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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
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DOE OSTI2024

Tomato Brown Rugose Fruit Virus Is Transmissible through a Greenhouse Hydroponic System but May Be Inactivated by Cold Plasma Ozone Treatment

Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus infecting tomatoes and peppers, resulting in a pandemic in recent years. In addition to its abilities of being seed-borne, transmitted mechanically and overcoming current resistance, we speculated other factors may also contribute to such catastrophic effect on tomato production in a hydroponic greenhouse. The objective of this study was to evaluate whether ToBRFV can be transmissible through recirculating hydroponic systems and, more importantly, search for an effective approach to contain its spread. We not only detected ToBRFV in the runoff water samples collected from three greenhouses but also determined the virus’ infectivity through a bioassay. We then conducted a water treatment using cold plasma ozone to assess its efficacy in inactivating ToBRFV. The results showed that, with a high concentration of ToBRFV (inoculum in 1:100 dilution), a prolonged exposure (72 min) to two higher ozone concentrations (0.6 mg/L and 1.0 mg/L) achieved partial effects. With a medium virus concentration (inoculum in 1:1000 dilution), an exposure to ozone for 48 min was sufficient to completely suppress the virus’ infectivity. However, with a low virus concentration (inoculum in 1:10,000 dilution), the virus was completely inactivated even with just a short ozone exposure (24 min). Future work will need to confirm the efficacy of the ozone treatment against ToBRFV as well as its impact on tomato plants in a hydroponic greenhouse.

Agriculture↗
DOE OSTI2023

Recruitment of Polo-like kinase couples synapsis to meiotic progression via inactivation of CHK-2

Meiotic chromosome segregation relies on synapsis and crossover (CO) recombination between homologous chromosomes. These processes require multiple steps that are coordinated by the meiotic cell cycle and monitored by surveillance mechanisms. In diverse species, failures in chromosome synapsis can trigger a cell cycle delay and/or lead to apoptosis. How this key step in ‘homolog engagement’ is sensed and transduced by meiotic cells is unknown. Here we report that in C. elegans , recruitment of the Polo-like kinase PLK-2 to the synaptonemal complex triggers phosphorylation and inactivation of CHK-2, an early meiotic kinase required for pairing, synapsis, and double-strand break (DSB) induction. Inactivation of CHK-2 terminates DSB formation and enables CO designation and cell cycle progression. These findings illuminate how meiotic cells ensure CO formation and accurate chromosome segregation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Compounds for central reactivation of organophosphorus-based compound-inhibited acetylcholinesterase and/or inactivation of organophosphorus-based acetylcholinesterase inhibitors and related compositions methods and systems for making and using them

Described herein are oxime compounds capable of inactivating OP-based AChE inhibitors, crossing the blood brain barrier (BBB), and/or reactivation of OP-inhibited acetylcholinesterase (AChE) and related methods, systems and compositions for inactivation of one or more OP-based AChE inhibitors, therapeutic and/or prophylactic treatment of an individual, and/or decomposition of OP-based AChE inhibitors for decontamination.

Valdez, Carlos A.↗
DOE OSTI2022

Efficacy of an inactivated Senecavirus A vaccine in weaned pigs and mature sows

Senecavirus A (SVA), commonly known as Seneca Valley virus (SVV) is a causative agent for vesicular disease in swine. It has been found across the globe including the United States, Brazil, and China. Clinical disease caused by this virus is identical to foot-and-mouth disease virus (FMDV). Since FMDV has the potential to cause severe economic consequences in FMDV-free countries, those countries are on high alert for signs of vesicles in swine and an investigation is performed to rule out the presence of FMDV if observed. In countries where SVA cases have continued to occur, investigations and testing can cause a burden on personnel and resources. The objectives of this study were to test the efficacy of a whole-virus inactivated SVA vaccine against challenge in nursery-aged pigs, mature sows, and to assess the protection of passive maternal immunity generated by immunized dams. Animals were given two doses of the vaccine intramuscularly three weeks apart and challenged intranasally two weeks after the second dose. Non-vaccinated animals challenged with SVA developed clinical signs of disease, replicated virus, and developed a neutralizing antibody response. Vaccinated animals had robust neutralizing titers after two doses; and after challenge, did not develop vesicular disease and had limited rectal shedding. Piglets suckling immunized dams and challenged with SVA at 3–6 days-of-age had neutralizing titers prior to challenge and did not replicate or shed virus. An efficacious vaccine could improve swine welfare and reduce the economic consequences of continued foreign animal disease investigations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Evaluation of Inactivation Methods for Rift Valley Fever Virus in Mouse Microglia

