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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 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

TSPAN12 promotes chemoresistance and proliferation of SCLC under the regulation of miR-495

Studies have shown that TSPAN12 serves as an oncogenic gene or tumor suppressor depending on the types of cancer. However, its role in the drug resistance of small cell lung cancer (SCLC) is still unknown. In this study, we investigated whether TSPAN12 regulates chemoresistance, proliferation and tumor growth of SCLC under the regulation of miR-495 using two drug resistant cell lines. The results showed that down-regulation of TSPAN12 inhibited cells chemoresistance, proliferation and tumor growth. Besides, TSPAN12 elevation in SCLC specimens correlated with poor pathologic stage and shorter survival time. In addition, the dual luciferase assay indicated that TSPAN12 was one of the directly targeted genes of miR-495. Our study revealed that TSPAN12 promoted chemoresistance of SCLC under the regulation of miR-495. TSPAN12 depletion is a promising strategy for inhibiting the chemoresistance in SCLC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level

The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC. - Highlights: • As a negative regulator of p27, COPS5 depression could inhibits the proliferation of serous ovarian cancer cells. • Knockdown of COPS5 resulted in the maintaining duration of the G1-phase accompanied by cytoplasm localization of p27. • Either inhibitor CSN5i-3 or COPS6 knockdown would result in COPS5 suppression and p27-mediated S arrest. • COPS5 suppression promotes the activity osf Akst and sensitizes SOC cells to MK2206.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A

Highlights: • Exosomal miR-93 is up-regulated both in HCC cell lines' media and HCC patients' serum. • Exosomal miR-93 promotes HCC proliferation and invasion by regulating TIMP2/TP53INP1/CDKN1A. • Exosomal miR-93 is correlated with clinical information including stage, tumor size and predict patients' survival rate. Hepatocellular carcinoma (HCC) is a malignant cancer worldwide; lacking biomarkers for early prognostication contributes to its high lethality. Herein, we report a novel biomarker, exosome delivered miR-93, is up-regulated in HCC cell line media and serum samples of HCC patients. We measured the proliferation and invasion ability of HCC cell lines following exosomal miR-93 treatment. After prediction with online algorithms, we further confirmed that TP53INP1, TIMP2 and CDKN1A are direct targets of miR-93 by dual-luciferase reporter assay. In addition, the diagnostic value of exosomal miR-93 was evaluated by qPCR and ROC analysis. The significant correlation between serum exosomal miR-93 and clinical information including stage, tumor size were observed. Furthermore, the survival differences of HCC patients with high or low miR-93 were statistically significant using Kaplan-Meier analysis. In summary, our work identified exosomal miR-93 as a novel biomarker for both diagnosis and prognosis in HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The ferroptosis inducer erastin promotes proliferation and differentiation in human peripheral blood mononuclear cells

Peripheral blood mononuclear cells (PBMCs) contain multipotent progenitor cell populations and possess the potential to differentiate into various types of immune cells under both physiological and pathological conditions. Ferroptosis is a type of oxidative stress-associated cell death that is mainly mediated by lipid peroxidation. However, the function of ferroptosis in cell differentiation remains unknown. Here, we showed that the ferroptosis inducer erastin did not cause cell death in human PBMCs. In contrast, erastin-induced lipid peroxidation promoted human PBMC proliferation and differentiation into B cells and natural killer cells through inhibition of bone morphogenetic protein family expression. These findings uncover a new immune modulation function of erastin in promoting PBMC proliferation and differentiation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Annexin A2-modulated proliferation of pulmonary arterial smooth muscle cells depends on caveolae and caveolin-1 in hepatopulmonary syndrome

