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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 577 records · Page 32
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

The Effect of Ballistic Impacts on the High Cycle Fatigue Properties of Ti-48Al-2Nb-2Cr (at.%)

The ability of gamma - TiAl to withstand potential foreign and/or domestic object damage is a technical risk to the implementation of gamma - TiAl in low pressure turbine (LPT) blade applications. The overall purpose of the present study was to determine the influence of ballistic impact damage on the high cycle fatigue strength of gamma - TiAl simulated LPT blades. Impact and specimen variables included ballistic impact energy, projectile hardness, impact temperature, impact location, and leading edge thickness. The level of damage induced by the ballistic impacting was studied and quantified on both the impact (front) and backside of the specimens. Multiple linear regression was used to model the cracking and fatigue response as a function of the impact variables. Of the impact variables studied, impact energy had the largest influence on the response of gamma - TiAl to ballistic impacting. Backside crack length was the best predictor of remnant fatigue strength for low energy impacts (<0.74J) whereas Hertzian crack length (impact side damage) was the best predictor for higher energy impacts. The impacted gamma - TiAl samples displayed a classical mean stress dependence on the fatigue strength. For the fatigue design stresses of a 6th stage LPT blade in a GE90 engine, a Ti-48Al-2Nb-2Cr LPT blade would survive an impact of normal service conditions.

Draper, S. L.↗
NASA NTRS2003

An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cells

Induction of checkpoint responses in G1, S, and G2 phases of the cell cycle after exposure of cells to ionizing radiation (IR) is essential for maintaining genomic integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating this response in all three phases of the cell cycle. However, cells lacking functional ATM exhibit a prolonged G2 arrest after IR, suggesting regulation by an ATM-independent checkpoint response. The mechanism for this ataxia telangiectasia (AT)-independent G2-checkpoint response remains unknown. We report here that the G2 checkpoint in irradiated human AT cells derives from an overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the IR-induced prolonged G2 checkpoint and radiosensitizes AT cells to killing. These results link the activation of ATR/CHK1 with the prolonged G2 arrest in AT cells and show that activation of this G2 checkpoint contributes to the survival of AT cells.

NASA Discipline Radiation Health↗
NASA NTRS2004

The Search for Young Planetary Systems And the Evolution of Young Stars

The Space Interferometer Mission (SIM) will provide a census of planetary systems by con- ducting a broad survey of 2,000 stars that will be sensitive to the presence of planets with masses as small as approx. 15 Earth masses (1 Uranus mass) and a deep survey of approx. 250 of the nearest, stars with a mass limit of approx.3 Earth masses. The broad survey will include stars spanning a wide range of ages, spectral types, metallicity, and other important parameters. Within this larger context, the Young Stars and Planets Key Project will study approx. 200 stars with ages from 1 Myr to 100 Myr to understand the formation and dynamical evolution of gas giant planets. The SIM Young Stars and Planets Project will investigate both the frequency of giant planet formation and the early dynamical history of planetary systems. We will gain insight into how common the basic architecture of our solar system is compared with recently discovered systems with close-in giant planets by examining 200 of the nearest (less than 150 pc) and youngest (1-100 Myr) solar-type stars for planets. The sensitivity of the survey for stars located 140 pc away is shown in the planet mass-separation plane. We expect to find anywhere from 10 (assuming that only the presently known fraction of stars. 5-7%, has planets) to 200 (all young stars have planets) planetary systems. W-e have set our sensitivity threshold to ensure the detection of Jupiter-mass planets in the critical orbital range of 1 to 5 AU. These observations, when combined with the results of planetary searches of mature stars, will allow us to test theories of planetary formation and early solar system evolution. By searching for planets around pre-main sequence stars carefully selected to span an age range from 1 to 100 Myr, we will learn a t what epoch and with what frequency giant planets are found at the water-ice snowline where they are expected to form. This will provide insight into the physical mechanisms by which planets form and migrate from their place of birth, and about their survival rate. With these data in hand, we will provide data, for the first time, on such important questions as: What processes affect the formation and dynamical evolution of planets? When and where do planets form? What is initial mass distribution of planetary systems around young stars? How might planets be destroyed? What is the origin of the eccentricity of planetary orbits? What is the origin of the apparent dearth of companion objects between planets and brown dwarfs seen in mature stars? The observational strategy is a compromise between the desire to extend the planetary mass function as low as possible and the essential need to build up sufficient statistics on planetary occurrence. About half of the sample will be used to address the "where" and "when" of planet formation. We will study classical T Tauri stars (cTTs) which have massive accretion disks and post- accretion, weak-lined T Tauri stars (wTTs). Preliminary estimates suggest the sample will consist of approx. 30% cTTs and approx. 70% wTTs, driven in part by the difficulty of making accurate astrometric measurements toward objects with strong variability or prominent disks.

