DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinotti, Simona; Ranzato, Elia, E-mail: ranzato@unipmn.it; Parodi, Monica

Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca{sup 2+}, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis,more » suggesting its possible use in MMe treatment. - Highlights: • Ascorbate/epigallocathechin-gallate/gemcitabine has been tested on mesothelioma cells • A synergistic mechanism has been shown for cell cycle arrest and apoptosis • PCR-array analysis has revealed the de-regulation of apoptosis and cell cycle genes • Maximum upregulation has been found for the Death-Associated Protein Kinase-2 gene • Data suggest that the mixture could be used as a clinical treatment.« less

Conserved cell cycle regulatory properties within the amino terminal domain of the Epstein-Barr virus nuclear antigen 3C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Nikhil; Knight, Jason S.; Robertson, Erle S.

The gammaherpesviruses Rhesus lymphocryptovirus (LCV) and Epstein-Barr virus (EBV) are closely related phylogenetically. Rhesus LCV efficiently immortalizes Rhesus B cells in vitro. However, despite a high degree of conservation between the Rhesus LCV and EBV genomes, Rhesus LCV fails to immortalize human B cells in vitro. This species restriction may, at least in part, be linked to the EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), known to be essential for B cell transformation. We compared specific properties of EBNA3C, a well-characterized and essential EBV protein, with its Rhesus counterpart to determine whether EBNA3C phenotypes which contribute to cellmore » cycle regulation are conserved in the Rhesus LCV. We show that both EBNA3C and Rhesus EBNA3C bind to a conserved region of mammalian cyclins, regulate pRb stability, and modulate SCF{sup Skp2}-dependent ubiquitination. These results suggest that Rhesus LCV restriction from human B cell immortalization is independent of the conserved cell cycle regulatory functions of the EBNA3C protein.« less

CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo

PubMed Central

Mende, Nicole; Kuchen, Erika E.; Lesche, Mathias; Grinenko, Tatyana; Kokkaliaris, Konstantinos D.; Hanenberg, Helmut; Lindemann, Dirk; Dahl, Andreas; Platz, Alexander; Höfer, Thomas; Calegari, Federico

2015-01-01

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1–CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1–CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1–CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis. PMID:26150472

CCND1-CDK4-mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo.

PubMed

Mende, Nicole; Kuchen, Erika E; Lesche, Mathias; Grinenko, Tatyana; Kokkaliaris, Konstantinos D; Hanenberg, Helmut; Lindemann, Dirk; Dahl, Andreas; Platz, Alexander; Höfer, Thomas; Calegari, Federico; Waskow, Claudia

2015-07-27

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1-CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1-CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1-CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis. © 2015 Mende et al.

A Darwinian approach to the origin of life cycles with group properties.

PubMed

Rashidi, Armin; Shelton, Deborah E; Michod, Richard E

2015-06-01

A selective explanation for the evolution of multicellular organisms from unicellular ones requires knowledge of both selective pressures and factors affecting the response to selection. Understanding the response to selection is particularly challenging in the case of evolutionary transitions in individuality, because these transitions involve a shift in the very units of selection. We develop a conceptual framework in which three fundamental processes (growth, division, and splitting) are the scaffold for unicellular and multicellular life cycles alike. We (i) enumerate the possible ways in which these processes can be linked to create more complex life cycles, (ii) introduce three genes based on growth, division and splitting that, acting in concert, determine the architecture of the life cycles, and finally, (iii) study the evolution of the simplest five life cycles using a heuristic model of coupled ordinary differential equations in which mutations are allowed in the three genes. We demonstrate how changes in the regulation of three fundamental aspects of colonial form (cell size, colony size, and colony cell number) could lead unicellular life cycles to evolve into primitive multicellular life cycles with group properties. One interesting prediction of the model is that selection generally favors cycles with group level properties when intermediate body size is associated with lowest mortality. That is, a universal requirement for the evolution of group cycles in the model is that the size-mortality curve be U-shaped. Furthermore, growth must decelerate with size. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of baicalein on canine osteosarcoma cell proliferation and death.

PubMed

Helmerick, E C; Loftus, J P; Wakshlag, J J

2014-12-01

Flavonoids are a group of modified triphenolic compounds from plants with medicinal properties. Baicalein, a specific flavone primarily isolated from plant roots (Scutellaria baicalensis), is commonly used in Eastern medicine for its anti-inflammatory and antineoplastic properties. Previous research shows greater efficacy for baicalein than most flavonoids; however, there has been little work examining their effects on sarcoma cells, let alone canine cells. Three canine osteosarcoma cell lines (HMPOS, D17 and OS 2.4) were treated with baicalein to examine cell viability, cell cycle kinetics, anchorage-independent growth and apoptosis. Results showed that osteosarcoma cells were sensitive to baicalein at concentrations from approximately 1 to 25 μM. Modest cell cycle changes were observed in one cell line. Baicalein was effective in inducing apoptosis and did not prevent doxorubicin cell proliferation inhibition in all the cell lines. The mechanism for induction of apoptosis has not been fully elucidated; however, changes in mitochondrial permeability supersede the apoptotic response. © 2012 Blackwell Publishing Ltd.

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ruoxing; Guo, Yan-Lin, E-mail: yanlin.guo@usm.edu

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remainsmore » unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black-Right-Pointing-Pointer Oct4 and Nanog are up-regulated via de novo synthesis by cell cycle interruption.« less

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles.

PubMed

Wheeler, Richard John

2015-11-05

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point "snapshot" of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes--cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)--as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. © 2015 Wheeler. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Biomedical research of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline.

PubMed

Zhang, Weipeng; Shao, Jianmin

2010-08-01

The biomedical properties of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline were analyzed in this article. The cytotoxicity of the copolymer films was tested in vitro using human embryonic kidney (HEK) 293 cells. The cell proliferation, cell cycle, cell apoptosis, and hemolysis of the polymers were also investigated. No significant cytotoxic response was detected statistically by cytotoxicity assay, and the results of cell apoptosis and cell cycle showed that there were no statistically significant differences in them. Generally, the cells spread and grew well on polymer film. Meanwhile, the extent of hemolysis on the polymers was acceptable. Evaluation of cytotoxicity by cell cycle and apoptosis as a supplementary assay is correspondingly discussed in this article. (c) 2010 Wiley Periodicals, Inc.

Temporal controls of the asymmetric cell division cycle in Caulobacter crescentus.

PubMed

Li, Shenghua; Brazhnik, Paul; Sobral, Bruno; Tyson, John J

2009-08-01

The asymmetric cell division cycle of Caulobacter crescentus is orchestrated by an elaborate gene-protein regulatory network, centered on three major control proteins, DnaA, GcrA and CtrA. The regulatory network is cast into a quantitative computational model to investigate in a systematic fashion how these three proteins control the relevant genetic, biochemical and physiological properties of proliferating bacteria. Different controls for both swarmer and stalked cell cycles are represented in the mathematical scheme. The model is validated against observed phenotypes of wild-type cells and relevant mutants, and it predicts the phenotypes of novel mutants and of known mutants under novel experimental conditions. Because the cell cycle control proteins of Caulobacter are conserved across many species of alpha-proteobacteria, the model we are proposing here may be applicable to other genera of importance to agriculture and medicine (e.g., Rhizobium, Brucella).

Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity

PubMed Central

Saitakis, Michael; Dogniaux, Stéphanie; Goudot, Christel; Bufi, Nathalie; Asnacios, Sophie; Maurin, Mathieu; Randriamampita, Clotilde; Asnacios, Atef; Hivroz, Claire

2017-01-01

T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4+ T cell functions are affected by stiffness within the physiological Young’s modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly. DOI: http://dx.doi.org/10.7554/eLife.23190.001 PMID:28594327

Lentiviral Delivery of HIV-1 Vpr Protein Induces Apoptosis in Transformed Cells

NASA Astrophysics Data System (ADS)

Stewart, Sheila A.; Poon, Betty; Jowett, Jeremy B. M.; Xie, Yiming; Chen, Irvin S. Y.

1999-10-01

Most current anticancer therapies act by inducing tumor cell stasis followed by apoptosis. HIV-1 Vpr effectively induces apoptosis of T cells after arrest of cells at a G2/M checkpoint. Here, we investigated whether this property of Vpr could be exploited for use as a potential anticancer agent. As a potentially safer alternative to transfer of genes encoding Vpr, we developed a method to efficiently introduce Vpr protein directly into cells. Vpr packaged into HIV-1 virions lacking a genome induced efficient cell cycle arrest and apoptosis. Introduction of Vpr into tumor cell lines of various tissue origin, including those bearing predisposing mutations in p53, XPA, and hMLH1, induced cell cycle arrest and apoptosis with high efficiency. Significantly, apoptosis mediated by virion-associated Vpr was more effective on rapidly dividing cells compared with slow-growing cells, thus, in concept, providing a potential differential effect between some types of tumor cells and surrounding normal cells. This model system provides a rationale and proof of concept for the development of potential cancer therapeutic agents based on the growth-arresting and apoptotic properties of Vpr.

Cell cycle dependent changes in the plasma membrane organization of mammalian cells.

PubMed

Denz, Manuela; Chiantia, Salvatore; Herrmann, Andreas; Mueller, Peter; Korte, Thomas; Schwarzer, Roland

2017-03-01

Lipid membranes are major structural elements of all eukaryotic and prokaryotic organisms. Although many aspects of their biology have been studied extensively, their dynamics and lateral heterogeneity are still not fully understood. Recently, we observed a cell-to-cell variability in the plasma membrane organization of CHO-K1 cells (Schwarzer et al., 2014). We surmised that cell cycle dependent changes of the individual cells from our unsynchronized cell population account for this phenomenon. In the present study, this hypothesis was tested. To this aim, CHO-K1 cells were arrested in different cell cycle phases by chemical treatments, and the order of their plasma membranes was determined by various fluorescent lipid analogues using fluorescence lifetime imaging microscopy. Our experiments exhibit significant differences in the membrane order of cells arrested in the G2/M or S phase compared to control cells. Our single-cell analysis also enabled the specific selection of mitotic cells, which displayed a significant increase of the membrane order compared to the control. In addition, the lipid raft marker GPImYFP was used to study the lateral organization of cell cycle arrested cells as well as mitotic cells and freely cycling samples. Again, significant differences were found between control and arrested cells and even more pronounced between control and mitotic cells. Our data demonstrate a direct correlation between cell cycle progression and plasma membrane organization, underlining that cell-to-cell heterogeneities of membrane properties have to be taken into account in cellular studies especially at the single-cell level. Copyright © 2016 Elsevier B.V. All rights reserved.

Features of the Phosphatidylinositol Cycle and its Role in Signal Transduction.

PubMed

Epand, Richard M

2017-08-01

The phosphatidylinositol cycle (PI-cycle) has a central role in cell signaling. It is the major pathway for the synthesis of phosphatidylinositol and its phosphorylated forms. In addition, some lipid intermediates of the PI-cycle, including diacylglycerol and phosphatidic acid, are also important lipid signaling agents. The PI-cycle has some features that are important for the understanding of its role in the cell. As a cycle, the intermediates will be regenerated. The PI-cycle requires a large amount of metabolic energy. There are different steps of the cycle that occur in two different membranes, the plasma membrane and the endoplasmic reticulum. In order to complete the PI-cycle lipid must be transferred between the two membranes. The role of the Nir proteins in the process has recently been elucidated. The lipid intermediates of the PI-cycle are normally highly enriched with 1-stearoyl-2-arachidonoyl molecular species in mammals. This enrichment will be retained as long as the intermediates are segregated from other lipids of the cell. However, there is a significant fraction (>15 %) of lipids in the PI-cycle of normal cells that have other acyl chains. Phosphatidylinositol largely devoid of arachidonoyl chains are found in cancer cells. Phosphatidylinositol species with less unsaturation will not be as readily converted to phosphatidylinositol-3,4,5-trisphosphate, the lipid required for the activation of Akt with resulting effects on cell proliferation. Thus, the cyclical nature of the PI-cycle, its dependence on acyl chain composition and its requirement for lipid transfer between two membranes, explain many of the biological properties of this cycle.

Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells.

PubMed

Ma, Li-Li; Wang, Da-Wei; Yu, Xu-Dong; Zhou, Yan-Ling

2016-07-01

Tangeretin (TANG), present in peel of citrus fruits, has been shown to various medicinal properties such as chemopreventive and neuroprotective. However, the chemopreventive effect of TANG on glioblastoma cells has not been examined. The present study was designed to explore the anticancer potential of TANG in glioblastoma cells and to investigate the related mechanism. Human glioblastoma U-87MG and LN-18 cells were treated with 45μM concentration of TANG and cell growth was measured by MTT assay. The cell cycle distribution and cell death were measured by flow cytometry. The expression of cell cycle and apoptosis related genes were analyzed by quantitative RT-PCR and western blot. The cells treated with TANG were significantly increased cell growth suppression and cell death effects than vehicle treated cells. Further, TANG treatment increases G2/M arrest and apoptosis by modulating PTEN and cell-cycle regulated genes such as cyclin-D and cdc-2 mRNA and protein expressions. Moreover, the ability of TANG to decrease cell growth and to induce cell death was compromised when PTEN was knockdown by siRNA. Taken together, the chemopreventive effect of TANG is associated with regulation of cell-cycle and apoptosis in glioblastoma, thereby attenuating glioblastoma cell growth. Hence, the present findings suggest that TANG may be a therapeutic agent for glioblastoma treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models

PubMed Central

Todd, Robert G.; van der Zee, Lucas

2016-01-01

Abstract The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network. PMID:27993914

Global Effects of DDX3 Inhibition on Cell Cycle Regulation Identified by a Combined Phosphoproteomics and Single Cell Tracking Approach.

PubMed

Heerma van Voss, Marise R; Kammers, Kai; Vesuna, Farhad; Brilliant, Justin; Bergman, Yehudit; Tantravedi, Saritha; Wu, Xinyan; Cole, Robert N; Holland, Andrew; van Diest, Paul J; Raman, Venu

2018-06-01

DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24 hours with RK-33 or vehicle control. Changes in phosphopeptide abundance were analyzed with quantitative mass spectrometry using isobaric mass tags (Tandem Mass Tags). At the proteome level we mainly observed changes in mitochondrial translation, cell division pathways and proteins related to cell cycle progression. Analysis of the phosphoproteome indicated decreased CDK1 activity after RK-33 treatment. To further evaluate the effect of DDX3 inhibition on cell cycle progression over time, we performed timelapse microscopy of Fluorescent Ubiquitin Cell Cycle Indicators labeled cells after RK-33 or siDDX3 exposure. Single cell tracking indicated that DDX3 inhibition resulted in a global delay in cell cycle progression in interphase and mitosis. In addition, we observed an increase in endoreduplication. Overall, we conclude that DDX3 inhibition affects cells in all phases and causes a global cell cycle progression delay. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Label-free cell-cycle analysis by high-throughput quantitative phase time-stretch imaging flow cytometry

NASA Astrophysics Data System (ADS)

Mok, Aaron T. Y.; Lee, Kelvin C. M.; Wong, Kenneth K. Y.; Tsia, Kevin K.

2018-02-01

Biophysical properties of cells could complement and correlate biochemical markers to characterize a multitude of cellular states. Changes in cell size, dry mass and subcellular morphology, for instance, are relevant to cell-cycle progression which is prevalently evaluated by DNA-targeted fluorescence measurements. Quantitative-phase microscopy (QPM) is among the effective biophysical phenotyping tools that can quantify cell sizes and sub-cellular dry mass density distribution of single cells at high spatial resolution. However, limited camera frame rate and thus imaging throughput makes QPM incompatible with high-throughput flow cytometry - a gold standard in multiparametric cell-based assay. Here we present a high-throughput approach for label-free analysis of cell cycle based on quantitative-phase time-stretch imaging flow cytometry at a throughput of > 10,000 cells/s. Our time-stretch QPM system enables sub-cellular resolution even at high speed, allowing us to extract a multitude (at least 24) of single-cell biophysical phenotypes (from both amplitude and phase images). Those phenotypes can be combined to track cell-cycle progression based on a t-distributed stochastic neighbor embedding (t-SNE) algorithm. Using multivariate analysis of variance (MANOVA) discriminant analysis, cell-cycle phases can also be predicted label-free with high accuracy at >90% in G1 and G2 phase, and >80% in S phase. We anticipate that high throughput label-free cell cycle characterization could open new approaches for large-scale single-cell analysis, bringing new mechanistic insights into complex biological processes including diseases pathogenesis.

A flexible and qualitatively stable model for cell cycle dynamics including DNA damage effects.

PubMed

Jeffries, Clark D; Johnson, Charles R; Zhou, Tong; Simpson, Dennis A; Kaufmann, William K

2012-01-01

This paper includes a conceptual framework for cell cycle modeling into which the experimenter can map observed data and evaluate mechanisms of cell cycle control. The basic model exhibits qualitative stability, meaning that regardless of magnitudes of system parameters its instances are guaranteed to be stable in the sense that all feasible trajectories converge to a certain trajectory. Qualitative stability can also be described by the signs of real parts of eigenvalues of the system matrix. On the biological side, the resulting model can be tuned to approximate experimental data pertaining to human fibroblast cell lines treated with ionizing radiation, with or without disabled DNA damage checkpoints. Together these properties validate a fundamental, first order systems view of cell dynamics. Classification Codes: 15A68.

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

PubMed Central

El-Aouar Filho, Rachid A.; Nicolas, Aurélie; De Paula Castro, Thiago L.; Deplanche, Martine; De Carvalho Azevedo, Vasco A.; Goossens, Pierre L.; Taieb, Frédéric; Lina, Gerard; Le Loir, Yves; Berkova, Nadia

2017-01-01

Some bacterial pathogens modulate signaling pathways of eukaryotic cells in order to subvert the host response for their own benefit, leading to successful colonization and invasion. Pathogenic bacteria produce multiple compounds that generate favorable conditions to their survival and growth during infection in eukaryotic hosts. Many bacterial toxins can alter the cell cycle progression of host cells, impairing essential cellular functions and impeding host cell division. This review summarizes current knowledge regarding cyclomodulins, a heterogeneous family of bacterial effectors that induce eukaryotic cell cycle alterations. We discuss the mechanisms of actions of cyclomodulins according to their biochemical properties, providing examples of various cyclomodulins such as cycle inhibiting factor, γ-glutamyltranspeptidase, cytolethal distending toxins, shiga toxin, subtilase toxin, anthrax toxin, cholera toxin, adenylate cyclase toxins, vacuolating cytotoxin, cytotoxic necrotizing factor, Panton-Valentine leukocidin, phenol soluble modulins, and mycolactone. Special attention is paid to the benefit provided by cyclomodulins to bacteria during colonization of the host. PMID:28589102

The B-MYB Transcriptional Network Guides Cell Cycle Progression and Fate Decisions to Sustain Self-Renewal and the Identity of Pluripotent Stem Cells

PubMed Central

Zhan, Ming; Riordon, Daniel R.; Yan, Bin; Tarasova, Yelena S.; Bruweleit, Sarah; Tarasov, Kirill V.; Li, Ronald A.; Wersto, Robert P.; Boheler, Kenneth R.

2012-01-01

Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity. PMID:22936984

The B-MYB transcriptional network guides cell cycle progression and fate decisions to sustain self-renewal and the identity of pluripotent stem cells.

PubMed

Zhan, Ming; Riordon, Daniel R; Yan, Bin; Tarasova, Yelena S; Bruweleit, Sarah; Tarasov, Kirill V; Li, Ronald A; Wersto, Robert P; Boheler, Kenneth R

2012-01-01

Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity.

Mixed Electronic and Ionic Conductor-Coated Cathode Material for High-Voltage Lithium Ion Battery.

PubMed

Shim, Jae-Hyun; Han, Jung-Min; Lee, Joon-Hyung; Lee, Sanghun

2016-05-18

A lithium ionic conductor, Li1.3Al0.3Ti1.7(PO4)3 (LATP), is introduced as a coating material on the surface of Mg-doped LiCoO2 to improve electrochemical performances for high-voltage (4.5 V) lithium ion batteries. Structure, morphology, elemental distribution, and electrical properties of the materials are thoroughly characterized by SEM, TEM, EELS, EDS, and C-AFM. The coating layer is electrically conductive with the aid of Mg ions which are used as a dopant for the active materials; therefore, this mixed electronic ionic conductor strongly enhances the electrochemical performances of initial capacity, cycling property, and rate capability. The LATP coating layer also demonstrates very promising applicability for 4.4 V prismatic full cells with graphite anode, which correspond to the 4.5 V half-cells with lithium anode. The 2900 mA h full cells show 85% of capacity retention after 500 cycles and more than 60% after 700 cycles.

Long cycle life rechargeable lithium batteries

NASA Technical Reports Server (NTRS)

Pasquariello, D. M.; Willstaedt, E. B.; Abraham, K. M.

1992-01-01

Cycle life and safety of delta-LiAl/TiS2 cells were evaluated using laboratory and AA-size cells. Analysis of the alloys (which contained 60, 70, 80, or 85 wt-pct. lithium and are designated 60 LiAl etc.) showed them to contain a mixture of elemental Li and Al4Li9. Cycling efficiencies correlated with the amount of free lithium in the anode. Using an electrolyte with the composition 48 v/o THF:48 v/o 2-MeTHF:4 v/o 2-MeF/LiAsF6(1.5M), a 70 LiAl/TiS2 laboratory cell yielded a cycling efficiency of 96.4 pct. when cycled at a 100 pct. discharge depth which compares well with Li anode cycling efficiencies of 96 to 97.5 pct. obtained previously in this electrolyte. The highest cycling efficiency of any delta-LiAl/TiS2 laboratory cell was 96.7 pct. when the 60 LiAl alloy was used with the 35 v/o PC:35 v/o EC:30 v/o triglyme/LiAsF6(1.0M) electrolyte. The 70 LiAl alloy was selected for further testing in AA cells since it was malleable for the fabrication of spirally wound electrodes, and its overall cycling performance was sufficiently good. AA-size 70 LiAl/TiS2 cells appear to have capacity/rate properties similar to those for identical Li/TiS2 cells. The use of the delta-LiAl alloy anodes does not appear to offer any safety advantage when cycled cells are shorted or heated.

CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL

PubMed Central

Cutrona, G; Tasso, P; Dono, M; Roncella, S; Ulivi, M; Carpaneto, E M; Fontana, V; Comis, M; Morabito, F; Spinelli, M; Frascella, E; Boffa, L C; Basso, G; Pistoia, V; Ferrarini, M

2002-01-01

CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 cases, 93.2±4.5%, MRFI 211±82 CD10-positive cells) or low (11 cases, 11.5±6.2%, MRFI 10±7 CD10-negative cells) expression of CD10. CD10-positive acute lymphoblastic leukaemia cells were cycling cells with elevated c-myc levels and propensity to apoptosis, whereas CD10-negative acute lymphoblastic leukaemia cells had lower cycling capacities and c-myc levels, and were resistant to apoptosis in vitro. A close correlation between all these properties was demonstrated by the observations that the few CD10-positive cells found in the CD10-negative acute lymphoblastic leukaemia group displayed elevated c-myc and cycling capacities and were apoptosis prone. Moreover, exposure of CD10-positive acute lymphoblastic leukaemia B cells to a peptide nucleic acid anti-gene specific for the second exon of c-myc caused inhibition of c-myc expression and reduced cell cycling and apoptotic abilities as well as decreased CD10 expression. British Journal of Cancer (2002) 86, 1776–1785. doi:10.1038/sj.bjc.6600329 www.bjcancer.com © 2002 Cancer Research UK PMID:12087466

Cell Cycle Synchronization of HeLa Cells to Assay EGFR Pathway Activation.

PubMed

Wee, Ping; Wang, Zhixiang

2017-01-01

Progression through the cell cycle causes changes in the cell's signaling pathways that can alter EGFR signal transduction. Here, we describe drug-derived protocols to synchronize HeLa cells in various phases of the cell cycle, including G1 phase, S phase, G2 phase, and mitosis, specifically in the mitotic stages of prometaphase, metaphase, and anaphase/telophase. The synchronization procedures are designed to allow synchronized cells to be treated for EGF and collected for the purpose of Western blotting for EGFR signal transduction components.S phase synchronization is performed by thymidine block, G2 phase with roscovitine, prometaphase with nocodazole, metaphase with MG132, and anaphase/telophase with blebbistatin. G1 phase synchronization is performed by culturing synchronized mitotic cells obtained by mitotic shake-off. We also provide methods to validate the synchronization methods. For validation by Western blotting, we provide the temporal expression of various cell cycle markers that are used to check the quality of the synchronization. For validation of mitotic synchronization by microscopy, we provide a guide that describes the physical properties of each mitotic stage, using their cellular morphology and DNA appearance. For validation by flow cytometry, we describe the use of imaging flow cytometry to distinguish between the phases of the cell cycle, including between each stage of mitosis.

Cell size control and a cell-intrinsic maturation program in proliferating oligodendrocyte precursor cells.

PubMed

Gao, F B; Raff, M

1997-09-22

We have used clonal analysis and time-lapse video recording to study the proliferative behavior of purified oligodendrocyte precursor cells isolated from the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from precursor cells isolated from postnatal day 7 (P7) or P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the precursor cells, just like single-celled eucaryotes, have to reach a threshold size before they can divide. These and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic events occurring in G1 proposed by "transition probability" models, may explain the random variability of cell cycle times seen within clonal cell lines in culture.

Cell Size Control and a Cell-intrinsic Maturation Program in Proliferating Oligodendrocyte Precursor Cells

PubMed Central

Gao, Fen-Biao; Raff, Martin

1997-01-01

We have used clonal analysis and time-lapse video recording to study the proliferative behavior of purified oligodendrocyte precursor cells isolated from the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from precursor cells isolated from postnatal day 7 (P7) or P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the precursor cells, just like single-celled eucaryotes, have to reach a threshold size before they can divide. These and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic events occurring in G1 proposed by “transition probability” models, may explain the random variability of cell cycle times seen within clonal cell lines in culture. PMID:9298991

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines.

PubMed

Haddad, A Q; Venkateswaran, V; Viswanathan, L; Teahan, S J; Fleshner, N E; Klotz, L H

2006-01-01

Epidemiologic studies have demonstrated an inverse association between flavonoid intake and prostate cancer (PCa) risk. The East Asian diet is very high in flavonoids and, correspondingly, men in China and Japan have the lowest incidence of PCa worldwide. There are thousands of different naturally occurring and synthetic flavonoids. However, only a few have been studied in PCa. Our aim was to identify novel flavonoids with antiproliferative effect in PCa cell lines, as well as determine their effects on cell cycle. We have screened a representative subgroup of 26 flavonoids for antiproliferative effect on the human PCa (LNCaP and PC3), breast cancer (MCF-7), and normal prostate stromal cell lines (PrSC). Using a fluorescence-based cell proliferation assay (Cyquant), we have identified five flavonoids, including the novel compounds 2,2'-dihydroxychalcone and fisetin, with antiproliferative and cell cycle arresting properties in human PCa in vitro. Most of the flavonoids tested exerted antiproliferative effect at lower doses in the PCa cell lines compared to the non-PCa cells. Flow cytometry was used as a means to determine the effects on cell cycle. PC3 cells were arrested in G2/M phase by flavonoids. LNCaP cells demonstrated different cell cycle profiles. Further studies are warranted to determine the molecular mechanism of action of 2,2'-DHC and fisetin in PCa, and to establish their effectiveness in vivo.

Temporal self-organization of the cyclin/Cdk network driving the mammalian cell cycle

PubMed Central

Gérard, Claude; Goldbeter, Albert

2009-01-01

We propose an integrated computational model for the network of cyclin-dependent kinases (Cdks) that controls the dynamics of the mammalian cell cycle. The model contains four Cdk modules regulated by reversible phosphorylation, Cdk inhibitors, and protein synthesis or degradation. Growth factors (GFs) trigger the transition from a quiescent, stable steady state to self-sustained oscillations in the Cdk network. These oscillations correspond to the repetitive, transient activation of cyclin D/Cdk4–6 in G1, cyclin E/Cdk2 at the G1/S transition, cyclin A/Cdk2 in S and at the S/G2 transition, and cyclin B/Cdk1 at the G2/M transition. The model accounts for the following major properties of the mammalian cell cycle: (i) repetitive cell cycling in the presence of suprathreshold amounts of GF; (ii) control of cell-cycle progression by the balance between antagonistic effects of the tumor suppressor retinoblastoma protein (pRB) and the transcription factor E2F; and (iii) existence of a restriction point in G1, beyond which completion of the cell cycle becomes independent of GF. The model also accounts for endoreplication. Incorporating the DNA replication checkpoint mediated by kinases ATR and Chk1 slows down the dynamics of the cell cycle without altering its oscillatory nature and leads to better separation of the S and M phases. The model for the mammalian cell cycle shows how the regulatory structure of the Cdk network results in its temporal self-organization, leading to the repetitive, sequential activation of the four Cdk modules that brings about the orderly progression along cell-cycle phases. PMID:20007375

The Formation of Tight Tumor Clusters Affects the Efficacy of Cell Cycle Inhibitors: A Hybrid Model Study

PubMed Central

Kim, MunJu; Reed, Damon; Rejniak, Katarzyna A.

2014-01-01

Cyclin-dependent kinases (CDKs) are vital in regulating cell cycle progression, and, thus, in highly proliferating tumor cells CDK inhibitors are gaining interest as potential anticancer agents. Clonogenic assay experiments are frequently used to determine drug efficacy against the survival and proliferation of cancer cells. While the anticancer mechanisms of drugs are usually described at the intracellular single-cell level, the experimental measurements are sampled from the entire cancer cell population. This approach may lead to discrepancies between the experimental observations and theoretical explanations of anticipated drug mechanisms. To determine how individual cell responses to drugs that inhibit CDKs affect the growth of cancer cell populations, we developed a spatially explicit hybrid agent-based model. In this model, each cell is equipped with internal cell cycle regulation mechanisms, but it is also able to interact physically with its neighbors. We model cell cycle progression, focusing on the G1 and G2/M cell cycle checkpoints, as well as on related essential components, such as CDK1, CDK2, cell size, and DNA damage. We present detailed studies of how the emergent properties (e.g., cluster formation) of an entire cell population depend on altered physical and physiological parameters. We analyze the effects of CDK1 and CKD2 inhibitors on population growth, time-dependent changes in cell cycle distributions, and the dynamic evolution of spatial cell patterns. We show that cell cycle inhibitors that cause cell arrest at different cell cycle phases are not necessarily synergistically super-additive. Finally, we demonstrate that the physical aspects of cell population growth, such as the formation of tight cell clusters versus dispersed colonies, alter the efficacy of cell cycle inhibitors, both in 2D and 3D simulations. This finding may have implications for interpreting the treatment efficacy results of in vitro experiments, in which treatment is applied before the cells can grow to produce clusters, especially because in vivo tumors, in contrast, form large masses before they are detected and treated. PMID:24607745

In vitro growth inhibition of human cancer cells by novel honokiol analogs.

PubMed

Lin, Jyh Ming; Prakasha Gowda, A S; Sharma, Arun K; Amin, Shantu

2012-05-15

Honokiol possesses many pharmacological activities including anti-cancer properties. Here in, we designed and synthesized honokiol analogs that block major honokiol metabolic pathway which may enhance their effectiveness. We studied their cytotoxicity in human cancer cells and evaluated possible mechanism of cell cycle arrest. Two analogs, namely 2 and 4, showed much higher growth inhibitory activity in A549 human lung cancer cells and significant increase of cell population in the G0-G1 phase. Further elucidation of the inhibition mechanism on cell cycle showed that analogs 2 and 4 inhibit both CDK1 and cyclin B1 protien levels in A549 cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anti-inflammatory properties of methylthioadenosine in experimental colitis

USDA-ARS?s Scientific Manuscript database

The methionine (Met) metabolic cycle is critical for normal cell functions. Met cycle disruption has been implicated in disease, such as alcoholic liver disease (ALD) and multiple sclerosis (MS). Studies in animal models of ALD and MS have shown that the Met metabolite methylthioadenosine (MTA) has ...

A robust and tunable mitotic oscillator in artificial cells

PubMed Central

Wang, Shiyuan; Barnes, Patrick M; Liu, Xuwen; Xu, Haotian; Jin, Minjun; Liu, Allen P

2018-01-01

Single-cell analysis is pivotal to deciphering complex phenomena like heterogeneity, bistability, and asynchronous oscillations, where a population ensemble cannot represent individual behaviors. Bulk cell-free systems, despite having unique advantages of manipulation and characterization of biochemical networks, lack the essential single-cell information to understand a class of out-of-steady-state dynamics including cell cycles. Here, by encapsulating Xenopus egg extracts in water-in-oil microemulsions, we developed artificial cells that are adjustable in sizes and periods, sustain mitotic oscillations for over 30 cycles, and function in forms from the simplest cytoplasmic-only to the more complicated ones involving nuclear dynamics, mimicking real cells. Such innate flexibility and robustness make it key to studying clock properties like tunability and stochasticity. Our results also highlight energy as an important regulator of cell cycles. We demonstrate a simple, powerful, and likely generalizable strategy of integrating strengths of single-cell approaches into conventional in vitro systems to study complex clock functions. PMID:29620527

Epidermal stem cells: location, potential and contribution to cancer.

PubMed

Ambler, C A; Määttä, A

2009-01-01

Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

Preparation and electrochemical properties of polyaniline nanofibers using ultrasonication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manuel, James; Kim, Miso; Fapyane, Deby

2014-10-15

Highlights: • Nanofibrous structured polyaniline (PANI) was prepared by simple ultrasonication. • PANI nanofibers prepared at 5 °C are uniform with an average diameter of 50 nm. • The conductivity is increased by 2 × 10{sup 8} times after doping with LiClO{sub 4}. • The cell with PANI-LiClO{sub 4} shows good cycle performance at high current densities. - Abstract: Polyaniline nanofibers have been successfully prepared by applying ultrasonic irradiation during oxidative polymerization of aniline in dilute hydrochloric acid and evaluated for suitability in lithium cells after doping with lithium perchlorate salt. Polyaniline nanofibers are confirmed by Fourier transform infrared spectroscopy,more » Fourier transform Raman spectroscopy, and transmission electron microscopy, and the efficiency of doping is confirmed by DC conductivity measurements at different temperatures. Electrochemical properties of nanofibers are evaluated, of which a remarkable increase in cycle stability is achieved when compared to polyaniline prepared by simple oxidative polymerization of aniline. The cell with nanofibrous polyaniline doped with LiClO{sub 4} delivers an initial discharge capacity value of 86 mA h g{sup −1} at 1 C-rate which is about 60% of theoretical capacity, and the capacity is slightly lowered during cycle and reaches 50% of theoretical capacity after 40 cycles. The cell delivers a stable and higher discharge capacity even at 2 C-rate compared to that of the cell prepared with bulk polyaniline doped with LiClO{sub 4}.« less

Preparation and electrochemical characterization of gel polymer electrolyte based on electrospun polyacrylonitrile nonwoven membranes for lithium batteries

NASA Astrophysics Data System (ADS)

Raghavan, Prasanth; Manuel, James; Zhao, Xiaohui; Kim, Dul-Sun; Ahn, Jou-Hyeon; Nah, Changwoon

Electrospun membranes of polyacrylonitrile are prepared, and the electrospinning parameters are optimized to get fibrous membranes with uniform bead-free morphology. The polymer solution of 16 wt.% in N, N-dimethylformamide at an applied voltage of 20 kV results in the nanofibrous membrane with average fiber diameter of 350 nm and narrow fiber diameter distribution. Gel polymer electrolytes are prepared by activating the nonwoven membranes with different liquid electrolytes. The nanometer level fiber diameter and fully interconnected pore structure of the host polymer membranes facilitate easy penetration of the liquid electrolyte. The gel polymer electrolytes show high electrolyte uptake (>390%) and high ionic conductivity (>2 × 10 -3 S cm -1). The cell fabricated with the gel polymer electrolytes shows good interfacial stability and oxidation stability >4.7 V. Prototype coin cells with gel polymer electrolytes based on a membrane activated with 1 M LiPF 6 in ethylene carbonate/dimethyl carbonate or propylene carbonate are evaluated for discharge capacity and cycle property in Li/LiFePO 4 cells at room temperature. The cells show remarkably good cycle performance with high initial discharge properties and low capacity fade under continuous cycling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pipin, V. V.; Kosovichev, A. G.

Recent helioseismology findings, as well as advances in direct numerical simulations of global dynamics of the Sun, have indicated that in each solar hemisphere meridional circulation may form more than one cell along the radius in the convection zone. In particular, recent helioseismology results revealed a double-cell structure of the meridional circulation. We investigate properties of a mean-field solar dynamo with such double-cell meridional circulation. The dynamo model also includes the realistic profile of solar differential rotation (including the tachocline and subsurface shear layer) and takes into account effects of turbulent pumping, anisotropic turbulent diffusivity, and conservation of magnetic helicity.more » Contrary to previous flux-transport dynamo models, we find that the dynamo model can robustly reproduce the basic properties of the solar magnetic cycles for a wide range of model parameters and circulation speeds. The best agreement with observations is achieved when the surface meridional circulation speed is about 12 m s{sup –1}. For this circulation speed, the simulated sunspot activity shows good synchronization with the polar magnetic fields. Such synchronization was indeed observed during previous sunspot Cycles 21 and 22. We compare theoretical and observed phase diagrams of the sunspot number and the polar field strength and discuss the peculiar properties of Cycle 23.« less

Impact of membrane characteristics on the performance and cycling of the Br₂–H₂ redox flow cell

DOE PAGES

Tucker, Michael C.; Cho, Kyu Taek; Spingler, Franz B.; ...

2015-03-04

The Br₂/H₂ redox flow cell shows promise as a high-power, low-cost energy storage device. In this paper, the effect of various aspects of material selection and processing of proton exchange membranes on the operation of the Br₂/H₂ redox flow cell is determined. Membrane properties have a significant impact on the performance and efficiency of the system. In particular, there is a tradeoff between conductivity and crossover, where conductivity limits system efficiency at high current density and crossover limits efficiency at low current density. The impact of thickness, pretreatment procedure, swelling state during cell assembly, equivalent weight, membrane reinforcement, and additionmore » of a microporous separator layer on this tradeoff is assessed. NR212 (50 μm) pretreated by soaking in 70 °C water is found to be optimal for the studied operating conditions. For this case, an energy efficiency of greater than 75% is achieved for current density up to 400 mA cm⁻², with a maximum obtainable energy efficiency of 88%. A cell with this membrane was cycled continuously for 3164 h. Membrane transport properties, including conductivity and bromine and water crossover, were found to decrease moderately upon cycling but remained higher than those for the as-received membrane.« less

Repetitive Supra-Physiological Shear Stress Impairs Red Blood Cell Deformability and Induces Hemolysis.

PubMed

Horobin, Jarod T; Sabapathy, Surendran; Simmonds, Michael J

2017-11-01

The supra-physiological shear stress that blood is exposed to while traversing mechanical circulatory assist devices affects the physical properties of red blood cells (RBCs), impairs RBC deformability, and may induce hemolysis. Previous studies exploring RBC damage following exposure to supra-physiological shear stress have employed durations exceeding clinical instrumentation, thus we explored changes in RBC deformability following exposure to shear stress below the reported "hemolytic threshold" using shear exposure durations per minute (i.e., duty-cycles) reflective of that employed by circulatory assist devices. Blood collected from 20 male donors, aged 18-38 years, was suspended in a viscous medium and exposed to an intermittent shear stress protocol of 1 s at 100 Pa, every 60 s for 60 duty-cycles. During the remaining 59 s/min, the cells were left at stasis until the subsequent duty-cycle commenced. At discrete time points (15/30/45/60 duty-cycles), an ektacytometer measured RBC deformability immediately after shear exposure at 100 Pa. Plasma-free hemoglobin, a measurement of hemolysis, was quantified via spectrophotometry. Supra-physiological shear stress impaired RBC properties, as indicated by: (1) decreased maximal elongation of RBCs at infinite shear stress following 15 duty-cycles (P <0.05); (2) increased real-time RBC deformability during application of the supra-physiological shear stress protocol (100 Pa) following exposure to 1 duty-cycle (F (1.891, 32.15) = 12.21, P = 0.0001); and (3) increased plasma-free hemoglobin following 60 duty-cycles (P < 0.01). The present study indicates that exposure of RBCs to short-term, repeated supra-physiological shear stress, impairs RBC deformability, with the extent of impairment exacerbated with each duty-cycle, and ultimately precipitates hemolysis. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state.

PubMed

El-Badawy, Ahmed; Ghoneim, Mohamed A; Gabr, Mahmoud M; Salah, Radwa Ayman; Mohamed, Ihab K; Amer, Marwa; El-Badri, Nagwa

2017-11-07

Mesenchymal stem cells (MSCs) play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs). The effect of soluble factors secreted from MCF7, Hela, and HepG2 cancer cell lines on BM-MSCs was assessed using a Transwell indirect coculture system. After 5 days of coculture, BM-MSCs were characterized by flow cytometry for surface marker expression, by qPCR for gene expression profile, and by confocal immunofluorescence for marker expression. We then measured the sensitivity of cocultured BM-MSCs to chemotherapeutic agents, their cell cycle profile, and their response to DNA damage. The sphere formation, invasive properties, and in-vivo performance of BM-MSCs after coculture with cancer cells were also measured. Indirect coculture of cancer cells and BM-MSCs, without direct cell contact, generated slow cycling, chemoresistant spheroid stem cells that highly expressed markers of pluripotency, cancer cells, and cancer stem cells (CSCs). They also displayed properties of a side population and enhanced sphere formation in culture. Accordingly, these cells were termed cancer-induced stem cells (CiSCs). CiSCs showed a more mesenchymal phenotype that was further augmented upon TGF-β stimulation and demonstrated a high expression of the β-catenin pathway and ALDH1A1. These findings demonstrate that MSCs, recruited to the tumor microenvironment in large numbers, may display cellular plasticity, acquire a more stem-like state, and acquire some properties of CSCs upon exposure to cancer cell-secreted factors. These acquired characteristics may contribute to tumor progression, survival, and metastasis. Our findings provide new insights into the interactions between MSCs and cancer cells, with the potential to identify novel molecular targets for cancer therapy.

Electrochemical properties of lithium iron phosphate cathode material using polymer electrolyte

NASA Astrophysics Data System (ADS)

Kim, Jae-Kwang; Choi, Jae-Won; Cheruvally, Gouri; Shin, Yong-Jo; Ahn, Jou-Hyeon; Cho, Kwon-Koo; Ahn, Hyo-Jun; Kim, Ki-Won

2007-12-01

Carbon-coated lithium iron phosphate (LiFePO4/C) cathode material was synthesized by mechano-chemical activation method. The performance of LiFePO4/C in lithium battery was tested with an electrospun polymer-based electrolyte. Liquid electrolyte of 1M lithium hexafluorophosphate (LiPF6) in ethylene carbonate/dimethyl carbonate (EC/DMC) (1 : 1vol) was incorporated in electrospun poly(vinylidene fluoride-co-hexafluoropropylene) (P(VdF-HFP)) microfibrous membrane to prepare the polymer electrolyte (PE). The cell based on Li|PE|Li FePO4/C exhibited an initial discharge capacity of 142 mAh g-1 at 0.1 C-rate at room temperature. Good cycling performance even under the high current density of 2 C could be obtained. Impedance spectroscopy was applied to investigate the material behavior during 0.1 C-rate charge-discharge cycling. When the fresh cell and the cell after different cycles were compared, impedance resistance was found to decrease with cycling. Impedance study indicated good cycle life for the cell when tested at room temperature.

Cellular plasticity enables adaptation to unforeseen cell-cycle rewiring challenges.

PubMed

Katzir, Yair; Stolovicki, Elad; Stern, Shay; Braun, Erez

2012-01-01

The fundamental dynamics of the cell cycle, underlying cell growth and reproduction, were previously found to be robust under a wide range of environmental and internal perturbations. This property was commonly attributed to its network structure, which enables the coordinated interactions among hundreds of proteins. Despite significant advances in deciphering the components and autonomous interactions of this network, understanding the interfaces of the cell cycle with other major cellular processes is still lacking. To gain insight into these interfaces, we used the process of genome-rewiring in yeast by placing an essential metabolic gene HIS3 from the histidine biosynthesis pathway, under the exclusive regulation of different cell-cycle promoters. In a medium lacking histidine and under partial inhibition of the HIS3p, the rewired cells encountered an unforeseen multitasking challenge; the cell-cycle regulatory genes were required to regulate the essential histidine-pathway gene in concert with the other metabolic demands, while simultaneously driving the cell cycle through its proper temporal phases. We show here that chemostat cell populations with rewired cell-cycle promoters adapted within a short time to accommodate the inhibition of HIS3p and stabilized a new phenotypic state. Furthermore, a significant fraction of the population was able to adapt and grow into mature colonies on plates under such inhibiting conditions. The adapted state was shown to be stably inherited across generations. These adaptation dynamics were accompanied by a non-specific and irreproducible genome-wide transcriptional response. Adaptation of the cell-cycle attests to its multitasking capabilities and flexible interface with cellular metabolic processes and requirements. Similar adaptation features were found in our previous work when rewiring HIS3 to the GAL system and switching cells from galactose to glucose. Thus, at the basis of cellular plasticity is the emergence of a yet-unknown general, non-specific mechanism allowing fast inherited adaptation to unforeseen challenges.

The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle

PubMed Central

Samuel, Temesgen; Fadlalla, Khalda; Turner, Timothy; Yehualaeshet, Teshome E.

2010-01-01

Quercetin is a flavonoid with anticancer properties. In this study, we examined the effects of quercetin on cell cycle, viability and proliferation of cancer cells, either singly or in combination with the microtubule-targeting drugs taxol and nocodazole. Although quercetin induced cell death in a dose dependent manner, 12.5-50μM quercetin inhibited the activity of both taxol and nocodazole to induce G2/M arrest in various cell lines. Quercetin also partially restored drug-induced loss in viability of treated cells for up to 72 hours. This antagonism of microtubule-targeting drugs was accompanied by a delay in cell cycle progression and inhibition of the buildup of cyclin-B1 at the microtubule organizing center of treated cells. However, quercetin did not inhibit the microtubule targeting of taxol or nocodazole. Despite the short-term protection of cells by quercetin, colony formation and clonogenicity of HCT116 cells were still suppressed by quercetin or quercetin-taxol combination. The status of cell adherence to growth matrix was critical in determining the sensitivity of HCT116 cells to quercetin. We conclude that while long-term exposure of cancer cells to quercetin may prevent cell proliferation and survival, the interference of quercetin with cell cycle progression diminishes the efficacy of microtubule-targeting drugs to arrest cells at G2/M. PMID:21058190

Characterization of physiochemical properties of polymeric and electrochemical materials for aerospace flight

NASA Technical Reports Server (NTRS)

Rock, M.; Kunigahalli, V.; Khan, S.; Mcnair, A.

1984-01-01

Nickel-cadmium rechargeable batteries are a vital and reliable energy storage source for aerospace applications. As the demand for longer life and more reliable space batteries increases, the understanding and solving of cell aging factors and mechanisms become essential. Over the years, many cell designs and manufacturing process changes have been developed and implemented. Cells fabricated with various design features were life cycled in a simulated low-Earth orbit regime. Following the test program, a comprehensive electrochemical analysis of cell components was undertaken to study cell degradation mechanisms. Discharge voltage degradation or voltage plateau has been observed during orbit cycling, but, its cause and explanation have been the subject of much discussion. A Hg/HgO reference electrode was used to monitor the reference versus each electrode potential during the discharge of a cycled cell. The results indicate that the negative electrode was responsible for the voltage plateau. Cell analysis revealed large crystals of cadmium hydroxide on the surface of the negative electrode and throughout the separator.

Herpes simplex virus 1 regulatory protein ICP22 interacts with a new cell cycle-regulated factor and accumulates in a cell cycle-dependent fashion in infected cells.

PubMed

Bruni, R; Roizman, B

1998-11-01

The herpes simplex virus 1 infected cell protein 22 (ICP22), the product of the alpha22 gene, is a nucleotidylylated and phosphorylated nuclear protein with properties of a transcriptional factor required for the expression of a subset of viral genes. Here, we report the following. (i) ICP22 interacts with a previously unknown cellular factor designated p78 in the yeast two-hybrid system. The p78 cDNA encodes a polypeptide with a distribution of leucines reminiscent of a leucine zipper. (ii) In uninfected and infected cells, antibody to p78 reacts with two major bands with an apparent Mr of 78,000 and two minor bands with apparent Mrs of 62, 000 and 55,000. (ii) p78 also interacts with ICP22 in vitro. (iii) In uninfected cells, p78 was dispersed largely in the nucleoplasm in HeLa cells and in the nucleoplasm and cytoplasm in HEp-2 cells. After infection, p78 formed large dense bodies which did not colocalize with the viral regulatory protein ICP0. (iv) Accumulation of p78 was cell cycle dependent, being highest very early in S phase. (v) The accumulation of ICP22 in synchronized cells was highest in early S phase, in contrast to the accumulation of another protein, ICP27, which was relatively independent of the cell cycle. (vi) In the course of the cell cycle, ICP22 was transiently modified in an aberrant fashion, and this modification coincided with expression of p78. The results suggest that ICP22 interacts with and may be stabilized by cell cycle-dependent proteins.

Atomic Force Microscopy Measurements of the Mechanical Properties of Cell Walls on Living Bacterial Cells

NASA Astrophysics Data System (ADS)

Bailey, Richard; Mullin, Nic; Turner, Robert; Foster, Simon; Hobbs, Jamie

2014-03-01

Staphylococcus aureus is a major cause of infection in humans, including the Methicillin resistant strain, MRSA. However, very little is known about the mechanical properties of these cells. Our investigations use AFM to examine live S. aureus cells to quantify mechanical properties. These were explored using force spectroscopy with different trigger forces, allowing the properties to be extracted at different indentation depths. A value for the cell wall stiffness has been extracted, along with a second, higher value which is found upon indenting at higher forces. This higher value drops as the cells are exposed to high salt, sugar and detergent concentrations, implying that this measurement contains a contribution from the internal turgor pressure. We have monitored these properties as the cells progress through the cell cycle. Force maps were taken over the cells at different stages of the growth process to identify changes in the mechanics throughout the progression of growth and division. The effect of Oxacillin has also been studied, to better understand its mechanism of action. Finally mutant strains of S. aureus and a second species Bacillus subtilis have been used to link the mechanical properties of the cell walls with the chain lengths and substructures involved.

Selecting the Best Graphite for Long-Life, High-Energy Li-Ion Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Chengyu; Wood, Marissa; David, Lamuel Abraham

Here, most lithium-ion batteries still rely on intercalation-type graphite materials for anodes, so it is important to consider their role in full cells for applications in electric vehicles. Here, we systematically evaluate the chemical and physical properties of six commercially-available natural and synthetic graphites to establish which factors have the greatest impact on the cycling stability of full cells with nickel-rich LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes. Electrochemical data and post-mortem characterization explain the origin of capacity fade. The NMC811 cathode shows large irreversible capacity loss and impedance growth, accounting for much of full cell degradation. However, six graphite anodes demonstrate significant differencesmore » with respect to structural change, surface area, impedance growth, and SEI chemistry, which impact overall capacity retention. We found long cycle life correlated most strongly with stable graphite crystallite size. In addition, graphites with lower surface area generally had higher coulombic efficiencies during formation cycles, which led to more stable long-term cycling. The best graphite screened here enables a capacity retention around 90% in full pouch cells over extensive long-term cycling compared to only 82% for cells with the lowest performing graphite. The results show that optimal graphite selection improves cycling stability of high energy lithium-ion cells.« less

Selecting the Best Graphite for Long-Life, High-Energy Li-Ion Batteries

DOE PAGES

Mao, Chengyu; Wood, Marissa; David, Lamuel Abraham; ...

2018-06-16

Here, most lithium-ion batteries still rely on intercalation-type graphite materials for anodes, so it is important to consider their role in full cells for applications in electric vehicles. Here, we systematically evaluate the chemical and physical properties of six commercially-available natural and synthetic graphites to establish which factors have the greatest impact on the cycling stability of full cells with nickel-rich LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes. Electrochemical data and post-mortem characterization explain the origin of capacity fade. The NMC811 cathode shows large irreversible capacity loss and impedance growth, accounting for much of full cell degradation. However, six graphite anodes demonstrate significant differencesmore » with respect to structural change, surface area, impedance growth, and SEI chemistry, which impact overall capacity retention. We found long cycle life correlated most strongly with stable graphite crystallite size. In addition, graphites with lower surface area generally had higher coulombic efficiencies during formation cycles, which led to more stable long-term cycling. The best graphite screened here enables a capacity retention around 90% in full pouch cells over extensive long-term cycling compared to only 82% for cells with the lowest performing graphite. The results show that optimal graphite selection improves cycling stability of high energy lithium-ion cells.« less

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells.

PubMed

Wang, Ruoxing; Guo, Yan-Lin

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. Copyright © 2012 Elsevier Inc. All rights reserved.

Scorpion (Androctonus bicolor) venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines

PubMed Central

Al-Asmari, Abdulrahman K.; Riyasdeen, Anvarbatcha; Abbasmanthiri, Rajamohamed; Arshaduddin, Mohammed; Al-Harthi, Fahad Ali

2016-01-01

Objectives: The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. Materials and Methods: Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231) and colorectal (HCT-8) cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4’,6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. Results: The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. Conclusions: The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom. PMID:27721540

Scorpion (Androctonus bicolor) venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines.

PubMed

Al-Asmari, Abdulrahman K; Riyasdeen, Anvarbatcha; Abbasmanthiri, Rajamohamed; Arshaduddin, Mohammed; Al-Harthi, Fahad Ali

2016-01-01

The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231) and colorectal (HCT-8) cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4',6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom.

The antiangiogenic activity of Kushecarpin D, a novel flavonoid isolated from Sophora flavescens Ait.

PubMed

Pu, Li-Ping; Chen, He-Ping; Cao, Mei-Ai; Zhang, Xiu-Li; Gao, Qing-Xiang; Yuan, Cheng-Shan; Wang, Chun-Ming

2013-11-13

Kushecarpin D (KD) is a novel flavonoid isolated from the traditional Chinese herbal medicine Kushen (the dried root of Sophora flavescens Ait). As part of our continuous effort to explore Chinese traditional medicinal herbs and to identify novel natural anticancer products, the antiangiogenic properties of KD were examined in vitro using a human umbilical vein endothelial cell line (ECV304). The SRB and Trypan Blue exclusion assays were used to evaluate the effect of KD on cell proliferation. The antiangiogenic activities of KD were evaluated through studies of cell migration, cell adhesion, and tube formation. DCFH-DA and DHE fluorescent assays were used to detect the reactive oxygen species (ROS) levels. Catalase activity was detected using the colorimetric ammonium molybdate method. Cell cycle and apoptosis were measured using flow cytometry and the Hoechst 33258 staining assay. The results indicated that KD showed antiangiogenic activity via inhibitory effects on cell proliferation, cell migration, cell adhesion, and tube formation. ROS levels were down-regulated and catalase activity was up-regulated after treatment with KD. The cell cycle was arrested at the G2/M phase, while no apoptosis was observed using the Hoechst 33258 staining assay or following the flow cytometric analysis of the sub-G1 proportion. The antiangiogenic properties of KD, in combination with its anti-proliferative effect and ability to induce cell cycle arrest without inducing apoptosis, make it a good candidate for development as antitumor agent. However, further studies are essential to elucidate its mechanism of action. © 2013.

Quantification of cell cycle kinetics by EdU (5-ethynyl-2′-deoxyuridine)-coupled-fluorescence-intensity analysis

PubMed Central

Cabrita, Marisa; Bekman, Evguenia; Braga, José; Rino, José; Santus, Renè; Filipe, Paulo L.; Sousa, Ana E.; Ferreira, João A.

2017-01-01

We propose a novel single-deoxynucleoside-based assay that is easy to perform and provides accurate values for the absolute length (in units of time) of each of the cell cycle stages (G1, S and G2/M). This flow-cytometric assay takes advantage of the excellent stoichiometric properties of azide-fluorochrome detection of DNA substituted with 5-ethynyl-2′-deoxyuridine (EdU). We show that by pulsing cells with EdU for incremental periods of time maximal EdU-coupled fluorescence is reached when pulsing times match the length of S phase. These pulsing times, allowing labelling for a full S phase of a fraction of cells in asynchronous populations, provide accurate values for the absolute length of S phase. We characterized additional, lower intensity signals that allowed quantification of the absolute durations of G1 and G2 phases. Importantly, using this novel assay data on the lengths of G1, S and G2/M phases are obtained in parallel. Therefore, these parameters can be estimated within a time frame that is shorter than a full cell cycle. This method, which we designate as EdU-Coupled Fluorescence Intensity (E-CFI) analysis, was successfully applied to cell types with distinctive cell cycle features and shows excellent agreement with established methodologies for analysis of cell cycle kinetics. PMID:28465489

Multiple Pharmacological Properties of a Novel Parthenin Analog P16 as Evident by its Cytostatic and Antiangiogenic Potential Against Pancreatic Adenocarcinoma PANC -1 Cells.

PubMed

Goswami, Akshra; Shah, Bhahwal Ali; Batra, Navneet; Kumar, Ajay; Guru, Santosh Kumar; Bhushan, Shashi; Malik, Fayaz Ahmad; Joshi, Amit; Singh, Jagtar

2016-01-01

Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest types of cancers. Median survival rate is very poor with the currently available chemotherapeutical regimens. Therefore, discovery of new antineoplastic agents against PDA is one of the focused areas of contemporary research. The present study was undertaken to explore the antitumour activity of a potent parthenin analog P16. Among PANC-1, Mia PaCa-2 and AsPC-1 pancreatic cancer cells, PANC-1 showed highest sensitivity to P16 with an IC50 value of 3.4 μM. Time dependent cell cycle studies revealed that P16 suppressed the growth of PANC-1 cells by arresting the progression through the cell cycle in G2/M phase via downregulation of cyclin B1 and cyclin A. However, P16 did not alter the expressions of CDK-1 and CDC25C in PANC-1 cells. The P16 induced cell cycle arrest, which consequently, led to induction of apoptosis, which was accompanied by activation of caspase-9 and -3. Interestingly, PANC-1 cells displayed increasing loss of mitochondrial potential, which seemed to be correlated to the activation of caspase-3. Additionally, P16 was also able to down-regulate the cell migration in PANC-1 cells. Furthermore, P16 treatment of hypoxic PANC-1 cells strongly suppressed the expression of proangiogenic factors VEGFR-2, HIF1α and HIF1β. Antiangiogenic ability of P16 was also reflected in the human umbilical vascular endothelial cells (HUVECs), where it effectively suppressed the migration and inhibited the formation of the tube in a matrigel based assay. Therefore, cytostatic and antiangiogenic properties of P16 against pancreatic adenocarcinoma cells make it a suitable candidate for further investigation.

A novel flavonoid isolated from Sophora flavescens exhibited anti-angiogenesis activity, decreased VEGF expression and caused G0/G1 cell cycle arrest in vitro.

PubMed

Zhang, Xiu-Li; Cao, Mei-Ai; Pu, Li-Ping; Huang, Shuang-Sheng; Gao, Qing-Xiang; Yuan, Cheng-Shan; Wang, Chun-Ming

2013-05-01

Kushen, the dried root of Sophora flavescens Ait, is a traditional Chinese herbal medicine. Kushen alkaloids have been developed in China as anticancer drugs, and more potent antitumor activities have been identified in kushen flavonoids than in kushen alkaloids. In this study, the anti-angiogenic properties of (2S)-7,2',4'-triihydroxy-5-methoxy-8-dimethylallyl flavanone (Compound 1, a novel flavonoid isolated from Kushen), were examined using the human umbilical vein endothelial cell line (ECV304) in vitro. The results indicated that compound 1 shows anti-angiogenesis activity via inhibitory effects on cell proliferation, cell migration, cell adhesion, and tube formation. Further studies indicated that compound 1 blocks cell cycles in the G0/G1 phase without inducing apoptosis, and down regulates vascular endothelial growth factor (VEGF) expression. The free radical scavenging activity of compound 1 was found through 2',7'-dichlorofluorescin diacetate (DCFH-DA) incubation assay in cells. The anti-angiogenic properties of compound 1 and its antiproliferative effect on endothelial cells without causing apoptosis make it a good candidate for development as a agent against development of tumors.

Epstein-Barr Virus: The Path from Latent to Productive Infection.

PubMed

Chiu, Ya-Fang; Sugden, Bill

2016-09-29

The intrinsic properties of different viruses have driven their study. For example, the capacity for efficient productive infection of cultured cells by herpes simplex virus 1 has made it a paradigm for this mode of infection for herpesviruses in general. Epstein-Barr virus, another herpesvirus, has two properties that have driven its study: It causes human cancers, and it exhibits a tractable transition from its latent to its productive cycle in cell culture. Here, we review our understanding of the path Epstein-Barr virus follows to move from a latent infection to and through its productive cycle. We use information from human infections to provide a framework for describing studies in cell culture and, where possible, the molecular resolutions from these studies. We also pose questions whose answers we think are pivotal to understanding this path, and we provide answers where we can.

Synthesis, characterization, DNA-binding study and anticancer properties of ternary metal(II) complexes of edda and an intercalating ligand.

PubMed

Ng, Chew Hee; Kong, King Chow; Von, Sze Tin; Balraj, Pauline; Jensen, Paul; Thirthagiri, Eswary; Hamada, Hirokazu; Chikira, Makoto

2008-01-28

A series of ternary metal(ii) complexes {M(phen)(edda); 1a (Cu), 1b (Co), 1c (Zn), 1d (Ni); H(2)edda = N,N(')-ethylenediaminediacetic acid} of N,N'-ethylene-bridged diglycine and 1,10-phenanthroline were synthesized and characterized by elemental analysis, FTIR, UV-visible spectroscopy and magnetic susceptibility measurement. The interaction of these complexes with DNA was investigated using CD and EPR spectroscopy. MTT assay results of 1a-1c , screened on MCF-7 cancer cell lines, show that synergy between the metal and ligands results in significant enhancement of their antiproliferative properties. Preliminary results from apoptosis and cell cycle analyses with flow cytometry are reported. seems to be able to induce cell cycle arrest at G(0)/G(1). The crystal structure of 1a is also included.

Comparative Evaluation of Silibinin Effects on Cell Cycling and Apoptosis in Human Breast Cancer MCF-7 and T47D Cell Lines.

PubMed

Jahanafrooz, Zohreh; Motameh, Nasrin; Bakhshandeh, Behnaz

2016-01-01

Silibinin is a natural polyphenol with high antioxidant and anticancer properties. In this study, its influence on two of the most commonly employed human breast cancer cell lines, MCF-7 and T47D, and one non-malignant MCF-10A cell line, were investigated and compared. Cell viability, the cell cycle distribution and apoptosis induction were analyzed by MTT and flow cytometry, respectively. The effect of silibinin on PTEN, Bcl-2, P21, and P27 mRNAs expression was also investigated by real-time RT-PCR. It was found that silibinin caused G1 cell cycle arrest in MCF-7 and MCF-10A cells but had no effect on the T47D cell cycle. Silibinin induced cytotoxic and apoptotic effects in T47D cells more than the MCF-7 cells and had no cytotoxic effect in MCF-10A cells under the same conditions. Silibinin upregulated PTEN in MCF-7 and caused slightly increased P21 mRNA expression in T47D cells and slightly increased PTEN and P21 expression in MCF-10A cells. Bcl-2 expression decreased in all of the examined cells under silibinin treatment. P27 mRNA expression upregulated in T47D and MCF-10A cells under silibinin treatment. PTEN mRNA in T47D and P21 and P27 mRNAsin MCF-7 were not affected by silibinin. These results suggest that silibinin has mostly different inhibitory effects in breast cancer cells and might be an effective anticancer agent for some cells linked to influence on cell cycle progression.

Host range and cell cycle activation properties of polyomavirus large T-antigen mutants defective in pRB binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freund, R.; Bauer, P.H.; Benjamin, T.L.

1994-11-01

The authors have examined the growth properties of polyomavirus large T-antigen mutants that ar unable to bind pRB, the product of the retinoblastoma tumor suppressor gene. These mutants grow poorly on primary mouse cells yet grow well on NIH 3T3 and other established mouse cell lines. Preinfection of primary baby mouse kidney (BMK) epithelial cells with wild-type simian virus 40 renders these cells permissive to growth of pRB-binding polyomavirus mutants. Conversely, NIH 3T3 cells transfected by and expressing wild-type human pRB become nonpermissive. Primary fibroblasts for mouse embryos that carry a homozygous knockout of the RB gene are permissive, whilemore » those from normal littermates are nonpermissive. The host range of polyomavirus pRB-binding mutants is thus determined by expression or lack of expression of functional pRB by the host. These results demonstrate the importance of pRB binding by large T antigen for productive viral infection in primary cells. Failure of pRB-binding mutants to grow well in BMK cells correlates with their failure to induce progression from G{sub 0} or G{sub 1} through the S phase of the cell cycle. Time course studies show delayed synthesis and lower levels of accumulation of large T antigen, viral DNA, and VP1 in mutant compared with wild-type virus-infected BMK cells. These results support a model in which productive infection by polyomavirus in normal mouse cells is tightly coupled to the induction and progression of the cell cycle. 48 refs., 6 figs., 5 tabs.« less

Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression.

