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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 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations. Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase family and is implicated in the demethylation of H3K4me3 and H3K36me2 and thereby removing active chromatin marks. However, the physiological role of FBXL10 in vivo remains largely unknown. Therefore, we established an inducible gain of function model to analyze the role of Fbxl10 and compared wild-type with Fbxl10 overexpressing mouse embryonic fibroblasts (MEFs). Our study shows that overexpression of Fbxl10 in MEFs doesn’t influence the proliferation capability but leads to an enhanced migration capacity in comparison to wild-type MEFs. Transcriptome and ChIP-seq experiments demonstrated that Fbxl10 binds to genes involved in migration like Areg, Mdk, Lmnb1, Thbs1, Mgp and Cxcl12. Taken together, our results strongly suggest that Fbxl10 plays a critical role in migration by binding to the promoter region of migration-associated genes and thereby might influences cell behaviour to a possibly more aggressive phenotype. - Highlights: • Migration capability of MEFs is enhanced after Fbxl10 upregulation. • Overexpression of Fbxl10 induced migration-associated genes. • Fbxl10 binds directly to migration-associated genes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

K-ras mutation promotes ionizing radiation-induced invasion and migration of lung cancer in part via the Cathepsin L/CUX1 pathway

Highlights: • CTSL has important roles in the regulation of invasion and migration in NSCLC and is promoted by mutated K-ras. • Mutated K-ras and IR-induced CTSL play crucial roles in the EMT in the lung cancer. • The regulatory effects of CTSL on the EMT are attributed to proteolytic processing of the transcription factor CUX1. • Inhibition of CTSL or CUX1 may be a promising therapeutic target. • CTSL is a promising therapeutic target to overcome the invasion and migration induced by IR. K-ras mutation is involved in cancer progression including invasion and migration, but the underlying mechanism is not yet clear. Cathepsin L is a lysosomal cysteine protease and has recently been associated with invasion and migration in human cancers when it is overexpressed. Our recent studies have shown that ionizing radiation (IR) enhanced expression of cathepsin L and increased invasion and migration of tumor cells, but the molecular mechanism is still unclear. In the present study, the effects of K-ras mutation and IR induced invasion and migration of lung cancer as well as the underlying mechanisms were investigated both in vitro and in vivo. Firstly, the levels of cathepsin L and epithelial mesenchymal transition (EMT) marker proteins remarkably changed in A549 (K-ras mutant) after irradiation compared with H1299 (K-ras wild), thereby promoting invasion and migration. Additionally, cathepsin L and its downstream transcription factor CUX1/p110 were increased after irradiation in A549 transfected with CUX1/p200, and the proteolytic processing of CUX1 by cathepsin L was remarkably increased after co-transfection of CUX1/p200 and cathepsin L-lentivirus in H1299. In addition, delivery of a mutant K-ras (V12) into HEK 293 cells stimulated EMT after irradiation due to the accumulation of cathepsin L. Moreover, mutated K-ras was associated with IR-induced cathepsin L and EMT in BALB/c nude mice. Finally, the level of cathepsin L expression was higher in samples carrying a K-ras mutation than in wild-type K-ras samples and the mesenchymal markers were upregulated in the samples of mutant K-ras, whereas the epithelial marker E-cadherin was downregulated in non-small cell lung cancers tissues. In conclusion, the findings demonstrated that mutated K-ras promotes cathepsin L expression and plays a pivotal role in EMT of human lung cancer. The regulatory effect of IR-induced cathepsin L on lung cancer invasion and migration was partially attributed to the Cathepsin L /CUX1-mediated EMT signaling pathway. This study will provide cathepsin L as a potential target for tumor therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The role and mechanism of KCa3.1 channels in human monocyte migration induced by palmitic acid