Beichman, Charles A.↗
DOE OSTI2021

Integrin alpha 6 as a stemness driver is a novel promising target for HPV (+) head and neck squamous cell carcinoma

Although the incidence rates of head and neck squamous cell carcinoma (HNSCC) associated with human papilloma virus (HPV) infection have recently been on the rise, the underlying mechanism of its tumorigenesis remains largely unknown. Here, we investigated whether HNSCC cells with high expression of integrin alpha 6 (ITGα6), one of the HPV receptors, have a preference during HPV infection. In addition, we examined the gain or loss of function of the ITGα6 gene in HPV + ve HNSCC cells, as well as its prognostic value in patients with HNSCC. HPV pseudovirus was found to be more infective, with HNSCC cells featuring an overexpressed ITGα6 gene compared to the control cells. Overexpression and suppression of ITGα6 respectively increases and decreases stemness phenotypes of HPV + ve HNSCC cells. Furthermore, ITGα6 can regulate stemness by partially mediating AKT pathway in HPV + ve HNSCC cells. Finally, patients with HPV + ve HNSCC had a poor prognosis in cases of elevated ITGα6 expression; however, the expression levels of ITGα6 did not influence the survival rates of HPV-negative HNSCC patients. In conclusion, ITGα6 can serve as a potential therapeutic target for HPV + ve HNSCC cancer-like stem cells (CSCs).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Factors affecting powerhouse passage of spring migrant smolts at federally operated hydroelectric dams of the Snake and Columbia rivers

From 2008 to 2018, acoustic telemetry studies were conducted to evaluate dam passage survival of spring migrant Chinook salmon and steelhead smolts at seven of the eight federally operated dams on the lower Snake and Columbia rivers. Data from over 87 000 dam passage events were evaluated using regression modeling to identify the effect of spill operations, environmental conditions, and fish characteristics on powerhouse passage probability. In general, powerhouse passage was positively correlated with discharge, negatively correlated with forebay temperature and fish size, and higher for fish that passed the dam at night and for those that approached from the powerhouse side of the river, suggesting powerhouse passage is largely a function of smolt activity level and swimming ability. As such, spilling large volumes of water to reduce powerhouse passage is likely to be most effective during times of reduced activity and swimming ability (e.g., at night, high flows, and cold temperatures). This information can be used to develop dam- and time-specific spill operations that optimize smolt passage, power generation, and other competing demands, such as adult passage.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2002

Comprehensive Evaluation of Power Supplies at Cryogenic Temperatures for Deep Space Applications

The operation of power electronic systems at cryogenic temperatures is anticipated in many future space missions such as planetary exploration and deep space probes. In addition to surviving the space hostile environments, electronics capable of low temperature operation would contribute to improving circuit performance, increasing system efficiency, and reducing development and launch costs. DC/DC converters are widely used in space power systems in the areas of power management, conditioning, and control. As part of the on-going Low Temperature Electronics Program at NASA, several commercial-off-the-shelf (COTS) DC/DC converters, with specifications that might fit the requirements of specific future space missions have been selected for investigation at cryogenic temperatures. The converters have been characterized in terms of their performance as a function of temperature in the range of 20 C to - 180 C. These converters ranged in electrical power from 8 W to 13 W, input voltage from 9 V to 72 V and an output voltage of 3.3 V. The experimental set-up and procedures along with the results obtained on the converters' steady state and dynamic characteristics are presented and discussed.