PubMed

Kim, Jung Ha; Park, Jong-Jae; Lee, Beom Jae; Joo, Moon Kyung; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

2016-05-23

Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines. The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed. The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27(kip-1) increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner. Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27(kip-1).

Solid-state sodium cells - An alternative to lithium cells?

NASA Astrophysics Data System (ADS)

West, K.; Zachau-Christiansen, B.; Jacobsen, T.; Skaarup, S.

1989-05-01

The cycling properties of laboratory cells based on the insertion of sodium into vanadium oxides using polymer electrolyte at 80 C are reported. In the best system: Na/PEO, NaClO4/V2O5 (modified), C, high reversibility, and an energy density comparable with the Li/TiS2 system have been obtained.

3,3′-Diindolylmethane Ameliorates Staphylococcal Enterotoxin B–Induced Acute Lung Injury through Alterations in the Expression of MicroRNA that Target Apoptosis and Cell-Cycle Arrest in Activated T Cells

PubMed Central

Elliott, David M.; Nagarkatti, Mitzi

2016-01-01

3,3′-Diindolylmethane (DIM), a natural indole found in cruciferous vegetables, has significant anti-cancer and anti-inflammatory properties. In this current study, we investigated the effects of DIM on acute lung injury (ALI) induced by exposure to staphylococcal enterotoxin B (SEB). We found that pretreatment of mice with DIM led to attenuation of SEB-induced inflammation in the lungs, vascular leak, and IFN-γ secretion. Additionally, DIM could induce cell-cycle arrest and cell death in SEB-activated T cells in a concentration-dependent manner. Interestingly, microRNA (miRNA) microarray analysis uncovered an altered miRNA profile in lung-infiltrating mononuclear cells after DIM treatment of SEB-exposed mice. Moreover, computational analysis of miRNA gene targets and regulation networks indicated that DIM alters miRNA in the cell death and cell-cycle progression pathways. Specifically, DIM treatment significantly downregulated several miRNA and a correlative increase associated gene targets. Furthermore, overexpression and inhibition studies demonstrated that DIM-induced cell death, at least in part, used miR-222. Collectively, these studies demonstrate for the first time that DIM treatment attenuates SEB-induced ALI and may do so through the induction of microRNAs that promote apoptosis and cell-cycle arrest in SEB-activated T cells. PMID:26818958

A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells.

PubMed

Hegde, Mahesh; Vartak, Supriya V; Kavitha, Chandagirikoppal V; Ananda, Hanumappa; Prasanna, Doddakunche S; Gopalakrishnan, Vidya; Choudhary, Bibha; Rangappa, Kanchugarakoppal S; Raghavan, Sathees C

2017-05-31

Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.

Gallium, a promising candidate to disrupt the vicious cycle driving osteolytic metastases.

PubMed

Strazic-Geljic, Ivana; Guberovic, Iva; Didak, Blanka; Schmid-Antomarchi, Heidy; Schmid-Alliana, Annie; Boukhechba, Florian; Bouler, Jean-Michel; Scimeca, Jean-Claude; Verron, Elise

2016-09-15

Bone metastases of breast cancer typically lead to a severe osteolysis due to an excessive osteoclastic activity. On the other hand, the semi-metallic element gallium (Ga) displays an inhibitory action on osteoclasts, and therefore on bone resorption, as well as antitumour properties. Thus, we explored in vitro Ga effects on osteoclastogenesis in an aggressive bone metastatic environment based on the culture of pre-osteoclast RAW 264.7 cells with conditioned medium from metastatic breast tumour cells, i.e. the breast tumour cell line model MDA-MB-231 and its bone-seeking clone MDA-231BO. We first observed that Ga dose-dependently inhibited the tumour cells-induced osteoclastic differentiation of RAW 264.7 cells. To mimic a more aggressive environment where pro-tumourigenic factors are released from bone matrix due to osteoclastic resorption, metastatic breast tumour cells were stimulated with TGF-β, a mayor cytokine in bone metastasis vicious cycle. In these conditions, we observed that Ga still inhibited cancer cells-driven osteoclastogenesis. Lastly, we evidenced that Ga affected directly and strongly the proliferation/viability of both cancer cell lines, as well as the expression of major osteolytic factors in MDA-231BO cells. With the exception of two small scale clinical studies from 1980s, this is the first time that antitumour properties of Ga have been specifically studied in the context of bone metastases. Our data strongly suggest that, through its action against the vicious cycle involving bone cells and tumour cells, Ga represents a relevant and promising candidate for the local treatment of bone metastases in patients with breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Microtubule-stabilizing properties of the avocado-derived toxins (+)-(R)-persin and (+)-(R)-tetrahydropersin in cancer cells and activity of related synthetic analogs.

PubMed

Field, Jessica J; Kanakkanthara, Arun; Brooke, Darby G; Sinha, Saptarshi; Pillai, Sushila D; Denny, William A; Butt, Alison J; Miller, John H

2016-06-01

The avocado toxin (+)-R-persin (persin) is active at low micromolar concentrations against breast cancer cells and synergizes with the estrogen receptor modulator 4-hydroxytamoxifen. Previous studies in the estrogen receptor-positive breast cancer cell line MCF-7 indicate that persin acts as a microtubule-stabilizing agent. In the present study, we further characterize the properties of persin and several new synthetic analogues in human ovarian cancer cells. Persin and tetrahydropersin cause G2M cell cycle arrest and increase intracellular microtubule polymerization. One analog (4-nitrophenyl)-deshydroxypersin prevents cell proliferation and blocks cells in G1 of the cell cycle rather than G2M, suggesting an additional mode of action of these compounds independent of microtubules. Persin can synergize with other microtubule-stabilizing agents, and is active against cancer cells that overexpress the P-glycoprotein drug efflux pump. Evidence from Flutax-1 competition experiments suggests that while the persin binding site on β-tubulin overlaps the classical taxoid site where paclitaxel and epothilone bind, persin retains activity in cell lines with single amino acid mutations that affect these other taxoid site ligands. This implies the existence of a unique binding location for persin at the taxoid site.

Impact of membrane characteristics on the performance and cycling of the Br-2-H-2 redox flow cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tucker, MC; Cho, KT; Spingler, FB

2015-06-15

The Br-2/H-2 redox flow cell shows promise as a high-power, low-cost energy storage device. In this paper, the effect of various aspects of material selection and processing of proton exchange membranes on the operation of the Br-2/H-2 redox flow cell is determined. Membrane properties have a significant impact on the performance and efficiency of the system. In particular, there is a tradeoff between conductivity and crossover, where conductivity limits system efficiency at high current density and crossover limits efficiency at low current density. The impact of thickness, pretreatment procedure, swelling state during cell assembly, equivalent weight, membrane reinforcement, and additionmore » of a microporous separator layer on this tradeoff is assessed. NR212 (50 mu m) pretreated by soaking in 70 degrees C water is found to be optimal for the studied operating conditions. For this case, an energy efficiency of greater than 75% is achieved for current density up to 400 mA cm(-2), with a maximum obtainable energy efficiency of 88%. A cell with this membrane was cycled continuously for 3164 h. Membrane transport properties, including conductivity and bromine and water crossover, were found to decrease moderately upon cycling but remained higher than those for the as-received membrane. (C) 2015 Elsevier B.V. All rights reserved.« less

Matrix Rigidity Regulates Cancer Cell Growth by Modulating Cellular Metabolism and Protein Synthesis

PubMed Central

Tilghman, Robert W.; Blais, Edik M.; Cowan, Catharine R.; Sherman, Nicholas E.; Grigera, Pablo R.; Jeffery, Erin D.; Fox, Jay W.; Blackman, Brett R.; Tschumperlin, Daniel J.; Papin, Jason A.; Parsons, J. Thomas

2012-01-01

Background Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy. Methodology/Principal Findings This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa), cells on soft substrates (150–300 Pa) exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins) and glycolysis (e.g., phosphofructokinase-1), whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway. Conclusions/Significance The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical environments encountered by cancer cells upon metastasis to distant sites. PMID:22623999

Battery Thermal Characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyser, Matthew; Saxon, Aron; Powell, Mitchell

2016-06-07

This poster shows the progress in battery thermal characterization over the previous year. NREL collaborated with U.S. DRIVE and USABC battery developers to obtain thermal properties of their batteries, obtained heat capacity and heat generation of cells under various power profiles, obtained thermal images of the cells under various drive cycles, and used the measured results to validate thermal models. Thermal properties are used for the thermal analysis and design of improved battery thermal management systems to support achieve life and performance targets.

Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)

PubMed Central

2003-01-01

This review focuses on the prodrugs used in suicide gene therapy. These prodrugs need to satisfy a number of criteria. They must be efficient and selective substrates for the activating enzyme, and be metabolized to potent cytotoxins preferably able to kill cells at all stages of the cell cycle. Both prodrugs and their activated species should have good distributive properties, so that the resulting bystander effects can maximize the effectiveness of the therapy, since gene transduction efficiencies are generally low. A total of 42 prodrugs explored for use in suicide gene therapy with 12 different enzymes are discussed, particularly in terms of their physiocochemical properties. An important parameter in determining bystander effects generated by passive diffusion is the lipophilicity of the activated form, a property conveniently compared by diffusion coefficients (log P for nonionizable compounds and log D7 for compounds containing an ionizable centre). Many of the early antimetabolite-based prodrugs provide very polar activated forms that have limited abilities to diffuse across cell membranes, and rely on gap junctions between cells for their bystander effects. Several later studies have shown that more lipophilic, neutral compounds have superior diffusion-based bystander effects. Prodrugs of DNA alkylating agents, that are less cell cycle-specific than antimetabolites and more effective against noncycling tumor cells, appear in general to be more active prodrugs, requiring less prolonged dosing schedules to be effective. It is expected that continued studies to optimize the bystander effects and other properties of prodrugs and the activated species they generate will contribute to improvements in the effectiveness of suicide gene therapy. PMID:12686722

Inhibition of Aurora-A kinase induces cell cycle arrest in epithelial ovarian cancer stem cells by affecting NFκB pathway

PubMed Central

Alvero, Ayesha B; Visintin, Irene

2011-01-01

Recurrent ovarian cancer is resistant to conventional chemotherapy. A sub-population of ovarian cancer cells, the epithelial ovarian cancer stem cells (EOC stem cells) have stemness properties, constitutive NFκB activity, and represent the chemoresistant population. Currently, there is no effective treatment that targets these cells. Aurora-A kinase (Aurora-A) is associated with tumor initiation and progression and is overexpressed in numerous malignancies. The aim of this study is to determine the effect of Aurora-A inhibition in EOC stem cells. EOC stem cells were treated with the Aurora-A inhibitor, MK-5108. Cell growth was monitored by Incucyte real-time imaging system, cell viability was measured using the Celltiter 96 assay and cytokine levels were quantified using xMAP technology. The intracellular changes associated with MK-5108 treatment are: (1) polyploidy and cell cycle arrest; (2) inhibition of NFκB activity; (3) decreased cytokine production; and (4) nuclear accumulation of IκBα. Thus, inhibition of Aurora-A decreases cell proliferation in the EOC stem cells by inducing cell cycle arrest and affecting the NFκB pathway. As EOC stem cells represent a source of recurrence and chemoresistance, these results suggest that Aurora-A inhibition may effectively target the cancer stem cell population in ovarian cancer. PMID:21623171

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

PubMed

Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako

2014-02-28

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.

A mathematical model for predicting the life of polymer electrolyte fuel cell membranes subjected to hydration cycling

NASA Astrophysics Data System (ADS)

Burlatsky, S. F.; Gummalla, M.; O'Neill, J.; Atrazhev, V. V.; Varyukhin, A. N.; Dmitriev, D. V.; Erikhman, N. S.

2012-10-01

Under typical Polymer Electrolyte Membrane Fuel Cell (PEMFC) fuel cell operating conditions, part of the membrane electrode assembly is subjected to humidity cycling due to variation of inlet gas RH and/or flow rate. Cyclic membrane hydration/dehydration would cause cyclic swelling/shrinking of the unconstrained membrane. In a constrained membrane, it causes cyclic stress resulting in mechanical failure in the area adjacent to the gas inlet. A mathematical modeling framework for prediction of the lifetime of a PEMFC membrane subjected to hydration cycling is developed in this paper. The model predicts membrane lifetime as a function of RH cycling amplitude and membrane mechanical properties. The modeling framework consists of three model components: a fuel cell RH distribution model, a hydration/dehydration induced stress model that predicts stress distribution in the membrane, and a damage accrual model that predicts membrane lifetime. Short descriptions of the model components along with overall framework are presented in the paper. The model was used for lifetime prediction of a GORE-SELECT membrane.

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)

PubMed Central

Alfieri, Claudio; Zhang, Suyang

2017-01-01

The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint. The past few years have witnessed significant progress in understanding the quantitative mechanisms underlying these varied APC/C functions. This review integrates the overall functions and properties of the APC/C with mechanistic insights gained from recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C complexes. PMID:29167309

Funneled potential and flux landscapes dictate the stabilities of both the states and the flow: Fission yeast cell cycle.

PubMed

Luo, Xiaosheng; Xu, Liufang; Han, Bo; Wang, Jin

2017-09-01

Using fission yeast cell cycle as an example, we uncovered that the non-equilibrium network dynamics and global properties are determined by two essential features: the potential landscape and the flux landscape. These two landscapes can be quantified through the decomposition of the dynamics into the detailed balance preserving part and detailed balance breaking non-equilibrium part. While the funneled potential landscape is often crucial for the stability of the single attractor networks, we have uncovered that the funneled flux landscape is crucial for the emergence and maintenance of the stable limit cycle oscillation flow. This provides a new interpretation of the origin for the limit cycle oscillations: There are many cycles and loops existed flowing through the state space and forming the flux landscapes, each cycle with a probability flux going through the loop. The limit cycle emerges when a loop stands out and carries significantly more probability flux than other loops. We explore how robustness ratio (RR) as the gap or steepness versus averaged variations or roughness of the landscape, quantifying the degrees of the funneling of the underlying potential and flux landscapes. We state that these two landscapes complement each other with one crucial for stabilities of states on the cycle and the other crucial for the stability of the flow along the cycle. The flux is directly related to the speed of the cell cycle. This allows us to identify the key factors and structure elements of the networks in determining the stability, speed and robustness of the fission yeast cell cycle oscillations. We see that the non-equilibriumness characterized by the degree of detailed balance breaking from the energy pump quantified by the flux is the cause of the energy dissipation for initiating and sustaining the replications essential for the origin and evolution of life. Regulating the cell cycle speed is crucial for designing the prevention and curing strategy of cancer.

Funneled potential and flux landscapes dictate the stabilities of both the states and the flow: Fission yeast cell cycle

PubMed Central

2017-01-01

Using fission yeast cell cycle as an example, we uncovered that the non-equilibrium network dynamics and global properties are determined by two essential features: the potential landscape and the flux landscape. These two landscapes can be quantified through the decomposition of the dynamics into the detailed balance preserving part and detailed balance breaking non-equilibrium part. While the funneled potential landscape is often crucial for the stability of the single attractor networks, we have uncovered that the funneled flux landscape is crucial for the emergence and maintenance of the stable limit cycle oscillation flow. This provides a new interpretation of the origin for the limit cycle oscillations: There are many cycles and loops existed flowing through the state space and forming the flux landscapes, each cycle with a probability flux going through the loop. The limit cycle emerges when a loop stands out and carries significantly more probability flux than other loops. We explore how robustness ratio (RR) as the gap or steepness versus averaged variations or roughness of the landscape, quantifying the degrees of the funneling of the underlying potential and flux landscapes. We state that these two landscapes complement each other with one crucial for stabilities of states on the cycle and the other crucial for the stability of the flow along the cycle. The flux is directly related to the speed of the cell cycle. This allows us to identify the key factors and structure elements of the networks in determining the stability, speed and robustness of the fission yeast cell cycle oscillations. We see that the non-equilibriumness characterized by the degree of detailed balance breaking from the energy pump quantified by the flux is the cause of the energy dissipation for initiating and sustaining the replications essential for the origin and evolution of life. Regulating the cell cycle speed is crucial for designing the prevention and curing strategy of cancer. PMID:28892489

Physangulidine A, a withanolide from Physalis angulata, perturbs the cell cycle and induces cell death by apoptosis in prostate cancer cells.

PubMed

Reyes-Reyes, E Merit; Jin, Zhuang; Vaisberg, Abraham J; Hammond, Gerald B; Bates, Paula J

2013-01-25

Recently, our group reported the discovery of three new withanolides, physangulidines A-C, from Physalis angulata. In this study, the biological effects of physangulidine A (1), which was the most active and abundant of the three new constituents, are described. It was found that 1 significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines. Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that 1 induces cell cycle arrest in the G(2)/M phase and causes defective mitosis. It was determined also that 1 produces programed cell death by apoptosis, as evidenced by biochemical markers and distinct changes in cell morphology. These results imply that the antimitotic and proapoptotic effects of 1 may contribute significantly to the biological activities and potential medicinal properties of its plant of origin.

Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression

PubMed Central

Kim, Jung Ha; Park, Jong-Jae; Lee, Beom Jae; Joo, Moon Kyung; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

2016-01-01

Background/Aims Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines. Methods The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed. Results The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27kip-1 increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner. Conclusions Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27kip-1. PMID:26470770

[Atomic force microscopy: a tool to analyze the viral cycle].

PubMed

Bernaud, Julien; Castelnovo, Martin; Muriaux, Delphine; Faivre-Moskalenko, Cendrine

2015-05-01

Each step of the HIV-1 life cycle frequently involves a change in the morphology and/or mechanical properties of the viral particle or core. The atomic force microscope (AFM) constitutes a powerful tool for characterizing these physical changes at the scale of a single virus. Indeed, AFM enables the visualization of viral capsids in a controlled physiological environment and to probe their mechanical properties by nano-indentation. Finally, AFM force spectroscopy allows to characterize the affinities between viral envelope proteins and cell receptors at the single molecule level. © 2015 médecine/sciences – Inserm.

Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: possible mechanism of anticancer activity.

PubMed

Rehman, Sayeed Ur; Zubair, Haseeb; Sarwar, Tarique; Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Nehar, Shamshun; Tabish, Mohammad

2015-02-01

6-Mercaptopurine (6MP) is a well-known purine antimetabolite used to treat childhood acute lymphoblastic leukemia and other diseases. Cancer cells as compared to normal cells are under increased oxidative stress and show high copper level. These differences between cancer cells and normal cells can be targeted to develop effective cancer therapy. Pro-oxidant property of 6MP in the presence of metal ions is not well documented. Redox cycling of Cu(II) to Cu(I) was found to be efficiently mediated by 6MP. We have performed a series of in vitro experiments to demonstrate the pro-oxidant property of 6MP in the presence of Cu(II). Studies on human lymphocytes confirmed the DNA damaging ability of 6MP in the presence of Cu(II). Since 6MP possesses DNA damaging ability by producing reactive oxygen species (ROS) in the presence of Cu(II), it may also possess apoptosis-inducing activity by involving endogenous copper ions. Essentially, this would be an alternative and copper-dependent pathway for anticancer activity of 6MP.

Tea polyphenols induce S phase arrest and apoptosis in gallbladder cancer cells

PubMed Central

Wang, Jiaqi; Pan, Yixuan; Hu, Jiacheng; Ma, Qiang; Xu, Yi; Zhang, Yijian; Zhang, Fei; Liu, Yingbin

2018-01-01

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer. PMID:29513793

A study of degradation of plates for nickel-cadmium spacecraft cells

NASA Technical Reports Server (NTRS)

Scott, W. R.

1974-01-01

The relative merits of coining and not coining of sintered nickel oxide and cadmium plates was investigated. Sample plate materials from most commercial cell suppliers were obtained and characterized for properties that may correlate with the tendency toward physical disintegration during handling and over long periods of time in the cell. Special test methods were developed to obtain comparative data in a short time. A wide range of physical properties and coining thickness was observed, resulting in a range of responses. The stronger materials resisted loss of sinter better than weaker materials whether or not coined. Coining improved handling and resistance to electrochemical cycling of weaker materials. The mechanism of break-down of positive plate edges under cycling appears to be the same as that of thickening and blistering. Brittle, nonadherent sinter, resulting from certain impregnation processes, is the most vulnerable to degradation. It is concluded that the latter type of materials should be coined, but coining of strong materials is optional.

Signal relay during the life cycle of Dictyostelium.

PubMed

Mahadeo, Dana C; Parent, Carole A

2006-01-01

A fundamental property of multicellular organisms is signal relay, the process by which information is transmitted from one cell to another. The integration of external information, such as nutritional status or developmental cues, is critical to the function of organisms. In addition, the spatial organizations of multicellular organisms require intricate signal relay mechanisms. Signal relay is remarkably exhibited during the life cycle of the social amoebae Dictyostelium discoideum, a eukaryote that retains a simple way of life, yet it has greatly contributed to our knowledge of the mechanisms cells use to communicate and integrate information. This chapter focuses on the molecules and mechanisms that Dictyostelium employs during its life cycle to relay temporal and spatial cues that are required for survival.

Biological evaluation of omega-(dialkylamino)alkyl derivatives of 6H-indolo[2,3-b]quinoline--novel cytotoxic DNA topoisomerase II inhibitors.

PubMed

Godlewska, Joanna; Luniewski, Wojciech; Zagrodzki, Bogdan; Kaczmarek, Lukasz; Bielawska-Pohl, Aleksandra; Dus, Danuta; Wietrzyk, Joanna; Opolski, Adam; Siwko, Magdalena; Jaromin, Anna; Jakubiak, Anna; Kozubek, Arkadiusz; Peczyñska-Czoch, Wanda

2005-01-01

A series of novel 6H-indolo[2,3-b]quinoline derivatives, substituted at C-2, C-9 or N-6 position with dialkyl(alkylamino)alkyl chains differing in the number of methylene groups, was prepared. These compounds were evaluated in vitro for their antimicrobial and cytotoxic activity against several cell lines of different origin and tested for their ability to influence the cell cycle and inhibit topoisomerase II activity. Liphophilic and calf thymus DNA-binding properties of these compounds were also investigated. All the compounds tested inhibited the growth of Gram-positive bacteria and fungi at MIC values ranging between 0.25 and 1 mM. They also showed cytotoxic activity against KB (human cervix carcinoma) cells (ID50 varied from 2.1 to 9.0 microM) and were able to overcome multidrug resistance in colorectal adenocarcinoma LoVo/DX, uterine sarcoma MES-SA/DX5 and promyelocytic leukemia HL-60/MX2 cells (the values of the resistance index RI fell between 0.54 and 2.4). The compounds induced G2M-phase cell cycle arrest in Jurkat T-cell leukemia cells, revealed DNA-binding properties and inhibited topoisomerase II activity.

Synchronized mammalian cell culture: part I--a physical strategy for synchronized cultivation under physiological conditions.

PubMed

Barradas, Oscar Platas; Jandt, Uwe; Becker, Max; Bahnemann, Janina; Pörtner, Ralf; Zeng, An-Ping

2015-01-01

Conventional analysis and optimization procedures of mammalian cell culture processes mostly treat the culture as a homogeneous population. Hence, the focus is on cell physiology and metabolism, cell line development, and process control strategy. Impact on cultivations caused by potential variations in cellular properties between different subpopulations, however, has not yet been evaluated systematically. One main cause for the formation of such subpopulations is the progress of all cells through the cell cycle. The interaction of potential cell cycle specific variations in the cell behavior with large-scale process conditions can be optimally determined by means of (partially) synchronized cultivations, with subsequent population resolved model analysis. Therefore, it is desirable to synchronize a culture with minimal perturbation, which is possible with different yield and quality using physical selection methods, but not with frequently used chemical or whole-culture methods. Conventional nonsynchronizing methods with subsequent cell-specific, for example, flow cytometric analysis, can only resolve cell-limited effects of the cell cycle. In this work, we demonstrate countercurrent-flow centrifugal elutriation as a useful physical method to enrich mammalian cell populations within different phases of a cell cycle, which can be further cultivated for synchronized growth in bioreactors under physiological conditions. The presented combined approach contrasts with other physical selection methods especially with respect to the achievable yield, which makes it suitable for bioreactor scale cultivations. As shown with two industrial cell lines (CHO-K1 and human AGE1.HN), synchronous inocula can be obtained with overall synchrony degrees of up to 82% in the G1 phase, 53% in the S phase and 60% in the G2/M phase, with enrichment factors (Ysync) of 1.71, 1.79, and 4.24 respectively. Cells are able to grow with synchrony in bioreactors over several cell cycles. This strategy, combined with population-resolved model analysis and parameter extraction as described in the accompanying paper, offers new possibilities for studies of cell lines and processes at levels of cell cycle and population under physiological conditions. © 2014 American Institute of Chemical Engineers.

Monitoring the elasticity changes of HeLa cells during mitosis by atomic force microscopy

NASA Astrophysics Data System (ADS)

Jiang, Ningcheng; Wang, Yuhua; Zeng, Jinshu; Ding, Xuemei; Xie, Shusen; Yang, Hongqin

2016-10-01

Cell mitosis plays a crucial role in cell life activity, which is one of the important phases in cell division cycle. During the mitosis, the cytoskeleton micro-structure of the cell changed and the biomechanical properties of the cell may vary depending upon different mitosis stages. In this study, the elasticity property of HeLa cells during mitosis was monitored by atomic force microscopy. Also, the actin filaments in different mitosis stages of the cells were observed by confocal imaging. Our results show that the cell in anaphase is stiffer than that in metaphase and telophase. Furthermore, lots of actin filaments gathered in cells' center area in anaphase, which contributes to the rigidity of the cell in this phase. Our findings demonstrate that the nano-biomechanics of living cells could provide a new index for characterizing cell physiological states.

Effects of silibinin on growth and invasive properties of human ovarian carcinoma cells through suppression of heregulin/HER3 pathway.

PubMed

Momeny, Majid; Ghasemi, Reza; Valenti, Giovanni; Miranda, Mariska; Zekri, Ali; Zarrinrad, Ghazaleh; Javadikooshesh, Sepehr; Yaghmaie, Marjan; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

2016-03-01

Epithelial ovarian cancer (EOC) is the most fatal gynecological malignancy due to its high proliferative and invasive capacities. A heregulin (HRG)/HER3 autocrine loop increases proliferative and metastatic properties of EOC cells, suggesting that modulators of this signaling pathway may prove effective to trammel growth and motility of these cells. This study aimed to evaluate the effects of multi-tyrosine kinase inhibitor silibinin on proliferative and invasive characteristics of EOC cell lines OVCAR8 and SKOV3 through suppression of the HRG/HER3 pathway. To achieve this, the effects of silibinin on proliferation, DNA synthesis, clonogenicity, cell cycle progression, cathepsin B enzymatic activity, and migration and invasion were explored in vitro. Silibinin suppressed proliferation, DNA synthesis, and clonogenic abilities of OVCAR8 and SKOV3 cells through inhibition of the autocrine HRG/HER3 circuit. Silibinin-mediated attenuation of the HER3 signaling disabled the HER3/AKT/survivin axis and thereby, induced G1/S cell cycle arrest. Furthermore, silibinin reduced invasive potentials of the EOC cells through quelling the HRG/HER3 pathway and suppression of cathepsin B activity. Altogether, these results suggest that silibinin is a potential anti-cancer drug to inhibit proliferative and invasive characteristics of the EOC cells that exhibit an autocrine HRG/HER3 pathway.

Regulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with ciclosporin on the homeostasis of human lymphocytes.

PubMed

Lee, Cheuk-Lun; Jiang, Pingping; Sit, Wai-Hung; Yang, Xiatong; Wan, Jennifer Man-Fan

2010-08-01

Lymphocyte homoeostasis is essential in inflammatory and autoimmune diseases. In search of natural fungal metabolites with effects on lymphocyte homoeostasis, we recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activity in controlling aberrant lymphocyte activation. This object of this study was to investigate its effect on lymphocyte homoeostasis. This was done by investigating the mechanistic actions of PSP in relation to ciclosporin by performing cell cycle and cell death analysis of human lymphocytes in vitro. We investigated the effect of PSP in the presence and absence of ciclosporin on cell proliferation, cell cycle, cell death, immunophenotype and cell cycle regulatory proteins in human lymphocytes. The data showed that PSP exhibited homoeostatic activity by promoting and inhibiting the proliferation of resting and phytohaemagglutinin (PHA)-stimulated lymphocytes, respectively. PHA-stimulated lymphocytes exhibited G0/G1 cell cycle arrest that was accompanied by a reduction of cyclin E expression with PSP treatment. Both PSP and ciclosporin blocked the reduction of the CD4/CD8 ratio in stimulated lymphocytes. PSP did not induce cell death in human lymphocytes, but the suppression of the Fasreceptor suggested a protective role of PSP against extrinsic cell death signals. These homoeostatic effects were more potent with combined PSP and ciclosporin treatment than with either fungal metabolite alone. Collectively, the results reveal certain novel effects of PSP in lymphocyte homoeostasis and suggest potential as a specific immunomodulatory adjuvant for clinical applications in the treatment of autoimmune diseases.

Effects of 12-crown-4 ether on the electrochemical performance of CoO2 and TiS2 cathodes in Li polymer electrolyte cells

NASA Technical Reports Server (NTRS)

Nagasubramanian, G.; Attia, Alan I.; Halpert, G.

1992-01-01

The effect of adding 12-crown-4 ether (12Cr4) to the polyethylene oxide (PEO) electrolyte on the electrochemical properties of cells with Li(x)CoO2 or TiS2 as the cathode was investigated. The polymer electrolyte films were: (1) PEO, LiBF4; (2) PEO, LiBF4 with 12Cr4; (3) Li(x)CoO2, PEO, and LiBF4; and (4) Li(x)CoO2, PEO, LiBF4, and 12Cr4. It was found that, although 12Cr4 improved the cell performance over cells without 12Cr4 in the shallow c/d cycles (cyclic voltammetric behavior), it did not seem to prolong the active life of the cell. The cells with CoO2 as the cathode failed after a few c/d cycles, while similar cells with TiS2 did not fail even after 12 c/d cycles. The probable cause of failure in the case of CoO2 is ascribed to the instability of the CoO2 cathode.

Critical Role of AMPK/FoxO3A Axis in Globular Adiponectin-Induced Cell Cycle Arrest and Apoptosis in Cancer Cells.

PubMed

Shrestha, Anup; Nepal, Saroj; Kim, Mi Jin; Chang, Jae Hoon; Kim, Sang-Hyun; Jeong, Gil-Saeng; Jeong, Chul-Ho; Park, Gyu Hwan; Jung, Sunghee; Lim, Jaecheong; Cho, Eunha; Lee, Soyoung; Park, Pil-Hoon

2016-02-01

Adiponectin predominantly secreted from adipose tissue has exhibited potent anti-proliferative properties in cancer cells via modulating cell cycle and apoptosis. FoxO3A, a Forkhead box O member of the transcription factor, plays a critical role in modulating expression of genes involved in cell death and/or survival. In this study, we investigated the role of FoxO3A signaling in anti-cancer activities of adiponectin. Herein, we have shown that treatment with globular adiponectin (gAcrp) increases p27 but decreases cyclinD1 expression in human hepatoma (HepG2) and breast (MCF-7) cancer cells. Gene ablation of FoxO3A prevented gAcrp-induced increase in p27 and decreased in cyclin D1 expression, and further ameliorated cell cycle arrest by gAcrp, indicating a critical role of FoxO3A in gAcrp-induced cell cycle arrest of cancer cells. Moreover, treatment with gAcrp also induced caspase-3/7 activation and increased Fas ligand (FasL) expression in both HepG2 and MCF-7 cells. Transfection with FoxO3A siRNA inhibited gAcrp-induced caspase-3/7 activation and FasL expression, suggesting that FoxO3A signaling also plays an important role in gAcrp-induced apoptosis of cancer cells. We also found that gene silencing of AMPK prevented gAcrp-induced nuclear translocation of FoxO3A in HepG2 and MCF-7 cells. In addition, suppression of AMPK also blocked gAcrp-induced cell cycle arrest and further attenuated gAcrp-induced caspase-3/7 activation, indicating that AMPK signaling plays a pivotal role in both gAcrp-induced cell cycle arrest and apoptosis via acting as an upstream signaling of FoxO3A. Taken together, our findings demonstrated that AMPK/FoxO3A axis plays a cardinal role in anti-proliferative effect of adiponectin in cancer cells. © 2015 Wiley Periodicals, Inc.

Antitumor Activity of Ethanolic Extract of Dendrobium formosum in T-Cell Lymphoma: An In Vitro and In Vivo Study

PubMed Central

Prasad, Ritika; Koch, Biplob

2014-01-01

Dendrobium, a genus of orchid, was found to possess useful therapeutic activities like anticancer, hypoglycaemic, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and neuroprotective activities. The study was aimed to evaluate the anticancer property of the ethanolic extract of Dendrobium formosum on Dalton's lymphoma. In vitro cytotoxicity was determined by MTT assay, apoptosis was determined by fluorescence microscopy, and cell cycle progression was analysed using flow cytometry; in vivo antitumor activity was performed in Dalton's lymphoma bearing mice. The IC50 value of ethanolic extract was obtained at 350 μg/mL in Dalton's lymphoma cells. Fluorescence microscopy analysis showed significant increase in apoptotic cell death in dose- and time-dependent manner which was further confirmed through the resulting DNA fragmentation. Further, flow cytometry analysis showed that the ethanolic extract arrests the cells in G2/M phase of the cell cycle. The in vivo anticancer activity study illustrates significant increase in the survival time of Dalton's lymphoma bearing mice on treatment with ethanolic extract when compared to control. These results substantiate the antitumor properties of ethanolic extract of Dendrobium formosum and suggest an alternative in treatment of cancer. Further studies are required regarding the isolation and characterization of bioactive components along with the analysis of molecular mechanism involved. PMID:24959588

Oximidine III, a new antitumor antibiotic against transformed cells from Pseudomonas sp. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity.

PubMed

Hayakawa, Yoichi; Tomikawa, Taijiro; Shin-ya, Kazuo; Arao, Nakako; Nagai, Koji; Suzuki, Ken-ichi

2003-11-01

Our screening for antitumor antibiotics against transformed cells resulted in the isolation of a new active metabolite, oximidine III, from Pseudomonas sp. QN05727. This substance selectively inhibited the growth of rat 3Y1 fibroblasts transformed with various oncogenes. In ras- or src-transformed cells, oximidine III arrested the cell cycle at G1 phase and increased the expression of p21WAF1.

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate.

PubMed

Baptista, Sofia; Lasgi, Charlène; Benstaali, Caroline; Milhazes, Nuno; Borges, Fernanda; Fontes-Ribeiro, Carlos; Agasse, Fabienne; Silva, Ana Paula

2014-09-01

Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10nM) decreased DG stem cell self-renewal, while 1nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase), which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10nM) did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10nM) decreased Sox2(+)/Sox2(+) while increased Sox2(-)/Sox2(-) pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA) signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10μM). Moreover, METH (10nM) increased doublecortin (DCX) protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers. Copyright © 2014. Published by Elsevier B.V.

FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

PubMed Central

Pietilä, Mika; Vijay, Geraldine V.; Soundararajan, Rama; Yu, Xian; Symmans, William F.; Sphyris, Nathalie; Mani, Sendurai A.

2016-01-01

Cancer cells with stem cell properties (CSCs) underpin the chemotherapy resistance and high therapeutic failure of triple-negative breast cancers (TNBCs). Even though CSCs are known to proliferate more slowly, they are sensitive to inhibitors of G2/M kinases such as polo-like kinase 1 (PLK1). Understanding the cell cycle regulatory mechanisms of CSCs will help target these cells more efficiently. Herein, we identify a novel role for the transcription factor FOXC2, which is mostly expressed in CSCs, in the regulation of cell cycle of CSC-enriched breast cancer cells. We demonstrate that FOXC2 expression is regulated in a cell cycle-dependent manner, with FOXC2 protein levels accumulating in G2, and rapidly decreasing during mitosis. Knockdown of FOXC2 in CSC-enriched TNBC cells delays mitotic entry without significantly affecting the overall proliferation rate of these cells. Moreover, PLK1 activity is important for FOXC2 protein stability, since PLK1 inhibition reduces FOXC2 protein levels. Indeed, FOXC2 expressing CSC-enriched TNBC cells are sensitive to PLK1 inhibition. Collectively, our findings demonstrate a novel role for FOXC2 as a regulator of the G2/M transition and elucidate the reason for the observed sensitivity of CSC-enriched breast cancer cells to PLK1 inhibitor. PMID:27064522

Stabilizing Motifs in Autonomous Boolean Networks and the Yeast Cell Cycle Oscillator

NASA Astrophysics Data System (ADS)

Sevim, Volkan; Gong, Xinwei; Socolar, Joshua

2009-03-01

Synchronously updated Boolean networks are widely used to model gene regulation. Some properties of these model networks are known to be artifacts of the clocking in the update scheme. Autonomous updating is a less artificial scheme that allows one to introduce small timing perturbations and study stability of the attractors. We argue that the stabilization of a limit cycle in an autonomous Boolean network requires a combination of motifs such as feed-forward loops and auto-repressive links that can correct small fluctuations in the timing of switching events. A recently published model of the transcriptional cell-cycle oscillator in yeast contains the motifs necessary for stability under autonomous updating [1]. [1] D. A. Orlando, et al. Nature (London), 4530 (7197):0 944--947, 2008.

Mesenchymal stem cells cancel azoxymethane-induced tumor initiation.

PubMed

Nasuno, Masanao; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hiroyuki; Onodera, Kei; Nakagaki, Suguru; Watanabe, Shuhei; Idogawa, Masashi; Yamashita, Kentaro; Naishiro, Yasuyoshi; Adachi, Yasushi; Suzuki, Hiromu; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

2014-04-01

The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our goal was to determine whether exogenous MSCs possess intrinsic antineoplastic or proneoplastic properties in azoxymethane (AOM)-induced carcinogenesis. Three in vivo models were studied: an AOM/dextran sulfate sodium colitis-associated carcinoma model, an aberrant crypt foci model, and a model to assess the acute apoptotic response of a genotoxic carcinogen (AARGC). We also performed in vitro coculture experiments. As a result, we found that MSCs partially canceled AOM-induced tumor initiation but not tumor promotion. Moreover, MSCs inhibited the AARGC in colonic epithelial cells because of the removal of O(6)-methylguanine (O(6) MeG) adducts through O(6) MeG-DNA methyltransferase activation. Furthermore, MSCs broadly affected the cell-cycle machinery, potentially leading to G1 arrest in vivo. Coculture of IEC-6 rat intestinal cells with MSCs not only arrested the cell cycle at the G1 phase, but also induced apoptosis. The anti-carcinogenetic properties of MSCs in vitro required transforming growth factor (TGF)-β signaling because such properties were completely abrogated by absorption of TGF-β under indirect coculture conditions. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and subsequently inducing G1 arrest in the initiated cells that escaped from the AARGC. Furthermore, tumor initiation perturbed by MSCs might potentially dysregulate WNT and TGF-β-Smad signaling pathways in subsequent tumorigenesis. Obtaining a better understanding of MSC functions in colon carcinogenesis is essential before commencing the broader clinical application of promising MSC-based therapies for cancer-prone patients with inflammatory bowel disease. © AlphaMed Press.

The steady-state level and stability of TLS polymerase eta are cell cycle dependent in the yeast S. cerevisiae.

PubMed

Plachta, Michal; Halas, Agnieszka; McIntyre, Justyna; Sledziewska-Gojska, Ewa

2015-05-01

Polymerase eta (Pol eta) is a ubiquitous translesion DNA polymerase that is capable of bypassing UV-induced pyrimidine dimers in an error-free manner. However, this specialized polymerase is error prone when synthesizing through an undamaged DNA template. In Saccharomyces cerevisiae, both depletion and overproduction of Pol eta result in mutator phenotypes. Therefore, regulation of the cellular abundance of this enzyme is of particular interest. However, based on the investigation of variously tagged forms of Pol eta, mutually contradictory conclusions have been reached regarding the stability of this polymerase in yeast. Here, we optimized a protocol for the detection of untagged yeast Pol eta and established that the half-life of the native enzyme is 80 ± 14 min in asynchronously growing cultures. Experiments with synchronized cells indicated that the cellular abundance of this translesion polymerase changes throughout the cell cycle. Accordingly, we show that the stability of Pol eta, but not its mRNA level, is cell cycle stage dependent. The half-life of the polymerase is more than fourfold shorter in G1-arrested cells than in those at G2/M. Our results, in concert with previous data for Rev1, indicate that cell cycle regulation is a general property of Y family TLS polymerases in S. cerevisiae. Copyright © 2015 Elsevier B.V. All rights reserved.

Cellular and functional characterization of buffalo (Bubalus bubalis) corpus luteum during the estrous cycle and pregnancy.

PubMed

Baithalu, Rubina Kumari; Singh, S K; Gupta, Chhavi; Raja, Anuj K; Saxena, Abhishake; Kumar, Yogendra; Singh, R; Agarwal, S K

2013-08-01

In the present paper, cellular composition of buffalo corpus luteum (CL) with its functional characterization based on 3β-HSD and progesterone secretory ability at different stages of estrous cycle and pregnancy was studied. Buffalo uteri along with ovaries bearing CL were collected from the local slaughter house. These were classified into different stages of estrous cycle (Stage I, II, III and IV) and pregnancy (Stage I, II and III) based on morphological appearance of CL, surface follicles on the ovary and crown rump length of conceptus. Luteal cell population, progesterone content and steroidogenic properties were studied by dispersion of luteal cells using collagenase type I enzyme, RIA and 3β-HSD activity, respectively. Large luteal cells (LLC) appeared as polyhedral or spherical in shape with a centrally placed large round nucleus and an abundance of cytoplasmic lipid droplets. However, small luteal cells (SLC) appeared to be spindle shaped with an eccentrically placed irregular nucleus and there was paucity of cytoplasmic lipid droplets. The size of SLC (range 12-23μm) and LLC (range 25-55μm) increased (P<0.01) with the advancement of stage of estrous cycle and pregnancy. The mean progesterone concentration per gram and per CL increased (P<0.01) from Stage I to III of estrous cycle with maximum concentration at Stage III of estrous cycle and pregnancy. The progesterone concentration decreased at Stage IV (day 17-20) of estrous cycle coinciding with CL regression. Total luteal cell number (LLC and SLC) also increased (P<0.01) from Stage I to III of estrous cycle and decreased (P<0.05), thereafter, at Stage IV indicating degeneration of luteal cells and regression of the CL. Total luteal cell population during pregnancy also increased (P<0.01) from Stage I to II and thereafter decreased (P>0.05) indicating cessation of mitosis. Increased (P<0.05) large luteal cell numbers from Stage I to III of estrous cycle and pregnancy coincided with the increased progesterone secretion and 3β-HSD activity of CL. Thus, proportionate increases of large compared with small luteal cells were primarily responsible for increased progesterone secretion during the advanced stages of the estrous cycle and pregnancy. Total luteal cells and progesterone content per CL during the mid-luteal stage in buffalo as observed in the present study seem to be less than with cattle suggesting inherent luteal deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

The effects of sulforaphane on canine osteosarcoma proliferation and invasion.

PubMed

Rizzo, V L; Levine, C B; Wakshlag, J J

2017-09-01

Recent evidence in in vitro and in vivo models suggests that sulforaphane (SFN), found in raw cruciferous vegetables, may have utility in chemoprevention, as an antineoplastic agent and as a free radical scavenger. The effects of SFN alone or with doxorubicin on cell viability were examined, as well as cell cycle kinetics, invasion capabilities and apoptosis in three canine osteosarcoma cell line (D17, OS 2.4 and HMPOS). Results showed that SFN could not induce cell death at potentially physiological concentrations (<50 μM), but significantly diminished cell invasion and downregulation of focal adhesion kinase (FAK) signaling. Modest cell cycle changes were observed in each cell line. When doxorubicin was used in conjunction with SFN, there was a protective effect to doxorubicin-induced cytotoxicity in D17 and OS 2.4 cells. Further studies examining SFN as a supplement are warranted, particularly in light of pro-proliferative and cytoprotective properties in canine osteosarcoma. © 2016 John Wiley & Sons Ltd.

The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in vitro and in vivo.

PubMed

Gao, Chang; Sun, Rui; Xie, Ya-Rong; Jiang, An-Li; Lin, Mei; Li, Min; Chen, Zheng-Wang; Zhang, Ping; Jin, Honglin; Feng, Jue-Ping

2017-05-01

Vglycin, a novel natural polypeptide isolated from pea seeds, possesses antidiabetic properties. Our previous studies have shown that Vglycin can induce the differentiation of human colon adenocarcinoma cells. We aimed to determine the anticancer activity of Vglycin against colon cancer cells and to elucidate related apoptosis-inducing mechanisms. Treatment with purified Vglycin significantly reduced growth, viability, and colony formation of CT-26, SW480, and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating the expression of proliferating cell nuclear antigen. Mouse xenograft studies showed a 38% inhibition of colon cancer growth in mice treated with Vglycin (20 mg/kg/day) at day 21. Furthermore, the potential mechanisms involved in Vglycin-induced cell apoptosis were examined using cell cycle studies, ultrastructural examination, as well as apoptosis-associated pathway analysis. The results showed that Vglycin significantly promoted apoptosis and G1/S phase cell cycle arrest. As revealed by Western blot, the expression of CDK2 and Cyclin D1 was down-regulated in all three Vglycin-treated colon cancer cells, indicating that the CDK2/Cyclin D1 cell cycle pathway involved in the initiation and progression of colon cancer. Moreover, the inhibition of Vglycin-induced cell proliferation in colon cancer cells was accompanied by alteration of the expression levels of the apoptosis-related proteins Bax, Bcl-2 and Mcl-1, and an increase of caspase-3 activity. Together, our results suggest that Vglycin may be another plant-derived peptide that suppresses colon cancer, supporting the continued investigation of Vglycin as therapeutic agent for colon cancer. Impact statement The antidiabetic properties and the capability of inducing differentiation of human colon adenocarcinoma cells of Vglycin have been reported in our previous studies. However, the anticancer potential of Vglycin on colon cancer cells and its possible related mechanisms were still unknown. In this study, we found that Vglycin could reduce growth, viability, and colony formation or colony size of CT-26, SW480, and NCL-H716 colon cancer cells. Moreover, Vglycin decreased tumor volume by 38% in xenograft mice transplanted with CT-26 cells. The mechanisms of these phenomena may be due to the down-regulated CDK2 and Cyclin D1, G1/S phase cell cycle arrest, and the dysregulated expression of Bax, Bcl-2, and Mcl-1. The findings highlight the anticancer potential of Vglycin against colon cancer cells, and suggest Vglycin may be another colon cancer potential suppressive component of plant-derived peptides.

Layered sulfur/PEDOT:PSS nano composite electrodes for lithium sulfur cell applications

NASA Astrophysics Data System (ADS)

Anilkumar, K. M.; Jinisha, B.; Manoj, M.; Pradeep, V. S.; Jayalekshmi, S.

2018-06-01

Lithium-Sulfur (Li-S) cells are emerging as the next generation energy storage devices owing to their impressive electrochemical properties with high theoretical specific capacity of 1675 mAh/g. Lack of electronic conductivity of sulfur, its volume expansion during high lithium intake and the shuttling effect due to the formation of soluble polysulfides are the main limitations, delaying the commercialization of this technology. To address these challenges, in the present work, the conducting polymer PEDOT:PSS is used as the covering matrix over the sulfur particles to improve their Li storage properties. The sulfur/PEDOT:PSS nanocomposite is synthesised using the hydrothermal process and its formation with the polymer coating over sulfur nanoparticles is established from the XRD, Raman spectroscopy, FE-SEM and TEM studies. The electrochemical studies show that the cells assembled using the sulfur/PEDOT:PSS nanocomposite as the cathode, with the components taken in the weight ratio of 9:1, offer a reversible capacity of 1191 mAh g-1 at 0.1C rate. These cells display stable electrochemical capacities over 200 cycles at gradually increasing current rates. The polymer layer facilitates electronic conduction and suppresses the polysulfide formation and the volume expansion of sulfur. A reversible capacity of 664 mAh g-1 is observed after 200 cycles at 1C rate with the capacity retention of 75 % of the initial stable capacity. The highlight of the present work is the possibility to achieve high discharge capacities at high C rates and the retention of a good percentage of the initial capacity over 200 cycles, for these Li-S cells.

MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jiangtao; Song, Kaifang; Feng, Xiaoshan, E-mail: xiaoshan.feng@aol.com

Purpose: In this study, we investigated whether microRNA-367 (miR-367) may serve as a circulating biomarker and tumor oncogene in esophageal squamous carcinoma (ESCC). Methods: Circulating serum miR-367 was compared by quantitative RT-PCR (qRT-PCR) between 35 ESCC patients and 35 normal control patients, as well paired ESCC tumor tissues and adjacent non-tumor esophageal epithelial tissues in 46 patients. The correlation between serum miR-367 and clinicopathological properties of ESCC patients was assessed. The overall survival (OS) was assessed by Kaplan–Meier method and compared by log-rank test between patients with high serum miR-367 and low serum miR-367. The possibility of miR-367 being independentmore » prognostic factor for ESCC was also assessed. Furthermore, lentivirus-mediated miR-367 downregulation was conducted in ESCC cell lines Kyse30 and TE-1 cells to assess the possible oncogenic effect of miR-367 on ESCC proliferation and cell cycle transition in vitro. Results: MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients, whereas downregulated in ESCC patients after the treatments of esophagectomy and chemotherapy. Serum miR-367 was found to be closely correlated with the clinicopathological properties of differentiation grades, clinical stage and tumor metastasis in ESCC patients. Serum miR-367 was also confirmed to be associated with OS, as well as serving independent prognostic factor in ESCC patients. Moreover, lentivirus-induced miR-367 downregulation inhibited cancer growth and cell cycle transition in Kyse30 and TE-1 cells. Conclusion: MiR-367 is a potential biomarker for ESCC and may act as an oncogene in regulating ESCC development. - Highlights: • MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients. • MiR-367 was downregulated in ESCC patients after esophagectomy or chemotherapy. • Serum miR-367 was correlated with the clinicopathological properties of ESCC patients. • Serum miR-367 was associated with OS in ESCC patients. • lentivirus-induced miR-367 downregulation inhibited ESCC growth and cell cycle transition.« less

Emergent multicellular life cycles in filamentous bacteria owing to density-dependent population dynamics.

PubMed

Rossetti, Valentina; Filippini, Manuela; Svercel, Miroslav; Barbour, A D; Bagheri, Homayoun C

2011-12-07

Filamentous bacteria are the oldest and simplest known multicellular life forms. By using computer simulations and experiments that address cell division in a filamentous context, we investigate some of the ecological factors that can lead to the emergence of a multicellular life cycle in filamentous life forms. The model predicts that if cell division and death rates are dependent on the density of cells in a population, a predictable cycle between short and long filament lengths is produced. During exponential growth, there will be a predominance of multicellular filaments, while at carrying capacity, the population converges to a predominance of short filaments and single cells. Model predictions are experimentally tested and confirmed in cultures of heterotrophic and phototrophic bacterial species. Furthermore, by developing a formulation of generation time in bacterial populations, it is shown that changes in generation time can alter length distributions. The theory predicts that given the same population growth curve and fitness, species with longer generation times have longer filaments during comparable population growth phases. Characterization of the environmental dependence of morphological properties such as length, and the number of cells per filament, helps in understanding the pre-existing conditions for the evolution of developmental cycles in simple multicellular organisms. Moreover, the theoretical prediction that strains with the same fitness can exhibit different lengths at comparable growth phases has important implications. It demonstrates that differences in fitness attributed to morphology are not the sole explanation for the evolution of life cycles dominated by multicellularity.

Cell Signalling Through Covalent Modification and Allostery

NASA Astrophysics Data System (ADS)

Johnson, Louise N.

Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases catalyze the transfer of the γ-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. This covalent modification allows activation or inhibition of enzyme activity, creates recognition sites for other proteins and promotes order/disorder or disorder/order transitions. These properties regulate ­signalling pathways and cellular processes that mediate metabolism, transcription, cell cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. In this lecture I shall review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase and the cell cycle cyclin dependent protein kinases as illustrations. Regulation of protein phosphorylation may be disrupted in the diseased state and protein kinases have become high profile targets for drug development. To date there are 11 compounds that have been approved for clinical use in the treatment of cancer.

The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells

PubMed Central

WANG, YIFEI; HAN, ALEX; CHEN, EVA; SINGH, RAKESH K.; CHICHESTER, CLINTON O.; MOORE, RICHARD G.; SINGH, AJAY P.; VORSA, NICHOLI

2015-01-01

Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phosphohistone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells. PMID:25776829

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle.

PubMed

Turkekul, Kader; Colpan, R Dilsu; Baykul, Talha; Ozdemir, Mehmet D; Erdogan, Suat

2018-03-01

Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated. Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting. Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c , p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue. Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed.

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle

PubMed Central

Turkekul, Kader; Colpan, R. Dilsu; Baykul, Talha; Ozdemir, Mehmet D.

2018-01-01

Background Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated. Methods Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting. Results Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c, p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue. Conclusions Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed. PMID:29629344

Effects of Plectin Depletion on Keratin Network Dynamics and Organization

PubMed Central

Moch, Marcin; Windoffer, Reinhard; Schwarz, Nicole; Pohl, Raphaela; Omenzetter, Andreas; Schnakenberg, Uwe; Herb, Fabian; Chaisaowong, Kraisorn; Merhof, Dorit; Ramms, Lena; Fabris, Gloria; Hoffmann, Bernd; Merkel, Rudolf; Leube, Rudolf E.

2016-01-01

The keratin intermediate filament cytoskeleton protects epithelial cells against various types of stress and is involved in fundamental cellular processes such as signaling, differentiation and organelle trafficking. These functions rely on the cell type-specific arrangement and plasticity of the keratin system. It has been suggested that these properties are regulated by a complex cycle of assembly and disassembly. The exact mechanisms responsible for the underlying molecular processes, however, have not been clarified. Accumulating evidence implicates the cytolinker plectin in various aspects of the keratin cycle, i.e., by acting as a stabilizing anchor at hemidesmosomal adhesion sites and the nucleus, by affecting keratin bundling and branching and by linkage of keratins to actin filament and microtubule dynamics. In the present study we tested these hypotheses. To this end, plectin was downregulated by shRNA in vulvar carcinoma-derived A431 cells. As expected, integrin β4- and BPAG-1-positive hemidesmosomal structures were strongly reduced and cytosolic actin stress fibers were increased. In addition, integrins α3 and β1 were reduced. The experiments furthermore showed that loss of plectin led to a reduction in keratin filament branch length but did not alter overall mechanical properties as assessed by indentation analyses using atomic force microscopy and by displacement analyses of cytoplasmic superparamagnetic beads using magnetic tweezers. An increase in keratin movement was observed in plectin-depleted cells as was the case in control cells lacking hemidesmosome-like structures. Yet, keratin turnover was not significantly affected. We conclude that plectin alone is not needed for keratin assembly and disassembly and that other mechanisms exist to guarantee proper keratin cycling under steady state conditions in cultured single cells. PMID:27007410

MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis

PubMed Central

Musa, Julian; Aynaud, Marie-Ming; Mirabeau, Olivier; Delattre, Olivier; Grünewald, Thomas GP

2017-01-01

Limitless cell proliferation, evasion from apoptosis, dedifferentiation, metastatic spread and therapy resistance: all these properties of a cancer cell contribute to its malignant phenotype and affect patient outcome. MYBL2 (alias B-Myb) is a transcription factor of the MYB transcription factor family and a physiological regulator of cell cycle progression, cell survival and cell differentiation. When deregulated in cancer cells, MYBL2 mediates the deregulation of these properties. In fact, MYBL2 is overexpressed and associated with poor patient outcome in numerous cancer entities. MYBL2 and players of its downstream transcriptional network can be used as prognostic and/or predictive biomarkers as well as potential therapeutic targets to offer less toxic and more specific anti-cancer therapies in future. In this review, we summarize current knowledge on the physiological roles of MYBL2 and highlight the impact of its deregulation on cancer initiation and progression. PMID:28640249

Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

PubMed Central

Wu, Yuanhao; He, Guanping; Zhang, Yu; Liu, Yang; Li, Mei; Wang, Xiaolan; Li, Nan; Li, Kang; Zheng, Guan; Zheng, Yufeng; Yin, Qingshui

2016-01-01

In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis. PMID:26907515

Effect of nanopatterning on mechanical properties of Lithium anode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, Colin; Lee, Yong Min; Cho, Kuk Young

One of the challenges in developing Lithium anodes for Lithium ion batteries (LIB) is controlling the formation of Li dendrites during cycling of the battery. Nanostructuring and nanopatterning of electrodes shows a promising way to suppress the growth of Li dendrites. However, in order to control this behavior, a fundamental understanding of the effect of nanopatterning on the electromechanical properties of Li metal is necessary. In this paper, we have investigated the mechanical and wear properties of Li metal using Atomic Force Microscopy (AFM) in an airtight cell. By using different load regimes, we determined the mechanical properties of Limore » metal. Here, we show that as a result of nanopatterning, Li metal surface underwent work hardening due to residual compressive stress. The presence of such stresses can help to improve cycle lifetime of LIBs with Li anodes and obtain very high energy densities.« less

Effect of nanopatterning on mechanical properties of Lithium anode

DOE PAGES

Campbell, Colin; Lee, Yong Min; Cho, Kuk Young; ...

2018-02-06

One of the challenges in developing Lithium anodes for Lithium ion batteries (LIB) is controlling the formation of Li dendrites during cycling of the battery. Nanostructuring and nanopatterning of electrodes shows a promising way to suppress the growth of Li dendrites. However, in order to control this behavior, a fundamental understanding of the effect of nanopatterning on the electromechanical properties of Li metal is necessary. In this paper, we have investigated the mechanical and wear properties of Li metal using Atomic Force Microscopy (AFM) in an airtight cell. By using different load regimes, we determined the mechanical properties of Limore » metal. Here, we show that as a result of nanopatterning, Li metal surface underwent work hardening due to residual compressive stress. The presence of such stresses can help to improve cycle lifetime of LIBs with Li anodes and obtain very high energy densities.« less

Mosaic-shaped cathode for highly durable solid oxide fuel cell under thermal stress

NASA Astrophysics Data System (ADS)

Joo, Jong Hoon; Jeong, Jaewon; Kim, Se Young; Yoo, Chung-Yul; Jung, Doh Won; Park, Hee Jung; Kwak, Chan; Yu, Ji Haeng

2014-02-01

In this study, we propose a novel "mosaic structure" for a SOFC (solid oxide fuel cell) cathode with high thermal expansion to improve the stability against thermal stress. Self-organizing mosaic-shaped cathode has been successfully achieved by controlling the amount of binder in the dip-coating solution. The anode-supported cell with mosaic-shaped cathode shows itself to be highly durable performance for rapid thermal cycles, however, the performance of the cell with a non-mosaic cathode exhibits severe deterioration originated from the delamination at the cathode/electrolyte interface after 7 thermal cycles. The thermal stability of an SOFC cathode can be evidently improved by controlling the surface morphology. In view of the importance of the thermal expansion properties of the cathode, the effects of cathode morphology on the thermal stress stability are discussed.

Identification of miR-133b and RB1CC1 as independent predictors for biochemical recurrence and potential therapeutic targets for prostate cancer.

PubMed

Li, Xia; Wan, Xuechao; Chen, Hongbing; Yang, Shu; Liu, Yiyang; Mo, Wenjuan; Meng, Delong; Du, Wenting; Huang, Yan; Wu, Hai; Wang, Jingqiang; Li, Tao; Li, Yao

2014-05-01

We aimed to investigate the contribution of microRNA-133b (miR-133b) in prostate cancer cell proliferation, cell cycle, and apoptosis. We also examined expression of miR-133b in prostate cancer tissues, and evaluated the prognostic significance of miR-133b, as well as its target gene RB1CC1 in patients with prostate cancer after radical prostatectomy. miR-133b mimics (miR-133bm) and anti-miR-133b were transfected into LNCaP and PC-3 cells. CCK-8 was used to look at cell proliferation, flow cytometric analysis was carried out to study cell cycle, and apoptosis was determined by caspase-3 activity. miR-133b expression was assessed by real-time reverse transcription PCR and in situ hybridization in prostatic cell lines and 178 prostate tissue samples, respectively. The protein level of RB1CC1 was examined by Western blot and immunohistochemistry in prostatic cell lines and prostate tissue samples, respectively. Overexpression of miR-133b in LNCaP cells boosted cell proliferation and cell-cycle progression, but inhibited apoptosis; in contrast, miR-133bm promoted cell apoptosis, but suppressed cell proliferation and cell-cycle progression in PC-3 cells. In LNCaP cells, silencing of RB1CC1, a target of miR-133b, inhibited cell apoptosis, and promoted cell-cycle progression. Moreover, miR-133b expression was significantly inversely correlated with RB1CC1 expression in prostate cancer tissues. Multivariate Cox analysis indicated that miR-133b and RB1CC1 might be two independent prognostic factors of biochemical recurrence. miR-133b might enhance tumor-promoting properties in less aggressive LNCaP cells, whereas this miR may act as a tumor suppressor in more aggressive PC-3 cells. miR-133b and RB1CC1 were independent prognostic indicators for prostate cancer. ©2014 AACR.

Architecture and material properties of diatom shells provide effective mechanical protection

NASA Astrophysics Data System (ADS)

Hamm, Christian E.; Merkel, Rudolf; Springer, Olaf; Jurkojc, Piotr; Maier, Christian; Prechtel, Kathrin; Smetacek, Victor

2003-02-01

Diatoms are the major contributors to phytoplankton blooms in lakes and in the sea and hence are central in aquatic ecosystems and the global carbon cycle. All free-living diatoms differ from other phytoplankton groups in having silicified cell walls in the form of two `shells' (the frustule) of manifold shape and intricate architecture whose function and role, if any, in contributing to the evolutionary success of diatoms is under debate. We explored the defence potential of the frustules as armour against predators by measuring their strength. Real and virtual loading tests (using calibrated glass microneedles and finite element analysis) were performed on centric and pennate diatom cells. Here we show that the frustules are remarkably strong by virtue of their architecture and the material properties of the diatom silica. We conclude that diatom frustules have evolved as mechanical protection for the cells because exceptional force is required to break them. The evolutionary arms race between diatoms and their specialized predators will have had considerable influence in structuring pelagic food webs and biogeochemical cycles.

New Ether-functionalized Morpholinium- and Piperidinium-based Ionic Liquids as Electrolyte Components in Lithium and Lithium-Ion Batteries.

PubMed

Navarra, Maria Assunta; Fujimura, Kanae; Sgambetterra, Mirko; Tsurumaki, Akiko; Panero, Stefania; Nakamura, Nobuhumi; Ohno, Hiroyuki; Scrosati, Bruno

2017-06-09

Here, two ionic liquids, N-ethoxyethyl-N-methylmorpholinium bis(trifluoromethanesulfonyl)imide (M 1,2O2 TFSI) and N-ethoxyethyl-N-methylpiperidinium bis(trifluoromethanesulfonyl)imide (P 1,2O2 TFSI) were synthesized and compared. Fundamental relevant properties, such as thermal and electrochemical stability, density, and ionic conductivity were analyzed to evaluate the effects caused by the presence of the ether bond in the side chain and/or in the organic cation ring. Upon lithium salt addition, two electrolytes suitable for lithium batteries applications were found. Higher conducting properties of the piperidinium-based electrolyte resulted in enhanced cycling performances when tested with LiFePO 4 (LFP) cathode in lithium cells. When mixing the P 1,2O2 TFSI/LiTFSI electrolyte with a tailored alkyl carbonate mixture, the cycling performance of both Li and Li-ion cells greatly improved, with prolonged cyclability delivering very stable capacity values, as high as the theoretical one in the case of Li/LFP cell configurations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Architecture and material properties of diatom shells provide effective mechanical protection.

