Maternal breast milk transforming growth factor beta and feeding intolerance in preterm infants

PubMed Central

Frost, Brandy L.; Jilling, Tamas; Lapin, Brittany; Maheshwari, Akhil; Caplan, Michael S.

2015-01-01

Background Feeding intolerance occurs commonly in the NICU. Breast milk contains a large pool of transforming growth factor-beta (TGF-beta). Few studies describe TGF-beta levels in preterm milk, and the relationship to feeding intolerance (FI) remains unexplored. We measured TGF-beta levels in preterm breast milk to investigate a correlation with FI in preterm infants. Methods Prospective observational trial of 100 mother-infant pairs, enrolling infants born below 32 weeks gestation and less than 1500 grams, and mothers who planned to provide breast milk. TGF-beta levels were measured using ELISA. Infant charts were reviewed for outcomes. Results TGF-beta declined postnatally, most elevated in colostrum (p<0.01). TGF-beta 2 levels were higher than TGF-beta 1 at all time points (p<0.01). Colostrum TGF-beta levels correlated inversely with birth weight (p<0.01) and gestational age (p<0.05). One week TGF-beta 2 levels were reduced in growth-restricted infants with FI (p<0.01). Of infants with NEC, TGF-beta 2 levels appeared low, but small sample size precluded meaningful statistical comparisons. Conclusions TGF-beta levels decline temporally in preterm milk. TGF-beta 1 colostrum levels correlate inversely with birth weight and gestational age. TGF-beta 2 may play a role in FI in growth-restricted infants. The relationship of TGF-beta 2 and NEC merits future investigation. PMID:24995914

Evaluation of data transformations used with the square root and schoolfield models for predicting bacterial growth rate.

PubMed Central

Alber, S A; Schaffner, D W

1992-01-01

A comparison was made between mathematical variations of the square root and Schoolfield models for predicting growth rate as a function of temperature. The statistical consequences of square root and natural logarithm transformations of growth rate use in several variations of the Schoolfield and square root models were examined. Growth rate variances of Yersinia enterocolitica in brain heart infusion broth increased as a function of temperature. The ability of the two data transformations to correct for the heterogeneity of variance was evaluated. A natural logarithm transformation of growth rate was more effective than a square root transformation at correcting for the heterogeneity of variance. The square root model was more accurate than the Schoolfield model when both models used natural logarithm transformation. PMID:1444367

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

PubMed Central

Lee, Jeffrey C; Vivanco, Igor; Beroukhim, Rameen; Huang, Julie H. Y; Feng, Whei L; DeBiasi, Ralph M; Yoshimoto, Koji; King, Jennifer C; Nghiemphu, Phioanh; Yuza, Yuki; Xu, Qing; Greulich, Heidi; Thomas, Roman K; Paez, J. Guillermo; Peck, Timothy C; Linhart, David J; Glatt, Karen A; Getz, Gad; Onofrio, Robert; Ziaugra, Liuda; Levine, Ross L; Gabriel, Stacey; Kawaguchi, Tomohiro; O'Neill, Keith; Khan, Haumith; Liau, Linda M; Nelson, Stanley F; Rao, P. Nagesh; Mischel, Paul; Pieper, Russell O; Cloughesy, Tim; Leahy, Daniel J; Sellers, William R; Sawyers, Charles L; Meyerson, Matthew; Mellinghoff, Ingo K

2006-01-01

Background Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and Findings Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma. PMID:17177598

Real-time contaminant detection and classification in a drinking water pipe using conventional water quality sensors: techniques and experimental results.

PubMed

Jeffrey Yang, Y; Haught, Roy C; Goodrich, James A

2009-06-01

Accurate detection and identification of natural or intentional contamination events in a drinking water pipe is critical to drinking water supply security and health risk management. To use conventional water quality sensors for the purpose, we have explored a real-time event adaptive detection, identification and warning (READiw) methodology and examined it using pilot-scale pipe flow experiments of 11 chemical and biological contaminants each at three concentration levels. The tested contaminants include pesticide and herbicides (aldicarb, glyphosate and dicamba), alkaloids (nicotine and colchicine), E. coli in terrific broth, biological growth media (nutrient broth, terrific broth, tryptic soy broth), and inorganic chemical compounds (mercuric chloride and potassium ferricyanide). First, through adaptive transformation of the sensor outputs, contaminant signals were enhanced and background noise was reduced in time-series plots leading to detection and identification of all simulated contamination events. The improved sensor detection threshold was 0.1% of the background for pH and oxidation-reduction potential (ORP), 0.9% for free chlorine, 1.6% for total chlorine, and 0.9% for chloride. Second, the relative changes calculated from adaptively transformed residual chlorine measurements were quantitatively related to contaminant-chlorine reactivity in drinking water. We have shown that based on these kinetic and chemical differences, the tested contaminants were distinguishable in forensic discrimination diagrams made of adaptively transformed sensor measurements.

Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

PubMed Central

Ciarmela, Pasquapina; Islam, Md. Soriful; Reis, Fernando M.; Gray, Peter C.; Bloise, Enrrico; Petraglia, Felice; Vale, Wylie; Castellucci, Mario

2011-01-01

BACKGROUND Growth factors are proteins secreted by a number of cell types that are capable of modulating cellular growth, proliferation and cellular differentiation. It is well accepted that uterine cellular events such as proliferation and differentiation are regulated by sex steroids and their actions in target tissues are mediated by local production of growth factors acting through paracrine and/or autocrine mechanisms. Myometrial mass is ultimately modified in pregnancy as well as in tumour conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumours of the uterus, considered to be one of the most frequent causes of infertility in reproductive years in women. METHODS For this review, we searched the database MEDLINE and Google Scholar for articles with content related to growth factors acting on myometrium; the findings are hereby reviewed and discussed. RESULTS Different growth factors such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), heparin-binding EGF (HB-EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and TGF-β perform actions in myometrium and in leiomyomas. In addition to these growth factors, activin and myostatin have been recently identified in myometrium and leiomyoma. CONCLUSIONS Growth factors play an important role in the mechanisms involved in myometrial patho-physiology. PMID:21788281

Substrate flexibility regulates growth and apoptosis of normal but not transformed cells

NASA Technical Reports Server (NTRS)

Wang, H. B.; Dembo, M.; Wang, Y. L.

2000-01-01

One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression.

PubMed

Chen, Yan; Huang, Shai; Wu, Bo; Fang, Jiankai; Zhu, Minsheng; Sun, Li; Zhang, Lifeng; Zhang, Yongsheng; Sun, Maomin; Guo, Lingling; Wang, Shouli

2017-07-25

Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

In vitro comparison of the efficacy of TGF-β1 and PDGF-BB in combination with freeze-dried bone allografts for induction of osteogenic differentiation in MG-63 osteoblast-like cells.

PubMed

Vahabi, Surena; Torshabi, Maryam; Esmaeil Nejad, Azadeh

2016-12-01

Predictable regeneration of alveolar bone defects has always been a challenge in implant dentistry. Bone allografts are widely used bone substitutes with controversial osteoinductive activity. This in vitro study aimed to assess the osteogenic potential of some commercially available freeze-dried bone allografts supplemented with human recombinant platelet-derived growth factor-BB and transforming growth factor beta-1. Cell viability, mineralization, and osteogenic gene expression of MG-63 osteoblast-like cells were compared among the allograft alone, allograft/platelet-derived growth factor-BB, allograft/transforming growth factor beta-1, and allograft/platelet-derived growth factor-BB/transforming growth factor beta-1 groups. The methyl thiazol tetrazolium assay, real-time quantitative reverse transcription polymerase chain reaction and alizarin red staining were performed, respectively, for assessment of cell viability, differentiation, and mineralization at 24-72 h post treatment. The allograft with greater cytotoxic effect on MG-63 cells caused the lowest differentiation among the groups. In comparison with allograft alone, allograft/transforming growth factor beta-1, and allograft/transforming growth factor beta-1/platelet-derived growth factor-BB caused significant upregulation of bone sialoprotein and osteocalcin osteogenic mid-late marker genes, and resulted in significantly higher amounts of calcified nodules especially in mineralized non-cytotoxic allograft group. Supplementation of platelet-derived growth factor-BB alone in 5 ng/mL concentration had no significant effect on differentiation or mineralization markers. According to the results, transforming growth factor beta-1 acts synergistically with bone allografts to enhance the osteogenic differentiation potential. Therefore, this combination may be useful for rapid transformation of undifferentiated cells into bone-forming cells for bone regeneration. However, platelet-derived growth factor-BB supplementation did not support this synergistic ability to enhance osteogenic differentiation and thus, further investigations are required.

