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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 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS2012

Characterizing Delamination Migration in Carbon/Epoxy Tape Laminates

A new test method is presented for the purpose of investigating migration of a delamination between neighboring ply interfaces in fiber-reinforced, polymer matrix tape laminates. The test is a single cantilever beam configuration consisting of a cross-ply laminate with a polytetrafluoroethylene (PTFE) insert implanted at the mid-plane and spanning part way along the length of the specimen. The insert is located between a 0-degree ply (specimen length direction) and a stack of four 90-degree plies (specimen width direction). The specimen is clamped at both ends onto a rigid baseplate and is loaded on its upper surface via a piano hinge. Tests were conducted with the load-application point located on the intact portion of the specimen in order to initiate delamination growth onset followed by migration of the delamination to a neighboring 90/0 ply interface by kinking through the 90- degree ply stack. Varying this position was found to affect the distance relative to the load-application point at which migration initiated. In each specimen, migration initiated by a gradual transition of the delamination at the 0/90 interface into the 90- degree ply stack. In contrast, transition of the kinked crack into the 90/0 interface was sudden. Fractography of the specimens indicated that delamination prior to migration was generally mixed mode-I/II. Inspection of the kink surface revealed mode-I fracture. In general, use of this test allows for the observation of the growth of a delamination followed by migration of the delamination to another ply interface, and should thus provide a means for validating analyses aimed at simulating migration.

Ratcliffe, James G.↗
NASA NTRS2013

A Test for Characterizing Delamination Migration in Carbon/Epoxy Tape Laminates

A new test method is presented for the purpose of investigating migration of a delamination between neighboring ply interfaces in fiber-reinforced, polymer matrix tape laminates. The test is a single cantilever beam configuration consisting of a cross-ply laminate with a polytetrafluoroethylene insert implanted at the mid-plane and spanning part way along the length of the specimen. The insert is located between a 0- degree ply (specimen length direction) and a stack of four 90-degree plies (specimen width direction). The specimen is clamped at both ends onto a rigid baseplate and is loaded on its upper surface via a piano hinge. Tests were conducted with the load-application point located on the intact portion of the specimen in order to initiate delamination growth onset followed by migration of the delamination to a neighboring 90/0 ply interface by kinking through the 90-degree ply stack. Varying this position was found to affect the distance relative to the load-application point at which migration initiated. In each specimen, migration initiated by a gradual transition of the delamination at the 0/90 interface into the 90-degree ply stack. In contrast, transition of the kinked crack into the 90/0 interface was sudden. Fractography of the specimens indicated that delamination prior to migration was generally mixed mode-I/II. Inspection of the kink surface revealed mode-I fracture. In general, use of this test allows for the observation of the growth of a delamination followed by migration of the delamination to another ply interface, and should thus provide a means for validating analyses aimed at simulating migration.

Ratcliffe, James G.↗
NASA NTRS2022

Continental Patterns of Bird Migration Linked to Climate Variability

For nearly 100 years, avian migration studies have divided North America into three or four primary flyways, at times based on subjective approaches or just for convenience. Those studies often fail to adequately reflect a critical characterization of migration —phenology. This shortcoming has been partly due to the lack of reliable continental-scale data, a gap filled by our current study. Here, we leveraged unique radar-based data quantifying migration phenology and used an objective regionalization approach to revisit the traditional spatial framework. Consequently, we identified two regions with distinct inter annual variability of spring migration across the contiguous U.S. This new data-driven framework has enabled us to explore the climatic cues affecting the inter annual variability of migration phenology, “specific to each region” across North America. For example, our “two-region” approach allowed us to identify an east-west dipole pattern in migratory behavior linked to atmospheric Ross by waves. Also, we revealed a low-frequency variability in migration movements over the western U.S. that is inversely related with temperature and the Pacific Decadal Oscillation (PDO). Our spatial platform would facilitate future work on better understanding the mechanisms responsible for broad-scale migration phenology and its potential future changes.