Patterson, Richard L.↗
NASA NTRS2020

Design and Test of an Electromechanical Rover Tether for the Exploration of Vertical Lunar Pit

Moon Diver is a proposed mission to land and deploy an extreme-terrain, tethered rover for the exploration of Tranquillitatis Pit, a large vertical cave entrance into the subsurface of Earth’s Moon. By leveraging a supportive tether, the Axel rover, developed by NASA’s Jet Propulsion Laboratory, would perform a controlled descent into the pit and deploy instruments along the pit wall. The purpose of this mission concept is to study a volcanic secondary crust as a function of depth in order to determine formation processes and chemical makeup. The lifeline of the mission would be the tether, which provides power from, and communication to the top-side lander. Critically, the tether also serves as mechanical support between the suspended rover and the lander, which acts as an anchor. While space tethers have been deployed both in orbit and terrestrially, the use of the proposed tether is unlike any known in the literature; the tether must come into contact with the terrain while under load. With respect to the environment, the tether must also survive abrasion from glassy regolith and volcanic rocks, bending around sharp edges, thermal extremes, and exposure to full spectrum ultra-violet (UV) radiation, all while reliably transferring up to 100 W of power and 1 Mbps of data. Furthermore, since the Axel rover pays out tether from an internal spool, the tether’s diameter must be minimized to increase spool capacity, allowing for up to a 300-m traverse while also meeting static and dynamic strength requirements. This paper covers several phases of the tether’s initial development, including i) a trade study of structure and materials with consideration for space heritage, ii) selected design justification, and iii) results from tests on prototype tethers looking into mechanical, electrical, and environmental properties, including exposure to rock regolith abrasion, load profiles at temperature, and degradation due to UV exposure while exposed to vacuum. Finally, we provide insights and lessons learned from lab and field tests, which inform our continued effort to design a tether capable of surviving rugged, lunar conditions.

Nensas, Issa↗
DOE OSTI2023

Engineering highly stable variants of Corynactis californica green fluorescent proteins

Fluorescent proteins (FPs) are versatile biomarkers that facilitate effective detection and tracking of macromolecules of interest in real time. Engineered FPs such as superfolder green fluorescent protein (sfGFP) and superfolder Cherry (sfCherry) have exceptional refolding capability capable of delivering fluorescent readout in harsh environments where most proteins lose their native functions. Our recent work on the development of a split FP from a species of strawberry anemone, Corynactis californica, delivered pairs of fragments with up to threefold faster complementation than split GFP. We present the biophysical, biochemical, and structural characteristics of five full-length variants derived from these split C. californica GFP (ccGFP). These ccGFP variants are more tolerant under chemical denaturation with up to 8 kcal/mol lower unfolding free energy than that of the sfGFP. It is likely that some of these ccGFP variants could be suitable as biomarkers under more adverse environments where sfGFP fails to survive. A structural analysis suggests explanations of the variations in stabilities among the ccGFP variants.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2003

Aerogel Composites for Aerospace Thermal Protection

Aerogel composites formed by infiltrating organic and/or inorganic aerogels into fiber matrix materials enable us to exploit the low thermal conductivity and low density of aerogels while maintaining the strength, structure and other useful properties of a porous fiber matrix. New materials for extreme heating ranges are needed to insulate future spacecraft against the extreme heat of planetary atmospheric entry, but the insulation mass must be minimized in order to maximize the payload. A reusable system passively insulates to survive heating unchanged for relatively low heating. Ablators, which sacrifice mass to control heating, are used to protect vehicles against more extreme heating for a single use thermal protection system (TPS). Aerogel composites were fabricated and tested for spacecraft thermal protection. The high-temperaturey high heat flux tests described in this paper were performed in NASA Ames arc-jet facilities to simulate spacecraft atmospheric entry, and include heating conditions predicted for the forebody and backshell of the Mars Science Lander (MSL) entry probe. The aerogel composites tested showed excellent thermal performance in the arc-jet tests, functioning both as reusuable insulation under lower heat fluxes, and as ablative aerogels under the extreme heating predicted for the MSL forebody.

