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At least 865 records · Page 48

Ocular Toxicity Testing of Lunar Dust

This slide presentation reviews the use of ocular testing to determine the toxicity of lunar dust. The OECD recommendations are reviewed. With these recommendations in mind the test methodology was to use EpiOcular, tissues derived from normal human epidermal keratinocytes, the cells of which have been differentiated on cell culture inserts to form a multi-layered structure, which closely parallels the corneal epithelium and to dose the tissue with 100 mg dust from various sources. The in-vitro study provides evidence that lunar dust is not severely corrosive or irritating, however, in vitro tests have limitations, and in vivo tests provides a more complete scenario, and information, it is recommended that in vivo tests be performed.

Meyers, Valerie E.↗

A Portable Electronic Nose For Toxic Vapor Detection, Identification, and Quantification

A new prototype instrument based on electronic nose (e-nose) technology has demonstrated the ability to identify and quantify many vapors of interest to the Space Program at their minimum required concentrations for both single vapors and two-component vapor mixtures, and may easily be adapted to detect many other toxic vapors. To do this, it was necessary to develop algorithms to classify unknown vapors, recognize when a vapor is not any of the vapors of interest, and estimate the concentrations of the contaminants. This paper describes the design of the portable e-nose instrument, test equipment setup, test protocols, pattern recognition algorithms, concentration estimation methods, and laboratory test results.

Linnell, B. R.↗

Non-Toxic, Non-Flammable, -80 C Phase Change Materials

The objective of this effort was to develop a non-toxic, non-flammable, -80 C phase change material (PCM) to be used in NASA's ICEPAC capsules for biological sample preservation in flight to and from Earth orbit. A temperature of about -68 C or lower is a critical temperature for maintaining stable cell, tissue, and cell fragment storage.

Cutbirth, J. Michael↗

Risk Analysis Associated with Loss of Toxic Gases During Orion Landing and Recovery Operations

Mission, landing and recovery operations for the Orion crew module involve reentry into the Earth's atmosphere and the deployment of three Nomex parachutes to slow the descent before landing along the west coast of the United States. Orion may have residual fuel (hydrazine, N2H4) or coolant (ammonia, NH3) on board which are both highly toxic to crew in the event of exposure. These risks were evaluated using a first principles analysis approach through fluid dynamics modeling. Plume calculations were first performed with the ANSYS Fluent computational fluid dynamics code. Data were then extracted at locations relevant to crew safety such as the snorkel fan inlet and the egress hatch. Mixing calculations were performed to quantify exposure concentrations within the crew bay before and during egress and departure. Finally, results included herein were used to inform the Orion post-landing Concept of Operations (ConOps) so that strategies could be formulated to maintain crew safety in the event of the loss of fuel or coolant.

Orion↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

59 BASIC BIOLOGICAL SCIENCES↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

59 BASIC BIOLOGICAL SCIENCES↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimers Disease or frontotemporal dementia.

Bielicki, John K.↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

59 BASIC BIOLOGICAL SCIENCES↗

Different reactivity to glutathione but similar tumor cell toxicity of chalcones and their quinolinone analogues

Non-enzyme catalyzed nucleophilic addition of reduced glutathione (GSH) onto two open-chain sulfonamide chalcones and two quinolinone-chalcone hybrids were studied to investigate the relationship between tumor cell cytotoxic activities and GSH-reactivities of the compounds. The consumption of the chalcones or the quinolinone-chalcone hybrids due to conjugation with GSH was evaluated by analytical high-performance liquid chromatography, and the formed diastereomeric adducts were identified by liquid chromatography–mass spectrometry. When the reaction was conducted with the open-chain chalcones, the equilibria were shifted towards formation of the respective GSH-conjugates. On the other hand, the cyclic chalcone derivatives with the quinolinone moiety were found to equilibrate to mixtures containing predominantly the reactants despite the strong electron withdrawing group present in the B-ring of the compounds. The observed opposite behavior can be rationalized by reduced thiol-reactivity of the quinolinone-chalcone hybrids and fast decomposition of their GSH-conjugates. A combined X-ray diffraction and theoretical approach were used to explain the observed difference in the reactivities towards GSH. However, structural differences did not influence tumor cell (SF-295, PC-3 and HCT-116) cytotoxicity of the evaluated compounds. Accordingly, the altered GSH-reactivity seems to be not a determining factor in the tested tumor cell cytotoxic activity of the investigated compounds.

