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At least 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs)

Cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs) are increasingly used in cardiac safety assessment, disease modeling and regenerative medicine. A vast majority of cardiotoxicity studies in the past have tested acute effects of compounds and drugs; however, these studies lack information on the morphological or physiological responses that may occur after prolonged exposure to a cardiotoxic compound. In this review, we focus on recent advances in chronic cardiotoxicity assays using hiPSC-CMs. We summarize recently published literature on hiPSC-CMs assays applied to chronic cardiotoxicity induced by anticancer agents, as well as non-cancer classes of drugs, including antibiotics, anti-hepatitis C virus (HCV) and antidiabetic drugs. We then review publications on the implementation of hiPSC-CMs-based assays to investigate the effects of non-pharmaceutical cardiotoxicants, such as environmental chemicals or chronic alcohol consumption. We also highlight studies demonstrating the chronic effects of smoking and implementation of hiPSC-CMs to perform genomic screens and metabolomics-based biomarker assay development. The acceptance and wide implementation of hiPSC-CMs-based assays for chronic cardiotoxicity assessment will require multi-site standardization of assay protocols, chronic cardiac maturity marker reproducibility, time points optimization, minimal cellular variation (commercial vs. lab reprogrammed), stringent and matched controls and close clinical setting resemblance. A comprehensive investigation of long-term repeated exposure-induced effects on both the structure and function of cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Antifungal and Phytotoxic Activities of Isolated Compounds from Helietta parvifolia Stems

The identification of natural and environmentally friendly pesticides is a key area of interest for the agrochemical industry, with many potentially active compounds being sourced from numerous plant species. In this study, we report the bioassay-guided isolation and identification of phytotoxic and antifungal compounds from the ethyl acetate extract of Helietta parvifolia stems. We identified eight compounds, consisting of two coumarins and six alkaloids. Among these, a new alkaloid, 2-hydroxy-3,6,7-trimethoxyquinoline-4-carbaldehyde (6), was elucidated, along with seven known compounds. The phytotoxicity of purified compounds was evaluated, and chalepin (4) was active against Agrostis stolonifera at 1 mM with 50% inhibition of seed germination and it reduced Lemna pausicotata (duckweed) growth by 50% (IC50) at 168 μM. Additionally, we evaluated the antifungal activity against the fungal plant pathogen Colletotrichum fragariae using a thin-layer chromatography bioautography assay, which revealed that three isolated furoquinoline alkaloids (flindersiamine (3), kokusagenine (7), and maculine (8)) among the isolated compounds had the strongest inhibitory effects on the growth of C. fragariae at all tested concentrations. Our results indicate that these active natural compounds, i.e., (3), (4), (7), and (8), could be scaffolds for the production of more active pesticides with better physicochemical properties.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1972

Proton irradiation of stem cells: Radiation damage and chemical radioprotection

Effects of high energy protons on erythropoietic stem cells and radioprotection by chemicals were investigated in NASA Space Radiation Effects Laboratory. The effects of a parallel beam of 600 MeV protons. The fluence, when converted to dose, were referenced to the synchrocyclotron beam monitors which were then used to administer radiation exposures. Mice were given graded doses to 300 rads to determine dose-response curve. Other mice received saline, AET, or 5-hydroxytryptamine 10 to 15 minutes before exposure.

Riley, R. C.↗
NASA NTRS1973

Extended torsional tests of an interlocked bi-stem satellite boom

The effect is reported of continued oscillations of a 1.27-cm interlocked bi-stem satellite boom. The test setup oscillated a boom continuously between set torque limits and periodically recorded its hysteresis characteristics. Results showed that repeated oscillations affected torsional characteristics and that torsional rigidity changed as a function of the number of cycles oscillated within certain torque limits. Torsional characteristics changes caused by repeated oscillations were retained.

Abercrombie, R. A.↗
NASA NTRS1973

Mach stem structure in exothermic systems.