We have established that annexin A2 (ANXA2) is an important factor in the experimental hepatopulmonary syndrome (HPS) serum-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs). However, the detailed mechanism remains unclear. ANXA2 translocated to the caveolin-enriched microdomains (caveolae) in PASMCs upon HPS serum stimulation. The disruption of caveolae by Methyl-β-cyclodextrin (MβCD) alleviated the caveolae recruitment of ANXA2 and the ANXA2-mediated activation of ERK1/2 and NF-κB, so that ANXA2-modulated PASMC proliferation was suppressed. The over-expression of Cav-1 resulted in the relocation of ANXA2 from caveolae and negatively regulated ERK1/2 and NF-κB activation, which inhibited the ANXA2-modulated PASMC proliferative behavior. These data indicate that caveolae function as a signaling platform for ANXA2-induced proliferative behavior and Cav-1 participates upstream of ANXA2 in the activation of ERK1/2 and NF-κB.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Wnt pathway activator TWS119 enhances the proliferation and cytolytic activity of human γδT cells against colon cancer

Highlights: • The wnt pathway activator TWS119 could improve the expansion, differentiation and survival of human γδT cells in vitro. • TWS119 enhances the cytolytic activity of γδT cells against human colon cancer cells, mainly through the perforin-granzyme pathway. • WS119 could be a potent stimulator for γδT cell expansion in tumour immune cell therapy. γδT cells are a distinct T-cell subset that display unique characteristics regarding T-cell receptor gene usage, tissue tropism and antigen recognition. Adoptive γδT cell transfer therapy has recently been gaining importance as an efficient approach in cancer immunotherapy. However, exploiting γδT cell response for tumour immunotherapy is a challenge due to cell numbers, activities and differentiation states that minimize the clinical therapeutic effects. Previous studies have indicated that the wnt/β-catenin signalling pathway plays a crucial role in the differentiation, survival and enhancement of the immune response of T lymphocytes. In this study, we sought to evaluate whether the activation of the wnt/β-catenin pathway through inhibition of glycogen synthase kinase-3β (GSK-3β) using 4,6-disubstituted pyrrolopyrimidine (TWS119) could be an efficient strategy to improve the proliferation, differentiation and cytolytic activity of γδT cells against colon cancer cells. Remarkably, we found that TWS119 significantly enhanced the proliferation and survival of γδT cells via activation of the mammalian target of rapamycin (mTOR) pathway, upregulation of the expression of the anti-apoptotic protein Bcl-2 and inhibition of cleaved caspase-3 in addition to the Wnt pathway. Our results also showed that enhancement of the cytolytic activity of γδT cells against human colon cancer cells by TWS119 was chiefly associated with upregulation of the expression of perforin and granzyme B in vitro and in vivo. Additionally, TWS119 can induce the expression of CD62L or CCR5 to generate a population of CD62L{sup +}γδT or CCR5{sup +}γδT cells in a dose-dependent manner. These findings suggested that TWS119 could be a useful complementary agent for improving γδT cell-based immunotherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts

Highlights: • Indirect effects of glucocorticoid treatment on cancer cells via CAFs are described. • Glucocorticoids decrease expression of MMP-2 by CAFs. • Glucocorticoids neutralize growth-promoting and pro-invasive effects of CAFs. • In vivo, glucocorticoid treatment inhibits tumor progression. Cancer-associated fibroblasts (CAFs) support cancer growth, invasion, and metastasis. Glucocorticoids (GCs), drugs often administered together with chemotherapy, are steroidal ligands of the glucocorticoid receptor (GR), a transcription factor which upon activation regulates expression of multiple genes involved in suppression of inflammation. We have previously shown that in dexamethasone (Dex)-treated CAFs derived from colon cancer, production and secretion of several factors related to cancer progression, such as tenascin C (TNC) and hepatocyte growth factor (HGF), were strongly suppressed. In this study we show that GCs can neutralize the cancer cell-promoting properties of CAFs. Conditioned medium from solvent-treated CAFs (CM{sup CTRL}) stimulates proliferation, motility and stretched morphotype of GR-deficient HCT8/E11 colon cancer cells. Yet, HCT8/E11 proliferation and stretched morphotype are impaired upon treatment with conditioned medium from Dex-treated CAFs (CM{sup DEX}), but HCT8/E11 cell migration is slightly increased under these conditions. Moreover, expression and potential activity of MMP-2 is also reduced in CM{sup DEX} compared with CM{sup CTRL}. These combined in vitro results concur with the results from in vivo chick chorioallantoic membrane assays, where the co-cultures of CAFs with colon cancer cells displayed impaired tumor formation and cancer cell invasion due to Dex administration. Combined, GC treatment influences cancer cell behavior indirectly through effects on CAFs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2