PubMed

Hamm, Christian E; Merkel, Rudolf; Springer, Olaf; Jurkojc, Piotr; Maier, Christian; Prechtel, Kathrin; Smetacek, Victor

2003-02-20

Diatoms are the major contributors to phytoplankton blooms in lakes and in the sea and hence are central in aquatic ecosystems and the global carbon cycle. All free-living diatoms differ from other phytoplankton groups in having silicified cell walls in the form of two 'shells' (the frustule) of manifold shape and intricate architecture whose function and role, if any, in contributing to the evolutionary success of diatoms is under debate. We explored the defence potential of the frustules as armour against predators by measuring their strength. Real and virtual loading tests (using calibrated glass microneedles and finite element analysis) were performed on centric and pennate diatom cells. Here we show that the frustules are remarkably strong by virtue of their architecture and the material properties of the diatom silica. We conclude that diatom frustules have evolved as mechanical protection for the cells because exceptional force is required to break them. The evolutionary arms race between diatoms and their specialized predators will have had considerable influence in structuring pelagic food webs and biogeochemical cycles.

ANT2 expression under hypoxic conditions produces opposite cell-cycle behavior in 143B and HepG2 cancer cells.

PubMed

Chevrollier, Arnaud; Loiseau, Dominique; Gautier, Fabien; Malthièry, Yves; Stepien, Georges

2005-01-01

Under hypoxic conditions, mitochondrial ATP production ceases, leaving cells entirely dependent on their glycolytic metabolism. The cytoplasmic and intramitochondrial ATP/ADP ratios, partly controlled by the adenine nucleotide translocator (ANT), are drastically modified. In dividing and growing cells that have a predominantly glycolytic metabolism, the ANT isoform 2, which has kinetic properties allowing ATP import into mitochondria, is over-expressed in comparison to control cells. We studied the cellular metabolic and proliferative response to hypoxia in two transformed human cell lines with different metabolic backgrounds: HepG2 and 143B, and in their rho(o) derivatives, i.e., cells with no mitochondrial DNA. Transformed 143B and rho(o) cells continued their proliferation whereas HepG2 cells, with a more differentiated phenotype, arrested their cell-cycle at the G(1)/S checkpoint. Hypoxia induced an increase in glycolytic activity, correlated to an induction of VEGF and hexokinase II (HK II) expression. Thus, according to their tumorigenicity, transformed cells may adopt one of two distinct behaviors to support hypoxic stress, i.e., proliferation or quiescence. Our study links the constitutive glycolytic activity and ANT2 expression levels of transformed cells with the loss of cell-cycle control after oxygen deprivation. ATP import by ANT2 allows cells to maintain their mitochondrial integrity while acquiring insensitivity to any alterations in the proteins involved in oxidative phosphorylation. This loss of cell dependence on oxidative metabolism is an important factor in the development of tumors.

Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.

PubMed

Davidson, E J; Morris, L S; Scott, I S; Rushbrook, S M; Bird, K; Laskey, R A; Wilson, G E; Kitchener, H C; Coleman, N; Stern, P L

2003-01-27

Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.

Role of asymmetric meridional circulation in producing north-south asymmetry in a solar cycle dynamo model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belucz, Bernadett; Dikpati, Mausumi

2013-12-10

Solar cycles in the north and south hemispheres differ in cycle length, amplitude, profile, polar fields, and coronal structure. To show what role differences in meridional flow could play in producing these differences, we present the results of three sets of numerical simulations from a flux transport dynamo in which one property of meridional circulation has been changed in the south only. The changes are in amplitude and the presence of a second cell in latitude or in depth. An ascending phase speedup causes weakening of polar and toroidal fields; a speed decrease in a late descending phase does notmore » change amplitudes. A long-duration speed increase leads to lower toroidal field peaks but unchanged polar field peaks. A second high-latitude circulation cell in an ascending phase weakens the next polar and toroidal field peaks, and the ascending phase is lengthened. A second cell in a late descending phase speeds up the cycle. A long-duration second cell leads to a poleward branch of the butterfly diagram and weaker polar fields. A second cell in depth reverses the tilt of the butterfly wing, decreasing polar fields when added during an ascending phase and increasing them during a late descending phase. A long-duration presence of a second cell in radius evolves the butterfly diagram far away from the observed one, with different dynamo periods in low and high latitudes. Thus, a second cell in depth is unlikely to persist more than a few years if the solar dynamo is advection-dominated. Our results show the importance of time variation and north-south asymmetry in meridional circulation in producing differing cycles in the north and south.« less

Electrochemical behavior of Li/LiV3O8 secondary cells

NASA Astrophysics Data System (ADS)

Bak, Hyo Rim; Lee, Jae Ha; Kim, Bok Ki; Yoon, Woo Young

2013-03-01

Li/LiV3O8 secondary cells with Li-foil and Li-powder anodes were fabricated, and their electrical properties were compared. Using the powder anode, a cell with an initial discharge capacity of 260 mAh g-1 that could be operated for over 100 cycles was obtained. The porous Li-powder electrode was safely synthesized by pressing an emulsion droplet onto an SUS mesh. A threefold increase in the electrical conductivity of the LiV3O8 cathode was achieved by the addition of carbon using a vibration pot mill. Using the powder anode resulted in 80% capacity retention at the 100th cycle, while that using the foil electrode was 46%; the 1.0 Crate/ 0.1 C-rate capacity ratio also increased from 44% to 60%. A cell employing the LiV3O8-carbon composite cathode showed better electrical performance, a capacity retention of 90% after 50 cycles, and an increase in rate capacity ratio. The crystal structure and morphology of the LiV3O8-C composite were investigated by x-ray diffraction and scanning electron microscopy.

Effects of Bauhinia championii (Benth.) Benth. polysaccharides on the proliferation and cell cycle of chondrocytes.

PubMed

Cai, Liangliang; Ye, Hongzhi; Yu, Fangrong; Li, Huiting; Chen, Jiashou; Liu, Xianxiang

2013-05-01

It has been recently shown that polysaccharides isolated from plants exhibit a number of beneficial therapeutic properties. Bauhinia championii (Benth.) Benth. has been widely used for the clinical treatment of knee osteoarthritis (OA) in China. However, the underlying molecular mechanisms of knee OA treatment have yet to be elucidated. In the present study, we investigated the effects of Bauhinia championii (Benth.) Benth. polysaccharides (BCBPs) on the proliferation and cell cycle of chondrocytes on 4-week-old male Sprague Dawley rats. Immunohistochemical staining was used to identify chondrocytes and an MTT assay was used to evaluate cell viability. Flow cytometry was used for cell cycle analysis. The mRNA and protein expression levels of cyclin D1, CDK4 and CDK6 in chondrocytes were detected using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. The data demonstrate that BCBP treatment increased the viability of chondrocytes. In addition, BCBP treatment reduced the cell population in the G0/G1 phase, whereas the cell population was increased in the S phase. Furthermore, BCBP treatment enhanced the expression of cyclin D1, CDK4 and CDK6. These results indicate that BCBP treatment promotes cell proliferation by accelerating the G1/S transition.

Corrosion resistance, mechanical properties, corrosion fatigue strength and cytocompatibility of new Ti alloys without Al and V.

PubMed

Okazaki, Y; Rao, S; Ito, Y; Tateishi, T

1998-07-01

The effects of various metallic ions using various metallic powders on the relative growth ratio of fibroblasts L929 and osteoblasts MC3T3-E1 cells were carried out. Ti, Zr, Sn, Nb and Ta had evidently no effect on the relative growth ratios of cells. Otherwise, Al and V ions exhibit cytotoxicity from a concentration of > or = 0.2 ppm. This Al effect on cells tend to be stronger in medium containing small quantity of V ions (< or = 0.03 ppm). The new Ti-15%Zr-4%Nb-4%Ta-0.2%Pd alloy exhibited a higher corrosion resistance in physiological saline solution. The addition of 0.02%O and 0.05%N to Ti-Zr alloy improved the mechanical properties at room temperature and corrosion fatigue strength. The relative growth ratios for the new Ti alloy plate and the alloy block extraction were unity. Further, the relative growth ratios were almost unity for the new Ti alloy against apatite ceramic pins up to 10(5) wear cycles in Eagle's MEM solution. However, there was a sharp decrease for Ti-6%Al-4%V ELI alloy from 3 x 10(4) wear cycles as V ion was released during wear into the wear test solution since the pH of the Eagle's MEM increases with increasing wear cycles.

Ionic liquids and oligomer electrolytes based on the B(CN)4(-) anion; ion association, physical and electrochemical properties.

PubMed

Scheers, Johan; Pitawala, Jagath; Thebault, Frederic; Kim, Jae-Kwang; Ahn, Jou-Hyeon; Matic, Aleksandar; Johansson, Patrik; Jacobsson, Per

2011-09-07

The role of B(CN)(4)(-) (Bison) as a component of battery electrolytes is addressed by investigating the ionic conductivity and phase behaviour of ionic liquids (ILs), ion association mechanisms, and the electrochemical stability and cycling properties of LiBison based electrochemical cells. For C(4)mpyrBison and C(2)mimBison ILs, and mixtures thereof, high ionic conductivities (3.4 ≤σ(ion)≤ 18 mS cm(-1)) are measured, which together with the glass transition temperatures (-80 ≤T(g)≤-76 °C) are found to shift systematically for most compositions. Unfortunately, poor solubility of LiBison in these ILs hinders their use as solvents for lithium salts, although good NaBison solubility offers an alternative application in Na(+) conducting electrolytes. The poor IL solubility of LiBison is predicted to be a result of a preferred monodentate ion association, according to first principles modelling, supported by Raman spectroscopy. The solubility is much improved in strongly Li(+) coordinating oligomers, for example polyethylene glycol dimethyl ether (PEGDME), with the practical performance tested in electrochemical cells. The electrolyte is found to be stable in Li/LiFePO(4) coin cells up to 4 V vs. Li and shows promising cycling performance, with a capacity retention of 99% over 22 cycles. This journal is © the Owner Societies 2011

KPU-300, a Novel Benzophenone–Diketopiperazine–Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase

PubMed Central

Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko

2015-01-01

KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300. PMID:26716455

KPU-300, a Novel Benzophenone-Diketopiperazine-Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase.

PubMed

Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko

2015-01-01

KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300.

New evidence for antioxidant properties of vitamin C.

PubMed

Vojdani, A; Bazargan, M; Vojdani, E; Wright, J

2000-01-01

This study was designed to examine the effect of 500 to 5,000 mg of ascorbic acid on DNA adducts, natural killer (NK) cell activity, programmed cell death, and cell cycle analysis of human peripheral blood leukocytes. According to our hypothesis, if ascorbic acid is a pro-oxidant, doses between 500 and 5,000 mg should enhance DNA adduct formation, decrease immune function, change the cell cycle progression, and increase the rate of apoptosis. Twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. On days 0, 1, 7, 15, and 21, blood was drawn from them, and the leukocytes were separated and examined for intracellular levels of ascorbic acid, the level of 8-hydroxyguanosine, NK cell activity, cell cycle progression, and apoptosis. Depending on the subjects, between a 0% and a 40% increase in cellular absorption of ascorbic acid was observed when daily doses of 500 mg were used. At doses greater than 500 mg, this cellular absorption was not increased further, and all doses produced equivalent increases in ascorbic acid on days 1 to 15. This increase in cellular concentration of ascorbic acid resulted in no statistically meaningful changes in the level of 8-hydroxyguanosine, increased NK cytotoxic activity, a reduced percentage of cells undergoing apoptosis, and switched cell cycle phases from S and G2/M to G0/G1. After a period of 1 week, with no placebo or vitamin washout, ascorbic acid levels along with functional assays returned to the baseline and became equivalent to placebos. In comparison with baseline values, no change (not more than daily assays variation) was seen in ascorbate concentrations or other assays during oral placebo treatment. We concluded that ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle.

KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laurila, Eeva; Vuorinen, Elisa; Fimlab Laboratories, Biokatu 4, 33520 Tampere

2014-03-10

Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700Tmore » pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.« less

Genistein and daidzein act on a panel of genes implicated in cell cycle and angiogenesis by polymerase chain reaction arrays in human prostate cancer cell lines.

PubMed

Rabiau, Nadège; Kossaï, Myriam; Braud, Martin; Chalabi, Nasséra; Satih, Samir; Bignon, Yves-Jean; Bernard-Gallon, Dominique J

2010-04-01

The prostate cancer most frequently affects men. The ethnic origin and family antecedents of prostate cancer are established as risk factors. The genetic factors associated with environmental factors such as the nutrition also play a role in the development of the cancer. Epidemiological studies showed that the Asian populations exhibited an incidence of prostate cancer markedly subordinate by comparison with the Western populations. This would be explained partially by their important consumption of soy. Both main phytoestrogens of soy, the genistein and the daidzein, present anti-proliferative properties. For that purpose, we used different prostate cancer cell lines (LNCaP, DU 145, PC-3) and, by flow cytometry, we determined the concentration of phytoestrogens inducing a cell cycle arrest and the required time of incubation. Then, the effects of 40microM genistein or 110microM daidzein for 48h were determined and studied on the expression of genes involved in the human cell cycle and angiogenesis and conducted by SYBR green quantitative PCR. We demonstrated modulations of cyclin-dependent kinase-related pathway genes, DNA damage-signaling pathway and a down-regulation of EGF and IGF.

A Cajal body-independent pathway for telomerase trafficking in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomlinson, Rebecca L.; Li, Jian; Culp, Bradley R.

2010-10-15

The intranuclear trafficking of human telomerase involves a dynamic interplay between multiple nuclear sites, most notably Cajal bodies and telomeres. Cajal bodies are proposed to serve as sites of telomerase maturation, storage, and assembly, as well as to function in the cell cycle-regulated delivery of telomerase to telomeres in human cells. Here, we find that telomerase RNA does not localize to Cajal bodies in mouse cells, and instead resides in separate nuclear foci throughout much of the cell cycle. However, as in humans, mouse telomerase RNA (mTR) localizes to subsets of telomeres specifically during S phase. The localization of mTRmore » to telomeres in mouse cells does not require coilin-containing Cajal bodies, as mTR is found at telomeres at similar frequencies in cells from wild-type and coilin knockout mice. At the same time, we find that human TR localizes to Cajal bodies (as well as telomeres) in mouse cells, indicating that the distinct trafficking of mTR is attributable to an intrinsic property of the RNA (rather than a difference in the mouse cell environment such as the properties of mouse Cajal bodies). We also find that during S phase, mTR foci coalesce into short chains, with at least one of the conjoined mTR foci co-localizing with a telomere. These findings point to a novel, Cajal body-independent pathway for telomerase biogenesis and trafficking in mice.« less

Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway

PubMed Central

Drosten, Matthias; Sum, Eleanor Y. M.; Lechuga, Carmen G.; Simón-Carrasco, Lucía; Jacob, Harrys K. C.; García-Medina, Raquel; Huang, Sidong; Beijersbergen, Roderick L.; Bernards, Rene; Barbacid, Mariano

2014-01-01

The Ras family of small GTPases constitutes a central node in the transmission of mitogenic stimuli to the cell cycle machinery. The ultimate receptor of these mitogenic signals is the retinoblastoma (Rb) family of pocket proteins, whose inactivation is a required step to license cell proliferation. However, little is known regarding the molecular events that connect Ras signaling with the cell cycle. Here, we provide genetic evidence to illustrate that the p53/p21 Cdk-interacting protein 1 (Cip1)/Rb axis is an essential component of the Ras signaling pathway. Indeed, knockdown of p53, p21Cip1, or Rb restores proliferative properties in cells arrested by ablation of the three Ras loci, H-, N- and K-Ras. Ras signaling selectively inactivates p53-mediated induction of p21Cip1 expression by inhibiting acetylation of specific lysine residues in the p53 DNA binding domain. Proliferation of cells lacking both Ras proteins and p53 can be prevented by reexpression of the human p53 ortholog, provided that it retains an active DNA binding domain and an intact lysine residue at position 164. These results unveil a previously unidentified role for p53 in preventing cell proliferation under unfavorable mitogenic conditions. Moreover, we provide evidence that cells lacking Ras and p53 proteins owe their proliferative properties to the unexpected retroactivation of the Raf/Mek/Erk cascade by a Ras-independent mechanism. PMID:25288756

Yeast-assisted synthesis of polypyrrole: Quantification and influence on the mechanical properties of the cell wall.

PubMed

Andriukonis, Eivydas; Stirke, Arunas; Garbaras, Andrius; Mikoliunaite, Lina; Ramanaviciene, Almira; Remeikis, Vidmantas; Thornton, Barry; Ramanavicius, Arunas

2018-04-01

In this study, the metabolism of yeast cells (Saccharomyces cerevisiae) was utilized for the synthesis of the conducting polymer - polypyrrole (Ppy).Yeast cells were modified in situ by synthesized Ppy. The Ppy was formed in the cell wall by redox-cycling of [Fe(CN) 6 ] 3-/4- , performed by the yeast cells. Fluorescence microscopy, enzymatic digestions, atomic force microscopy and isotope ratio mass spectroscopy were applied to determine both the polymerization reaction itself and the polymer location in yeast cells. Ppy formation resulted in enhanced resistance to lytic enzymes, significant increase of elasticity and alteration of other mechanical cell wall properties evaluated by atomic force microscopy (AFM). The suggested method of polymer synthesis allows the introduction of polypyrrole structures within the cell wall, which is build up from polymers consisting of carbohydrates. This cell wall modification strategy could increase the usefulness of yeast as an alternative energy source in biofuel cells, and in cell based biosensors. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular mechanism of action of oxazolinoanthracyclines in cells derived from human solid tumors. Part 2.

PubMed

Denel-Bobrowska, Marta; Łukawska, Małgorzata; Bukowska, Barbara; Gajek, Arkadiusz; Oszczapowicz, Irena; Marczak, Agnieszka

2018-02-01

Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity. Experimental model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the concentration of 80nM. Intracellular accumulation, drug uptake, and proteasome 20S activity were evaluated by fluorimetric methods. The effects on the cell cycle and phosphatidylserine externalization were measured by flow cytometry. O-DOX was equivalent to DOX in terms of inducing G2/M arrest, but O-DAU was less potent in SKOV-3, HepG2, and A549 cells. O-DOX had the greatest effect on initiating apoptosis in all tested cells. Externalization of phosphatidylserine was significantly higher following O-DOX treatment compared with control cells and cells incubated with DOX. The intracellular accumulation and uptake of the derivatives were similar to those of the reference drugs. Tested compounds are able to activate proteasome 20S activity. Our results extended the understanding of the toxicity, mechanism of action, and biochemical properties of oxazoline derivatives of doxorubicin and daunorubicin, including their effects on cell cycle, apoptosis and DNA degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Anacardium occidentale leaf extract on human acute lymphoblastic leukaemia cell lines.

PubMed

Santos, Janaína M; Cury, Nathalia M; Yunes, José A; López, Jorge A; Hernández-Macedo, Maria L

2018-01-16

Anacardium occidentale leaves are used in folk medicine due its therapeutic properties attributed to phenolic compounds. Therefore, this study was undertaken on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE interfered in the cell cycle progression, inducing apoptosis by activation of casp3 at lower concentrations, thence, a promising candidate for the development of new cancer drugs.

From quiescence to proliferation: Cdk oscillations drive the mammalian cell cycle

PubMed Central

Gérard, Claude; Goldbeter, Albert

2012-01-01

We recently proposed a detailed model describing the dynamics of the network of cyclin-dependent kinases (Cdks) driving the mammalian cell cycle (Gérard and Goldbeter, 2009). The model contains four modules, each centered around one cyclin/Cdk complex. Cyclin D/Cdk4–6 and cyclin E/Cdk2 promote progression in G1 and elicit the G1/S transition, respectively; cyclin A/Cdk2 ensures progression in S and the transition S/G2, while the activity of cyclin B/Cdk1 brings about the G2/M transition. This model shows that in the presence of sufficient amounts of growth factor the Cdk network is capable of temporal self-organization in the form of sustained oscillations, which correspond to the ordered, sequential activation of the various cyclin/Cdk complexes that control the successive phases of the cell cycle. The results suggest that the switch from cellular quiescence to cell proliferation corresponds to the transition from a stable steady state to sustained oscillations in the Cdk network. The transition depends on a finely tuned balance between factors that promote or hinder progression in the cell cycle. We show that the transition from quiescence to proliferation can occur in multiple ways that alter this balance. By resorting to bifurcation diagrams, we analyze the mechanism of oscillations in the Cdk network. Finally, we show that the complexity of the detailed model can be greatly reduced, without losing its key dynamical properties, by considering a skeleton model for the Cdk network. Using such a skeleton model for the mammalian cell cycle we show that positive feedback (PF) loops enhance the amplitude and the robustness of Cdk oscillations with respect to molecular noise. We compare the relative merits of the detailed and skeleton versions of the model for the Cdk network driving the mammalian cell cycle. PMID:23130001

Semi-empirical long-term cycle life model coupled with an electrolyte depletion function for large-format graphite/LiFePO4 lithium-ion batteries

NASA Astrophysics Data System (ADS)

Park, Joonam; Appiah, Williams Agyei; Byun, Seoungwoo; Jin, Dahee; Ryou, Myung-Hyun; Lee, Yong Min

2017-10-01

To overcome the limitation of simple empirical cycle life models based on only equivalent circuits, we attempt to couple a conventional empirical capacity loss model with Newman's porous composite electrode model, which contains both electrochemical reaction kinetics and material/charge balances. In addition, an electrolyte depletion function is newly introduced to simulate a sudden capacity drop at the end of cycling, which is frequently observed in real lithium-ion batteries (LIBs). When simulated electrochemical properties are compared with experimental data obtained with 20 Ah-level graphite/LiFePO4 LIB cells, our semi-empirical model is sufficiently accurate to predict a voltage profile having a low standard deviation of 0.0035 V, even at 5C. Additionally, our model can provide broad cycle life color maps under different c-rate and depth-of-discharge operating conditions. Thus, this semi-empirical model with an electrolyte depletion function will be a promising platform to predict long-term cycle lives of large-format LIB cells under various operating conditions.

Variable cycle control model for intersection based on multi-source information

NASA Astrophysics Data System (ADS)

Sun, Zhi-Yuan; Li, Yue; Qu, Wen-Cong; Chen, Yan-Yan

2018-05-01

In order to improve the efficiency of traffic control system in the era of big data, a new variable cycle control model based on multi-source information is presented for intersection in this paper. Firstly, with consideration of multi-source information, a unified framework based on cyber-physical system is proposed. Secondly, taking into account the variable length of cell, hysteresis phenomenon of traffic flow and the characteristics of lane group, a Lane group-based Cell Transmission Model is established to describe the physical properties of traffic flow under different traffic signal control schemes. Thirdly, the variable cycle control problem is abstracted into a bi-level programming model. The upper level model is put forward for cycle length optimization considering traffic capacity and delay. The lower level model is a dynamic signal control decision model based on fairness analysis. Then, a Hybrid Intelligent Optimization Algorithm is raised to solve the proposed model. Finally, a case study shows the efficiency and applicability of the proposed model and algorithm.

Active Mechanisms of Vibration Encoding and Frequency Filtering in Central Mechanosensory Neurons.

PubMed

Azevedo, Anthony W; Wilson, Rachel I

2017-10-11

To better understand biophysical mechanisms of mechanosensory processing, we investigated two cell types in the Drosophila brain (A2 and B1 cells) that are postsynaptic to antennal vibration receptors. A2 cells receive excitatory synaptic currents in response to both directions of movement: thus, twice per vibration cycle. The membrane acts as a low-pass filter, so that voltage and spiking mainly track the vibration envelope rather than individual cycles. By contrast, B1 cells are excited by only forward or backward movement, meaning they are sensitive to vibration phase. They receive oscillatory synaptic currents at the stimulus frequency, and they bandpass filter these inputs to favor specific frequencies. Different cells prefer different frequencies, due to differences in their voltage-gated conductances. Both Na + and K + conductances suppress low-frequency synaptic inputs, so cells with larger voltage-gated conductances prefer higher frequencies. These results illustrate how membrane properties and voltage-gated conductances can extract distinct stimulus features into parallel channels. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnolol suppresses the proliferation and invasion of cholangiocarcinoma cells via inhibiting the NF-κB signaling pathway.

PubMed

Zhang, Fu-Hui; Ren, Hong-Yue; Shen, Jin-Xing; Zhang, Xiao-Yun; Ye, Hui-Ming; Shen, Dong-Yan

2017-10-01

Magnolol has shown the potential anticancer properties against a variety of cancers. However, the role of magnolol in cholangiocarcinoma (CCA) cells is unknown. In this study, we assessed the effect of magnolol on the CCA cells. CCA cells were treated with magnolol in the absence or presence of TNFα, the activator for NF-κB. After co-incubation with magnolol, cell proliferation and growth were examined by MTT, colony formation and xenograft tumors; cell cycle was analyzed by flow cytometry; cell migration and invasion were detected by wound healing and transwell assays; the expression of PCNA, Ki67, CyclinD1, MMP-2, MMP-7 and MMP-9 and NF-κB pathway were evaluated by using Western blot. Magnolol inhibited the abilities of CCA cell growth, migration and invasion accompanying with a decreased expression of PCNA, Ki67, MMP-2, MMP-7 and MMP-9 (all P<0.05). with magnolol induced cell cycle arrest in G1 phase with a downregulation of cell cycle protein CyclinD1 (all P<0.05). In addition, magnolol suppressed the expression of p-IκBα and p-P65 and the effect of magnolol on CCA cells could be inhibited by TNFα. Magnolol could inhibit the growth, migration and invasion of CCA cells through regulation of NF-κB pathway, and these data indicate that magnolol is a potential candidate for treating of CCA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines

PubMed Central

Esmaeelian, Babak; Benkendorff, Kirsten; Johnston, Martin R.; Abbott, Catherine A.

2013-01-01

Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and 1H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC50 = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC50 = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer. PMID:24152558

BTG/Tob family members Tob1 and Tob2 inhibit proliferation of mouse embryonic stem cells via Id3 mRNA degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yuanfan; Wang, Chenchen; Peking University Stem Cell Research Center, China National Center for International Research, Peking University Health Science Center, Beijing 100191

2015-07-03

The mammalian BTG/Tob family is a group of proteins with anti-proliferative ability, and there are six members including BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2. Among them, Tob subfamily members, specifically Tob1/Tob and Tob2, have the most extensive C-terminal regions. As previously reported, overexpression of BTG/Tob proteins is associated with the inhibition of G1 to S-phase cell cycle progression and decreased cell proliferation in a variety of cell types. Tob subfamily proteins have similar anti-proliferative effects on cell cycle progression in cultured tumor cells. An important unresolved question is whether or not they have function in rapidly proliferating cells, suchmore » as embryonic stem cells (ESCs). Tob1 and Tob2 were expressed ubiquitously in mouse ESCs (mESCs), suggesting a possible role in early embryonic development and mESCs. To address the above question and explore the possible functions of the Tob subfamily in ESCs, we established ESCs from different genotypic knockout inner cell mass (ICM). We found that Tob1{sup −/−}, Tob2{sup −/−}, and Tob1/2 double knockout (DKO, Tob1{sup −/−} & Tob2{sup −/−}) ESCs grew faster than wild type (WT) ESCs without losing pluripotency, and we provide a possible mechanistic explanation for these observations: Tob1 and Tob2 inhibit the cell cycle via degradation of Id3 mRNA, which is a set of directly targeted genes of BMP4 signaling in mESCs that play critical roles in the maintenance of ESC properties. Together, our data suggest that BTG/Tob family protein Tob1 and Tob2 regulation cell proliferation does not compromise the basic properties of mESCs. - Highlights: • We established mouse Tob1/2 double knockout embryonic stem cells. • Tob1 and Tob2 inhibit the proliferation of ESCs without effect on pluripotency. • Tob1 and Tob2 involved in the degradation of Id3 in mESCs.« less

Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

PubMed Central

2012-01-01

Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma. PMID:22475227

Novel Gold(I) Thiolate Derivatives Synergistic with 5-Fluorouracil as Potential Selective Anticancer Agents in Colon Cancer.

PubMed

Atrián-Blasco, Elena; Gascón, Sonia; Rodrı Guez-Yoldi, Ma Jesus; Laguna, Mariano; Cerrada, Elena

2017-07-17

New gold(I) thiolate complexes have been synthesized and characterized, and their physicochemical properties and anticancer activity have been tested. The coordination of PTA derivatives provides optimal hydrophilicity/lipophilicity properties to the complexes, which present high solution stability. Moreover, the complexes show a high anticancer activity against Caco-2 cells, comparable to that of auranofin, and a very low cytotoxic activity against enterocyte-like differentiated cells. Their activity has been shown to produce cell death by apoptosis and arrest of the cell cycle because of interaction with the reductase enzymes and consequent reactive oxygen species production. Some of these new complexes are also able to decrease the necessary dose of 5-fluorouracil, a drug used for the treatment of colon cancer, by a synergistic mechanism.

Graviola: A Novel Promising Natural-Derived Drug That Inhibits Tumorigenicity and Metastasis of Pancreatic Cancer Cells In Vitro and In Vivo Through Altering Cell Metabolism

PubMed Central

Torres, María P.; Rachagani, Satyanarayana; Purohit, Vinee; Pandey, Poomy; Joshi, Suhasini; Moore, Erik D.; Johansson, Sonny L.; Singh, Pankaj K.; Ganti, Apar K.; Batra, Surinder K.

2012-01-01

Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease. PMID:22475682

Semi-automatic spray pyrolysis deposition of thin, transparent, titania films as blocking layers for dye-sensitized and perovskite solar cells.

PubMed

Krýsová, Hana; Krýsa, Josef; Kavan, Ladislav

2018-01-01

For proper function of the negative electrode of dye-sensitized and perovskite solar cells, the deposition of a nonporous blocking film is required on the surface of F-doped SnO 2 (FTO) glass substrates. Such a blocking film can minimise undesirable parasitic processes, for example, the back reaction of photoinjected electrons with the oxidized form of the redox mediator or with the hole-transporting medium can be avoided. In the present work, thin, transparent, blocking TiO 2 films are prepared by semi-automatic spray pyrolysis of precursors consisting of titanium diisopropoxide bis(acetylacetonate) as the main component. The variation in the layer thickness of the sprayed films is achieved by varying the number of spray cycles. The parameters investigated in this work were deposition temperature (150, 300 and 450 °C), number of spray cycles (20-200), precursor composition (with/without deliberately added acetylacetone), concentration (0.05 and 0.2 M) and subsequent post-calcination at 500 °C. The photo-electrochemical properties were evaluated in aqueous electrolyte solution under UV irradiation. The blocking properties were tested by cyclic voltammetry with a model redox probe with a simple one-electron-transfer reaction. Semi-automatic spraying resulted in the formation of transparent, homogeneous, TiO 2 films, and the technique allows for easy upscaling to large electrode areas. The deposition temperature of 450 °C was necessary for the fabrication of highly photoactive TiO 2 films. The blocking properties of the as-deposited TiO 2 films (at 450 °C) were impaired by post-calcination at 500 °C, but this problem could be addressed by increasing the number of spray cycles. The modification of the precursor by adding acetylacetone resulted in the fabrication of TiO 2 films exhibiting perfect blocking properties that were not influenced by post-calcination. These results will surely find use in the fabrication of large-scale dye-sensitized and perovskite solar cells.

Differential association of S100A9, an inflammatory marker, and p53, a cell cycle marker, expression with epicardial adipocyte size in patients with cardiovascular disease.

PubMed

Agra, Rosa María; Fernández-Trasancos, Ángel; Sierra, Juan; González-Juanatey, José Ramón; Eiras, Sonia

2014-10-01

S100A9 (calgranulin B) has inflammatory and oxidative stress properties and was found to be associated with atherosclerosis and obesity. One of the proteins that can regulate S100A9 transcription is p53, which is involved in cell cycle, apoptosis and adipogenesis. Thus, it triggers adipocyte enlargement and finally obesity. Because epicardial adipose tissue (EAT) volume and thickness is related to coronary artery disease (CAD), we studied the gene expression of this pathway in patients with cardiovascular disease and its association with obesity. Adipocytes and stromal cells from EAT and subcutaneous adipose tissue (SAT) from 48 patients who underwent coronary artery bypass graft and/or valve replacement were obtained after collagenase digestion and differential centrifugation. The expression levels of the involved genes on adipogenesis and cell cycle like fatty acid-binding protein (FABP) 4, retinol-binding protein (RBP)4, p53 and S100A9 were determined by real-time polymerase chain reaction (PCR). Adipocyte diameter was measured by optical microscopy. We found that epicardial adipocytes expressed significantly lower levels of adipogenic genes (FABP4 and RBP4) and cell cycle-related genes (S100A9 and p53) than subcutaneous adipocytes. However, in obese patients, upregulation of adipogenic and cell cycle-related genes in subcutaneous and epicardial adipocytes, respectively, was observed. The enlargement of adipocyte size was related to FABP4, S100A9 and p53 expression levels in stromal cells. But only the p53 association was maintained in epicardial stromal cells from obese patients (p=0.003). The expression of p53, but not S100A9, in epicardial stromal cells is related to adipocyte enlargement in obese patients with cardiovascular disease. These findings suggest new mechanisms for understanding the relationship between epicardial fat thickness, obesity and cardiovascular disease.

Role of PP2Cα in cell growth, in radio- and chemosensitivity, and in tumorigenicity

PubMed Central

Lammers, Twan; Peschke, Peter; Ehemann, Volker; Debus, Jürgen; Slobodin, Boris; Lavi, Sara; Huber, Peter

2007-01-01

Background PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis. Results It was found that knockdown of PP2Cα did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Cα siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Cα siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased. Conclusion Based on these findings, we conclude that PP2Cα is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Cα may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer. PMID:17941990

Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae.

PubMed

Desfossés-Baron, Kristelle; Hammond-Martel, Ian; Simoneau, Antoine; Sellam, Adnane; Roberts, Stephen; Wurtele, Hugo

2016-10-26

The mechanism of action of valproate (VPA), a widely prescribed short chain fatty acid with anticonvulsant and anticancer properties, remains poorly understood. Here, the yeast Saccharomyces cerevisiae was used as model to investigate the biological consequences of VPA exposure. We found that low pH strongly potentiates VPA-induced growth inhibition. Transcriptional profiling revealed that under these conditions, VPA modulates the expression of genes involved in diverse cellular processes including protein folding, cell wall organisation, sexual reproduction, and cell cycle progression. We further investigated the impact of VPA on selected processes and found that this drug: i) activates markers of the unfolded protein stress response such as Hac1 mRNA splicing; ii) modulates the cell wall integrity pathway by inhibiting the activation of the Slt2 MAP kinase, and synergizes with cell wall stressors such as micafungin and calcofluor white in preventing yeast growth; iii) prevents activation of the Kss1 and Fus3 MAP kinases of the mating pheromone pathway, which in turn abolishes cellular responses to alpha factor; and iv) blocks cell cycle progression and DNA replication. Overall, our data identify heretofore unknown biological responses to VPA in budding yeast, and highlight the broad spectrum of cellular pathways influenced by this chemical in eukaryotes.

Enterolactone induces G1-phase cell cycle arrest in non-small cell lung cancer cells by down-regulating cyclins and cyclin-dependent kinases

PubMed Central

Chikara, Shireen; Lindsey, Kaitlin; Dhillon, Harsharan; Mamidi, Sujan; Kittilson, Jeffrey; Christofidou-Solomidou, Melpo; Reindl, Katie M.

2017-01-01

Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG) which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anti-cancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study we investigated the anti-cancer effects of EL for several non-small cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners. The anti-proliferative effects of EL for lung cancer cells were not due to enhanced cell death, but rather due to G1-phase cell cycle arrest. Molecular studies revealed that EL- decreased mRNA or protein expression levels of the G1-phase promoters cyclin D1, cyclin E, cyclin-dependent kinases (CDK)-2, -4, and -6, and p-cdc25A; decreased phosphorylated retinoblastoma (p-pRb) protein levels; and simultaneously increased levels of p21WAF1/CIP1, a negative regulator of the G1-phase. The results suggest that EL inhibits the growth of NSCLC cell lines by down-regulating G1-phase cyclins and CDKs, and up-regulating p21WAF1/CIP1, which leads to G1-phase cell cycle arrest. Therefore, EL may hold promise as an adjuvant treatment for lung cancer therapy. PMID:28323486

Enterolactone Induces G1-phase Cell Cycle Arrest in Nonsmall Cell Lung Cancer Cells by Downregulating Cyclins and Cyclin-dependent Kinases.

PubMed

Chikara, Shireen; Lindsey, Kaitlin; Dhillon, Harsharan; Mamidi, Sujan; Kittilson, Jeffrey; Christofidou-Solomidou, Melpo; Reindl, Katie M

2017-01-01

Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG), which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anticancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study, we investigated the anticancer effects of EL for several nonsmall cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners. The antiproliferative effects of EL for lung cancer cells were not due to enhanced cell death, but rather due to G 1 -phase cell cycle arrest. Molecular studies revealed that EL decreased mRNA or protein expression levels of the G 1 -phase promoters cyclin D1, cyclin E, cyclin-dependent kinases (CDK)-2, -4, and -6, and p-cdc25A; decreased phosphorylated retinoblastoma (p-pRb) protein levels; and simultaneously increased levels of p21 WAF1/CIP1 , a negative regulator of the G 1 phase. The results suggest that EL inhibits the growth of NSCLC cell lines by downregulating G 1 -phase cyclins and CDKs, and upregulating p21 WAF1/CIP1 , which leads to G 1 -phase cell cycle arrest. Therefore, EL may hold promise as an adjuvant treatment for lung cancer therapy.

Rheological properties of RBC in the microcirculation of mammalian skeletal muscle. [red blood cells

NASA Technical Reports Server (NTRS)

Ehrenberg, M. H.

1974-01-01

In the investigation the established technique of direct microscopic viewing was combined with the use of a closed circuit television system and cinematography. The red cell flow patterns in all capillaries were found to be oscillatory with characteristic cycle frequencies and amplitudes for all concentrations of inspired oxygen greater than 8%. Generally, there was a transient decrease in mean flow rate with increasing severity of hypoxia, with a gradual return toward control values. Red cell flow patterns are discussed along with questions of red cell configuration.

Novel pyrimidinic selenourea induces DNA damage, cell cycle arrest, and apoptosis in human breast carcinoma.

PubMed

Barbosa, Flavio A R; Siminski, Tâmila; Canto, Rômulo F S; Almeida, Gabriela M; Mota, Nádia S R S; Ourique, Fabiana; Pedrosa, Rozangela Curi; Braga, Antonio Luiz

2018-06-11

Novel pyrimidinic selenoureas were synthesized and evaluated against tumour and normal cell lines. Among these, the compound named 3j initially showed relevant cytotoxicity and selectivity for tumour cells. Three analogues of 3j were designed and synthesized keeping in view the structural requirements of this compound. Almost all the tested compounds displayed considerable cytotoxicity. However, 8a, one of the 3j analogues, was shown to be highly selective and cytotoxic, especially for breast carcinoma cells (MCF-7) (IC 50  = 3.9 μM). Furthermore, 8a caused DNA damage, inhibited cell proliferation, was able to arrest cell cycle in S phase, and induced cell death by apoptosis in human breast carcinoma cells. Moreover, predictions of pharmacokinetic properties showed that 8a may present good absorption and permeation characteristics for oral administration. Overall, the current study established 8a as a potential drug prototype to be employed as a DNA interactive cytotoxic agent for the treatment of breast cancer. Copyright © 2018. Published by Elsevier Masson SAS.

Development and Validation of a Slurry Model for Chemical Hydrogen Storage in Fuel Cell Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brooks, Kriston P.; Pires, Richard P.; Simmons, Kevin L.

2014-07-25

The US Department of Energy's (DOE) Hydrogen Storage Engineering Center of Excellence (HSECoE) is developing models for hydrogen storage systems for fuel cell-based light duty vehicle applications for a variety of promising materials. These transient models simulate the performance of the storage system for comparison to the DOE’s Technical Targets and a set of four drive cycles. The purpose of this research is to describe the models developed for slurry-based chemical hydrogen storage materials. The storage systems of both a representative exothermic system based on ammonia borane and endothermic system based on alane were developed and modeled in Simulink®. Oncemore » complete the reactor and radiator components of the model were validated with experimental data. The model was then run using a highway cycle, an aggressive cycle, cold-start cycle and hot drive cycle. The system design was adjusted to meet these drive cycles. A sensitivity analysis was then performed to identify the range of material properties where these DOE targets and drive cycles could be met. Materials with a heat of reaction greater than 11 kJ/mol H2 generated and a slurry hydrogen capacity of greater than 11.4% will meet the on-board efficiency and gravimetric capacity targets, respectively.« less

Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability.

PubMed

Gao, Guangxun; Chen, Liang; Li, Jingxia; Zhang, Dongyun; Fang, Yong; Huang, Haishan; Chen, Xiequn; Huang, Chuanshu

2014-05-15

The cancer chemopreventive property of Chinese herb new isolate isorhapontigenin (ISO) and mechanisms underlying its activity have never been explored. Here we demonstrated that ISO treatment with various concentrations for 3 weeks could dramatically inhibit TPA/EGF-induced cell transformation of Cl41 cells in Soft Agar assay, whereas co-incubation of cells with ISO at the same concentrations could elicit G0/G1 cell-cycle arrest without redundant cytotoxic effects on non-transformed cells. Further studies showed that ISO treatment resulted in cyclin D1 downregulation in dose- and time-dependent manner. Our results indicated that ISO regulated cyclin D1 at transcription level via targeting JNK/C-Jun/AP-1 activation. Moreover, we found that ISO-inhibited JNK/C-Jun/AP-1 activation was mediated by both upregulation of MKP-1 expression through increasing its mRNA stability and deactivating MKK7. Most importantly, MKP-1 knockdown could attenuate ISO-mediated suppression of JNK/C-Jun activation and cyclin D1 expression, as well as G0/G1 cell cycle arrest and cell transformation inhibition, while ectopic expression of FLAG-cyclin D1 T286A mutant also reversed ISO-induced G0/G1 cell-cycle arrest and inhibition of cell transformation. Our results demonstrated that ISO is a promising chemopreventive agent via upregulating mkp-1 mRNA stability, which is distinct from its cancer therapeutic effect with downregulation of XIAP and cyclin D1 expression.

Single-cell vs. bulk activity properties of coastal bacterioplankton over an annual cycle in a temperate ecosystem.

PubMed

Morán, Xosé Anxelu G; Calvo-Díaz, Alejandra

2009-01-01

The connections between single-cell activity properties of heterotrophic planktonic bacteria and whole community metabolism are still poorly understood. Here, we show flow cytometry single-cell analysis of membrane-intact (live), high nucleic acid (HNA) content and actively respiring (CTC+) bacteria with samples collected monthly during 2006 in northern Spain coastal waters. Bulk activity was assessed by measuring 3H-Leucine incorporation and specific growth rates. Consistently, different single-cell relative abundances were found, with 60-100% for live, 30-84% for HNA and 0.2-12% for CTC+ cells. Leucine incorporation rates (2-153 pmol L(-1) h(-1)), specific growth rates (0.01-0.29 day(-1)) and the total and relative abundances of the three single-cell groups showed marked seasonal patterns. Distinct depth distributions during summer stratification and different relations with temperature, chlorophyll and bacterial biovolume suggest the existence of different controlling factors on each single-cell property. Pooled leucine incorporation rates were similarly correlated with the abundance of all physiological groups, while specific growth rates were only substantially explained by the percentage of CTC+ cells. However, the ability to reduce CTC proved notably better than the other two single-cell properties at predicting bacterial bulk rates within seasons, suggesting a tight linkage between bacterial individual respiration and biomass production at the community level.

Synthesis and biological evaluation of novel N-phenyl ureidobenzenesulfonate derivatives as potential anticancer agents. Part 2. Modulation of the ring B.

PubMed

Gagné-Boulet, Mathieu; Moussa, Hanane; Lacroix, Jacques; Côté, Marie-France; Masson, Jean-Yves; Fortin, Sébastien

2015-10-20

DNA double strand-breaks (DSBs) are the most deleterious lesions that can affect the genome of living beings and are lethal if not quickly and properly repaired. Recently, we discovered a new family of anticancer agents designated as N-phenyl ureidobenzenesulfonates (PUB-SOs) that are blocking the cells cycle progression in S-phase and inducing DNA DSBs. Previously, we have studied the effect of several modifications on the molecular scaffold of PUB-SOs on their cytocidal properties. However, the effect of the nature and the position of substituents on the aromatic ring B is still poorly studied. In this study, we report the preparation and the biological evaluation of 45 new PUB-SO derivatives substituted by alkyl, alkoxy, halogen and nitro groups at different positions on the aromatic ring B. All PUB-SOs were active in the submicromolar to low micromolar range (0.24-20 μM). The cell cycle progression analysis showed that PUB-SOs substituted at position 2 by alkyl, halogen or nitro groups or substituted at position 4 by a hydroxyl group arrest the cell cycle progression in S-phase. Interestingly, all others PUB-SOs substituted at positions 3 and 4 arrested the cell cycle in G2/M-phase. PUB-SOs arresting the cell cycle progression in S-phase also induced the phosphorylation of H2AX (γH2AX) which is indicating the generation of DNA DSBs. We evidenced that few modifications on the ring B of PUB-SOs scaffold lead to cytocidal derivatives arresting the cell cycle in S-phase and inducing γH2AX and DSBs. In addition, this study shows that these new anticancer agents are promising and could be used as alternative to circumvent some of the biopharmaceutical complications that might be encountered during the development of PUB-SOs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Cycling performance of lithium metal polymer cells assembled with ionic liquid and poly(3-methyl thiophene)/carbon nanotube composite cathode

NASA Astrophysics Data System (ADS)

Kim, Dong-Won; Sivakkumar, S. R.; MacFarlane, Douglas R.; Forsyth, Maria; Sun, Yang-Kook

A poly(3-methylthiophene) (PMT)/multi-walled carbon nanotube (CNT) composite is synthesized by in situ chemical polymerization. The PMT/CNT composite is used as an active cathode material in lithium metal polymer cells assembled with ionic liquid (IL) electrolytes. The IL electrolyte consists of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF 4) and LiBF 4. A small amount of vinylene carbonate is added to the IL electrolyte to prevent the reductive decomposition of the imidazolium cation in EMIBF 4. A porous poly(vinylidene fluoride- co-hexafluoropropylene) (P(VdF- co-HFP)) film is used as a polymer membrane for assembling the cells. Electrochemical properties of the PMT/CNT composite electrode in the IL electrolyte are evaluated and the effect of vinylene carbonate on the cycling performance of the lithium metal polymer cells is investigated. The cells assembled with a non-flammable IL electrolyte and a PMT/CNT composite cathode are promising candidates for high-voltage-power sources with enhanced safety.

Electrolyte volume effects on electrochemical performance and solid electrolyte interphase in Si-graphite/NMC lithium-ion pouch cells

DOE PAGES

An, Seong Jin; Li, Jianlin; Daniel, Claus; ...

2017-05-15

This study aims to explore the correlations between electrolyte volume, electrochemical performance, and properties of the solid electrolyte interphase in pouch cells with Si-graphite composite anodes. The electrolyte is 1.2 M LiPF 6 in ethylene carbonate:ethylmethyl carbonate with 10 wt.% fluoroethylene carbonate. Single layer pouch cells (100 mAh) were constructed with 15 wt.% Si-graphite/LiNi 0.5Mn 0.3CO 0.2O 2 electrodes. It is found that a minimum electrolyte volume factor of 3.1 times the total pore volume of cell components (cathode, anode, and separator) is needed for better cycling stability. Less electrolyte causes increases in ohmic and charge transfer resistances. Lithium dendritesmore » are observed when the electrolyte volume factor is low. The resistances from the anodes become significant as the cells are discharged. As a result, solid electrolyte interphase thickness grows as the electrolyte volume factor increases and is non-uniform after cycling.« less

Organic solar cells and physics education

NASA Astrophysics Data System (ADS)

Csernovszky, Zoltán; Horváth, Ákos

2018-07-01

This paper explains the operational principles of a home-made organic solar cell with the representation of an electron-cycle on an energy-level diagram. We present test data for a home-made organic solar cell which operates as a galvanic cell and current source in an electrical circuit. To determine the maximum power of the cell, the optimal current was estimated with a linear approximation. Using different light sources and dyes, the electrical properties of organic solar cells were compared. The solar cells were studied by looking at spectrophotometric data from different sensitizer dyes, generated by a do-it-yourself diffraction grating spectroscope. The sensitizer dyes of solar cells were tested by the diffraction grating spectroscope. The data were analysed on a light-intensity‑wavelength diagram to discover which photons were absorbed and to understand the colours of the fruits containing these dyes. In terms of theoretical applications, the paper underlines the analogous nature of organic solar cells, a conventional single p‑n junction solar cell and the light-dependent reactions of photosynthesis, using energy-level diagrams of electron-cycles. To conclude, a classification of photon‑electron interactions in molecular systems and crystal lattices is offered, to show the importance of organic solar cells.

Nickel/metal hydride secondary batteries using an alkaline solid polymer electrolyte

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vassal, N.; Salmon, E.; Fauvarque, J.F.

1999-01-01

Sealed alkaline solid polymer electrolyte nickel/metal hydride laboratory cells have been constructed and tested to evaluate their properties. Studies of the cycle life, self-discharge, and behavior of cells at different temperatures were carried out. The first results on the electrochemical behavior of an alkaline solid polymer electrolyte [based on poly(ethylene oxide), potassium hydroxide, and water] medium are presented here and show good reversibility of this all-solid-state system for more than 500 cycles, without significant loss of capacity and with a reasonable average discharge efficiency (close to 80%). The temperature-dependence study allowed the determination of optimum operating conditions between 0 andmore » 40 C. Characteristics of the solid polymer electrolyte based Ni/MH cells are compared to those of several other rechargeable battery systems.« less

Quantification of the degradation of Ni-YSZ anodes upon redox cycling

NASA Astrophysics Data System (ADS)

Song, Bowen; Ruiz-Trejo, Enrique; Bertei, Antonio; Brandon, Nigel P.

2018-01-01

Ni-YSZ anodes for Solid Oxide Fuel Cells are vulnerable to microstructural damage during redox cycling leading to a decrease in the electrochemical performance. This study quantifies the microstructural changes as a function of redox cycles at 800 °C and associates it to the deterioration of the mechanical properties and polarisation resistance. A physically-based model is used to estimate the triple-phase boundary (TPB) length from impedance spectra, and satisfactorily matches the TPB length quantified by FIB-SEM tomography: within 20 redox cycles, the TPB density decreases from 4.63 μm-2 to 1.06 μm-2. Although the polarisation resistance increases by an order of magnitude after 20 cycles, after each re-reduction the electrode polarisation improves consistently due to the transient generation of Ni nanoparticles around the TPBs. Nonetheless, the long-term degradation overshadows this transient improvement due to the nickel agglomeration. In addition, FIB-SEM tomography reveals fractures along YSZ grain boundaries, Ni-YSZ detachment and increased porosity in the composite that lead to irreversible mechanical damage: the elastic modulus diminishes from 36.4 GPa to 20.2 GPa and the hardness from 0.40 GPa to 0.15 GPa. These results suggest that microstructural, mechanical and electrochemical properties are strongly interdependent in determining the degradation caused by redox cycling.

Structural Fluctuations of the Chromatin Fiber within Topologically Associating Domains.

PubMed

Tiana, Guido; Amitai, Assaf; Pollex, Tim; Piolot, Tristan; Holcman, David; Heard, Edith; Giorgetti, Luca

2016-03-29

Experiments based on chromosome conformation capture have shown that mammalian genomes are partitioned into topologically associating domains (TADs), within which the chromatin fiber preferentially interacts. TADs may provide three-dimensional scaffolds allowing genes to contact their appropriate distal regulatory DNA sequences (e.g., enhancers) and thus to be properly regulated. Understanding the cell-to-cell and temporal variability of the chromatin fiber within TADs, and what determines them, is thus of great importance to better understand transcriptional regulation. We recently described an equilibrium polymer model that can accurately predict cell-to-cell variation of chromosome conformation within single TADs, from chromosome conformation capture-based data. Here we further analyze the conformational and energetic properties of our model. We show that the chromatin fiber within TADs can easily fluctuate between several conformational states, which are hierarchically organized and are not separated by important free energy barriers, and that this is facilitated by the fact that the chromatin fiber within TADs is close to the onset of the coil-globule transition. We further show that in this dynamic state the properties of the chromatin fiber, and its contact probabilities in particular, are determined in a nontrivial manner not only by site-specific interactions between strongly interacting loci along the fiber, but also by nonlocal correlations between pairs of contacts. Finally, we use live-cell experiments to measure the dynamics of the chromatin fiber in mouse embryonic stem cells, in combination with dynamical simulations, and predict that conformational changes within one TAD are likely to occur on timescales that are much shorter than the duration of one cell cycle. This suggests that genes and their regulatory elements may come together and disassociate several times during a cell cycle. These results have important implications for transcriptional regulation as they support the concept of highly dynamic interactions driven by a complex interplay between site-specific interactions and the intrinsic biophysical properties of the chromatin fiber. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Aglycone Ebselen and β-d-Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen β-d-Xyloside-Induced Cytotoxicity.

PubMed

Tang, Yang; Zhang, Siqi; Chang, Yajing; Fan, Dacheng; Agostini, Ariane De; Zhang, Lijuan; Jiang, Tao

2018-04-12

Most β-d-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to d-xylose, d-glucose, d-galactose, and d-lactose (8A-D), only Ebselen β-d-xyloside (8A) showed significant cytotoxicity in human cancer cells. The following facts indicated that the aglycone Ebselen and β-d-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase cancer cell apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-β-d-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans.

Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jung-Jin; Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764; Zhang, Wei-Yun

2011-07-22

Highlights: {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner with no apparent cytotoxicity. {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced phosphorylation of Erk1/2 and PLC{gamma}1. {yields} 2-Decylamino-DMNQ arrested a G{sub 0}/G{sub 1} cell cycle progression in association with pRb phosphorylation and PCNA expression. {yields} Both U0126, an Erk inhibitor, and U73122, a PLC{gamma} inhibitor, arrested a G{sub 0}/G{sub 1} phase of the cell cycle. -- Abstract: Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferationmore » and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-R{beta} or Akt, it did inhibit the phosphorylation of Erk1/2 and PLC{gamma}1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G{sub 0}/G{sub 1} phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLC{gamma} inhibitor, increased the proportion of cells in the G{sub 0}/G{sub 1} phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G{sub 0}/G{sub 1} phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.« less

Cytotoxicity of mequindox and its metabolites in HepG2 cells in vitro and murine hepatocytes in vivo.

PubMed

Liu, Yingchun; Jiang, Wei; Chen, Yongjun; Liu, Yanyan; Zeng, Peng; Xue, Feiqun; Wang, Quan

2016-02-01

Mequindox, a quinoxaline 1,4-dioxide, is widely used as a feed additive in the Chinese livestock industry because of its effective antibacterial properties. Many recent studies have found that mequindox is rapidly metabolized to numerous metabolites following administration to animals. There have, however, been few reports describing the cytotoxicity of mequindox metabolites. In this study, HepG2 cells were treated with mequindox (0, 2, 10, 50 or 100 μg/ml) or its major metabolites (0, 40, 100, 250 or 500 μg/ml) for 24h. Mice were administrated with mequindox (0, 50, 200 or 500 mg/kg.bw) for five days. DNA damage in the HepG2 cells and mouse hepatocytes was then assessed using an SCGE assay. The cell cycle of the HepG2 cells was also determined by flow cytometry. Mequindox was found to induce cell cycle arrest to the G2/M phase and cause dose-dependent DNA damage in HepG2 cells in vitro and in murine hepatocytes in vivo. Compared with mequindox, the major metabolites had much smaller effects on the cell cycle and caused much less DNA damage in HepG2 cells. And the results indicated that the process of metabolites formed by reduction of the MEQ acetyl group or reduction of the N → O groups could contribute to DNA damage in murine hepatocytes in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional coordinator of invasion, apoptosis and cell cycle

PubMed Central

Singh, Mahendra K.; Cowell, Lauren; Seo, Sachiko; O’Neill, Geraldine M.; Golemis, Erica A.

2007-01-01

Upregulation of the scaffolding protein HEF1, also known as NEDD9 and Cas-L, has recently been identified as a pro-metastatic stimulus in a number of different solid tumors, and has also been strongly associated with pathogenesis of BCR-Abl-dependent tumors. As the evidence mounts for HEF1/NEDD9/Cas-L as a key player in metastatic cancer, it is timely to review the molecular regulation of HEF1/NEDD9/Cas-L. Most of the mortality associated with cancer arises from uncontrolled metastases, thus a better understanding of the properties of proteins specifically associated with promotion of this process may yield insights that improve cancer diagnosis and treatment. In this review, we summarize the extensive literature regarding HEF1/NEDD9/CAS-L expression and function in signaling relevant to cell attachment, migration, invasion; cell cycle; apoptosis; and oncogenic signal transduction. The complex function of HEF1/NEDD9/CAS-L revealed by this analysis leads us to propose a model in which alleviation of cell cycle checkpoints and acquired resistance to apoptosis is permissive for a HEF1/NEDD9/CAS-L-promoted pro-metastatic phenotype. PMID:17703068

Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

PubMed

Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

2009-10-01

Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

[Effects of HOXB2 antisense oligodeoxynucleotides on the biological properties of primary human umbilical vein endothelial cells].

PubMed

Zhang, Xiaoqi; Liu, Xusheng

2002-07-01

To explore the effects of HOXB2 antisense oligodeoxynuc leotides (Asodn) on the biological properties of primary human umbilical vein endothelial cells (ECs). Fluorescent labelled Asodn was transfected into the endothelial cells of human unbilical vein mediated liposome and its distribution within endothelia was observed. (3)H-TdR incorporation test was employed to determine its effects on the DNA synthesis. Flow cytometry was applied to determine the change of the cell cycle. In the same time, RT-PCR was adopted to study the influence of Asodn on the expression of target genes. Fifteen minutes after the transfection, weak nucleic staining was observed. The fluorescent staining was the strongest 4 approximately 8 hours after the transfection and began to weaken in 16 hours. The proportion of cells in G1/0 phase in Asodn group was 53.4 +/- 3.1, significantly higher than that in control group (35.8 +/- 7.3, P < 0.01), and the proportion of cells in S phase in Asodn group was 42.2 +/- 3.5, significantly lower than that in control group (60.8 +/- 6.2, P < 0.01). The expression of HOXB2 mRNA was remarkably decreased during 24 to 48 hours. HOXB2 Asodn exerts inhibitory effects on EC proliferation dose-dependently, delays the conversion of G1 phase to S Phase, and inhibits the expression of HOXB2 mRNA. HOXB2 gene plays an important role in proliferation of endothelial cells and the mechanism is related to cell cycle.

A transient plasticity study and low cycle fatigue analysis of the Space Station Freedom photovoltaic solar array blanket

NASA Technical Reports Server (NTRS)

Armand, Sasan C.; Liao, Mei-Hwa; Morris, Ronald W.

1990-01-01

The Space Station Freedom photovoltaic solar array blanket assembly is comprised of several layers of materials having dissimilar elastic, thermal, and mechanical properties. The operating temperature of the solar array, which ranges from -75 to +60 C, along with the material incompatibility of the blanket assembly components combine to cause an elastic-plastic stress in the weld points of the assembly. The weld points are secondary structures in nature, merely serving as electrical junctions for gathering the current. The thermal mechanical loading of the blanket assembly operating in low earth orbit continually changes throughout each 90 min orbit, which raises the possibility of fatigue induced failure. A series of structural analyses were performed in an attempt to predict the fatigue life of the solar cell in the Space Station Freedom photovoltaic array blanket. A nonlinear elastic-plastic MSC/NASTRAN analysis followed by a fatigue calculation indicated a fatigue life of 92,000 to 160,000 cycles for the solar cell weld tabs. Additional analyses predict a permanent buckling phenomenon in the copper interconnect after the first loading cycle. This should reduce or eliminate the pulling of the copper interconnect on the joint where it is welded to the silicon solar cell. It is concluded that the actual fatigue life of the solar array blanket assembly should be significantly higher than the calculated 92,000 cycles, and thus the program requirement of 87,500 cycles (orbits) will be met. Another important conclusion that can be drawn from the overall analysis is that, the strain results obtained from the MSC/NASTRAN nonlinear module are accurate to use for low-cycle fatigue analysis, since both thermal cycle testing of solar cells and analysis have shown higher fatigue life than the minimum program requirement of 87,500 cycles.

In vitro recapitulation of the urea cycle using murine embryonic stem cell-derived in vitro liver model.

PubMed

Tamai, Miho; Aoki, Mami; Nishimura, Akihito; Morishita, Koji; Tagawa, Yoh-ichi

2013-12-01

Ammonia, a toxic metabolite, is converted to urea in hepatocytes via the urea cycle, a process necessary for cell/organismal survival. In liver, hepatocytes, polygonal and multipolar structures, have a few sides which face hepatic sinusoids and adjacent hepatocytes to form intercellular bile canaliculi connecting to the ductules. The critical nature of this three-dimensional environment should be related to the maintenance of hepatocyte function such as urea synthesis. Recently, we established an in vitro liver model derived from murine embryonic stem cells, IVL(mES), which included the hepatocyte layer and a surrounding sinusoid vascular-like network. The IVL(mES) culture, where the hepatocyte is polarized in a similar fashion to its in vivo counterpart, could successfully recapitulate in vivo results. L-Ornithine is an intermediate of the urea cycle, but supplemental L-ornithine does not activate the urea cycle in the apolar primary hepatocyte of monolayer culture. In the IVL(mES), supplemental L-ornithine could activate the urea cycle, and also protect against ammonium/alcohol-induced hepatocyte death. While the IVL(mES) displays architectural and functional properties similar to the liver, primary hepatocyte of monolayer culture fail to model critical functional aspects of liver physiology. We propose that the IVL(mES) will represent a useful, humane alternative to animal studies for drug toxicity and mechanistic studies of liver injury.

CIP-36, a novel topoisomerase II-targeting agent, induces the apoptosis of multidrug-resistant cancer cells in vitro.

PubMed

Cao, Bo; Chen, Hong; Gao, Ying; Niu, Cong; Zhang, Yuan; Li, Ling

2015-03-01

The need to overcome cancer multidrug resistance (MDR) has fueled considerable interest in the development of novel synthetic antitumor agents with cytotoxicity against cancer cell lines with MDR. In this study, we aimed to investigate CIP-36, a novel podophyllotoxin derivative, for its inhibitory effects on human cancer cells from multiple sources, particularly cells with MDR in vitro. The human leukemia cell line, K562, and the adriamycin-resistant subline, K562/A02, were exposed to CIP-36 or anticancer agents, and various morphological and biochemical properties were assessed by Hoechst 33342 staining under a fluorescence microscope. Subsequently, cytotoxicity, cell growth curves and the cell cycle were analyzed. Finally, the effects of CIP-36 on topoisomerase IIα (Topo IIα) activity were determined. Treatment with CIP-36 significantly inhibited the growth of the K562 and MDR K562/A02 cells. Our data demonstrated that CIP-36 induced apoptosis, inhibited cell cycle progression and inhibited Topo IIα activity. These findings suggest that CIP-36 has the potential to overcome the multidrug resistance of K562/A02 cells by mediating Topo IIα activity.

Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells.

PubMed

He, Liu-Jun; Yang, Dong-Lin; Li, Shi-Qiang; Zhang, Ya-Jun; Tang, Yan; Lei, Jie; Frett, Brendan; Lin, Hui-Kuan; Li, Hong-Yu; Chen, Zhong-Zhu; Xu, Zhi-Gang

2018-06-12

Colorectal cancer (CRC) is one of the most frequent, malignant gastrointestinal tumors, and strategies and effectiveness of current therapy are limited. A series of benzimidazole-isoquinolinone derivatives (BIDs) was synthesized and screened to identify novel scaffolds for CRC. Of the compounds evaluated, 7g exhibited the most promising anti-cancer properties. Employing two CRC cell lines, SW620 and HT29, 7g was found to suppress growth and proliferation of the cell lines at a concentration of ∼20 µM. Treatment followed an increase in G 2 /M cell cycle arrest, which was attributed to cyclin B1 and cyclin-dependent kinase 1 (CDK1) signaling deficiencies with simultaneous enhancement in p21 and p53 activity. In addition, mitochondrial-mediated apoptosis was induced in CRC cells. Interestingly, 7g decreased phosphorylated AKT, mTOR and 4E-BP1 levels, while promoting the expression/stability of PTEN. Since PTEN controls input into the PI3K/AKT/mTOR pathway, antiproliferative effects can be attributed to PTEN-mediated tumor suppression. Collectively, these results suggest that BIDs exert antitumor activity in CRC by impairing PI3K/AKT/mTOR signaling. Against a small kinase panel, 7g exhibited low affinity at 5 µM suggesting anticancer properties likely stem through a non-kinase mechanism. Because of the novelty of BIDs, the structure can serve as a lead scaffold to design new CRC therapies. Copyright © 2018. Published by Elsevier Ltd.

Genistein and daidzein: different molecular effects on prostate cancer.