Comparative immunoexpression of ICAM-1, TGF-β1 and ki-67 in periapical and residual cysts

PubMed Central

Armada, Luciana; dos Santos, Teresa-Cristina; Pires, Fabio-Ramoa

2017-01-01

Background This study compared the immunohistochemical expression of ki-67, transforming growth factor beta 1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in inflammatory periapical cysts and residual cysts. Material and Methods The study sample was composed by 25 periapical cysts and 25 residual cysts and immunohistochemical reactions were carried out using antibodies directed against ICAM-1, TGF-β1 and ki-67. Clinical, radiological, gross, histological and immunohistochemical data were tabulated for descriptive and comparative analysis using the SPSS software and differences were considered statistically significant when p<0.05%. Results There were no differences between the expression of ICAM-1 (p=0.239) and TGF-β1 (p=0.258) when comparing both groups. Ki-67 labeling index was higher in residual cysts compared to periapical cysts (p=0.017). Conclusions Results from the present study suggest that some specific inflammatory stimuli on residual cysts would modulate their mechanisms of etiopathogenesis, growing and repair. Key words:Periapical cyst, radicular cyst, residual cyst, transforming growth factor beta 1 (TGF-β1), intercellular adhesion molecule 1 (ICAM-1), ki-67. PMID:27918735

Herpesvirus Saimiri Transforms Human T-Cell Clones to Stable Growth without Inducing Resistance to Apoptosis

PubMed Central

Kraft, Michael S.; Henning, Golo; Fickenscher, Helmut; Lengenfelder, Doris; Tschopp, Jürg; Fleckenstein, Bernhard; Meinl, Edgar

1998-01-01

Herpesvirus saimiri (HVS) transforms human T cells to stable growth in vitro. Since HVS codes for two different antiapoptotic proteins, growth transformation by HVS might be expected to confer resistance to apoptosis. We found that the expression of both viral antiapoptotic genes was restricted to cultures with viral replication and absent in growth-transformed human T cells. A comparative examination of HVS-transformed T-cell clones and their native parental clones revealed that the expression of Bcl-2, Bcl-XL, Bax, and members of the tumor necrosis factor receptor (TNF-R) superfamily with a death domain, namely, TNF-RI, CD95, and TRAMP, were not modulated by HVS. Expression of CD30 was induced in HVS-transformed T cells, and these cells also expressed the CD30 ligand. Uninfected and transformed T cells were sensitive to CD95 ligation but resistant to apoptosis mediated by TRAIL or soluble TNF-α. CD95 ligand was constitutively expressed on transformed but not uninfected parental T cells. Both cell types showed similar sensitivity to cell death induction or inhibition of T-cell activation mediated by irradiation, oxygen radicals, dexamethasone, cyclosporine, and prostaglandin E2. Altogether, this study strongly suggests that growth transformation by HVS is based not on resistance to apoptosis but, rather, on utilization of normal cellular activation pathways. PMID:9525639

Natural Transformation of Campylobacter jejuni Occurs Beyond Limits of Growth

PubMed Central

Vegge, Christina S.; Brøndsted, Lone; Ligowska-Marzęta, Małgorzata; Ingmer, Hanne

2012-01-01

Campylobacter jejuni is a human bacterial pathogen. While poultry is considered to be a major source of food borne campylobacteriosis, C. jejuni is frequently found in the external environment, and water is another well-known source of human infections. Natural transformation is considered to be one of the main mechanisms for mediating transfer of genetic material and evolution of the organism. Given the diverse habitats of C. jejuni we set out to examine how environmental conditions and physiological processes affect natural transformation of C. jejuni. We show that the efficiency of transformation is correlated to the growth conditions, but more importantly that transformation occurs at growth-restrictive conditions as well as in the late stationary phase; hence revealing that growth per se is not required for C. jejuni to be competent. Yet, natural transformation of C. jejuni is an energy dependent process, that occurs in the absence of transcription but requires an active translational machinery. Moreover, we show the ATP dependent ClpP protease to be important for transformation, which possibly could be associated with reduced protein glycosylation in the ClpP mutant. In contrast, competence of C. jejuni was neither found to be involved in DNA repair following DNA damage nor to provide a growth benefit. Kinetic studies revealed that several transformation events occur per cell cycle indicating that natural transformation of C. jejuni is a highly efficient process. Thus, our findings suggest that horizontal gene transfer by natural transformation takes place in various habitats occupied by C. jejuni. PMID:23049803

Role of Activin A in Immune Response to Breast Cancer

DTIC Science & Technology

2016-12-01

the response to radiotherapy (RT). 2 KEYWORDS Breast cancer, metastasis, transforming growth factor-beta (TGFβ) superfamily, activin- A, radiotherapy... Transforming Growth Factor-beta (TGFβ) and activin A (actA) are members of the TGFβ superfamily with overlapping as well as distinct functions in many...Vaccination C. Vanpouille-Box, S. Formenti, and S. Demaria; Weill Cornell Medical College, New York, NY Purpose/Objective(s): Transforming Growth

In vitro analysis of multistage carcinogenesis

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

Nettesheim, P.; Fitzgerald, D.J.; Kitamura, H.

1987-11-01

Several key events in the multistep process of neoplastic transformation of rat tracheal epithelium (RTE) are described. Whether tracheal epithelium is exposed in vivo to carcinogenic agents or whether primary tracheal epithelial cells are exposed in vitro to carcinogens, initiated stem cells can be detected soon after the exposure by their ability to grow under selective conditions in culture. These initiated stem cells differ fundamentally from normal stem cells in their response to factors normally constraining proliferation and self-renewal. Thus, disruption of inhibitory control mechanisms of stem cell replication appears to be the first event in RTE cell transformation. Whilemore » the probability of self-renewal (PSR) is clearly increased in initiated stem cells, most of the descendants derived form such stem cells differentiate and become terminal and do not express transformed characteristics. Progression from the first to the second stage of RTE cell transformation, the stage of the immortal growth variant (IGV), is characterized by loss of responsiveness to the growth-restraining effects of retinoic acid. In the third stage of neoplastic transformation, the stage during which neoplastic growth variants (NGV) appear, a growth factor receptor gene is inappropriately expressed in some of the transformants. Thus, it appears that loss of growth-restraining mechanisms may be an early event, and activation of a growth stimulatory mechanism a late event, in neoplastic transformation of RTE cells.« less

IL-3 induces apoptosis in a ras-transformed myeloid cell line.

PubMed

Ahmed, N; Anderson, S M; Berridge, M V

1999-04-01

Growth factors promote cell survival and proliferation. Homeostasis is maintained by programmed cell death which occurs when the growth stimulus is withdrawn, in response to negative growth regulators such as interferons, TNF-alpha and CD95 ligand, or following differentiation. Although acutely-transforming oncogenes often overcome the need for growth factors, growth regulatory cytokines can influence proliferative responses of transformed cells. In this study we investigated the effects of IL-3 on the proliferative responses of parental bone marrow-derived 32D cells and cells transformed with ras and abl oncogenes. We show that treatment of ras-transformed 32D cells with IL-3 reduced proliferative responses and decreased colony-forming ability. These effects were exacerbated in the absence of serum and associated with inhibition of tyrosine kinase activity, down-regulation of RAS and MYC expression, and induction of apoptosis as indicated by DNA fragmentation. In contrast, treatment of parental 32D cells with IL-3, which is obligatory for cell survival and proliferation, increased tyrosine kinase activity, upregulated MYC and RAS expression and maintained DNA integrity. With abl-transformed cells, proliferation and colony-forming ability were also inhibited by IL-3. Tyrosine kinase activity and MYC expression were reduced, but early apoptosis was not evident. Calcium uptake however, was stimulated by IL-3 in both parental and oncogene-transformed cells. These results suggest that threshold levels of tyrosine kinase activity are necessary for cell survival and proliferation and that with ras-transformed cells, IL-3 treatment may result in this threshold being breached. We conclude that in some situations, growth-promoting cytokines can inhibit proliferation of transformed cells and induce cell death by apoptosis.

TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

EPA Science Inventory

TITLE:
TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

Lactose/whey utilization and ethanol production by transformed Saccharomyces cerevisiae cells.

PubMed

Porro, D; Martegani, E; Ranzi, B M; Alberghina, L

1992-04-05

Strains of Saccharomyces cerevisiae transformed with a multicopy expression vector bearing both the Escherichia coli beta-galactosidase gene under the control of the upstream activating sequence of the GAL1-10 genes and the GAL4 activator gene release part of beta-galactosidase in the growth medium. This release is due to cell lysis of the older mother cells; the enzyme maintains its activity in buffered growth media. Fermentation studies with transformed yeast strains showed that the release of beta-galactosidase allowed an efficient growth on buffered media containing lactose as carbon source as well as on whey-based media. The transformed strains utilized up to 95% of the lactose and a high growth yield was obtained in rich media. High productions of ethanol were also observed in stationary phase after growth in lactose minimal media.

Minor Distortions with Major Consequences: Correcting Distortions in Imaging Spectrographs

PubMed Central

Esmonde-White, Francis W. L.; Esmonde-White, Karen A.; Morris, Michael D.

2010-01-01

Projective transformation is a mathematical correction (implemented in software) used in the remote imaging field to produce distortion-free images. We present the application of projective transformation to correct minor alignment and astigmatism distortions that are inherent in dispersive spectrographs. Patterned white-light images and neon emission spectra were used to produce registration points for the transformation. Raman transects collected on microscopy and fiber-optic systems were corrected using established methods and compared with the same transects corrected using the projective transformation. Even minor distortions have a significant effect on reproducibility and apparent fluorescence background complexity. Simulated Raman spectra were used to optimize the projective transformation algorithm. We demonstrate that the projective transformation reduced the apparent fluorescent background complexity and improved reproducibility of measured parameters of Raman spectra. Distortion correction using a projective transformation provides a major advantage in reducing the background fluorescence complexity even in instrumentation where slit-image distortions and camera rotation were minimized using manual or mechanical means. We expect these advantages should be readily applicable to other spectroscopic modalities using dispersive imaging spectrographs. PMID:21211158

The Molecular Epidemiology of Malaria in Western Kenya

DTIC Science & Technology

2002-09-01

including tumor necrosis factor alpha (TNF- α), interleukin-10 (IL-10), transforming growth factor beta (TGF-β), interleukin-6 (IL-6), and interferon gamma...Ricard S, Troesch A, Mallet C, Generenaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O. Polymorphisms of the transforming growth factor- beta 1...transforming growth factor- beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol 1998 6(3): 193-7. 36. Olomolaiye OO

Restoration of Immune Surveillance in Lung Cancer by Natural Killer Cells

DTIC Science & Technology

2017-10-01

microenvironment, Transforming Growth Factor-beta, nicotine, tobacco smokers, e-cigarette-users, lung cancer, microRNA-183, DAP12, NKp44, NKp46...to recognize tumor cells. This loss is caused by transforming growth factor beta (TGFb) produced by tumor cells that can induce microRNA (miR)-183...any effect on NK activation markers, whether they were measured by flow cytometry, western blotting, qPCR. In all experiments, transforming growth

GROWTH REGULATION IN RSV INFECTED CHECKEN EMBRYO FIBROBLASTS: THE ROLE OF THE src GENE

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

Parry, G.; Bartholomew, J.C.; Bissell, M.J.

1980-03-01

The relationship between growth regulation and cell transformation has been studied in many cultured cell lines transformed by a range of oncogenic agents. The main conclusion derived from these investigations is that the nature of the growth regulatory lesion in transformed cells is a function of the agent used to induce transformation. For example, when 3T3 fibroblasts are rendered stationary by serum deprivation, normal cells accumulate in G{sub 1} but SV40 transformed cells are arrested at all stages of the cell cycle. In contrast, 3T3 cells transformed with Rous sarcoma virus B77, accumulate in G{sub 1} upon serum deprivation. Thismore » is also true when mouse sarcoma virus (MSV) is used as the transforming agent. MSV-transformed cells accumulate in G{sub 1}, just as do normal cells. In this letter we report a detailed study of the mechanisms leading to loss of growth control in chicken embryo fibroblasts transformed by Rous sarcoma virus (RSV). We have been particularly concerned with the role of the src gene in the process, and have used RSV mutants temperature sensitive (ts) for transformation to investigate the nature of the growth regulatory lesion. Two principal findings have emerged: (a) the stationary phase of the cell cycle (G{sub 1}) in chick embryo fibroblasts has two distinct compartments, (for simplicity referred to as G{sub 1} and G{sub 0} states), (b) when rendered stationary at 41.5{sup o} by serum deprivation, normal cells enter a G{sub 0}-like state, but cells infected with the ts-mutant occupy a G{sub 1} state, even though a known src gene product, a kinase, should be inactive at this temperature. The possibility is discussed that viral factors other than the active src protein kinase influence growth control.« less

Methods for transforming and expression screening of filamentous fungal cells with a DNA library

DOEpatents

Teter, Sarah; Lamsa, Michael; Cherry, Joel; Ward, Connie

2015-06-02

The present invention relates to methods for expression screening of filamentous fungal transformants, comprising: (a) isolating single colony transformants of a DNA library introduced into E. coli; (b) preparing DNA from each of the single colony E. coli transformants; (c) introducing a sample of each of the DNA preparations of step (b) into separate suspensions of protoplasts of a filamentous fungus to obtain transformants thereof, wherein each transformant contains one or more copies of an individual polynucleotide from the DNA library; (d) growing the individual filamentous fungal transformants of step (c) on selective growth medium, thereby permitting growth of the filamentous fungal transformants, while suppressing growth of untransformed filamentous fungi; and (e) measuring activity or a property of each polypeptide encoded by the individual polynucleotides. The present invention also relates to isolated polynucleotides encoding polypeptides of interest obtained by such methods, to nucleic acid constructs, expression vectors, and recombinant host cells comprising the isolated polynucleotides, and to methods of producing the polypeptides encoded by the isolated polynucleotides.

Separation of cell survival, growth, migration, and mesenchymal transdifferentiation effects of fibroblast secretome on tumor cells of head and neck squamous cell carcinoma.

PubMed

Metzler, Veronika Maria; Pritz, Christian; Riml, Anna; Romani, Angela; Tuertscher, Raphaela; Steinbichler, Teresa; Dejaco, Daniel; Riechelmann, Herbert; Dudás, József

2017-11-01

Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast-secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial-mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial-mesenchymal transition-related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects.

Aurora A Is Critical for Survival in HPV-Transformed Cervical Cancer.

