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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Variation in Flooding Tolerance in Populus deltoides ‘D-124’ and P. trichocarpa x P. deltoides Hybrid ‘52–225’

Flooding poses a substantial challenge to plant survival and productivity, particularly in riparian genus like Populus. This study examines the physiological, morphological, metabolic, and molecular responses of Populus deltoides ‘D-124’ and P. trichocarpa x P. deltoides hybrid clone ‘52–225’ under control and inundated conditions to identify differences in flooding tolerance. Under flooding conditions, physiological and cellular stress was more pronounced in P. deltoides ‘D-124’ than in the hybrid clone ‘52–225,’ as evidenced by lower transpiration (E), photosynthesis (A), and chlorophyll content. In contrast, ‘52–225’ showed reduced ROS accumulation suggesting better cellular function under stress. Morphologically, ‘52–225’ produced more shoot-born roots, which likely enhance oxygen transport and metabolic activity during flooding. Metabolite profiling revealed both overlapping and distinct patterns of sugar and amino acid accumulation between genotypes. Gene expression analysis revealed that flooding-responsive genes, including ALCOHOL DEHYDROGENASE 1 and HYPOXIA RESPONSIVE ERF 2, were activated in both genotypes, with a more pronounced response noted in ‘52–225.’ These findings extend our understanding of flooding tolerance mechanisms in Populus by connecting physiological traits, stress responses, and genetic regulation. This research contributes to the development of more flooding-resilient poplar varieties, with potential applications in breeding and restoration programs for flooding-prone environments.

Flooding stress↗
DOE OSTI2023

Sel1-like proteins and peptides are the major Oxalobacter formigenes -derived factors stimulating oxalate transport by human intestinal epithelial cells

Kidney stones (KSs) are very common, excruciating, and associated with tremendous healthcare cost, chronic kidney disease (CKD), and kidney failure (KF). Most KSs are composed of calcium oxalate and small increases in urinary oxalate concentration significantly enhance the stone risk. Oxalate also potentially contributes to CKD progression, kidney disease-associated cardiovascular diseases, and poor renal allograft survival. This emphasizes the urgent need for plasma and urinary oxalate lowering therapies, which can be achieved by enhancing enteric oxalate secretion. We previously identified Oxalobacter formigenes (O. formigenes)-derived factors secreted in its culture-conditioned medium (CM), which stimulate oxalate transport by human intestinal Caco2-BBE (C2) cells and reduce urinary oxalate excretion in hyperoxaluric mice by enhancing colonic oxalate secretion. Given their remarkable therapeutic potential, we now identified Sel1-like proteins as the major O. formigenes-derived secreted factors using mass spectrometry and functional assays. Crystal structures for six proteins were determined to confirm structures and better understand functions. OxBSel1-14-derived small peptides P8 and P9 were identified as the major factors, with P8 + 9 closely recapitulating the CM’s effects, acting through the oxalate transporters SLC26A2 and SLC26A6 and PKA activation. Besides C2 cells, P8 + 9 also stimulate oxalate transport by human ileal and colonic organoids, confirming that they work in human tissues. Finally, P8 and P9 peptides are identified as the major O. formigenes-derived secreted factors and they have significant therapeutic potential for hyperoxalemia, hyperoxaluria, and related disorders, impacting the outcomes of patients suffering from KSs, enteric hyperoxaluria, primary hyperoxaluria, CKD, KF, and renal transplant recipients.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

EMC3 regulates mesenchymal cell survival via control of the mitotic spindle assembly

Eukaryotic cells transit through the cell cycle to produce two daughter cells. Dysregulation of the cell cycle leads to cell death or tumorigenesis. Herein, we found a subunit of the ER membrane complex, EMC3, as a key regulator of cell cycle. Conditional deletion of Emc3 in mouse embryonic mesoderm led to reduced size and patterning defects of multiple organs. Emc3 deficiency impaired cell proliferation, causing spindle assembly defects, chromosome mis-segregation, cell cycle arrest at G2/M, and apoptosis. Upon entry into mitosis, mesenchymal cells upregulate EMC3 protein levels and localize EMC3 to the mitotic centrosomes. Further analysis indicated that EMC3 works together with VCP to tightly regulate the levels and activity of Aurora A, an essential factor for centrosome function and mitotic spindle assembly: while overexpression of EMC3 or VCP degraded Aurora A, their loss led to increased Aurora A stability but reduced Aurora A phosphorylation in mitosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Structural modeling and dynamic analysis of condensate storage tanks in nuclear power plants

Condensate storage tanks (CSTs) in nuclear power plants (NPPs) are classified as critical equipment capable of surviving strong shaking in a design basis earthquake to assure the ability to subsequently provide cooling water. Structural modeling and dynamic analysis of CSTs are complicated due to fluid-structure interaction (FSI) and coupling issues, which could have significant effects on seismic response. The capability of a number of approximate models to capture seismic response is investigated using dynamic analysis results from detailed finite element models. Modal analyses and time history analyses are carried out using both 2D and 3D models to predict the dynamic behavior of CSTs as a function of ground motion intensity. Although 2D simplified models can be used to quickly evaluate the dynamic response of CSTs when there is substantial margin to failure, a detailed 3D model is required when it is necessary to examine a limit state associated with the failure mode of the tank. The findings show good agreement between the natural frequencies of convective modes determined from the 2D and 3D CST models. The difference between the frequencies of impulsive modes were found to be equal to or less than 25%.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
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↗
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↗
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↗
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↗
DOE OSTI2022

Core cysteine residues in the Plasminogen-Apple-Nematode (PAN) domain are critical for HGF/c-MET signaling