Highlights: • Knock-down of Pax2 inhibits the osteogenesis of mouse MSCs in vitro and in vivo. • Pax2 promotes the proliferation of mouse MSCs. • Pax2 enhances transcriptional activity of Runx2 and activates MAPK pathways. • Pax2 promotes the osteogenesis of mouse MSCs and may serve as a target for future clinical treatment. Mesenchymal stem cells (MSCs) have been widely studied in the field of regenerative medicine with the potential to solve osteoporosis. Paired box 2 (Pax2), as a transcription factor, is the master regulator of embryogenesis and oncogenesis. However, the function of Pax2 in osteogenesis is unknown. Here, we reported for the first time that the expression of Pax2 gradually increased during osteogenic differentiation of mouse MSCs, and osteoprogenitor cells. However, detected in osteoblastic cells of mouse tibia, the expression of Pax2 in the embryonic stage was higher than that in adulthood. In C3H/10/T1/2 cells and compact bone-derived mouse MSCs (mMSCs), Pax2 knock-down inhibited the proliferation of these cells, down-regulated the expression of osteogenic marker genes, as well as repressed the ALP activity and mineralization. In addition, Pax2 enhanced the transcriptional activity of Runx2, and activated the MAPK pathway genes (ERK, JNK and p38). Furthermore, knock-down of Pax2 repressed the mMSCs-mediated bone regeneration in an ectopic bone formation model. In conclusion, Pax2 promotes osteogenesis of mouse MSCs, suggesting that Pax2 has a role in the pathophysiology of bone related diseases, and has potential application in bone tissue regeneration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

PDRG1 predicts a poor prognosis and facilitates the proliferation and metastasis of colorectal cancer

Highlights: • PDRG1 is overexpressed in colorectal cancer tissues and is associated with poor prognosis of colorectal cancer patients. • PDRG1 regulates the proliferation, apoptosis, cell cycle progression and metastasis of colorectal cancer cells. • PDRG1 promotes the proliferation, migration and invasion of colorectal cancer via p21-mediated cell cycle progression. The incidence and mortality of colorectal cancer (CRC) is increasing yearly and CRC patients are becoming younger in global. Evidences have revealed the carcinogenic effect of p53 and DNA damage-regulated gene 1 (PDRG1) in several types of tumors. However, its biological function is yet to be investigated in CRC. This study aimed to unveil the prooncogenic role of PDRG1 in CRC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Twin Proliferation and Prolongation under Kinetic Control: Pd–Au Janus Icosahedra versus Pd@Au Core–Shell Starfishes

Heterogeneous bimetallic nanocrystals featuring explicit spatial configurations and abundant twin defects can simultaneously enable geometric and ligand effects to enhance catalytic and photonic applications. Herein, we report two growth patterns of Au atoms on penta-twinned Pd decahedra, involving twin proliferation to generate asymmetric Pd–Au Janus icosahedra and twin elongation to produce anisotropic Pd@Au core–shell starfishes, respectively. Mechanistic analysis indicates that the injection rate determines the lower-limit number (n low ) of Au(III) ions in the steady state and thus controls the growth pattern. When n low ≤ 5.5, the kinetic rate is slow enough to initiate asymmetrical one-side growth but fast enough to outpace surface diffusion; Au tetrahedral subunits are successively proliferated along the axial $\langle$110$\rangle$ direction of Pd decahedra to form Pd–Au Janus icosahedra. Composed of five Pd and 15 Au tetrahedral subunits, such a heterogeneous icosahedron supports high (2.2 GPa) tensile strain and high strain difference up to +21.9%. In contrast, when n low > 5.5, the fast reduction kinetics promotes symmetric growth with inadequate surface diffusion. As such, Au atoms are laterally deposited along five high-indexed $\langle$211$\rangle$ ridges of Pd decahedra to generate concave Pd@Au core–shell starfishes with tunable sizes (28–40 nm), twin elongation ratios (33.82–162.08%), and lattice expansion ratios (8.82–20.10%).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content