Rift Valley fever phlebovirus (RVFV) is a highly pathogenic mosquito-borne virus with bioweapon potential due to its ability to be spread by aerosol transmission. Neurological symptoms are among the worst outcomes of infection, and understanding of pathogenesis mechanisms within the brain is limited. RVFV is classified as an overlap select agent by the CDC and USDA; therefore, experiments involving fully virulent strains of virus are tightly regulated. Here, we present two methods for inactivation of live virus within samples derived from mouse microglia cells using commercially available kits for the preparation of cells for flow cytometry and RNA extraction. Using the flow cytometry protocol, we demonstrate key differences in the response of primary murine microglia to infection with fully virulent versus attenuated RVFV.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Ribosome-inactivation by a class of widely distributed C-tail anchored membrane proteins

Ribosome hibernation is a commonly used strategy that protects ribosomes under unfavorable conditions and regulates developmental processes. Multiple ribosome-hibernation factors have been identified in all domains of life, but due to their structural diversity and the lack of a common inactivation mechanism, it is currently unknown how many different hibernation factors exist. Here, we show that the YqjD/ElaB/YgaM paralogs, initially discovered as membrane-bound ribosome binding proteins in E. coli, constitute an abundant class of ribosome-hibernating proteins, which are conserved across all proteobacteria and some other bacterial phyla. Our data demonstrate that they inhibit in vitro protein synthesis by interacting with the 50S ribosomal subunit. In vivo cross-linking combined with mass spectrometry revealed their specific interactions with proteins surrounding the ribosomal tunnel exit and even their penetration into the ribosomal tunnel. Thus, YqjD/ElaB/YgaM inhibit translation by blocking the ribosomal tunnel and thus mimic the activity of antimicrobial peptides and macrolide antibiotics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Inactivated STAT5 pathway underlies a novel inhibitory role of EBF1 in chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia (CLL) is a disease caused by gradual accumulation of functionally incompetent lymphocytes. The majority of CLL cases are accompanied by chemoresistance. Early B cell factor 1 (EBF1) is a crucial contributor to B-cell lymphopoiesis. This study is to explore the effect of EBF1 on CLL cell progression and its involvement in regulating the signal transducers and activators of transcription 5 (STAT5) pathway. We conducted a correlation analysis between EBF1 and the clinical characteristics of CLL patients. Subsequently, EBF1 was overexpressed by transfection with EBF1 overexpression plasmid and the STAT5 pathway was also blocked by treatment with SH-4-54 in isolated CD20{sup +} B lymphocytes to investigate their roles in the regulation of cellular functions. STAT5, Janus kinase 2 (JAK2) expression and their phosphorylation levels were determined by quantitative PCR and Western blot analyses. The in vivo effects of EBF1 on tumor growth were evaluated using a xenotransplant model. Downregulation of EBF1 was observed in CD20{sup +} B lymphocytes of CLL patients. EBF1 overexpression disrupted the activation of STAT5 pathway, as evidenced by decreased expression and phosphorylation levels of STAT5 and JAK2. Furthermore, overexpression of EBF1 repressed viability and cell cycle entry, and increased apoptosis of CD20{sup +} B lymphocytes by inhibiting the STAT5 pathway. Finally, EBF1 exerted antitumor effects in nude mice. Overall, our study elucidates the inhibitory role of EBF1 in CLL through inactivation of the STAT5 pathway, which may provide new targets for CLL treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Combinatorial gene inactivation of aldehyde dehydrogenases mitigates aldehyde oxidation catalyzed by E. coli resting cells

Aldehydes are attractive chemical targets both as end products in the flavors and fragrances industry and as synthetic intermediates due to their propensity for C–C bond formation. Here, in this study, we identify and address unexpected oxidation of a model collection of aromatic aldehydes, including many that originate from biomass degradation. When diverse aldehydes are supplemented to E. coli cells grown under aerobic conditions, as expected they are either reduced by the wild-type MG1655 strain or stabilized by a strain engineered for reduced aromatic aldehyde reduction (the E. coli RARE strain). Surprisingly, when these same aldehydes are supplemented to resting cell preparations of either E. coli strain, under many conditions we observe substantial oxidation. By performing combinatorial inactivation of six candidate aldehyde dehydrogenase genes in the E. coli genome using multiplexed automatable genome engineering (MAGE), we demonstrate that this oxidation can be substantially slowed, with greater than 50% retention of 6 out of 8 aldehydes when assayed 4 h after their addition. Given that our newly engineered strain exhibits reduced oxidation and reduction of aromatic aldehydes, we dubbed it the E. coli ROAR strain. We applied the new strain to resting cell biocatalysis for two kinds of reactions – the reduction of 2-furoic acid to furfural and the condensation of 3-hydroxybenzaldehyde and glycine to form a non-standard β-hydroxy-α-amino acid. In each case, we observed substantial improvements in product titer 20 h after reaction initiation (9-fold and 10-fold, respectively). Moving forward, the use of this strain to generate resting cells should allow aldehyde product isolation, further enzymatic conversion, or chemical reactivity under cellular contexts that better accommodate aldehyde toxicity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Inactivation-mimicking block of the epithelial calcium channel TRPV6