Highlights: • Palmitic acid upregulates K{sub Ca}3.1 channels in human monocytes. • TLR2/4, p38-MAPK and NF-κB pathway is involved in the effect of palmitic acid. • The migration of monocytes induced by palmitic acid is mediated by K{sub Ca}3.1 channels. • K{sub Ca}3.1 channels contribute to palmitic acid-induced MCP-1 production in monocytes. Monocyte migration into diseased tissues contributes to the pathogenesis of diseases. Intermediate-conductance Ca{sup 2+}-activated K{sup +} (K{sub Ca}3.1) channels play an important role in cell migration. However, the role of K{sub Ca}3.1 channels in mediating monocyte migration induced by palmitic acid (PA) is still unclear. Using cultured THP-1 cells and peripheral blood mononuclear cells from healthy subjects, we investigated the role and signaling mechanisms of K{sub Ca}3.1 channels in mediating the migration induced by PA. Using methods of Western blotting analysis, RNA interference, cell migration assay and ELISA, we found that PA-treated monocytes exhibited increment of the protein levels of K{sub Ca}3.1 channel and monocyte chemoattractant protein-1 (MCP-1), and the effects were reversed by co-incubation of PA with anti-TLR2/4 antibodies or by specific inhibitors of p38-MAPK, or NF-κB. In addition, PA increased monocyte migration, which was abolished by a specific K{sub Ca}3.1 channel blocker, TRAM-34, or K{sub Ca}3.1 small interfering RNA (siRNA). The expression and secretion of MCP-1 induced by PA was also similarly prevented by TRAM-34 and K{sub Ca}3.1 siRNA. These results demonstrate for the first time that PA upregulates K{sub Ca}3.1 channels through TLR2/4, p38-MAPK and NF-κB pathway to promote the expression of MCP-1, and then induce the trans-endothelial migration of monocytes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Extended live-tracking and quantitative characterization of wound healing and cell migration with SiR-Hoechst

Highlights: • SiR-Hoechst is a nuclear dye that enables cell tracking without affecting migration. • Single cell analysis provides multiple migration metrics during wound healing. • Cell density-based report of wound healing is less susceptible to subjective bias. • Cell directionality is an important contributor of early wound recovery. Cell migration is essential to many life processes, including immune response, tissue repair, and cancer progression. A reliable quantitative characterization of the cell migration can therefore aid in the high throughput screening of drug efficacy in wound healing and cancer treatments. In this work, we report what we believe is the first use of SiR-Hoechst for extended live tracking and automated analysis of cell migration and wound healing. We showed through rigorous statistical comparisons that this far-red label does not affect migratory behavior. We observed excellent automated tracking of random cell migration, in which the motility parameters (speed, displacement, path length, directionality ratio, persistence time, and direction autocorrelation) obtained closely match those obtained from manual tracking. We also present an analysis framework to characterize the healing of a scratch wound from the perspective of single cells. The use of SiR-Hoechst is advantageous for the crowded environments in wound healing assays because as long as cell nuclei do not overlap, continuous tracking can be maintained even if there is cell-cell contact. In this paper, we report wound recovery based on the number of cells migrating into the wound over time, normalized by the initial cell count prior to the infliction of the wound. This normalized cell count approach is impervious to operator bias during the arbitration of wound edges and is also robust against variability that arises due to differences in the cell density of different samples. Additional wound healing characteristics were also defined based on the evolution of cell speed and directionality during healing. Not unexpected, the wound healing cells exhibited much higher tendency to maintain the same migratory direction in comparison to the randomly migrating cells. The use of SiR-Hoechst thus greatly simplified the automation of single cell and whole population analysis with high spatial and temporal resolution over extended periods of time.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Migration of 60 Co, 133 Ba, 137 Cs, and 152 Eu from cementitious wasteforms in field lysimeter experiments

Safe and effective storage of radioactive waste is essential to protect environmental health. Due to the potential for accidental releases and the severity of the associated risks, it is imperative to further understand radionuclide transport should an accident occur. This work analyzed the vadose zone migration of radionuclides from cementitious wasteforms at the Savannah River Site after ten years. The observed radionuclides are prominent constituents of radioactive waste or analogs for other groups or series of radionuclides. Lysimeters were first analyzed in 2016 using a collimated high-purity germanium gamma-ray spectrometer to non-destructively measure the concentration of each radionuclide in the sediment column as a function of depth. Following these measurements, the lysimeters were redeployed in the field for another 4 years. All radionuclides in all lysimeters were observed to transport further during the redeployment period; however, the extent of migration varied with the material used for introduction. Except for 137 Cs, migration through the sediment control system increased with decreasing ionic potential (ionic charge/radius); migration order: 152 Eu< 137 Cs< 60 Co< 133 Ba. Overall, the cementitious wasteforms were observed to decrease radionuclide migration extent relative to the filter paper. In both cementitious wasteforms, the migration extent increased in the order 152 Eu< 133 Ba< 60 Co< 137 Cs. However, less migration was measured when the radionuclides were incorporated into a reducing grout wasteform. The novelty of this paper is the demonstration of a technique capable of creating non-destructive measurements over decade time scales. Ultimately, this work provides insight into the long-term migration of alkali, alkali earth, divalent transition metal, and trivalent actinide element isotopes.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
NASA NTRS2003