Transcription Factor 4 ( TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4 . We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression

Lipodystrophy and obesity are associated with insulin resistance and metabolic syndrome accompanied by fat tissue dysregulation. Here, we show that serine protease inhibitor A1 (SerpinA1) expression in the liver is increased during recovery from lipodystrophy caused by the adipocyte-specific loss of insulin signaling in mice. SerpinA1 induces the proliferation of white and brown preadipocytes and increases the expression of uncoupling protein 1 (UCP1) to promote mitochondrial activation in mature white and brown adipocytes. Liver-specific SerpinA1 transgenic mice exhibit increased browning of adipose tissues, leading to increased energy expenditure, reduced adiposity and improved glucose tolerance. Conversely, SerpinA1 knockout mice exhibit decreased adipocyte mitochondrial function, impaired thermogenesis, obesity, and systemic insulin resistance. SerpinA1 forms a complex with the Eph receptor B2 and regulates its downstream signaling in adipocytes. These results demonstrate that SerpinA1 is an important hepatokine that improves obesity, energy expenditure and glucose metabolism by promoting preadipocyte proliferation and activating mitochondrial UCP1 expression in adipocytes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Proliferation transitions from a topological phase in 2+1 dimensions

We consider phase transitions out of a general topological phase in 2+1 dimensions. We assume that the transition is triggered by a single Abelian anyon, which becomes light near the transition and whose worldlines proliferate after the transition. (This proliferation is often referred to as “condensation.”) We describe the transition using a continuum field theory obtained by coupling the corresponding topological quantum field theory (TQFT) to a single complex scalar field associated with this anyon. With these assumptions, we find the most general relativistic field theory for such a transition. Even though for a given TQFT and a choice of anyon, there are infinitely many such field theories, the transition theory depends on only a single additional integer parameter. We analyze all these theories, their global symmetries, and their phases. In generic cases, the theory after the transition can be related to the original one via an Abelian hierarchy construction. In special cases, the theory after the transition is gapless, and with a particular deformation, it is related to the original TQFT by gauging an anomaly-free one-form global symmetry. We also explore the enrichment of this setup by a global U⁡(1) symmetry. In some cases, enriching the original TQFT is incompatible with the full transition theory. Lastly, we demonstrate our construction with many specific examples.

Anyons↗
DOE OSTI2022

Proliferation Resistance and Physical Protection Crosscutting Topics

This report is a companion document to a series of six white papers, prepared jointly by the Proliferation Resistance and Physical Protection Working Group (PRPPWG) and the six System Steering Committees (SSCs) and provisional System Steering Committees (pSSCs). This publication is an update to a similar series published in 2011 presenting crosscutting Proliferation Resistance & Physical Protection (PR&PP) characteristics for the six systems selected by the Generation IV International Forum (GIF) for further research and development, namely: the Lead-cooled Fast Reactor (LFR), the Sodium-cooled fast Reactor (SFR), the Very high temperature reactor (VHTR), the gas-cooled fast reactor (GFR), the Molten salt reactor (MSR) and the Supercritical water–cooled reactor (SCWR).