PubMed

Adjakly, Mawussi; Ngollo, Marjolaine; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2013-01-01

Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

The mucin MUC4 and its membrane partner ErbB2 regulate biological properties of human CAPAN-2 pancreatic cancer cells via different signalling pathways.

PubMed

Jonckheere, Nicolas; Skrypek, Nicolas; Merlin, Johann; Dessein, Anne Frédérique; Dumont, Patrick; Leteurtre, Emmanuelle; Harris, Ann; Desseyn, Jean-Luc; Susini, Christiane; Frénois, Frédéric; Van Seuningen, Isabelle

2012-01-01

The mucin MUC4 and its membrane partner the ErbB2 oncogenic receptor are potential interacting partners in human pancreatic tumour development. However, the way they function is still largely unknown. In this work, we aimed to identify the cellular mechanisms and the intracellular signalling pathways under the control of both ErbB2 and MUC4 in a human pancreatic adenocarcinomatous cell line. Using co-immunoprecipitation and GST pull-down, we show that MUC4 and ErbB2 interact in the human pancreatic adenocarcinomatous cell line CAPAN-2 via the EGF domains of MUC4. Stable cell clones were generated in which either MUC4 or ErbB2 were knocked down (KD) by a shRNA approach. Biological properties of these cells were then studied in vitro and in vivo. Our results show that ErbB2-KD cells are more apoptotic and less proliferative (decreased cyclin D1 and increased p27kip1 expression) while migration and invasive properties were not altered. MUC4-KD clones were less proliferative with decreased cyclin D1 expression, G1 cell cycle arrest and altered ErbB2/ErbB3 expression. Their migration properties were reduced whereas invasive properties were increased. Importantly, inhibition of ErbB2 and MUC4 expression did not impair the same signalling pathways (inhibition of MUC4 expression affected the JNK pathway whereas that of ErbB2 altered the MAPK pathway). Finally, ErbB2-KD and MUC4-KD cells showed impaired tumour growth in vivo. Our results show that ErbB2 and MUC4, which interact physically, activate different intracellular signalling pathways to regulate biological properties of CAPAN-2 pancreatic cancer cells.

Stem/progenitor cell-like properties of desmoglein 3dim cells in primary and immortalized keratinocyte lines.

PubMed

Wan, Hong; Yuan, Ming; Simpson, Cathy; Allen, Kirsty; Gavins, Felicity N E; Ikram, Mohammed S; Basu, Subham; Baksh, Nuzhat; O'Toole, Edel A; Hart, Ian R

2007-05-01

We showed previously that primary keratinocytes selected for low desmoglein 3 (Dsg3) expression levels exhibited increased colony-forming efficiency and heightened proliferative potential relative to cells with higher Dsg3 expression levels, characteristics consistent with a more "stem/progenitor cell-like" phenotype. Here, we have confirmed that Dsg3(dim) cells derived from cultured primary human adult keratinocytes have comparability with alpha(6)(bri)/CD71(dim) stem cells in terms of colony-forming efficiency. Moreover, these Dsg3(dim) cells exhibit increased reconstituting ability in in vitro organotypic culture on de-epidermalized dermis (DED); they are small, actively cycling cells, and they express elevated levels of various p63 isoforms. In parallel, using the two immortalized keratinocyte cell lines HaCaT and NTERT, we obtained essentially similar though occasionally different findings. Thus, reduced colony-forming efficiency by Dsg3(bri) cells consistently was observed in both cell lines even though the cell cycle profile and levels of p63 isoforms in the bri and dim populations differed between these two cell lines. Dsg3(dim) cells from both immortalized lines produced thicker and better ordered hierarchical structural organization of reconstituted epidermis relative to Dsg3(bri) and sorted control cells. Dsg3(dim) HaCaT cells also show sebocyte-like differentiation in the basal compartment of skin reconstituted after a 4-week organotypic culture. No differences in percentages of side population cells (also a putative marker of stem cells) were detected between Dsg3(dim) and Dsg3(bri) populations. Taken together our data indicate that Dsg3(dim) populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties, although the side population characteristic is not one of these features. Disclosure of potential conflicts of interest is found at the end of this article.

Viscoelastic Properties of Confluent MDCK II Cells Obtained from Force Cycle Experiments.

PubMed

Brückner, Bastian Rouven; Nöding, Helen; Janshoff, Andreas

2017-02-28

The local mechanical properties of cells are frequently probed by force indentation experiments carried out with an atomic force microscope. Application of common contact models provides a single parameter, the Young's modulus, to describe the elastic properties of cells. The viscoelastic response of cells, however, is generally measured in separate microrheological experiments that provide complex shear moduli as a function of time or frequency. Here, we present a straightforward way to obtain rheological properties of cells from regular force distance curves collected in typical force indentation measurements. The method allows us to record the stress-strain relationship as well as changes in the weak power law of the viscoelastic moduli. We derive an analytical function based on the elastic-viscoelastic correspondence principle applied to Hertzian contact mechanics to model both indentation and retraction curves. Rheological properties are described by standard viscoelastic models and the paradigmatic weak power law found to interpret the viscoelastic properties of living cells best. We compare our method with atomic force microscopy-based active oscillatory microrheology and show that the method to determine the power law coefficient is robust against drift and largely independent of the indentation depth and indenter geometry. Cells were subject to Cytochalasin D treatment to provoke a drastic change in the power law coefficient and to demonstrate the feasibility of the approach to capture rheological changes extremely fast and precisely. The method is easily adaptable to different indenter geometries and acquires viscoelastic data with high spatiotemporal resolution. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Design solutions for the solar cell interconnect fatigue fracture problem

NASA Technical Reports Server (NTRS)

Mon, G. R.; Ross, R. G., Jr.

1982-01-01

Mechanical fatigue of solar cell interconnects is a major failure mechanism in photovoltaic arrays. A comprehensive approach to the reliability design of interconnects, together with extensive design data for the fatigue properties of copper interconnects, has been published. This paper extends the previous work, developing failure prediction (fatigue) data for additional interconnect material choices, including aluminum and a variety of copper-Invar and copper-steel claddings. An improved global fatigue function is used to model the probability-of-failure statistics of each material as a function of level and number of cycles of applied strain. Life-cycle economic analyses are used to evaluate the relative merits of each material choce. The copper-Invar clad composites demonstrate superior performance over pure copper. Aluminum results are disappointing.

Instability of lithium bis(fluorosulfonyl)imide (LiFSI)-potassium bis(fluorosulfonyl)imide (KFSI) system with LiCoO2 at high voltage

NASA Astrophysics Data System (ADS)

Zhang, Shu; Li, Wen-Jun; Ling, Shi-Gang; Li, Hong; Zhou, Zhi-Bin; Chen, Li-Quan

2015-07-01

The cycling performance, impedance variation, and cathode surface evolution of the Li/LiCoO2 cell using LiFSI-KFSI molten salt electrolyte are reported. It is found that this battery shows poor cycling performance, with capacity retention of only about 67% after 20 cycles. It is essential to understand the origin of the instability. It is noticed that the polarization voltage and the impedance of the cell both increase slowly upon cycling. The structure and the properties of the pristine and the cycled LiCoO2 cathodes are investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, x-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). It is found that the LiCoO2 particles are corroded by this molten salt electrolyte, and the decomposition by-product covers the surface of the LiCoO2 cathode after 20 cycles. Therefore, the surface side reaction explains the instability of the molten salt electrolyte with LiCoO2. Project supported by the Beijing S&T Project, China (Grant No. Z13111000340000), the National Basic Research Program of China (Grant No. 2012CB932900), and the National Natural Science Foundation of China (Grants Nos. 51325206 and 51421002).

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

PubMed Central

Wong, Yi Li; Wong, Won Fen; Ali Mohd, Mustafa; Hadi, A. Hamid A.

2014-01-01

Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development. PMID:24808916

N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing.

PubMed

Mao, Gaowei; Goswami, Monali; Kalen, Amanda L; Goswami, Prabhat C; Sarsour, Ehab H

2016-01-01

The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) using a uni-directional wound healing assay. NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans.

Characterization of physio-chemical properties of polymeric and electrochemical materials for aerospace flight

NASA Technical Reports Server (NTRS)

Rock, M.; Kunigahalli, V.; Khan, S.; Mcnair, A.

1984-01-01

Sealed nickel cadmium cells having undergone a large number of cycles were discharged using the Hg/HgO reference electrode. The negative electrode exhibited the second plateau. SEM of negative plates of such cells show clusters of large crystals of cadmium hydroxide. These large crystals on the negative plates disappear after continuous overcharging in flooded cells. Atomic Absorption Spectroscopy and standard wet chemical methods are being used to determine the cell materials viz: nickel, cadmium, cobalt, potassum and carbonate. The anodes and cathodes are analyzed after careful examination and the condition of the separator material is evaluated.

Immunomodulatory properties of 1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15.

PubMed

Malfitano, Anna Maria; Laezza, Chiara; Bertini, Simone; Marasco, Daniela; Tuccinardi, Tiziano; Bifulco, Maurizio; Manera, Clementina

2017-04-01

1,2-Dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins. We found that VL15 reduces PBMC proliferation slightly affecting cell vitality, blocks the cell cycle progression and down-regulates the levels of T cell activation markers as well as the expression of phosphorylated proteins, NF-kB, IKKαβ, IKBα, ERK and Akt. VL15 was also used in drug-permeability assays on Caco-2 cell line to evaluate its oral bioavailability and on MDCKII-hMDR1 cell lines to estimate its propensity to cross the blood-brain barrier by passive diffusion, in order to potentially maintain its efficiency on the infiltrating auto-reactive lymphocytes in the central nervous system. In these models, VL15 showed high intestinal absorption and good blood-brain barrier penetration. Our findings suggest that VL15, by controlling the immune response, might find potential application as orally administered drug in pathologies like multiple sclerosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Subpopulation-proteomics in prokaryotic populations.

PubMed

Jahn, Michael; Seifert, Jana; von Bergen, Martin; Schmid, Andreas; Bühler, Bruno; Müller, Susann

2013-02-01

Clonal microbial cells do not behave in an identical manner and form subpopulations during cultivation. Besides varying micro-environmental conditions, cell inherent features like cell cycle dependent localization and concentration of regulatory proteins as well as epigenetic properties are well accepted mechanisms creating cell heterogeneity. Another suspected reason is molecular noise on the transcriptional and translational level. A promising tool to unravel reasons for cell heterogeneity is the combination of cell sorting and subpopulation proteomics. This review summarizes recent developments in prokaryotic single-cell analytics and provides a workflow for selection of single cells, low cell number mass spectrometry, and proteomics evaluation. This approach is useful for understanding the dependency of individual cell decisions on inherent protein profiles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays

PubMed Central

Johnen, Sandra; Meißner, Frank; Krug, Mario; Baltz, Thomas; Endler, Ingolf; Mokwa, Wilfried; Walter, Peter

2016-01-01

Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue. PMID:27200182

Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays.

PubMed

Johnen, Sandra; Meißner, Frank; Krug, Mario; Baltz, Thomas; Endler, Ingolf; Mokwa, Wilfried; Walter, Peter

2016-01-01

Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue.

Characterization and functional analysis of a slow-cycling subpopulation in colorectal cancer enriched by cell cycle inducer combined chemotherapy.

PubMed

Wu, Feng-Hua; Mu, Lei; Li, Xiao-Lan; Hu, Yi-Bing; Liu, Hui; Han, Lin-Tao; Gong, Jian-Ping

2017-10-03

The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo . Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo . Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro . Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.

Characterization and functional analysis of a slow-cycling subpopulation in colorectal cancer enriched by cell cycle inducer combined chemotherapy

PubMed Central

Wu, Feng-Hua; Mu, Lei; Li, Xiao-Lan; Hu, Yi-Bing; Liu, Hui; Han, Lin-Tao; Gong, Jian-Ping

2017-01-01

The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo. Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo. Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro. Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence. PMID:29108242

Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells.

PubMed

Kumar, Vikash; Jagadish, Nirmala; Suri, Anil

2017-08-08

Ovarian cancer represents one of the most common malignancies among women with very high mortality rate worldwide. A-kinase anchor protein 4 (AKAP4), a unique cancer testis (CT) antigen has been shown to be associated with various malignant properties of cancer cells. However, its involvement in various molecular pathways in ovarian cancer remains unknown. In present investigation, employing gene silencing approach, we examined the role of AKAP4 in cell cycle, apoptosis and epithelial-mesenchymal transition (EMT). Further, we also investigated the effect of ablation of AKAP4 on tumor growth in SCID mice ovarian cancer xenograft mouse model. Our results showed that ablation of AKAP4 resulted in increased reactive oxygen species (ROS) generation, DNA damage, cell cycle arrest and apoptosis in ovarian cancer cells. AKAP4 knockdown lead to degradation of protien kinase A (PKA) which was rescued by proteosome inhibitor MG-132. ROS quencher N-acetyl cysteine (NAC) treatment rescued cell cycle arrest and resumed cell division. Subsequently, increased expression of pro-apoptotic molecules and decreased expression of pro-survival/anti-apoptotic factors was observed. As a result of AKAP4 depletion, DNA damage response proteins p-γH2AX, p-ATM and p21 were upregulated. Also, knockdown of CREB resulted in similar findings. Further, PKA inhibitor (H89) and oxidative stress resulted in similar phenotype of ovarian cancer cells as observed in AKAP4 ablated cells. Collectively, for the first time our data showed the involvement of AKAP4 in PKA degradation and perturbed signaling through PKA-CREB axis in AKAP4 ablated ovarian cancer cells.

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets

PubMed Central

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-01-01

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms. PMID:24903657

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.

PubMed

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-06-06

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms.

Characterization of the Properties of Photopatterned Hydrogels for Use in Regenerative Medicine

NASA Astrophysics Data System (ADS)

Fiedler, Callie Irene

The goal of this thesis was to locally photopattern cytocompatible hydrogels to exhibit a wide range of mechanical properties and to probe the fundamental parameters governing these materials printed via stereolithography (SLA). Fabricating cell-laden structures with locally defined mechanical properties is non-trivial because the use of multiple precursor materials is wasteful, slow, and can lead to cell-death. To investigate the range of mechanical properties a single precursor solution can produce, I initially formed a single-network hydrogel and cyclically in- swelled fresh precursor solution followed by photo-exposure of the swollen gel ("swelling + exposure" or SE cycle). Because transport (i.e., diffusion and swelling) can occur on the same time scale as photopolymerization reaction kinetics, I first characterized the variable modulus hydrogels in bulk to isolate the reaction kinetics. In these experiments, I demonstrated the ability modify the mechanical and chemical (i.e., compressive modulus, toughness, crosslink density, swelling ratio) properties by up to 10-fold using only 2-4 SE cycles. I then used the understanding gained via these bulk experiments to locally photopattern the elastic modulus of a cytocompatible hydrogel with pixel-limited resolution (˜10s mum) employing a custom SLA system. Here I demonstrated the ability to fabricate hydrogels with a 500% elastic moduli increase with respect to the unpatterned hydrogel using atomic force microscopy. I monitored monomer attachment to the existing matrix as a function of SE cycle using confocal fluorescence microscopy to characterize the shape and size of printed features. I validated that the dependence of these features on material and processing conditions could be explained by a first-order reaction/diffusion model. With this understanding, I fabricated SLA 3D printed, soft, cytocompatible hydrogels (˜10s kPa) with ˜250 mum channels in addition to fabricating 3D printed stiff, cytocompatible hydrogels (39 MPa) both with ˜10 mum resolution.

Lipoic acid functionalized SiO2@Ag nanoparticles. Synthesis, characterization and evaluation of biological activity.

PubMed

Tudose, Madalina; Culita, Daniela Cristina; Musuc, Adina Magdalena; Somacescu, Simona; Ghica, Cornel; Chifiriuc, Mariana Carmen; Bleotu, Coralia

2017-10-01

A novel nanocomposite was obtained through the covalent immobilization of lipoic acid on the surface of silver nanoparticles-decorated silica nanoparticles (SiO 2 @Ag). The hybrid organic - inorganic material obtained was characterized by Fourier transform infrared spectroscopy, thermal analysis, scanning and transmision electron microscopy, X-ray photoelectron spectroscopy and UV-Visible spectroscopy. Its antioxidant, cytotoxic, antimicrobial activity and influence on mammalian cells cycle were evaluated. The results of this study have shown that the functionalization of SiO 2 @Ag with lipoic acid resulted in a composite with increased specificity of interaction with different mammalian cell lines and antioxidant activity, but with decreased cytotoxicity and antimicrobial properties. Therefore, the SiO 2 @Ag functionalized with lipoic acid could be successfully used in certain concentrations to modulate the cell cycle, in order to obtain the desired anti-proliferative or stimulatory therapeutic effect. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro Antioxidant and Antiproliferative Activities of Various Solvent Fractions from Clerodendrum viscosum Leaves.

PubMed

Shendge, Anil Khushalrao; Basu, Tapasree; Chaudhuri, Dipankar; Panja, Sourav; Mandal, Nripendranath

2017-07-01

Free radicals such as reactive oxygen and nitrogen species, generated in the body, play an important role in the fulfillment of various physiological functions but their imbalance in the body lead to cellular injury and various clinical disorders such as cancer, neurodegenaration, and inflammation. The objective of this study is to fight this problem, natural antioxidant from plants can be considered as possible protective agents against various diseases such as cancer which might also modify the redox microenvironment to reduce the genetic instability. This study was designed to evaluate the antioxidant and antiproliferative potential of Clerodendrum viscosum fractions against various carcinomas. In this present study, 70% methanolic extract of C. viscosum leaves have been fractionated to obtain hexane, chloroform, ethyl acetate, butanol, and water fractions, which were tested for their antioxidant and anticancer properties. It was observed that chloroform and ethyl acetate fractions showed good free radical scavenging properties as well as inhibited the proliferation of human lung cancer (A459), breast (MCF-7), and brain (U87) cells. Moreover, they arrested the cell cycle at G2/M phase of breast and brain cancer. These inhibitory effects were further confirmed by bromodeoxyuridine uptake imaging. Phytochemical investigations further indicate the presence of tannic acid, quercetin, ellagic caid, gallic acid, reserpine, and methyl gallate which might be the reason for these fractions' antioxidant and antiproliferative activities. Clerodendrum viscosum leaf chloroform and Clerodendrum viscosum leaf ethyl acetate fractions from C. viscosum showed good reactive oxygen species and reactive nitrogen species scavenging potential. Both the fractions arrested cell cycle at G2/M phase in MCF-7 and U87 cells which lead to induce apoptosis. Crude extract of Clerodendrum viscosum leaves was fractionated using different solventsAmong them, chloroform and ethyl acetate fractions exhibited excellent free radical scavenging propertiesThe same fractions inhibited the proliferation of human lung cancer (A459), breast (MCF-7), and brain (U87) cellsChloroform and ethyl acetate fractions arrested the cell cycle at G2/M phase of breast and brain cancerPhytochemical investigations further indicate the presence of several bioactive principles present in them. Abbreviations used: CVLME: Clerodendrum viscosum leaf methanolic extract; CVLH: Clerodendrum viscosum leaf hexane; CVLC: Clerodendrum viscosum leaf chloroform; CVLE: Clerodendrum viscosum leaf ethyl acetate; CVLB: Clerodendrum viscosum leaf butanol; CVLW: Clerodendrum viscosum leaf water; BrdU: Bromodeoxyuridine; WST-1: Water soluble tetrazolium salt.

Diel Variations in Optical Properties of Micromonas pusilla, a Prasinophyte

NASA Technical Reports Server (NTRS)

DuRand, Michele D.; Green, Rebecca E.; Sosik, Heidi M.; Olson, Robert J.

2001-01-01

A laboratory experiment was conducted on cultures of Micromonas pusilla, a marine prasinophyte, to investigate how cell growth and division affect the optical properties over the light:dark cycle. Measurements were made of cell size and concentration, attenuation and absorption coefficients, flow cytometric light scattering (in forward and side directions), chlorophyll and carbon content. Refractive index was calculated using the anomalous diffraction approximation Cells were about 1.5 micrometers in diameter and exhibited phased division, with the major division burst occurring during the night. Typical diel variations were observed, with cells increasing in size and light scattering during the day as they photosynthesize and decreasing at night upon division. The cells were in ultradian growth, with more than one division per day, at a light level of 120 Mu-mol photons m/sq/sec. Since these cells are similar in size to small phytoplankton that are typically abundant in field samples, these results can be used in the interpretation of diel variations in light scattering in natural populations of phytoplankton.

Pterostilbene induces apoptosis through caspase activation in ovarian cancer cells.

PubMed

Dong, J; Guo, H; Chen, Y

2016-01-01

Pterostilbene, an analog of resveratrol increasing bioavailability has shown to offer antioxidant and anticancer properties in vitro and in vivo. Dietary compounds with anti-oxidant properties have been shown to gain importance due to therapeutic applications. In addition, compounds with higher bioavailability levels show great interest in present scenario. Thus, the present study aimed at investigating the cytotoxic role of pterostilbene and its mechanism of cell death in ovarian cancer cells line. The effect of pterostilbene was determined on SKOV-3 cells, by cytotoxicity assays, oxidative stress levels, [Ca2+]i levels, mitochondrial depolarization, cell cycle analysis and caspase 3, 8, and 9 activities. The study revealed that pterostilbene offered cytotoxic effect at a concentration of IC50-55 uM. Further, pterostilbene induced reactive oxygen species (ROS) mediated intrinsic pathway of apoptosis through enhancing oxidative stress, [Ca2+]i levels, mitochondrial depolarization, Sub G1 accumulation, and activation of caspase 3 and 9. The study demonstrates for the first time the cytotoxic potential of pterostilbene against ovarian cancer cells.

Biology and relevance of human acute myeloid leukemia stem cells.

PubMed

Thomas, Daniel; Majeti, Ravindra

2017-03-23

Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

Ascorbic Acid-Assisted Eco-friendly Synthesis of NiCo2O4 Nanoparticles as an Anode Material for High-Performance Lithium-Ion Batteries

NASA Astrophysics Data System (ADS)

Karunakaran, Gopalu; Maduraiveeran, Govindhan; Kolesnikov, Evgeny; Balasingam, Suresh Kannan; Viktorovich, Lysov Dmitry; Ilinyh, Igor; Gorshenkov, Mikhail V.; Sasidharan, Manickam; Kuznetsov, Denis; Kundu, Manab

2018-05-01

We have synthesized NiCo2O4 nanoparticles (NCO NPs) using an ascorbic acid-assisted co-precipitation method for the first time. When NCO NPs are used as an anode material for lithium-ion batteries, the cell exhibits superior lithium storage properties, such as high capacity (700 mA h g-1 after 300 cycles at 200 mA g-1), excellent rate capabilities (applied current density range 100-1200 mA g-1), and impressive cycling stability (at 1200 mA g-1 up to 650 cycles). The enhanced electrochemical properties of NCO NPs are due to the nanometer dimensions which not only offers a smooth charge-transport pathway and short diffusion paths of the lithium ions but also adequate spaces for volume expansion during Li storage. Hence, this eco-friendly synthesis approach will provide a new strategy for the synthesis of various nanostructured metal oxide compounds, for energy conversion and storage systems applications.

Material-induced Senescence (MIS): Fluidity Induces Senescent Type Cell Death of Lung Cancer Cells via Insulin-Like Growth Factor Binding Protein 5.

PubMed

Mano, Sharmy Saimon; Uto, Koichiro; Ebara, Mitsuhiro

2017-01-01

Objective: We propose here material-induced senescence (MIS) as a new therapeutic concept that limits cancer progression by stable cell cycle arrest. This study examined for the first time the effect of material fluidity on cellular senescence in lung carcinoma using poly(ε-caprolactone- co -D, L-lactide) (P(CL- co -DLLA)) with tunable elasticity and fluidity. Methods: The fluidity was varied by chemically crosslinking the polymer networks: the crosslinked P(CL- co -DLLA) shows solid-like properties with a stiffness of 260 kPa, while the non-crosslinked polymer exists in a quasi-liquid state with loss and storage moduli of 33 kPa and 11 kPa, respectively. Results: We found that cancer cells growing on the non-crosslinked, fluidic substrate undergo a non-apoptotic form of cell death and the cell cycle was accumulated in a G0/G1 phase. Next, we investigated the expression of biomarkers that are associated with cancer pathways. The cancer cells on the fluidic substrate expressed several biomarkers associated with senescence such as insulin-like growth factor binding protein 5 (IGFBP5). This result indicates that when cancer cells sense fluidity in their surroundings, the cells express IGFBP5, which in turn triggers the expression of tumor suppressor protein 53 and initiates cell cycle arrest at the G1 phase followed by cellular senescence. Furthermore, the cancer cells on the fluidic substrate maintained their epithelial phenotype, suggesting that the cancer cells do not undergo epithelial to mesenchymal transition. Conclusion: By considering these results as the fundamental information for MIS, our system could be applied to induce senescence in treatment-resistant cancers such as metastatic cancer or cancer stem cells.

Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line

PubMed Central

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Abdul, Ahmad Bustamam; Zeenathul, Nazariah Allaudin; Othman, Hemn Hassan; Yeap, Swee Keong; How, Chee Wun; Hafiza, Wan Abd Ghani Wan Nor

2014-01-01

This investigation evaluated the antileukemia properties of a zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat) cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans. PMID:24549090

Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A.

PubMed

Zhang, Xuan; Samadi, Abbas K; Roby, Katherine F; Timmermann, Barbara; Cohen, Mark S

2012-03-01

Withaferin A, a natural withanolide, has shown anti-cancer properties in various cancers including breast cancer, but its effects in ovarian cancer remain unexplored. Notch 1 and Notch3 are critically involved in ovarian cancer progression. We decided to examine the effects of Withaferin A in ovarian carcinoma cell lines and its molecular mechanism of action including its regulation of Notch. The effects of Withaferin A were examined in CaOV3 and SKOV3 ovarian carcinoma cell lines using MTS assay, clonogenic assay, annexin V/propidium iodide flow cytometry, and cell cycle analysis. Western analysis was conducted to examine the molecular mechanisms of action. Withaferin A inhibited the growth and colony formation of CaOV3 and SKOV3 cells by inducing apoptosis and cell cycle arrest. These changes correlated with down-regulation of Notch1, Notch3, cdc25C, total and phosphorylated Akt, and bcl-2 proteins. Withaferin A inhibits CaOV3 and SKOV3 ovarian carcinoma cell growth, at least in part by targeting Notch1 and Notch3. Copyright © 2011 Elsevier Inc. All rights reserved.

Cell surface acid-base properties of the cyanobacterium Synechococcus: Influences of nitrogen source, growth phase and N:P ratios

NASA Astrophysics Data System (ADS)

Liu, Yuxia; Alessi, D. S.; Owttrim, G. W.; Kenney, J. P. L.; Zhou, Qixing; Lalonde, S. V.; Konhauser, K. O.

2016-08-01

The distribution of many trace metals in the oceans is controlled by biological uptake. Recently, Liu et al. (2015) demonstrated the propensity for a marine cyanobacterium to adsorb cadmium from seawater, suggesting that cell surface reactivity might also play an important role in the cycling of metals in the oceans. However, it remains unclear how variations in cyanobacterial growth rates and nutrient supply might affect the chemical properties of their cellular surfaces. In this study we used potentiometric titrations and Fourier Transform Infrared (FT-IR) spectrometry to profile the key metabolic changes and surface chemical responses of a Synechococcus strain, PCC 7002, during different growth regimes. This included testing various nitrogen (N) to phosphorous (P) ratios (both nitrogen and phosphorous dependent), nitrogen sources (nitrate, ammonium and urea) and growth stages (exponential, stationary, and death phase). FT-IR spectroscopy showed that varying the growth substrates on which Synechococcus cells were cultured resulted in differences in either the type or abundance of cellular exudates produced or a change in the cell wall components. Potentiometric titration data were modeled using three distinct proton binding sites, with resulting pKa values for cells of the various growth conditions in the ranges of 4.96-5.51 (pKa1), 6.67-7.42 (pKa2) and 8.13-9.95 (pKa3). According to previous spectroscopic studies, these pKa ranges are consistent with carboxyl, phosphoryl, and amine groups, respectively. Comparisons between the titration data (for the cell surface) and FT-IR spectra (for the average cellular changes) generally indicate (1) that the nitrogen source is a greater determinant of ligand concentration than growth phase, and (2) that phosphorus limitation has a greater impact on Synechococcus cellular and extracellular properties than does nitrogen limitation. Taken together, these techniques indicate that nutritional quality during cell growth can noticeably influence the expression of cell surface ligands and their measurable densities. Given that cell surface charge ultimately affects metal adsorption, our results suggest that the cycling of metals by Synechococcus cells in the oceans may vary regionally.

ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties.

PubMed

Wang, Fang; Liang, Yong-Ju; Wu, Xing-Ping; Su, Xiao-Dong; Fu, Li-Wu

2012-03-01

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

Growth inhibitory and proapoptotic effects of l-asparaginase from Fusarium culmorum ASP-87 on human leukemia cells (Jurkat).

PubMed

Meghavarnam, Anil K; Salah, Maryam; Sreepriya, Meenakshisundaram; Janakiraman, Savitha

2017-06-01

The objective of this study was to evaluate the anticancer properties of l-asparaginase purified from fungal isolate Fusarium culmorum ASP-87 against human T-cell leukemia cell line (Jurkat). The growth inhibitory and proapoptotic effects of purified l-asparaginase on Jurkat cell lines were investigated by determining its influence on cell viability, colony formation, DNA fragmentation, and cell cycle progression. The results revealed that purified l-asparaginase showed significant decrease in cell survival with IC 50 value of 90 μg/mL (9 IU/mL). The enzyme inhibited colony formation and showed characteristic laddering pattern on agarose gel thereby confirming the induction of apoptosis. Further, cell cycle analysis revealed that the enzyme induced apoptotic cell death by arresting the growth of cells at G 2 -M phase. However, the enzyme did not elicit any toxic effects on human erythrocytes. l-asparaginase purified from F. culmorum ASP-87 showed significant and selective cytotoxic and apoptotic effects on human T-cell leukemic cells in dose-dependent manner. Results of the study give leads for the anticancer effects of fungal l-asparaginase and its potential usefulness in the chemotherapy of leukemia. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Reversible thermodynamic cycle for AMTEC power conversion. [Alkali Metal Thermal-to-Electric Converter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vining, C.B.; Williams, R.M.; Underwood, M.L.

1993-10-01

An AMTEC cell, may be described as performing two distinct energy conversion processes: (i) conversion of heat to mechanical energy via a sodium-based heat engine and (ii) conversion of mechanical energy to electrical energy by utilizing the special properties of the electrolyte material. The thermodynamic cycle appropriate to an alkali metal thermal-to-electric converter cell is discussed for both liquid- and vapor-fed modes of operation, under the assumption that all processes can be performed reversibly. In the liquid-fed mode, the reversible efficiency is greater than 89.6% of Carnot efficiency for heat input and rejection temperatures (900--1,300 and 400--800 K, respectively) typicalmore » of practical devices. Vapor-fed cells can approach the efficiency of liquid-fed cells. Quantitative estimates confirm that the efficiency is insensitive to either the work required to pressurize the sodium liquid or the details of the state changes associated with cooling the low pressure sodium gas to the heat rejection temperature.« less

A study of degradation of plates for nickel-cadmium spacecraft cells. [feasibility of coining

NASA Technical Reports Server (NTRS)

Scott, W. R.

1973-01-01

The relative merits of coining and not coining of sintered nickel-oxide and cadmium plates was investigated. A survey of the industry including cell manufactures and users was made and results summarized. Sample plate materials from most commercial cell suppliers were obtained and characterized for properties that may correlate with the tendency toward physical disintegration during handling and over long periods of time in the cell. Special test methods were developed to obtain comparative data in a short time. A wide range of physical properties and coining thicknesses was observed, resulting in a range of responses. The stronger, less brittle materials resisted loss of sinter better than weaker materials whether or not coined. Coining improved handling and resistance to electrochemical cycling in all materials tested. An apparent exception was found to be due to improper coining of a tapered edge.

Genoprotective properties of astaxanthin revealed by ionizing radiation exposure in vitro on human peripheral blood lymphocytes.

PubMed

Pilinska, M A; Кurinnyi, D A; Rushkovsky, S R; Dybska, O B

2016-12-01

to identify possible radioprotective properties of astaxanthin by means of cytogenetic criteria. Cultivation of peripheral blood lymphocytes from five apparently healthy volunteers; treatment of lym phocytes' cultures by astaxanthin in final concentrations 20 μg/ml in Go phase of mitotic cycle, prior to ? irradia tion in vitro in a dose 1 Gy; cytogenetic analysis the uniformly stained slides of metaphase chromosomes. The elec trophoresis of individual cells (Comet assay); visualization of results under fluorescent microscope; accounting the number of nucleoid the fourth grade that correspond to apoptosis of the cells. Established that astaxanthin in final concentration 20.0 μg/ml exposed to the culture of human peripher al blood lymphocytes in the early G0 phase of mitotic cycle leads to significant reduction of cytogenetic effects induced by gamma irradiation in vitro in dose 1.0 Gy (from 26.05 ± 1.81 to 9.08 ± 0.78 per 100 cells, respectively) and to significant increase the frequency of apoptotic cells at the 48 hour of cultivation (from (3.78 ± 0.24) to (8.26 ± 0.91) %, respectively). The results obtained show the ability of astaxanthin to considerable weakening of radioinduced muta genic effect in human peripheral blood lymphocytes, which testify its powerful radioprotective potential. M. А. Pilinska, D. А. Кurinnyi, S. R. Rushkovsky, О. B. Dybska.

Initial characterization of a low-molecular-weight factor enhancing the checkpoint response.

PubMed

Fan, Xiaoxiang; Cheong, Nge; Iliakis, George

2010-10-01

In higher eukaryotes, DNA double-strand breaks (DSBs) induced by ionizing radiation activate checkpoints that delay progression through the cell cycle. Compared to delays in other phases of the cell cycle, delays induced in G(2) are longer and frequently correlate with resistance to killing by radiation. Therefore, modulation of the G(2) checkpoint offers a means to modulate cellular radiosensitivity. Although compounds are known that reduce the G(2) checkpoint and act as radiosensitizers, compounds enhancing this checkpoint have not been reported. Here we summarize evidence for a factor with such properties. We show that a highly radioresistant rat embryo fibroblast (REF) cell line displays a strong G(2) checkpoint partly as a result of a factor excreted into the growth medium by nonirradiated cells. Various tests indicate that this G(2)-arrest modulating activity (GAMA) is a small molecule showing detectable retention only after passing through filters with a molecular weight cutoff limit of less than 1,000 Da. GAMA is heat stable and resistant to treatment with proteases or nucleases. Electroelution tests show that GAMA is uncharged at neutral pH, a result that is in agreement with the observed failure to bind S- or Q-Sepharose. Investigations on the mechanism of GAMA function indicate ligand-receptor interactions and allow the classification of cells as producers, responders or both. Compounds with properties such as those of GAMA bridge intercellular communication with the DNA damage response and may function as radioprotectors.

Medicinal properties of alpha-santalol, a naturally occurring constituent of sandalwood oil: review.

PubMed

Bommareddy, Ajay; Brozena, Sarah; Steigerwalt, James; Landis, Terra; Hughes, Sarah; Mabry, Erica; Knopp, Aaron; VanWert, Adam L; Dwivedi, Chandradhar

2017-11-13

Alpha-santalol is a naturally occurring sesquiterpene that is derived from sandalwood oil. Its wide range of health benefits have been attributed to the modulation of various signalling pathways involved in the development of a particular disease. For example, the antitumour and cancer preventive properties of alpha-santalol have been shown to involve cell death induction through apoptosis and cell cycle arrest in various cancer models. A marked decrease in inflammatory markers have also been shown with alpha-santalol administration in skin tissue models. The current review is aimed at bringing the most recent advances of alpha-santalol against various disease-specific models and highlighting its associated mechanistic details.

Optical characterization of polymer liquid crystal cell exhibiting polymer blue phases.

PubMed

Zhang, Bao-Yan; Meng, Fan-Bao; Cong, Yue-Hua

2007-08-06

The optical properties of polymer liquid crystal cell exhibiting polymer blue phases (PBPs) have been determined using ultraviolet-visible spectrophotometry, polarizing optical microscopy (POM), differential scanning calorimetry (DSC), X-ray measurements, FTIR imaging and optical rotation technique. PBPs are thermodynamically stabile mesophases, which appear in chiral systems between isotropic and liquid crystal phases. A series of cyclosiloxane-based blue phase polymers were synthesized using a cholesteric LC monomer and a nematic LC monomer, and some of the polymers exhibit PBPs in temperature range over 300 degrees in cooling cycles. The unique property based on their structure and different twists formed and expect to open up new photonic application and enrich polymer blue phase contents and theory.

Apoptosis induction and anti-cancer activity of LeciPlex formulations.

PubMed

Dhawan, Vivek V; Joshi, Ganesh V; Jain, Ankitkumar S; Nikam, Yuvraj P; Gude, Rajiv P; Mulherkar, Rita; Nagarsenker, Mangal S

2014-10-01

Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

Induction of tumor cell death through targeting tubulin and evoking dysregulation of cell cycle regulatory proteins by multifunctional cinnamaldehydes.

PubMed

Nagle, Amrita A; Gan, Fei-Fei; Jones, Gavin; So, Choon-Leng; Wells, Geoffrey; Chew, Eng-Hui

2012-01-01

Multifunctional trans-cinnamaldehyde (CA) and its analogs display anti-cancer properties, with 2-benzoyloxycinnamaldehyde (BCA) and 5-fluoro-2-hydroxycinnamaldehyde (FHCA) being identified as the ortho-substituted analogs that possess potent anti-tumor activities. In this study, BCA, FHCA and a novel analog 5-fluoro-2-benzoyloxycinnamaldehyde (FBCA), were demonstrated to decrease growth and colony formation of human colon-derived HCT 116 and mammary-derived MCF-7 carcinoma cells under non-adhesive conditions. The 2-benzoyloxy and 5-fluoro substituents rendered FBCA more potent than BCA and equipotent to FHCA. The cellular events by which these cinnamaldehydes caused G(2)/M phase arrest and halted proliferation of HCT 116 cells were thereby investigated. Lack of significant accumulation of mitosis marker phospho-histone H3 in cinnamaldehyde-treated cells indicated that the analogs arrested cells in G(2) phase. G(2) arrest was brought about partly by cinnamaldehyde-mediated depletion of cell cycle proteins involved in regulating G(2) to M transition and spindle assembly, namely cdk1, cdc25C, mad2, cdc20 and survivin. Cyclin B1 levels were found to be increased, which in the absence of active cdk1, would fail to drive cells into M phase. Concentrations of cinnamaldehydes that brought about dysregulation of levels of cell cycle proteins also caused tubulin aggregation, as evident from immunodetection of dose-dependent tubulin accumulation in the insoluble cell lysate fractions. In a cell-free system, reduced biotin-conjugated iodoacetamide (BIAM) labeling of tubulin protein pretreated with cinnamaldehydes was indicative of drug interaction with the sulfhydryl groups in tubulin. In conclusion, cinnamaldehydes treatment at proapoptotic concentrations caused tubulin aggregation and dysegulation of cell cycle regulatory proteins cdk1 and cdc25C that contributed at least in part to arresting cells at G(2) phase, resulting in apoptotic cell death characterized by emergence of cleaved forms of caspase 3 and poly (ADP-ribose) polymerase (PARP). Results presented in this study have thus provided further insights into the intricate network of cellular events by which cinnamaldehydes induce tumor cell death.

Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest.

PubMed

Li, Lirong; Sun, Jin; Xia, Shufang; Tian, Xu; Cheserek, Maureen Jepkorir; Le, Guowei

2016-04-01

We investigated the antifungal properties and anti-candidal mechanism of antimicrobial peptide APP. The minimum inhibitory concentration of APP was 8 μM against Candida albicans and Aspeogillus flavus, the concentration against Saccharomyces cerevisiae and Cryptococcus neoformans was 16 μM, while 32 μM inhibited Aspergilla niger and Trichopyton rubrum. APP caused slight depolarization (12.32 ± 0.87%) of the membrane potential of intact C. albicans cells when it exerted its anti-candidal activity and only caused 21.52 ± 0.48% C. albicans cell membrane damage. APP interacted with cell wall membrane, caused potassium efflux and nucleotide leakage. However, confocal fluorescence microscopy experiment and flow cytometry confirmed that FITC-labeled APP penetrated C. albicans cell membrane with 52.31 ± 1.88% cell-penetrating efficiency and accumulated in the cytoplasm. Then, APP interact with C. albicans genomic DNA and completely suppressed DNA migration above weight ratio (peptide/DNA) of 2, and significantly arrested cell cycles during the S-phase (S-phase cell population was 27.09 ± 0.73%, p < 0.05) after penetrating the cell membrane. Results indicated that APP kills C. albicans for efficient cell-penetrating efficiency, strong DNA-binding affinity and significant physiological changes inducing S-phase arrest in intracellular environment.

Releasing metal catalysts via phase transition: (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 as a redox stable anode material for solid oxide fuel cells.

PubMed

Xiao, Guoliang; Wang, Siwei; Lin, Ye; Zhang, Yanxiang; An, Ke; Chen, Fanglin

2014-11-26

Donor-doped perovskite-type SrTiO3 experiences stoichiometric changes at high temperatures in different Po2 involving the formation of Sr or Ti-rich impurities. NiO is incorporated into the stoichiometric strontium titanate, SrTi0.8Nb0.2O3-δ (STN), to form an A-site deficient perovskite material, (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 (Ni-STN), for balancing the phase transition. Metallic Ni nanoparticles can be released upon reduction instead of forming undesired secondary phases. This material design introduces a simple catalytic modification method with good compositional control of the ceramic backbones, by which transport property and durability of solid oxide fuel cell anodes are largely determined. Using Ni-STN as anodes for solid oxide fuel cells, enhanced catalytic activity and remarkable stability in redox cycling have been achieved. Electrolyte-supported cells with the cell configuration of Ni-STN-SDC anode, La0.8Sr0.2Ga0.87Mg0.13O3 (LSGM) electrolyte, and La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) cathode produce peak power densities of 612, 794, and 922 mW cm(-2) at 800, 850, and 900 °C, respectively, using H2 as the fuel and air as the oxidant. Minor degradation in fuel cell performance resulted from redox cycling can be recovered upon operating the fuel cells in H2. Such property makes Ni-STN a promising regenerative anode candidate for solid oxide fuel cells.

TOPOTACTIC LITHIUM INSERTION/EXTRACTION PROPERTIES OF A NEW POLYANION MATERIAL LiXCo2(MoO4)3 [0 ≤ X < 3] FOR RECHARGEABLE LITHIUM BATTERIES

NASA Astrophysics Data System (ADS)

Begam, K. M.; Michael, M. S.; Prabaharan, S. R. S.

An open framework type new material LixCo2(MoO4)3 [0 ≤ x < 3] possessing NASICON structure was identified as positive electrode material for use in 3V class lithium batteries. The new material was synthesized in its non-lithiated phase employing a metal/organic precursor method using a soft-combustion approach. We report here on the structural and electrochemical Li+ insertion/extraction properties of the resultant product. XRD revealed a single phase Co2(MoO4)3 powders and the annealed powders were found to contain ultrafine spherical grains. The redox behavior of the new material was demonstrated in lithium containing cells using the conventional wet cell configuration under Li+ aprotic organic electrolyte environment. The material offered a discharge capacity of 110 mAh/g between 3.5V and 1.5V during the first cycle and 50% of the initial capacity was retained at the end of 20th cycle.

Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression.

PubMed

Tseng, Tsui-Hwa; Chien, Ming-Hsien; Lin, Wea-Lung; Wen, Yu-Ching; Chow, Jyh-Ming; Chen, Chi-Kuan; Kuo, Tsang-Chih; Lee, Wei-Jiunn

2017-02-01

Apigenin (4',5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21 WAF1/CIP1 and increased the interaction of p21 WAF1/CIP1 with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21 WAF1/CIP1 promoter region, resulting in the increase of p21 WAF1/CIP1 transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21 WAF1/CIP1 and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017. © 2016 Wiley Periodicals, Inc.

Semi-automatic spray pyrolysis deposition of thin, transparent, titania films as blocking layers for dye-sensitized and perovskite solar cells

PubMed Central

Krýsová, Hana; Kavan, Ladislav

2018-01-01

For proper function of the negative electrode of dye-sensitized and perovskite solar cells, the deposition of a nonporous blocking film is required on the surface of F-doped SnO2 (FTO) glass substrates. Such a blocking film can minimise undesirable parasitic processes, for example, the back reaction of photoinjected electrons with the oxidized form of the redox mediator or with the hole-transporting medium can be avoided. In the present work, thin, transparent, blocking TiO2 films are prepared by semi-automatic spray pyrolysis of precursors consisting of titanium diisopropoxide bis(acetylacetonate) as the main component. The variation in the layer thickness of the sprayed films is achieved by varying the number of spray cycles. The parameters investigated in this work were deposition temperature (150, 300 and 450 °C), number of spray cycles (20–200), precursor composition (with/without deliberately added acetylacetone), concentration (0.05 and 0.2 M) and subsequent post-calcination at 500 °C. The photo-electrochemical properties were evaluated in aqueous electrolyte solution under UV irradiation. The blocking properties were tested by cyclic voltammetry with a model redox probe with a simple one-electron-transfer reaction. Semi-automatic spraying resulted in the formation of transparent, homogeneous, TiO2 films, and the technique allows for easy upscaling to large electrode areas. The deposition temperature of 450 °C was necessary for the fabrication of highly photoactive TiO2 films. The blocking properties of the as-deposited TiO2 films (at 450 °C) were impaired by post-calcination at 500 °C, but this problem could be addressed by increasing the number of spray cycles. The modification of the precursor by adding acetylacetone resulted in the fabrication of TiO2 films exhibiting perfect blocking properties that were not influenced by post-calcination. These results will surely find use in the fabrication of large-scale dye-sensitized and perovskite solar cells. PMID:29719764

Classification of Bacillus beneficial substances related to plants, humans and animals.

PubMed

Mongkolthanaruk, Wiyada

2012-12-01

Genus Bacillus is a spore-forming bacterium that has unique properties in cell differentiation, allowing the forming of spores in stress conditions and activated in the vegetative cell, with suitable environments occurring during the life cycle acting as a trigger. Their habitat is mainly in soil; thus, many species of Bacillus are associated with plants as well as rhizosphere bacteria and endophytic bacteria. Signal transduction is the principal mechanism of interactions, both within the cell community and with the external environment, which provides the subsequent functions or properties for the cell. The antimicrobial compounds of Bacillus sp. are potentially useful products, which have been used in agriculture for the inhibition of phytopathogens, for the stimulation of plant growth, and in the food industry as probiotics. There are two systems for the synthesis of these substances: nonribosomal synthesis of cyclic lipopeptides (NRPS) and polyketides (PKS). For each group, the structures, properties, and genes of the main products are described. The different compounds described and the way in which they co-exist exhibit the relationship of Bacillus substances to plants, humans, and animals.

Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process.

PubMed

Laranjeiro, Ricardo; Tamai, T Katherine; Letton, William; Hamilton, Noémie; Whitmore, David

2018-04-01

Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles.

Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process

PubMed Central

Tamai, T. Katherine; Letton, William; Hamilton, Noémie; Whitmore, David

2018-01-01

Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles. PMID:29444612

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Hui; Wei, Yang; Wang, Cheng

The excessive volume changes during cell cycling of Si-based anode in lithium ion batteries impeded its application. One major reason for the cell failure is particle isolation during volume shrinkage in delithiation process, which makes strong adhesion between polymer binder and anode active material particles a highly desirable property. Here, a biomimetic side-chain conductive polymer incorporating catechol, a key adhesive component of the mussel holdfast protein, was synthesized. Atomic force microscopy-based single-molecule force measurements of mussel-inspired conductive polymer binder contacting a silica surface revealed a similar adhesion toward substrate when compared with an effective Si anode binder, homo-poly(acrylic acid), withmore » the added benefit of being electronically conductive. Electrochemical experiments showed a very stable cycling of Si-alloy anodes realized via this biomimetic conducting polymer binder, leading to a high loading Si anode with a good rate performance. We attribute the ability of the Si-based anode to tolerate the volume changes during cycling to the excellent mechanical integrity afforded by the strong interfacial adhesion of the biomimetic conducting polymer.« less

The Citrus Flavanone Naringenin Protects Myocardial Cells against Age-Associated Damage

PubMed Central

Costa, Barbara; Cavallini, Chiara; Testai, Lara; Martelli, Alma; Calderone, Vincenzo; Martini, Claudia

2017-01-01

In recent years, the health-promoting effects of the citrus flavanone naringenin have been examined. The results have provided evidence for the modulation of some key mechanisms involved in cellular damage by this compound. In particular, naringenin has been revealed to have protective properties such as an antioxidant effect in cardiometabolic disorders. Very recently, beneficial effects of naringenin have been demonstrated in old rats. Because aging has been demonstrated to be directly related to the occurrence of cardiac disorders, in the present study, the ability of naringenin to prevent cardiac cell senescence was investigated. For this purpose, a cellular model of senescent myocardial cells was set up and evaluated using colorimetric, fluorimetric, and immunometric techniques. Relevant cellular senescence markers, such as X-gal staining, cell cycle regulator levels, and the percentage of cell cycle-arrested cells, were found to be reduced in the presence of naringenin. In addition, cardiac markers of aging-induced damage, including radical oxidative species levels, mitochondrial metabolic activity, mitochondrial calcium buffer capacity, and estrogenic signaling functions, were also modulated by the compound. These results suggested that naringenin has antiaging effects on myocardial cells. PMID:28386313

Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells.

PubMed

Zhao, Guangming; Han, Xiaodong; Cheng, Wei; Ni, Jing; Zhang, Yunfei; Lin, Jingrong; Song, Zhiqi

2017-04-01

Malignant melanoma is the most invasive and fatal form of cutaneous cancer. Moreover it is extremely resistant to conventional chemotherapy and radiotherapy. Apigenin, a non-mutagenic flavonoid, has been found to exhibit chemopreventive and/or anticancerogenic properties in many different types of human cancer cells. Therefore, apigenin may have particular relevance for development as a chemotherapeutic agent for cancer treatment. In the present study, we investigated the effects of apigenin on the viability, migration and invasion potential, dendrite morphology, cell cycle distribution, apoptosis, phosphorylation of the extracellular signal-regulated protein kinase (ERK) and the AKT/mTOR signaling pathway in human melanoma A375 and C8161 cell lines in vitro. Apigenin effectively suppressed the proliferation of melanoma cells in vitro. Moreover, it inhibited cell migration and invasion, lengthened the dendrites, and induced G2/M phase arrest and apoptosis. Furthermore, apigenin promoted the activation of cleaved caspase-3 and cleaved PARP proteins and decreased the expression of phosphorylated (p)‑ERK1/2 proteins, p-AKT and p-mTOR. Consequently, apigenin is a novel therapeutic candidate for melanoma.

Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells.

PubMed

Shi, Wei; Deng, Jiagang; Tong, Rongsheng; Yang, Yong; He, Xia; Lv, Jianzhen; Wang, Hailian; Deng, Shaoping; Qi, Ping; Zhang, Dingding; Wang, Yi

2016-04-01

Mangiferin, which is a C‑glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources, has recently gained attention due to its various biological activities. The present study aimed to determine the apoptotic effects of mangiferin on A549 human lung adenocarcinoma cells. In vitro studies demonstrated that mangiferin exerted growth‑inhibitory and apoptosis-inducing effects against A549 cells. In addition, mangiferin exhibited anti-tumor properties in A549 xenograft mice in vivo. Mangiferin triggered G2/M phase cell cycle arrest via downregulating the cyclin-dependent kinase 1-cyclin B1 signaling pathway, and induced apoptotic cell death by inhibiting the protein kinase C-nuclear factor-κB pathway. In addition, mangiferin was able to enhance the antiproliferative effects of cisplatin on A549 cells, thus indicating the potential for a combined therapy. Notably, mangiferin exerted anticancer effects in vivo, where it was able to markedly decrease the volume and weight of subcutaneous tumor mass, and expand the lifespan of xenograft mice. The present study clarified the molecular mechanisms underlying mangiferin-induced antitumor activities, and suggested that mangiferin may be considered a potential antineoplastic drug for the future treatment of cancer.

The effect of thermal cycling on the structure and properties of a Co, Cr, Ni-TaC directionally solidified eutectic composite

NASA Technical Reports Server (NTRS)

Dunlevey, F. M.; Wallace, J. F.

1973-01-01

The effect of thermal cycling on the structure and properties of a cobalt, chromium, nickel, tantalum carbide directionally solidified eutectic composite is reported. It was determined that the stress rupture properties of the alloy were decreased by the thermal cycling. The loss in stress rupture properties varied with the number of cycles with the loss in properties after about 200 cycles being relatively high. The formation of serrations and the resulting changes in the mechanical properties of the material are discussed.

Disabled infectious single cycle-herpes simplex virus (DISC-HSV) as a vector for immunogene therapy of cancer.

PubMed

Rees, Robert C; McArdle, Stephanie; Mian, Shahid; Li, Geng; Ahmad, Murrium; Parkinson, Richard; Ali, Selman A

2002-02-01

Disabled infectious single cycle-herpes simplex viruses (DISC-HSV) have been shown to be safe for use in humans and may be considered efficacious as vectors for immunogene therapy in cancer. Preclinical studies show that DISC-HSV is an efficient delivery system for cytokine genes and antigens. DISC-HSV infects a high proportion of cells, resulting in rapid gene expression for at least 72 h. The DISC-HSV-mGM-CSF vector, when inoculated into tumors, induces tumor regression in a high percentage of animals, concomitant with establishing a cytotoxic T-cell response, which is MHC class I restricted and directed against peptides of known tumor antigens. The inherent properties of DISC-HSV makes it a suitable vector for consideration in human immunogene therapy trials.

The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability

PubMed Central

Dilworth, David; Gudavicius, Geoff; Xu, Xiaoxue; Boyce, Andrew K J; O’Sullivan, Connor; Serpa, Jason J; Bilenky, Misha; Petrochenko, Evgeniy V; Borchers, Christoph H; Hirst, Martin; Swayne, Leigh Anne; Howard, Perry; Nelson, Christopher J

2018-01-01

Abstract FK506 binding proteins (FKBPs) catalyze the interconversion of cis-trans proline conformers in proteins. Importantly, FK506 drugs have anti-cancer and neuroprotective properties, but the effectors and mechanisms underpinning these properties are not well understood because the cellular function(s) of most FKBP proteins are unclear. FKBP25 is a nuclear prolyl isomerase that interacts directly with nucleic acids and is associated with several DNA/RNA binding proteins. Here, we show the catalytic FKBP domain binds microtubules (MTs) directly to promote their polymerization and stabilize the MT network. Furthermore, FKBP25 associates with the mitotic spindle and regulates entry into mitosis. This interaction is important for mitotic spindle dynamics, as we observe increased chromosome instability in FKBP25 knockdown cells. Finally, we provide evidence that FKBP25 association with chromatin is cell-cycle regulated by Protein Kinase C phosphorylation. This disrupts FKBP25–DNA contacts during mitosis while maintaining its interaction with the spindle apparatus. Collectively, these data support a model where FKBP25 association with chromatin and MTs is carefully choreographed to ensure faithful genome duplication. Additionally, they highlight that FKBP25 is a MT-associated FK506 receptor and potential therapeutic target in MT-associated diseases. PMID:29361176

RNA-seq analysis of Drosophila clock and non-clock neurons reveals neuron-specific cycling and novel candidate neuropeptides.

PubMed

Abruzzi, Katharine C; Zadina, Abigail; Luo, Weifei; Wiyanto, Evelyn; Rahman, Reazur; Guo, Fang; Shafer, Orie; Rosbash, Michael

2017-02-01

Locomotor activity rhythms are controlled by a network of ~150 circadian neurons within the adult Drosophila brain. They are subdivided based on their anatomical locations and properties. We profiled transcripts "around the clock" from three key groups of circadian neurons with different functions. We also profiled a non-circadian outgroup, dopaminergic (TH) neurons. They have cycling transcripts but fewer than clock neurons as well as low expression and poor cycling of clock gene transcripts. This suggests that TH neurons do not have a canonical circadian clock and that their gene expression cycling is driven by brain systemic cues. The three circadian groups are surprisingly diverse in their cycling transcripts and overall gene expression patterns, which include known and putative novel neuropeptides. Even the overall phase distributions of cycling transcripts are distinct, indicating that different regulatory principles govern transcript oscillations. This surprising cell-type diversity parallels the functional heterogeneity of the different neurons.

Dendrobium chrysanthum ethanolic extract induces apoptosis via p53 up-regulation in HeLa cells and inhibits tumor progression in mice.

PubMed

Prasad, Ritika; Rana, Nishant Kumar; Koch, Biplob

2017-06-01

Background Dendrobium is one of the diverse genus of orchid plants. It possesses a number of pharmacological activities and has long been used in traditional system of medicine. The goal of this study was to investigate the apoptosis inducing property of the ethanolic extract from the leaves of Dendrobium chrysanthum, a species of Dendrobium whose anticancer role has not been ascertained yet. Methods To evaluate the anticancer activity of the ethanolic extract of D. chrysanthum in vitro in HeLa (human cervical cancer) cells, cytotoxic activity, generation of reactive oxygen species (ROS), induction of apoptosis and effect on cell cycle were determined. The in vivo study was carried out in Dalton's lymphoma (DL) bearing mice to assess the tumor growth delay. Results Our study demonstrated that the ethanolic extract showed dose-dependent cytotoxicity against HeLa cells. The extract exhibited dose-dependent increase in ROS production as well as apoptotic cell death which was further confirmed through presence of DNA fragmentation. Cell cycle analysis by flow cytometry suggests that the ethanolic extract perturbed cell cycle progression and leads to the delay of the cells in S phase. Further, the real-time PCR studies also showed up-regulation of apoptotic genes p53 and Bax. The in vivo antitumor activity exhibited significant increase in the life span of DL bearing mice as compared to control with significant decrease in abdominal size along with reduced tumor ascites. Conclusions These observations demonstrate the anticancer potential of the D. chrysanthum ethanolic extract mediated through p53-dependent apoptosis.

N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing

PubMed Central

Mao, Gaowei; Goswami, Monali; Kalen, Amanda L.; Goswami, Prabhat C.; Sarsour, Ehab H.

2016-01-01

Background The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) in this study. Methods and Results By using a uni-directional wound healing assay, NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. Conclusions These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans. PMID:26671656

Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest.

PubMed

Zargan, Jamil; Sajad, Mir; Umar, Sadiq; Naime, Mohammad; Ali, Shakir; Khan, Haider A

2011-08-01

The purpose of study was to examine the cytotoxic and anti-cancer properties along with addressing the plausible pathway followed by scorpion venom to reduce cell viability in SH-SY5Y and MCF-7 cells. Following exposure of cells with scorpion venom, cytotoxicity was estimated using MTT and lactate dehydrogenase assays. Apoptotic effects were measured by assessment of mitochondrial membrane potential, reactive nitrogen species, DNA fragmentation, and caspase-3 activity whereas antiproliferative effect was assayed using BrdU incorporation. Our results indicate that scorpion venom causes suppression of proliferation by arresting S-phase and induction of apoptosis through increased nitric oxide production, caspase-3 activity and depolarization of mitochondrial membrane. Induction of apoptosis and arrest of DNA synthesis are critical determinant factors for development of anti cancer drugs. These properties may lead to isolation of effective molecule(s) with potential anticancer activity from scorpion venom of Androctonus crassicauda. Copyright © 2011 Elsevier Inc. All rights reserved.

In Situ Encapsulating α-MnS into N,S-Codoped Nanotube-Like Carbon as Advanced Anode Material: α → β Phase Transition Promoted Cycling Stability and Superior Li/Na-Storage Performance in Half/Full Cells.

PubMed

Liu, Dai-Huo; Li, Wen-Hao; Zheng, Yan-Ping; Cui, Zheng; Yan, Xin; Liu, Dao-Sheng; Wang, Jiawei; Zhang, Yu; Lü, Hong-Yan; Bai, Feng-Yang; Guo, Jin-Zhi; Wu, Xing-Long

2018-04-02

Incorporation of N,S-codoped nanotube-like carbon (N,S-NTC) can endow electrode materials with superior electrochemical properties owing to the unique nanoarchitecture and improved kinetics. Herein, α-MnS nanoparticles (NPs) are in situ encapsulated into N,S-NTC, preparing an advanced anode material (α-MnS@N,S-NTC) for lithium-ion/sodium-ion batteries (LIBs/SIBs). It is for the first time revealed that electrochemical α → β phase transition of MnS NPs during the 1st cycle effectively promotes Li-storage properties, which is deduced by the studies of ex situ X-ray diffraction/high-resolution transmission electron microscopy and electrode kinetics. As a result, the optimized α-MnS@N,S-NTC electrode delivers a high Li-storage capacity (1415 mA h g -1 at 50 mA g -1 ), excellent rate capability (430 mA h g -1 at 10 A g -1 ), and long-term cycling stability (no obvious capacity decay over 5000 cycles at 1 A g -1 ) with retained morphology. In addition, the N,S-NTC-based encapsulation plays the key roles on enhancing the electrochemical properties due to its high conductivity and unique 1D nanoarchitecture with excellent protective effects to active MnS NPs. Furthermore, α-MnS@N,S-NTC also delivers high Na-storage capacity (536 mA h g -1 at 50 mA g -1 ) without the occurrence of such α → β phase transition and excellent full-cell performances as coupling with commercial LiFePO 4 and LiNi 0.6 Co 0.2 Mn 0.2 O 2 cathodes in LIBs as well as Na 3 V 2 (PO 4 ) 2 O 2 F cathode in SIBs. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature as a universal resetting cue for mammalian circadian oscillators

PubMed Central

Buhr, Ethan D.; Yoo, Seung-Hee; Takahashi, Joseph S.

2011-01-01

Environmental temperature cycles are a universal entraining cue for all circadian systems at the organismal level with the exception of homeothermic vertebrates. We report here that resistance to temperature entrainment is a property of the suprachiasmatic nucleus (SCN) network and is not a cell autonomous property of mammalian clocks. This differential sensitivity to temperature allows the SCN to drive circadian rhythms in body temperature which can then act as a universal cue for the entrainment of cell autonomous oscillators throughout the body. Pharmacological experiments show that network interactions in the SCN are required for temperature resistance and that the heat shock pathway is integral to temperature resetting and temperature compensation in mammalian cells. These results suggest that the evolutionarily ancient temperature resetting response can be utilized in homeothermic animals to enhance internal circadian synchronization. PMID:20947768

Temperature as a universal resetting cue for mammalian circadian oscillators.

PubMed

Buhr, Ethan D; Yoo, Seung-Hee; Takahashi, Joseph S

2010-10-15

Environmental temperature cycles are a universal entraining cue for all circadian systems at the organismal level with the exception of homeothermic vertebrates. We report here that resistance to temperature entrainment is a property of the suprachiasmatic nucleus (SCN) network and is not a cell-autonomous property of mammalian clocks. This differential sensitivity to temperature allows the SCN to drive circadian rhythms in body temperature, which can then act as a universal cue for the entrainment of cell-autonomous oscillators throughout the body. Pharmacological experiments show that network interactions in the SCN are required for temperature resistance and that the heat shock pathway is integral to temperature resetting and temperature compensation in mammalian cells. These results suggest that the evolutionarily ancient temperature resetting response can be used in homeothermic animals to enhance internal circadian synchronization.

Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation.

PubMed

Samokhvalov, V; Ignatov, V; Kondrashova, M

2004-01-01

We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), alpha-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.

The Flavonoid Jaceosidin from Artemisia princeps Induces Apoptotic Cell Death and Inhibits the Akt Pathway in Oral Cancer Cells.

PubMed

Han, Hye-Yeon; Kim, Hyung Joon; Jeong, Seung-Hwa; Kim, Jiyeon; Jeong, Sung-Hee; Kim, Gyoo Cheon; Hwang, Dae-Seok; Kim, Uk-Kyu; Ryu, Mi Heon

2018-01-01

Jaceosidin is a single compound from the Japanese mugwort Artemisia princeps , which is used as a food and a traditional medicinal herb. A. princeps extracts and flavonoid components have been shown to have antihyperglycaemic, antioxidant, and anti-inflammatory properties. Although the anticancer properties of these extracts were recently demonstrated, the related mechanisms have not been characterised. In this study, we investigated the effects of jaceosidin in oral squamous cell carcinoma (OSCC) cells and initially showed selective suppression of proliferation (IC 50 = 82.1  μ M in HSC-3 cells and 97.5  μ M in Ca9.22 cells) and accumulation of cells at the sub-G1 stage of the cell cycle. In addition, jaceosidin increased cleavage of caspase-9 and caspase-3 in OSCC cells, although caspase-8 was not detected. In further experiments, jaceosidin downregulated Akt phosphorylation and ectopic activation of Akt blocked the antiproliferative effects of jaceosidin. Finally, we showed that jaceosidin has no effects on HaCaT normal epithelial cell viability, indicating selective chemotherapeutic potential of jaceosidin and that tumour-specific downregulation of Akt increases apoptosis and inhibits growth in OSCC cells.