PubMed

Gabrielli, Brian; Bokhari, Fawzi; Ranall, Max V; Oo, Zay Yar; Stevenson, Alexander J; Wang, Weili; Murrell, Melanie; Shaikh, Mushfiq; Fallaha, Sora; Clarke, Daniel; Kelly, Madison; Sedelies, Karin; Christensen, Melinda; McKee, Sara; Leggatt, Graham; Leo, Paul; Skalamera, Dubravka; Soyer, H Peter; Gonda, Thomas J; McMillan, Nigel A J

2015-12-01

Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selectively promoted apoptosis in the HPV cancers. The apoptosis was driven by an extended mitotic delay in the Alisertib-treated HPV E7-expressing cells. This had the effect of reducing Mcl-1 levels, which is destabilized in mitosis, and increasing BIM levels, normally destabilized by Aurora A in mitosis. Overexpression of Mcl-1 reduced sensitivity to the drug. The level of HPV E7 expression influenced the extent of Alisertib-induced mitotic delay and Mcl-1 reduction. Xenograft experiments with three cervical cancer cell lines showed Alisertib inhibited growth of HPV and non-HPV xenografts during treatment. Growth of non-HPV tumors was delayed, but in two separate HPV cancer cell lines, regression with no resumption of growth was detected, even at 50 days after treatment. A transgenic model of premalignant disease driven solely by HPV E7 also demonstrated sensitivity to drug treatment. Here, we show for the first time that targeting of the Aurora A kinase in mice using drugs such as Alisertib results in a curative sterilizing therapy that may be useful in treating HPV-driven cancers. ©2015 American Association for Cancer Research.

Expression and functional studies of genes involved in transport and metabolism of glycerol in Pachysolen tannophilus

PubMed Central

2013-01-01

Background Pachysolen tannophilus is a non-conventional yeast, which can metabolize many of the carbon sources found in low cost feedstocks including glycerol and xylose. The xylose utilisation pathways have been extensively studied in this organism. However, the mechanism behind glycerol metabolism is poorly understood. Using the recently published genome sequence of P. tannophilus CBS4044, we searched for genes with functions in glycerol transport and metabolism by performing a BLAST search using the sequences of the relevant genes from Saccharomyces cerevisiae as queries. Results Quantitative real-time PCR was performed to unveil the expression patterns of these genes during growth of P. tannophilus on glycerol and glucose as sole carbon sources. The genes predicted to be involved in glycerol transport in P. tannophilus were expressed in S. cerevisiae to validate their function. The S. cerevisiae strains transformed with heterologous genes showed improved growth and glycerol consumption rates with glycerol as the sole carbon source. Conclusions P. tannophilus has characteristics relevant for a microbial cell factory to be applied in a biorefinery setting, i.e. its ability to utilise the carbon sources such as xylose and glycerol. However, the strain is not currently amenable to genetic modification and transformation. Heterologous expression of the glycerol transporters from P. tannophilus, which has a relatively high growth rate on glycerol, could be used as an approach for improving the efficiency of glycerol assimilation in other well characterized and applied cell factories such as S. cerevisiae. PMID:23514356

Role of transformational leadership on employee productivity of teaching hospitals: using structural equation modeling

PubMed Central

Vatankhah, Soudabeh; Alirezaei, Samira; Khosravizadeh, Omid; Mirbahaeddin, Seyyed Elmira; Alikhani, Mahtab; Alipanah, Mobarakeh

2017-01-01

Background In today’s transforming world, increased productivity and efficient use of existing facilities are practically beyond a choice and become a necessity. In this line, attention to change and transformation is one of the affecting factors on the growth of productivity in organizations, especially in hospitals. Aim To examine the effect of transformational leadership on the productivity of employees in teaching hospitals affiliated to Iran University of Medical Sciences. Methods This cross-sectional study was conducted on 254 participants from educational and medical centers affiliated to Iran University of Medical Sciences (Tehran, Iran) in 2016. The standard questionnaires of Bass & Avolio and of Hersi & Goldsmith were used to respectively assess transformational leadership and level of productivity. The research assumptions were tested in a significance level of 0.05 by applying descriptive statistics and structural equations modeling (SEM) using SPSS 19 and Amos 24. Results Results of the fitting indicators of the assessing model after amending includes Chi-square two to degrees of freedom of 2.756, CFI indicator 0.95, IFI indicator 0.92, Root mean square error of approximation (RMSEA) indicator 0.10. These results indicate that the assessing model is well fitting after the amendment. Also, analysis of the model’s assumptions and the final model of the research reveals the effect of transformational leadership on employees’ productivity with a significance level of 0.83 (p=0.001). Conclusion This research indicates that the more the leadership and decision-making style in hospitals lean towards transformational mode, the more positive outcomes it brings among employees and the organization due to increased productivity. Therefore, it is essential to pay focused attention to training/educational programs in organizations to create and encourage transformational leadership behaviors which hopefully lead to more productive employees. PMID:28979731

Loss of N-Cadherin Expression in Tumor Transplants Produced From As+3- and Cd+2-Transformed Human Urothelial (UROtsa) Cell Lines.

PubMed

Sandquist, Elizabeth J; Somji, Seema; Dunlevy, Jane R; Garrett, Scott H; Zhou, Xu Dong; Slusser-Nore, Andrea; Sens, Donald A

2016-01-01

Epithelial to mesenchymal transition is a process in which a cell experiences a loss of epithelial cell characteristics and acquires a more mesenchymal cell phenotype. In cancer, epithelial to mesenchymal transition has been proposed to play an important role during specific stages of tumor progression. The role epithelial to mesenchymal transition and mesenchymal to epithelial transition might play in toxicant-induced urothelial cancer is unknown. Real-time PCR, Western blotting, immuno-histochemistry and immuno-fluorescence were used to determine the expression of E- and N-cadherin in the UROtsa parent, the As+3- and Cd+2-transformed cell lines, the spheroids isolated from these cell lines as well as the tumor heterotransplants that were produced by the injection of the transformed cells into immune compromised mice. This study showed that N-cadherin expression was increased in 6 As+3- and 7 Cd+2- transformed cell lines generated from human urothelial cells (UROtsa). The expression varied within each cell line, with 10% to 95% of the cells expressing N-cadherin. Tumors produced from these cell lines showed no expression of the N-cadherin protein. Spheroids which are made up of putative cancer initiating cells produced from these cell lines showed only background expression of N-cadherin mRNA, increased expression of aldehyde dehydrogenase 1 mRNA and produced tumors which did not express N-cadherin. There was no change in the expression of E-cadherin in the tumors, and the tumors formed by all the As+3 and Cd+2-transformed cell lines and cancer initiating cells stained intensely and uniformly for E-cadherin. The finding that the cells expressing N-cadherin gave rise to tumors with no expression of N-cadherin is in agreement with the classical view of epithelial to mesenchymal transition. Epithelial to mesenchymal transition and N-cadherin are associated with dissemination and not with the ability to establish new tumor growth. Mesenchymal to epithelial transition and E-cadherin are viewed as necessary for a cell to establish a new metastatic site. The lack of N-cadherin expression in tumor transplants is consistent with E-cadherin expressing cells "seeding" a site for tumor growth. The study shows that a minority population of cultured cells can be the initiators of tumor growth.

ROLES OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-A) IN MEDIATION OF DIOXIN (TCDD)-INDUCED DELAYS IN DEVELOPMENT OF THE MOUSE MAMMARY GLAND

EPA Science Inventory

Roles of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a) in Mediation of Dioxin (TCDD)-Induced Delays in Development of the Mouse Mammary Gland.
Suzanne E. Fenton, Barbara Abbott, Lamont Bryant, and Angela Buckalew. U.S. EPA, NHEERL, Reproductive Tox...

Ectopic Expression of a Horseradish Peroxidase Enhances Growth Rate and Increases Oxidative Stress Resistance in Hybrid Aspen

PubMed Central

Kawaoka, Akiyoshi; Matsunaga, Etsuko; Endo, Saori; Kondo, Shinkichi; Yoshida, Kazuya; Shinmyo, Atsuhiko; Ebinuma, Hiroyasu

2003-01-01

We previously demonstrated that overexpression of the horseradish (Armoracia rusticana) peroxidase prxC1a gene stimulated the growth rate of tobacco (Nicotiana tabacum) plants. Here, the cauliflower mosaic virus 35S::prxC1a construct was introduced into hybrid aspen (Populus sieboldii × Populus grandidentata). The growth rate of these transformed hybrid aspen plants was substantially increased under greenhouse conditions. The average stem length of transformed plants was 25% greater than that of control plants. There was no other obvious phenotypic difference between the transformed and control plants. Fast-growing transformed hybrid aspen showed high levels of expression of prxC1a and had elevated peroxidase activities toward guaiacol and ascorbate. However, there was no increase of the endogenous class I ascorbate peroxidase activities in the transformed plants by separate assay and activity staining of native polyacrylamide gel electrophoresis. Furthermore, calli derived from the transformed hybrid aspen grew faster than those from control plants and were resistant to the oxidative stress imposed by hydrogen peroxide. Therefore, enhanced peroxidase activity affects plant growth rate and oxidative stress resistance. PMID:12857800

Ectopic expression of a horseradish peroxidase enhances growth rate and increases oxidative stress resistance in hybrid aspen.