Atmosphere↗
DOE OSTI2019

Method and apparatus for inter-lane thread migration

Briefly, methods and apparatus to migrate a software thread from one wavefront executing on one execution unit to another wavefront executing on another execution unit whereby both execution units are associated with a compute unit of a processing device such as, for example, a GPU. The methods and apparatus may execute compiled dynamic thread migration swizzle buffer instructions that when executed allow access to a dynamic thread migration swizzle buffer that allows for the migration of register context information when migrating software threads. The register context information may be located in one or more locations of a register file prior to storing the register context information into the dynamic thread migration swizzle buffer. The method and apparatus may also return the register context information from the dynamic thread migration swizzle buffer to one or more different register file locations of the register file.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

Dynamic cellular finite-element method for modelling large-scale cell migration and proliferation under the control of mechanical and biochemical cues: a study of re-epithelialization

Computational modelling of cells can reveal insight into the mechanisms of the important processes of tissue development. However, current cell models have limitations and are challenged to model detailed changes in cellular shapes and physical mechanics when thousands of migrating and interacting cells need to be modelled. In this paper we describe a novel dynamic cellular finite-element model (DyCelFEM), which accounts for changes in cellular shapes and mechanics. It also models the full range of cell motion, from movements of individual cells to collective cell migrations. The transmission of mechanical forces regulated by intercellular adhesions and their ruptures are also accounted for. Intra-cellular protein signalling networks controlling cell behaviours are embedded in individual cells. We employ DyCelFEM to examine specific effects of biochemical and mechanical cues in regulating cell migration and proliferation, and in controlling tissue patterning using a simplified re-epithelialization model of wound tissue. Our results suggest that biochemical cues are better at guiding cell migration with improved directionality and persistence, while mechanical cues are better at coordinating collective cell migration. Finally and overall, DyCelFEM can be used to study developmental processes when a large population of migrating cells under mechanical and biochemical controls experience complex changes in cell shapes and mechanics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Cation Migration in Physically Paired 2D and 3D Lead Halide Perovskite Films

2D/3D interfaces provide long-term stability for the operation of metal halide perovskite solar cells. However, the cation migration under heat and light can disturb the interface and create a graded cation interface. This study has now probed the cation migration by physically pairing X 2 PbI 4 (X = butylammonium BA, oleylammonium OA, or phenethylammonium PEA) 2D film and (CH 3 NH 3 , MA)PbI 3 3D film at different temperatures and recording changes in the absorption and emission spectra. The migration of the methyl ammonium cation toward the 2D film slowly transforms the n = 1 layered phase into n = 2 and 3 layered phases. The 3D film, on the other hand, exhibits relatively small changes, as the inclusion of spacer cation has little effect on its phase. The apparent activation energy determined from the temperature-dependent cation migration kinetics (E a = 29– 50 kJ mol –1 ) indicates alkyl ammonium cations such as butyl ammonium migrate more readily into the 3D layer than aromatic cations such as PEA. As a result, the ease of migration of spacer cations between physically paired films suggests that the varied composition at the interface should be considered while evaluating the effectiveness of the 2D/3D design strategy for improving the performance of perovskite solar cells.

2D/3D perovskite↗
DOE OSTI2016

Agkihpin, a novel SVAE may inhibit the migration and invasion of liver cancer cells associated with the inversion of EMT induced by Wnt/β-catenin signaling inhibition

In our previous work, agkihpin, a snake venom arginine esterase (SVAE), was isolated from the Gloydius halys Pallas, which could attenuate the migration of liver cancer cells. However, the mechanism of the effect of agkihpin on attenuating migration of liver cancer cell is unknown yet. Here, to learn more about agkihpin and explore the possibility of agkihpin as an anti-metastatic drug in the future, a series of experiments about the migration and invasion of liver cancer cells with agkihpin, HepG 2 and SMMC-7721, was conducted. Epithelial-mesenchymal transition (EMT) is an initial step and a major phenotype of cancer metastasis and invasion, while a number of EMT opposite phenomenons were observed, for example, epithelial marker E-cadherin was up-regulated, mesenchymal markers N-cadherin and Vimentin, and transcription regulators Snail and twist were down-regulated after treating with agkihpin in liver cancer cells; canonical Wnt/β-catenin pathway, one of the signals initiated EMT, was inhibited by decreased expressions of FZD7 and β-catenin, phosphorylation of GSK3β (Ser9), and nuclear β-catenin accumulation in agkihpin treated cancer cells. By using bioinformatics analysis and protease activity analysis in vitro we also found that agkihpin might bind and degrade FZD7. As a result, we hypothesized that agkihpin could inhibit the Wnt/β-catenin signaling pathway by cleaving FZD7, leading to the inactivation of the TCF/LEF transcription factor, which contributed to the inversion of EMT, and finally attenuated the migration and invasion of liver cancer cells. Therefore, our findings provided novel mechanistic insights into the role of SVAEs in liver cancer controlling, and raised the possibility that agkihpin may be used therapeutically in liver cancer. - Highlights: • We found for the first time that SVAE may inhibit the migration and invasion of liver cancer cells. • The inhibition of migration and invasion was associated with the inversion of EMT. • The inversion of EMT was induced by Wnt/β-catenin signaling inhibition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