The Flavonoid Jaceosidin from Artemisia princeps Induces Apoptotic Cell Death and Inhibits the Akt Pathway in Oral Cancer Cells

PubMed Central

Han, Hye-Yeon; Kim, Hyung Joon; Jeong, Seung-Hwa; Kim, Jiyeon; Jeong, Sung-Hee; Kim, Gyoo Cheon; Hwang, Dae-Seok; Kim, Uk-Kyu

2018-01-01

Jaceosidin is a single compound from the Japanese mugwort Artemisia princeps, which is used as a food and a traditional medicinal herb. A. princeps extracts and flavonoid components have been shown to have antihyperglycaemic, antioxidant, and anti-inflammatory properties. Although the anticancer properties of these extracts were recently demonstrated, the related mechanisms have not been characterised. In this study, we investigated the effects of jaceosidin in oral squamous cell carcinoma (OSCC) cells and initially showed selective suppression of proliferation (IC50 = 82.1 μM in HSC-3 cells and 97.5 μM in Ca9.22 cells) and accumulation of cells at the sub-G1 stage of the cell cycle. In addition, jaceosidin increased cleavage of caspase-9 and caspase-3 in OSCC cells, although caspase-8 was not detected. In further experiments, jaceosidin downregulated Akt phosphorylation and ectopic activation of Akt blocked the antiproliferative effects of jaceosidin. Finally, we showed that jaceosidin has no effects on HaCaT normal epithelial cell viability, indicating selective chemotherapeutic potential of jaceosidin and that tumour-specific downregulation of Akt increases apoptosis and inhibits growth in OSCC cells. PMID:29861773

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells*

PubMed Central

Borahay, Mostafa A.; Kilic, Gokhan S.; Yallampalli, Chandrasekha; Snyder, Russell R.; Hankins, Gary D. V.; Al-Hendy, Ayman; Boehning, Darren

2014-01-01

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery. PMID:25359773

Momordica charantia: a popular health-promoting vegetable with multifunctionality.

PubMed

Wang, Shuzhen; Li, Zhiliang; Yang, Guliang; Ho, Chi-Tang; Li, Shiming

2017-05-24

Products derived from edible medicinal plants have been used for centuries to prevent, treat, and even cure multiple diseases. Momordica charantia L., widely cultivated around the world, is a typical one bred for vegetables and medicinal usage. All parts of M. charantia possess important medicinal properties, including antidiabetic, anticancer, hypotensive, anti-obesity, antimicrobial, antihyperlipidemic, antioxidant, anti-inflammatory, immuno-modulatory, anthelmintic, neuro-protective, as well as hepato-protective properties both in vitro and in vivo. This review summarizes the active components and medicinal properties of M. charantia, especially the activities and mechanisms of its anti-diabetic and anti-cancer properties. The anti-diabetic properties involve inhibiting intestinal α-glucosidase and glucose transport, protecting islet β-cells, enhancing insulin secretion, increasing hepatic glucose disposal, decreasing gluconeogenesis, and even ameliorating insulin resistance. Moreover, the expressions of PPARs could also be activated and up-regulated. Meanwhile, its anticancer properties are mostly due to apoptosis, cell cycle arrest, and expression of serum factors associated with immunity. In this review, we aim to provide an overview of M. charantia and its benefits for development as a functional food.

Glassy materials for lithium batteries: electrochemical properties and devices performances

NASA Astrophysics Data System (ADS)

Duclot, Michel; Souquet, Jean-Louis

Amorphous or glassy materials may be used as electrolyte or electrode materials for lithium primary or secondary batteries. A first generation proceeded from classical coin cells in which the organic electrolyte was replaced by a high lithium conductive glassy electrolyte. The solid components were assembled under isostatic pressure. The main advantages of such cells are a good storage stability and ability to operate until 200°C. Nevertheless, the high resistivity of the glassy electrolyte below room temperature and a limited depth for charge and discharge cycles makes these cells not competitive compared to conventional lithium-ion batteries. More promising, are the thin films solid state microbatteries realised by successive depositions of electrodes and electrolyte. The low resistance of the electrolyte amorphous layer allows cycling at temperatures as low as -10°C. The total thickness of thin film batteries, including packaging is less than 100 μm. A capacity of about 100 μAh cm -2 with over 10 4 charge-discharge cycles at 90% in depth of discharge is well suited for energy independent smart cards or intelligent labels, which represent for these devices a large and unrivalled market.

Dihydroptychantol A, a macrocyclic bisbibenzyl derivative, induces autophagy and following apoptosis associated with p53 pathway in human osteosarcoma U2OS cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Xia; School of Ocean, Shandong University, Weihai 264209; Wu, William K.K.

2011-03-01

Dihydroptychantol A (DHA), a novel macrocyclic bisbibenzyl compound extracted from liverwort Asterella angusta, has antifungal and multi-drug resistance reversal properties. Here, the chemically synthesized DHA was employed to test its anti-cancer activities in human osteosarcoma U2OS cells. Our results demonstrated that DHA induced autophagy followed by apoptotic cell death accompanied with G{sub 2}/M-phase cell cycle arrest in U2OS cells. DHA-induced autophagy was morphologically characterized by the formation of double membrane-bound autophagic vacuoles recognizable at the ultrastructural level. DHA also increased the levels of LC3-II, a marker of autophagy. Surprisingly, DHA-mediated apoptotic cell death was potentiated by the autophagy inhibitor 3-methyladenine,more » suggesting that autophagy may play a protective role that impedes the eventual cell death. Furthermore, p53 was shown to be involved in DHA-meditated autophagy and apoptosis. In this connection, DHA increased nuclear expression of p53, induced p53 phosphorylation, and upregulated p53 target gene p21{sup Waf1/Cip1}. In contrast, cytoplasmic p53 was reduced by DHA, which contributed to the stimulation of autophagy. In relation to the cell cycle, DHA decreased the expression of cyclin B{sub 1}, a cyclin required for progression through the G{sub 2}/M phase. Taken together, DHA induces G{sub 2}/M-phase cell cycle arrest and apoptosis in U2OS cells. DHA-induced apoptosis was preceded by the induction of protective autophagy. DHA-mediated autophagy and apoptosis are associated with the cytoplasmic and nuclear functions of p53.« less

Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells.

PubMed

Vijayarathna, Soundararajan; Oon, Chern Ein; Chen, Yeng; Kanwar, Jagat R; Sasidharan, Sreenivasan

2017-05-01

Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC 50 ) and pro-oxidant (IC 50 and double IC 50 ) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC 50 concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A map of protein dynamics during cell-cycle progression and cell-cycle exit

PubMed Central

Gookin, Sara; Min, Mingwei; Phadke, Harsha; Chung, Mingyu; Moser, Justin; Miller, Iain; Carter, Dylan

2017-01-01

The cell-cycle field has identified the core regulators that drive the cell cycle, but we do not have a clear map of the dynamics of these regulators during cell-cycle progression versus cell-cycle exit. Here we use single-cell time-lapse microscopy of Cyclin-Dependent Kinase 2 (CDK2) activity followed by endpoint immunofluorescence and computational cell synchronization to determine the temporal dynamics of key cell-cycle proteins in asynchronously cycling human cells. We identify several unexpected patterns for core cell-cycle proteins in actively proliferating (CDK2-increasing) versus spontaneously quiescent (CDK2-low) cells, including Cyclin D1, the levels of which we find to be higher in spontaneously quiescent versus proliferating cells. We also identify proteins with concentrations that steadily increase or decrease the longer cells are in quiescence, suggesting the existence of a continuum of quiescence depths. Our single-cell measurements thus provide a rich resource for the field by characterizing protein dynamics during proliferation versus quiescence. PMID:28892491

Quercetin conjugated with silica nanoparticles inhibits tumor growth in MCF-7 breast cancer cell lines.

PubMed

Aghapour, Fahimeh; Moghadamnia, Ali Akbar; Nicolini, Andrea; Kani, Seydeh Narges Mousavi; Barari, Ladan; Morakabati, Payam; Rezazadeh, Leyla; Kazemi, Sohrab

2018-06-12

Quercetin is a plant polyphenol from the flavonoid group that plays a fundamental role in controlling homeostasis due to its potent antioxidant properties. However, quercetin has extremely low water solubility, which is a major challenge in drug absorption. In this study, we described a simple method for the synthesis of quercetin nanoparticles. The quercetin nanoparticles had an average diameter of 82 nm and prominent yellow emission under UV irradiation. Therefore, we used an in vitro model treated with quercetin and quercetin nanoparticles to investigate the effects of quercetin nanoparticles on MCF-7 breast cancer cell line. MCF-7 cells were cultured with different concentrations (1-100 μM) of quercetin nanoparticles at the 24th, 48th and 72 nd hours, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In this study, we found that quercetin nanoparticles (1-100 μM) could significantly reduce cell vitality, growth rate and colony formation of MCF-7 cells. Quercetin nanoparticles can inhibit cell growth by blocking the cell cycle and promoting apoptosis in MCF-7 cells more than quercetin. As a result, quercetin nanoparticles may be useful therapy or prevention on breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

PubMed

Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua

2017-05-01

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

Senescence-associated reprogramming promotes cancer stemness.

PubMed

Milanovic, Maja; Fan, Dorothy N Y; Belenki, Dimitri; Däbritz, J Henry M; Zhao, Zhen; Yu, Yong; Dörr, Jan R; Dimitrova, Lora; Lenze, Dido; Monteiro Barbosa, Ines A; Mendoza-Parra, Marco A; Kanashova, Tamara; Metzner, Marlen; Pardon, Katharina; Reimann, Maurice; Trumpp, Andreas; Dörken, Bernd; Zuber, Johannes; Gronemeyer, Hinrich; Hummel, Michael; Dittmar, Gunnar; Lee, Soyoung; Schmitt, Clemens A

2018-01-04

Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16 INK4a , p21 CIP1 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from Eμ-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct stem-cell markers in senescence. Using genetically switchable models of senescence targeting H3K9me3 or p53 to mimic spontaneous escape from the arrested condition, we found that cells released from senescence re-entered the cell cycle with strongly enhanced and Wnt-dependent clonogenic growth potential compared to virtually identical populations that had been equally exposed to chemotherapy but had never been senescent. In vivo, these previously senescent cells presented with a much higher tumour initiation potential. Notably, the temporary enforcement of senescence in p53-regulatable models of acute lymphoblastic leukaemia and acute myeloid leukaemia was found to reprogram non-stem bulk leukaemia cells into self-renewing, leukaemia-initiating stem cells. Our data, which are further supported by consistent results in human cancer cell lines and primary samples of human haematological malignancies, reveal that senescence-associated stemness is an unexpected, cell-autonomous feature that exerts its detrimental, highly aggressive growth potential upon escape from cell-cycle blockade, and is enriched in relapse tumours. These findings have profound implications for cancer therapy, and provide new mechanistic insights into the plasticity of cancer cells.

Tailoring cyanobacterial cell factory for improved industrial properties.

PubMed

Luan, Guodong; Lu, Xuefeng

Photosynthetic biomanufacturing provides a promising solution for sustainable production of biofuels and biochemicals. Cyanobacteria are among the most promising microbial platforms for the construction of photosynthetic cell factories. Metabolic engineering of cyanobacteria has enabled effective photosynthetic synthesis of diverse natural or non-natural metabolites, while commercialization of photosynthetic biomanufacturing is usually restricted by process and economic feasibilities. In actual outdoor conditions, active cell growth and product synthesis is restricted to narrow light exposure windows of the day-night cycles and is threatened by diverse physical, chemical, and biological environmental stresses. For biomass harvesting and bioproduct recovery, energy and cost consuming processing and equipment is required, which further decreases the economic and environmental competitiveness of the entire process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts have been made to engineer cyanobacterial cell properties required by robust & continual cultivation and convenient & efficient recovery. In this review, we specifically summarized recently reported engineering strategies on optimizing industrial properties of cyanobacterial cells. Through systematically re-editing the metabolism, morphology, mutualism interaction of cyanobacterial chassis cells, the adaptabilities and compatibilities of the cyanobacterial cell factories to the industrial process could be significantly improved. Cell growth and product synthesis of the tailored cyanobacterial cells could be expanded and maintained at night and in stressful environments, while convenient biomass harvesting could also be expected. For developing more feasible cyanobacterial photosynthetic biomanufacturing in large scale, we here propose the importance of tailoring industrial properties of cyanobacteria and outline the directions that should be exploited in the future. Copyright © 2018 Elsevier Inc. All rights reserved.

Landscape and flux reveal a new global view and physical quantification of mammalian cell cycle

PubMed Central

Li, Chunhe; Wang, Jin

2014-01-01

Cell cycles, essential for biological function, have been investigated extensively. However, enabling a global understanding and defining a physical quantification of the stability and function of the cell cycle remains challenging. Based upon a mammalian cell cycle gene network, we uncovered the underlying Mexican hat landscape of the cell cycle. We found the emergence of three local basins of attraction and two major potential barriers along the cell cycle trajectory. The three local basins of attraction characterize the G1, S/G2, and M phases. The barriers characterize the G1 and S/G2 checkpoints, respectively, of the cell cycle, thus providing an explanation of the checkpoint mechanism for the cell cycle from the physical perspective. We found that the progression of a cell cycle is determined by two driving forces: curl flux for acceleration and potential barriers for deceleration along the cycle path. Therefore, the cell cycle can be promoted (suppressed), either by enhancing (suppressing) the flux (representing the energy input) or by lowering (increasing) the barrier along the cell cycle path. We found that both the entropy production rate and energy per cell cycle increase as the growth factor increases. This reflects that cell growth and division are driven by energy or nutrition supply. More energy input increases flux and decreases barrier along the cell cycle path, leading to faster oscillations. We also identified certain key genes and regulations for stability and progression of the cell cycle. Some of these findings were evidenced from experiments whereas others lead to predictions and potential anticancer strategies. PMID:25228772

Identification of Cell Cycle-Regulated Genes by Convolutional Neural Network.

PubMed

Liu, Chenglin; Cui, Peng; Huang, Tao

2017-01-01

The cell cycle-regulated genes express periodically with the cell cycle stages, and the identification and study of these genes can provide a deep understanding of the cell cycle process. Large false positives and low overlaps are big problems in cell cycle-regulated gene detection. Here, a computational framework called DLGene was proposed for cell cycle-regulated gene detection. It is based on the convolutional neural network, a deep learning algorithm representing raw form of data pattern without assumption of their distribution. First, the expression data was transformed to categorical state data to denote the changing state of gene expression, and four different expression patterns were revealed for the reported cell cycle-regulated genes. Then, DLGene was applied to discriminate the non-cell cycle gene and the four subtypes of cell cycle genes. Its performances were compared with six traditional machine learning methods. At last, the biological functions of representative cell cycle genes for each subtype are analyzed. Our method showed better and more balanced performance of sensitivity and specificity comparing to other machine learning algorithms. The cell cycle genes had very different expression pattern with non-cell cycle genes and among the cell-cycle genes, there were four subtypes. Our method not only detects the cell cycle genes, but also describes its expression pattern, such as when its highest expression level is reached and how it changes with time. For each type, we analyzed the biological functions of the representative genes and such results provided novel insight to the cell cycle mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cell cycle phases in the unequal mother/daughter cell cycles of Saccharomyces cerevisiae.

PubMed

Brewer, B J; Chlebowicz-Sledziewska, E; Fangman, W L

1984-11-01

During cell division in the yeast Saccharomyces cerevisiae mother cells produce buds (daughter cells) which are smaller and have longer cell cycles. We performed experiments to compare the lengths of cell cycle phases in mothers and daughters. As anticipated from earlier indirect observations, the longer cell cycle time of daughter cells is accounted for by a longer G1 interval. The S-phase and the G2-phase are of the same duration in mother and daughter cells. An analysis of five isogenic strains shows that cell cycle phase lengths are independent of cell ploidy and mating type.

Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines.

PubMed

Foglietta, Federica; Serpe, Loredana; Canaparo, Roberto; Vivenza, Nicoletta; Riccio, Giovanna; Imbalzano, Erica; Gasco, Paolo; Zara, Gian Paolo

2014-01-01

Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints. In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis. In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB. Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.

Functional characterization of T cells in abdominal aortic aneurysms.

PubMed

Forester, Nerys D; Cruickshank, Sheena M; Scott, D Julian A; Carding, Simon R

2005-06-01

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4.5 x 10(6) cells per gram of AAA tissue. The majority (58.1+/-5.3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41.1+/-5.7%, natural killer cells 7.3+/-2.5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help.

The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle

PubMed Central

Zhou, Bo; Schrader, Jared M.; Kalogeraki, Virginia S.; Abeliuk, Eduardo; Dinh, Cong B.; Pham, James Q.; Cui, Zhongying Z.; Dill, David L.; McAdams, Harley H.; Shapiro, Lucy

2015-01-01

Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5′ RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle. PMID:25569173

Indirect-fired gas turbine dual fuel cell power cycle

DOEpatents

Micheli, Paul L.; Williams, Mark C.; Sudhoff, Frederick A.

1996-01-01

A fuel cell and gas turbine combined cycle system which includes dual fuel cell cycles combined with a gas turbine cycle wherein a solid oxide fuel cell cycle operated at a pressure of between 6 to 15 atms tops the turbine cycle and is used to produce CO.sub.2 for a molten carbonate fuel cell cycle which bottoms the turbine and is operated at essentially atmospheric pressure. A high pressure combustor is used to combust the excess fuel from the topping fuel cell cycle to further heat the pressurized gas driving the turbine. A low pressure combustor is used to combust the excess fuel from the bottoming fuel cell to reheat the gas stream passing out of the turbine which is used to preheat the pressurized air stream entering the topping fuel cell before passing into the bottoming fuel cell cathode. The CO.sub.2 generated in the solid oxide fuel cell cycle cascades through the system to the molten carbonate fuel cell cycle cathode.

The global regulatory architecture of transcription during the Caulobacter cell cycle.

PubMed

Zhou, Bo; Schrader, Jared M; Kalogeraki, Virginia S; Abeliuk, Eduardo; Dinh, Cong B; Pham, James Q; Cui, Zhongying Z; Dill, David L; McAdams, Harley H; Shapiro, Lucy

2015-01-01

Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5' RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle.

Raman spectrum reveals the cell cycle arrest of Triptolide-induced leukemic T-lymphocytes apoptosis

NASA Astrophysics Data System (ADS)

Zhang, Daosen; Feng, Yanyan; Zhang, Qinnan; Su, Xin; Lu, Xiaoxu; Liu, Shengde; Zhong, Liyun

2015-04-01

Triptolide (TPL), a traditional Chinese medicine extract, possesses anti-inflammatory and anti-tumor properties. Though some research results have implicated that Triptolide (TPL) can be utilized in the treatment of leukemia, it remains controversial about the mechanism of TPL-induced leukemic T-lymphocytes apoptosis. In this study, combining Raman spectroscopic data, principal component analysis (PCA) and atomic force microscopy (AFM) imaging, both the biochemical changes and morphological changes during TPL-induced cell apoptosis were presented. In contrast, the corresponding data during Daunorubicin (DNR)-induced cell apoptosis was also exhibited. The obtained results showed that Raman spectral changes during TPL-induced cell apoptosis were greatly different from DNR-induced cell apoptosis in the early stage of apoptosis but revealed the high similarity in the late stage of apoptosis. Moreover, above Raman spectral changes were respectively consistent with the morphological changes of different stages during TPL-induced apoptosis or DNR-induced apoptosis, including membrane shrinkage and blebbing, chromatin condensation and the formation of apoptotic bodies. Importantly, it was found that Raman spectral changes with TPL-induced apoptosis or DNR-induced apoptosis were respectively related with the cell cycle G1 phase arrest or G1 and S phase arrest.

Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis

PubMed Central

Arora, Sumit; Tyagi, Nikhil; Bhardwaj, Arun; Rusu, Lilia; Palanki, Rohan; Vig, Komal; Singh, Shree R.; Singh, Ajay P.; Palanki, Srinivas; Miller, Michael E.; Carter, James E.; Singh, Seema

2015-01-01

Ultraviolet (UV)-B radiation from the sun is an established etiological cause of skin cancer, which afflicts more than a million lives each year in the United States alone. Here, we tested the chemopreventive efficacy of silver-nanoparticles (AgNPs) against UVB-irradiation-induced DNA damage and apoptosis in human immortalized keratinocytes (HaCaT). AgNPs were synthesized by reduction-chemistry and characterized for their physicochemical properties. AgNPs were well tolerated by HaCaT cells and their pretreatment protected them from UVB-irradiation-induced apoptosis along with significant reduction in cyclobutane-pyrimidine-dimer formation. Moreover, AgNPs pre-treatment led to G1-phase cell-cycle arrest in UVB-irradiated HaCaT cells. AgNPs were efficiently internalized in UVB-irradiated cells and localized into cytoplasmic and nuclear compartments. Furthermore, we observed an altered expression of various genes involved in cell-cycle, apoptosis and nucleotide-excision repair in HaCaT cells treated with AgNPs prior to UVB-irradiation. Together, these findings provide support for potential utility of AgNPs as novel chemopreventive agents against UVB-irradiation-induced skin carcinogenesis. PMID:25804413

Measuring cell cycle progression kinetics with metabolic labeling and flow cytometry.

PubMed

Fleisig, Helen; Wong, Judy

2012-05-22

Precise control of the initiation and subsequent progression through the various phases of the cell cycle are of paramount importance in proliferating cells. Cell cycle division is an integral part of growth and reproduction and deregulation of key cell cycle components have been implicated in the precipitating events of carcinogenesis. Molecular agents in anti-cancer therapies frequently target biological pathways responsible for the regulation and coordination of cell cycle division. Although cell cycle kinetics tend to vary according to cell type, the distribution of cells amongst the four stages of the cell cycle is rather consistent within a particular cell line due to the consistent pattern of mitogen and growth factor expression. Genotoxic events and other cellular stressors can result in a temporary block of cell cycle progression, resulting in arrest or a temporary pause in a particular cell cycle phase to allow for instigation of the appropriate response mechanism. The ability to experimentally observe the behavior of a cell population with reference to their cell cycle progression stage is an important advance in cell biology. Common procedures such as mitotic shake off, differential centrifugation or flow cytometry-based sorting are used to isolate cells at specific stages of the cell cycle. These fractionated, cell cycle phase-enriched populations are then subjected to experimental treatments. Yield, purity and viability of the separated fractions can often be compromised using these physical separation methods. As well, the time lapse between separation of the cell populations and the start of experimental treatment, whereby the fractionated cells can progress from the selected cell cycle stage, can pose significant challenges in the successful implementation and interpretation of these experiments. Other approaches to study cell cycle stages include the use of chemicals to synchronize cells. Treatment of cells with chemical inhibitors of key metabolic processes for each cell cycle stage are useful in blocking the progression of the cell cycle to the next stage. For example, the ribonucleotide reductase inhibitor hydroxyurea halts cells at the G1/S juncture by limiting the supply of deoxynucleotides, the building blocks of DNA. Other notable chemicals include treatment with aphidicolin, a polymerase alpha inhibitor for G1 arrest, treatment with colchicine and nocodazole, both of which interfere with mitotic spindle formation to halt cells in M phase and finally, treatment with the DNA chain terminator 5-fluorodeoxyridine to initiate S phase arrest. Treatment with these chemicals is an effective means of synchronizing an entire population of cells at a particular phase. With removal of the chemical, cells rejoin the cell cycle in unison. Treatment of the test agent following release from the cell cycle blocking chemical ensures that the drug response elicited is from a uniform, cell cycle stage-specific population. However, since many of the chemical synchronizers are known genotoxic compounds, teasing apart the participation of various response pathways (to the synchronizers vs. the test agents) is challenging. Here we describe a metabolic labeling method for following a subpopulation of actively cycling cells through their progression from the DNA replication phase, through to the division and separation of their daughter cells. Coupled with flow cytometry quantification, this protocol enables for measurement of kinetic progression of the cell cycle in the absence of either mechanically- or chemically- induced cellular stresses commonly associated with other cell cycle synchronization methodologies. In the following sections we will discuss the methodology, as well as some of its applications in biomedical research.

The cell cycle as a brake for β-cell regeneration from embryonic stem cells.

PubMed

El-Badawy, Ahmed; El-Badri, Nagwa

2016-01-13

The generation of insulin-producing β cells from stem cells in vitro provides a promising source of cells for cell transplantation therapy in diabetes. However, insulin-producing cells generated from human stem cells show deficiency in many functional characteristics compared with pancreatic β cells. Recent reports have shown molecular ties between the cell cycle and the differentiation mechanism of embryonic stem (ES) cells, assuming that cell fate decisions are controlled by the cell cycle machinery. Both β cells and ES cells possess unique cell cycle machinery yet with significant contrasts. In this review, we compare the cell cycle control mechanisms in both ES cells and β cells, and highlight the fundamental differences between pluripotent cells of embryonic origin and differentiated β cells. Through critical analysis of the differences of the cell cycle between these two cell types, we propose that the cell cycle of ES cells may act as a brake for β-cell regeneration. Based on these differences, we discuss the potential of modulating the cell cycle of ES cells for the large-scale generation of functionally mature β cells in vitro. Further understanding of the factors that modulate the ES cell cycle will lead to new approaches to enhance the production of functional mature insulin-producing cells, and yield a reliable system to generate bona fide β cells in vitro.

Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells

PubMed Central

Johard, Helena; Mahdessian, Diana; Fedr, Radek; Marks, Carolyn; Medalová, Jiřina; Souček, Karel; Lundberg, Emma; Linnarsson, Sten; Bryja, Vítězslav; Sekyrova, Petra; Altun, Mikael; Andäng, Michael

2017-01-01

The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development. PMID:29228002

The Mucin MUC4 and Its Membrane Partner ErbB2 Regulate Biological Properties of Human CAPAN-2 Pancreatic Cancer Cells via Different Signalling Pathways

PubMed Central

Jonckheere, Nicolas; Skrypek, Nicolas; Merlin, Johann; Dessein, Anne Frédérique; Dumont, Patrick; Leteurtre, Emmanuelle; Harris, Ann; Desseyn, Jean-Luc; Susini, Christiane; Frénois, Frédéric; Van Seuningen, Isabelle

2012-01-01

The mucin MUC4 and its membrane partner the ErbB2 oncogenic receptor are potential interacting partners in human pancreatic tumour development. However, the way they function is still largely unknown. In this work, we aimed to identify the cellular mechanisms and the intracellular signalling pathways under the control of both ErbB2 and MUC4 in a human pancreatic adenocarcinomatous cell line. Using co-immunoprecipitation and GST pull-down, we show that MUC4 and ErbB2 interact in the human pancreatic adenocarcinomatous cell line CAPAN-2 via the EGF domains of MUC4. Stable cell clones were generated in which either MUC4 or ErbB2 were knocked down (KD) by a shRNA approach. Biological properties of these cells were then studied in vitro and in vivo. Our results show that ErbB2-KD cells are more apoptotic and less proliferative (decreased cyclin D1 and increased p27kip1 expression) while migration and invasive properties were not altered. MUC4-KD clones were less proliferative with decreased cyclin D1 expression, G1 cell cycle arrest and altered ErbB2/ErbB3 expression. Their migration properties were reduced whereas invasive properties were increased. Importantly, inhibition of ErbB2 and MUC4 expression did not impair the same signalling pathways (inhibition of MUC4 expression affected the JNK pathway whereas that of ErbB2 altered the MAPK pathway). Finally, ErbB2-KD and MUC4-KD cells showed impaired tumour growth in vivo. Our results show that ErbB2 and MUC4, which interact physically, activate different intracellular signalling pathways to regulate biological properties of CAPAN-2 pancreatic cancer cells. PMID:22393391

Determination of thermal properties of commercial Ni-MH cells

NASA Astrophysics Data System (ADS)

Darcy, Eric C.

1994-02-01

The test objectives were to evaluate the electrical and thermal performance of commercial Ni-MH cells, evaluate the effectiveness of commercial charge control circuits, assess the abuse tolerance of these cells, and correlate performance and abuse tolerances to cell design via disassembly. Design objectives were to determine which cell designs are most suitable for scale-up and to guide the design of future shuttle and space station based battery chargers. Results, displayed in viewgraph format, include: reflex charging with ICS circuit resulted in premature charge termination; Ni-MH cells appear very tolerant to overcharge at low rates; Enstore's charger is more electrically and thermally efficient at high rates; and Ni-MH cycles much more efficiently than Ni-Cd with the delta-V/delta-t termination.

Determination of thermal properties of commercial Ni-MH cells

NASA Technical Reports Server (NTRS)

Darcy, Eric C.

1994-01-01

The test objectives were to evaluate the electrical and thermal performance of commercial Ni-MH cells, evaluate the effectiveness of commercial charge control circuits, assess the abuse tolerance of these cells, and correlate performance and abuse tolerances to cell design via disassembly. Design objectives were to determine which cell designs are most suitable for scale-up and to guide the design of future shuttle and space station based battery chargers. Results, displayed in viewgraph format, include: reflex charging with ICS circuit resulted in premature charge termination; Ni-MH cells appear very tolerant to overcharge at low rates; Enstore's charger is more electrically and thermally efficient at high rates; and Ni-MH cycles much more efficiently than Ni-Cd with the delta-V/delta-t termination.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cell - Update II

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1992-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent KOH electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel (IPV) nickel-hydrogen cells has been previously reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40,000 LEO cycles, compared to 3500 cycles for cells containing 31 percent KOH. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min discharge (2X normal rate). The depth-of-discharge was 80 percent. Six 48-Ah Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells), and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The three 31 percent KOH cells failed (cycles 3729, 4165, and 11355). One of the 26 percent KOH cells failed at cycle 15314. The other two 26 percent KOH cells were cycled for over 16,000 cycles during the continuing test.

Concise Review: Regeneration in Mammalian Cochlea Hair Cells: Help from Supporting Cells Transdifferentiation.

PubMed

Franco, Bénédicte; Malgrange, Brigitte

2017-03-01

It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth. Here, we review the molecular mechanisms that are involved in mammalian hair cell development and regeneration. Manipulating pathways used during development constitute good candidates for inducing hair cell regeneration after injury. Despite these promising studies, there is still no evidence for a recovery following hair cells loss in adult mammals. Stem Cells 2017;35:551-556. © 2017 AlphaMed Press.

Life cycle of cytosolic prions.

PubMed

Hofmann, Julia; Vorberg, Ina

2013-01-01

Prions are self-templating protein aggregates that were originally identified as the causative agent of prion diseases in mammals, but have since been discovered in other kingdoms. Mammalian prions represent a unique class of infectious agents that are composed of misfolded prion protein. Prion proteins usually exist as soluble proteins but can refold and assemble into highly ordered, self-propagating prion polymers. The prion concept is also applicable to a growing number of non-Mendelian elements of inheritance in lower eukaryotes. While prions identified in mammals are clearly pathogens, prions in lower eukaryotes can be either detrimental or beneficial to the host. Prion phenotypes in fungi are transmitted vertically from mother to daughter cells during cell division and horizontally during mating or abortive mating, but extracellular phases have not been reported. Recent findings now demonstrate that in a mammalian cell environment, protein aggregates derived from yeast prion domains exhibit a prion life cycle similar to mammalian prions propagated ex vivo. This life cycle includes a soluble state of the protein, an induction phase by exogenous prion fibrils, stable replication of prion entities, vertical transmission to progeny and natural horizontal transmission to neighboring cells. Our data reveal that mammalian cells contain all co-factors required for cytosolic prion propagation and dissemination. This has important implications for understanding prion-like properties of disease-related protein aggregates. In light of the growing number of identified functional amyloids, cell-to-cell propagation of cytosolic protein conformers might not only be relevant for the spreading of disease-associated proteins, but might also be of more general relevance under non-disease conditions.

Differences in the rate of oestrogen-induced apoptosis in breast cancer by oestradiol and the triphenylethylene bisphenol

PubMed Central

Obiorah, I E; Jordan, V C

2014-01-01

Background and Purpose Triphenylethylene (TPE)-like compounds were the first agents to be used in the treatment of metastatic breast cancer in postmenopausal women. Although structurally related to the anti-oestrogen, 4-hydroxytamoxifen, TPEs possess oestrogenic properties in fully oestrogenized breast cancer cells but do not induce apoptosis with short-term treatment in long-term oestrogen-deprived breast cancer cells. This study determined the differential effects of bisphenol, a TPE, on growth and apoptosis based on the modulation of the shape of the ligand–oestrogen receptor complex. Experimental Approach Apoptotic flow cytometric studies were used to evaluate apoptosis over time. Proliferation of the breast cancer cells was assessed using DNA quantification and cell cycle analysis. Real-time PCR was performed to quantify mRNA levels of apoptotic genes. Regulation of cell cycle and apoptotic genes was determined using PCR-based arrays. Key Results Bisphenol induced an up-regulation of cell cycle genes similar to those induced by 17β oestradiol (E2). Unlike the changes induced by E2 that occur after 24 h, the apoptosis evoked by bisphenol occurred after 4 days, with quantifiable apoptotic changes noted at 6 days. A prolonged up-regulation of endoplasmic reticulum stress and inflammatory stress response genes was observed with subsequent activation of apoptosis-related genes in the second week of treatment with bisphenol. Conclusions and Implications The bisphenol: ERα complex induces delayed biological effects on the growth and apoptosis of breast cancer cells. Both the shape of the complex and the duration of treatment control the initiation of apoptosis. PMID:24819221

The cell cycle.

PubMed

Singh, N; Lim, R B; Sawyer, M A

2000-07-01

The cell cycle and the cell cycle control system are the engines that drive life. They allow for the processes of cell renewal and the growth of organisms, under controlled conditions. The control system is essential for the monitoring of normal cell growth and replication of genetic material and to ensure that normal, functional daughter cells are produced at completion of each cell cycle. Although certain clinical applications exist which take advantage of the events of the cell cycle, our understanding of its mechanisms and how to manipulate them is infantile. The next decades will continue to see the effort of many researchers focused upon unlocking the mysteries of the cell cycle and the cell cycle control system.

Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

PubMed

Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

2015-08-01

Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Radioprotective effect of orally administered beta-d-glucan derived from Saccharomyces cerevisiae.

PubMed

Liu, Fang; Wang, Zhuanzi; Liu, Jia; Li, Wenjian

2018-04-21

The present study was to evaluate the in vivo radioprotective effect of oral administration of Saccharomyces cerevisiae-derived-beta-d-glucan (S. cerevisiae-BG) and to investigate the protective mechanism. The results demonstrated that oral pretreatment with 350 mg/kg S. cerevisiae-BG once daily for 14 consecutive days significantly increased the survival rate of mice from 6 Gy X-rays irradiation. At the 30th day after irradiation, cellularity and the percentage of hematopoietic stem/progenitor cells in bone marrow (BM) of surviving mice were increased by S. cerevisiae-BG. Further studies showed that S. cerevisiae-BG decreased BM cell DNA damage and improved BM cell cycle progress in irradiated mice. And the reactive oxygen species (ROS) levels in BM cells of irradiated mice were also decreased by S. cerevisiae-BG. These results indicated that oral S. cerevisiae-BG exhibited obviously radioprotective effect in mice and the protective effect may be attributed to the polysaccharide's hematopoiesis-modulating action and free radical scavenging property. S. cerevisiae-BG protects BM cells from radiation damage through scavenging BM cell ROS, mitigating BM cell DNA damage and improving cell cycle progress, and thus mitigated myelosuppression induced by irradiation and stimulated hematopoiesis, ultimately increased the survival of radiated mice. Copyright © 2018. Published by Elsevier B.V.

Cytotoxic effect of Erythroxylum daphnites extract is associated with G1 cell cycle arrest and apoptosis in oral squamous cell carcinoma.

PubMed

Elias, Silvia T; Macedo, Carolina C S; Simeoni, Luiz A; Silveira, Dâmaris; Magalhães, Pérola O; Lofrano-Porto, Adriana; Coletta, Ricardo D; Neves, Francisco A R; Guerra, Eliete N S

2016-01-01

Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.

Correlation of microstructure and thermo-mechanical properties of a novel hydrogen transport membrane

NASA Astrophysics Data System (ADS)

Zhang, Yongjun

A key part of the FutureGen concept is to support the production of hydrogen to fuel a "hydrogen economy," with the use of clean burning hydrogen in power-producing fuel cells, as well as for use as a transportation fuel. One of the key technical barriers to FutureGen deployment is reliable and efficient hydrogen separation technology. Most Hydrogen Transport Membrane (HTM) research currently focuses on separation technology and hydrogen flux characterization. No significant work has been performed on thermo-mechanical properties of HTMs. The objective of the thesis is to understand the structure-property correlation of HTM and to characterize (1) thermo mechanical properties under different reducing environments and thermal cycles (thermal shock), and (2) evaluate the stability of the novel HTM material. A novel HTM cermet bulk sample was characterized for its physical and mechanical properties at both room temperature and at elevated temperature up to 1000°C. Micro-structural properties and residual stresses were evaluated in order to understand the changing mechanism of the microstructure and its effects on the mechanical properties of materials. A correlation of the microstructural and thermo mechanical properties of the HTM system was established for both HTM and the substrate material. Mechanical properties of both selected structural ceramics and the novel HTM cermet bulk sample are affected mainly by porosity and microstructural features, such as grain size and pore size-distribution. The Young's Modulus (E-value) is positively correlated to the flexural strength for materials with similar crystallographic structure. However, for different crystallographic materials, physical properties are independent of mechanical properties. Microstructural properties, particularly, grain size and crystallographic structure, and thermodynamic properties are the main factors affecting the mechanical properties at both room and high temperatures. The HTM cermet behaves more like an elastic material at room temperature and as a ductile material at temperature above 850°C. The oxidation and the plasticity of Pd phase mainly affected the mechanical properties of HTM cermet at high temperature, also as a result of thermal cycling. Residual stress induced in the HTM by thermo cycles also plays a very critical role in defining the thermo-mechanical properties.

In Vivo and In Vitro Suppression of Hepatocellular Carcinoma by EF24, a Curcumin Analog

PubMed Central

Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers. PMID:23118928

In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

PubMed

Liu, Haitao; Liang, Yingjian; Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.

Zebrafish vitamin K epoxide reductases: expression in vivo, along extracellular matrix mineralization and under phylloquinone and warfarin in vitro exposure.

PubMed

Fernández, Ignacio; Vijayakumar, Parameswaran; Marques, Carlos; Cancela, M Leonor; Gavaia, Paulo J; Laizé, Vincent

2015-06-01

Vitamin K (VK) acts as a cofactor driving the biological activation of VK-dependent proteins and conferring calcium-binding properties to them. As a result, VK is converted into VK epoxide, which must be recycled by VK epoxide reductases (Vkors) before it can be reused. Although VK has been shown to play a central role in fish development, particularly during skeletogenesis, pathways underlying VK actions are poorly understood, while good and reliable molecular markers for VK cycle/homeostasis are still lacking in fish. In the present work, expression of 2 zebrafish vkor genes was characterized along larval development and in adult tissues through qPCR analysis. Zebrafish cell line ZFB1 was used to evaluate in vitro regulation of vkors and other VK cycle-related genes during mineralization and upon 24 h exposure to 0.16 and 0.8 µM phylloquinone (VK1), 0.032 µM warfarin, or a combination of both molecules. Results showed that zebrafish vkors are differentially expressed during larval development, in adult tissues, and during cell differentiation/mineralization processes. Further, several VK cycle intermediates were differentially expressed in ZFB1 cells exposed to VK1 and/or warfarin. Present work provides data identifying different developmental stages and adult tissues where VK recycling is probably highly required, and shows how genes involved in VK cycle respond to VK nutritional status in skeletal cells. Expression of vkor genes can represent a reliable indicator to infer VK nutritional status in fish, while ZFB1 cells could represent a suitable in vitro tool to get insights into the mechanisms underlying VK action on fish bone.

Pathological implications of cell cycle re-entry in Alzheimer disease.

PubMed

Bonda, David J; Lee, Hyun-pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2010-06-29

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Optimized anion exchange membranes for vanadium redox flow batteries.

PubMed

Chen, Dongyang; Hickner, Michael A; Agar, Ertan; Kumbur, E Caglan

2013-08-14

In order to understand the properties of low vanadium permeability anion exchange membranes for vanadium redox flow batteries (VRFBs), quaternary ammonium functionalized Radel (QA-Radel) membranes with three ion exchange capacities (IECs) from 1.7 to 2.4 mequiv g(-1) were synthesized and 55-60 μm thick membrane samples were evaluated for their transport properties and in-cell battery performance. The ionic conductivity and vanadium permeability of the membranes were investigated and correlated to the battery performance through measurements of Coulombic efficiency, voltage efficiency and energy efficiency in single cell tests, and capacity fade during cycling. Increasing the IEC of the QA-Radel membranes increased both the ionic conductivity and VO(2+) permeability. The 1.7 mequiv g(-1) IEC QA-Radel had the highest Coulombic efficiency and best cycling capacity maintenance in the VRFB, while the cell's voltage efficiency was limited by the membrane's low ionic conductivity. Increasing the IEC resulted in higher voltage efficiency for the 2.0 and 2.4 mequiv g(-1) samples, but the cells with these membranes displayed reduced Coulombic efficiency and faster capacity fade. The QA-Radel with an IEC of 2.0 mequiv g(-1) had the best balance of ionic conductivity and VO(2+) permeability, achieving a maximum power density of 218 mW cm(-2) which was higher than the maximum power density of a VRFB assembled with a Nafion N212 membrane in our system. While anion exchange membranes are under study for a variety of VRFB applications, this work demonstrates that the material parameters must be optimized to obtain the maximum cell performance.

Ionizing radiation changes the electronic properties of melanin and enhances the growth of melanized fungi.

PubMed

Dadachova, Ekaterina; Bryan, Ruth A; Huang, Xianchun; Moadel, Tiffany; Schweitzer, Andrew D; Aisen, Philip; Nosanchuk, Joshua D; Casadevall, Arturo

2007-05-23

Melanin pigments are ubiquitous in nature. Melanized microorganisms are often the dominating species in certain extreme environments, such as soils contaminated with radionuclides, suggesting that the presence of melanin is beneficial in their life cycle. We hypothesized that ionizing radiation could change the electronic properties of melanin and might enhance the growth of melanized microorganisms. Ionizing irradiation changed the electron spin resonance (ESR) signal of melanin, consistent with changes in electronic structure. Irradiated melanin manifested a 4-fold increase in its capacity to reduce NADH relative to non-irradiated melanin. HPLC analysis of melanin from fungi grown on different substrates revealed chemical complexity, dependence of melanin composition on the growth substrate and possible influence of melanin composition on its interaction with ionizing radiation. XTT/MTT assays showed increased metabolic activity of melanized C. neoformans cells relative to non-melanized cells, and exposure to ionizing radiation enhanced the electron-transfer properties of melanin in melanized cells. Melanized Wangiella dermatitidis and Cryptococcus neoformans cells exposed to ionizing radiation approximately 500 times higher than background grew significantly faster as indicated by higher CFUs, more dry weight biomass and 3-fold greater incorporation of (14)C-acetate than non-irradiated melanized cells or irradiated albino mutants. In addition, radiation enhanced the growth of melanized Cladosporium sphaerospermum cells under limited nutrients conditions. Exposure of melanin to ionizing radiation, and possibly other forms of electromagnetic radiation, changes its electronic properties. Melanized fungal cells manifested increased growth relative to non-melanized cells after exposure to ionizing radiation, raising intriguing questions about a potential role for melanin in energy capture and utilization.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting.

PubMed

Kabani, Sarah; Waterfall, Martin; Matthews, Keith R

2010-01-01

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting

PubMed Central

Kabani, Sarah; Waterfall, Martin; Matthews, Keith R.

2010-01-01

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase. PMID:19729042

Decursin inhibits growth of human bladder and colon cancer cells via apoptosis, G1-phase cell cycle arrest and extracellular signal-regulated kinase activation.

PubMed

Kim, Wun-Jae; Lee, Se-Jung; Choi, Young Deuk; Moon, Sung-Kwon

2010-04-01

Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, has demonstrated anti-cancer properties. In the present study, we found that decursin inhibited cell viability in cultured human urinary bladder cancer 235J cells and colon cancer HCT116 cells. The inhibited proliferation was due to apoptotic induction, because both cells treated with decursin dose-dependently showed a sub-G1 phase accumulation and an increased cytoplasmic DNA-histone complex. Cell death caused by decursin was also associated with the down-regulation of anti-apoptotic factor Bcl-2 and the up-regulation of pro-apoptotic molecules cytochrome c, caspase 3 and Bax. Treatment of both types of cancer cells with decursin resulted in G1-phase cell cycle arrest, as revealed by FACS analyses. In addition, decursin increased protein levels of p21WAF1 with a decrease in cyclins and cyclin dependent kinases (CDKs). Furthermore, decursin induced the activation of extracellular signal-regulated kinases (ERK) in both cancer cell lines, with the notable exceptions of c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase. Finally, pretreatment with ERK-specific inhibitor PD98059 reversed decursin-induced p21WAF1 expression and decursin-inhibited cell growth. Thus, these findings suggest that decursin has potential therapeutic efficacy for the treatment of bladder and colon cancer.

The Alternaria alternata Mycotoxin Alternariol Suppresses Lipopolysaccharide-Induced Inflammation

PubMed Central

Grover, Shivani; Lawrence, Christopher B.

2017-01-01

The Alternaria mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) have been shown to possess genotoxic and cytotoxic properties. In this study, the ability of AOH and AME to modulate innate immunity in the human bronchial epithelial cell line (BEAS-2B) and mouse macrophage cell line (RAW264.7) were investigated. During these studies, it was discovered that AOH and to a lesser extent AME potently suppressed lipopolysaccharide (LPS)-induced innate immune responses in a dose-dependent manner. Treatment of BEAS-2B cells with AOH resulted in morphological changes including a detached pattern of growth as well as elongated arms. AOH/AME-related immune suppression and morphological changes were linked to the ability of these mycotoxins to cause cell cycle arrest at the G2/M phase. This model was also used to investigate the AOH/AME mechanism of immune suppression in relation to aryl hydrocarbon receptor (AhR). AhR was not found to be important for the immunosuppressive properties of AOH/AME, but appeared important for the low levels of cell death observed in BEAS-2B cells. PMID:28726766

Cathodic Properties of Al-DOPED LiCoO2 Prepared by Molten Salt Method for Li-Ion Batteries

NASA Astrophysics Data System (ADS)

Reddy, M. V.; Rao, G. V. Subba; Chowdari, B. V. R.

2006-06-01

Layered Li(Co1-xAlx)O2, x=0.05-0.25 phases have been prepared by using the one-pot molten salt method at 850 °C in air and characterized by X-ray diffraction, Rietveld refinement, SEM-EDAX, chemical analysis, BET surface area and density methods. Cathodic properties were studied at ambient temperature in cells with Li-metal as the counter electrode by cyclic voltammetry (CV), galvanostatic charge-discharge cycling (up to 130 cycles) and Impedance spectroscopy. Single-phase compounds with hexagonal layer structure formed for all x. Results showed that for x≥0.05, the Li-de-intercalation potential during the first charge-cycle occurs at a value slightly higher than that shown by pure LiCoO2 and the structural transitions that occur at ˜4.1 V and ˜ 4.2 V are suppressed. However, the transition at ˜4.5 V is not suppressed. As a consequence, the long-term cyclability of Li(Co1-xAlx)O2 is greatly improved, when cycled in the potential ranges 2.5-4.3 V and 2.5-4.4 V at the current rate of 30 mA/g. Higher 10th cycle capacities were noted for x≥0.1-0.2 in the 2.5-4.5 V range but capacity-fading was noted, by 5-7 % at the end of 55 cycles. The observed CV and impedance data have been analyzed and interpreted.

Influence of Mixed Solvent on the Electrochemical Property of Hybrid Capacitor.

PubMed

Lee, Byunggwan; Yoon, J R

2015-11-01

The hybrid capacitors (2245 size, cylindrical type) were prepared by using activated carbon cathode and Li4Ti5O12 anode. In order to improve the cell operation at high temperature range, propylene carbonate (PC) was used in combination with acetonitrile (AN) with volume ratio of 7:3, 5:5, and 3:7, respectively. We investigated the electrochemical behavior of the hybrid capacitors that enabled cell operation with stability at high temperature. The organic electrolyte of hybrid capacitor containing PC and AN with a volume ratio 7:3 intended to exhibit highly reversible cycle performance with good capacity retention at 60 degrees C after 2200 cycles. From this study, it has been found that the very strong influence of the solvent nature on the characteristics of hybrid capacitor, and the difference in performance associated with the two solvents.

Bi-directional signaling: Extracellular Matrix and Integrin Regulation of Breast Tumor Progression

PubMed Central

Gehler, Scott; Ponik, Suzanne M.; Riching, Kristin M; Keely, Patricia J.

2016-01-01

Cell transformation and tumor progression involves a common set of acquired capabilities, including increased proliferation, failure of cell death, self-sufficiency in growth, angiogenesis, and tumor cell invasion and metastasis (1). The stromal environment consists of many cell types, including fibroblasts, macrophages, and endothelial cells, in addition to various extracellular matrix (ECM) proteins that function to support normal tissue maintenance, but have also been implicated in tumor progression (2). Both the chemical and mechanical properties of the ECM have been shown to influence normal and malignant cell behavior. For instance, mesenchymal stem cells differentiate into specific lineages that are dependent on matrix stiffness (3), while tumor cells undergo changes in cell behavior and gene expression in response to matrix stiffness (4). ECM remodeling is implicated in tumor progression and includes changes in both the chemical and mechanical properties of the ECM (5) that can be a result of 1.) increased deposition of stromal ECM, 2.) enhanced contraction of ECM fibrils, and 3.) altered collagen alignment and ECM stiffness. In addition, remodeling of the ECM may alter whether tumor cells employ proteolytic degradation mechanisms during invasion and metastasis. Tumor cells respond to such changes in ECM remodeling through altered intracellular signaling and cell cycle control that lead to enhanced proliferation, loss of normal tissue architecture, and local tumor cell migration and invasion into the surrounding stromal tissue (6). This review will focus on the bi-directional interplay between the mechanical properties of the ECM and changes in integrin-mediated signal transduction events in an effort to elucidate cell behaviors during tumor progression. PMID:23582036

Hierarchical TiO2-B composed of nanosheets with exposed {010} facets as a high-performance anode for lithium ion batteries

NASA Astrophysics Data System (ADS)

Liu, Yubin; Chen, Wenqiang; Yang, Chengyu; Wei, Qiaohua; Wei, Mingdeng

2018-07-01

Facet engineering of electrode materials with a special facet provides a new strategy to enhance their electrochemical properties. In the present work, hierarchical TiO2-B composed of nanosheets with exposed {010} facets are successfully synthesized via a facial hydrothermal route. When used as an anode for lithium ion batteries, this material demonstrates high capacities, excellent rata capability and remarkable cycling performance. For instance, it displays a reversible capacity of 200.9 mA h g-1 after 200 cycles at a current density of 1.675 A g-1 (5 C). Furthermore, a full cell consisted of hierarchical TiO2-B composed of nanosheets with exposed {010} facets anode and LiFePO4 cathode exhibits a high capacity of 125.6 mA h g-1 after 1000 cycles at a current density of 2 A g-1. Such outstanding electrochemical properties of this material can be attributed to hierarchical structure and the presence of exposed {010} facets which provides favorable lithium transport channels.

Tracking the Chemical and Structural Evolution of the TiS2 Electrode in the Lithium-Ion Cell Using Operando X-ray Absorption Spectroscopy.

PubMed

Zhang, Liang; Sun, Dan; Kang, Jun; Wang, Hsiao-Tsu; Hsieh, Shang-Hsien; Pong, Way-Faung; Bechtel, Hans A; Feng, Jun; Wang, Lin-Wang; Cairns, Elton J; Guo, Jinghua

2018-06-06

As the lightest and cheapest transition metal dichalcogenide, TiS 2 possesses great potential as an electrode material for lithium batteries due to the advantages of high energy density storage capability, fast ion diffusion rate, and low volume expansion. Despite the extensive investigation of its electrochemical properties, the fundamental discharge-charge reaction mechanism of the TiS 2 electrode is still elusive. Here, by a combination of ex situ and operando X-ray absorption spectroscopy with density functional theory calculations, we have clearly elucidated the evolution of the structural and chemical properties of TiS 2 during the discharge-charge processes. The lithium intercalation reaction is highly reversible and both Ti and sulfur are involved in the redox reaction during the discharge and charge processes. In contrast, the conversion reaction of TiS 2 is partially reversible in the first cycle. However, Ti-O related compounds are developed during electrochemical cycling over extended cycles, which results in the decrease of the conversion reaction reversibility and the rapid capacity fading. In addition, the solid electrolyte interphase formed on the electrode surface is found to be highly dynamic in the initial cycles and then gradually becomes more stable upon further cycling. Such understanding is important for the future design and optimization of TiS 2 based electrodes for lithium batteries.

Blueberry and malvidin inhibit cell cycle progression and induce mitochondrial-mediated apoptosis by abrogating the JAK/STAT-3 signalling pathway.

PubMed

Baba, Abdul Basit; Nivetha, Ramesh; Chattopadhyay, Indranil; Nagini, Siddavaram

2017-11-01

Blueberries, a rich source of anthocyanins have attracted considerable attention as functional foods that confer immense health benefits including anticancer properties. Herein, we assessed the potential of blueberry and its major constituent malvidin to target STAT-3, a potentially druggable oncogenic transcription factor with high therapeutic index. We demonstrate that blueberry abrogates the JAK/STAT-3 pathway and modulates downstream targets that influence cell proliferation and apoptosis in a hamster model of oral oncogenesis. Further, we provide mechanistic evidence that blueberry and malvidin function as STAT-3 inhibitors in the oral cancer cell line SCC131. Blueberry and malvidin suppressed STAT-3 phosphorylation and nuclear translocation thereby inducing cell cycle arrest and mitochondrial-mediated apoptosis. However, the combination of blueberry and malvidin with the STAT-3 inhibitor S3I-201 was more efficacious in STAT-3 inhibition relative to single agents. The present study has provided leads for the development of novel combinations of compounds that can serve as inhibitors of STAT-mediated oncogenic signalling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alteration of cell cycle progression by Sindbis virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Veromore » cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.« less

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment.

PubMed

Puccinelli, Michael T; Stan, Silvia D

2017-07-28

Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.

Cyclin-dependent kinase inhibitor p21(Waf1): contemporary view on its role in senescence and oncogenesis.

PubMed

Romanov, V S; Pospelov, V A; Pospelova, T V

2012-06-01

p21(Waf1) was identified as a protein suppressing cyclin E/A-CDK2 activity and was originally considered as a negative regulator of the cell cycle and a tumor suppressor. It is now considered that p21(Waf1) has alternative functions, and the view of its role in cellular processes has begun to change. At present, p21(Waf1) is known to be involved in regulation of fundamental cellular programs: cell proliferation, differentiation, migration, senescence, and apoptosis. In fact, it not only exhibits antioncogenic, but also oncogenic properties. This review provides a contemporary understanding of the functions of p21(Waf1) depending on its intracellular localization. On one hand, when in the nucleus, it serves as a negative cell cycle regulator and tumor suppressor, in particular by participating in the launch of a senescence program. On the other hand, when p21(Waf1) is localized in the cytoplasm, it acts as an oncogene by regulating migration, apoptosis, and proliferation.

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

PubMed Central

Puccinelli, Michael T.; Stan, Silvia D.

2017-01-01

Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent. PMID:28788092

Nitrogen-doped three-dimensional graphene-supported platinum catalysts for polymer electrolyte membrane fuel cells application

NASA Astrophysics Data System (ADS)

Chu, Fuqiang; Li, Xingxing; Yuan, Wensen; Zhu, Huanhuan; Qin, Yong; Zhang, Shuai; Yuan, Ningyi; Lin, Bencai; Ding, Jianning

Catalysts are a key component of polymer electrolyte membrane fuel cells (PEMFCs). In this work, nitrogen-doped three-dimensional graphene-supported platinum (Pt-3DNG) catalysts are successfully prepared and characterized. SEM and TEM images show the Pt nanoparticles are uniformly dispersed in the sheets of nitrogen-doped 3DNG. Compared with that of the commercial Pt/C catalysts, Pt-3DNG show much better oxygen reduction reaction (ORR) activity and cycling stability, and the reduction in limit current density after 1000 cycles is only about 1.6% for the Pt-3DNG catalysts, whereas 7.2% for the commercial Pt/C catalysts. The single cell using Pt-3DNG catalysts in both the anode and the cathode show a higher peak power density (21.47mW cm-2) than that using commercial Pt/C catalysts (20.17mW cm-2) under the same conditions. These properties make this type of catalyst suitable for the application in PEMFCs.

Age-related Deterioration of Hematopoietic Stem Cells.

PubMed

Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

2008-11-01

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

Age-related Deterioration of Hematopoietic Stem Cells

PubMed Central

Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

2008-01-01

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail. PMID:24855509

Development of SnS2/RGO nanosheet composite for cost-effective aqueous hybrid supercapacitors.

PubMed

Chauhan, Himani; Singh, Manoj K; Kumar, Praveen; Hashmi, Safir Ahmad; Deka, Sasanka

2017-01-13

The development of low cost supercapacitor cells with unique capacitive properties is essential for many domestic and industrial purposes. Here we report the first ever application of SnS 2 -reduced graphene oxide (SnS 2 /RGO) layered nanocomposite as a superior electrode material for symmetric aqueous hybrid supercapacitors. We synthesized SnS 2 /RGO nanocomposite comprised of nanosheets of SnS 2 and graphene oxide via a one-pot hydrothermal approach. in situ as-synthesized SnS 2 /RGO is devised for the first time to give high specific capacitance 500 Fg -1 , energy density 16.67 Wh kg -1 and power density 488 W kg -1 . The cell retains 95% charge/discharge cycle stability up to 1000 cycles. In-short, the SnS 2 /RGO nanosheet composite presented is a novel and advanced material for application in high stability moderate value hybrid supercapacitors. All the currently available surveys in literature state the potential applicability of SnS 2 as the anode material for reversible lithium/sodium ion batteries (LIBs/NIBs) but there is a lack of equivalent studies on electrochemical capacitors. We filled up this knowledge gap by the use of the same material in a cost-effective, highly active hybrid supercapacitor application by utilizing its pseudocapacitance property combined with the layered capacitance property of graphene sheets.

In vitro Antioxidant and Antiproliferative Activities of Various Solvent Fractions from Clerodendrum viscosum Leaves

PubMed Central

Shendge, Anil Khushalrao; Basu, Tapasree; Chaudhuri, Dipankar; Panja, Sourav; Mandal, Nripendranath

2017-01-01

Background: Free radicals such as reactive oxygen and nitrogen species, generated in the body, play an important role in the fulfillment of various physiological functions but their imbalance in the body lead to cellular injury and various clinical disorders such as cancer, neurodegenaration, and inflammation. Objective: The objective of this study is to fight this problem, natural antioxidant from plants can be considered as possible protective agents against various diseases such as cancer which might also modify the redox microenvironment to reduce the genetic instability. This study was designed to evaluate the antioxidant and antiproliferative potential of Clerodendrum viscosum fractions against various carcinomas. Materials and Methods: In this present study, 70% methanolic extract of C. viscosum leaves have been fractionated to obtain hexane, chloroform, ethyl acetate, butanol, and water fractions, which were tested for their antioxidant and anticancer properties. Results: It was observed that chloroform and ethyl acetate fractions showed good free radical scavenging properties as well as inhibited the proliferation of human lung cancer (A459), breast (MCF-7), and brain (U87) cells. Moreover, they arrested the cell cycle at G2/M phase of breast and brain cancer. These inhibitory effects were further confirmed by bromodeoxyuridine uptake imaging. Phytochemical investigations further indicate the presence of tannic acid, quercetin, ellagic caid, gallic acid, reserpine, and methyl gallate which might be the reason for these fractions’ antioxidant and antiproliferative activities. Conclusion: Clerodendrum viscosum leaf chloroform and Clerodendrum viscosum leaf ethyl acetate fractions from C. viscosum showed good reactive oxygen species and reactive nitrogen species scavenging potential. Both the fractions arrested cell cycle at G2/M phase in MCF-7 and U87 cells which lead to induce apoptosis. SUMMARY Crude extract of Clerodendrum viscosum leaves was fractionated using different solventsAmong them, chloroform and ethyl acetate fractions exhibited excellent free radical scavenging propertiesThe same fractions inhibited the proliferation of human lung cancer (A459), breast (MCF-7), and brain (U87) cellsChloroform and ethyl acetate fractions arrested the cell cycle at G2/M phase of breast and brain cancerPhytochemical investigations further indicate the presence of several bioactive principles present in them. Abbreviations used: CVLME: Clerodendrum viscosum leaf methanolic extract; CVLH: Clerodendrum viscosum leaf hexane; CVLC: Clerodendrum viscosum leaf chloroform; CVLE: Clerodendrum viscosum leaf ethyl acetate; CVLB: Clerodendrum viscosum leaf butanol; CVLW: Clerodendrum viscosum leaf water; BrdU: Bromodeoxyuridine; WST-1: Water soluble tetrazolium salt. PMID:28808404

Adhesion properties of an elastomer enhanced by the presence of liquid drops in its structure

NASA Astrophysics Data System (ADS)

Giustiniani, Anais; Drenckhan, Wiebke; Poulard, Christophe

Macro-cellular polymers present rich mechanical properties due to the internal structuration of the material, in which discrete cells are tightly packed within a continuous polymeric solid matrix. The size, shape, organisation and volume fraction of these cells have an important influence on the overall material properties. Here, we study a solid emulsion which consist of liquid polyethylene glycol drops in a crosslinked PDMS (polydimethylsiloxane). These present novel rheological and adhesive properties. Results show an important hysteresis of the normal stress in a compression/decompression cycle with a significant force at rupture when this force is close to zero for the bare PDMS. This was reported for 2D systems, and in this work we study the influence of the drop sizes inside the matrix, their density and the viscosity of the liquid on the adhesion energy of the 3D material. The overall motivation of this system is to allow to independently control the elastic and viscous properties of the matrix and the drops respectively, in opposition to the viscoelastic fluids commonly used as adhesives such as PSA and gels.

Hepatitis C Virus core+1/ARF Protein Modulates the Cyclin D1/pRb Pathway and Promotes Carcinogenesis.

PubMed

Moustafa, Savvina; Karakasiliotis, Ioannis; Mavromara, Penelope

2018-05-01

Viruses often encompass overlapping reading frames and unconventional translation mechanisms in order to maximize the output from a minimum genome and to orchestrate their timely gene expression. Hepatitis C virus (HCV) possesses such an unconventional open reading frame (ORF) within the core-coding region, encoding an additional protein, initially designated ARFP, F, or core+1. Two predominant isoforms of core+1/ARFP have been reported, core+1/L, initiating from codon 26, and core+1/S, initiating from codons 85/87 of the polyprotein coding region. The biological significance of core+1/ARFP expression remains elusive. The aim of the present study was to gain insight into the functional and pathological properties of core+1/ARFP through its interaction with the host cell, combining in vitro and in vivo approaches. Our data provide strong evidence that the core+1/ARFP of HCV-1a stimulates cell proliferation in Huh7-based cell lines expressing either core+1/S or core+1/L isoforms and in transgenic liver disease mouse models expressing core+1/S protein in a liver-specific manner. Both isoforms of core+1/ARFP increase the levels of cyclin D1 and phosphorylated Rb, thus promoting the cell cycle. In addition, core+1/S was found to enhance liver regeneration and oncogenesis in transgenic mice. The induction of the cell cycle together with increased mRNA levels of cell proliferation-related oncogenes in cells expressing the core+1/ARFP proteins argue for an oncogenic potential of these proteins and an important role in HCV-associated pathogenesis. IMPORTANCE This study sheds light on the biological importance of a unique HCV protein. We show here that core+1/ARFP of HCV-1a interacts with the host machinery, leading to acceleration of the cell cycle and enhancement of liver carcinogenesis. This pathological mechanism(s) may complement the action of other viral proteins with oncogenic properties, leading to the development of hepatocellular carcinoma. In addition, given that immunological responses to core+1/ARFP have been correlated with liver disease severity in chronic HCV patients, we expect that the present work will assist in clarifying the pathophysiological relevance of this protein as a biomarker of disease progression. Copyright © 2018 American Society for Microbiology.

Antitumorigenic Effects of ZAKβ, an Alternative Splicing Isoform of ZAK.