Incident waves having grossly similar characteristics were obtained by passing a shock wave over a ramp mounted on the divergent part of a convergent-divergent nozzle. The range of triple point parameters in both the naturally occurring detonative Mach stems and those generated in the ramp experiments compared favorably, but some differences were observed in the triple point trajectories and the decay rates of the lead waves. Whereas the lead waves in detonations have been found to decay at rates between those of planar and cylindrical blast waves, the decay observed in the ramp experiments was more like that of planar blast waves. The dominant factor in determining a triple point trajectory was found to be the orientation of the lead wave at the triple point. Comparison of reactive and nonreactive cases indicated a faster rate of decay of the lead wave and a steeper triple point trajectory for the reactive cases than for the nonreactive ones. Also, a sensitivity of the trajectory to initial pressure was observed in the former, although none was present in the nonreactive cases.

Liaugminas, R.↗
NASA NTRS1976

Mn-53 in the Apollo 15 and 16 drill stems - Evidence for surface mixing

The activity of cosmic ray produced Mn-53 has been measured in a series of samples from the upper 10 cm of the Apollo 15 and 16 drill stems. The activity profiles for both cores indicate disturbance to depths of about 3 g/sq cm within the last 6 m.y. In at least one case (Apollo 16) the soil has been gardened to at least 14 g/sq cm within the last 10 m.y., and material from the upper less than 2 g/sq cm has been buried to 14 g/sq cm by this gardening. The results for the Apollo 15 core are compatible with a wide variety of possible histories including loss or gain of material.

Nishiizumi, K.↗
NASA NTRS1980

Differentiation and radiosensitivity of hemopoietic stem cells of mice during hypokinesia

The potential for differentiation and radiosensitivity of the stem hemopoietic cells (KOE) under conditions of initial and later hypokinesia is examined. It is established that in the initial period of hypokinesia (3 days) when a stress reaction prevails, changes occur in the erythroid differentiation and radiosensitivity of KOE. This effect is associated with redistribution of T-lymphocytes that increase in number in the bone marrow of mice during hypokinesia. At later periods of hypokinesia (30 days) when changes in the organism are related to hypokinesia proper, differentiation and radiosensitivity of KOE were normalized.

Shvets, V. N.↗
NASA NTRS1984

Gravitropism in leafy dicot stems

In an attempt to separate plant responses to mechanical stresses from responses to gravity compensation, six treatments were automated: (1) upright stationary controls; (2) horizontal clinostat; (3) intermittent clinostat (plants upright 3.3 minutes out of every 4 minutes, horizontal and rotated once in the remaining time); (4) inversion every ten minutes (plants upside down half the time); (5) inversion and immediate return to the vertical; and (6) vertical rotation. Epinasty appeared only on clinostated and on inverted plants, both subjected to gravity compensation. The mechanics of gravitropic stem bending and the effects of a unilateral application of ethephon of gravitropic bending were also investigated.

Salisbury, F. B.↗
NASA NTRS1991

Soybean stem growth under high-pressure sodium with supplemental blue lighting

To study high-pressure sodium (HPS) lamps used for plant lighting because of their high energy conversion efficiencies, 'McCall' soybean plants were grown for 28 days in growth chambers utilizing HPS lamps, with/without supplemental light from blue phosphor fluorescent lamps. Total photosynthetic photon flux levels, including blue fluorescent, were maintained near 300 or 500 micromol/sq m s. Results indicate that employment of HPS or other blue-deficient sources for lighting at low to moderate photosynthetic photon flux levels may cause abnormal stem elongation, but this can be prevented by the addition of a small amount of supplemental blue light.

Wheeler, R. M.↗
NASA NTRS2000

BOREAS RSS-17 Stem, Soil, and Air Temperature Data

The BOREAS RSS-17 team collected several data sets in support of its research in monitoring and analyzing environmental and phenological states using radar data. This data set consists of tree bole and soil temperature measurements from various BOREAS flux tower sites. Temperatures were measured with thermistors implanted in the hydroconductive tissue of the trunks of several trees at each site and at various depths in the soil. Data were stored on a data logger at intervals of either 1 or 2 hours. The majority of the data were acquired between early 1994 and early 1995. The primary product of this data set is the diurnal stem temperature measurements acquired for selected trees at five BOREAS tower sites. The data are provided in tabular ASCII format. The data files are available on a CD-ROM (see document number 20010000884) or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

Zimmerman, Reiner↗