Objective: Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-α36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. - Highlights: • ER-α36 is expressed on both cervical cell lines and cervical cancer tissues. • ER-α36 mediates estrogen-stimulated cell invasion, migration and proliferation of cervical cancer cell lines. • ER-α36 mediates estrogen-stimulated MAPK/ERK activation in cervical cancer cell lines.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

The sGC activator inhibits the proliferation and migration, promotes the apoptosis of human pulmonary arterial smooth muscle cells via the up regulation of plasminogen activator inhibitor-2

Background: Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process. Objectives: We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration. Methods: After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured human PASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated. Results: BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis. Conclusions: PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of human PASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2. - Highlights: • sGC activator BAY41-2272 up regulated PAI-2 in PASMCs, on the mRNA and protein level. • PAI-2 overexpression inhibits the proliferation and migration of human PASMCs. • PAI-2 overexpression promotes the apoptosis of human PASMCs. • sGC activator might alleviate the vascular remodeling in pulmonary hypertension.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Wip1 knockout inhibits the proliferation and enhances the migration of bone marrow mesenchymal stem cells

Mesenchymal stem cells (MSCs), a unique population of multipotent adult progenitor cells originally found in bone marrow (BM), are extremely useful for multifunctional therapeutic approaches. However, the growth arrest and premature senescence of MSCs in vitro prevent the in-depth characterization of these cells. In addition, the regulatory factors involved in MSCs migration remain largely unknown. Given that protein phosphorylation is associated with the processes of MSCs proliferation and migration, we focused on wild-type p53-inducible phosphatase-1 (Wip1), a well-studied modulator of phosphorylation, in this study. Our results showed that Wip1 knockout significantly inhibited MSCs proliferation and induced G2-phase cell-cycle arrest by reducing cyclinB1 expression. Compared with WT-MSCs, Wip1{sup −/−} MSCs displayed premature growth arrest after six passages in culture. Transwell and scratch assays revealed that Wip1{sup −/−} MSCs migrate more effectively than WT-MSCs. Moreover, the enhanced migratory response of Wip1{sup −/−} MSCs may be attributed to increases in the induction of Rac1-GTP activity, the pAKT/AKT ratio, the rearrangement of filamentous-actin (f-actin), and filopodia formation. Based on these results, we then examined the effect of treatment with a PI3K/AKT and Rac1 inhibitor, both of which impaired the migratory activity of MSCs. Therefore, we propose that the PI3K/AKT/Rac1 signaling axis mediates the Wip1 knockout-induced migration of MSCs. Our findings indicate that the principal function of Wip1 in MSCs transformation is the maintenance of proliferative capacity. Nevertheless, knocking out Wip1 increases the migratory capacity of MSCs. This dual effect of Wip1 provides the potential for purposeful routing of MSCs. - Highlights: • Wip1 knockout inhibited MSCs proliferation through reducing cyclinB1 expression. • Wip1{sup −/−} MSCs displayed premature growth arrest in vitro after six passages. • Knocking out Wip1 increases the migratory capacity of MSCs. • The PI3K/AKT/Rac1 pathway mediates the Wip1-knockout-induced migration of MSCs. • Overexpression of Wip1 reversed premature senescence and migration of Wip1{sup −/−} MSCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Mapping the pathways of photo-induced ion migration in organic-inorganic hybrid halide perovskites

