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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 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Aberrant increase of NMR signal in hydrogen exchange experiments. Observation and explanation

Hydrogen exchange (HX) NMR spectroscopy is widely used for monitoring structure, stability and dynamics of proteins at the level of individual residues. The stochastic replacement of protons by deuterons typically leads to an exponential decrease of the NMR signals. However, an unusual signal increase was observed in HX of several amides for T4 lysozyme L99A. This effect can be attributed to peak sharpening as a result of reduced dipolar relaxation from proximal amide protons that experience more rapid hydrogen/deuterium (H/D) exchange. The behavior was specifically observed at the termini of secondary structure elements, where large differences in protection against H/D exchange are observed. This effect is expected to be more widespread in NMR HX studies, and is important for the accurate determination of protection factors. - Highlights: • Unusual NMR signal increase in hydrogen/deuterium exchange experiments. • The suppression of the effect of dipole-dipole interactions leads to peak sharpening and NMR signal increase. • Taking the effects of dipole-dipole interactions into account improves analysis of hydrogen exchange in general.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Novel mechanism of aberrant ZIP4 expression with zinc supplementation in oral tumorigenesis

Zrt-Irt-like protein 4 (ZIP4) is critical molecule for proper mammalian development and releasing zinc from vesicular compartments. Recent studies suggested that ZIP4 plays an important role of tumor progression in pancreatic, prostate, and hepatocellular cancers, however, little is known about the detail mechanism of ZIP4 in their cancers. In the present study, we examined the possibility of ZIP4 as a new molecular target for oral squamous cell carcinoma (OSCC). We evaluated ZIP4 expression in OSCC-derived cell lines and primary OSCC samples by quantitative RT-PCR, immunoblotting, and immunohistochemistry (IHC). We also analyzed the clinical correlation between ZIP4 status and clinical behaviors in patients with OSCC. In addition, ZIP4 knockdown cells (shZIP4 cells) and ZnCl{sub 2} treatment were used for functional experiments, including cellular proliferation assay, zinc uptake assay, and cell-cycle analysis. ZIP4 mRNA and protein were up-regulated significantly in OSCCs compared with normal counterparts in vitro and in vivo. IHC showed that ZIP4 expression in the primary OSCC was positively correlated with primary tumoral size. The shZIP4 cells showed decrease accumulation of intercellular zinc and decreased cellular growth by cell-cycle arrest at the G1 phase, resulting from up-regulation of cyclin-dependent kinase inhibitors and down-regulation of cyclins and cyclin-dependent kinases. Since cellular growth of OSCC cells after treatment with zinc was significantly greater than control cells, we speculated that intercellular ZnCl{sub 2} accumulation is an important factor for cellular growth. Consistent with our hypothesis, not only decreased zinc uptake by ZIP4 knockdown but also chelating agent, N,N,N′,N′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), showed inhibitory effects of cellular proliferation. Therefore, our data provide evidence for an essential role of ZIP4 and intracellular zinc for tumoral growth in OSCC, suggesting that zinc uptake might be a potential therapeutic targeting event for OSCCs. - Highlights: • ZIP4 contributes to tumor progression in OSCCs. • ZIP4 regulated the cell-cycle arrest at G1/S phase in OSCC cells. • Intercellular ZnCl{sub 2} accumulation is an important factor for cellular growth. • TPEN, a chelating agent, might be a new therapeutic tool for the patients with OSCC. • ZIP4 would be a potential therapeutic target for OSCCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The influence of aberrant expression of GLI1/p-S6K on colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide. Recent studies have reported that PI3K/AKT/mTOR pathway regulated the GLI1 expression level via SMO-independent pathway in a variety of tumor types. We detected the expression level of GLI1/p-S6K in CRC tissues. We found the expression of GLI1/p-S6K was apparently close with lymph node metastasis and TNM stage and patients with positive GLI1/p-S6K expression had shorter survival time and patients with both GLI1 and p-S6K positive expression had an even worse overall survival than those with single positive expression. Moreover, GLI1 and p-S6K expression was considered to be independent prognostic factors in CRC patient and the positive co-expression of GLI1/p-S6K had greater influence than single expression positive on the prognosis of postoperative patients with tumor size≥5 cm, well differentiation, positive lymph node metastasis, venous invasion, neural invasion and TNM III-IV. Meanwhile, the GLI1/p-S6K expression had impact on more clinicopathologic features in colon-side carcinoma than in rectum-side carcinoma and the mTOR/S6K/GLI1 axis played an important role in CRC especially in advanced stage. Hence, further studies are underway to explore the molecular mechanism between GLI1 and p-S6K in CRC, and in addition, it offers novel facilities for molecular targeting therapy for CRC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Reelin deficiency leads to aberrant lipid composition in mouse brain

Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

A novel sector mass spectrograph design for high-order coded aperture Mass Spectrometry with stigmatic aberration correction

Previous works experimentally demonstrated that the application of spatially-coded apertures to simple sector mass spectrographs can result in increased signal intensity while maintaining spectral resolution comparable to that of a conventional slit aperture.[Chen, E.X., et al.: J Am Soc Mass Spectr. 26, 1633 (2015)][Russell, Z.E., et al.: J Am Soc Mass Spectr. 26, 248 (2015)] This spatial coding technique was later applied to a double-focusing Mattauch-Herzog mass spectrograph, and shown to be generally compatible with the architecture.[Russell, Z.E., et al.: J Am Soc Mass Spectr. 27, 1 (2016)] However, the achieved signal gain was limited by the spatial size of the electric sector gap. In this work, we introduce a modified version of the Mattauch-Herzog mass spectrograph with a wide-gap electric sector that is enabled by a novel, segmented-electrode approach, and show via simulation that this modified architecture alone (without aperture coding) achieves a 1.8x improvement in mass resolving power compared to a conventional Mattauch-Herzog spectrograph of equivalent size. Further, simulation of an aperture-coded version of the instrument supports a predicted signal strength increase of 50x with minimal loss of aperture clarity on the sensor due to the increased open area of the high-order coded aperture which can be passed.

47 OTHER INSTRUMENTATION↗
DOE OSTI2015

Aberrant miR-21 and miR-200b expression and its pro-fibrotic potential in hypertrophic scars

The post-traumatic hypertrophic scar (HS) is a fibrotic disease with excessive extracellular matrix (ECM) production by fibroblasts in response to tissue injury. Although dysregulation of miRNAs is known to be involved in a variety of pathophysiologic processes, the role of miRNA in hypertrophic scar formation is unclear. Abnormal expression of miRNA in fibrosis has been investigated in several studies. The transforming growth factor β1 (TGF-β1) promotes fibroblasts proliferation, the synthesis of collagen and other extracellular matrix, and ultimately leads to the formation of the HS by inducing excessive deposition of ECM. We identified two miRNAs whose expression was correlated with fibrotic diseases: miR-21 and miR-200b. This study further confirmed that after stimulation with TGF-β1, the expression of miR-21 was increased, whereas the mRNA level of SMAD7 was decreased in fibroblasts. TGF-β1 reduced the expression of miR-200b, while it augmented that of Zinc finger E-box-binding homeobox 1(Zeb1). Our experiments demonstrated that the expression of miR-21 and miR-200b are related to a disorder, and the TGF-β/miR-21/Smad7 and TGF-β/miR200b/Zeb1 pathways might participate in the pathogenesis of HS. Thus, a novel, beyond the traditional methods, approach for HS treatment via miRNA therapeutics could have been provided. - Highlights: • HS tissue had increased expression of miR-21 and decreased expression of Smad7, lower expression of miR-200b and higher expression of Zeb1. • TGF-β1 downregulated Smad7, which was correlated with the upregulation of miR-21. • TGF-β1 upregulated Zeb1, which was correlated with the downregulation of miR-200b. • miR-200b decreased the expression of Col1A1,Col3A1, Fn, and α-SMA, as well as that of the target Zeb1. • The miR-21 inhibitor decreased expression of Col1A1, Col3A1, Fn, and α-SMA and increased the expression of Smad7.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression

p300 is a multifunctional transcriptional coactivator that interacts with numerous transcription factors and exhibits protein/histone acetyltransferase activity. Loss of p300 function in humans and in mice leads to craniofacial defects. In this study, we demonstrated that inhibition of p300 histone acetyltransferase activity with the compound, C646, altered the expression of several genes, including Cdh1 (E-cadherin) in mouse maxillary mesenchyme cells, which are the cells that give rise to the secondary palate. The increased expression of plasma membrane-bound E-cadherin was associated with reduced cytosolic β-catenin, that led to attenuated signaling through the canonical Wnt pathway. Furthermore, C646 reduced both cell proliferation and the migratory ability of these cells. These results suggest that p300 histone acetyltransferase activity is critical for Wnt-dependent palate mesenchymal cell proliferation and migration, both processes that play a significant role in morphogenesis of the palate. - Highlights: • Inhibition of p300 HAT in cultured palate cells increased E-cadherin expression. • Inhibition of p300 HAT perturbed canonical Wnt signaling in cultured palate cells. • Blocking p300 HAT in palate cells altered rates of apoptosis, proliferation, and migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Patients with idiopathic endplate inflammation displayed aberrant Th17 responses resulting in proinflammatory monocyte activation

Endplate inflammation remains a difficult task to diagnose and treat, partly due to the absence of in-depth understanding of the cellular and molecular factors driving this condition. In the current study, we investigated the circulating immune cells in patients with idiopathic endplate inflammation. Compared to healthy controls, the patients with endplate inflammation presented a significant upregulation of Th17 cells, characterized by higher frequencies of circulating IL-17{sup +}CD4{sup +} T cells examined directly ex vivo and after PMA and ionomycin (PMA/I) stimulation. The frequency of Th17 cells in patients was not correlated with patient age, sex, or smoking status, but was significantly correlated with patient BMI. The total CD4{sup +} T cells from patients with end plate inflammation also presented significantly higher levels of IL-17 secretion directly ex vivo and after PMA/I stimulation. The IL-17 secretion was primarily mediated by CCR4{sup +}CCR6{sup +} CD4{sup +} T cells, followed by CCR4{sup -}CCR6{sup +} CD4{sup +} T cells and was nearly absent in CCR4{sup -}CCR6{sup -} CD4{sup +} T cells. Monocytes incubated with CCR4{sup +}CCR6{sup +} CD4{sup +} T cells presented significantly higher MHC class II expression, as well as higher CD80 and CD86 expression. The secretion of IL-6 and TNF was significantly higher in cell cultures containing CCR4{sup +}CCR6{sup +} CD4{sup +} T cells than in cell cultures containing CCR4{sup -}CCR6{sup -} CD4{sup +} T cells. These effects were reduced when the IL-17A cytokine was neutralized. Together, we identified a systemic upregulation of Th17 responses that could contribute to proinflammatory monocyte activation in patients with endplate inflammation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Aberrant electronic and structural alterations in pressure tuned perovskite NaOsO 3

The perovskite NaOsO 3 has a metal–insulator transition at temperature 410 K, which is delicate, intriguing, and provokes a lot of debate on its nature. Our combined electrical resistance, Raman, and synchrotron x-ray diffraction experiments show that the insulating ground state in this osmate endures under high pressure up to at least 35 GPa. In this pressure range, compression reveals hidden hysteretic resistance properties with a transient metallic state near 200 K, manifested three electronic character anomalies (at 1.7, 9.0, and 25.5 GPa), and a structural transition to the singular polar phase (at ~18 GPa). We distinguish NaOsO 3 from the regular crystallographic behavior of perovskites, though the electrical specificities resemble iridates and nickelates. The theoretical first-principle band structure and lattice dynamics calculations demonstrate that the magnetically itinerant Lifshitz-type mechanism with spin–orbit and spin–phonon interactions is responsible for these pressure-induced changes. Our findings provide another new playground for the emergence of new states in 5d materials by using high-pressure methods.

36 MATERIALS SCIENCE↗