60 APPLIED LIFE SCIENCES↗

Evaluation of Potential Toxic Metals Accumulation in Wheat Irrigated with Wastewater

The present study was carried out to ascertain the level of various metals in wheat variety (Chagi–4) irrigated with diverse doses of wastewater. The concentration of metals in soil, water and wheat grain samples was examined through an atomic absorption spectrophotometer. In wheat grains, the mean values of metals (mg/kg) varied from 0.06 to 0.2 for Pb, 1.2 to 1.6 for Cd, 0.6 to 0.9 for Ni, 0.8 to 1.6 for Fe, 0.4 to 1.0 for Mn, 0.7 to 1.4 for Cu, 0.3 to 0.5 for Cr, 0.1 to 0.9 for Zn and 0.03 to 0.2 for Co, correspondingly. Measured concentrations were found within the permissible limit given by FAO/WHO except for cadmium whose concentration exceeded an acceptable limit 0.2 mg/kg suggested by FAO/WHO. It might be due to high soil pH, which hinders the efficient transfer of metals between different mediums. Wastewater irrigated soil, wheat and water had high metal values, but the low rate of transfer was noticed from soil to grains. Higher bioconcentration factor was obtained for manganese and cadmium; cadmium had even higher pollution load index, which could indicate the contamination status of soil. Therefore, regular monitoring of wastewater is necessary to prevent the excessive build-up of metals.

54 ENVIRONMENTAL SCIENCES↗

EDTA-Assisted Metal Uptake in Raphanus sativus L. and Brassica oleracea L.: Assessment of Toxicity and Food Safety

A study was conducted to determine the effect of ethylenediaminetetraacetic acid (EDTA) on phytoextraction potential of radish and cabbage. Plant biomass, photosynthetic pigments, proline and phenolics were significantly affected by the accumulation of heavy metals (HM). The metal uptake potential was increased significantly by the application of EDTA. Target hazard quotient (THQ) associated with exposure of these contaminants to food chain was calculated. Agronomic interventions to increase mineral levels in crops often increases the leaf concentrations only, the mineral concentration in edible portions are not increased at desired level due to low mobility of Zn in phloem. Since the leaves of both these crops are edible and a component of staple vegetarian diet, biofortification through Zn present in soil and its solubilization and mobilization through chelators can be implemented. However in no such instance these crops should be consumed when grown on Pb contaminated soil due to associated hazards.

54 ENVIRONMENTAL SCIENCES↗

The Characterization of Dissolved Organic Matter in Reclaimed Water and Its Influence on Copper Toxicity

Water samples were collected from five phases of treatment in a municipal sewage reclaimed water plant and the DOM was characterized. Results indicated that the components and properties of DOM varied notably with sequential treatments, such as the fluorescence intensity, the molecular weight and the total acidity. Meanwhile the accumulation of Cu in Daphnia magna was analyzed following exposure to samples spiked with 50 µg/L copper, which were decreased by the presence of DOM in those water samples. Furthermore, this study found significant associations between fluorescence intensity and Cu accumulation (r{sup 2} = 0.778, p < 0.05), while increased total acidity was found to enhance the unit total organic carbon-Cu accumulation (r{sup 2} = 0.979, p < 0.01). This study provides useful information on the safety and effective management of reclaimed water as a potential water resource.

54 ENVIRONMENTAL SCIENCES↗

Toxicity of Doxorubicin on Pig Liver After Chemoembolization with Doxorubicin-loaded Microspheres: A Pilot DNA-microarrays and Histology Study