PubMed

Kawaoka, Akiyoshi; Matsunaga, Etsuko; Endo, Saori; Kondo, Shinkichi; Yoshida, Kazuya; Shinmyo, Atsuhiko; Ebinuma, Hiroyasu

2003-07-01

We previously demonstrated that overexpression of the horseradish (Armoracia rusticana) peroxidase prxC1a gene stimulated the growth rate of tobacco (Nicotiana tabacum) plants. Here, the cauliflower mosaic virus 35S::prxC1a construct was introduced into hybrid aspen (Populus sieboldii x Populus grandidentata). The growth rate of these transformed hybrid aspen plants was substantially increased under greenhouse conditions. The average stem length of transformed plants was 25% greater than that of control plants. There was no other obvious phenotypic difference between the transformed and control plants. Fast-growing transformed hybrid aspen showed high levels of expression of prxC1a and had elevated peroxidase activities toward guaiacol and ascorbate. However, there was no increase of the endogenous class I ascorbate peroxidase activities in the transformed plants by separate assay and activity staining of native polyacrylamide gel electrophoresis. Furthermore, calli derived from the transformed hybrid aspen grew faster than those from control plants and were resistant to the oxidative stress imposed by hydrogen peroxide. Therefore, enhanced peroxidase activity affects plant growth rate and oxidative stress resistance.

Performance Evaluation of Frequency Transform Based Block Classification of Compound Image Segmentation Techniques

NASA Astrophysics Data System (ADS)

Selwyn, Ebenezer Juliet; Florinabel, D. Jemi

2018-04-01

Compound image segmentation plays a vital role in the compression of computer screen images. Computer screen images are images which are mixed with textual, graphical, or pictorial contents. In this paper, we present a comparison of two transform based block classification of compound images based on metrics like speed of classification, precision and recall rate. Block based classification approaches normally divide the compound images into fixed size blocks of non-overlapping in nature. Then frequency transform like Discrete Cosine Transform (DCT) and Discrete Wavelet Transform (DWT) are applied over each block. Mean and standard deviation are computed for each 8 × 8 block and are used as features set to classify the compound images into text/graphics and picture/background block. The classification accuracy of block classification based segmentation techniques are measured by evaluation metrics like precision and recall rate. Compound images of smooth background and complex background images containing text of varying size, colour and orientation are considered for testing. Experimental evidence shows that the DWT based segmentation provides significant improvement in recall rate and precision rate approximately 2.3% than DCT based segmentation with an increase in block classification time for both smooth and complex background images.

Holotransformations of bacterial colonies and genome cybernetics

NASA Astrophysics Data System (ADS)

Ben-Jacob, Eshel; Tenenbaum, Adam; Shochet, Ofer; Avidan, Orna

1994-01-01

We present a study of colony transformations during growth of Bacillus subtilis under adverse environmental conditions. It is a continuation of our pilot study of “Adaptive self-organization during growth of bacterial colonies” (Physica A 187 (1992) 378). First we identify and describe the transformations pathway, i.e. the excitation of the branching modes from Bacillus subtilis 168 (grown under diffusion limited conditions) and the phase transformations between the tip-splitting phase (phase T) and the chiral phase (phase C) which belong to the same mode. This pathway shows the evolution of complexity as the bacteria are exposed to adverse growth conditions. We present the morphology diagram of phases T and C as a function of agar concentration and pepton level. As expected, the growth of phase T is ramified (fractal-like or DLA-like) at low pepton level (about 1 g/1) and turns compact at high pepton level (about 10 g/1). The growth of phase C is also ramified at low pepton level and turns denser and finally compact as the pepton level increases. Generally speaking, the colonies develop more complex patterns and higher micro-level organization for more adverse environments. We use the growth velocity as a response function to describe the growth. At low agar concentration (and low pepton level) phase C grows faster than phase T, and for a high agar concentration (about 2%) phase T grows faster. We observe colony transformations between the two phases (phase transformations). They are found to be consistent with the “fastest growing morphology” selection principle adopted from azoic systems. The transformations are always from the slower phase to the faster one. Hence, we observe T→ C transformations at low agar concentrations and C→ T transformations at high agar concentrations. We have observed both localized and extended transformations. Usually, the transformations are localized for more adverse growth conditions, and extended for growth conditions close to the boundaries between morphologies. We have observed also transformations between different branching modes, as well as transformations via virtual states. Motivated by the contemporary knowledge about phages and plasmids, we postulate a theoretical framework to comply with our experimental findings. We explain our observations using these assumptions as well as our proposal of co-mutations and auto-catalytic mutations as presented in the above mentioned pilot paper. This theoretical framework is a part of the new evolving picture of genome cybernetics. We also discuss the concept of adaptive genome changes which are based on pre-existing knowledge as well as the concept of genetic learning. i.e. changes (in response to a new problem) which develop the potential for adaptive genome changes. These concepts follow naturally if the picture of genome cybernetics is accepted. We conclude with a discussion of the implications and with further predictions (to be tested experimentally) derived from our assumptions.

Neoplastic transformation of human cells

NASA Technical Reports Server (NTRS)

Goth-Goldstein, Regine

1995-01-01

The goal of this project was to gain a better understanding of the cellular mechanisms of cancer induction by ionizing radiation as a risk assessment for workers subjected to high LET irradiation such as that found in space. The following ions were used for irradiation: Iron, Argon, Neon, and Lanthanum. Two tests were performed: growth in low serum and growth in agar were used as indicators of cell transformation. The specific aims of this project were to: (1) compare the effectiveness of various ions on degree of transformation of a single dose of the same RBE; (2) determine if successive irradiations with the same ion (Ge 600 MeV/u) increases the degree of transformation; (3) test if clones with the greatest degree of transformation produce tumors in nude mice; and (4) construct a cell hybrid of a transformed and control (non-transformed) clone. The cells used for this work are human mammary epithelial cells with an extended lifespan and selected for growth in MEM + 10% serum.

A Model System to Investigate the Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and Transformation Potential of the Ovarian Epithelium

DTIC Science & Technology

2009-10-01

Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and Transformation Potential of the Ovarian Epithelium PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER A Model System To Investigate the Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and... effects of loss of function of BRCA1 or BRCA1 and Trp53 in the stroma on the growth and neoplastic transformation of epithelial cells using 2D and 3D in

Regulation of adhesion and growth of fibrosarcoma cells by NF-kappa B RelA involves transforming growth factor beta.