Abstract Organic-inorganic hybrid perovskites exhibiting exceptional photovoltaic and optoelectronic properties are of fundamental and practical interest, owing to their tunability and low manufacturing cost. For practical applications, however, challenges such as material instability and the photocurrent hysteresis occurring in perovskite solar cells under light exposure need to be understood and addressed. While extensive investigations have suggested that ion migration is a plausible origin of these detrimental effects, detailed understanding of the ion migration pathways remains elusive. Here, we report the characterization of photo-induced ion migration in perovskites using in situ laser illumination inside a scanning electron microscope, coupled with secondary electron imaging, energy-dispersive X-ray spectroscopy and cathodoluminescence with varying primary electron energies. Using methylammonium lead iodide and formamidinium lead iodide as model systems, we observed photo-induced long-range migration of halide ions over hundreds of micrometers and elucidated the transport pathways of various ions both near the surface and inside the bulk of the samples, including a surprising finding of the vertical migration of lead ions. Our study provides insights into ion migration processes in perovskites that can aid perovskite material design and processing in future applications.

14 SOLAR ENERGY↗
DOE OSTI2021

The use of nocturnal flights for barrier crossing in a diurnally migrating songbird

The migration patterns of land birds can generally be divided into those species that migrate principally during the day and those that migrate during the night. Some species may show individual plasticity in the use of day or night flight, particularly when crossing large, open-water or desert barriers. However, individual plasticity in circadian patterns of migratory flights in diurnally migrating songbirds has never been investigated. We used high precision GPS tracking of a diurnal, migratory swallow, the purple martin (Progne subis), to determine whether individuals were flexible in their spring migration strategies to include some night flight, particularly at barrier crossing. Most (91%) of individuals made large (sometimes > 1000 km), open-water crossings of the Caribbean Sea and the Gulf of Mexico that included the use of night flight. 32% of all water crossings were initiated at night, demonstrating that night flight is not only used to complete large crossings but may confer other advantages for diurnal birds. Birds were not more likely to initiate crossings with supportive winds, however crossings were more likely when they reduced travel distances. Our results are consistent with diurnal birds using night flight to help achieve time- and energy-savings through ‘short cuts’ at barrier crossings, at times and locations when foraging opportunities are not available. Overall, our results demonstrate the use of nocturnal flight and a high degree of individual plasticity in migration strategies on a circadian scale in a species generally considered to be a diurnal migrant. Nocturnal flights at barrier crossing may provide time and energy savings where foraging opportunities are low in an otherwise diurnal strategy. Future research should target how diel foraging and refueling strategies support nocturnal flights and barrier crossing in this and other diurnal species.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor

Schwann cells (SCs) play an essentially supportive role in the regeneration of injured peripheral nerve system (PNS). As Netrin-1 is crucial for the normal development of nervous system (NS) and can direct the process of damaged PNS regeneration, our study was designed to determine the role of Netrin-1 in RSC96 Schwann cells (an immortalized rat Schwann cell line) proliferation and migration. Our studies demonstrated that Netrin-1 had no effect on RSC96 cells proliferation, while significantly promoted RSC96 cells migration. The Netrin-1-induced RSC96 cells migration was significantly attenuated by inhibition of p38 and PI3K through pretreatment with SB203580 and LY294002 respectively, but not inhibition of MEK1/2 and JNK by U0126-EtOH and SP600125 individually. Treatment with Netrin-1 enhanced the phosphorylation of p38 and Akt. QRT-PCR indicated that Netrin-1 and only its receptors Unc5a, Unc5b and Neogenin were expressed in RSC96 cells, among which Unc5b expressed the most. And UNC5B protein was significantly increased after stimulated by Netrin-1. In conclusion, we show here that Netrin-1-enhanced SCs migration is mediated by activating p38 MAPK and PI3K-Akt signal cascades via receptor UNC5B, which suggests that Netrin-1 could serve as a new therapeutic strategy and has potential application value for PNS regeneration. - Highlights: • Netrin-1 attracts RSC96 Schwann cells migration in a dose dependent manner. • Netrin-1 induced Schwann cells migration is p38 and PI3K-Akt signaling dependent. • UNC5B may be dominant receptor mediating Netrin-1′ effect on RSC96 cells motility. • Netrin-1 may promote peripheral nerve repair by enhancing Schwann cells motility.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