Non-Migrating Tides, with Zonally Symmetric Component, Generated in the Mesosphere

For comparison with measurements from the TIMED satellite and coordinated ground based observations, we discuss results from our Numerical Spectral Model (NSM) that incorporates the Doppler Spread Parameterization (Hines, 1997) for small-scale gravity waves (GWs). The NSM extends from the ground into the thermosphere and describes the major dynamical features of the atmosphere including the wave driven equatorial oscillations (QBO and SAO), and the seasonal variations of tides and planetary waves. With emphasis on the non-migrating tides, having periods of 24 and 12 hours, we discuss our modeling results that account for the classical migrating solar excitation sources only. As reported earlier, the NSM reproduces the observed seasonal variations and in particular the large equinoctial maxima in the amplitude of the migrating diurnal tide at altitudes around 90 km. Filtering of the tide by the zonal circulation and GW momentum deposition was identified as the cause. The GWs were also shown to produce a strong non-linear interaction between the diurnal and semi-diurnal tides. Confined largely to the mesosphere, the NSM produces through dynamical interactions a relatively large contribution of non-migrating tides. A striking feature is seen in the diurnal and semi-diurnal oscillations of the zonal mean (m = 0). Eastward propagating tides are also generated for zonal wave numbers m = 1 to 4. When the NSM is run without GWs, the amplitudes for the non-migrating tides, including m = 0, are generally small. Planetary wave interaction and non-linear coupling that involves the filtering of GWs and related height integration of dynamical features are discussed as possible mechanisms for generating these non-migrating tides in the NSM. As is the case for the solar migrating tides, the non-migrating tides reveal persistent seasonal variations. Under the influence of the QBO and SAO, interannual variations are produced.

Mayr, H. G.↗
NASA NTRS2005

Space Based Ornithology: On the Wings of Migration and Biophysics

The study of bird migration on a global scale is one of the compelling and challenging problems of modern biology with major implications for human health and conservation biology. Migration and conservation efforts cross national boundaries and are subject to numerous international agreements and treaties. Space based technology offers new opportunities to shed understanding on the distribution and migration of organisms on the planet and their sensitivity to human disturbances and environmental changes. Migration is an incredibly diverse and complex behavior. A broad outline of space based research must address three fundamental questions: (1) where could birds be, i.e. what is their fundamental niche constrained by their biophysical limits? (2) where do we actually find birds, i.e. what is their realizable niche as modified by local or regional abiotic and biotic factors, and (3) how do they get there (and how do we know?), that is what are their migration patterns and associated mechanisms? Our working hypothesis is that individual organism biophysical models of energy and water balance, driven by satellite measurements of spatio-temporal gradients in climate and habitat, will help us to explain the variability in avian species richness and distribution. Dynamic state variable modeling provides one tool for studying bird migration across multiple scales and can be linked to mechanistic models describing the time and energy budget states of migrating birds. Such models yield an understanding of how a migratory flyway and its component habitats function as a whole and link stop-over ecology with biological conservation and management. Further these models provide an ecological forecasting tool for science and application users to address what are the possible consequences of loss of wetlands, flooding, drought or other natural disasters such as hurricanes on avian biodiversity and bird migration.

Smith, James A.↗
NASA NTRS2016

Migration of Accreting Planets in Radiative Discs From Dynamical Torques

We present the results of hydrodynamical simulations of the orbital evolution of planets undergoing runaway gas accretion in radiative discs. We consider accreting disc models with constant mass flux through the disc, and where radiative cooling balances the effect of viscous heating and stellar irradiation. We assume that 20–30 M(sub ⨁) giant planet cores are formed in the region where viscous heating dominates and migrate outward under the action of a strong entropy-related corotation torque. In the case where gas accretion is neglected and for an α viscous stress parameter α = 2 × 10(exp -3), we find evidence for strong dynamical torques in accreting discs with accretion rates M ̇ ≳ 7 × 10(exsp -8)M(sub ⨀) yr(exp -1). Their main effect is to increase outward migration rates by a factor of ∼2 typically. In the presence of gas accretion, however, runaway outward migration is observed with the planet passing through the zero-torque radius and the transition between the viscous heating and stellar heating dominated regimes. The ability for an accreting planet to enter a fast migration regime is found to depend strongly on the planet growth rate but can occur for values of the mass flux through the disc of M ̇ ≳ 5 × 10(exp -8)M(sub ⨀) yr(exp -1).We find that an episode of runaway outward migration can cause an accreting planet formed in the 5–10 au region to temporarily orbit at star–planet separations as large as∼60–70 au. However, increase in the amplitude of the Lindblad torque associated with planet growth plus change in the streamline topology near the planet systematically cause the direction of migration to be reversed. Subsequent evolution corresponds to the planet migrating inward rapidly until it becomes massive enough to open a gap in the disc and migrate in the type II regime. Our results indicate that a planet can reach large orbital distances under the combined effect of dynamical torques and gas accretion, but an alternative mechanism is required to explain the presence of massive planets on wide orbits.