PubMed Central

Perez, J R; Higgins-Sochaski, K A; Maltese, J Y; Narayanan, R

1994-01-01

The NF-kappa B transcription factor is a pleiotropic activator that participates in the induction of a wide variety of cellular genes. Antisense oligomer inhibition of the RelA subunit of NF-kappa B results in a block of cellular adhesion and inhibition of tumor cell growth. Investigation of the molecular basis for these effects showed that in vitro inhibition of the growth of transformed fibroblasts by relA antisense oligonucleotides can be reversed by the parental-cell-conditioned medium. Cytokine profile analysis of these cells treated with relA antisense oligonucleotides revealed inhibition of transforming growth factor beta 1 (TGF-beta 1 to the transformed fibroblasts reversed the inhibitory effects of relA antisense oligomers on soft agar colony formation and cell adhesion to the substratum. Direct inhibition of TGF-beta 1 expression by antisense phosphorothioates to TGF-beta 1 mimicked the in vitro effects of blocking cell adhesion that are elicited by antisense relA oligomers. These results may explain the in vitro effects of relA antisense oligomers on fibrosarcoma cell growth and adhesion. Images PMID:8035811

Mexico City air quality research initiative. Volume 2, Problem definition, background, and summary of prior research

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

Not Available

1994-06-01

Air pollution in Mexico City has increased along with the growth of the city, the movement of its population, and the growth of employment created by industry. The main cause of pollution in the city is energy consumption. Therefore, it is necessary to take into account the city`s economic development and its prospects when considering the technological relationships between well-being and energy consumption. Air pollution in the city from dust and other particles suspended in the air is an old problem. However, pollution as we know it today began about 50 years ago with the growth of industry, transportation, andmore » population. The level of well-being attained in Mexico City implies a high energy use that necessarily affects the valley`s natural air quality. However, the pollution has grown so fast that the City must act urgently on three fronts: first, following a comprehensive strategy, transform the economic foundation of the city with nonpolluting activities to replace the old industries, second, halt pollution growth through the development of better technologies; and third, use better fuels, emission controls, and protection of wooded areas.« less

Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is paralleled by a decrease in epidermal-growth-factor receptor expression.

PubMed Central

Van Zoelen, E J; Peters, P H; Afink, G B; Van Genesen, S; De Roos, D G; Van Rotterdam, W; Theuvenet, A P

1994-01-01

Normal rat kidney fibroblasts, grown to density arrest in the presence of epidermal growth factor (EGF), can be induced to undergo phenotypic transformation by treatment with transforming growth factor beta or retinoic acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of density-dependent growth arrest by a specific receptor-mediated mechanism. The effects of bradykinin are specific, and are not mimicked by other phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot analysis and receptor-binding studies demonstrate that bradykinin also inhibits the retinoic acid-induced increase in EGF receptor levels in these cells. These studies provide additional evidence that EGF receptor levels modulate EGF-induced expression of the transformed phenotype in these cells. Images Figure 5 PMID:8135739

Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation

PubMed Central

Bettoun, Audrey; Surdez, Didier; Vallerand, David; Gundogdu, Ramazan; Sharif, Ahmad A.D.; Gomez, Marta; Cascone, Ilaria; Meunier, Brigitte; White, Michael A.; Codogno, Patrice; Parrini, Maria Carla; Camonis, Jacques H.; Hergovich, Alexander

2016-01-01

Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options. Particularly, considering that autophagy inhibition can impair the survival of Ras-transformed cells in tissue culture and mouse models, an understanding of factors regulating the balance between autophagy and apoptosis in Ras-transformed human cells is needed. Here, we report critical roles of the STK38 protein kinase in oncogenic Ras transformation. STK38 knockdown impaired anoikis resistance, anchorage-independent soft agar growth, and in vivo xenograft growth of Ras-transformed human cells. Mechanistically, STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. Even more importantly, upon cell detachment STK38 is required to sustain the removal of damaged mitochondria by mitophagy, a selective autophagic process, to prevent excessive mitochondrial reactive oxygen species production that can negatively affect cancer cell survival. Significantly, knockdown of PINK1 or Parkin, two positive regulators of mitophagy, also impaired anoikis resistance and anchorage-independent growth of Ras-transformed human cells, while knockdown of USP30, a negative regulator of PINK1/Parkin-mediated mitophagy, restored anchorage-independent growth of STK38-depleted Ras-transformed human cells. Therefore, our findings collectively reveal novel molecular players that determine whether Ras-transformed human cells die or survive upon cell detachment, which potentially could be exploited for the development of novel strategies to target Ras-transformed cells. PMID:27283898

Phase transformation and sustained load crack growth in ZrO[sub 2] + 3 mol% Y[sub 2]O[sub 3]: Experiments and kinetic modeling

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

Yin, H.; Gao, M.; Wei, R.P.

1995-01-01

To better understand environmentally assisted crack growth (SCG) in yttria stabilized zirconia, experimental studies were undertaken to characterize the kinetics of crack growth and the associated stress/moisture induced phase transformation in ZrO[sub 2] + 3 mol% Y[sub 2]O[sub 3] (3Y-TZP) in water, dry nitrogen and toluene from 3 to 70 C. The results showed that crack growth in water depended strongly on stress intensity factor (K[sub 1]) and temperature (T) and involved the transformation of a thin layer of material near the crack tip from the tetragonal (t) to the monoclinic (m) phase. These results, combined with literature data onmore » moisture-induced phase transformation, suggested that crack growth enhancement by water is controlled by the rate of this transformation and reflects the environmental cracking susceptibility of the transformed m-phase. A model was developed to link subcritical crack growth (SCG) rate to the kinetics of t [yields] m phase transformation. The SCG rate is expressed as an exponential function of stress-free activation energy, a stress-dependent contribution in terms of the mode 1 stress intensity factor K[sub I] and actuation volume, and temperature. The stress-free activation energies for water and the inert environments were determined to be 82 [+-] 3 and 169 [+-] 4 kJ/mol, respectively, at the 95% confidence level, and the corresponding activation volumes were 14 and 35 unit cells. The decreases in activation energy and activation volume may be attributed to a change in surface energy by water.« less

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

Wan, Li; Thompson, Gregory, E-mail: gthompson@eng.ua.edu

A series of 40–2 nm bilayer spacing Ti/Fe multilayers were sputter-deposited. As the length scale of individual Ti layers equaled to 2 nm, Ti phase transforms from a hexagonal close packed (hcp)-to-body centered cubic (bcc) crystal structures for equal layer thicknesses in Ti/Fe multilayers. Further equal reductions in bilayer spacing to less than 1 nm resulted in an additional transformation from a crystalline to amorphous structure. Atom probe tomography reveals significant intermixing between layers which contributes to the observed phase transformations. Real-time, intrinsic growth stress measurements were also performed to relate the adatom mobility to these phase transformations. For the hcp Ti/bcc Femore » multilayers of equivalent volume fractions, the multilayers undergo an overall tensile stress state to a compressive stress state with decreasing bilayer thickness for the multilayers. When the above phase transformations occurred, a modest reduction in the overall compressive stress of the multilayer was noted. Depending on the Fe thickness, the Ti growth was observed to be a tensile to compressive growth change to a purely compressive growth for thinner bilayer spacing. Fe retained a tensile growth stress regardless of the bilayer spacing studied.« less

EFFECTS OF EPIDERMAL GROWTH FACTOR (EGF), TRANSFORMING GROWTH FACTOR- (TGF), AND 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON FUSION OF EMBRYONIC PALATES IN SERUM-FREE ORGAN CULTURE USING WILD-TYPE, EGF KNOCKOUT, AND TGF KNOCKOUT MOUSE STRAINS

EPA Science Inventory

Backround: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, producing cleft palate (CP). TCDD exposure disrupts expression of epidermal growth factor (EGF) receptor, EGF, and transforming growth factor- (TGF) in the palate and affects proliferation and different...

The Skeletal Site-Specific Role of Connective Tissue Growth Factor in Prenatal Osteogenesis

PubMed Central

Lambi, Alex G.; Pankratz, Talia L.; Mundy, Christina; Gannon, Maureen; Barbe, Mary F.; Richtsmeier, Joan T.; Popoff, Steven N.