White, Susan↗
NASA NTRS1999

Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

Non-NASA Center↗
NASA NTRSDate not supplied

The Impacts of Heating Actuators in Extremely Cold Space Environments

Conventional, grease-lubricated actuators for space mechanisms can achieve long life but must be heated above about 213 K, or -60 °C, to function in extremely cold environments. This paper first overviews a new NASA project that is developing two rotational actuators that can achieve long life without the need for supplemental heating. Then, the impacts of heating conventional, grease-lubricated actuators are studied for operation in a lunar permanently shadowed region. To facilitate the assessment, a novel total efficiency metric is introduced that relates the average power output to the average total power input (i.e., the power to heat plus the power to actuate/rotate). The assessment employs a thermal analysis of the energy required to heat an actuator from a survival temperature of 30 K to 213 K as well as the power required to subsequently maintain 213 K while in an operational state. Two concepts of actuator operation are considered that separately highlight the impacts of warmup heating energy and maintenance heater power. It is shown that in practical situations, the perceived efficiency of an actuator with 100% conventional operating efficiency can reach 10% or lower, particularly when the actuator has a high emissivity and is operated at lower duty cycles for durations less than 10 hours. Other impacts are presented along with a method of mitigating the impacts in some applications.

Extreme Environments↗
NASA NTRSDate not supplied

The Impacts of Heating Actuators in Extremely Cold Space Environments

Conventional, grease-lubricated actuators for space mechanisms can achieve long life but must be heated above about 213 K, or -60 °C, to function in extremely cold environments. This paper first overviews a new NASA project that is developing two rotational actuators that can achieve long life without the need for supplemental heating. Then, the impacts of heating conventional, grease-lubricated actuators are studied for operation in a lunar permanently shadowed region. To facilitate the assessment, a novel total efficiency metric is introduced that relates the average power output to the average total power input (i.e., the power to heat plus the power to actuate/rotate). The assessment employs a thermal analysis of the energy required to heat an actuator from a survival temperature of 30 K to 213 K as well as the power required to subsequently maintain 213 K while in an operational state. Two concepts of actuator operation are considered that separately highlight the impacts of warmup heating energy and maintenance heater power. It is shown that in practical situations, the perceived efficiency of an actuator with 100% conventional operating efficiency can reach 10% or lower, particularly when the actuator has a high emissivity and is operated at lower duty cycles for durations less than 10 hours. Other impacts are presented along with a method of mitigating the impacts in some applications.

space actuator↗
DOE OSTI2022

Laser Doppler vibrometry for piezoelectric coefficient ($d_{33}$) measurements in irradiated aluminum nitride

Sensors used for experiments in advanced reactors must survive in harsh environments. Few material systems can be used to construct sensors viable for extreme conditions. Aluminum nitride (AlN) is one such material because it has high thermal stability and radiation resistance and sustains good piezoelectric and dielectric properties at high temperatures. In this work, the piezoelectric coefficient $d_{33}$ of the AlN single-crystal with thermal and irradiation damage was investigated using an indirect method with a laser Doppler vibrometer (LDV). Surface electrodes were deposited on the AlN samples, and the vibration response of the samples to an applied voltage was monitored using the LDV as a function of the excitation frequency. The $d_{33}$ estimation was based on the excitation voltage and the thickness-mode displacement extracted from the LDV measurements. Further, six AlN substrates were irradiated with 8 MeV Al 2+ at three fluences (10 15 , 10 16 , and 10 17 ions/cm 2 ) and two temperatures (300 °C and 500 °C). The $d_{33}$ for the six irradiated samples and one pristine sample were measured, and the measurement uncertainty was estimated based on five repeated tests. All samples were also measured by a commercial piezometer for comparison. The experimental results demonstrate that the piezoelectric coefficients obtained by LDV were about 0.8–1.16 pm/V lower than those obtained by the piezometer. With the compensation of the clamping effect, the corrected LDV values are similar to the piezometer results. Both show similar trends in all samples, which validates the feasibility of the proposed method for $d_{33}$ measurement. Based on the LDV results, the irradiated samples show a 12%–22% decrease in $d_{33}$ compared with the pristine samples. The samples irradiated under the same fluence at a higher temperature (500 °C) demonstrated a lower $d_{33}$ than those at 300 °C. The effect of the retro-reflective tape, sample temperature, and sample size on the $d_{33}$ measurement were also studied.