Accretion↗
DOE OSTI2017

Experimental investigation on oil migration and accumulation in tight sandstones

Here, this study presents an experimental investigation to simulate and analyze the physical processes of oil migration and accumulation with 19 tight sandstone cores. Characteristic curves of oil migration were obtained by using the experimental results. It shows that the curve variations were mainly influenced by two factors: the permeability of the core and the viscosity of the injected oil. Based on the experimental results, we introduced three important parameters to quantitatively characterize and determine the processes of oil migration and accumulation in tight sandstones. The apparent permeability was introduced to describe the level of oil migration during experiments. The minimum migration pressure gradient (MMPG) and the terminal oil saturation were proposed to evaluate the features of the beginning and final stages of the migration, respectively. The relationships between MMPG, terminal oil saturation and mobility were analyzed, all showed strong linear relationships in the double logarithmic coordinate system. Furthermore, a prediction map of tight oil accumulation was plotted according to the measured oil saturation data, which could be used for estimating the scale and size of oil accumulation in tight reservoirs. Lastly, the concepts and results in this study provide valuable insight for understanding and quantitatively analyzing the processes of oil migration and accumulation in tight sandstones.

58 GEOSCIENCES↗
DOE OSTI2018

Depressurization-Induced Fines Migration in Sediments Containing Methane Hydrate: X-Ray Computed Tomography Imaging Experiments

Depressurization of hydrate-bearing sediments (HBS) can cause the movement of fine particles, and in turn, such fines migration affects fluid flow and mechanical behavior of sediments, ultimately affecting long-term hydrocarbon production and wellbore stability. In this work, we investigate how and to what extent depressurization of HBS causes fines migration using X-ray computed tomography (CT) imaging. Methane hydrate was synthesized in sediments with 10% fines content (FC), composed of sands with silt and/or clay, and the hydrate-bearing samples were stepwisely depressurized while acquiring CT images. The CT images were analyzed to quantify the spatial changes in FC in the host sediment and thus to capture the fines migration during depressurization. It was found that the FC changes began occurring from the hydrate dissociation regions. This confirms that the multiphase flow caused by depressurization accompanies fines migration. Depressurization of HBS with a hydrate saturation of ~20–40% caused FC reduction from ~10% to ~6–9%, and the extent of fines migration differed with the particle sizes of the host sands and the types of fines. It was found that fines migration was more pronounced with coarse sands and with silty fines. Such observed level of FC reduction is estimated to increase sediment permeability by several factors based on the Kozeny-type permeability model. In conclusion, our results support the notion that the extent of fines migration and its effect on fluid flow behavior need to be assessed in consideration of physical properties of host sediment and fine particles to identify optimum depressurization strategies.

42 ENGINEERING↗
DOE OSTI2017

The role of crystallography and the mechanisms associated with migration of incoherent twin grain boundaries

With twin grain boundaries playing an important role in numerous materials, it is important to understand their behavior across the full range of possible boundary plane orientations. This work examines the migration of 41 computed Σ3 nickel grain boundaries over a range of temperatures. The boundary plane orientation appears to play the determining role in the nature of the migration observed, which is evident when the data are plotted in the fundamental zone of possible boundary plane orientations. GBs whose boundary plane lie between (1 1 1) and (2 1 1) exhibit thermally activated migration and the atoms do not move in a coordinated fashion. The remaining GBs, including the (1 0 1) GB, exhibit some form of thermally damped migration. The thermally damped migration is characterized by inverse temperature dependence where the GBs migrate faster at lower temperatures and move in a coordinated fashion involving Shockley partial dislocations. The inverse temperature dependence, which is confirmed by random walk simulations, appears to be consistent with dislocation drag, which could be related to the Shockley partial dislocations. At least one GB exhibits mixed mobility trends due to the presence of both thermally activated and thermally damped migration characteristics.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Calculation of multi-group migration areas in deterministic transport simulations