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗
DOE OSTI2022

A synthetic cell density signal can drive proliferation in chick embryonic tendon cells and tendon cells from a full size rooster can produce high levels of procollagen in cell culture

Cell density signaling drives tendon morphogenesis by regulating both procollagen production and cell proliferation. The signal is composed of a small, highly conserved protein (SNZR P) tightly bound to a tissue-specific, unique lipid (SNZR L). This allows the complex (SNZR PL) to bind to the membrane of the cell and locally diffuse over a radius of ~1 mm. The cell produces low levels of this signal but the binding to the membrane increases with the number of tendon cells in the local environment. In this article SNZR P was produced in E.coli and SNZR L was chemically synthesized. The two bind together when heated to 60 °C in the presence of Ca ++ and Mg ++ and the synthesized SNZR PL at ng/ml levels can replace serum. Adding SNZR PL to the medium was also tested on primary tendon cells from adult roosters. The older cells were in a maintenance state in vivo and in cell culture they proliferate more slowly than embryonic cells. Nevertheless, after reaching a moderately high cell density, they produced high levels of procollagen similar to the embryonic cells. This data was not expected from older cells but suggests that adult tendon cells can regenerate the tissue after injury when given the correct signals.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1992

Effect of spaceflight on lymphocyte proliferation and interleukin-2 production

In this study, inguinal lymp node lymphocytes from rats flown on the Cosmos 2044 mission were tested for proliferation and interleukin-2 (IL-2) production. Cells cultured with mitogenic lectins, phorbol ester, and calcium ionophore, or T-cell mitogen and lymphokine, were assayed for DNA synthesis by (H-3) thymidine incorporation. Lymphocytes incubated with a T-cell mitogen alone also were tested for IL-2 production. Proliferation of lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from control and flown rats produced similar amounts of IL-23. Thus microgravity may act on lymphocytes in a tissue-specific manner, a new finding that could impact on the evaluation of spaceflight effects on immunocompetence.

Nash, Patricia V.↗
NASA NTRS1994

Importance of dose-rate and cell proliferation in the evaluation of biological experimental results

The nuclei of cells within the bodies of astronauts traveling on extended missions outside the geomagnetosphere will experience single traversals of particles with high Linear Energy Transfer (LET) (e.g., one iron ion per one hundred years, on average) superimposed on a background of tracks with low LET (approximately one proton every two to three days, and one helium ion per month). In addition, some cell populations within the body will be proliferating, thus possibly providing increasing numbers of cells with 'initiated' targets for subsequent radiation hits. These temporal characteristics are not generally reproduced in laboratory experimental protocols. Implications of the differences in the temporal patterns of radiation delivery between conventionally designed radiation biology experiments and the pattern to be experienced in space are examined and the importance of dose-rate and cell proliferation are pointed out in the context of radiation risk assessment on long mission in space.

Curtis, S. B.↗
NASA NTRS1994

Experiment K-7-23: Effect of Spaceflight on Level and Function of Immune Cells: Proliferation and Cytokines - Part 2

Lymphocytes from the superficial inguinal lymph nodes of rats flown on the Cosmos 2044 space mission were tested for proliferation in response to polyclonal activators. Cells were cultured with T or B cell mitogens, phorbol ester and calcium ionophore, or T cell mitogen and the lymphokines interleukin-1 (IL-1) or interleukin-2 (IL-2), and assayed for DNA synthesis by (3)H-thymidine incorporation. Lymphocytes also were incubated with concanavalin A (Con A), a T cell mitogen, and tested for IL-2 production. Mitogen-stimulated proliferation of lymphocytes from rats exposed to microgravity was not significantly different from synchronous or vivarium controls. Responses to Con A and IL-2, and Con A and IL-1 likewise were unaffected by space flight. Lymphocytes from all of these groups responded well to phorbol ester and calcium ionophore stimulation. Furthermore, lymph node cells (LNC) from control rats and rats flown on Cosmos 2044 produced similar amounts of IL-2. The results obtained using hindlimb suspended rats were notably different from those of flight and control animals. LNC from suspended rats generally had greater proliferative responses to T cell mitogens than did lymphocytes from other groups. Responsiveness to a B cell mitogen was not enhanced. Con A-stimulated LNC from hindlimb suspended rats also produced more IL-2 than did lymphocytes from the other groups. This difference was statistically significant at both IL-2 induction times tested.

Nash, P. V.↗