Epithelial calcium channel TRPV6 plays vital roles in calcium homeostasis, and its dysregulation is implicated in multifactorial diseases, including cancers. Here, we study the molecular mechanism of selective nanomolar-affinity TRPV6 inhibition by (4-phenylcyclohexyl)piperazine derivatives (PCHPDs). We use x-ray crystallography and cryo–electron microscopy to solve the inhibitor-bound structures of TRPV6 and identify two types of inhibitor binding sites in the transmembrane region: (i) modulatory sites between the S1-S4 and pore domains normally occupied by lipids and (ii) the main site in the ion channel pore. Our structural data combined with mutagenesis, functional and computational approaches suggest that PCHPDs plug the open pore of TRPV6 and convert the channel into a nonconducting state, mimicking the action of calmodulin, which causes inactivation of TRPV6 channels under physiological conditions. This mechanism of inhibition explains the high selectivity and potency of PCHPDs and opens up unexplored avenues for the design of future-generation biomimetic drugs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Photocatalytic Material Surfaces for SARS-CoV-2 Virus Inactivation

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) can be spread through close contact or through fomite mediated transmission. This study details the fabrication and analysis of a photocatalyst surface which can rapidly inactivate SARS-COV-2 to limit spread of the virus by fomite mediated transmission. The surface being developed at Sandia for this purpose is a minimally hazardous Ag-Ti0 2 nanomaterial which is engineered to have high photocatalytic activity. Initial results at Sandia California in a BSL-2 safe surrogate virus- Vesicular Stomatitis Virus (VSV) show a significant difference between the photocatalyst material under exposure to visible light than controls. Additionally, UV-A light (365 nm) was found to eliminate SARS-COV-2 after 9 hours on all tested surfaces with irradiance of 15 mW/cm 2 equivalent to direct circumsolar irradiance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Nanopore Readable Activity Probes for Ribosomal Inactivating Protein (RIP) Toxins

Ribosome inactivating proteins (RIPs) such as ricin and abrin depurinate an adenine base in the sarcin/ricin loop in the large ribosomal subunit, leading to inhibtion of protein synthesis and cell death. Here, we demonstrate that RIP toxin activity can be detected via nanopore-based DNA sequencing using synthetic oligonucleotide substrates. This is achieved by monitoring the mismatch proportion at the canonical target sequences incorporated into the synthetic substrate and determining the sequence length distribution throughout the entire substrate sequence. The mismatch proportion increases and sequence length distribution decreases with increasing toxin concentration for both ricin and abrin in buffer as well as in more complex backgrounds such as saliva and nasal secretions.

Turner, Matthew W [Pacific Northwest National Labo↗
DOE OSTI2020

π‐Extended Donor–Acceptor Porphyrins and Metalloporphyrins for Antimicrobial Photodynamic Inactivation

Abstract Free base, zinc and palladium π‐extended porphyrins containing fused naphthalenediamide units were employed as photosensitizers in antimicrobial photodynamic therapy (aPDT). Their efficacy, assessed by photophysical and in vitro photobiological studies on Gram‐positive bacteria, was found to depend on metal coordination, showing a dramatic enhancement of photosensitizing activity for the palladium complex.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Growth and inactivation of Listeria monocytogenes in sterile extracts of fruits and vegetables: Impact of the intrinsic factors pH, sugar and organic acid content

Intrinsic characteristics of fresh produce, such as pH, water activity, acid content and nutrient availability are critical factors in determining the survival and growth of Listeria monocytogenes (Lm). In this study, sterile fresh produce juice was used to analyze Lm growth potential among 14 different commodities and to identify physicochemical characteristics in those juices that affect Lm growth. Significant growth of Lm was observed in juices with pH ≥5.6 and low acidity (0.04–0.07 % titratable acidity (TA)) (cantaloupe, carrot, celery, green pepper, parsley, and romaine lettuce), slight reduction of Lm was observed in juices with pH 4.1 (tomato) and pH 3.9 (mango), and no Lm counts were recovered from juices with pH ≤3.8 and high acidity (0.28–1.17 % TA) (apple, blueberry, grape, peach, and pineapple). Although these acidic fruit juices possessed a high sugar content, the pH and acidity of produce juice seemed to be the primary determinants for Lm growth. The neutralization of acidic juices (i.e., Fuji and Gala apple, blueberry, grape, mango, pineapple, peach, and tomato) enabled Lm growth at 37 °C in all juices except for Gala apple and peach. Strong decline in Lm populations in Gala apple, grape and peach juices might be linked to sensitivity to organic acids, such as malic acid. As a result, Lm populations significantly decreased in pH-neutral (7.6) cauliflower juice, suggesting that potential antilisterial substances may play a role in Lm decline in cauliflower juice.

60 APPLIED LIFE SCIENCES↗