36 MATERIALS SCIENCE↗
NASA NTRS2017

Oxygen Candle Background for Subs and Space

"At any time and without warning, a submarine may have to remain submerged for several days on account of the presence of the enemy, or rough weather, or serious accident to the machinery. Fortunately such occurrences are rare; but every commanding officer must be prepared to meet such an emergency that will afford his men the greatest possible chance of survival." Reference (1) This quotation is taken from a review of submarine air purification technology published by the Bureau of Medicine and Surgery in 1919. At that time, the U.S. Navy had just begun to experiment with possible air purification devices and supplies of oxygen that might permit submarines to remain submerged longer that the untreated closed atmosphere would allow. Submariners were exposed to elevated levels of carbon dioxide and reduced levels of oxygen that would be considered completely unacceptable by current standards. It was a different world, but humans are still humans, and the requirements for safe and effective functioning in a self-contained environment are really unchanged. The maximum submergence time for submarines as published in that work was approximately 48 hours, reference (1) In early submarines, the preferred supply of oxygen was 1800 psig compressed gas bled into the boat as needed, references (1,2). The need for added oxygen was occasionally "measured" by the physiological impact on the crew rather than a reliable instrument, reference (1). The design of submarine oxygen supply was limited to approximately 25 day submerged operation, reference (2). It was not until 1958 that U.S. submarines were able to carry out dives beyond that period and necessitated new sources of oxygen, reference (2). A curious second source of oxygen at the time was compressed air vessels that were bled into the boat while "vitiated" air (air with reduced oxygen and elevated carbon dioxide) from the opposite end of the boat was compressed into waiting empty vessels, reference (1). The periodic use of pressurized air to control oxygen caused swings in ambient pressure that was uncomfortable to the crew, reference (1). As early as 1919, liquid oxygen was a commercially available product and its use on submarines was contemplated, reference (1). It is interesting that even at this date, 1919, the danger of oils or greases when exposed to compressed or liquid oxygen was recognized: "One precaution must be always taken. No oil or grease should be used in the gauge or fittings or a dangerous explosion may result."

Graf, John↗
DOE OSTI2024

Chlorophyllase from Arabidopsis thaliana Reveals an Emerging Model for Controlling Chlorophyll Hydrolysis

Chlorophyll (Chl) is one of Nature’s most complex pigments to biosynthesize and derivatize. This pigment is vital for survival and also paradoxically toxic if overproduced or released from a protective protein scaffold. Therefore, along with the mass production of Chl, organisms also invest in mechanisms to control its degradation and recycling. One important enzyme that is involved in these latter processes is chlorophyllase. This enzyme is employed by numerous photosynthetic organisms to hydrolyze the phytol tail of Chl. Although traditionally thought to catalyze the first step of Chl degradation, recent work suggests that chlorophyllase is instead employed during times of abiotic stress or conditions that produce reactive oxygen species. However, the molecular details regarding how chlorophyllases are regulated to function under such conditions remain enigmatic. Here, we investigate the Arabidopsis thaliana chlorophyllase isoform AtCLH2 using site-directed mutagenesis, mass spectrometry, dynamic light scattering, size-exclusion multiangle light scattering, and both steady-state enzyme kinetic and thermal stability measurements. Through these experiments, we show that AtCLH2 exists as a monomer in solution and contains two disulfide bonds. One disulfide bond putatively maps to the active site, whereas the other links two N-terminal Cys residues together. These disulfide bonds are cleaved by chemical or chemical and protein-based reductants, respectively, and are integral to maintaining the activity, stability, and substrate scope of the enzyme. This work suggests that Cys residue oxidation in chlorophyllases is an emerging regulatory strategy for controlling the hydrolysis of Chl pigments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The influence of microbial colonization on inflammatory versus pro-healing trajectories in combat extremity wounds