Recent work on the Cumulative Migration Method (CMM) has demonstrated that it is possible to define multi-group transport cross sections directly from Monte Carlo spectral calculations by utilizing edits of the energy-dependent neutron migration areas. However, it is difficult to demonstrate that downstream deterministic transport calculations actually preserve Monte Carlo migration areas. This paper addresses this issue by: 1) demonstrating the relationship of migration area with the concept of mean squared displacement, 2) deriving, and validating vs. Monte Carlo, an analytic expression for computing one-group migration areas for a homogeneous medium with energy-independent cross sections, 3) deriving, and validating vs. Monte Carlo, an analytic expression for computing multi-group migration areas for a homogenized medium with energy-dependent cross sections, and 4) rigorously proving that energy condensation of multi-group transport cross section must be inverse flux weighted in order to preserve Monte Carlo neutron migration areas.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2015

Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair

Background: Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo. Methods: Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated. Results: M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs. Conclusion: M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration. - Highlights: • M2 macrophages-derived MVs elevated migration and proliferation of SCs. • M2 macrophages-derived MVs up-regulated NFG and Laminin expression of SCs. • MiR-223 expression was increased in M2 macrophages-derived MVs. • MiR-223 inhibitor reduced migration and proliferation of SCs co-incubated with MVs. • MiR-223 inhibitor down-regulated NFG and Laminin levels of SCs co-incubated with MVs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5

Long noncoding RNAs (lncRNAs) have been proved to play important roles in cellular processes of cancer, including the development, proliferation, and migration of cancer cells. In the present study, we demonstrated small nucleolar RNA host gene 16 (SNHG16) as an oncogene on cell migration in breast cancer. Expression levels of SNHG16 were found to be frequently higher in breast cancer tissues than in the paired noncancerous tissues. Gain- and loss-of-function studies proved that SNHG16 significantly promoted breast cancer cell migration. We predicted SNHG16 as a competitive endogenous RNA (ceRNA) of E2F transcription factor 5 protein (E2F5) via competition for the shared miR-98 through bioinformatics analysis, and proved this regulation using relative quantitative real-time PCR (qRT-PCR), western blot, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. In addition, we identified a positive correlation between SNHG16 and E2F5 in breast cancer tissues. Furthermore, we demonstrated that forced expression of miR-98 could partially abrogate SNHG16-mediated increase of breast cancer cells migration, suggesting that SNHG16 promoted cell migration in a miR-98 dependent manner. Taken together, our findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5, and SNHG16 can serve as a potential therapeutic target for breast cancer treatment. - Highlights: • SNHG16 was first shown to work as a ceRNA by competitively binding miR-98 with E2F5. • SNHG16 promotes breast cancer cell migration in a miR98-dependent manner. • Direct combination of SNHG16 with miR-98 was proved using RIP and luciferase assay. • The positive regulation of E2F5 by SNHG16 in breast cancer was revealed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The blocking of aquaporin-3 (AQP3) impairs extravillous trophoblast cell migration

Highlights: • AQP1, AQP3 and AQP9 are expressed in the extravillous trophoblast cell line, Swan 71. • CuSO{sub 4}, a potent inhibitor of AQP3, significantly reduced Swan 71 cell migration. • AQP3 silencing significantly attenuates Swan 71 cell migration. • AQP3 participates in extravillous trophoblast cell migration. Several aquaporins (AQPs) are expressed in extravillous (EVT) and villous trophoblast cells. Among them, AQP3 is the most abundant AQP expressed in chorionic villi samples from first trimester, followed by AQP1 and AQP9. Although AQP3 expression persists in term placentas, it is significantly decreased in placentas from preeclamptic pregnancies. AQP3 is involved in the migration of different cell types, however its role in human placenta is still unknown. Here, we evaluated the role of AQP3 in the migration of EVT cells during early gestation. Our results showed that Swan 71 cells expressed AQP1, AQP3 and AQP9 but only the blocking of AQP3 by CuSO{sub 4} or the silencing of its expression by siRNA significantly attenuates EVT cell migration. Our work provides evidence that AQP3 is required for EVT cell migration and suggests that an altered expression of placental AQP3 may produce failures in placentation such as in preeclampsia.

60 APPLIED LIFE SCIENCES↗