New insights into the role of mitochondrial calcium homeostasis in cell migration

Highlights: • Mitochondrial calcium dynamics control cell migration. • MCU and regulators are involved in development and cancer invasion. • MCU regulates cytoskeletal dynamics. • MCUM modulates ATP and ROS production, and intracellular calcium signalling. Mitochondria are dynamic organelles involved in numerous physiological functions. Beyond their function in ATP production, mitochondria regulate cell death, reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria also play a key role in the buffering of cytosolic calcium, and calcium transported into the matrix regulates mitochondrial metabolism. Recently, the identification of the mitochondrial calcium uniporter (MCU) and associated regulators has allowed the characterization of new physiological roles for calcium in both mitochondrial and cellular homeostasis. Indeed, recent work has highlighted the importance of mitochondrial calcium homeostasis in regulating cell migration. Cell migration is a property common to all metazoans and is critical to embryogenesis, cancer progression, wound-healing and immune surveillance. Previous work has established that cytoplasmic calcium is a key regulator of cell migration, as oscillations in cytosolic calcium activate cytoskeletal remodelling, actin contraction and focal adhesion (FA) turnover necessary for cell movement. Recent work using animal models and in cellulo experiments to genetically modulate MCU and partners have shed new light on the role of mitochondrial calcium dynamics in cytoskeletal remodelling through the modulation of ATP and ROS production, as well as intracellular calcium signalling. This review focuses on MCU and its regulators in cell migration during physiological and pathophysiological processes including development and cancer. We also present hypotheses to explain the molecular mechanisms by which MCU may regulate mitochondrial dynamics and motility to drive cell migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Fibulin-5 promotes airway smooth muscle cell proliferation and migration via modulating Hippo-YAP/TAZ pathway

Asthma is a common chronic disease mainly occurs from childhood. Increased airway smooth muscle mass is involved in the pathogenesis of asthma. Fibulin-5 was upregulated in the lung tissues of patients with COPD and idiopathic pulmonary fibrosis. This study aimed to investigate Fibulin-5 expression in asthmatic patients and the effect and mechanism of Fibulin-5 on the proliferation and migration of airway smooth muscle cells (ASMCs). The expression of Fibulin-5, YAP, and TAZ in the induced sputum of 38 asthmatic children (19 mild and 19 moderate asthmatics) and 19 healthy controls was determined. The effects and mechanisms of Fibulin-5 on the proliferation and migration of ASMCs were analyzed through upregulating Fibulin-5. We found compared with healthy controls, the expression of Fibulin-5, YAP, and TAZ was increased in the induced sputum of asthmatic children and much higher in moderate asthmatics. Fibulin-5 overexpression promoted the proliferation and migration of ASMCs, upregulated the expression of YAP and TAZ, and reduced the levels of p-YAP and p-TAZ. YAP inhibitor (Peptide 17) abrogated the proliferation and migration of ASMCs induced by Fibulin-5 overexpression in a dose-dependent manner. Additionally, Fibulin-5 overexpression enhanced its binding capacity of β1 integrin, and β1 integrin blocking antibody partly reversed the effect of Fibulin-5 overexpression on the levels of YAP and TAZ. In conclusion, Fibulin-5 expression is correlated with the pathogenesis of childhood asthma. It may function at least partly through binding to β1 integrin and modulating Hippo-YAP/TAZ pathway to promote the proliferation and migration of ASMCs. - Highlights: • Fibulin-5 expression is increased in the induced sputum of asthmatic patients. • Overexpression of Fibulin-5 promotes the proliferation and migration of ASMCs. • Fibulin-5 functions via modulating Hippo-YAP/TAZ signaling pathway. • Fibulin-5 binding to β1 integrin to activate YAP/TAZ signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A catalytically inactive gelatinase B/MMP-9 mutant impairs homing of chronic lymphocytic leukemia cells by altering migration regulatory pathways