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

RNA binding protein DAZAP1 promotes HCC progression and regulates ferroptosis by interacting with SLC7A11 mRNA

Highlights: • DAZAP1 effectively promotes HCC progression. • DAZAP1 negatively regulates ferroptosis in HCC cells. • DAZAP1 interacts with SLC7A11 mRNA, and positively regulates its stability. RNA-binding proteins (RBPs) closely regulate the whole lifecycle of most RNA molecules, from the very early stage of transcription to RNA decay. Dysregulation of RBPs significantly affects the fate of cancer-related transcripts. Therefore, it is imperative to fully understand the complicated RBP-RNA regulatory networks in malignant diseases and to explore novel therapeutic targets. The RBP DAZAP1 (deleted in azoospermia-associated protein 1), originally identified as an important protein in spermatogenesis, had rarely been studied in the context of carcinogenesis. The role of DAZAP1 in hepatocellular carcinoma (HCC) was unveiled in this study. The relative expression of DAZAP1 was significantly upregulated in HCC and was positively associated with several key malignant characteristics and poor postoperative survival in patients. DAZAP1 knockdown by small interfering RNA markedly inhibited HCC cell proliferation, migration and invasion. Furthermore, DAZAP1 significantly reduced cellular sensitivity to sorafenib (SF), which had been proven to be an inducer of ferroptosis by targeting the system Xc{sup −} (composed of a light chain, xCT/SLC7A11, and a heavy chain, 4F2 heavy chain). At the mechanistic level, DAZAP1 was identified as a potent inhibitor of ferroptosis and an efficient binding partner of SLC7A11 mRNA. Further study revealed that DAZAP1 interacted with the 3′UTR (untranslated region) of SLC7A11 mRNA and positively regulated its stability. In our work, we clarified novel functions of DAZAP1 and preliminarily revealed its underlying mechanism in ferroptosis, which may be conducive to the exploration of biomarkers and therapeutic targets in HCC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Genome-wide association of the metabolic shifts underpinning dark-induced senescence in Arabidopsis

Dark-induced senescence provokes profound metabolic shifts to recycle nutrients and to guarantee plant survival. To date, research on these processes has largely focused on characterizing mutants deficient in individual pathways. Here, we adopted a time-resolved genome-wide association-based approach to characterize dark-induced senescence by evaluating the photochemical efficiency and content of primary and lipid metabolites at the beginning, or after 3 or 6 days in darkness. We discovered six patterns of metabolic shifts and identified 215 associations with 81 candidate genes being involved in this process. Among these associations, we validated the roles of four genes associated with glycine, galactinol, threonine, and ornithine levels. We also demonstrated the function of threonine and galactinol catabolism during dark-induced senescence. Intriguingly, we determined that the association between tyrosine contents and TYROSINE AMINOTRANSFERASE 1 influences enzyme activity of the encoded protein and transcriptional activity of the gene under normal and dark conditions, respectively. Moreover, the single-nucleotide polymorphisms affecting the expression of THREONINE ALDOLASE 1 and the amino acid transporter gene AVT 1 B, respectively, only underlie the variation in threonine and glycine levels in the dark. Taken together, these results allow us to present a very detailed model of the metabolic aspects of dark-induced senescence, as well as the process itself.

59 BASIC BIOLOGICAL SCIENCES↗