PubMed

Lee, Jin-Sun; Lin, Yuh-Yih; Wang, Tsu-Shing; Liu, Jer-Yuh; Lin, Wei-Wen; Yang, Jaw-Ji

2018-02-28

Sterile alpha motif (SAM)- and leucine-zipper-containing kinase (ZAK) plays a role in the regulation of cell cycle progression and oncogenic transformation. The ZAK gene generates two transcript variants, ZAKα and ZAKβ, through alternative splicing. In this study, we identified that ZAKα proteins were upregulated in tumor tissues, whereas ZAKβ proteins were mostly expressed in corresponding normal tissues. The ectopically expressed ZAKβ proteins in cancer cells inhibited cancer cell proliferation as well as anchorage-independent growth. The ZAKβ:ZAKα protein ratio played a role in the regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway, whereas high ZAKβ protein levels led to the activation of cAMP response element binding protein 1 (CREB1) and exerted antitumor properties. Overexpression of ZAKβ or CREB1 cDNAs in cancer cells inhibited anchorage-independent growth and also reduced the levels of cyclooxygenase 2 (Cox2) and β-catenin proteins. Cancer cells treated with doxorubicin (Doxo) resulted in the switching from the expression of ZAKα to ZAKβ and also inhibited cancer cell growth in soft agar, demonstrating that pharmacological drugs could be used to manipulate endogenous reprogramming splicing events and resulting in the activation of endogenous antitumorigenic properties. We showed that the two ZAK transcript variants, ZAKα and ZAKβ, had opposite biological functions in the regulation of tumor cell proliferation in that ZAKβ had powerful antitumor properties and that ZAKα could promote tumor growth.

Quantitative imaging with Fucci and mathematics to uncover temporal dynamics of cell cycle progression.

PubMed

Saitou, Takashi; Imamura, Takeshi

2016-01-01

Cell cycle progression is strictly coordinated to ensure proper tissue growth, development, and regeneration of multicellular organisms. Spatiotemporal visualization of cell cycle phases directly helps us to obtain a deeper understanding of controlled, multicellular, cell cycle progression. The fluorescent ubiquitination-based cell cycle indicator (Fucci) system allows us to monitor, in living cells, the G1 and the S/G2/M phases of the cell cycle in red and green fluorescent colors, respectively. Since the discovery of Fucci technology, it has found numerous applications in the characterization of the timing of cell cycle phase transitions under diverse conditions and various biological processes. However, due to the complexity of cell cycle dynamics, understanding of specific patterns of cell cycle progression is still far from complete. In order to tackle this issue, quantitative approaches combined with mathematical modeling seem to be essential. Here, we review several studies that attempted to integrate Fucci technology and mathematical models to obtain quantitative information regarding cell cycle regulatory patterns. Focusing on the technological development of utilizing mathematics to retrieve meaningful information from the Fucci producing data, we discuss how the combined methods advance a quantitative understanding of cell cycle regulation. © 2015 Japanese Society of Developmental Biologists.

Differences in the Mechanical Properties of the Developing Cerebral Cortical Proliferative Zone between Mice and Ferrets at both the Tissue and Single-Cell Levels.

PubMed

Nagasaka, Arata; Shinoda, Tomoyasu; Kawaue, Takumi; Suzuki, Makoto; Nagayama, Kazuaki; Matsumoto, Takeo; Ueno, Naoto; Kawaguchi, Ayano; Miyata, Takaki

2016-01-01

Cell-producing events in developing tissues are mechanically dynamic throughout the cell cycle. In many epithelial systems, cells are apicobasally tall, with nuclei and somata that adopt different apicobasal positions because nuclei and somata move in a cell cycle-dependent manner. This movement is apical during G2 phase and basal during G1 phase, whereas mitosis occurs at the apical surface. These movements are collectively referred to as interkinetic nuclear migration, and such epithelia are called "pseudostratified." The embryonic mammalian cerebral cortical neuroepithelium is a good model for highly pseudostratified epithelia, and we previously found differences between mice and ferrets in both horizontal cellular density (greater in ferrets) and nuclear/somal movements (slower during G2 and faster during G1 in ferrets). These differences suggest that neuroepithelial cells alter their nucleokinetic behavior in response to physical factors that they encounter, which may form the basis for evolutionary transitions toward more abundant brain-cell production from mice to ferrets and primates. To address how mouse and ferret neuroepithelia may differ physically in a quantitative manner, we used atomic force microscopy to determine that the vertical stiffness of their apical surface is greater in ferrets (Young's modulus = 1700 Pa) than in mice (1400 Pa). We systematically analyzed factors underlying the apical-surface stiffness through experiments to pharmacologically inhibit actomyosin or microtubules and to examine recoiling behaviors of the apical surface upon laser ablation and also through electron microscopy to observe adherens junction. We found that although both actomyosin and microtubules are partly responsible for the apical-surface stiffness, the mouse

X box binding protein XBP-1s transactivates the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF50 promoter, linking plasma cell differentiation to KSHV reactivation from latency.

PubMed

Wilson, Sam J; Tsao, Edward H; Webb, Benjamin L J; Ye, Hongtao; Dalton-Griffin, Lucy; Tsantoulas, Christoforos; Gale, Catherine V; Du, Ming-Qing; Whitehouse, Adrian; Kellam, Paul

2007-12-01

Reactivation of lytic replication from viral latency is a defining property of all herpesviruses. Despite this, the authentic physiological cues for the latent-lytic switch are unclear. Such cues should ensure that viral lytic replication occurs under physiological conditions, predominantly in sites which facilitate transmission to permissive uninfected cells and new susceptible hosts. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with the B-cell neoplasm primary effusion lymphoma (PEL), in which the virus remains latent. We have previously shown that PEL cells have the gene expression profile and immunophenotype of cycling preplasma cells (plasmablasts). Here, we show that the highly active spliced isoform of plasma cell transcription factor X box binding protein 1 (XBP-1s) is a lytic switch for KSHV. XBP-1s is normally absent in PEL, but the induction of endoplasmic reticulum stress leads to XBP-1s generation, plasma cell-like differentiation, and lytic reactivation of KSHV. XBP-1s binds to and activates the KSHV immediate-early gene ORF50 and synergizes with the ORF50 gene product RTA to induce a full lytic cycle. These data suggest that KSHV remains latent until B-cell terminal differentiation into plasma cells, the transcriptional environment of which provides the physiological "lytic switch" through XBP-1s. This links B-cell terminal differentiation to KSHV lytic reactivation.

Cell Cycle Control in the Early Embryonic Development of Aquatic Animal Species

PubMed Central

Siefert, Joseph C.; Clowdus, Emily A.; Sansam, Christopher L.

2016-01-01

The cell cycle is integrated with many aspects of embryonic development. Not only is proper control over the pace of cell proliferation important, but also the timing of cell cycle progression is coordinated with transcription, cell migration, and cell differentiation. Due to the ease with which the embryos of aquatic organisms can be observed and manipulated, they have been a popular choice for embryologists throughout history. In the cell cycle field, aquatic organisms have been extremely important because they have played a major role in the discovery and analysis of key regulators of the cell cycle. In particular, the frog Xenopus laevis has been instrumental for understanding how the basic embryonic cell cycle is regulated. More recently, the zebrafish has been used to understand how the cell cycle is remodeled during vertebrate development and how it is regulated during morphogenesis. This review describes how some of the unique strengths of aquatic species have been leveraged for cell cycle research and suggests how species such as Xenopus and zebrafish will continue to reveal the roles of the cell cycle in human biology and disease. PMID:26475527

Magnetic field effects on mitochondrion-activity-related optical properties in slime mold and bone forming cells.

PubMed

Mizukawa, Yuri; Iwasaka, Masakazu

2013-01-01

In the present study, a cellular level response of Cyto-aa3 oxidation was investigated in real time under both time-varying and strong static magnetic fields of 5 T. Two kinds of cells, a slime mold, Physarum polycephalum, and bone forming cells, MC-3T3-E1, were used for the experiments. The oxidation level of the Cyto-aa3 was calculated by optical absorptions at 690 nm, 780 nm and 830 nm. The sample, fiber-optics and an additional optical fiber for light stimulation were set in a solenoidal coil or the bore of a 5-T superconducting magnet. The solenoidal coil for time-varying magnetic fields produced sinusoidal magnetic fields of 6 mT. The slime mold showed a periodic change in Cyto-aa3 oxidation, and the oxidation-reduction cycle of Cyto-aa3 was apparently changed when visible-light irradiated the slime mold. Similarly to the case with light, time-varying magnetic stimulations changed the oxidation-reduction cycle during and after the stimulation for 10 minutes. The same phenomena were observed in the MC-3T3-E1 cell assembly, although their cycle rhythm was comparatively random. Finally, magnetic field exposure of up to 5 T exhibited a distinct suppression of Cyto-aa3 oscillation in the bone forming cells. Exposure up to 5 T was repeated five times, and the change in Cyto-aa3 oxidation reproducibly occurred.

Marine Cyanobacteria Compounds with Anticancer Properties: A Review on the Implication of Apoptosis

PubMed Central

Costa, Margarida; Costa-Rodrigues, João; Fernandes, Maria Helena; Barros, Piedade; Vasconcelos, Vitor; Martins, Rosário

2012-01-01

Marine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been the most explored and, besides cytotoxicity in tumor cell lines, several compounds have emerged as templates for the development of new anticancer drugs. The mechanisms implicated in the cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still largely overlooked but several studies point to an implication in apoptosis. This association has been related to several apoptotic indicators such as cell cycle arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase cascade, alterations in specific proteins levels and alterations in the membrane sodium dynamics. In the present paper a compilation of the described marine cyanobacterial compounds with potential anticancer properties is presented and a review on the implication of apoptosis as the mechanism of cell death is discussed. PMID:23170077

Capacity Fade and Its Mitigation in Li-Ion Cells with Silicon-Graphite Electrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bareno, Javier; Shkrob, Ilya A.; Gilbert, James A.

Silicon-graphite (Si-Gr) electrodes typically contain lithiated carboxylates as polymer binders that are introduced through aqueous processing. Li-ion cells with such electrodes show significantly faster capacity fade than cells with graphite (Gr) electrodes. Here we examine the causes for capacity loss in Si-Gr cells containing LiPF 6-based electrolytes. The presence of SiO xF y in the Si-Gr electrode, fluorophosphate species in the electrolyte, and silica on the positive electrode indicates the crucial role of the hydrolytic cycle. In particular, HF acid that is generated through LiPF 6 hydrolysis corrodes Si particles. As it reacts, the released water re-enters the cycle. Wemore » trace the moisture initiating this detrimental cycle to the hydration water in the lithiated binders that cannot be fully removed by thermal treatment. The rate of HF corrosion can be reduced through the use of electrolyte additives. For the fluoroethylene carbonate (FEC) additive, the improved performance arises from changes to the solid electrolyte interphase (SEI) that serves as a barrier against HF attack. Here, we propose that the greater extent of polymer cross-linking, that gives FEC-derived SEI elastomer properties, slows down HF percolation through this SEI membrane and inhibits the formation of deep cracks through which HF can access and degrade the Si surface.« less

Capacity Fade and Its Mitigation in Li-Ion Cells with Silicon-Graphite Electrodes

DOE PAGES

Bareno, Javier; Shkrob, Ilya A.; Gilbert, James A.; ...

2017-09-06

Silicon-graphite (Si-Gr) electrodes typically contain lithiated carboxylates as polymer binders that are introduced through aqueous processing. Li-ion cells with such electrodes show significantly faster capacity fade than cells with graphite (Gr) electrodes. Here we examine the causes for capacity loss in Si-Gr cells containing LiPF 6-based electrolytes. The presence of SiO xF y in the Si-Gr electrode, fluorophosphate species in the electrolyte, and silica on the positive electrode indicates the crucial role of the hydrolytic cycle. In particular, HF acid that is generated through LiPF 6 hydrolysis corrodes Si particles. As it reacts, the released water re-enters the cycle. Wemore » trace the moisture initiating this detrimental cycle to the hydration water in the lithiated binders that cannot be fully removed by thermal treatment. The rate of HF corrosion can be reduced through the use of electrolyte additives. For the fluoroethylene carbonate (FEC) additive, the improved performance arises from changes to the solid electrolyte interphase (SEI) that serves as a barrier against HF attack. Here, we propose that the greater extent of polymer cross-linking, that gives FEC-derived SEI elastomer properties, slows down HF percolation through this SEI membrane and inhibits the formation of deep cracks through which HF can access and degrade the Si surface.« less

Cell cycle arrest in the jewel wasp Nasonia vitripennis in larval diapause.

PubMed

Shimizu, Yuta; Mukai, Ayumu; Goto, Shin G

2018-04-01

Insects enter diapause to synchronise their life cycle with biotic and abiotic environmental conditions favourable for their development, reproduction, and survival. One of the most noticeable characteristics of diapause is the blockage of ontogeny. Although this blockage should occur with the cessation of cellular proliferation, i.e. cell cycle arrest, it was confirmed only in a few insect species and information on the molecular pathways involved in cell cycle arrest is limited. In the present study, we investigated developmental and cell cycle arrest in diapause larvae of the jewel wasp Nasonia vitripennis. Developmental and cell cycle arrest occur in the early fourth instar larval stage of N. vitripennis under short days. By entering diapause, the S fraction of the cell cycle disappears and approximately 80% and 20% of cells arrest their cell cycle in the G0/G1 and G2 phases, respectively. We further investigated expression of cell cycle regulatory genes and some housekeeping genes to dissect molecular mechanisms underlying the cell cycle arrest. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accumulation of Poly(3-hydroxybutyrate) Helps Bacterial Cells to Survive Freezing

PubMed Central

Krzyzanek, Vladislav; Mravec, Filip; Hrubanova, Kamila; Samek, Ota; Kucera, Dan; Benesova, Pavla; Marova, Ivana

2016-01-01

Accumulation of polyhydroxybutyrate (PHB) seems to be a common metabolic strategy adopted by many bacteria to cope with cold environments. This work aimed at evaluating and understanding the cryoprotective effect of PHB. At first a monomer of PHB, 3-hydroxybutyrate, was identified as a potent cryoprotectant capable of protecting model enzyme (lipase), yeast (Saccharomyces cerevisiae) and bacterial cells (Cupriavidus necator) against the adverse effects of freezing-thawing cycles. Further, the viability of the frozen–thawed PHB accumulating strain of C. necator was compared to that of the PHB non-accumulating mutant. The presence of PHB granules in cells was revealed to be a significant advantage during freezing. This might be attributed to the higher intracellular level of 3-hydroxybutyrate in PHB accumulating cells (due to the action of parallel PHB synthesis and degradation, the so-called PHB cycle), but the cryoprotective effect of PHB granules seems to be more complex. Since intracellular PHB granules retain highly flexible properties even at extremely low temperatures (observed by cryo-SEM), it can be expected that PHB granules protect cells against injury from extracellular ice. Finally, thermal analysis indicates that PHB-containing cells exhibit a higher rate of transmembrane water transport, which protects cells against the formation of intracellular ice which usually has fatal consequences. PMID:27315285

Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells

PubMed Central

SHI, WEI; DENG, JIAGANG; TONG, RONGSHENG; YANG, YONG; HE, XIA; LV, JIANZHEN; WANG, HAILIAN; DENG, SHAOPING; QI, PING; ZHANG, DINGDING; WANG, YI

2016-01-01

Mangiferin, which is a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources, has recently gained attention due to its various biological activities. The present study aimed to determine the apoptotic effects of mangiferin on A549 human lung adenocarcinoma cells. In vitro studies demonstrated that mangiferin exerted growth-inhibitory and apoptosis-inducing effects against A549 cells. In addition, mangiferin exhibited anti-tumor properties in A549 xenograft mice in vivo. Mangiferin triggered G2/M phase cell cycle arrest via down-regulating the cyclin-dependent kinase 1-cyclin B1 signaling pathway, and induced apoptotic cell death by inhibiting the protein kinase C-nuclear factor-κB pathway. In addition, mangiferin was able to enhance the antiproliferative effects of cisplatin on A549 cells, thus indicating the potential for a combined therapy. Notably, mangiferin exerted anticancer effects in vivo, where it was able to markedly decrease the volume and weight of subcutaneous tumor mass, and expand the lifespan of xenograft mice. The present study clarified the molecular mechanisms underlying mangiferin-induced antitumor activities, and suggested that mangiferin may be considered a potential antineoplastic drug for the future treatment of cancer. PMID:26935347

Enhanced lithium battery with polyethylene oxide-based electrolyte containing silane-Al2 O3 ceramic filler.

PubMed

Zewde, Berhanu W; Admassie, Shimelis; Zimmermann, Jutta; Isfort, Christian Schulze; Scrosati, Bruno; Hassoun, Jusef

2013-08-01

A solid polymer electrolyte prepared by using a solvent-free, scalable technique is reported. The membrane is formed by low-energy ball milling followed by hot-pressing of dry powdered polyethylene oxide polymer, LiCF3 SO3 salt, and silane-treated Al2 O3 (Al2 O3 -ST) ceramic filler. The effects of the ceramic fillers on the properties of the ionically conducting solid electrolyte membrane are characterized by using electrochemical impedance spectroscopy, XRD, differential scanning calorimeter, SEM, and galvanostatic cycling in lithium cells with a LiFePO4 cathode. We demonstrate that the membrane containing Al2 O3 -ST ceramic filler performs well in terms of ionic conductivity, thermal properties, and lithium transference number. Furthermore, we show that the lithium cells, which use the new electrolyte together with the LiFePO4 electrode, operate within 65 and 90 °C with high efficiency and long cycle life. Hence, the Al2 O3 -ST ceramic can be efficiently used as a ceramic filler to enhance the performance of solid polymer electrolytes in lithium batteries. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modelling cell cycle synchronisation in networks of coupled radial glial cells.

PubMed

Barrack, Duncan S; Thul, Rüdiger; Owen, Markus R

2015-07-21

Radial glial cells play a crucial role in the embryonic mammalian brain. Their proliferation is thought to be controlled, in part, by ATP mediated calcium signals. It has been hypothesised that these signals act to locally synchronise cell cycles, so that clusters of cells proliferate together, shedding daughter cells in uniform sheets. In this paper we investigate this cell cycle synchronisation by taking an ordinary differential equation model that couples the dynamics of intracellular calcium and the cell cycle and extend it to populations of cells coupled via extracellular ATP signals. Through bifurcation analysis we show that although ATP mediated calcium release can lead to cell cycle synchronisation, a number of other asynchronous oscillatory solutions including torus solutions dominate the parameter space and cell cycle synchronisation is far from guaranteed. Despite this, numerical results indicate that the transient and not the asymptotic behaviour of the system is important in accounting for cell cycle synchronisation. In particular, quiescent cells can be entrained on to the cell cycle via ATP mediated calcium signals initiated by a driving cell and crucially will cycle in near synchrony with the driving cell for the duration of neurogenesis. This behaviour is highly sensitive to the timing of ATP release, with release at the G1/S phase transition of the cell cycle far more likely to lead to near synchrony than release during mid G1 phase. This result, which suggests that ATP release timing is critical to radial glia cell cycle synchronisation, may help us to understand normal and pathological brain development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distinct transcriptional networks in quiescent myoblasts: a role for Wnt signaling in reversible vs. irreversible arrest.

PubMed

Subramaniam, Sindhu; Sreenivas, Prethish; Cheedipudi, Sirisha; Reddy, Vatrapu Rami; Shashidhara, Lingadahalli Subrahmanya; Chilukoti, Ravi Kumar; Mylavarapu, Madhavi; Dhawan, Jyotsna

2014-01-01

Most cells in adult mammals are non-dividing: differentiated cells exit the cell cycle permanently, but stem cells exist in a state of reversible arrest called quiescence. In damaged skeletal muscle, quiescent satellite stem cells re-enter the cell cycle, proliferate and subsequently execute divergent programs to regenerate both post-mitotic myofibers and quiescent stem cells. The molecular basis for these alternative programs of arrest is poorly understood. In this study, we used an established myogenic culture model (C2C12 myoblasts) to generate cells in alternative states of arrest and investigate their global transcriptional profiles. Using cDNA microarrays, we compared G0 myoblasts with post-mitotic myotubes. Our findings define the transcriptional program of quiescent myoblasts in culture and establish that distinct gene expression profiles, especially of tumour suppressor genes and inhibitors of differentiation characterize reversible arrest, distinguishing this state from irreversibly arrested myotubes. We also reveal the existence of a tissue-specific quiescence program by comparing G0 C2C12 myoblasts to isogenic G0 fibroblasts (10T1/2). Intriguingly, in myoblasts but not fibroblasts, quiescence is associated with a signature of Wnt pathway genes. We provide evidence that different levels of signaling via the canonical Wnt pathway characterize distinct cellular states (proliferation vs. quiescence vs. differentiation). Moderate induction of Wnt signaling in quiescence is associated with critical properties such as clonogenic self-renewal. Exogenous Wnt treatment subverts the quiescence program and negatively affects clonogenicity. Finally, we identify two new quiescence-induced regulators of canonical Wnt signaling, Rgs2 and Dkk3, whose induction in G0 is required for clonogenic self-renewal. These results support the concept that active signal-mediated regulation of quiescence contributes to stem cell properties, and have implications for pathological states such as cancer and degenerative disease.

Construction and biological evaluation of different self-assembled nanoarchitectures of FZU-03,010.

PubMed

Lv, Tingting; Xu, Liang; Wu, Guolin; Li, Cailong; Wen, Yibo; Zhang, Tao; Chen, Haijun; Gao, Yu

2018-06-13

Chemotherapy is currently one of the promising therapeutic methods for non-small-cell lung cancer (NSCLC), but the emergence of multidrug resistance (MDR) is the greatest obstacle to efficient drug delivery for successful chemotherapy. Nanotechnology-based drug delivery holds great promise to promote intracellular drug delivery to reverse MDR. In this work, we used our previously synthesized ursolic acid (UA) derivative, FZU-03,010 (F3), to prepare nanodrugs of F3 with different architectures and study the role of the structure on the physiochemical properties and the biological effects against A549 and its PTX-resistant A549/PTX lung cancer cells. Using different preparation methods, amphiphilic F3 could self-assemble into different structures such as nanoaggregates (F3-NA), vesicles (F3-VC), or nanoparticles (F3-NP) with different physiochemical properties. The self-assembled nanodrugs could be utilized for the entrapment of fluorophores and showed different cellular uptake efficiencies. The cytotoxicity results demonstrated that compared with UA, F3-NA and F3-NP could suppress A549 and A549/PTX cells viability more potently at lower concentration. In addition, F3-NA and F3-NP could induce G1 cell cycle arrest, cell apoptosis and caspase-3 activation more efficiently than that of UA. Furthermore, F3-NA and F3-NP could effectively inhibit PI3K/Akt pathway and decrease the expression of Bcl-2 and the cell cycle-dependent kinase inhibitors p-ERK1/2 and Cyclin D1 in both A549 and A549/PTX cells. In conclusion, our results suggest that the UA derivative F3 is more potent in inhibiting cancer cell proliferation, and F3-NA and F3-NP have the potential to be developed as a therapeutic for resistant NSCLC cells. Copyright © 2017. Published by Elsevier B.V.

Unraveling Interfaces between Energy Metabolism and Cell Cycle in Plants.

PubMed

Siqueira, João Antonio; Hardoim, Pablo; Ferreira, Paulo C G; Nunes-Nesi, Adriano; Hemerly, Adriana S

2018-06-19

Oscillation in energy levels is widely variable in dividing and differentiated cells. To synchronize cell proliferation and energy fluctuations, cell cycle-related proteins have been implicated in the regulation of mitochondrial energy-generating pathways in yeasts and animals. Plants have chloroplasts and mitochondria, coordinating the cell energy flow. Recent findings suggest an integrated regulation of these organelles and the nuclear cell cycle. Furthermore, reports indicate a set of interactions between the cell cycle and energy metabolism, coordinating the turnover of proteins in plants. Here, we discuss how cell cycle-related proteins directly interact with energy metabolism-related proteins to modulate energy homeostasis and cell cycle progression. We provide interfaces between cell cycle and energy metabolism-related proteins that could be explored to maximize plant yield. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

PubMed

Solomon, Lauren A; Podder, Shreya; He, Jessica; Jackson-Chornenki, Nicholas L; Gibson, Kristen; Ziliotto, Rachel G; Rhee, Jess; DeKoter, Rodney P

2017-05-15

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1 , an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. Copyright © 2017 American Society for Microbiology.

Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line.

PubMed

Montemurro, Chiara; Vadrevu, Suryakiran; Gurlo, Tatyana; Butler, Alexandra E; Vongbunyong, Kenny E; Petcherski, Anton; Shirihai, Orian S; Satin, Leslie S; Braas, Daniel; Butler, Peter C; Tudzarova, Slavica

2017-01-01

Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca 2+ are critical for permitting cells to progress through the cell cycle. Here, we investigated these parameters in the replication-competent beta-cell line INS 832/13. Cell cycle synchronization of this line permitted evaluation of cell metabolism, mitochondrial network, and cellular Ca 2+ compartmentalization at key cell cycle stages. The mitochondrial network is interconnected and filamentous at G1/S but fragments during the S and G2/M phases, presumably to permit sorting to daughter cells. Pyruvate anaplerosis peaks at G1/S, consistent with generation of biomass for daughter cells, whereas mitochondrial Ca 2+ and respiration increase during S and G2/M, consistent with increased energy requirements for DNA and lipid synthesis. This synchronization approach may be of value to investigators performing live cell imaging of Ca 2+ or mitochondrial dynamics commonly undertaken in INS cell lines because without synchrony widely disparate data from cell to cell would be expected depending on position within cell cycle. Our findings also offer insight into why replicating beta-cells are relatively nonfunctional secreting insulin in response to glucose. They also provide guidance on metabolic requirements of beta-cells for the transition through the cell cycle that may complement the efforts currently restricted to manipulating cell cycle to drive beta-cells through cell cycle.

Non-gassing nickel-cadmium battery electrodes and cells

NASA Technical Reports Server (NTRS)

Luksha, E.; Gordy, D. J.

1972-01-01

The concept of a negative limited nongassing nickel-cadmium battery was demonstrated by constructing and testing practical size experimental cells of approximately 25 Ah capacity. These batteries operated in a gas-free manner and had measured energy densities of 10-11 Wh/lb. Thirty cells were constructed for extensive testing. Some small cells were tested for over 200 cycles at 100% depth. For example, a small cell with an electrodeposited cadmium active mass on a silver screen still had 55% of its theoretical capacity (initial efficiency was 85%). There was no evidence of deterioration of gassing properties with cycling of the nickel electrodes. The charge temperature was observed to be the most critical variable governing nickel electrode gassing. This variable was shown to be age dependent. Four types of cadmium electrodes were tested: an electrodeposited cadmium active mass on a cadmium or silver substrate, a porous sintered silver substrate based electrode, and a Teflon bonded pressed cadmium electrode. The electrodeposited cadmium mass on a silver screen was found to be the best all-around electrode from a performance point of view and from the point of view of manufacturing them in a size required for a 25 Ah size battery.

A Short-Term Advantage for Syngamy in the Origin of Eukaryotic Sex: Effects of Cell Fusion on Cell Cycle Duration and Other Effects Related to the Duration of the Cell Cycle-Relationship between Cell Growth Curve and the Optimal Size of the Species, and Circadian Cell Cycle in Photosynthetic Unicellular Organisms.

PubMed

Mancebo Quintana, J M; Mancebo Quintana, S

2012-01-01

The origin of sex is becoming a vexatious issue for Evolutionary Biology. Numerous hypotheses have been proposed, based on the genetic effects of sex, on trophic effects or on the formation of cysts and syncytia. Our approach addresses the change in cell cycle duration which would cause cell fusion. Several results are obtained through graphical and mathematical analysis and computer simulations. (1) In poor environments, cell fusion would be an advantageous strategy, as fusion between cells of different size shortens the cycle of the smaller cell (relative to the asexual cycle), and the majority of mergers would occur between cells of different sizes. (2) The easiest-to-evolve regulation of cell proliferation (sexual/asexual) would be by modifying the checkpoints of the cell cycle. (3) A regulation of this kind would have required the existence of the G2 phase, and sex could thus be the cause of the appearance of this phase. Regarding cell cycle, (4) the exponential curve is the only cell growth curve that has no effect on the optimal cell size in unicellular species; (5) the existence of a plateau with no growth at the end of the cell cycle explains the circadian cell cycle observed in unicellular algae.

Effects of cerium on the hydrogen absorption-desorption properties of rare earth-Mg-Ni hydrogen-absorbing alloys

NASA Astrophysics Data System (ADS)

Yasuoka, Shigekazu; Ishida, Jun; Kishida, Kyosuke; Inui, Haruyuki

2017-04-01

The influence of Ce addition on the phase constitution, microstructure, hydrogen absorption/desorption properties and battery performances of newly developed rare earth (RE)-Mg-Ni hydrogen-absorbing superlattice alloys for negative electrode materials in Ni-metal hydride (MH) batteries were investigated. The partial substitution of RE (La and Nd) with Ce results in a higher discharge performance and a lower cycle life in the battery. The Ce addition greatly affects the phase constitution, which is mainly characterized by increased formation of the AB2 phase (A = RE or Mg and B = Ni or Al). The existence of the AB2 phase is found to accelerate alloy pulverization and oxidation when the alloys are used as negative electrode materials in Ni-MH model cells. The accelerated pulverization and oxidation are considered to be responsible for the observed higher discharge performance and lower cycle life in the batteries, respectively.

A balance of FGF and BMP signals regulates cell cycle exit and Equarin expression in lens cells

PubMed Central

Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena

2012-01-01

In embryonic and adult lenses, a balance of cell proliferation, cell cycle exit, and differentiation is necessary to maintain physical function. The molecular mechanisms regulating the transition of proliferating lens epithelial cells to differentiated primary lens fiber cells are poorly characterized. To investigate this question, we used gain- and loss-of-function analyses to modulate fibroblast growth factor (FGF) and/or bone morphogenetic protein (BMP) signals in chick lens/retina explants. Here we show that FGF activity plays a key role for proliferation independent of BMP signals. Moreover, a balance of FGF and BMP signals regulates cell cycle exit and the expression of Ccdc80 (also called Equarin), which is expressed at sites where differentiation of lens fiber cells occurs. BMP activity promotes cell cycle exit and induces Equarin expression in an FGF-dependent manner. In contrast, FGF activity is required but not sufficient to induce cell cycle exit or Equarin expression. Furthermore, our results show that in the absence of BMP activity, lens cells have increased cell cycle length or are arrested in the cell cycle, which leads to decreased cell cycle exit. Taken together, these findings suggest that proliferation, cell cycle exit, and early differentiation of primary lens fiber cells are regulated by counterbalancing BMP and FGF signals. PMID:22718906

Transcription Factor Binding Profiles Reveal Cyclic Expression of Human Protein-coding Genes and Non-coding RNAs

PubMed Central

Cheng, Chao; Ung, Matthew; Grant, Gavin D.; Whitfield, Michael L.

2013-01-01

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and a combination of the two types of features can further improve prediction accuracy. We apply our model to a complete list of GENCODE promoters to predict novel cell cycle driving promoters for both protein-coding genes and non-coding RNAs such as lincRNAs. We find that a similar percentage of lincRNAs are cell cycle regulated as protein-coding genes, suggesting the importance of non-coding RNAs in cell cycle division. The model we propose here provides not only a practical tool for identifying novel cell cycle genes with high accuracy, but also new insights on cell cycle regulation by TFs and cis-regulatory elements. PMID:23874175

Cycle life test and failure model of nickel-hydrogen cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1983-01-01

Six ampere hour individual pressure vessel nickel hydrogen cells were charge/discharge cycled to failure. Failure as used here is defined to occur when the end of discharge voltage degraded to 0.9 volts. They were cycled under a low earth orbit cycle regime to a deep depth of discharge (80 percent of rated ampere hour capacity). Both cell designs were fabricated by the same manufacturer and represent current state of the art. A failure model was advanced which suggests both cell designs have inadequate volume tolerance characteristics. The limited existing data base at a deep depth of discharge (DOD) was expanded. Two cells of each design were cycled. One COMSAT cell failed at cycle 1712 and the other failed at cycle 1875. For the Air Force/Hughes cells, one cell failed at cycle 2250 and the other failed at cycle 2638. All cells, of both designs, failed due to low end of discharge voltage (0.9 volts). No cell failed due to electrical shorts. After cell failure, three different reconditioning tests (deep discharge, physical reorientation, and open circuit voltage stand) were conducted on all cells of each design. A fourth reconditioning test (electrolyte addition) was conducted on one cell of each design. In addition post cycle cell teardown and failure analysis were performed on the one cell of each design which did not have electrolyte added after failure.

Cell Cycle Control by PTEN.

PubMed

Brandmaier, Andrew; Hou, Sheng-Qi; Shen, Wen H

2017-07-21

Continuous and error-free chromosome inheritance through the cell cycle is essential for genomic stability and tumor suppression. However, accumulation of aberrant genetic materials often causes the cell cycle to go awry, leading to malignant transformation. In response to genotoxic stress, cells employ diverse adaptive mechanisms to halt or exit the cell cycle temporarily or permanently. The intrinsic machinery of cycling, resting, and exiting shapes the cellular response to extrinsic stimuli, whereas prevalent disruption of the cell cycle machinery in tumor cells often confers resistance to anticancer therapy. Phosphatase and tensin homolog (PTEN) is a tumor suppressor and a guardian of the genome that is frequently mutated or deleted in human cancer. Moreover, it is increasingly evident that PTEN deficiency disrupts the fundamental processes of genetic transmission. Cells lacking PTEN exhibit cell cycle deregulation and cell fate reprogramming. Here, we review the role of PTEN in regulating the key processes in and out of cell cycle to optimize genomic integrity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of the interface between polyester and spent coffee grounds in polysaccharide membranes: Preparation, cell proliferation, antioxidant activity and tyrosinase activity.

PubMed

Wu, Chin-San

2017-09-01

The structural, antioxidant and cytocompatibility properties of membranes prepared from polyhydroxyalkanoate (PHA) and spent coffee ground (SCG) blends (PHA/SCG) were studied. Acrylic acid-grafted PHA (PHA-g-AA) was used to enhance the desirable characteristics of these membranes, which had better tensile properties than the corresponding PHA/SCG membranes. The water resistance of the PHA-g-AA/SCG membranes was greater than that of the PHA/SCG membranes, and a cytocompatibility evaluation with mouse normal tail fibroblasts (FBs) indicated that both materials were nontoxic. Cell cycle assays of FBs on PHA/SCG and PHA-g-AA/SCG membrane samples were not affected by the DNA content related to damage. Moreover, SCG enhanced the saccharide and polyphenol contents, and antioxidant properties, of the PHA-g-AA/SCG and PHA/SCG membranes. Therefore, we analysed the effects of these compounds' membranes on melanogenesis in B16-F10 melanoma cells. The results demonstrated that PHA/SCG and PHA-g-AA/SCG membranes reduced cellular tyrosinase activities in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets.

PubMed

Rojas, Ángela; Del Campo, Jose A; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D; Rosenberg, Arielle R; Negro, Francesco; Romero-Gómez, Manuel

2016-08-22

Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV.

Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets

PubMed Central

Rojas, Ángela; Del Campo, Jose A.; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D.; Rosenberg, Arielle R.; Negro, Francesco; Romero-Gómez, Manuel

2016-01-01

Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

Al/Pb lightweight grids prepared by molten salt electroless plating for application in lead-acid batteries

NASA Astrophysics Data System (ADS)

Hong, Bo; Jiang, Liangxing; Hao, Ketao; Liu, Fangyang; Yu, Xiaoying; Xue, Haitao; Li, Jie; Liu, Yexiang

2014-06-01

In this paper, a lightweight Pb plated Al (Al/Pb) grid was prepared by molten salt electroless plating. The SEM and bonding strength test show that the lead coating is deposited with a smooth surface and firm combination. CV test shows that the electrochemical properties of Al/Pb electrodes are stable. 2.0 V single-cell flooded lead-acid batteries with Al/Pb grids as negative collectors are assembled and the performances including 20 h capacity, rate capacity, cycle life, internal resistance are investigated. The results show that the cycle life of Al/Pb-grid cells is about 475 cycles and can meet the requirement of lead-acid batteries. Al/Pb grids are conducive to the refinement of PbSO4 grain, and thereby reduce the internal resistance of battery and advance the utilization of active mass. Moreover, weight of Al/Pb grid is only 55.4% of the conventional-grid. In this way, mass specific capacity of Al/Pb-grid negatives is 17.8% higher and the utilization of active mass is 6.5% higher than conventional-grid negatives.

Mussel-Inspired Conductive Polymer Binder for Si-Alloy Anode in Lithium-Ion Batteries

DOE PAGES

Zhao, Hui; Wei, Yang; Wang, Cheng; ...

2018-01-15

The excessive volume changes during cell cycling of Si-based anode in lithium ion batteries impeded its application. One major reason for the cell failure is particle isolation during volume shrinkage in delithiation process, which makes strong adhesion between polymer binder and anode active material particles a highly desirable property. Here, a biomimetic side-chain conductive polymer incorporating catechol, a key adhesive component of the mussel holdfast protein, was synthesized. Atomic force microscopy-based single-molecule force measurements of mussel-inspired conductive polymer binder contacting a silica surface revealed a similar adhesion toward substrate when compared with an effective Si anode binder, homo-poly(acrylic acid), withmore » the added benefit of being electronically conductive. Electrochemical experiments showed a very stable cycling of Si-alloy anodes realized via this biomimetic conducting polymer binder, leading to a high loading Si anode with a good rate performance. We attribute the ability of the Si-based anode to tolerate the volume changes during cycling to the excellent mechanical integrity afforded by the strong interfacial adhesion of the biomimetic conducting polymer.« less

Redox-Active Supramolecular Polymer Binders for Lithium–Sulfur Batteries That Adapt Their Transport Properties in Operando

DOE PAGES

Frischmann, Peter D.; Hwa, Yoon; Cairns, Elton J.; ...

2016-10-25

π-Stacked perylene bisimide (PBI) molecules are implemented here as highly networked, redox-active supramolecular polymer binders in sulfur cathodes for lightweight and energy-dense Li-S batteries. We show that the in operando reduction and lithiation of these PBI binders sustainably reduces Li-S cell impedance relative to nonredox active conventional polymer binders. This lower impedance enables high-rate cycling in Li-S cells with excellent durability, a critical step toward unlocking the full potential of Li-S batteries for electric vehicles and aviation.

Protective mechanisms of p53-p21-pRb proteins against DNA damage-induced cell death.

PubMed

Garner, Elizabeth; Raj, Kenneth

2008-02-01

There have been innumerate demonstrations of p53's activity as a tumour suppressor protein with the ability to stimulate cell signalling that can lead to cell cycle arrest and cell death in the event of DNA damage. Despite the solid body of evidence to support these properties of p53, reports have emerged that suggest a role for p53 in protecting cells from cell death. Our recent report highlighted a mechanism by which p53 activity can promote cell survival in the event of DNA damage. Here we present the various mechanisms that are activated by p53 signalling that can confer protection to cells with damaged DNA and emphasise the practical and clinical implications of a more balanced and context-dependent understanding of p53's pro-apoptotic and pro-survival activities.

Live cell imaging reveals marked variability in myoblast proliferation and fate

PubMed Central

2013-01-01

Background During the process of muscle regeneration, activated stem cells termed satellite cells proliferate, and then differentiate to form new myofibers that restore the injured area. Yet not all satellite cells contribute to muscle repair. Some continue to proliferate, others die, and others become quiescent and are available for regeneration following subsequent injury. The mechanisms that regulate the adoption of different cell fates in a muscle cell precursor population remain unclear. Methods We have used live cell imaging and lineage tracing to study cell fate in the C2 myoblast line. Results Analyzing the behavior of individual myoblasts revealed marked variability in both cell cycle duration and viability, but similarities between cells derived from the same parental lineage. As a consequence, lineage sizes and outcomes differed dramatically, and individual lineages made uneven contributions toward the terminally differentiated population. Thus, the cohort of myoblasts undergoing differentiation at the end of an experiment differed dramatically from the lineages present at the beginning. Treatment with IGF-I increased myoblast number by maintaining viability and by stimulating a fraction of cells to complete one additional cell cycle in differentiation medium, and as a consequence reduced the variability of the terminal population compared with controls. Conclusion Our results reveal that heterogeneity of responses to external cues is an intrinsic property of cultured myoblasts that may be explained in part by parental lineage, and demonstrate the power of live cell imaging for understanding how muscle differentiation is regulated. PMID:23638706

Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype.

PubMed

Mosieniak, Grażyna; Sliwinska, Małgorzata A; Przybylska, Dorota; Grabowska, Wioleta; Sunderland, Piotr; Bielak-Zmijewska, Anna; Sikora, Ewa

2016-05-01

Cellular senescence is recognized as a potent anticancer mechanism that inhibits carcinogenesis. Cancer cells can also undergo senescence upon chemo- or radiotherapy. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, shows anticancer properties both in vitro and in vivo. Previously, we have shown that treatment with curcumin leads to senescence of human cancer cells. Now we identified the molecular mechanism underlying this phenomenon. We observed a time-dependent accumulation of mitotic cells upon curcumin treatment. The time-lapse analysis proved that those cells progressed through mitosis for a significantly longer period of time. A fraction of cells managed to divide or undergo mitotic slippage and then enter the next phase of the cell cycle. Cells arrested in mitosis had an improperly formed mitotic spindle and were positive for γH2AX, which shows that they acquired DNA damage during prolonged mitosis. Moreover, the DNA damage response pathway was activated upon curcumin treatment and the components of this pathway remained upregulated while cells were undergoing senescence. Inhibition of the DNA damage response decreased the number of senescent cells. Thus, our studies revealed that the induction of cell senescence upon curcumin treatment resulted from aberrant progression through the cell cycle. Moreover, the DNA damage acquired by cancer cells, due to mitotic disturbances, activates an important molecular mechanism that determines the potential anticancer activity of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergistic Effect of Curcumin in Combination with Anticancer Agents in Human Retinoblastoma Cancer Cell Lines.

PubMed

Sreenivasan, Seethalakshmi; Krishnakumar, Subramanian

2015-01-01

Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of the herb Curcuma longa, is known to have anti-proliferative and anti-tumor properties. In this study, we evaluated the cytotoxic effect of curcumin alone and in combination with individual drugs like carboplatin, etoposide, or vincristine in a human retinoblastoma (RB) cancer cell line. A drug-drug interaction was analyzed using the median effect/isobologram method and combination index values were used to characterize the interaction as synergistic or additive. We also performed the apoptosis and cell-cycle kinetics study with single drugs in combination with curcumin in a human RB cell lines (Y79 and Weri-Rb1). Curcumin caused concentration-dependent decrease in cell proliferation, cell kinetics, and also induced apoptosis in both the RB cell lines. When combination of curcumin with individual drugs like carboplatin or etoposide or vincristine was treated on to RB cells, both cell viability and cell cycling were reduced and increased apoptosis was noted, in comparison with single drug treatment. These effects were significant in both the cell lines, indicating the ability of curcumin to increase the sensitivity of RB cells to chemotherapy drugs. Our in vitro findings showed that the combination of curcumin with single drug treatment showed marked synergistic inhibitory effect against RB cell lines. These results suggest that curcumin can be used as a modulator which may have a potential therapeutic value for the treatment of RB cancer patients.

Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest.

PubMed

Omer, Fatima Abdelmutaal Ahmed; Hashim, Najihah Binti Mohd; Ibrahim, Mohamed Yousif; Dehghan, Firouzeh; Yahayu, Maizatulakmal; Karimian, Hamed; Salim, Landa Zeenelabdin Ali; Mohan, Syam

2017-11-01

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G 0 /G 1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G 0 /G 1 phase and prompted the intrinsic apoptosis pathway.

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I'm-Yunity™ (PSP)

PubMed Central

Hsieh, Tze-chen; Wu, Peili; Park, Spencer; Wu, Joseph M

2006-01-01

Background I'm-Yunity™ (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I'm-Yunity™ (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I'm-Yunity™ (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I'm-Yunity™ (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I'm-Yunity™ (PSP) elicits these effects. Methods Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I'm-Yunity™ (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins. Results Aqueous extracts of I'm-Yunity™ (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G1/S and G2/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I'm-Yunity™ (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-κB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I'm-Yunity™ (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase). Conclusion Aqueous extracts of I'm-Yunity™ (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I'm-Yunity™ (PSP). PMID:16965632

Functional characterization of T cells in abdominal aortic aneurysms

PubMed Central

Forester, Nerys D; Cruickshank, Sheena M; Scott, D Julian A; Carding, Simon R

2005-01-01

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4·5 × 106 cells per gram of AAA tissue. The majority (58·1 ± 5·3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41·1 ± 5·7%, natural killer cells 7·3 ± 2·5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-α, interferon-γ, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help. PMID:15885133

The therapeutic potential of cell cycle targeting in multiple myeloma.

PubMed

Maes, Anke; Menu, Eline; Veirman, Kim De; Maes, Ken; Vand Erkerken, Karin; De Bruyne, Elke

2017-10-27

Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells. Importantly, several of these cell cycle regulatory proteins have also been proposed as therapeutic targets in the plasma cell malignancy multiple myeloma (MM). Despite the enormous progress in the treatment of MM the past 5 years, MM still remains most often incurable due to the development of drug resistance. Deregulated expression of the cyclins D is observed in virtually all myeloma patients, emphasizing the potential therapeutic interest of cyclin-dependent kinase inhibitors in MM. Furthermore, other targets have also been identified in MM, such as microtubules, kinesin motor proteins, aurora kinases, polo-like kinases and the anaphase promoting complex/cyclosome. This review will provide an overview of the cell cycle proteins and checkpoint pathways deregulated in MM and discuss the therapeutic potential of targeting proteins or protein complexes involved in cell cycle control in MM.

NASA Lewis advanced IPV nickel-hydrogen technology

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Britton, Doris L.

1993-01-01

Individual pressure vessel (IPV) nickel-hydrogen technology was advanced at NASA Lewis and under Lewis contracts. Some of the advancements are as follows: to use 26 percent potassium hydroxide electrolyte to improve cycle life and performance, to modify the state of the art cell design to eliminate identified failure modes and further improve cycle life, and to develop a lightweight nickel electrode to reduce battery mass, hence reduce launch and/or increase satellite payload. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen battery cells was reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 accelerated LEO cycles at 80 percent DOD compared to 3,500 cycles for cells containing 31 percent KOH. Results of the boiler plate cell tests have been validated at NWSC, Crane, Indiana. Forty-eight ampere-hour flight cells containing 26 and 31 percent KOH have undergone real time LEO cycle life testing at an 80 percent DOD, 10 C. The three cells containing 26 percent KOH failed on the average at cycle 19,500. The three cells containing 31 percent KOH failed on the average at cycle 6,400. Validation testing of NASA Lewis 125 Ah advanced design IPV nickel-hydrogen flight cells is also being conducted at NWSC, Crane, Indiana under a NASA Lewis contract. This consists of characterization, storage, and cycle life testing. There was no capacity degradation after 52 days of storage with the cells in the discharged state, on open circuit, 0 C, and a hydrogen pressure of 14.5 psia. The catalyzed wall wick cells have been cycled for over 22,694 cycles with no cell failures in the continuing test. All three of the non-catalyzed wall wick cells failed (cycles 9,588; 13,900; and 20,575). Cycle life test results of the Fibrex nickel electrode has demonstrated the feasibility of an improved nickel electrode giving a higher specific energy nickel-hydrogen cell. A nickel-hydrogen boiler plate cell using an 80 mil thick, 90 percent porous Fibrex nickel electrode has been cycled for 10,000 cycles at 40 percent DOD.

Effect of cycling on the lithium/electrolyte interface in organic electrolytes

NASA Technical Reports Server (NTRS)

Surampudi, S.; Shen, D. H.; Huang, C.-K.; Narayanan, S. R.; Attia, A.; Halpert, G.; Peled, E.

1993-01-01

Nondestructive methods such as ac impedance spectroscopy and microcalorimetry are used to study the effect of cell cycling on the lithium/electrolyte interface. The reactivity of both uncycled and cycled lithium towards various electrolytes is examined by measuring the heat evolved from the cells under open-circuit conditions at 25 C by microcalorimetry. Cycled cells at the end of charge/discharge exhibited considerably higher heat output compared with the uncycled cells. After 30 d of storage, the heat output of the cycled cells is similar to that of the uncycled cells. The cell internal resistance increases with cycling, and this is attributed to the degradation of the electrolyte with cycling.

The protective effect of niacinamide on CHO AA8 cell line against ultraviolet radiation in the context of main cytoskeletal proteins.

PubMed

Izdebska, Magdalena; Hałas-Wiśniewska, Marta; Adamczyk, Iwona; Lewandowska, Ismena; Kwiatkowska, Iga; Gagat, Maciej; Grzanka, Alina

2018-03-13

Niacinamide is a stable and water-soluble form of vitamin B3, a valuable and versatile cosmetic ingredient, which is well absorbed and tolerated by the skin. A large body of literature has reported on the antioxidant and cell repair properties of niacinamide. Therefore, it has been shown to be useful in the protection of the skin against ultraviolet B (UVB) radiation and free radicals. Despite numerous hypotheses on the mechanism of vitamin B3, its protective effects have not yet been fully elucidated. The aim of the study was to determine the protective effects of niacinamide on CHO AA8 cell line against UVB radiation. We assessed the following factors: cell death, cell cycle phase distributions, reorganization of main cytoskeletal proteins, such as F-actin, vimentin and β-tubulin, and also alterations at the ultrastructural level. The material used for our research was Chinese hamster ovary cell line (CHO AA8). We used 4 research groups: 1) control cells; 2) cells treated with niacinamide; 3) cells exposed to UV radiation; and 4) cells co-incubated with niacinamide and next exposed to ultraviolet. The cell death and cell cycle were evaluated by a Tali® based-image cytometer. A fluorescence microscope was used to assess the reorganization of cytoskeletal proteins, whereas a transmission electron microscope enabled the evaluation of the alterations at the ultrastructural level of cells. We showed that UV-induced apoptosis and cell cycle distributions during treatment with niacinamide resulted in a non-statistical significance in cell survival and no significant changes in the morphology and cytoskeleton in comparison to the control group. In turn, a combination of both factors led to an increase in the population of live cells and a decreased level of apoptotic cells in comparison to UV-exposed cells. Our results confirmed the harmful effects of UV radiation on CHO AA8 cell line. Furthermore, niacinamide can protect cells against these factors, and the mechanism of action may be related to the stabilization of the cell cytoskeleton.

Silver deposition on titanium surface by electrochemical anodizing process reduces bacterial adhesion of Streptococcus sanguinis and Lactobacillus salivarius.

PubMed

Godoy-Gallardo, Maria; Rodríguez-Hernández, Ana G; Delgado, Luis M; Manero, José M; Javier Gil, F; Rodríguez, Daniel

2015-10-01

The aim of this study was to determine the antibacterial properties of silver-doped titanium surfaces prepared with a novel electrochemical anodizing process. Titanium samples were anodized with a pulsed process in a solution of silver nitrate and sodium thiosulphate at room temperature with stirring. Samples were processed with different electrolyte concentrations and treatment cycles to improve silver deposition. Physicochemical properties were determined by X-ray photoelectron spectroscopy, contact angle measurements, white-light interferometry, and scanning electron microscopy. Cellular cytotoxicity in human fibroblasts was studied with lactate dehydrogenase assays. The in vitro effect of treated surfaces on two oral bacteria strains (Streptococcus sanguinis and Lactobacillus salivarius) was studied with viable bacterial adhesion measurements and growth curve assays. Nonparametric statistical Kruskal-Wallis and Mann-Whitney U-tests were used for multiple and paired comparisons, respectively. Post hoc Spearman's correlation tests were calculated to check the dependence between bacteria adhesion and surface properties. X-ray photoelectron spectroscopy results confirmed the presence of silver on treated samples and showed that treatments with higher silver nitrate concentration and more cycles increased the silver deposition on titanium surface. No negative effects in fibroblast cell viability were detected and a significant reduction on bacterial adhesion in vitro was achieved in silver-treated samples compared with control titanium. Silver deposition on titanium with a novel electrochemical anodizing process produced surfaces with significant antibacterial properties in vitro without negative effects on cell viability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eryptosis and hemorheological responses to maximal exercise in athletes: Comparison between running and cycling.

PubMed

Nader, E; Guillot, N; Lavorel, L; Hancco, I; Fort, R; Stauffer, E; Renoux, C; Joly, P; Germain, M; Connes, P

2018-05-01

We compared the effects of cycling and running exercise on hemorheological and hematological properties, as well as eryptosis markers. Seven endurance-trained subjects randomly performed a progressive and maximal exercise test on a cycle ergometer and a treadmill. Blood was sampled at rest and at the end of the exercise to analyze hematological and blood rheological parameters including hematocrit (Hct), red blood cell (RBC) deformability, aggregation, and blood viscosity. Hemoglobin saturation (SpO2), blood lactate, and glucose levels were also monitored. Red blood cell oxidative stress, calcium content, and phosphatidylserine exposure were determined by flow cytometry to assess eryptosis level. Cycling exercise increased blood viscosity and RBC aggregation whereas it had no significant effect on RBC deformability. In contrast, blood viscosity remained unchanged and RBC deformability increased with running. The increase in Hct, lactate, and glucose concentrations and the loss of weight at the end of exercise were not different between running and cycling. Eryptosis markers were not affected by exercise. A significant drop in SpO2 was noted during running but not during cycling. Our study showed that a progressive and maximal exercise test conducted on a cycle ergometer increased blood viscosity while the same test conducted on a treadmill did not change this parameter because of different RBC rheological behavior between the 2 tests. We also demonstrated that a short maximal exercise does not alter RBC physiology in trained athletes. We suspect that exercise-induced hypoxemia occurring during running could be at the origin of the RBC rheological behavior differences with cycling. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle

PubMed Central

Le Van Quyen, Michel; Muller, Lyle E.; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G.; Dehghani, Nima; Destexhe, Alain

2016-01-01

Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake–sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS. PMID:27482084

A holistic view of polyhydroxyalkanoate metabolism in Pseudomonas putida.

PubMed

Prieto, Auxiliadora; Escapa, Isabel F; Martínez, Virginia; Dinjaski, Nina; Herencias, Cristina; de la Peña, Fernando; Tarazona, Natalia; Revelles, Olga

2016-02-01

Polyhydroxyalkanoate (PHA) metabolism has been traditionally considered as a futile cycle involved in carbon and energy storage. The use of cutting-edge technologies linked to systems biology has improved our understanding of the interaction between bacterial physiology, PHA metabolism and other cell functions in model bacteria such as Pseudomonas putida KT2440. PHA granules or carbonosomes are supramolecular complexes of biopolyester and proteins that are essential for granule segregation during cell division, and for the functioning of the PHA metabolic route as a continuous cycle. The simultaneous activities of PHA synthase and depolymerase ensure the carbon flow to the transient demand for metabolic intermediates to balance the storage and use of carbon and energy. PHA cycle also determines the number and size of bacterial cells. The importance of PHAs as nutrients for members of the microbial community different to those that produce them is illustrated here via examples of bacterial predators such as Bdellovibrio bacteriovorus that prey on PHA producers and produces specific extra-cellular depolymerases. PHA hydrolysis confers Bdellovibrio ecological advantages in terms of motility and predation efficiency, demonstrating the importance of PHA producers predation in population dynamics. Metabolic modulation strategies for broadening the portfolio of PHAs are summarized and their properties are compiled. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

High-frequency oscillations in human and monkey neocortex during the wake-sleep cycle.

PubMed

Le Van Quyen, Michel; Muller, Lyle E; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G; Dehghani, Nima; Destexhe, Alain

2016-08-16

Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake-sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS.

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

PubMed

Ahn, Eunyong; Kumar, Praveen; Mukha, Dzmitry; Tzur, Amit; Shlomi, Tomer

2017-11-06

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Playing with the cell cycle to build the spinal cord.

PubMed

Molina, Angie; Pituello, Fabienne

2017-12-01

A fundamental issue in nervous system development and homeostasis is to understand the mechanisms governing the balance between the maintenance of proliferating progenitors versus their differentiation into post-mitotic neurons. Accumulating data suggest that the cell cycle and core regulators of the cell cycle machinery play a major role in regulating this fine balance. Here, we focus on the interplay between the cell cycle and cellular and molecular events governing spinal cord development. We describe the existing links between the cell cycle and interkinetic nuclear migration (INM). We show how the different morphogens patterning the neural tube also regulate the cell cycle machinery to coordinate proliferation and patterning. We give examples of how cell cycle core regulators regulate transcriptionally, or post-transcriptionally, genes involved in controlling the maintenance versus the differentiation of neural progenitors. Finally, we describe the changes in cell cycle kinetics occurring during neural tube patterning and at the time of neuronal differentiation, and we discuss future research directions to better understand the role of the cell cycle in cell fate decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

mir-300 promotes self-renewal and inhibits the differentiation of glioma stem-like cells.

PubMed

Zhang, Daming; Yang, Guang; Chen, Xin; Li, Chunmei; Wang, Lu; Liu, Yaohua; Han, Dayong; Liu, Huailei; Hou, Xu; Zhang, Weiguang; Li, Chenguang; Han, Zhanqiang; Gao, Xin; Zhao, Shiguang

2014-08-01

MicroRNAs (miRNAs) are small noncoding RNAs that have been critically implicated in several human cancers. miRNAs are thought to participate in various biological processes, including proliferation, cell cycle, apoptosis, and even the regulation of the stemness properties of cancer stem cells. In this study, we explore the potential role of miR-300 in glioma stem-like cells (GSLCs). We isolated GSLCs from glioma biopsy specimens and identified the stemness properties of the cells through neurosphere formation assays, multilineage differentiation ability analysis, and immunofluorescence analysis of glioma stem cell markers. We found that miR-300 is commonly upregulated in glioma tissues, and the expression of miR-300 was higher in GSLCs. The results of functional experiments demonstrated that miR-300 can enhance the self-renewal of GSLCs and reduce differentiation toward both astrocyte and neural fates. In addition, LZTS2 is a direct target of miR-300. In conclusion, our results demonstrate the critical role of miR-300 in GSLCs and its functions in LZTS2 inhibition and describe a new approach for the molecular regulation of tumor stem cells.

Cell cycle proteins as promising targets in cancer therapy.

PubMed

Otto, Tobias; Sicinski, Piotr

2017-01-27

Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.

Cell cycle nucleic acids, polypeptides and uses thereof

DOEpatents

Gordon-Kamm, William J [Urbandale, IA; Lowe, Keith S [Johnston, IA; Larkins, Brian A [Tucson, AZ; Dilkes, Brian R [Tucson, AZ; Sun, Yuejin [Westfield, IN

2007-08-14

The invention provides isolated nucleic acids and their encoded proteins that are involved in cell cycle regulation. The invention further provides recombinant expression cassettes, host cells, transgenic plants, and antibody compositions. The present invention provides methods and compositions relating to altering cell cycle protein content, cell cycle progression, cell number and/or composition of plants.

Quantitative Cell Cycle Analysis Based on an Endogenous All-in-One Reporter for Cell Tracking and Classification.

PubMed

Zerjatke, Thomas; Gak, Igor A; Kirova, Dilyana; Fuhrmann, Markus; Daniel, Katrin; Gonciarz, Magdalena; Müller, Doris; Glauche, Ingmar; Mansfeld, Jörg

2017-05-30

Cell cycle kinetics are crucial to cell fate decisions. Although live imaging has provided extensive insights into this relationship at the single-cell level, the limited number of fluorescent markers that can be used in a single experiment has hindered efforts to link the dynamics of individual proteins responsible for decision making directly to cell cycle progression. Here, we present fluorescently tagged endogenous proliferating cell nuclear antigen (PCNA) as an all-in-one cell cycle reporter that allows simultaneous analysis of cell cycle progression, including the transition into quiescence, and the dynamics of individual fate determinants. We also provide an image analysis pipeline for automated segmentation, tracking, and classification of all cell cycle phases. Combining the all-in-one reporter with labeled endogenous cyclin D1 and p21 as prime examples of cell-cycle-regulated fate determinants, we show how cell cycle and quantitative protein dynamics can be simultaneously extracted to gain insights into G1 phase regulation and responses to perturbations. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Interplay between cancer cell cycle and metabolism: Challenges, targets and therapeutic opportunities.

PubMed

Roy, Debmalya; Sheng, Gao Ying; Herve, Semukunzi; Carvalho, Evandro; Mahanty, Arpan; Yuan, Shengtao; Sun, Li

2017-05-01

A growing interest has emerged in the field of studying the cross-talk between cancer cell cycle and metabolism. In this review, we aimed to present how metabolism and cell cycle are correlated and how cancer cells get energy to drive cell cycle. Cell proliferation and cell death largely depend on the metabolic activity of the cell. Cell cycle proteins, e.g. cyclin D, cyclin dependent kinase (CDK), some pro-apoptotic and anti-apoptotic proteins, and P53 have been shown to be regulated by metabolic crosstalk. Dysregulation of this cross-talk between metabolism and cell cycle leads to degenerative disorder(s) and cancer. It is not fully understood the actual reason of aberration between metabolism and cell cycle, but it is a hallmark of cancer research. Herein, we discussed the role of some regulatory molecules relative of cell cycle and metabolism and highlight how they control the function of each other. We also pointed out, current therapeutic opportunities and some additional crucial therapeutic targets on these fields that could be a breakthrough in cancer research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cells. An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent potassium hydroxide (KOH) electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen cells is reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cells - An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent potassium hydroxide (KOH) electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen cells is reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH.

Effect of LEO cycling on 125 Ah advanced design IPV nickel-hydrogen flight cells - An update

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in LEO cycle life of nickel-hydrogen cells containing 26 percent potassium hydroxide (KOH) electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen cells is reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH.

SR4 Uncouples Mitochondrial Oxidative Phosphorylation, Modulates AMP-dependent Kinase (AMPK)-Mammalian Target of Rapamycin (mTOR) Signaling, and Inhibits Proliferation of HepG2 Hepatocarcinoma Cells*

PubMed Central

Figarola, James L.; Singhal, Jyotsana; Tompkins, Joshua D.; Rogers, George W.; Warden, Charles; Horne, David; Riggs, Arthur D.; Awasthi, Sanjay; Singhal, Sharad S.

2015-01-01

Mitochondrial oxidative phosphorylation produces most of the energy in aerobic cells by coupling respiration to the production of ATP. Mitochondrial uncouplers, which reduce the proton gradient across the mitochondrial inner membrane, create a futile cycle of nutrient oxidation without generating ATP. Regulation of mitochondrial dysfunction and associated cellular bioenergetics has been recently identified as a promising target for anticancer therapy. Here, we show that SR4 is a novel mitochondrial uncoupler that causes dose-dependent increase in mitochondrial respiration and dissipation of mitochondrial membrane potential in HepG2 hepatocarcinoma cells. These effects were reversed by the recoupling agent 6-ketocholestanol but not cyclosporin A and were nonexistent in mitochondrial DNA-depleted HepG2 cells. In isolated mouse liver mitochondria, SR4 similarly increased oxygen consumption independent of adenine nucleotide translocase and uncoupling proteins, decreased mitochondrial membrane potential, and promoted swelling of valinomycin-treated mitochondria in potassium acetate medium. Mitochondrial uncoupling in HepG2 cells by SR4 results in the reduction of cellular ATP production, increased ROS production, activation of the energy-sensing enzyme AMPK, and inhibition of acetyl-CoA carboxylase and mammalian target of rapamycin signaling pathways, leading to cell cycle arrest and apoptosis. Global analysis of SR4-associated differential gene expression confirms these observations, including significant induction of apoptotic genes and down-regulation of cell cycle, mitochondrial, and oxidative phosphorylation pathway transcripts at 24 h post-treatment. Collectively, our studies demonstrate that the previously reported indirect activation of AMPK and in vitro anticancer properties of SR4 as well as its beneficial effects in both animal xenograft and obese mice models could be a direct consequence of its mitochondrial uncoupling activity. PMID:26534958

Exploring the Underlying Mechanisms of the Xenopus laevis Embryonic Cell Cycle.

PubMed

Zhang, Kun; Wang, Jin

2018-05-31

The cell cycle is an indispensable process in proliferation and development. Despite significant efforts, global quantification and physical understanding are still challenging. In this study, we explored the mechanisms of the Xenopus laevis embryonic cell cycle by quantifying the underlying landscape and flux. We uncovered the Mexican hat landscape of the Xenopus laevis embryonic cell cycle with several local basins and barriers on the oscillation path. The local basins characterize the different phases of the Xenopus laevis embryonic cell cycle, and the local barriers represent the checkpoints. The checkpoint mechanism of the cell cycle is revealed by the landscape basins and barriers. While landscape shape determines the stabilities of the states on the oscillation path, the curl flux force determines the stability of the cell cycle flow. Replication is fundamental for biology of living cells. We quantify the input energy (through the entropy production) as the thermodynamic requirement for initiation and sustainability of single cell life (cell cycle). Furthermore, we also quantify curl flux originated from the input energy as the dynamical requirement for the emergence of a new stable phase (cell cycle). This can provide a new quantitative insight for the origin of single cell life. In fact, the curl flux originated from the energy input or nutrition supply determines the speed and guarantees the progression of the cell cycle. The speed of the cell cycle is a hallmark of cancer. We characterized the quality of the cell cycle by the coherence time and found it is supported by the flux and energy cost. We are also able to quantify the degree of time irreversibility by the cross correlation function forward and backward in time from the stochastic traces in the simulation or experiments, providing a way for the quantification of the time irreversibility and the flux. Through global sensitivity analysis upon landscape and flux, we can identify the key elements for controlling the cell cycle speed. This can help to design an effective strategy for drug discovery against cancer.

