform a data-driven model evaluation where simulations of eight widely used P-enabled models were confronted with observations from a long-term free-air CO 2 enrichment experiment in a mature, P-limited Eucalyptus forest. We show that most models predicted the correct sign and magnitude of the CO 2 effect on ecosystem carbon (C) sequestration, but they generally overestimated the effects on plant C uptake and growth. We identify leaf-to-canopy scaling of photosynthesis, plant tissue stoichiometry, plant belowground C allocation, and the subsequent consequences for plant-microbial interaction as key areas in which models of ecosystem C-P interaction can be improved. Together, this data-model intercomparison reveals data-driven insights into the performance and functionality of P-enabled models and adds to the existing evidence that the global CO 2 -driven carbon sink is overestimated by models.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRSDate not supplied

Neurovascular effects of simulated space radiation

A major health risk for human deep space exploration is central nervous system (CNS) damage by ionizing radiation. Simulated galactic cosmic rays or their components, especially high-linear energy transfer particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of BBB permeability and also modulate neuroinflammation and neurodegeneration. However, BBB and astrocyte functions in regulating CNS responses to space radiation remain little investigated, especially in human organ analogs. Therefore, we developed and utilized a high-throughput 3D human neurovascular organ-on-a-chip model, seeded with induced pluripotent stem cell-derived cells. The effects of time course, ionizing radiation dose and dose rate were mapped by exposing the model to either acute, high dose rate radiation with simulated galactic cosmic rays or 600 MeV/n 56Fe particles, or protracted, low dose rate gamma radiation using a 57Co sealed source setup. We investigated BBB permeability, oxidative stress, cellular damage and secreted factors over the time period between 24 hours – 2 weeks after 0.1 – 0.8 Gy irradiation. We observed that ionizing radiation exposure increased BBB permeability, caused oxidative stress, damaged endothelial cells and altered expression of inflammatory cytokines with a subset of outcomes dependent on ionizing radiation dose rate. Furthermore, our results indicated that astrocyte functions were primarily deleterious at early time points and protective later after irradiation, resembling CNS responses to injury in vivo. Our findings in organ models were complemented by studies on true spaceflight using mouse spatial and single cell multi-omics, which similarly indicated spaceflight-mediated changes in astrocyte functions. In summary, our study evaluates the regulation of neurovascular responses to simulated space radiation, suggesting astrocytes as targets for countermeasures to mitigate CNS damage in deep space exploration.

Radiation↗
NASA NTRS1985

Computer simulation studies in fluid and calcium regulation and orthostatic intolerance

The systems analysis approach to physiological research uses mathematical models and computer simulation. Major areas of concern during prolonged space flight discussed include fluid and blood volume regulation; cardiovascular response during shuttle reentry; countermeasures for orthostatic intolerance; and calcium regulation and bone atrophy. Potential contributions of physiologic math models to future flight experiments are examined.

Source record↗
DOE OSTI2024

Structural basis of DNA recognition of the Campylobacter jejuni CosR regulator

Campylobacter jejuni is a foodborne pathogen commonly found in the intestinal tracts of animals. This pathogen is a leading cause of gastroenteritis in humans. Besides its highly infectious nature, C. jejuni is increasingly resistant to a number of clinically administrated antibiotics. As a consequence, the Centers for Disease Control and Prevention has designated antibiotic-resistant Campylobacter as a serious antibiotic resistance threat in the United States. The C. jejuni CosR regulator is essential to the viability of this bacterium and is responsible for regulating the expression of a number of oxidative stress defense enzymes. Importantly, it also modulates the expression of the CmeABC multidrug efflux system, the most predominant and clinically important system in C. jejuni that mediates resistance to multiple antimicrobials. Here, we report structures of apo-CosR and CosR bound with a 21 bp DNA sequence located at the cmeABC promotor region using both single-particle cryo-electron microscopy and X-ray crystallography. These structures allow us to propose a novel mechanism for CosR regulation that involves a long-distance conformational coupling and rearrangement of the secondary structural elements of the regulator to bind target DNA.

CosR-DNA complex↗
NASA NTRS1985

Incrementally Variable High-Voltage Supply

Programable power supply provides regulated output ranging from 2.5 to 2,500 volts. Exponential digital-to-analog converter provides low-voltage analog signal to power converter and to negative and positive high-voltage regulators. In response, converter furnishes voltage of approximate magnitude represented by analog signal, and regulators adjust voltage to precise magnitude. Entire voltage range covered in 169 steps. Total power consumption expected to be less than 2 watts.

Potter, D. W.↗
NASA NTRS2020

Circulating Mirna Spaceflight Signature Reveals Targets to Mitigate Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration, and long-duration spaceflight and regulates vascular damage caused by simulated deep space radiation. In previous studies, we had identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have confirmed the expression of these proposed spaceflight associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twins Study via direct quantification of miRNAs, miRNA sequencing, and inferring miRNA target levels based on single-cell RNA (scRNA-seq) and single-cell chromatin (scATAC-seq) sequencing data. To demonstrate the physiological relevance of key spaceflight associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs.

Sherina Malkani↗