The Plasminogen-Apple-Nematode (PAN) domain, with a core of four to six cysteine residues, is found in > 28,000 proteins across 959 genera. Still, its role in protein function is not fully understood. The PAN domain was initially characterized in numerous proteins, including HGF. Dysregulation of HGF-mediated signaling results in multiple deadly cancers. The binding of HGF to its cell surface receptor, c-MET, triggers all biological impacts. Here, we show that mutating four core cysteine residues in the HGF PAN domain reduces c-MET interaction, subsequent c-MET autophosphorylation, and phosphorylation of its downstream targets, perinuclear localization, cellular internalization of HGF, and its receptor, c-MET, and c-MET ubiquitination. Furthermore, transcriptional activation of HGF/c-MET signaling-related genes involved in cancer progression, invasion, metastasis, and cell survival were impaired. Thus, targeting the PAN domain of HGF may represent a mechanism for selectively regulating the binding and activation of the c-MET pathway.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

The effect of high-power transient events on tungsten and tungsten coatings used for radio frequency launcher applications

High-temperature plasma-facing material coatings used for radio frequency (RF) launchers need to be robust enough to survive RF breakdown arcing or other transient events from the plasma (e.g., an edge localized mode) without causing a catastrophic failure of the coating. High-power transient effects are being explored by using an RF-induced vacuum arc to determine the robustness of tungsten coatings made by a variety of manufacturing methods. A 1/4-wavelength resonant section of vacuum transmission line terminated with an open circuit electrode structure with a well-defined electric field (30-60 kV/mm) produces repeatable arcing conditions. The initial focus is on tungsten as a plasma-facing material, including sintered tungsten, tungsten coatings on steel produced via physical vapor deposition (PVD), and functionally graded tungsten/steel coatings deposited by low-pressure plasma-spraying (LPPS). Thin PVD coatings (1-2 microns) fail catastrophically from an arc and result in severe delamination of the coating. The arc-induced damage of thicker coatings, such as those made via LPPS, tend to be restricted to the top few microns of the surface. Arcing often initiates on sharp surface microstructures and causes localized melting of tungsten at the surface of all the materials studied and results in resolidified melt pools with surface cracks. The resolidified surface results in a reduction in overall deuterium retention when exposed to typical RF plasma sheath conditions.

Caughman, John [ORNL] (ORCID:0000000206091164)↗
DOE OSTI2025

Unraveling Bacterial Adaptation Strategies in the Microbiome Shaped by the Chemical Environment of the Plant Rhizosphere

The rhizosphere is a dynamic environment where rhizodeposits that include primary and secondary metabolites and mucilage serve as nutrient sources for soil microorganisms, attracting them toward plant roots. However, understanding how these microbes specifically respond to plant root chemical signals has been hindered by the challenges of disentangling physical and chemical interactions between the microbes and plant roots. To address this, we implemented an innovative filter-based experimental setup on plant roots that creates a physical barrier while facilitating the exchange of chemical signals. The proteomic analysis of 10 Populus root-associated bacterial strains grown in the presence or absence of a plant in either individual or mixed community conditions provided detailed insights into the functional responses of these strains to the root chemical environment. Additionally, this approach allowed us to discern the impact of root exudates on overall community dynamics. In particular, metaproteomic analyses revealed that each of these 10 microbial members responds uniquely to the presence of the plant, with Bacillus and Pantoea exhibiting the most dramatic favorable impact. Proteomic examination revealed the details of metabolism fine-tuning, including processes such as chemotaxis and ATP-binding cassette transporter proteins. This study demonstrates the application of a filter-based experimental setup to study microbial responses to plant chemicals and sheds light on adaptation strategies employed by various bacterial strains for survival in the rhizosphere.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Fungal diversity and function in metagenomes sequenced from extreme environments

Fungi are increasingly recognized as key players in various extreme environments. Here we present an analysis of publicly-sourced metagenomes from global extreme environments, focusing on fungal taxonomy and function. The majority of 855 selected metagenomes contained scaffolds assigned to fungi. Relative abundance of fungi was as high as 10% of protein-coding genes with taxonomic annotation, with up to 289 fungal genera per sample. Despite taxonomic clustering by environment, fungal communities were more dissimilar than archaeal and bacterial communities, both for within- and between-environment comparisons. Relatively abundant fungal classes in extreme environments included Dothideomycetes, Eurotiomycetes, Leotiomycetes, Pezizomycetes, Saccharomycetes, and Sordariomycetes. Broad generalists and prolific aerial spore formers were the most relatively abundant fungal genera detected in most of the extreme environments, bringing up the question of whether they are actively growing in those environments or just surviving as spores. More specialized fungi were common in some environments, such as zoosporic taxa in cryosphere water and hot springs. Relative abundances of genes involved in adaptation to general, thermal, oxidative, and osmotic stress were greatest in soda lake, acid mine drainage, and cryosphere water samples.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Fracture and fatigue of thin crystalline SrTiO 3 membranes

The increasing availability of a variety of two-dimensional materials has generated enormous growth in the field of nanoengineering and nanomechanics. Recent developments in thin film synthesis have enabled the fabrication of freestanding functional oxide membranes that can be readily incorporated in nanomechanical devices. While many oxides are extremely brittle in bulk, recent studies have shown that, in thin membrane form, they can be much more robust to fracture as compared to their bulk counterparts. Here, we investigate the ultimate tensile strength of SrTiO 3 membranes by probing freestanding SrTiO 3 drumheads using an atomic force microscope. We demonstrate that SrTiO 3 membranes can withstand an elastic deformation with an average strain of ~6% in the sub-20 nm thickness regime, which is more than an order of magnitude beyond the bulk limit. Further, we also show that these membranes are highly resilient upon a high cycle fatigue test, surviving up to a billion cycles of force modulation at 85% of their fracture strain, demonstrating their high potential for use in nanomechanical applications.

36 MATERIALS SCIENCE↗