2013-01-01

Background Connective tissue growth factor (CTGF/CCN2) is a matricellular protein that is highly expressed during bone development. Mice with global CTGF ablation (knockout, KO) have multiple skeletal dysmorphisms and perinatal lethality. A quantitative analysis of the bone phenotype has not been conducted. Results We demonstrated skeletal site-specific changes in growth plate organization, bone microarchitecture, and shape and gene expression levels in CTGF KO compared with wild-type mice. Growth plate malformations included reduced proliferation zone and increased hypertrophic zone lengths. Appendicular skeletal sites demonstrated decreased metaphyseal trabecular bone, while having increased mid-diaphyseal bone and osteogenic expression markers. Axial skeletal analysis showed decreased bone in caudal vertebral bodies, mandibles, and parietal bones in CTGF KO mice, with decreased expression of osteogenic markers. Analysis of skull phenotypes demonstrated global and regional differences in CTGF KO skull shape resulting from allometric (size-based) and nonallometric shape changes. Localized differences in skull morphology included increased skull width and decreased skull length. Dysregulation of the transforming growth factor-β-CTGF axis coupled with unique morphologic traits provides a potential mechanistic explanation for the skull phenotype. Conclusions We present novel data on a skeletal phenotype in CTGF KO mice, in which ablation of CTGF causes site-specific aberrations in bone formation. PMID:23073844

Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals.

PubMed Central

Diaz-Meco, M T; Dominguez, I; Sanz, L; Municio, M M; Berra, E; Cornet, M E; Garcia de Herreros, A; Johansen, T; Moscat, J

1992-01-01

Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1. Images PMID:1309592

Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells

PubMed Central

2010-01-01

Background Ephrin A1 (EFNA1) is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. In malignancy, the precise role of EFNA1 and its preferred receptor, EPHA2, is controversial. Several studies have found that EFNA1 may suppress EPHA2-mediated oncogenesis, or enhance it, depending on cell type and context. However, little is known about the conditions that influence whether EFNA1 promotes or suppresses tumorigenicity. EFNA1 exists in a soluble form as well as a glycophosphatidylinositol (GPI) membrane attached form. We investigated whether the contradictory roles of EFNA1 in malignancy might in part be related to the existence of both soluble and membrane attached forms of EFNA1 and potential differences in the manner in which they interact with EPHA2. Results Using a RNAi strategy to reduce the expression of endogenous EFNA1 and EPHA2, we found that both EFNA1 and EPHA2 are required for growth of HeLa and SK-BR3 cells. The growth defects could be rescued by conditioned media from cells overexpressing soluble EFNA1. Interestingly, we found that overexpression of the membrane attached form of EFNA1 suppresses growth of HeLa cells in 3D but not 2D. Knockdown of endogenous EFNA1, or overexpression of full-length EFNA1, resulted in relocalization of EPHA2 from the cell surface to sites of cell-cell contact. Overexpression of soluble EFNA1 however resulted in more EPHA2 distributed on the cell surface, away from cell-cell contacts, and promoted the growth of HeLa cells. Conclusions We conclude that soluble EFNA1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation. PMID:20979646

Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats

PubMed Central

2012-01-01

Background At present there is no effective and accepted therapy for hepatic fibrosis. Transforming growth factor (TGF)-β1 signaling pathway contributes greatly to hepatic fibrosis. Reducing TGF-β synthesis or inhibiting components of its complex signaling pathway represent important therapeutic targets. The aim of the study was to investigate the effect of curcumin on liver fibrosis and whether curcumin attenuates the TGF-β1 signaling pathway. Methods Sprague–Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six weeks together with or without curcumin, and hepatic histopathology and collagen content were employed to quantify liver necro-inflammation and fibrosis. Moreover, the mRNA and protein expression levels of TGF-β1, Smad2, phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) were determined by quantitative real time-PCR, Western blot, or immunohistochemistry. Results Rats treated with curcumin improved liver necro-inflammation, and reduced liver fibrosis in association with decreased α-smooth muscle actin expression, and decreased collagen deposition. Furthermore, curcumin significantly attenuated expressions of TGFβ1, Smad2, phosphorylated Smad2, Smad3, and CTGF and induced expression of the Smad7. Conclusions Curcumin significantly attenuated the severity of CCl4-induced liver inflammation and fibrosis through inhibition of TGF-β1/Smad signalling pathway and CTGF expression. These data suggest that curcumin might be an effective antifibrotic drug in the prevention of liver disease progression. PMID:22978413

Efficient Plastid Transformation in Arabidopsis.

PubMed

Yu, Qiguo; Lutz, Kerry Ann; Maliga, Pal

2017-09-01

Plastid transformation is routine in tobacco ( Nicotiana tabacum ) but 100-fold less frequent in Arabidopsis ( Arabidopsis thaliana ), preventing its use in plastid biology. A recent study revealed that null mutations in ACC2 , encoding a plastid-targeted acetyl-coenzyme A carboxylase, cause hypersensitivity to spectinomycin. We hypothesized that plastid transformation efficiency should increase in the acc2 background, because when ACC2 is absent, fatty acid biosynthesis becomes dependent on translation of the plastid-encoded ACC β-carboxylase subunit. We bombarded ACC2 -defective Arabidopsis leaves with a vector carrying a selectable spectinomycin resistance ( aadA ) gene and gfp , encoding the green fluorescence protein GFP. Spectinomycin-resistant clones were identified as green cell clusters on a spectinomycin medium. Plastid transformation was confirmed by GFP accumulation from the second open reading frame of a polycistronic messenger RNA, which would not be translated in the cytoplasm. We obtained one to two plastid transformation events per bombarded sample in spectinomycin-hypersensitive Slavice and Columbia acc2 knockout backgrounds, an approximately 100-fold enhanced plastid transformation frequency. Slavice and Columbia are accessions in which plant regeneration is uncharacterized or difficult to obtain. A practical system for Arabidopsis plastid transformation will be obtained by creating an ACC2 null background in a regenerable Arabidopsis accession. The recognition that the duplicated ACCase in Arabidopsis is an impediment to plastid transformation provides a rational template to implement plastid transformation in related recalcitrant crops. © 2017 American Society of Plant Biologists. All Rights Reserved.

The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy

PubMed Central

Tal, Reshef; Segars, James H.

2014-01-01

Background It is well established that tumors are dependent on angiogenesis for their growth and survival. Although uterine fibroids are known to be benign tumors with reduced vascularization, recent work demonstrates that the vasculature of fibroids is grossly and microscopically abnormal. Accumulating evidence suggests that angiogenic growth factor dysregulation may be implicated in these vascular and other features of fibroid pathophysiology. Methods Literature searches were performed in PubMed and Google Scholar for articles with content related to angiogenic growth factors and myometrium/leiomyoma. The findings are hereby reviewed and discussed. Results Multiple growth factors involved in angiogenesis are differentially expressed in leiomyoma compared with myometrium. These include epidermal growth factor (EGF), heparin-binding-EGF, vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-β and adrenomedullin. An important paradox is that although leiomyoma tissues are hypoxic, leiomyoma feature down-regulation of key molecular regulators of the hypoxia response. Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid development and growth. Notably, common treatments for fibroids such as GnRH agonists and uterine artery embolization (UAE) are shown to work at least partly via anti-angiogenic mechanisms. Conclusions Angiogenic growth factors play an important role in mechanisms of fibroid pathophysiology, including abnormal vasculature and fibroid growth and survival. Moreover, the fibroid's abnormal vasculature together with its aberrant hypoxic and angiogenic response may make it especially vulnerable to disruption of its vascular supply, a feature which could be exploited for treatment. Further experimental studies are required in order to gain a better understanding of the growth factors that are involved in normal and pathological myometrial angiogenesis, and to assess the potential of anti-angiogenic treatment strategies for uterine fibroids. PMID:24077979

Background Independence and Duality Invariance in String Theory.

PubMed

Hohm, Olaf

2017-03-31

Closed string theory exhibits an O(D,D) duality symmetry on tori, which in double field theory is manifest before compactification. I prove that to first order in α^{'} there is no manifestly background independent and duality invariant formulation of bosonic string theory in terms of a metric, b field, and dilaton. To this end I use O(D,D) invariant second order perturbation theory around flat space to show that the unique background independent candidate expression for the gauge algebra at order α^{'} is inconsistent with the Jacobi identity. A background independent formulation exists instead for frame variables subject to α^{'}-deformed frame transformations (generalized Green-Schwarz transformations). Potential applications for curved backgrounds, as in cosmology, are discussed.

Breather-to-soliton transformation rules in the hierarchy of nonlinear Schrödinger equations.