Mechanism for ginkgolic acid (15 : 1)-induced MDCK cell necrosis: Mitochondria and lysosomes damages and cell cycle arrest.

PubMed

Yao, Qing-Qing; Liu, Zhen-Hua; Xu, Ming-Cheng; Hu, Hai-Hong; Zhou, Hui; Jiang, Hui-Di; Yu, Lu-Shan; Zeng, Su

2017-05-01

Ginkgolic acids (GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA (15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA (15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA (15 : 1) on MDCK cells displayed a time- and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA (15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential (ΔΨm). In propidium iodide (PI) staining analysis, GA (15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA (15 : 1) induced renal toxicity. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines.

PubMed

Tarjan, Gabor; Haines, G Kenneth; Vesper, Benjamin J; Xue, Jiaping; Altman, Michael B; Yarmolyuk, Yaroslav R; Khurram, Huma; Elseth, Kim M; Roeske, John C; Aydogan, Bulent; Radosevich, James A

2011-02-01

It is not understood why some head and neck squamous cell carcinomas, despite having identical morphology, demonstrate different tumor aggressiveness, including radioresistance. High levels of the free radical nitric oxide (NO) and increased expression of the NO-producing enzyme nitric oxide synthase (NOS) have been implicated in tumor progression. We previously adapted three human tongue cancer cell lines to high NO (HNO) levels by gradually exposing them to increasing concentrations of an NO donor; the HNO cells grew faster than their corresponding untreated ("parent") cells, despite being morphologically identical. Herein we initially characterize the HNO cells and compare the biological properties of the HNO and parent cells. HNO/parent cell line pairs were analyzed for cell cycle distribution, DNA damage, X-ray and ultraviolet radiation response, and expression of key cellular enzymes, including NOS, p53, glutathione S-transferase-pi (GST-pi), apurinic/apyrimidinic endonuclease-1 (APE1), and checkpoint kinases (Chk1, Chk2). While some of these properties were cell line-specific, the HNO cells typically exhibited properties associated with a more aggressive behavior profile than the parent cells (greater S-phase percentage, radioresistance, and elevated expression of GST-pi/APE1/Chk1/Chk2). To correlate these findings with conditions in primary tumors, we examined the NOS, GST-pi, and APE1 expression in human tongue squamous cell carcinomas. A majority of the clinical samples exhibited elevated expression levels of these enzymes. Together, the results herein suggest cancer cells exposed to HNO levels can develop resistance to free radicals by upregulating protective mechanisms, such as GST-pi and APE1. These upregulated defense mechanisms may contribute to their aggressive expression profile.

Identification of epithelial label-retaining cells at the transition between the anal canal and the rectum in mice

PubMed Central

Runck, Laura A; Kramer, Megan; Ciraolo, Georgianne; Lewis, Alfor G

2010-01-01

In certain regions of the body, transition zones exist where stratified squamous epithelia directly abut against other types of epithelia. Certain transition zones are especially prone to tumorigenesis an example being the anorectal junction, although the reason for this is not known. One possibility is that the abrupt transition of the simple columnar epithelium of the colon to the stratified squamous epithelium of the proximal portion of the anal canal may contain a unique stem cell niche. We investigated whether the anorectal region contained cells with stem cell properties relative to the adjacent epithelium. We utilized a tetracycline-regulatable histone H2B-GFP transgenic mice model, previously used to identify hair follicle stem cells, to fluorescently label slow-cycling anal epithelial cells (e.g., prospective stem cells) in combination with a panel of putative stem cell markers. We identified a population of long-term GFP label-retaining cells concentrated at the junction between the anal canal and the rectum. These cells are BrdU-retaining cells and expressed the stem cell marker CD34. Moreover, tracking the fate of the anal label-retaining cells in vivo revealed that the slow-cycling cells only gave rise to progeny of the anal epithelium. In conclusion, we identified a unique population of cells at the anorectal junction which can be separated from the other basal anal epithelial cells based upon the expression of the stem cell marker CD34 and integrin α6, and thus represent a putative anal stem cell population. PMID:20647777

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight cells-update 2

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1991-01-01

An update of validation test results confirming the breakthrough in low earth orbit (LEO) cycle life of nickel-hydrogen cells containing 26 percent KOH electrolyte is presented. A breakthrough in the LEO cycle life of individual pressure vessel (IPV nickel-hydrogen cells has been previously reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40 000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH. This test was conducted at Hughes Aircraft Company under a NASA Lewis contract. The purpose was to investigate the effect of KOH concentration on cycle life. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min discharge (2x normal rate). The depth of discharge (DOD) was 80 percent. The cell temperature was maintained at 23 C. The boiler plate test results are in the process of being validated using flight hardware and real time LEO test at the Naval Weapons Support Center (NWSC), Crane, Indiana under a NASA Lewis Contract. Six 48 Ah Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells), and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The three 31 percent KOH cells failed (cycles 3729, 4165, and 11355). One of the 26 percent KOH cells failed at cycle 15314. The other two 26 percent KOH cells were cycled for over 16600 cycles during the continuing test.

Cell-cycle control in the face of damage--a matter of life or death.

PubMed

Clarke, Paul R; Allan, Lindsey A

2009-03-01

Cells respond to DNA damage or defects in the mitotic spindle by activating checkpoints that arrest the cell cycle. Alternatively, damaged cells can undergo cell death by the process of apoptosis. The correct balance between these pathways is important for the maintenance of genomic integrity while preventing unnecessary cell death. Although the molecular mechanisms of the cell cycle and apoptosis have been elucidated, the links between them have not been clear. Recent work, however, indicates that common components directly link the regulation of apoptosis with cell-cycle checkpoints operating during interphase, whereas in mitosis, the control of apoptosis is directly coupled to the cell-cycle machinery. These findings shed new light on how the balance between cell-cycle progression and cell death is controlled.

Relationship between unit cell type and porosity and the fatigue behavior of selective laser melted meta-biomaterials.

PubMed

Amin Yavari, S; Ahmadi, S M; Wauthle, R; Pouran, B; Schrooten, J; Weinans, H; Zadpoor, A A

2015-03-01

Meta-materials are structures when their small-scale properties are considered, but behave as materials when their homogenized macroscopic properties are studied. There is an intimate relationship between the design of the small-scale structure and the homogenized properties of such materials. In this article, we studied that relationship for meta-biomaterials that are aimed for biomedical applications, otherwise known as meta-biomaterials. Selective laser melted porous titanium (Ti6Al4V ELI) structures were manufactured based on three different types of repeating unit cells, namely cube, diamond, and truncated cuboctahedron, and with different porosities. The morphological features, static mechanical properties, and fatigue behavior of the porous biomaterials were studied with a focus on their fatigue behavior. It was observed that, in addition to static mechanical properties, the fatigue properties of the porous biomaterials are highly dependent on the type of unit cell as well as on porosity. None of the porous structures based on the cube unit cell failed after 10(6) loading cycles even when the applied stress reached 80% of their yield strengths. For both other unit cells, higher porosities resulted in shorter fatigue lives for the same level of applied stress. When normalized with respect to their yield stresses, the S-N data points of structures with different porosities very well (R(2)>0.8) conformed to one single power law specific to the type of the unit cell. For the same level of normalized applied stress, the truncated cuboctahedron unit cell resulted in a longer fatigue life as compared to the diamond unit cell. In a similar comparison, the fatigue lives of the porous structures based on both truncated cuboctahedron and diamond unit cells were longer than that of the porous structures based on the rhombic dodecahedron unit cell (determined in a previous study). The data presented in this study could serve as a basis for design of porous biomaterials as well as for corroboration of relevant analytical and computational models. Copyright © 2014 Elsevier Ltd. All rights reserved.

The cell cycle of early mammalian embryos: lessons from genetic mouse models.

PubMed

Artus, Jérôme; Babinet, Charles; Cohen-Tannoudji, Michel

2006-03-01

Genes coding for cell cycle components predicted to be essential for its regulation have been shown to be dispensable in mice, at the whole organism level. Such studies have highlighted the extraordinary plasticity of the embryonic cell cycle and suggest that many aspects of in vivo cell cycle regulation remain to be discovered. Here, we discuss the particularities of the mouse early embryonic cell cycle and review the mutations that result in cell cycle defects during mouse early embryogenesis, including deficiencies for genes of the cyclin family (cyclin A2 and B1), genes involved in cell cycle checkpoints (Mad2, Bub3, Chk1, Atr), genes involved in ubiquitin and ubiquitin-like pathways (Uba3, Ubc9, Cul1, Cul3, Apc2, Apc10, Csn2) as well as genes the function of which had not been previously ascribed to cell cycle regulation (Cdc2P1, E4F and Omcg1).

Ionizing Radiation Changes the Electronic Properties of Melanin and Enhances the Growth of Melanized Fungi

PubMed Central

Dadachova, Ekaterina; Bryan, Ruth A.; Huang, Xianchun; Moadel, Tiffany; Schweitzer, Andrew D.; Aisen, Philip; Nosanchuk, Joshua D.; Casadevall, Arturo

2007-01-01

Background Melanin pigments are ubiquitous in nature. Melanized microorganisms are often the dominating species in certain extreme environments, such as soils contaminated with radionuclides, suggesting that the presence of melanin is beneficial in their life cycle. We hypothesized that ionizing radiation could change the electronic properties of melanin and might enhance the growth of melanized microorganisms. Methodology/Principal Findings Ionizing irradiation changed the electron spin resonance (ESR) signal of melanin, consistent with changes in electronic structure. Irradiated melanin manifested a 4-fold increase in its capacity to reduce NADH relative to non-irradiated melanin. HPLC analysis of melanin from fungi grown on different substrates revealed chemical complexity, dependence of melanin composition on the growth substrate and possible influence of melanin composition on its interaction with ionizing radiation. XTT/MTT assays showed increased metabolic activity of melanized C. neoformans cells relative to non-melanized cells, and exposure to ionizing radiation enhanced the electron-transfer properties of melanin in melanized cells. Melanized Wangiella dermatitidis and Cryptococcus neoformans cells exposed to ionizing radiation approximately 500 times higher than background grew significantly faster as indicated by higher CFUs, more dry weight biomass and 3-fold greater incorporation of 14C-acetate than non-irradiated melanized cells or irradiated albino mutants. In addition, radiation enhanced the growth of melanized Cladosporium sphaerospermum cells under limited nutrients conditions. Conclusions/Significance Exposure of melanin to ionizing radiation, and possibly other forms of electromagnetic radiation, changes its electronic properties. Melanized fungal cells manifested increased growth relative to non-melanized cells after exposure to ionizing radiation, raising intriguing questions about a potential role for melanin in energy capture and utilization. PMID:17520016

Model-Based Analysis of Cell Cycle Responses to Dynamically Changing Environments

PubMed Central

Seaton, Daniel D; Krishnan, J

2016-01-01

Cell cycle progression is carefully coordinated with a cell’s intra- and extracellular environment. While some pathways have been identified that communicate information from the environment to the cell cycle, a systematic understanding of how this information is dynamically processed is lacking. We address this by performing dynamic sensitivity analysis of three mathematical models of the cell cycle in Saccharomyces cerevisiae. We demonstrate that these models make broadly consistent qualitative predictions about cell cycle progression under dynamically changing conditions. For example, it is shown that the models predict anticorrelated changes in cell size and cell cycle duration under different environments independently of the growth rate. This prediction is validated by comparison to available literature data. Other consistent patterns emerge, such as widespread nonmonotonic changes in cell size down generations in response to parameter changes. We extend our analysis by investigating glucose signalling to the cell cycle, showing that known regulation of Cln3 translation and Cln1,2 transcription by glucose is sufficient to explain the experimentally observed changes in cell cycle dynamics at different glucose concentrations. Together, these results provide a framework for understanding the complex responses the cell cycle is capable of producing in response to dynamic environments. PMID:26741131

Preparation and photovoltaic properties of CdS quantum dot-sensitized solar cell based on zinc tin mixed metal oxides.

PubMed

Cao, Jiupeng; Zhao, Yifan; Zhu, Yatong; Yang, Xiaoyu; Shi, Peng; Xiao, Hongdi; Du, Na; Hou, Wanguo; Qi, Genggeng; Liu, Jianqiang

2017-07-15

The present study reports a new type of quantum dot sensitized solar cells (QDSSCs) using the zinc tin mixed metal oxides (MMO) as the anode materials, which were obtained from the layered double hydroxide (LDH) precursor. The successive ionic layer adsorption and reaction (SILAR) method is applied to deposit CdS quantum dots. The effects of sensitizing cycles on the performance of CdS QDSSC are studied. Scanning electron microscopy (SEM), Transmission electron microscope (TEM) and X-ray diffraction (XRD) are used to identify the surface profile and crystal structure of the mixed metal oxides anode. The photovoltaic performance of the QDSSC is studied by the electrochemical method. The new CdS QDSSC exhibits power conversion efficiency (PCE) up to 0.48% when the anode was sensitized for eight cycles. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of melatonin in the epigenetic regulation of breast cancer.

PubMed

Korkmaz, Ahmet; Sanchez-Barcelo, Emilio J; Tan, Dun-Xian; Reiter, Russel J

2009-05-01

The oncostatic properties of melatonin as they directly or indirectly involve epigenetic mechanisms of cancer are reviewed with a special focus on breast cancer. Five lines of evidence suggest that melatonin works via epigenetic processes: (1) melatonin influences transcriptional activity of nuclear receptors (ERalpha, GR and RAR) involved in the regulation of breast cancer cell growth; (2) melatonin down-regulates the expression of genes responsible for the local synthesis or activation of estrogens including aromatase, an effect which may be mediated by methylation of the CYP19 gene or deacetylation of CYP19 histones; (3) melatonin inhibits telomerase activity and expression induced by either natural estrogens or xenoestrogens; (4) melatonin modulates the cell cycle through the inhibition of cyclin D1 expression; (5) melatonin influences circadian rhythm disturbances dependent on alterations of the light/dark cycle (i.e., light at night) with the subsequent deregulation of PER2 which acts as a tumor suppressor gene.

Processing and Mechanical Properties of Various Zirconia/Alumina Composites for Fuel Cell Applications

NASA Technical Reports Server (NTRS)

Choi, Sung R.; Bansal, Narottam P.

2002-01-01

Various electrolyte materials for solid oxide fuel cells were fabricated by hot pressing 10 mol% yttria-stabilized zirconia (10-YSZ) reinforced with two different forms of alumina, particulates and platelets, each containing 0 to 30 mol% alumina. Flexure strength and fracture toughness of both particulate and platelet composites at ambient temperature increased with increasing alumina content, reaching a maximum at 30 mot% alumina. For a given alumina content, strength of particulate composites was greater than that of platelet composites, whereas, the difference in fracture toughness between the two composite systems was negligible. No virtual difference in elastic modulus and density was observed for a given alumina content between particulate and platelet composites. Thermal cycling up to 10 cycles between 200 to 1000 C did not show any effect on strength degradation of the 30 mol% platelet composites, indicative of negligible influence of CTE mismatches between YSZ matrix and alumina grains.

A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis.

PubMed

Yin, Ke; Ueda, Minako; Takagi, Hitomi; Kajihara, Takehiro; Sugamata Aki, Shiori; Nobusawa, Takashi; Umeda-Hara, Chikage; Umeda, Masaaki

2014-11-01

Visualization of the spatiotemporal pattern of cell division is crucial to understand how multicellular organisms develop and how they modify their growth in response to varying environmental conditions. The mitotic cell cycle consists of four phases: S (DNA replication), M (mitosis and cytokinesis), and the intervening G1 and G2 phases; however, only G2/M-specific markers are currently available in plants, making it difficult to measure cell cycle duration and to analyze changes in cell cycle progression in living tissues. Here, we developed another cell cycle marker that labels S-phase cells by manipulating Arabidopsis CDT1a, which functions in DNA replication origin licensing. Truncations of the CDT1a coding sequence revealed that its carboxy-terminal region is responsible for proteasome-mediated degradation at late G2 or in early mitosis. We therefore expressed this region as a red fluorescent protein fusion protein under the S-specific promoter of a histone 3.1-type gene, HISTONE THREE RELATED2 (HTR2), to generate an S/G2 marker. Combining this marker with the G2/M-specific CYCB1-GFP marker enabled us to visualize both S to G2 and G2 to M cell cycle stages, and thus yielded an essential tool for time-lapse imaging of cell cycle progression. The resultant dual-color marker system, Cell Cycle Tracking in Plant Cells (Cytrap), also allowed us to identify root cells in the last mitotic cell cycle before they entered the endocycle. Our results demonstrate that Cytrap is a powerful tool for in vivo monitoring of the plant cell cycle, and thus for deepening our understanding of cell cycle regulation in particular cell types during organ development. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Capacity of wild-type and chemokine-armed parvovirus H-1PV for inhibiting neo-angiogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavie, Muriel; Struyf, Sofie; Stroh-Dege, Alexandra

2013-12-15

Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumormore » growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors. - Highlights: • The oncolytic parvovirus H-1PV can target endothelial cells. • Abortive viral cycle upon infection of endothelial cells with H-1PV. • Inhibition of VEGF expression and KS-IMM tumor growth by H-1PV.« less

Hard clam extracts induce atypical apoptosis in human gastric cancer cells

PubMed Central

Song, Eing-Ju; Chan, Michael W.Y.; Shin, Jyh-Wei; Chen, Che-Chun

2017-01-01

Hard clams (HCs) are a nutritionally high-quality and popular seafood, and are established to be a potent antitumor food. The aim of the present study was to determine whether HC extracts induce apoptosis in the human gastric cancer cell line, AGS. In contrast with previously reported methods of extraction, crude extracts of HC were obtained by freezing and thawing and by a method free of hot water or organic solvents. The composition, quality and properties of the HC extracts were demonstrated to be stable since the extracts that were evaluated by capillary electrophoresis and HPLC analysis at different timepoints were similar. HC extracts also have an inhibitory effect against the survival of AGS cells. Treatment with HC extracts induced a marked sub-G1 DNA peak and reduced the expression of the anti-apoptotic genes BIRC5 and KPNA2. However, hallmarks of classical apoptosis such as DNA fragmentation and apoptotic body formation were not observed, indicating atypical apoptosis. Furthermore, it was revealed that HC extracts interrupted cell cycle progression in AGS cells through altered expression of six cell cycle-associated genes: CDC20, KPNA2, BIRC5, ANAPC2, CDKN1A and RB1. The present findings suggest that HC may contribute to a novel future anticancer agent. PMID:28810604

A Short-Term Advantage for Syngamy in the Origin of Eukaryotic Sex: Effects of Cell Fusion on Cell Cycle Duration and Other Effects Related to the Duration of the Cell Cycle—Relationship between Cell Growth Curve and the Optimal Size of the Species, and Circadian Cell Cycle in Photosynthetic Unicellular Organisms

PubMed Central

Mancebo Quintana, J. M.; Mancebo Quintana, S.

2012-01-01

The origin of sex is becoming a vexatious issue for Evolutionary Biology. Numerous hypotheses have been proposed, based on the genetic effects of sex, on trophic effects or on the formation of cysts and syncytia. Our approach addresses the change in cell cycle duration which would cause cell fusion. Several results are obtained through graphical and mathematical analysis and computer simulations. (1) In poor environments, cell fusion would be an advantageous strategy, as fusion between cells of different size shortens the cycle of the smaller cell (relative to the asexual cycle), and the majority of mergers would occur between cells of different sizes. (2) The easiest-to-evolve regulation of cell proliferation (sexual/asexual) would be by modifying the checkpoints of the cell cycle. (3) A regulation of this kind would have required the existence of the G2 phase, and sex could thus be the cause of the appearance of this phase. Regarding cell cycle, (4) the exponential curve is the only cell growth curve that has no effect on the optimal cell size in unicellular species; (5) the existence of a plateau with no growth at the end of the cell cycle explains the circadian cell cycle observed in unicellular algae. PMID:22666626

Cell Cycle Regulation of Stem Cells by MicroRNAs.

PubMed

Mens, Michelle M J; Ghanbari, Mohsen

2018-06-01

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster.

PubMed

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-07-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed D: rosophila, R: bf, E: 2F A: nd M: yb/ M: ulti-vulva class B: (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. Copyright © 2016 by the Genetics Society of America.

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

PubMed Central

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-01-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. PMID:27184390

Cytotoxic Effect on Human Myeloma Cells and Leukemic Cells by the Agaricus blazei Murill Based Mushroom Extract, Andosan™

PubMed Central

Holien, Toril; Mirlashari, Mohammad Reza; Misund, Kristine

2017-01-01

Agaricus blazei Murill is an edible mushroom of the Basidiomycetes family, which has been found to contain a number of compounds with antitumor properties, such as proteoglycans and ergosterol. In the present investigation, we show that the commercial mushroom product Andosan, which contains 82.4% Agaricus blazei Murill, together with medicinal mushrooms Hericium erinaceus (14.7%) and Grifola frondosa (2.9%), has a cytotoxic effect on primary myeloma cells, other myeloma cell lines, and leukemia cell lines in vitro. Although the exact content and hence the mechanisms of action of the Andosan extract are unknown, we have found in this investigation indications of cell cycle arrest when myeloma cell lines are cultivated with Andosan. This may be one of the possible explanations for the cytotoxic effects of Andosan. PMID:29238712

Cytotoxic Effect on Human Myeloma Cells and Leukemic Cells by the Agaricus blazei Murill Based Mushroom Extract, Andosan™.

PubMed

Tangen, Jon-Magnus; Holien, Toril; Mirlashari, Mohammad Reza; Misund, Kristine; Hetland, Geir

2017-01-01

Agaricus blazei Murill is an edible mushroom of the Basidiomycetes family, which has been found to contain a number of compounds with antitumor properties, such as proteoglycans and ergosterol. In the present investigation, we show that the commercial mushroom product Andosan, which contains 82.4% Agaricus blazei Murill, together with medicinal mushrooms Hericium erinaceus (14.7%) and Grifola frondosa (2.9%), has a cytotoxic effect on primary myeloma cells, other myeloma cell lines, and leukemia cell lines in vitro. Although the exact content and hence the mechanisms of action of the Andosan extract are unknown, we have found in this investigation indications of cell cycle arrest when myeloma cell lines are cultivated with Andosan. This may be one of the possible explanations for the cytotoxic effects of Andosan.

Porous α-Fe2O3 nanostructures and their lithium storage properties as full cell configuration against LiFePO4

NASA Astrophysics Data System (ADS)

Veluri, P. S.; Shaligram, A.; Mitra, S.

2015-10-01

A two step approach for synthesis of porous α-Fe2O3 nanostructures has been realized via polyol method by complexing iron oxalate with ethylene glycol. Crystalline Fe2O3 samples with different porosities are obtained by calcination of Fe-Ethylene glycol complex at various temperatures. The as-prepared porous Fe2O3 structures exhibit promising lithium storage performance at high current rates. It is observed that the calcination temperature and the resultant porosity have a significant effect on capacity and cycling stability. Samples calcined at high temperature (600 °C) demonstrates stable cycle life with capacity retention of 1077 mAh g-1 at 500 mA g-1 current rate after 50 charge-discharge cycles. Samples calcined at temperatures of 500 and 600 °C display stable cycle life and high rate capability with reversible capacity of 930 mAh g-1 and 688 mAh g-1 at 5 A g-1, respectively. Impregnation of electrodes with electrolyte before cell fabrication shows enhanced electrochemical performance. The viability of Fe2O3 porous nanostructures as prospective anode material examined against commercial LiFePO4 cathode shows promising electrochemical performance.

Molecular basis of sodium butyrate-dependent proapoptotic activity in cancer cells.

PubMed

Pajak, B; Orzechowski, A; Gajkowska, B

2007-01-01

This review outlines the molecular events that accompany the antitumor action of sodium butyrate (NaBt). Butyrate, a low-molecular weight four-carbon chain volatile fatty acid (VFA) has been previously shown to withdraw cells from cell cycle or to promote cell differentiation, and finally to induce programmed cell death. Recent advances in molecular biology indicate, that this product of large bowel microbial fermentation of dietary fiber, might evoke the above-mentioned effects by indirect action on genes. NaBt was shown to inhibit histone deacetylase activity, allowing DNA binding of several transcription factors. Higher genomic activity leads to the higher expression of proapoptotic genes, higher level of their protein products and elevated sensitivity to death ligand-induced apoptosis. Cancer cells might be arrested in G1 phase of cell cycle in a p21-dependent manner. Proapoptotic activity of NaBt includes higher expression of membrane death receptors (DR4/5), higher level and activation of Smad3 protein in TGF-beta-dependent apoptotic pathway, lower level of antiapoptotic proteins (cFLIP, XIAP) and activation ofproapoptotic tBid protein. Thus, both intrinsic and extrinsic apoptotic pathways are stimulated to ampify the apoptotic signals. These effects are specific for tumor but not for regular cells. Unique properties of NaBt make this agent a promising metabolic inhibitor to retard tumorigenesis to suppress tumor growth.

Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages.

PubMed

Jiao, Fei; Wang, Juan; Dong, Zhao-Lun; Wu, Min-Juan; Zhao, Ting-Bao; Li, Dan-Dan; Wang, Xin

2012-08-01

Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them "human limb bud-derived mesenchymal stem cells" (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro.

Mequindox induced cellular DNA damage via generation of reactive oxygen species.

PubMed

Liu, Jing; Ouyang, Man; Jiang, Jun; Mu, Peiqiang; Wu, Jun; Yang, Qi; Zhang, Caihui; Xu, Weiying; Wang, Lijuan; Huen, Michael S Y; Deng, Yiqun

2012-01-24

Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS. © 2011 Elsevier B.V. All rights reserved.

Scratch2 prevents cell cycle re-entry by repressing miR-25 in postmitotic primary neurons.

PubMed

Rodríguez-Aznar, Eva; Barrallo-Gimeno, Alejandro; Nieto, M Angela

2013-03-20

During the development of the nervous system the regulation of cell cycle, differentiation, and survival is tightly interlinked. Newly generated neurons must keep cell cycle components under strict control, as cell cycle re-entry leads to neuronal degeneration and death. However, despite their relevance, the mechanisms controlling this process remain largely unexplored. Here we show that Scratch2 is involved in the control of the cell cycle in neurons in the developing spinal cord of the zebrafish embryo. scratch2 knockdown induces postmitotic neurons to re-enter mitosis. Scratch2 prevents cell cycle re-entry by maintaining high levels of the cycle inhibitor p57 through the downregulation of miR-25. Thus, Scratch2 appears to safeguard the homeostasis of postmitotic primary neurons by preventing cell cycle re-entry.

An extensive program of periodic alternative splicing linked to cell cycle progression

PubMed Central

Dominguez, Daniel; Tsai, Yi-Hsuan; Weatheritt, Robert; Wang, Yang; Blencowe, Benjamin J; Wang, Zefeng

2016-01-01

Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control. DOI: http://dx.doi.org/10.7554/eLife.10288.001 PMID:27015110

Biological properties of human skeletal myoblasts genetically modified to simultaneously overexpress the pro-angiogenic factors vascular endothelial growth factor-A and fibroblast growth factor-4.

PubMed

Zimna, A; Janeczek, A; Rozwadowska, N; Fraczek, M; Kucharzewska, P; Rucinski, M; Mietkiewski, T; Kurpisz, M

2014-04-01

Myocardial infarction results in cardiomyocyte loss and may eventually lead to cardiac failure. Skeletal myoblast transplantation into the scar area may compensate for this observed cell loss by strengthening the weakened myocardium and inducing myogenesis. Moreover, skeletal myoblasts may serve as potential transgene carriers for the myocardium (i.e., delivering pro-angiogenic factors, which may potentially improve blood perfusion in infarcted heart). We examined the influence of the simultaneous overexpression of two potent pro-angiogenic factors, fibroblast growth factor-4 (FGF-4) and vascular endothelial growth factor (VEGF), on human primary myoblast proliferation, cell cycle, resistance to hypoxic stress conditions and myogenic gene expression, as well as the induction of pro-angiogenic activities. We used a bicistronic plasmid vector encoding two factors introduced via an efficient myoblast electroporation method. The levels of overexpressed proteins were assessed, and their functionality at capillary formation was evaluated. This combined approach led to a high level of non-viral transient overexpression of both pro-angiogenic proteins, which proved to be potent regulators of blood vessel development assayed in capillary formation tests. We demonstrated in in vitro conditions that the transfection of human skeletal myoblasts with both FGF-4 and VEGF did not affect their basic biological properties such as the cell cycle, proliferation or expression of myogenic lineage-specific genes, and the modified cells adapted to oxidative stress conditions. Overall, the results obtained suggest that the applied combined approach with the use of two pro-angiogenic genes overexpressed in skeletal muscle stem cells may be an interesting alternative for the effective therapy of myocardial infarction in animal models and/or prospective clinical trials.

Analysis of growth of tetraploid nuclei in roots of Vicia faba.

PubMed

Bansal, J; Davidson, D

1978-03-01

Growth of nuclei of a marked population of cells was determined from G1 to prophase in roots of Vicia faba. The cells were marked by inducing them to become tetraploid by treatment with 0.002% colchicine for 1 hr. Variation in nuclear volume is large; it is established in early G1 and maintained through interphase and into prophase. One consequence of this variation is that there is considerable overlap between volumes of nuclei of different ages in the cell cycle; nuclear volume, we suggest, cannot be used as an accurate indicator of the age of the cell in its growth cycle. Nuclei exhibit considerable variation in their growth rate through the cell cycle. Of the marked population of cells, about 65% had completed a cell cycle 14--15 hr after they were formed. These tetraploid nuclei have a cell cycle duration similar to that of fast cycling diploid cells of the same roots. Since they do complete a cell cycle, at least 65% of the nuclei studied must come from rapidly proliferating cells, showing that variability in nuclear volumes must be present in growing cells and cannot be attributed solely to the presence, in our samples, of non-cycling cells.

RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Houcai; Yu, Jing; Zhang, Lixia

2014-04-18

Highlights: • RPS27a expression was up-regulated in advanced-phase CML and AL patients. • RPS27a knockdown changed biological property of K562 and K562/G01 cells. • RPS27a knockdown affected Raf/MEK/ERK, P21 and BCL-2 signaling pathways. • RPS27a knockdown may be applicable for new combination therapy in CML patients. - Abstract: Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL)more » patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.« less

Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Y.-J.; Department of Biotechnology, Asia University, Taichung, Taiwan; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan

2009-01-23

Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. In the present study, we investigated the effects of the PR isoflavones puerarin, daidzein, and genistein on the growth of breast cancer cells. Our data revealed that after treatment with PR isoflavones, a dose-dependent inhibition of cell growth occurred in HS578T, MDA-MB-231, and MCF-7 cell lines. Results from cell cycle distribution and apoptosis assays revealed that PR isoflavones induced cell apoptosis through a caspase-3-dependent pathway and mediated cell cycle arrest in the G2/M phase. Furthermore, wemore » observed that the serum metabolites of PR (daidzein sulfates/glucuronides) inhibited proliferation of the breast cancer cells at a 50% cell growth inhibition (GI{sub 50}) concentration of 2.35 {mu}M. These results indicate that the daidzein constituent of PR can be metabolized to daidzein sulfates or daidzein glucuronides that exhibit anticancer activities. The protein expression levels of the active forms of caspase-9 and Bax in breast cancer cells were significantly increased by treatment with PR metabolites. These metabolites also increased the protein expression levels of p53 and p21. We therefore suggest that PR may act as a chemopreventive and/or chemotherapeutic agent against breast cancer by reducing cell viability and inducing apoptosis.« less

A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer.

PubMed

Dijkgraaf, Eveline M; Santegoets, Saskia J A M; Reyners, An K L; Goedemans, Renske; Nijman, Hans W; van Poelgeest, Mariëtte I E; van Erkel, Arien R; Smit, Vincent T H B M; Daemen, Toos A H H; van der Hoeven, Jacobus J M; Melief, Cornelis J M; Welters, Marij J P; Kroep, Judith R; van der Burg, Sjoerd H

2015-10-13

Preclinical tumor models show that chemotherapy has immune modulatory properties which can be exploited in the context of immunotherapy. The purpose of this study was to determine the feasibility and immunogenicity of combinations of such an immunomodulatory chemotherapeutic agent with immunotherapy, p53 synthetic long peptide (SLP) vaccine and Pegintron (IFN-α) in patients with platinum-resistant p53-positive epithelial ovarian cancer (EOC). This is a phase 1/2 trial in which patients sequential 6 cycles of gemcitabine (1000 mg/kg2 iv; n = 3), gemcitabine with Pegintron before and after the first gemcitabine cycle (Pegintron 1 μg/kg sc; n = 6), and gemcitabine and Pegintron combined with p53 SLP vaccine (0.3 mg/peptide, 9 peptides; n = 6). At baseline, 22 days after the 2nd and 6th cycle, blood was collected for immunomonitoring. Toxicity, CA-125, and radiologic response were evaluated after 3 and 6 cycles of chemotherapy. None of the patients enrolled experienced dose-limiting toxicity. Predominant grade 3/4 toxicities were nausea/vomiting and dyspnea. Grade 1/2 toxicities consisted of fatigue (78%) and Pegintron-related flu-like symptoms (72%). Gemcitabine reduced myeloid-derived suppressor cells (p = 0.0005) and increased immune-supportive M1 macrophages (p = 0.04). Combination of gemcitabine and Pegintron stimulated higher frequencies of circulating proliferating CD4+ and CD8+ T-cells but not regulatory T-cells. All vaccinated patients showed strong vaccine-induced p53-specific T-cell responses. Combination of gemcitabine, the immune modulator Pegintron and therapeutic peptide vaccination is a viable approach in the development of combined chemo-immunotherapeutic regimens to treat cancer.

Life Cycle Characterization of Sulfolobus Monocaudavirus 1, an Extremophilic Spindle-Shaped Virus with Extracellular Tail Development

PubMed Central

Uldahl, Kristine B.; Jensen, Signe B.; Bhoobalan-Chitty, Yuvaraj; Martínez-Álvarez, Laura; Papathanasiou, Pavlos

2016-01-01

ABSTRACT We provide here, for the first time, insights into the initial infection stages of a large spindle-shaped archaeal virus and explore the following life cycle events. Our observations suggest that Sulfolobus monocaudavirus 1 (SMV1) exhibits a high adsorption rate and that virions adsorb to the host cells via three distinct attachment modes: nosecone association, body association, and body/tail association. In the body/tail association mode, the entire virion, including the tail(s), aligns to the host cell surface and the main body is greatly flattened, suggesting a possible fusion entry mechanism. Upon infection, the intracellular replication cycle lasts about 8 h, at which point the virions are released as spindle-shaped tailless particles. Replication of the virus retarded host growth but did not cause lysis of the host cells. Once released from the host and at temperatures resembling that of its natural habitat, SMV1 starts developing one or two tails. This exceptional property of undergoing a major morphological development outside, and independently of, the host cell has been reported only once before for the related Acidianus two-tailed virus. Here, we show that SMV1 can develop tails of more than 900 nm in length, more than quadrupling the total virion length. IMPORTANCE Very little is known about the initial life cycle stages of viruses infecting hosts of the third domain of life, Archaea. This work describes the first example of an archaeal virus employing three distinct association modes. The virus under study, Sulfolobus monocaudavirus 1, is a representative of the large spindle-shaped viruses that are frequently found in acidic hot springs. The results described here will add valuable knowledge about Archaea, the least studied domain in the virology field. PMID:27053548

Life Cycle Characterization of Sulfolobus Monocaudavirus 1, an Extremophilic Spindle-Shaped Virus with Extracellular Tail Development.

PubMed

Uldahl, Kristine B; Jensen, Signe B; Bhoobalan-Chitty, Yuvaraj; Martínez-Álvarez, Laura; Papathanasiou, Pavlos; Peng, Xu

2016-06-15

We provide here, for the first time, insights into the initial infection stages of a large spindle-shaped archaeal virus and explore the following life cycle events. Our observations suggest that Sulfolobus monocaudavirus 1 (SMV1) exhibits a high adsorption rate and that virions adsorb to the host cells via three distinct attachment modes: nosecone association, body association, and body/tail association. In the body/tail association mode, the entire virion, including the tail(s), aligns to the host cell surface and the main body is greatly flattened, suggesting a possible fusion entry mechanism. Upon infection, the intracellular replication cycle lasts about 8 h, at which point the virions are released as spindle-shaped tailless particles. Replication of the virus retarded host growth but did not cause lysis of the host cells. Once released from the host and at temperatures resembling that of its natural habitat, SMV1 starts developing one or two tails. This exceptional property of undergoing a major morphological development outside, and independently of, the host cell has been reported only once before for the related Acidianus two-tailed virus. Here, we show that SMV1 can develop tails of more than 900 nm in length, more than quadrupling the total virion length. Very little is known about the initial life cycle stages of viruses infecting hosts of the third domain of life, Archaea This work describes the first example of an archaeal virus employing three distinct association modes. The virus under study, Sulfolobus monocaudavirus 1, is a representative of the large spindle-shaped viruses that are frequently found in acidic hot springs. The results described here will add valuable knowledge about Archaea, the least studied domain in the virology field. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight battery cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1990-01-01

A breakthrough in low earth orbit (LEO) cycle life of individual pressure vessel (IPV) nickel hydrogen battery cells was reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH. The effect of KOH concentration on cycle life was studied. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min charge (2 x normal rate). The depth of discharge (DOD) was 80 percent. The cell temperature was maintained at 23 C. The next step is to validate these results using flight hardware and a real time LEO test. NASA Lewis has a contract with the Naval Weapons Support Center (NWSC), Crane, Indiana, to validate the boiler plate test results. Six 48 A-hr Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells) and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The cells were cycled for over 8000 cycles in the continuing test. There were no failures for the cells containing 26 percent KOH. There was two failures, however, for the cells containing 31 percent KOH.

Effect of KOH concentration on LEO cycle life of IPV nickel-hydrogen flight battery cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1990-01-01

A breakthrough in the low-earth-orbit (LEO) cycle life of individual pressure vessel (IPV) nickel hydrogen battery cells is reported. The cycle life of boiler plate cells containing 26 percent potassium hydroxide (KOH) electrolyte was about 40,000 LEO cycles compared to 3500 cycles for cells containing 31 percent KOH. The effect of KOH concentration on cycle life was studied. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min charge (2 x normal rate). The depth of discharge (DOD) was 80 percent. The cell temperature was maintained at 23 C. The next step is to validate these results using flight hardware and real time LEO test. NASA Lewis has a contract with the Naval Weapons Support Center (NWSC), Crane, Indiana to validate the boiler plate test results. Six 48 A-hr Hughes recirculation design IPV nickel-hydrogen flight battery cells are being evaluated. Three of the cells contain 26 percent KOH (test cells) and three contain 31 percent KOH (control cells). They are undergoing real time LEO cycle life testing. The cycle regime is a 90-min LEO orbit consisting of a 54-min charge followed by a 36-min discharge. The depth-of-discharge is 80 percent. The cell temperature is maintained at 10 C. The cells were cycled for over 8000 cycles in the continuing test. There were no failures for the cells containing 26 percent KOH. There were two failures, however, for the cells containing 31 percent KOH.

Cell cycle in egg cell and its progression during zygotic development in rice.

PubMed

Sukawa, Yumiko; Okamoto, Takashi

2018-03-01

Rice egg is arrested at G1 phase probably by OsKRP2. After fusion with sperm, karyogamy, OsWEE1-mediated parental DNA integrity in zygote nucleus, zygote progresses cell cycle to produce two-celled embryo. In angiosperms, female and male gametes exist in gametophytes after the complementation of meiosis and the progression of nuclear/cell division of the haploid cell. Within the embryo sac, the egg cell is specially differentiated for fertilization and subsequent embryogenesis, and cellular programs for embryonic development, such as restarting the cell cycle and de novo gene expression, are halted. There is only limited knowledge about how the cell cycle in egg cells restarts toward zygotic division, although the conversion of the cell cycle from a quiescent and arrested state to an active state is the most evident transition of cell status from egg cell to zygote. This is partly due to the difficulty in direct access and analysis of egg cells, zygotes and early embryos, which are deeply embedded in ovaries. In this study, precise relative DNA amounts in the nuclei of egg cells, developing zygotes and cells of early embryos were measured, and the cell cycle of a rice egg cell was estimated as the G1 phase with a 1C DNA level. In addition, increases in DNA content in zygote nuclei via karyogamy and DNA replication were also detectable according to progression of the cell cycle. In addition, expression profiles for cell cycle-related genes in egg cells and zygotes were also addressed, and it was suggested that OsKRP2 and OsWEE1 function in the inhibition of cell cycle progression in egg cells and in checkpoint of parental DNA integrity in zygote nucleus, respectively.

Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arcangeletti, Maria-Cristina, E-mail: mariacristina.arcangeletti@unipr.it; Germini, Diego; Rodighiero, Isabella

2013-05-25

Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promotingmore » cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle. - Highlights: ► We studied HCMV infection impact on THP-1 macrophage cell cycle. ► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection. ► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle. ► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication. ► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.« less

Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

PubMed Central

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H.; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID:22073316

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

PubMed

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Effects of La2O3 content and particle size on the long-term stability and thermal cycling property of La2O3-dispersed SUS430 alloys for SOFC interconnect materials

NASA Astrophysics Data System (ADS)

Lee, Jung-Won; Mehran, Muhammad Taqi; Song, Rak-Hyun; Lee, Seung-Bok; Lee, Jong-Won; Lim, Tak-Hyoung; Park, Seok-Joo; Hong, Jong-Eun; Shim, Joon-Hyung

2017-11-01

We developed oxide-dispersed alloys as interconnect materials for a solid oxide fuel cell by adding La2O3 to SUS430 ferritic steels. For this purpose, we prepared two types of La2O3 with different particle sizes and added different amounts of La2O3 to SUS430 powder. Then, we mixed the powders using a high energy ball mill, so that nano-sized as well as micro-sized oxide particles were able to mix uniformly with the SUS430 powders. After preparing hexahedral green samples using uni-axial and cold isostatic presses, we were finally able to obtain oxide-dispersed alloys having high relative densities after firing at 1,400 °C under hydrogen atmosphere. The nano-sized La2O3 dispersed alloys showed properties superior to those of micro-sized dispersed alloys in terms of long-term stability and thermal cycling. Moreover, we determined the optimum amounts of added La2O3. Finally we were able to develop a new oxide-dispersed alloy showing excellent properties of low area specific resistance (16.23 mΩ cm2) after 1000 h at 800 °C, and no degradation after 10 iterations of thermal cycling under oxidizing atmosphere.

Electrochemical and thermal studies of lithium ion batteries

NASA Astrophysics Data System (ADS)

Lu, Wenquan

The structural, electrochemical, and thermal characteristics of carbonaceous anodes and LiNi0.8Co0.2O2 cathode in Li-ion cells were investigated using various electrochemical and calorimetric techniques. The electrode-electrolyte interface was investigated for various carbonaceous materials such as graphite with different shapes, surface modified graphite with copper, and novel carbon material derived from sepiolite template. The structural and morphological properties were determined using XRD, TGA, SEM, BET techniques. The electrochemical characteristics were studied using conventional electrochemical techniques such as galvanostatic charge/discharge cycling, cyclic voltammetry, and impedance (AC and DC) methods. It was observed that the electrochemical active surface area instead of the BET area plays a critical role in the irreversible capacity loss associated with the carbonaceous anodes. It was also found that the exfoliation of carbon anodes especially in PC based electrolyte could be significantly reduced by protective copper coating of the natural graphite. LiNi0.8Co0.2O2 cathode material was found to possess high energy density and excellent cycling characteristics. The structural and electrochemical properties of LiNi0.8Co 0.2O2 synthesized by sol-gel and solid-state methods were studied. Results of the AC impedance spectroscopy carried out on LiNi 0.8Co0.2O2 cathodes revealed that the charge transfer resistance is a function of the state of charge. The solid state Li + diffusion was calculated to be around 10-13 cm2/s in the oxide particle by Warburg impedance method. In addition, the cell fabricated with LiNi0.8Co0.2O 2 cathode showed excellent energy and power performance under static and dynamic load conditions that prevail in Electric and Hybrid Vehicles. Thermal properties of the LiNi0.8Co0.2O2 cathode, carbonaceous anodes, and Li-ion cells fabricated with these electrodes were also investigated using isothermal microcalorimetry (IMC), differential scanning calorimetry (DSC) and accelerated rate calorimetry (ARC). Isothermal micro-calorimeter was used to investigate the thermal behavior of the Li-ion cell and its electrodes. The overall heat changes during charge-discharge processes were explained in terms of the irreversible (resistive) and reversible (entropic) heats. It was observed that the reversible heat strongly depends on the structural or phase change occurring in the electrodes during Li-ion insertion and extraction reactions. It was also found that the contribution of the reversible heat to the overall cell heat generation rate was significant only at low cycling rates.

Slow-cycling stem cells in hydra contribute to head regeneration

PubMed Central

Govindasamy, Niraimathi; Murthy, Supriya; Ghanekar, Yashoda

2014-01-01

ABSTRACT Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU) and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8–10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals. PMID:25432513

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans

PubMed Central

Sierra, Crystal S.; Haase, Steven B.

2016-01-01

The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation. PMID:27918582

AS160 controls eukaryotic cell cycle and proliferation by regulating the CDK inhibitor p21.

PubMed

Gongpan, Pianchou; Lu, Yanting; Wang, Fang; Xu, Yuhui; Xiong, Wenyong

2016-07-02

AS160 (TBC1D4) has been implicated in multiple biological processes. However, the role and the mechanism of action of AS160 in the regulation of cell proliferation remain unclear. In this study, we demonstrated that AS160 knockdown led to blunted cell proliferation in multiple cell types, including fibroblasts and cancer cells. The results of cell cycle analysis showed that these cells were arrested in the G1 phase. Intriguingly, this inhibition of cell proliferation and the cell cycle arrest caused by AS160 depletion were glucose independent. Moreover, AS160 silencing led to a marked upregulation of the expression of the cyclin-dependent kinase inhibitor p21. Furthermore, whereas AS160 overexpression resulted in p21 downregulation and rescued the arrested cell cycle in AS160-depeleted cells, p21 silencing rescued the inhibited cell cycle and proliferation in the cells. Thus, our results demonstrated that AS160 regulates glucose-independent eukaryotic cell proliferation through p21-dependent control of the cell cycle, and thereby revealed a molecular mechanism of AS160 modulation of cell cycle and proliferation that is of general physiological significance.

A dual transcriptional reporter and CDK-activity sensor marks cell cycle entry and progression in C. elegans

PubMed Central

van Rijnberk, Lotte M.; van der Horst, Suzanne E. M.; van den Heuvel, Sander; Ruijtenberg, Suzan

2017-01-01

Development, tissue homeostasis and tumor suppression depend critically on the correct regulation of cell division. Central in the cell division process is the decision whether to enter the next cell cycle and commit to going through the S and M phases, or to remain temporarily or permanently arrested. Cell cycle studies in genetic model systems could greatly benefit from visualizing cell cycle commitment in individual cells without the need of fixation. Here, we report the development and characterization of a reporter to monitor cell cycle entry in the nematode C. elegans. This reporter combines the mcm-4 promoter, to reveal Rb/E2F-mediated transcriptional control, and a live-cell sensor for CDK-activity. The CDK sensor was recently developed for use in human cells and consists of a DNA Helicase fragment fused to eGFP. Upon phosphorylation by CDKs, this fusion protein changes in localization from the nucleus to the cytoplasm. The combined regulation of transcription and subcellular localization enabled us to visualize the moment of cell cycle entry in dividing seam cells during C. elegans larval development. This reporter is the first to reflect cell cycle commitment in C. elegans and will help further genetic studies of the mechanisms that underlie cell cycle entry and exit. PMID:28158315

Structural and genomic properties of the hyperthermophilic archaeal virus ATV with an extracellular stage of the reproductive cycle.

PubMed

Prangishvili, David; Vestergaard, Gisle; Häring, Monika; Aramayo, Ricardo; Basta, Tamara; Rachel, Reinhard; Garrett, Roger A

2006-06-23

A novel virus, ATV, of the hyperthermophilic archaeal genus Acidianus has the unique property of undergoing a major morphological development outside of, and independently of, the host cell. Virions are extruded from host cells as lemon-shaped tail-less particles, after which they develop long tails at each pointed end, at temperatures close to that of the natural habitat, 85 degrees C. The extracellularly developed tails constitute tubes, which terminate in an anchor-like structure that is not observed in the tail-less particles. A thin filament is located within the tube, which exhibits a periodic structure. Tail development produces a one half reduction in the volume of the virion, concurrent with a slight expansion of the virion surface. The circular, double-stranded DNA genome contains 62,730 bp and is exceptional for a crenarchaeal virus in that it carries four putative transposable elements as well as genes, which previously have been associated only with archaeal self-transmissable plasmids. In total, it encodes 72 predicted proteins, including 11 structural proteins with molecular masses in the range of 12 to 90 kDa. Several of the larger proteins are rich in coiled coil and/or low complexity sequence domains, which are unusual for archaea. One protein, in particular P800, resembles an intermediate filament protein in its structural properties. It is modified in the two-tailed, but not in the tail-less, virion particles and it may contribute to viral tail development. Exceptionally for a crenarchaeal virus, infection with ATV results either in viral replication and subsequent cell lysis or in conversion of the infected cell to a lysogen. The lysogenic cycle involves integration of the viral genome into the host chromosome, probably facilitated by the virus-encoded integrase and this process can be interrupted by different stress factors.

Accessing the genomic effects of naked nanoceria in murine neuronal cells.

PubMed

Lee, Tin-Lap; Raitano, Joan M; Rennert, Owen M; Chan, Siu-Wai; Chan, Wai-Yee

2012-07-01

Cerium oxide nanoparticles (nanoceria) are engineered nanoparticles whose versatility is due to their unique redox properties. We and others have demonstrated that naked nanoceria can act as antioxidants to protect cells against oxidative damage. Although the redox properties may be beneficial, the genome-wide effects of nanoceria on gene transcription and associated biological processes remain elusive. Here we applied a functional genomic approach to examine the genome-wide effects of nanoceria on global gene transcription and cellular functions in mouse neuronal cells. Importantly, we demonstrated that nanoceria induced chemical- and size-specific changes in the murine neuronal cell transcriptome. The nanoceria contributed more than 83% of the population of uniquely altered genes and were associated with a unique spectrum of genes related to neurological disease, cell cycle control, and growth. These observations suggest that an in-depth assessment of potential health effects of naked nanoceria and other naked nanoparticles is both necessary and imminent. Cerium oxide nanoparticles are important antioxidants, with potential applications in neurodegenerative conditions. This team of investigators demonstrated the genomic effects of nanoceria, showing that it induced chemical- and size-specific changes in the murine neuronal cell transcriptome. Published by Elsevier Inc.

Hollow fiber: a biophotonic implant for live cells

NASA Astrophysics Data System (ADS)

Silvestre, Oscar F.; Holton, Mark D.; Summers, Huw D.; Smith, Paul J.; Errington, Rachel J.

2009-02-01

The technical objective of this study has been to design, build and validate biocompatible hollow fiber implants based on fluorescence with integrated biophotonics components to enable in fiber kinetic cell based assays. A human osteosarcoma in vitro cell model fiber system has been established with validation studies to determine in fiber cell growth, cell cycle analysis and organization in normal and drug treated conditions. The rationale for implant development have focused on developing benchmark concepts in standard monolayer tissue culture followed by the development of in vitro hollow fiber designs; encompassing imaging with and without integrated biophotonics. Furthermore the effect of introducing targetable biosensors into the encapsulated tumor implant such as quantum dots for informing new detection readouts and possible implant designs have been evaluated. A preliminary micro/macro imaging approach has been undertaken, that could provide a mean to track distinct morphological changes in cells growing in a 3D matrix within the fiber which affect the light scattering properties of the implant. Parallel engineering studies have showed the influence of the optical properties of the fiber polymer wall in all imaging modes. Taken all together, we show the basic foundation and the opportunities for multi-modal imaging within an in vitro implant format.

Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization.

PubMed

Gismondi, Angelo; Nanni, Valentina; Reina, Giacomo; Orlanducci, Silvia; Terranova, Maria Letizia; Canini, Antonella

2016-01-01

For the first time, we coupled reduced detonation nanodiamonds (NDs) with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin), and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy.

Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

PubMed Central

Gismondi, Angelo; Nanni, Valentina; Reina, Giacomo; Orlanducci, Silvia; Terranova, Maria Letizia; Canini, Antonella

2016-01-01

For the first time, we coupled reduced detonation nanodiamonds (NDs) with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin), and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy. PMID:26893562

Gelam honey attenuated radiation-induced cell death in human diploid fibroblasts by promoting cell cycle progression and inhibiting apoptosis

PubMed Central

2014-01-01

Background The interaction between ionizing radiation and substances in cells will induce the production of free radicals. These free radicals inflict damage to important biomolecules such as chromosomes, proteins and lipids which consequently trigger the expression of genes which are involved in protecting the cells or repair the oxidative damages. Honey has been known for its antioxidant properties and was used in medical and cosmetic products. Currently, research on honey is ongoing and diversifying. The aim of this study was to elucidate the role of Gelam honey as a radioprotector in human diploid fibroblast (HDFs) which were exposed to gamma-rays by determining the expression of genes and proteins involved in cell cycle regulation and cell death. Methods Six groups of HDFs were studied viz. untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/ml of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma-rays at the dose rate of 0.25 Gy/min. Results Our findings showed that, gamma-irradiation at 1 Gy up-regulated ATM, p53, p16ink4a and cyclin D1 genes and subsequently initiated cell cycle arrest at G0/G1 phase and induced apoptosis (p < 0.05). Pre-treatment with Gelam honey however caused down regulation of these genes in irradiated HDFs while no significant changes was observed on the expression of GADD45 and PAK genes. The expression of ATM and p16 proteins was increased in irradiated HDFs but the p53 gene was translated into p73 protein which was also increased in irradiated HDFs. Gelam honey treatment however significantly decreased the expression of ATM, p73, and p16 proteins (p < 0.05) while the expression of cyclin D1 remained unchanged. Analysis on cell cycle profile showed that cells progressed to S phase with less percentage of cells in G0/G1 phase with Gelam honey treatment while apoptosis was inhibited. Conclusion Gelam honey acts a radioprotector against gamma-irradiation by attenuating radiation-induced cell death. PMID:24655584

Gelam honey attenuated radiation-induced cell death in human diploid fibroblasts by promoting cell cycle progression and inhibiting apoptosis.

PubMed

Tengku Ahmad, Tengku Ahbrizal Farizal; Jaafar, Faizul; Jubri, Zakiah; Abdul Rahim, Khairuddin; Rajab, Nor Fadilah; Makpol, Suzana

2014-03-24

The interaction between ionizing radiation and substances in cells will induce the production of free radicals. These free radicals inflict damage to important biomolecules such as chromosomes, proteins and lipids which consequently trigger the expression of genes which are involved in protecting the cells or repair the oxidative damages. Honey has been known for its antioxidant properties and was used in medical and cosmetic products. Currently, research on honey is ongoing and diversifying. The aim of this study was to elucidate the role of Gelam honey as a radioprotector in human diploid fibroblast (HDFs) which were exposed to gamma-rays by determining the expression of genes and proteins involved in cell cycle regulation and cell death. Six groups of HDFs were studied viz. untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/ml of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma-rays at the dose rate of 0.25 Gy/min. Our findings showed that, gamma-irradiation at 1 Gy up-regulated ATM, p53, p16ink4a and cyclin D1 genes and subsequently initiated cell cycle arrest at G0/G1 phase and induced apoptosis (p < 0.05). Pre-treatment with Gelam honey however caused down regulation of these genes in irradiated HDFs while no significant changes was observed on the expression of GADD45 and PAK genes. The expression of ATM and p16 proteins was increased in irradiated HDFs but the p53 gene was translated into p73 protein which was also increased in irradiated HDFs. Gelam honey treatment however significantly decreased the expression of ATM, p73, and p16 proteins (p < 0.05) while the expression of cyclin D1 remained unchanged. Analysis on cell cycle profile showed that cells progressed to S phase with less percentage of cells in G0/G1 phase with Gelam honey treatment while apoptosis was inhibited. Gelam honey acts a radioprotector against gamma-irradiation by attenuating radiation-induced cell death.

Impedance measurements on a spiral-wound nickel/metal hydride cell cycled in a simulated Leo orbit

NASA Technical Reports Server (NTRS)

Reid, Margaret A.

1993-01-01

A spiral-wound size C cell was cycled at 25 C in a low earth orbit (LEO) regime at 50 percent depth of discharge (DOD) with approximately five percent over-charge. The nominal capacity was 3.5 AH. The cell was cycled for 2000 cycles. Capacity checks and impedance measurements over the complete range of state of charge were made upon receipt and after 500, 1000, and 2000 cycles. The capacity of the cell was essentially unchanged until after the impedance measurements at 2000 cycles. Only small changes in the impedance parameters were observed, but there was somewhat more scatter in the data after 2000 cycles. When the cell was returned to LEO cycling after 2000 cycles, only 38 percent of the capacity could be obtained. It is believed that the cell failed because of an equipment failure at the end of the final impedance measurements which allowed an over-discharge.

Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

PubMed

Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

2016-01-01

Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

Immobilization of Acetobacter sp. CCTCC M209061 for efficient asymmetric reduction of ketones and biocatalyst recycling

PubMed Central

2012-01-01

Background The bacterium Acetobacter sp. CCTCC M209061 is a promising whole-cell biocatalyst with exclusive anti-Prelog stereoselectivity for the reduction of prochiral ketones that can be used to make valuable chiral alcohols such as (R)-4-(trimethylsilyl)-3-butyn-2-ol. Although it has promising catalytic properties, its stability and reusability are relatively poor compared to other biocatalysts. Hence, we explored various materials for immobilizing the active cells, in order to improve the operational stability of biocatalyst. Results It was found that Ca-alginate give the best immobilized biocatalyst, which was then coated with chitosan to further improve its mechanical strength and swelling-resistance properties. Conditions were optimized for formation of reusable immobilized beads which can be used for repeated batch asymmetric reduction of 4′-chloroacetophenone. The optimized immobilized biocatalyst was very promising, with a specific activity of 85% that of the free-cell biocatalyst (34.66 μmol/min/g dw of cells for immobilized catalyst vs 40.54 μmol/min/g for free cells in the asymmetric reduction of 4′-chloroacetophenone). The immobilized cells showed better thermal stability, pH stability, solvent tolerance and storability compared with free cells. After 25 cycles reaction, the immobilized beads still retained >50% catalytic activity, which was 3.5 times higher than degree of retention of activity by free cells reused in a similar way. The cells could be recultured in the beads to regain full activity and perform a further 25 cycles of the reduction reaction. The external mass transfer resistances were negligible as deduced from Damkohler modulus Da < <1, and internal mass transfer restriction affected the reduction action but was not the principal rate-controlling step according to effectiveness factors η < 1 and Thiele modulus 0.3<∅ <1. Conclusions Ca-alginate coated with chitosan is a highly effective material for immobilization of Acetobacter sp. CCTCC M209061 cells for repeated use in the asymmetric reduction of ketones. Only a small cost in terms of the slightly lower catalytic activity compared to free cells could give highly practicable immobilized biocatalyst. PMID:22947394

Immobilization of Acetobacter sp. CCTCC M209061 for efficient asymmetric reduction of ketones and biocatalyst recycling.

PubMed

Chen, Xiao-Hong; Wang, Xiao-Ting; Lou, Wen-Yong; Li, Ying; Wu, Hong; Zong, Min-Hua; Smith, Thomas J; Chen, Xin-De

2012-09-04

The bacterium Acetobacter sp. CCTCC M209061 is a promising whole-cell biocatalyst with exclusive anti-Prelog stereoselectivity for the reduction of prochiral ketones that can be used to make valuable chiral alcohols such as (R)-4-(trimethylsilyl)-3-butyn-2-ol. Although it has promising catalytic properties, its stability and reusability are relatively poor compared to other biocatalysts. Hence, we explored various materials for immobilizing the active cells, in order to improve the operational stability of biocatalyst. It was found that Ca-alginate give the best immobilized biocatalyst, which was then coated with chitosan to further improve its mechanical strength and swelling-resistance properties. Conditions were optimized for formation of reusable immobilized beads which can be used for repeated batch asymmetric reduction of 4'-chloroacetophenone. The optimized immobilized biocatalyst was very promising, with a specific activity of 85% that of the free-cell biocatalyst (34.66 μmol/min/g dw of cells for immobilized catalyst vs 40.54 μmol/min/g for free cells in the asymmetric reduction of 4'-chloroacetophenone). The immobilized cells showed better thermal stability, pH stability, solvent tolerance and storability compared with free cells. After 25 cycles reaction, the immobilized beads still retained >50% catalytic activity, which was 3.5 times higher than degree of retention of activity by free cells reused in a similar way. The cells could be recultured in the beads to regain full activity and perform a further 25 cycles of the reduction reaction. The external mass transfer resistances were negligible as deduced from Damkohler modulus Da < <1, and internal mass transfer restriction affected the reduction action but was not the principal rate-controlling step according to effectiveness factors η < 1 and Thiele modulus 0.3<∅ <1. Ca-alginate coated with chitosan is a highly effective material for immobilization of Acetobacter sp. CCTCC M209061 cells for repeated use in the asymmetric reduction of ketones. Only a small cost in terms of the slightly lower catalytic activity compared to free cells could give highly practicable immobilized biocatalyst.

TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Li; College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158; Huang, Yong

2014-03-07

Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressedmore » cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.« less

Analysis of space environment damage to solar cell assemblies from LDEF experiment A0171-GSFC test plate

NASA Technical Reports Server (NTRS)

Hill, David C.; Rose, M. Frank

1994-01-01

The results of the postflight analysis of the solar cell assemblies from the LDEF (Long Duration Exposure facility) experiment A0171 is provided in this NASA sponsored research project. The following data on this research are provided as follows: (1) solar cell description, including, substrate composition and thickness, crystal orientation, anti-reflective coating composition and thickness; (2) preflight characteristics of the solar cell assemblies with respect to current and voltage; and (3) post-flight characteristics of the solar cell assemblies with respect to voltage and current. These solar cell assemblies are part of the Goddard Space Flight Center test plate which was designed to test the space environment effects (radiation, atomic oxygen, thermal cycling, meteoroid and debris) on conductively coated solar cell coversheets, various electrical bond materials, solar cell performance, and other material properties where feasible.

Redifferentiation of human hepatoma cells (SMMC-7721) induced by two new highly oxygenated bisabolane-type sesquiterpenes.

PubMed

Miao, Ruidong; Wei, Juan; Zhang, Qi; Sajja, Venkateswara; Yang, Jinbo; Wang, Qin

2008-12-01

Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl transferase activity. In addition,we found that HOBS inhibited the anchorage- independent growth of SMMC-7721 cells in a dose-dependent manner.Taken together,all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.

A single cyclin–CDK complex is sufficient for both mitotic and meiotic progression in fission yeast

PubMed Central

Gutiérrez-Escribano, Pilar; Nurse, Paul

2015-01-01

The dominant model for eukaryotic cell cycle control proposes that cell cycle progression is driven by a succession of CDK complexes with different substrate specificities. However, in fission yeast it has been shown that a single CDK complex generated by the fusion of the Cdc13 cyclin with the CDK protein Cdc2 can drive the mitotic cell cycle. Meiosis is a modified cell cycle programme in which a single S-phase is followed by two consecutive rounds of chromosome segregation. Here we systematically analyse the requirements of the different fission yeast cyclins for meiotic cell cycle progression. We also show that a single Cdc13–Cdc2 complex, in the absence of the other cyclins, can drive the meiotic cell cycle. We propose that qualitatively different CDK complexes are not absolutely required for cell cycle progression either during mitosis or meiosis, and that a single CDK complex can drive both cell cycle programmes. PMID:25891897

Piperlongumine decreases cell proliferation and the expression of cell cycle-associated proteins by inhibiting Akt pathway in human lung cancer cells.