Highlights: • MMP-9MutE (non-catalytic) impairs migration and in vivo homing of CLL cells. • MMP-9MutE-impaired migration does not involve RhoAGTPase activity. • MMP-9MutE downregulates p-ERK and increases PTEN expression. • MMP-9MutE affects signaling pathways regulating CLL cell migration. • MMP-9 contributes to CLL progression by catalytic and non-catalytic activities. We previously showed that MMP-9 overexpression impairs migration of primary CLL cells and MEC-1 cells transfected with MMP-9. To determine the contribution of non-proteolytic activities to this effect we generated MEC-1 transfectants stably expressing catalytically inactive MMP-9MutE (MMP-9MutE-cells). In xenograft models in mice, MMP-9MutE-cells showed impaired homing to spleen and bone marrow, compared to cells transfected with empty vector (Mock-cells). In vitro transendothelial and random migration of MMP-9MutE-cells were also reduced. Biochemical analyses indicated that RhoAGTPase and p-Akt were not downregulated by MMP-9MutE, at difference with MMP-9. However, MMP-9MutE-cells or primary cells incubated with MMP-9MutE had significantly reduced p-ERK and increased PTEN, accounting for the impaired migration. Our results emphasize the role of non-proteolytic MMP-9 functions contributing to CLL progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A Prdm8 target gene Ebf3 regulates multipolar-to-bipolar transition in migrating neocortical cells

Highlights: • Precise control of neuronal migration is essential for the development of the neocortex. • We identified helix-loop-helix transcription factor Ebf3 as a Prdm8 target gene. • Ebf3 is a key regulator of neuronal migration via multipolar-to-bipolar transition. • Ebf3 knockdown cells exhibited severe defects in the formation of leading processes. • Ebf3 in multipolar-to-bipolar transition via positive feedback regulation of NeuroD1. Precise control of neuronal migration is essential for the development of the neocortex. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here we identified helix-loop-helix transcription factor Ebf3 as a Prdm8 target gene, and found that Ebf3 is a key regulator of neuronal migration via multipolar-to-bipolar transition. Ebf3 knockdown cells exhibited severe defects in the formation of leading processes and an inhibited shift to the locomotion mode. Moreover, we found that Ebf3 knockdown represses NeuroD1 transcription, and NeuroD1 overexpression partially rescued migration defects in Ebf3 knockdown cells. Our findings highlight the critical role of Ebf3 in multipolar-to-bipolar transition via positive feedback regulation of NeuroD1 in the developing neocortex.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA-MALAT1 promotes CPC proliferation and migration in hypoxia by up-regulation of JMJD6 via sponging miR-125

Highlights: • MALAT1 was up-regulated in CPCs in hypoxia conditions. • MALAT1 suppression inhibited CPCs proliferation and migration after hypoxia-inducing stimuli. • MALAT1 modulated CPCs proliferation and migration through MALAT1/miR-125/JMJD6 axis under hypoxia conditions. The death of cardiomyocytes after myocardial infarction (MI) often leads to ventricular remodeling as well as heart failure (HF). The cardiac progenitor cells (CPCs) have the ability to regenerate functional heart muscle in patients after MI, which provides a promising method for MI-induced HF therapy. However, to date, CPCs can easily lose their proliferation ability in the infarcted myocardium. Therefore, exploring the mechanism for CPC proliferation is essential for CPC-based therapy in MI-induced HF. A previous study indicated that a hypoxic environment is essential for CPC proliferation, but the mechanism is not yet clear. In this work, we discovered that CoCl{sub 2}-induced hypoxia can promote CPC proliferation and migration. Additionally, long non-coding RNA MALAT1 expression was significantly up-regulated in the CoCl{sub 2}-induced hypoxia CPC model. MALAT1 suppression inhibited CPC proliferation and migration under hypoxic conditions. In addition, MALAT1 acted as a sponge for miR-125. The miR-125 inhibitor restored the proliferation and migration potentials of CPCs after a MALAT1 knockdown in hypoxia. A further study demonstrated that JMJD6 was a target of miR-125 whose expression was negatively regulated by miR-125. JMJD6 knockdown blocked miR-125 inhibitor's protective effect on CPC function in hypoxia. Ultimately, our finding demonstrated that MALAT1 can modulate CPC proliferation and migration potential through the miR-125/JMJD6 axis in hypoxia. Our finding provided a new regulatory mechanism for CPC proliferation in hypoxia, which provided a new target for MI-induced HF therapy.

60 APPLIED LIFE SCIENCES↗