The potential mechanisms accounting for the hepatotoxicity of doxorubicin-loaded microspheres in chemoembolization were examined by combining histology and DNA-microarray techniques.The left hepatic arteries of two pigs were embolized with 1 mL of doxorubicin-loaded (25 mg; (DoxMS)) or non-loaded (BlandMS) microspheres. The histopathological effects of the embolization were analyzed at 1 week. RNAs extracted from both the embolized and control liver areas were hybridized onto Agilent porcine microarrays. Genes showing significantly different expression (p < 0.01; fold-change > 2) between two groups were classified by biological process. At 1 week after embolization, DoxMS caused arterial and parenchymal necrosis in 51 and 38 % of embolized vessels, respectively. By contrast, BlandMS did not cause any tissue damage. Up-regulated genes following embolization with DoxMS (vs. BlandMS, n = 353) were mainly involved in cell death, apoptosis, and metabolism of doxorubicin. Down-regulated genes (n = 120) were mainly related to hepatic functions, including enzymes of lipid and carbohydrate metabolisms. Up-regulated genes included genes related to cell proliferation (growth factors and transcription factors), tissue remodeling (MMPs and several collagen types), inflammatory reaction (interleukins and chemokines), and angiogenesis (angiogenic factors and HIF1a pathway), all of which play an important role in liver healing and regeneration. DoxMS caused lesions to the liver, provoked cell death, and disturbed liver metabolism. An inflammatory repair process with cell proliferation, tissue remodeling, and angiogenesis was rapidly initiated during the first week after chemoembolization. This pilot study provides a comprehensive method to compare different types of DoxMS in healthy animals or tumor models.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Environmentally Responsive Poly(N-isopropylacrylamide)-co-poly(acrylic acid) Hydrogels for Separation of Toxic Metals and Organic Explosive Compounds from Water

Temperature and pH-sensitive hydrogels were prepared from N-isopropyl acrylamide and polyacrylic acid through co-polymerization using ammonium persulfate as the initiator, N,N,N’,N’-tetramethylenediamine as the activator and N,N’-methylene bisacrylamide as crosslinker. The gels were characterized on the basis of FTIR and NMR spectral analysis, SEM micrograms and swelling studies. The effect of pH and temperature on swelling behavior of these gels was investigated. Preliminary batch absorption experiments were conducted to explore the feasibility of separating As(V), Cr(VI), the explosive components cyclotrimethylene-trinitramine (RDX), and cyclotetramethylene-tetranitramine (HMX), from aqueous medium using the hydrogels. The results of the study indicated that the hydrogels prepared are stable and the gels have potential environmental applications for separating pollutants from water.

54 ENVIRONMENTAL SCIENCES↗

Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

Highlights: Black-Right-Pointing-Pointer BoNT and NTNHA proteins share a similar protein architecture. Black-Right-Pointing-Pointer NTNHA and BoNT were both identified as zinc-binding proteins. Black-Right-Pointing-Pointer NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. Black-Right-Pointing-Pointer Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structure classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X{sub 35}-D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.

60 APPLIED LIFE SCIENCES↗

Formation of non-toxic Aβ fibrils by small heat shock protein under heat-stress conditions

Highlights: ► We examined effect of the quaternary structure of yeast sHsp on Aβ aggregation. ► Aβ aggregation was inhibited by the oligomeric form of sHsp, but not by dimeric sHsp. ► The fibrillar amyloids consisted of both Aβ and dimeric sHsp. ► They exhibited different inner structure and cytotoxicity from authentic Aβ amyloids. ► These results suggest the formation of new type fibrillar Aβ amyloid by sHsp. -- Abstract: Small heat shock protein (sHsp) is a molecular chaperone with a conserved alpha-crystallin domain that can prevent protein aggregation. It has been shown that sHsps exist as oligomers (12–40 mer) and their dissociation into small dimers or oligomers is functionally important. Since several sHsps are upregulated and co-localized with amyloid-β (Aβ) in senile plaques of patients with Alzheimer’s disease (AD), sHsps are thought to be involved in AD. Previous studies have also shown that sHsp can prevent Aβ aggregation in vitro. However, it remains unclear how the quaternary structure of sHsp influences Aβ aggregation. In this study, we report for the first time the effect of the quaternary structure of sHsp on Aβ aggregation using sHsp from the fission yeast Schizosaccharomyces pombe (SpHsp16.0) showing a clear temperature-dependent structural transition between an oligomer (30 °C) and dimer (50 °C) state. Aβ aggregation was inhibited by the oligomeric form of SpHsp16.0. In contrast, amyloid fibrils were formed in the presence of dimeric SpHsp16.0. Interestingly, these amyloid fibrils consisted of both Aβ and SpHsp16.0 and showed a low ThT intensity and low cytotoxicity due to their low binding affinity to the cell surface. These results suggest the formation of novel fibrillar Aβ amyloid with different characteristics from that of the authentic Aβ amyloid fibrils formed in the absence of sHsp. Our results also suggest the potential protective role of sHsp in AD under stress conditions.

60 APPLIED LIFE SCIENCES↗