PubMed

Seok, Jin Sil; Jeong, Chang Hee; Petriello, Michael C; Seo, Han Geuk; Yoo, Hyunjin; Hong, Kwonho; Han, Sung Gu

2018-01-01

Piperlongumine (PL) is an alkaloid of a pepper plant found in Southeast Asia. PL is known to induce selective toxicity towards a variety of cancer cell types. To explore the possible anti-lung cancer effects of PL, A549 cells were treated with PL (0-40 μM) for 24 h. Alterations in the expression of cell cycle-associated proteins (cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6 and retinoblastoma (Rb)) and intracellular signaling molecules (extracellular signal receptor-activated kinase 1/2 (ERK1/2), Akt, p38 and nuclear factor-κB (NF-κB)) were examined in cells following treatment of PL using Western blot analysis. Results showed that proliferation of cells were significantly decreased by PL in a dose-dependent manner. Flow cytometry results demonstrated increased number of cells in G1 phase in PL (40 μM)-treated group. Reactive oxygen species was significantly increased in cells treated with PL at 20-40 μM. The expression of cyclin D1, CDK4, CDK6 and p-Rb were markedly decreased in cells treated with PL at 40 μM. Treatment of cells with PL suppressed phosphorylation of Akt but increased ERK1/2 phosphorylation. Treatment of PL significantly decreased nuclear translocation of NF-κB p65 in cells. These results suggest that PL possesses antiproliferative properties in A549 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resveratrol Differentially Regulates NAMPT and SIRT1 in Hepatocarcinoma Cells and Primary Human Hepatocytes

PubMed Central

Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Petzold-Quinque, Stefanie; Damm, Georg; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

2014-01-01

Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells) and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells. PMID:24603648

Genome of a Low-Salinity Ammonia-Oxidizing Archaeon Determined by Single-Cell and Metagenomic Analysis

PubMed Central

Potanina, Anastasia; Francis, Christopher A.; Quake, Stephen R.

2011-01-01

Ammonia-oxidizing archaea (AOA) are thought to be among the most abundant microorganisms on Earth and may significantly impact the global nitrogen and carbon cycles. We sequenced the genome of AOA in an enrichment culture from low-salinity sediments in San Francisco Bay using single-cell and metagenomic genome sequence data. Five single cells were isolated inside an integrated microfluidic device using laser tweezers, the cells' genomic DNA was amplified by multiple displacement amplification (MDA) in 50 nL volumes and then sequenced by high-throughput DNA pyrosequencing. This microscopy-based approach to single-cell genomics minimizes contamination and allows correlation of high-resolution cell images with genomic sequences. Statistical properties of coverage across the five single cells, in combination with the contrasting properties of the metagenomic dataset allowed the assembly of a high-quality draft genome. The genome of this AOA, which we designate Candidatus Nitrosoarchaeum limnia SFB1, is ∼1.77 Mb with >2100 genes and a G+C content of 32%. Across the entire genome, the average nucleotide identity to Nitrosopumilus maritimus, the only AOA in pure culture, is ∼70%, suggesting this AOA represents a new genus of Crenarchaeota. Phylogenetically, the 16S rRNA and ammonia monooxygenase subunit A (amoA) genes of this AOA are most closely related to sequences reported from a wide variety of freshwater ecosystems. Like N. maritimus, the low-salinity AOA genome appears to have an ammonia oxidation pathway distinct from ammonia oxidizing bacteria (AOB). In contrast to other described AOA, these low-salinity AOA appear to be motile, based on the presence of numerous motility- and chemotaxis-associated genes in the genome. This genome data will be used to inform targeted physiological and metabolic studies of this novel group of AOA, which may ultimately advance our understanding of AOA metabolism and their impacts on the global carbon and nitrogen cycles. PMID:21364937

Genome of a low-salinity ammonia-oxidizing archaeon determined by single-cell and metagenomic analysis.

PubMed

Blainey, Paul C; Mosier, Annika C; Potanina, Anastasia; Francis, Christopher A; Quake, Stephen R

2011-02-22

Ammonia-oxidizing archaea (AOA) are thought to be among the most abundant microorganisms on Earth and may significantly impact the global nitrogen and carbon cycles. We sequenced the genome of AOA in an enrichment culture from low-salinity sediments in San Francisco Bay using single-cell and metagenomic genome sequence data. Five single cells were isolated inside an integrated microfluidic device using laser tweezers, the cells' genomic DNA was amplified by multiple displacement amplification (MDA) in 50 nL volumes and then sequenced by high-throughput DNA pyrosequencing. This microscopy-based approach to single-cell genomics minimizes contamination and allows correlation of high-resolution cell images with genomic sequences. Statistical properties of coverage across the five single cells, in combination with the contrasting properties of the metagenomic dataset allowed the assembly of a high-quality draft genome. The genome of this AOA, which we designate Candidatus Nitrosoarchaeum limnia SFB1, is ∼1.77 Mb with >2100 genes and a G+C content of 32%. Across the entire genome, the average nucleotide identity to Nitrosopumilus maritimus, the only AOA in pure culture, is ∼70%, suggesting this AOA represents a new genus of Crenarchaeota. Phylogenetically, the 16S rRNA and ammonia monooxygenase subunit A (amoA) genes of this AOA are most closely related to sequences reported from a wide variety of freshwater ecosystems. Like N. maritimus, the low-salinity AOA genome appears to have an ammonia oxidation pathway distinct from ammonia oxidizing bacteria (AOB). In contrast to other described AOA, these low-salinity AOA appear to be motile, based on the presence of numerous motility- and chemotaxis-associated genes in the genome. This genome data will be used to inform targeted physiological and metabolic studies of this novel group of AOA, which may ultimately advance our understanding of AOA metabolism and their impacts on the global carbon and nitrogen cycles.

Hypoxia induces p53 accumulation in the S-phase and accumulation of hypophosphorylated retinoblastoma protein in all cell cycle phases of human melanoma cells.

PubMed Central

Danielsen, T.; Hvidsten, M.; Stokke, T.; Solberg, K.; Rofstad, E. K.

1998-01-01

Hypoxia has been shown to induce accumulation of p53 and of hypophosphorylated retinoblastoma protein (pRb) in tumour cells. In this study, the cell cycle dependence of p53 accumulation and pRb hypophosphorylation in four human melanoma cell lines that are wild type for p53 was investigated using two-parameter flow cytometry measurements of p53 or pRb protein content and DNA content. The hypoxia-induced increase in p53 protein was higher in S-phase than in G1 and G2 phases in all cell lines. The accumulation of p53 in S-phase during hypoxia was not related to hypoxia-induced apoptosis or substantial cell cycle specific cell inactivation during the first 24 h of reoxygenation. pRb was hypophosphorylated in all cell cycle phases by hypoxia treatment. The results did not support a direct link between p53 and pRb during hypoxia because p53 was induced in a cell cycle-specific manner, whereas no cell cycle-dependent differences in pRb hypophosphorylation were detected. Only a fraction of the cell populations (0.60+/-0.10) showed hypophosphorylated pRb. Thus, pRb is probably not the only mediator of the hypoxia-induced cell cycle block seen in all cells and all cell cycle phases. Moreover, the cell cycle-dependent induction of p53 by hypoxia suggests that the primary function of p53 accumulation during hypoxia is other than to arrest the cells. Images Figure 4 Figure 7 PMID:9862563

Properties of large Li ion cells using a nickel based mixed oxide

NASA Astrophysics Data System (ADS)

Broussely, M.; Blanchard, Ph; Biensan, Ph; Planchat, J. P.; Nechev, K.; Staniewicz, R. J.

The possible use of LiNiO 2 similar to LiCoO 2, as a positive material in rechargeable lithium batteries was recognized 20 years ago and starting 10 years later, many research studies led to material improvement through substitution of some of the nickel ions by other metallic ions. These modifications improve the thermal stability at high charge level or overcharge, as well as cycling and storage properties. Commercial material is now available at large industrial scale, which allows its use in big "industrial" Li ion batteries. Using low cost raw material (Ni), it is expected to be cost competitive with the manganese based systems usually mentioned as low cost on the total cell $/Wh basis. Providing higher energy density, and demonstrating excellent behavior on storage and extended cycle life, LiNiO 2 has definite advantages over the manganese system. Thanks to their properties, these batteries have demonstrated their ability to be used in lot of applications, either for transportation or standby. Their light weight makes them attractive for powering satellites. Although safety improvements are always desirable for all non-aqueous batteries using flammable organic electrolytes, suitable battery designs allow the systems to reach the acceptable level of safety required by many users. Beside the largely distributed lead acid and nickel cadmium batteries, Li ion will found its place in the "industrial batteries" market, in a proportion directly linked to its future cost reduction.

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

PubMed

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

PubMed Central

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PMID:17901127

Cell cycle gene expression under clinorotation

NASA Astrophysics Data System (ADS)

Artemenko, Olga

2016-07-01

Cyclins and cyclin-dependent kinase (CDK) are main regulators of the cell cycle of eukaryotes. It's assumes a significant change of their level in cells under microgravity conditions and by other physical factors actions. The clinorotation use enables to determine the influence of gravity on simulated events in the cell during the cell cycle - exit from the state of quiet stage and promotion presynthetic phase (G1) and DNA synthesis phase (S) of the cell cycle. For the clinorotation effect study on cell proliferation activity is the necessary studies of molecular mechanisms of cell cycle regulation and development of plants under altered gravity condition. The activity of cyclin D, which is responsible for the events of the cell cycle in presynthetic phase can be controlled by the action of endogenous as well as exogenous factors, but clinorotation is one of the factors that influence on genes expression that regulate the cell cycle.These data can be used as a model for further research of cyclin - CDK complex for study of molecular mechanisms regulation of growth and proliferation. In this investigation we tried to summarize and analyze known literature and own data we obtained relatively the main regulators of the cell cycle in altered gravity condition.

KOH concentration effect on cycle life of nickel-hydrogen cells

NASA Technical Reports Server (NTRS)

Lim, Hong S.; Verzwyvelt, S. A.

1987-01-01

A cycle life test of Ni/H2 cells containing electrolytes of various KOH concentrations and a sintered type nickel electrode was carried out at 23 C using a 45 min accelerated low Earth orbit (LEO) cycle regime at 80 percent depth of discharge. One of three cells containing 26 percent KOH has achieved over 28,000 cycles, and the other two 19,000 cycles, without a sign of failure. Two other cells containing 31 percent KOH electrolyte, which is the concentration presently used in aerospace cells, failed after 2,979 and 3,620 cycles. This result indicates that the cycle life of the present type of Ni/H2 cells may be extended by a factor of 5 to 10 simply by lowering the KOH concentration. Long cycle life of a Ni/H2 battery at high depth-of-discharge operation is desired, particularly for an LEO spacecraft application. Typically, battery life of about 30,000 cycles is required for a five year mission in an LEO. Such a cycle life with presently available cells can be assured only at a very low depth-of-discharge operation. Results of testing already show that the cycle life of an Ni/H2 cell is tremendously improved by simply using an electrolyte of low KOH concentration.

The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

PubMed

Mizejewski, G J

2016-09-01

The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

Sodium-Oxygen Batteries: A Comparative Review from Chemical and Electrochemical Fundamentals to Future Perspective.

PubMed

Yadegari, Hossein; Sun, Qian; Sun, Xueliang

2016-09-01

Alkali metal-oxygen (Li-O2 , Na-O2 ) batteries have attracted a great deal of attention recently due to their high theoretical energy densities, comparable to gasoline, making them attractive candidates for application in electrical vehicles. However, the limited cycling life and low energy efficiency (high charging overpotential) of these cells hinder their commercialization. The Li-O2 battery system has been extensively studied in this regard during the past decade. Compared to the numerous reports of Li-O2 batteries, the research on Na-O2 batteries is still in its infancy. Although, Na-O2 batteries show a number of attractive properties such as low charging overpotential and high round-trip energy efficiency, their cycling life is currently limited to a few tens of cycles. Therefore, understanding the chemistry behind Na-O2 cells is critical towards enhancing their performance and advancing their development. Chemical and electrochemical reactions of Na-O2 batteries are reviewed and compared with those of Li-O2 batteries in the present review, as well as recent works on the chemical composition and morphology of the discharge products in these batteries. Furthermore, the determining kinetics factors for controlling the chemical composition of the discharge products in Na-O2 cells are discussed and the potential research directions toward improving Na-O2 cells are proposed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel evidence for curcumin and boswellic acid induced chemoprevention through regulation of miR-34a and miR-27a in colorectal cancer

PubMed Central

Toden, Shusuke; Okugawa, Yoshinaga; Buhrmann, Constanze; Nattamai, Durgha; Anguiano, Esperanza; Baldwin, Nicole; Shakibaei, Mehdi; Boland, C. Richard; Goel, Ajay

2015-01-01

Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality worldwide, but it is truly a preventable disease. Both curcumin and boswellic acids are well-established dietary botanicals with potent anti-tumorigenic properties which have been shown to modulate multiple oncogenic pathways. Recent data suggest that the chemopreventive effects of these botanicals may in part be mediated through regulation of key cancer-related microRNAs (miRNAs) and their downstream gene targets. Here, we investigated the anti-tumorigenic effects of curcumin and 3 acetyl-11-keto-β-boswellic acid (AKBA) on modulation of specific cancer-related miRNAs in CRC cells and validated their protective effects in vivo using a xenograft mouse model. Both curcumin and AKBA inhibited cellular proliferation, induced apoptosis and cell cycle arrest in CRC cell lines, and these effects were significantly enhanced with combined treatment. Gene-expression arrays revealed that curcumin and AKBA regulated distinct cancer signaling pathways including key cell-cycle regulatory genes. Combined bioinformatics and in-silico analysis identified apoptosis, proliferation and cell-cycle regulatory signaling pathways as key modulators of curcumin and AKBA-induced anti-cancer effects. We discovered that curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in CRC cells. Furthermore, we demonstrated in a mouse xenograft model that both curcumin and AKBA treatments suppressed tumor growth, which corresponded with alterations in the expression of miR-34a and miR-27a, consistent with our in vitro findings. Herein we provide novel mechanistic evidence for the chemopreventive effects of curcumin and AKBA through regulation of specific miRNAs in colorectal cancer. PMID:25712055

Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant1[C][W

PubMed Central

Hudik, Elodie; Yoshioka, Yasushi; Domenichini, Séverine; Bourge, Mickaël; Soubigout-Taconnat, Ludivine; Mazubert, Christelle; Yi, Dalong; Bujaldon, Sandrine; Hayashi, Hiroyuki; De Veylder, Lieven; Bergounioux, Catherine; Benhamed, Moussa; Raynaud, Cécile

2014-01-01

The majority of research on cell cycle regulation is focused on the nuclear events that govern the replication and segregation of the genome between the two daughter cells. However, eukaryotic cells contain several compartmentalized organelles with specialized functions, and coordination among these organelles is required for proper cell cycle progression, as evidenced by the isolation of several mutants in which both organelle function and overall plant development were affected. To investigate how chloroplast dysfunction affects the cell cycle, we analyzed the crumpled leaf (crl) mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for a chloroplastic protein and displays particularly severe developmental defects. In the crl mutant, we reveal that cell cycle regulation is altered drastically and that meristematic cells prematurely enter differentiation, leading to reduced plant stature and early endoreduplication in the leaves. This response is due to the repression of several key cell cycle regulators as well as constitutive activation of stress-response genes, among them the cell cycle inhibitor SIAMESE-RELATED5. One unique feature of the crl mutant is that it produces aplastidic cells in several organs, including the root tip. By investigating the consequence of the absence of plastids on cell cycle progression, we showed that nuclear DNA replication occurs in aplastidic cells in the root tip, which opens future research prospects regarding the dialogue between plastids and the nucleus during cell cycle regulation in higher plants. PMID:25037213

The Influence of the Polymer Amount on the Biological Properties of PCL/ZrO2 Hybrid Materials Synthesized via Sol-Gel Technique

PubMed Central

Tranquillo, Elisabetta; Illiano, Michela; Sapio, Luigi; Spina, Annamaria; Naviglio, Silvio

2017-01-01

Organic/inorganic hybrid materials are attracting considerable attention in the biomedical area. The sol-gel process provides a convenient way to produce many bioactive organic–inorganic hybrids. Among those, poly(e-caprolactone)/zirconia (PCL/ZrO2) hybrids have proved to be bioactive with no toxic materials. The aim of this study was to investigate the effects of these materials on the cellular response as a function of the PCL content, in order to evaluate their potential use in the biomedical field. For this purpose, PCL/ZrO2 hybrids containing 6, 12, 24, and 50 wt % of PCL were synthesized by the sol-gel method. The effects of their presence on the NIH-3T3 fibroblast cell line carrying out direct cell number counting, MTT, cell damage assays, flow cytometry-based analysis of cell-cycle progression, and immunoblotting experiments. The results confirm and extend the findings that PCL/ZrO2 hybrids are free from toxicity. The hybrids containing 12 and 24 wt % PCL, (more than 6 and 50 wt % ones) enhance cell proliferation when compared to pure ZrO2 by affecting cell cycle progression. The finding that the content of PCL in PCL/ZrO2 hybrids differently supports cell proliferation suggests that PCL/ZrO2 hybrids could be useful tools with different potential clinical applications. PMID:29039803

In vitro biocompatibility and proliferative effects of polar and non-polar extracts of cucurbita ficifolia on human mesenchymal stem cells.

PubMed

Aristatile, Balakrishnan; Alshammari, Ghedeir M

2017-05-01

Cucurbita ficifolia (C. ficifolia) has been traditionally known for its medicinal properties as an antioxidant, anti-diabetic and anti-inflammatory agent. However, there has been an enduring attention towards the identification of unique method, to isolate the natural components for therapeutic applications. Our study focuses on different polar and non-polar solvents (methanol, hexane and chloroform) to extract the bioactive components from C. ficifolia (pumpkin) and to study the biocompatibility and cytotoxicity effects on human bone marrow-mesenchymal stem cells (hBM-MSCs). The extracts were screened for their effects on cytotoxicity, cell proliferation and cell cycle on the hBM-MSCs cell line. The assays demonstrated that the chloroform extract was highly biocompatible, with less cytotoxic effect, and enhanced the cell proliferation. The methanol extract did not exhibit significant cytotoxicity when compare to the control. Concordantly, the cell cycle analysis confirmed that chloroform extract enhances the proliferation at lower concentrations. On the other hand, hexane extract showed high level of cytotoxicity with apoptotic and necrotic changes in hBM-MSCs. Collectively, our data revealed that chloroform is a good candidate to extract the bioactive components from C. ficifolia. Furthermore, our results suggest that specific gravity and density of the solvent might play a crucial role in the extraction process, which warrants further investigations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics.

PubMed

Rumman, Mohammad; Majumder, Abhijit; Harkness, Linda; Venugopal, Balu; Vinay, M B; Pillai, Malini S; Kassem, Moustapha; Dhawan, Jyotsna

2018-05-17

Several studies have suggested that bone marrow stromal steam cells (BMSC) exist in a quiescent state (G0) within the in vivo niche; however, an explicit analysis of the biology of G0 state-BMSC has not been reported. We hypothesized that induction of G0 in BMSC might enhance their stem cell properties. Thus, we induced quiescence in BMSC in vitro by (a) suspension culture in a viscous medium or (b) culture on soft polyacrylamide substrate; and examined their molecular and functional phenotype. Induction of G0 was confirmed by bromo-deoxyuridine (BrdU) labelling and analysis of cell cycle gene expression. Upon reactivation and re-entry into cell cycle, G0 state-BMSC exhibited enhanced clonogenic self-renewal, preferential differentiation into osteoblastic rather than adipocytic cells and increased ectopic bone formation when implanted subcutaneously in vivo in immune-deficient mice, compared to asynchronous proliferating (pre-G0) BMSC. Global gene expression profiling revealed reprogramming of the transcriptome during G0 state including significant alterations in relevant pathways and expression of secreted factors, suggesting altered autocrine and paracrine signaling by G0 state-BMSC and a possible mechanism for enhanced bone formation. G0 state-BMSC might provide a clinically relevant model for understanding the in vivo biology of BMSC. Copyright © 2018. Published by Elsevier B.V.

Human Mesenchymal Stem Cells Derived From Limb Bud Can Differentiate into All Three Embryonic Germ Layers Lineages

PubMed Central

Jiao, Fei; Wang, Juan; Dong, Zhao-lun; Wu, Min-juan; Zhao, Ting-bao; Li, Dan-dan

2012-01-01

Abstract Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them “human limb bud–derived mesenchymal stem cells” (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro. PMID:22775353

Coherent assembly of phytoplankton communities in diverse temperate ocean ecosystems

PubMed Central

Li, William K.W; Glen Harrison, W; Head, Erica J.H

2006-01-01

The annual cycle of phytoplankton cell abundance is coherent across diverse ecosystems in the temperate North Atlantic Ocean. In Bedford Basin, on the Scotian Shelf and in the Labrador Sea, the numerical abundance of phytoplankton is low in spring and high in autumn, thus in phase with the temperature cycle. Temperature aligns abundance on a common basis, effectively adjusting apparent cell discrepancies in waters that are colder or warmer than the regional norm. As an example of holistic simplicity arising from underlying complexity, the variance in a community variable (total abundance) is explained by a single predictor (temperature) to the extent of 75% in the marginal seas. In the estuarine basin, weekly averages of phytoplankton and temperature computed from a 13 year time-series yield a predictive relationship with 91% explained variance. Temperature-directed assembly of individual phytoplankton cells to form communities is statistically robust, consistent with observed biomass changes, amenable to theoretical analysis, and a sentinel for long-term change. Since cell abundance is a community property in the same units for all marine microbes at any trophic level and at any phylogenetic position, it promises to integrate biological oceanography into general ecology and evolution. PMID:16822757

Origin of bistability underlying mammalian cell cycle entry

PubMed Central

Yao, Guang; Tan, Cheemeng; West, Mike; Nevins, Joseph R; You, Lingchong

2011-01-01

Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb–E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb–E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb–E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb–E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point. PMID:21525871

Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium-Induced Colon Cancer in C57BL/6J Mice.

PubMed

Lee, Hyun Ah; Kim, Hyunung; Lee, Kwang-Won; Park, Kun-Young

2016-01-01

This study was undertaken to evaluate enhancement of the chemopreventive properties of kimchi by dietary nanosized Lactobacillus (Lab.)plantarum (nLp) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated colorectal cancer C57BL/6J mouse model. nLp is a dead, shrunken, processed form of Lab. Plantarum isolated from kimchi that is 0.5-1.0 µm in size. The results obtained showed that animals fed kimchi with nLp (K-nLp) had longer colons and lower colon weights/length ratios and developed fewer tumors than mice fed kimchi alone (K). In addition, K-nLp administration reduced levels of proinflammatory cytokine serum levels and mediated the mRNA and protein expressions of inflammatory, apoptotic, and cell-cycle markers to suppress inflammation and induce tumor-cell apoptosis and cell-cycle arrest. Moreover, it elevated natural killer-cell cytotoxicity. The study suggests adding nLp to kimchi could improve the suppressive effect of kimchi on AOM/DSS-induced colorectal cancer. These findings indicate nLp has potential use as a functional chemopreventive ingredient in the food industry.

High resolution microscopy reveals the nuclear shape of budding yeast during cell cycle and in various biological states

PubMed Central

Kamgoue, Alain; Normand, Christophe; Léger-Silvestre, Isabelle; Mangeat, Thomas

2016-01-01

ABSTRACT How spatial organization of the genome depends on nuclear shape is unknown, mostly because accurate nuclear size and shape measurement is technically challenging. In large cell populations of the yeast Saccharomyces cerevisiae, we assessed the geometry (size and shape) of nuclei in three dimensions with a resolution of 30 nm. We improved an automated fluorescence localization method by implementing a post-acquisition correction of the spherical microscopic aberration along the z-axis, to detect the three dimensional (3D) positions of nuclear pore complexes (NPCs) in the nuclear envelope. Here, we used a method called NucQuant to accurately estimate the geometry of nuclei in 3D throughout the cell cycle. To increase the robustness of the statistics, we aggregated thousands of detected NPCs from a cell population in a single representation using the nucleolus or the spindle pole body (SPB) as references to align nuclei along the same axis. We could detect asymmetric changes of the nucleus associated with modification of nucleolar size. Stereotypical modification of the nucleus toward the nucleolus further confirmed the asymmetric properties of the nuclear envelope. PMID:27831493

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gabrielson, Marike; Reizer, Edwin; Stål, Olle

An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclearmore » Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G{sub 1}-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G{sub 1}-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. - Highlights: • Proposed cell cycle regulation through the mitochondrial transporter SLC25A43. • SLC25A43 alters cell proliferation rate and cell cycle progression. • Suppressed SLC25A43 influences transcription of cell cycle regulatory genes.« less

Deregulated expression of Cdc6 as BCR/ABL-dependent survival factor in chronic myeloid leukemia cells.

PubMed

Zhang, Jia-Hua; He, Yan-Li; Zhu, Rui; Du, Wen; Xiao, Jun-Hua

2017-06-01

Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated. In this study, our data showed that cell division cycle protein 6 expression was significantly upregulated in primary chronic myeloid leukemia cells and the chronic myeloid leukemia cell line K562 cells, as compared to the normal bone marrow mononuclear cells. BCR/ABL kinase inhibitor STI571 or BCR/ABL small interfering RNA could significantly downregulate cell division cycle protein 6 messenger RNA expression in K562 cells. Moreover, phosphoinositide 3-kinase/AKT pathway inhibitor LY294002 and Janus kinase/signal transducer and activator of transcription pathway inhibitor AG490 could downregulate cell division cycle protein 6 expression in K562 cells, but not RAS/mitogen-activated protein kinase pathway inhibitor PD98059 had such effect. Cell division cycle protein 6 gene silencing by small interfering RNA effectively resulted in decrease of proliferation, increase of apoptosis, and arrest of cell cycle in K562 cells. These findings have demonstrated that cell division cycle protein 6 overexpression may contribute to the high proliferation and low apoptosis in chronic myeloid leukemia cells and can be regulated by BCR/ABL signal transduction through downstream phosphoinositide 3-kinase/Akt and Janus kinase/signal transducer and activator of transcription pathways, suggesting cell division cycle protein 6 as a potential therapeutic target in chronic myeloid leukemia.

Modeling Bi-modality Improves Characterization of Cell Cycle on Gene Expression in Single Cells

PubMed Central

Danaher, Patrick; Finak, Greg; Krouse, Michael; Wang, Alice; Webster, Philippa; Beechem, Joseph; Gottardo, Raphael

2014-01-01

Advances in high-throughput, single cell gene expression are allowing interrogation of cell heterogeneity. However, there is concern that the cell cycle phase of a cell might bias characterizations of gene expression at the single-cell level. We assess the effect of cell cycle phase on gene expression in single cells by measuring 333 genes in 930 cells across three phases and three cell lines. We determine each cell's phase non-invasively without chemical arrest and use it as a covariate in tests of differential expression. We observe bi-modal gene expression, a previously-described phenomenon, wherein the expression of otherwise abundant genes is either strongly positive, or undetectable within individual cells. This bi-modality is likely both biologically and technically driven. Irrespective of its source, we show that it should be modeled to draw accurate inferences from single cell expression experiments. To this end, we propose a semi-continuous modeling framework based on the generalized linear model, and use it to characterize genes with consistent cell cycle effects across three cell lines. Our new computational framework improves the detection of previously characterized cell-cycle genes compared to approaches that do not account for the bi-modality of single-cell data. We use our semi-continuous modelling framework to estimate single cell gene co-expression networks. These networks suggest that in addition to having phase-dependent shifts in expression (when averaged over many cells), some, but not all, canonical cell cycle genes tend to be co-expressed in groups in single cells. We estimate the amount of single cell expression variability attributable to the cell cycle. We find that the cell cycle explains only 5%–17% of expression variability, suggesting that the cell cycle will not tend to be a large nuisance factor in analysis of the single cell transcriptome. PMID:25032992

Different Material States of Pub1 Condensates Define Distinct Modes of Stress Adaptation and Recovery.

PubMed

Kroschwald, Sonja; Munder, Matthias C; Maharana, Shovamayee; Franzmann, Titus M; Richter, Doris; Ruer, Martine; Hyman, Anthony A; Alberti, Simon

2018-06-12

How cells adapt to varying environmental conditions is largely unknown. Here, we show that, in budding yeast, the RNA-binding and stress granule protein Pub1 has an intrinsic property to form condensates upon starvation or heat stress and that condensate formation is associated with cell-cycle arrest. Release from arrest coincides with condensate dissolution, which takes minutes (starvation) or hours (heat shock). In vitro reconstitution reveals that the different dissolution rates of starvation- and heat-induced condensates are due to their different material properties: starvation-induced Pub1 condensates form by liquid-liquid demixing and subsequently convert into reversible gel-like particles; heat-induced condensates are more solid-like and require chaperones for disaggregation. Our data suggest that different physiological stresses, as well as stress durations and intensities, induce condensates with distinct physical properties and thereby define different modes of stress adaptation and rates of recovery. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Equilibrium between cell division and apoptosis in immortal cells as an alternative to the G1 restriction mechanism in mammalian cells.

PubMed

Dedov, Vadim N; Dedova, Irina V; Nicholson, Garth A

2004-04-01

Starvation arrests cultured mammalian cells in the G(1) restriction point of the cell cycle, whereas cancer cells generally lose the regulatory control of the cell cycle. Human lymphocytes, infected with Epstein-Barr virus (EBV), also lose their cell cycle control and produce immortal lymphoblastoid cell lines. We show that during starvation, EBV-lymphoblasts override the cell cycle arrest in the G(1) restriction point and continue cell division. Simultaneously, starvation activates apoptosis in an approximately half of the daughter cells in each cell generation. Continuos cell division and partial removal of cells by apoptosis results in stabilization of viable cell numbers, where a majority of viable cells are in the G(1) phase of the cell cycle. In contrast to starvation, anticancer drug etoposide activates apoptosis indiscriminately in all EBV-lymphoblasts and convertes all the viable cells into apoptotic. We conclude that the removal of surplus cells by apoptosis may represent a survival mechanism of transformed (i.e., cancer) cell population in nutrient restricted conditions, whereas nontransformed mammalian cells are arrested in the G(1) restriction point of the cell cycle.

[Effects of methyl tertiary butyl ether on cell cycle and cell apoptosis].

PubMed

Zhou, W; Huang, G; Zhang, H; Ye, S

2000-07-01

To explore the effects of the new gasoline additive, methyl tertiary butyl ether (MTBE) on cell cycle and cell apoptosis. Flow cytometry was used to evaluate the effect of MTBE (1, 2, 4 microl/ml, 24 h) on NIH/3T3 cell cycles; and the effect of MTBE on Hela cell apoptosis was evaluated by detecting cell survival using crystal violet staining. Flow cytometry showed that MTBE could change NIH/3T3 cell cycles, decrease the number of cells in S stage, and arrest cells at G(2) + M stage. The results suggested that MTBE could affect NIH/3T3 cell cycles and induce cell proliferation. This situation existed 48 hours after the treatment, and cell cycles came back normal 96 hours after the treatment. By detecting cell survival using crystal violet staining, we found that MTBE could inhibit the apoptosis of Hela cells which was induced by tumor necrosis factor (TNF)alpha and cycloheximide. MTBE's carcinogenicity to animals may relate to induction of cell proliferation and inhibition of cell apoptosis.

KOH concentration effect on the cycle life of nickel-hydrogen cells. 4: Results of failure analyse

NASA Technical Reports Server (NTRS)

Lim, H. S.; Verzwyvelt, S. A.

1989-01-01

Effects of KOH concentrations on failure modes and mechanisms of nickel-hydrogen cells were studied using long cycled boiler plate cells containing electrolytes of various KOH concentrations ranging 21 to 36 percent. Life of these cells were up to 40,000 cycles in an accelerated low earth orbit (LEO) cycle regime at 80 percent depth of discharge. An interim life test results were reported earlier in J. Power Sources, 22, 213-220, 1988. The results of final life test, end-of-life cell performance, and teardown analyses are discussed. These teardown analyses included visual observations, measurements of nickel electrode capacity in an electrolyte-flooded cell, dimensional changes of cell components, SEM studies on cell cross section, BET surface area and pore volume distribution in cycled nickel electrodes, and chemical analyses. Cycle life of a nickel-hydrogen cell was improved tremendously as KOH concentration was decreased from 36 to 31 percent and from 31 to 26 percent while effect of further concentration decrease was complicated as described in our earlier report. Failure mode of high concentration (31 to 36 percent) cells was gradual capacity decrease, while that of low concentration (21 to 26 percent) cells was mainly formation of a soft short. Long cycled (25,000 to 40,000 cycles) nickel electrodes were expanded more than 50 percent of the initial value, but no correlation was found between this expansion and measured capacity. All electrodes cycled in low concentration (21 to 26 percent) cells had higher capacity than those cycled in high concentration (31 to 36 percent) cells.

The cell-cycle interactome: a source of growth regulators?

PubMed

Blomme, Jonas; Inzé, Dirk; Gonzalez, Nathalie

2014-06-01

When plants develop, cell proliferation and cell expansion are tightly controlled in order to generate organs with a determinate final size such as leaves. Several studies have demonstrated the importance of the cell proliferation phase for leaf growth, illustrating that cell-cycle regulation is crucial for correct leaf development. A large and complex set of interacting proteins that constitute the cell-cycle interactome controls the transition from one cell-cycle phase to another. Here, we review the current knowledge on cell-cycle regulators from this interactome affecting final leaf size when their expression is altered, mainly in Arabidopsis. In addition to the description of mutants of CYCLIN-DEPENDENT KINASES (CDKs), CYCLINS (CYCs), and their transcriptional and post-translational regulators, a phenotypic analysis of gain- and loss-of-function mutants for 27 genes encoding proteins that interact with cell-cycle proteins is presented. This compilation of information shows that when cell-cycle-related genes are mis-expressed, leaf growth is often altered and that, seemingly, three main trends appear to be crucial in the regulation of final organ size by cell-cycle-related genes: (i) cellular compensation; (ii) gene dosage; and (iii) correct transition through the G2/M phase by ANAPHASE PROMOTING COMPLEX/CYCLOSOME (APC/C) activation. In conclusion, this meta-analysis shows that the cell-cycle interactome is enriched in leaf growth regulators, and illustrates the potential to identify new leaf growth regulators among putative new cell-cycle regulators. © The Author 2013. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Performance of Li-Ion Cells Under Battery Voltage Charge Control

NASA Technical Reports Server (NTRS)

Rao, Gopalakrishna M.; Vaidyanathan, Hari; Day, John H. (Technical Monitor)

2001-01-01

A study consisting of electrochemical characterization and Low-Earth-Orbit (LEO) cycling of Li-Ion cells from three vendors was initiated in 1999 to determine the cycling performance and to infuse the new technology in the future NASA missions. The 8-cell batteries included in this evaluation are prismatic cells manufactured by Mine Safety Appliances Company (MSA), cylindrical cells manufactured by SAFT and prismatic cells manufactured by Yardney Technical Products, Inc. (YTP). The three batteries were cycle tested in the LEO regime at 40% depth of discharge, and under a charge control technique that consists of battery voltage clamp with a current taper. The initial testing was conducted at 20 C; however, the batteries were cycled also intermittently at low temperatures. YTP 20 Ah cells consisted of mixed-oxide (Co and Ni) positive, graphitic carbon negative, LIPF6 salt mixed with organic carbonate solvents. The battery voltage clamp was 32 V. The low temperature cycling tests started after 4575 cycles at 20 C. The cells were not capable of cycling. at low temperature since the charge acceptance at battery level was poor. There was a cell in the battery that showed too high an end-of-charge (EOC) voltage thereby limiting the ability to charge the rest of the cells in the battery. The battery has completed 6714 cycles. SAFT 12 Ah cells consisted of mixed-oxide (Co and NO positive, graphitic carbon negative, LiPF6 salt mixed with organic carbonate solvents. The battery voltage clamp was for 30.8 V. The low temperature cycling tests started after 4594 cycles at 20 C. A cell that showed low end of discharge (EOD) and EOC voltages and three other cells that showed higher EOC voltages limited the charge acceptance at the selected voltage limit during charge. The cells were capable of cycling at 10 C and 0 C but the charge voltage limit had to be increased to 34.3 V (4.3 V per cell). The low temperature cycling may have induced poor chargeability since the voltage had to be increased to achieve the required charge input. The battery has completed 6226 cycles. MSA 10 Ah cells consisted of Co oxide positive, graphitic carbon negative, LiPF6 salt mixed with organic carbonate solvents. The battery voltage clamp was 30.8 V. The low temperature cycling tests were started after 2182 cycles at 20 C. The cells were capable of cycling at 10 C and 0 C. Like SAFT, the voltage limit on charge had to be increased to 36 V (4.5 V per cell). There was a cell (cell S/N 13) in the battery that showed poor performance features such as low EOD voltage and high EOC voltage. The battery has completed 3441 cycles. A reconditioning procedure that consisted of C15 charge to a taper current of C/100 and C/20 discharge improved the voltage behavior of SAFT and MSA cells with no significant effect on YTP cells. We have demonstrated that the charge operation with VT clamp at battery rather than at cell level is feasible for onboard Li-Ion battery operation.

A Comprehensive Review of Punica granatum (Pomegranate) Properties in Toxicological, Pharmacological, Cellular and Molecular Biology Researches

PubMed Central

Rahimi, Hamid Reza; Arastoo, Mohammad; Ostad, Seyed Nasser

2012-01-01

Punica granatum (Pg), commonly known as pomegranate (Pg), is a member of the monogeneric family, Punicaceae, and is mainly found in Iran which is considered to be its primary centre of origin. Pg and its chemical components possess various pharmacological and toxicological properties including antioxidant, anti-inflammatory (by inhibiting pro-inflammatory cytokines), anti-cancer and anti-angiogenesis activities. They also show inhibitory effects on invasion/motility, cell cycle, apoptosis, and vital enzymes such as cyclooxygenase (COX), lipooxygenase (LOX), cytochrome P450 (CYP450), phospholipase A2 (PLA2), ornithine decarboxylase (ODC), carbonic anhydrase (CA), 17beta-hydroxysteroid dehydrogenase (17β-HSDs) and serine protease (SP). Furthermore, they can stimulate cell differentiation and possess anti-mutagenic effects. Pg can also interfere with several signaling pathways including PI3K/AKT, mTOR, PI3K, Bcl-X, Bax, Bad, MAPK, ERK1/2, P38, JNK, and caspase. However, the exact mechanisms for its pharmacological and toxicological properties remain to be unclear and need further evaluation. These properties strongly suggest a wide range use of Pg for clinical applications. This review will discuss the areas for which Pg has shown therapeutic properties in different mechanisms. PMID:24250463

Boletus edulis biologically active biopolymers induce cell cycle arrest in human colon adenocarcinoma cells.

PubMed

Lemieszek, Marta Kinga; Cardoso, Claudia; Ferreira Milheiro Nunes, Fernando Hermínio; Ramos Novo Amorim de Barros, Ana Isabel; Marques, Guilhermina; Pożarowski, Piotr; Rzeski, Wojciech

2013-04-25

The use of biologically active compounds isolated from edible mushrooms against cancer raises global interest. Anticancer properties are mainly attributed to biopolymers including mainly polysaccharides, polysaccharopeptides, polysaccharide proteins, glycoproteins and proteins. In spite of the fact that Boletus edulis is one of the widely occurring and most consumed edible mushrooms, antitumor biopolymers isolated from it have not been exactly defined and studied so far. The present study is an attempt to extend this knowledge on molecular mechanisms of their anticancer action. The mushroom biopolymers (polysaccharides and glycoproteins) were extracted with hot water and purified by anion-exchange chromatography. The antiproliferative activity in human colon adenocarcinoma cells (LS180) was screened by means of MTT and BrdU assays. At the same time fractions' cytotoxicity was examined on the human colon epithelial cells (CCD 841 CoTr) by means of the LDH assay. Flow cytometry and Western blotting were applied to cell cycle analysis and protein expression involved in anticancer activity of the selected biopolymer fraction. In vitro studies have shown that fractions isolated from Boletus edulis were not toxic against normal colon epithelial cells and in the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells. The best results were obtained in the case of the fraction designated as BE3. The tested compound inhibited cancer cell proliferation which was accompanied by cell cycle arrest in the G0/G1-phase. Growth inhibition was associated with modulation of the p16/cyclin D1/CDK4-6/pRb pathway, an aberration of which is a critical step in the development of many human cancers including colon cancer. Our results indicate that a biopolymer BE3 from Boletus edulis possesses anticancer potential and may provide a new therapeutic/preventive option in colon cancer chemoprevention.

Inhibitor effects during the cell cycle in Chlamydomonas reinhardtii. Determination of transition points in asynchronous cultures

PubMed Central

1975-01-01

A wide variety of inhibitors (drugs, antibiotics, and antimetabolites) will block cell division within an ongoing cell cycle in autotrophic cultures of Chlamydomonas reinhardtii. To determine when during the cell cycle a given inhibitor is effective in preventing cell division, a technique is described which does not rely on the use of synchronous cultures. The technique permits the measurement of transition points, the cell cycle stage at which the subsequent cell division becomes insensitive to the effects of an inhibitor. A map of transition points in the cell cycle reveals that they are grouped into two broad periods, the second and fourth quarters. In general, inhibitors which block organellar DNA, RNA, and protein synthesis have second-quarter transition points, while those which inhibit nuclear cytoplasmic macromolecular synthesis have fourth-quarter transition points. The specific grouping of these transition points into two periods suggests that the synthesis of organellar components is completed midway through the cell cycle and that the synthesis of nonorganellar components required for cell division is not completed until late in the cell cycle. PMID:1176526

Interferon-inducible effector mechanisms in cell-autonomous immunity

PubMed Central

MacMicking, John D.

2014-01-01

Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells — a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world. PMID:22531325

Investigation of grafted ETFE-based polymer membranes as alternative electrolyte for direct methanol fuel cells

NASA Astrophysics Data System (ADS)

Aricò, A. S.; Baglio, V.; Cretı̀, P.; Di Blasi, A.; Antonucci, V.; Brunea, J.; Chapotot, A.; Bozzi, A.; Schoemans, J.

Low cost ethylene-tetrafluoroethylene (ETFE)-based grafted membranes have been prepared by a process based on electron beam irradiation, subsequent grafting, cross-linking and sulfonation procedure. Two different grafted membranes varying by their grafting and cross-linking levels have been investigated for applications in direct methanol fuel cells (DMFCs) operating between 90 and 130 °C. DMFC assemblies based on these membranes showed cell resistance and performance values comparable to Nafion 117. Stable electrochemical performance was recorded during 1 month of cycled operation. Tailoring of grafting and cross-linking properties allows a significant reduction of methanol cross-over while maintaining suitable conductivity and performance levels.

Identification of Primary Transcriptional Regulation of Cell Cycle-Regulated Genes upon DNA Damage

PubMed Central

Zhou, Tong; Chou, Jeff; Mullen, Thomas E.; Elkon, Rani; Zhou, Yingchun; Simpson, Dennis A.; Bushel, Pierre R.; Paules, Richard S.; Lobenhofer, Edward K.; Hurban, Patrick; Kaufmann, William K.

2007-01-01

The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of >400 cell cycle-regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation (IR)-treated normal human fibroblasts identified 150 of 406 cycle-regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization. PMID:17404513

The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression.

PubMed

Ewald, Jennifer C; Kuehne, Andreas; Zamboni, Nicola; Skotheim, Jan M

2016-05-19

Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin-dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation. Copyright © 2016 Elsevier Inc. All rights reserved.

Composite materials for space applications

NASA Technical Reports Server (NTRS)

Rawal, Suraj P.; Misra, Mohan S.; Wendt, Robert G.

1990-01-01

The objectives of the program were to: generate mechanical, thermal, and physical property test data for as-fabricated advanced materials; design and fabricate an accelerated thermal cycling chamber; and determine the effect of thermal cycling on thermomechanical properties and dimensional stability of composites. In the current program, extensive mechanical and thermophysical property tests of various organic matrix, metal matrix, glass matrix, and carbon-carbon composites were conducted, and a reliable database was constructed for spacecraft material selection. Material property results for the majority of the as-fabricated composites were consistent with the predicted values, providing a measure of consolidation integrity attained during fabrication. To determine the effect of thermal cycling on mechanical properties, microcracking, and thermal expansion behavior, approximately 500 composite specimens were exposed to 10,000 cycles between -150 and +150 F. These specimens were placed in a large (18 cu ft work space) thermal cycling chamber that was specially designed and fabricated to simulate one year low earth orbital (LEO) thermal cycling in 20 days. With this rate of thermal cycling, this is the largest thermal cycling unit in the country. Material property measurements of the thermal cycled organic matrix composite laminate specimens exhibited less than 24 percent decrease in strength, whereas, the remaining materials exhibited less than 8 percent decrease in strength. The thermal expansion response of each of the thermal cycled specimens revealed significant reduction in hysteresis and residual strain, and the average CTE values were close to the predicted values.

Investigation of thermal fatigue in fiber composite materials. [(thermal cycling tests)

NASA Technical Reports Server (NTRS)

Fahmy, A. A.; Cunningham, T. G.

1976-01-01

Graphite-epoxy laminates were thermally cycled to determine the effects of thermal cycles on tensile properties and thermal expansion coefficients of the laminates. Three 12-ply laminate configurations were subjected to up to 5,000 thermal cycles. The cumulative effect of the thermal cycles was determined by destructive inspection (electron micrographs and tensile tests) of samples after progressively larger numbers of cycles. After thermal cycling, the materials' tensile strengths, moduli, and thermal expansion coefficients were significantly lower than for the materials as fabricated. Most of the degradation of properties occurred after only a few cycles. The property degradation was attributed primarily to the progressive development of matrix cracks whose locations depended upon the layup orientation of the laminate.

Lithium dendrite growth through solid polymer electrolyte membranes

NASA Astrophysics Data System (ADS)

Harry, Katherine; Schauser, Nicole; Balsara, Nitash

2015-03-01

Replacing the graphite-based anode in current batteries with a lithium foil will result in a qualitative increase in the energy density of lithium batteries. The primary reason for not adopting lithium-foil anodes is the formation of dendrites during cell charging. In this study, stop-motion X-ray microtomography experiments were used to directly monitor the growth of lithium dendrites during electrochemical cycling of symmetric lithium-lithium cells with a block copolymer electrolyte. In an attempt to understand the relationship between viscoelastic properties of the electrolyte on dendrite formation, a series of complementary experiments including cell cycling, tomography, ac impedance, and rheology, were conducted above and below the glass transition temperature of the non-conducting poly(styrene) block; the conducting phase is a mixture of rubbery poly(ethylene oxide) and a lithium salt. The tomography experiments enable quantification of the evolution of strain in the block copolymer electrolyte. Our work provides fundamental insight into the dynamics of electrochemical deposition of metallic films in contact with high modulus polymer electrolytes. Rational approaches for slowing down and, perhaps, eliminating dendrite growth are proposed.

Towards Predicting the Response of a Solid Tumour to Chemotherapy and Radiotherapy Treatments: Clinical Insights from a Computational Model

PubMed Central

Powathil, Gibin G.; Adamson, Douglas J. A.; Chaplain, Mark A. J.

2013-01-01

In this paper we use a hybrid multiscale mathematical model that incorporates both individual cell behaviour through the cell-cycle and the effects of the changing microenvironment through oxygen dynamics to study the multiple effects of radiation therapy. The oxygenation status of the cells is considered as one of the important prognostic markers for determining radiation therapy, as hypoxic cells are less radiosensitive. Another factor that critically affects radiation sensitivity is cell-cycle regulation. The effects of radiation therapy are included in the model using a modified linear quadratic model for the radiation damage, incorporating the effects of hypoxia and cell-cycle in determining the cell-cycle phase-specific radiosensitivity. Furthermore, after irradiation, an individual cell's cell-cycle dynamics are intrinsically modified through the activation of pathways responsible for repair mechanisms, often resulting in a delay/arrest in the cell-cycle. The model is then used to study various combinations of multiple doses of cell-cycle dependent chemotherapies and radiation therapy, as radiation may work better by the partial synchronisation of cells in the most radiosensitive phase of the cell-cycle. Moreover, using this multi-scale model, we investigate the optimum sequencing and scheduling of these multi-modality treatments, and the impact of internal and external heterogeneity on the spatio-temporal patterning of the distribution of tumour cells and their response to different treatment schedules. PMID:23874170

A Multiplexed High-Content Screening Approach Using the Chromobody Technology to Identify Cell Cycle Modulators in Living Cells.

PubMed

Schorpp, Kenji; Rothenaigner, Ina; Maier, Julia; Traenkle, Bjoern; Rothbauer, Ulrich; Hadian, Kamyar

2016-10-01

Many screening hits show relatively poor quality regarding later efficacy and safety. Therefore, small-molecule screening efforts shift toward high-content analysis providing more detailed information. Here, we describe a novel screening approach to identify cell cycle modulators with low toxicity by combining the Cell Cycle Chromobody (CCC) technology with the CytoTox-Glo (CTG) cytotoxicity assay. The CCC technology employs intracellularly functional single-domain antibodies coupled to a fluorescent protein (chromobodies) to visualize the cell cycle-dependent redistribution of the proliferating cell nuclear antigen (PCNA) in living cells. This image-based cell cycle analysis was combined with determination of dead-cell protease activity in cell culture supernatants by the CTG assay. We adopted this multiplex approach to high-throughput format and screened 960 Food and Drug Administration (FDA)-approved drugs. By this, we identified nontoxic compounds, which modulate different cell cycle stages, and validated selected hits in diverse cell lines stably expressing CCC. Additionally, we independently validated these hits by flow cytometry as the current state-of-the-art format for cell cycle analysis. This study demonstrates that CCC imaging is a versatile high-content screening approach to identify cell cycle modulators, which can be multiplexed with cytotoxicity assays for early elimination of toxic compounds during screening. © 2016 Society for Laboratory Automation and Screening.

Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration.

PubMed

Wani, Willayat Yousuf; Kandimalla, Ramesh J L; Sharma, Deep Raj; Kaushal, Alka; Ruban, Anand; Sunkaria, Aditya; Vallamkondu, Jayalakshmi; Chiarugi, Alberto; Reddy, P Hemachandra; Gill, Kiran Dip

2017-07-01

In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF-differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G 0 /G 1 phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Decoupling of Nuclear Division Cycles and Cell Size during the Coenocytic Growth of the Ichthyosporean Sphaeroforma arctica.

PubMed

Ondracka, Andrej; Dudin, Omaya; Ruiz-Trillo, Iñaki

2018-06-18

Coordination of the cell division cycle with the growth of the cell is critical to achieve cell size homeostasis [1]. Mechanisms coupling the cell division cycle with cell growth have been described across diverse eukaryotic taxa [2-4], but little is known about how these processes are coordinated in organisms that undergo more complex life cycles, such as coenocytic growth. Coenocytes (multinucleate cells formed by sequential nuclear divisions without cytokinesis) are commonly found across the eukaryotic kingdom, including in animal and plant tissues and several lineages of unicellular eukaryotes [5]. Among the organisms that form coenocytes are ichthyosporeans, a lineage of unicellular holozoans that are of significant interest due to their phylogenetic placement as one of the closest relatives of animals [6]. Here, we characterize the coenocytic cell division cycle in the ichthyosporean Sphaeroforma arctica. We observe that, in laboratory conditions, S. arctica cells undergo a uniform and easily synchronizable coenocytic cell cycle, reaching up to 128 nuclei per cell before cellularization and release of daughter cells. Cycles of nuclear division occur synchronously within the coenocyte and in regular time intervals (11-12 hr). We find that the growth of cell volume is dependent on concentration of nutrients in the media; in contrast, the rate of nuclear division cycles is constant over a range of nutrient concentrations. Together, the results suggest that nuclear division cycles in the coenocytic growth of S. arctica are driven by a timer, which ensures periodic and synchronous nuclear cycles independent of the cell size and growth. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Bo; Sun, Ding; Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215004

2015-12-25

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primarymore » liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. • NanoCurcumin and sorafenib significantly decreased the population of CD133-positive HCC cells.« less

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation

PubMed Central

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J.; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L.; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D.; Weninger, Wolfgang

2015-01-01

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways. PMID:25709008

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

PubMed

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

2015-02-24

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response

PubMed Central

Guidi, Riccardo; Guerra, Lina; Levi, Laura; Stenerlöw, Bo; Fox, James G.; Josenhans, Christine; Masucci, Maria G.; Frisan, Teresa

2014-01-01

Summary Epidemiological evidence links chronic bacterial infections to the increased incidence of certain types of cancer but the molecular mechanisms by which bacteria contribute to tumour initiation and progression are still poorly characterized. Here we show that chronic exposure to the genotoxin cytolethal distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and acquisition of phenotypic properties of malignancy in fibroblasts and colon epithelial cells. Cells grown for more than 30 weeks in the presence of sublethal doses of CDT showed increased mutation frequency, and accumulation of chromatin and chromosomal aberrations in the absence of significant alterations of cell cycle distribution, decreased viability or senescence. Cell survival was dependent on sustained activity of the p38 MAP kinase. The ongoing genomic instability was associated with impaired activation of the DNA damage response and failure to efficiently activate cell cycle checkpoints upon exposure to genotoxic stress. Independently selected sublines showed enhanced anchorage-independent growth as assessed by the formation of colonies in semisolid agarose. These findings support the notion that chronic infection by CDT-producing bacteria may promote malignant transformation, and point to the impairment of cellular control mechanisms associated with the detection and repair of DNA damage as critical events in the process. PMID:22998585

Identification of Cell Cycle-regulated Genes in Fission YeastD⃞

PubMed Central

Peng, Xu; Karuturi, R. Krishna Murthy; Miller, Lance D.; Lin, Kui; Jia, Yonghui; Kondu, Pinar; Wang, Long; Wong, Lim-Soon; Liu, Edison T.; Balasubramanian, Mohan K.; Liu, Jianhua

2005-01-01

Cell cycle progression is both regulated and accompanied by periodic changes in the expression levels of a large number of genes. To investigate cell cycle-regulated transcriptional programs in the fission yeast Schizosaccharomyces pombe, we developed a whole-genome oligonucleotide-based DNA microarray. Microarray analysis of both wild-type and cdc25 mutant cell cultures was performed to identify transcripts whose levels oscillated during the cell cycle. Using an unsupervised algorithm, we identified 747 genes that met the criteria for cell cycle-regulated expression. Peaks of gene expression were found to be distributed throughout the entire cell cycle. Furthermore, we found that four promoter motifs exhibited strong association with cell cycle phase-specific expression. Examination of the regulation of MCB motif-containing genes through the perturbation of DNA synthesis control/MCB-binding factor (DSC/MBF)-mediated transcription in arrested synchronous cdc10 mutant cell cultures revealed a subset of functional targets of the DSC/MBF transcription factor complex, as well as certain gene promoter requirements. Finally, we compared our data with those for the budding yeast Saccharomyces cerevisiae and found ∼140 genes that are cell cycle regulated in both yeasts, suggesting that these genes may play an evolutionarily conserved role in regulation of cell cycle-specific processes. Our complete data sets are available at http://giscompute.gis.a-star.edu.sg/~gisljh/CDC. PMID:15616197

Altered cell cycle-related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer's disease [amyloid precursor protein/presenilin 1 (PS1)].

PubMed

Esteras, Noemí; Bartolomé, Fernando; Alquézar, Carolina; Antequera, Desireé; Muñoz, Úrsula; Carro, Eva; Martín-Requero, Ángeles

2012-09-01

Cumulative evidence indicates that aberrant re-expression of many cell cycle-related proteins and inappropriate neuronal cell cycle control are critical events in Alzheimer's disease (AD) pathogenesis. Evidence of cell cycle activation in post-mitotic neurons has also been observed in murine models of AD, despite the fact that most of these mice do not show massive loss of neuronal bodies. Dysfunction of the cell cycle appears to affect cells other than neurons, as peripheral cells, such as lymphocytes and fibroblasts from patients with AD, show an altered response to mitogenic stimulation. We sought to determine whether cell cycle disturbances are present simultaneously in both brain and peripheral cells from the amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD, in order to validate the use of peripheral cells from patients not only to study cell cycle abnormalities as a pathogenic feature of AD, but also as a means to test novel therapeutic approaches. By using cell cycle pathway-specific RT(2)Profiler™ PCR Arrays, we detected changes in a number of cell cycle-related genes in brain as well as in lymphocytes from APP/PS1 mice. Moreover, we found enhanced 5'-bromo-2'-deoxyuridine incorporation into DNA in lymphocytes from APP/PS1 mice, and increased expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), and the cyclin-dependent kinase (CDK) inhibitor Cdkn2a, as detected by immunohistochemistry in cortical neurons of the APP/PS1 mice. Taken together, the cell cycle-related changes in brain and blood cells reported here support the mitosis failure hypothesis in AD and validate the use of peripheral cells as surrogate tissue to study the molecular basis of AD pathogenesis. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blazek, Ed R.; Foutch, Jennifer L.; Maki, Guitta

2007-01-01

Purpose: Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line. Methods and Materials: Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed formore » marker stability, cell cycle distribution, and radiosensitivity. Results: CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the {beta}-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their {alpha}-parameters and cell cycle distributions were identical. Conclusions: Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response.« less

Pseudolaric Acid B Induced Cell Cycle Arrest, Autophagy and Senescence in Murine Fibrosarcoma L929 Cell

PubMed Central

hua Yu, Jing; yu Liu, Chun; bin Zheng, Gui; Zhang, Li Ying; hui Yan, Ming; yan Zhang, Wen; ying Meng, Xian; fang Yu, Xiao

2013-01-01

Objective: PAB induced various cancer cell apoptosis, cell cycle arrest and senescence. But in cell line murine fibrosarcoma L929, PAB did not induce apoptosis, but autophagy, therefore it was thought by us as a good model to research the relationship of cell cycle arrest, autophagy and senescence bypass apoptosis. Methods: Inhibitory ratio was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Phase contrast microscopy visualized cell morphology. Hoechst 33258 staining for nuclear change, propidium iodode (PI) staining for cell cycle, monodansylcadaverine (MDC) staining for autophagy, and rodanmine 123 staining for mitochondrial membrane potential (MMP) were measured by fluorescence microscopy or flowcytometry. Apoptosis was determined by DNA ladder test. Protein kinase C (PKC) activity was detected by PKC assay kit. SA-β-galactosidase assay was used to detect senescence. Protein expression was examined by western blot. Results: PAB inhibited L929 cell growth in time-and dose-dependent manner. At 12 h, 80 μmol/L PAB induced obvious mitotic arrest; at 24 h, PAB began to induce autophagy; at 36 h, cell-treated with PAB slip into G1 cell cycle; and 3 d PAB induced senescence. In time sequence PAB induced firstly cell cycle arrest, then autophagy, then slippage into G1 phase, lastly senescence. Senescent cells had high level of autophagy, inhibiting autophagy led to apoptosis, and no senescence. PAB activated PKC activity to induce cell cycle arrest, autophagy and senescence, inhibiting PKC activity suppressed cell cycle arrest, autophagy and senescence. Conclusion: PAB induced cell cycle arrest, autophagy and senescence in murine fibrosarcoma L929 cell through PKC. PMID:23630435

Nutraceutical properties of cumin residue generated from Ayurvedic industries using cell line models.

PubMed

Arun, K B; Aswathi, U; Venugopal, V V; Madhavankutty, T S; Nisha, P

2016-10-01

Spent cumin (SC), generated from Ayurvedic industry, was evaluated for its nutraceutical potential in terms of antioxidant, antidiabetic and anticancer properties, and compared with that of the raw cumin (RC). SC and RC seeds were extracted with ethyl acetate (E) and methanol (M). SCM (methanol extract) were rich in p-coumaric acid, ferulic acid, ellagic acid and cinnamic acid (6.4445, 5.8286, 2.1519, 4.3085 mg/g dry extract). SCM reduced Fe 2+ ion (89.68 µM AA/g dry weight), scavenged DPPH radical (IC 50 -238.6 µg/mL), better α-amylase inhibition (IC 50 -337.22 µg/mL) and glucose uptake activity in 30.7% of L6 cells. SCM inhibited viability, retarded migration area up to 41.02%, arrested cell cycle at S phase and induced apoptosis in 2.45% of HT29 colon cancer cells. The results indicated that dietary interventions using nutraceutical food formulation made out of SC can play a significant role in the prevention and management of degenerative diseases.

In vitro evaluation of anti-pathogenic surface coating nanofluid, obtained by combining Fe3O4/C12 nanostructures and 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)-benzamides

PubMed Central

2012-01-01

In this paper, we report the design of a new nanofluid for anti-pathogenic surface coating. For this purpose, new 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)-benzamides were synthesized and used as an adsorption shell for Fe3O4/C12 core/shell nanosized material. The functionalized specimens were tested by in vitro assays for their anti-biofilm properties and biocompatibility. The optimized catheter sections showed an improved resistance to Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 in vitro biofilm development, as demonstrated by the viable cell counts of biofilm-embedded bacterial cells and by scanning electron microscopy examination of the colonized surfaces. The nanofluid proved to be not cytotoxic and did not influence the eukaryotic cell cycle. These results could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with improved anti-biofilm properties. PMID:22992217

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonifati, Serena; Daly, Michele B.; St Gelais, Corine

SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterationsmore » correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.« less

Novel tag-and-exchange (RMCE) strategies generate master cell clones with predictable and stable transgene expression properties.

PubMed

Qiao, Junhua; Oumard, André; Wegloehner, Wolfgang; Bode, Juergen

2009-07-24

Site-specific recombinases have revolutionized the systematic generation of transgenic cell lines and embryonic stem cells/animals and will ultimately also reveal their potential in the genetic modification of induced pluripotent stem cells. Introduced in 1994, our Flp recombinase-mediated cassette exchange strategy permits the exchange of a target cassette for a cassette with the gene of interest, introduced as a part of an exchange vector. The process is "clean" in the sense that it does not co-introduce prokaryotic vector parts; neither does it leave behind a selection marker. Stringent selection principles provide master cell lines permitting subsequent recombinase-mediated cassette exchange cycles in the absence of a drug selection and with a considerable efficiency (approximately 10%). Exemplified by Chinese hamster ovary cells, the strategy proves to be successful even for cell lines with an unstable genotype.

Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

PubMed

Cooper, Stephen

2017-11-01

Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

Molecular machinery of signal transduction and cell cycle regulation in Plasmodium.

PubMed

Koyama, Fernanda C; Chakrabarti, Debopam; Garcia, Célia R S

2009-05-01

The regulation of the Plasmodium cell cycle is not understood. Although the Plasmodium falciparum genome is completely sequenced, about 60% of the predicted proteins share little or no sequence similarity with other eukaryotes. This feature impairs the identification of important proteins participating in the regulation of the cell cycle. There are several open questions that concern cell cycle progression in malaria parasites, including the mechanism by which multiple nuclear divisions is controlled and how the cell cycle is managed in all phases of their complex life cycle. Cell cycle synchrony of the parasite population within the host, as well as the circadian rhythm of proliferation, are striking features of some Plasmodium species, the molecular basis of which remains to be elucidated. In this review we discuss the role of indole-related molecules as signals that modulate the cell cycle in Plasmodium and other eukaryotes, and we also consider the possible role of kinases in the signal transduction and in the responses it triggers.

Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

PubMed

Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

2015-01-01

In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast and colorectal cancers.

The Abbreviated Pluripotent Cell Cycle

PubMed Central

Kapinas, Kristina; Grandy, Rodrigo; Ghule, Prachi; Medina, Ricardo; Becker, Klaus; Pardee, Arthur; Zaidi, Sayyed K.; Lian, Jane; Stein, Janet; van Wijnen, Andre; Stein, Gary

2013-01-01

Human embryonic stem cells and induced pluripotent stem cells proliferate rapidly and divide symmetrically producing equivalent progeny cells. In contrast, lineage committed cells acquire an extended symmetrical cell cycle. Self-renewal of tissue-specific stem cells is sustained by asymmetric cell division where one progeny cell remains a progenitor while the partner progeny cell exits the cell cycle and differentiates. There are three principal contexts for considering the operation and regulation of the pluripotent cell cycle: temporal, regulatory andstructural. The primary temporal context that the pluripotent self-renewal cell cycle of human embryonic stem cells (hESCs) is a short G1 period without reducing periods of time allocated to S phase, G2, and mitosis. The rules that govern proliferation in hESCs remain to be comprehensively established. However, several lines of evidence suggest a key role for the naïve transcriptome of hESCs, which is competent to stringently regulate the ESC cell cycle. This supports the requirements of pluripotent cells to self propagate while suppressing expression of genes that confer lineage commitment and/or tissue specificity. However, for the first time, we consider unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency. From both fundamental biological and clinical perspectives, understanding control of the abbreviated embryonic stem cell cycle can provide options to coordinate control of proliferation versus differentiation. Wound healing, tissue engineering, and cell-based therapy to mitigate developmental aberrations illustrate applications that benefit from knowledge of the biology of the pluripotent cell cycle. PMID:22552993