PubMed

Chowdury, Amdad; Krolikowski, Wieslaw

2017-06-01

We study the exact first-order soliton and breather solutions of the integrable nonlinear Schrödinger equations hierarchy up to fifth order. We reveal the underlying physical mechanism which transforms a breather into a soliton. Furthermore, we show how the dynamics of the Akhmediev breathers which exist on a constant background as a result of modulation instability, is connected with solitons on a zero background. We also demonstrate that, while a first-order rogue wave can be directly transformed into a soliton, higher-order rogue wave solutions become rational two-soliton solutions with complex collisional structure on a background. Our results will have practical implications in supercontinuum generation, turbulence, and similar other complex nonlinear scenarios.

Efficient production of human acidic fibroblast growth factor in pea (Pisum sativum L.) plants by agroinfection of germinated seeds

PubMed Central

2011-01-01

Background For efficient and large scale production of recombinant proteins in plants transient expression by agroinfection has a number of advantages over stable transformation. Simple manipulation, rapid analysis and high expression efficiency are possible. In pea, Pisum sativum, a Virus Induced Gene Silencing System using the pea early browning virus has been converted into an efficient agroinfection system by converting the two RNA genomes of the virus into binary expression vectors for Agrobacterium transformation. Results By vacuum infiltration (0.08 Mpa, 1 min) of germinating pea seeds with 2-3 cm roots with Agrobacteria carrying the binary vectors, expression of the gene for Green Fluorescent Protein as marker and the gene for the human acidic fibroblast growth factor (aFGF) was obtained in 80% of the infiltrated developing seedlings. Maximal production of the recombinant proteins was achieved 12-15 days after infiltration. Conclusions Compared to the leaf injection method vacuum infiltration of germinated seeds is highly efficient allowing large scale production of plants transiently expressing recombinant proteins. The production cycle of plants for harvesting the recombinant protein was shortened from 30 days for leaf injection to 15 days by applying vacuum infiltration. The synthesized aFGF was purified by heparin-affinity chromatography and its mitogenic activity on NIH 3T3 cells confirmed to be similar to a commercial product. PMID:21548923

Human microRNA-1245 down-regulates the NKG2D receptor in natural killer cells and impairs NKG2D-mediated functions

PubMed Central

Espinoza, J. Luis; Takami, Akiyoshi; Yoshioka, Katsuji; Nakata, Katsuya; Sato, Tokiharu; Kasahara, Yoshihito; Nakao, Shinji

2012-01-01

Background NKG2D is an activating receptor expressed by natural killer and T cells, which have crucial functions in tumor and microbial immunosurveillance. Several cytokines have been identified as modulators of NKG2D receptor expression. However, little is known about NKG2D gene regulation. In this study, we found that microRNA 1245 attenuated the expression of NKG2D in natural killer cells. Design and Methods We investigated the potential interactions between the 3′-untranslated region of the NKG2D gene and microRNA as well as their functional roles in the regulation of NKG2D expression and cytotoxicity in natural killer cells. Results Transforming growth factor-β1, a major negative regulator of NKG2D expression, post-transcriptionally up-regulated mature microRNA-1245 expression, thus down-regulating NKG2D expression and impairing NKG2D-mediated immune responses in natural killer cells. Conversely, microRNA-1245 down-regulation significantly increased the expression of NKG2D expression in natural killer cells, resulting in more efficient NKG2D-mediated cytotoxicity. Conclusions These results reveal a novel NKG2D regulatory pathway mediated by microRNA-1245, which may represent one of the mechanisms used by transforming growth factor-β1 to attenuate NKG2D expression in natural killer cells. PMID:22491735

Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells

PubMed Central

Chen, Danqi; Fang, Lei; Mei, Shenglin; Li, Hongjie; Xu, Xia; Des Marais, Thomas L.; Lu, Kun; Liu, X. Shirley

2017-01-01

Background: Formaldehyde (FA) is an environmental and occupational chemical carcinogen. Recent studies have shown that exogenous FA causes only a modest increase in DNA adduct formation compared with the amount of adducts formed by endogenous FA, raising the possibility that epigenetic mechanisms may contribute to FA-mediated carcinogenicity. Objectives: We investigated the effects of FA exposure on histone modifications and chromatin assembly. We also examined the role of defective chromatin assembly in FA-mediated transcription and cell transformation. Methods: Cellular fractionation and Western blot analysis were used to measure the levels of histone modifications in human bronchial epithelial BEAS-2B cells and human nasal RPMI2650 cells in the presence of FA. Chromatin immunoprecipitation (ChIP) and micrococcal nuclease (MNase) digest assays were performed to examine the changes in chromatin assembly and accessibility after FA exposure. RNA sequencing (RNA-seq) and real-time polymerase chain reaction (PCR) were used to examine transcriptional dysregulation. Finally, anchorage-independent cell growth ability was tested by soft agar assay following FA exposure. Results: Exposure to FA dramatically decreased the acetylation of the N-terminal tails of cytosolic histones. These modifications are important for histone nuclear import and subsequent chromatin assembly. Histone proteins were depleted in both the chromatin fraction and at most of the genomic loci tested following FA exposure, suggesting that FA compromises chromatin assembly. Moreover, FA increased chromatin accessibility and altered the expression of hundreds of cancer-related genes. Knockdown of the histone H3.3 gene (an H3 variant), which mimics inhibition of chromatin assembly, facilitated FA-mediated anchorage-independent cell growth. Conclusions: We propose that the inhibition of chromatin assembly represents a novel mechanism of cell transformation induced by the environmental and occupational chemical carcinogen FA. https://doi.org/10.1289/EHP1275 PMID:28937961

Parthenocarpic potential in Capsicum annuum L. is enhanced by carpelloid structures and controlled by a single recessive gene

PubMed Central

2011-01-01

Background Parthenocarpy is a desirable trait in Capsicum annuum production because it improves fruit quality and results in a more regular fruit set. Previously, we identified several C. annuum genotypes that already show a certain level of parthenocarpy, and the seedless fruits obtained from these genotypes often contain carpel-like structures. In the Arabidopsis bel1 mutant ovule integuments are transformed into carpels, and we therefore carefully studied ovule development in C. annuum and correlated aberrant ovule development and carpelloid transformation with parthenocarpic fruit set. Results We identified several additional C. annuum genotypes with a certain level of parthenocarpy, and confirmed a positive correlation between parthenocarpic potential and the development of carpelloid structures. Investigations into the source of these carpel-like structures showed that while the majority of the ovules in C. annuum gynoecia are unitegmic and anatropous, several abnormal ovules were observed, abundant at the top and base of the placenta, with altered integument growth. Abnormal ovule primordia arose from the placenta and most likely transformed into carpelloid structures in analogy to the Arabidopsis bel1 mutant. When pollination was present fruit weight was positively correlated with seed number, but in the absence of seeds, fruit weight proportionally increased with the carpelloid mass and number. Capsicum genotypes with high parthenocarpic potential always showed stronger carpelloid development. The parthenocarpic potential appeared to be controlled by a single recessive gene, but no variation in coding sequence was observed in a candidate gene CaARF8. Conclusions Our results suggest that in the absence of fertilization most C. annuum genotypes, have parthenocarpic potential and carpelloid growth, which can substitute developing seeds in promoting fruit development. PMID:22018057

Pirfenidone inhibits transforming growth factor-β1-induced fibrogenesis by blocking nuclear translocation of Smads in human retinal pigment epithelial cell line ARPE-19

PubMed Central

Choi, Kyungsun; Lee, Kihwang; Ryu, Seung-Wook; Im, Minju; Kook, Koung Hoon

2012-01-01

Purpose Transforming growth factor-β (TGF-β) plays a key role in transforming retinal pigment epithelial (RPE) cells into mesenchymal fibroblastic cells, which are implicated in proliferative vitreoretinopathy. Herein, we tested the effect of pirfenidone, a novel antifibrotic agent, on TGF-β1-mediated fibrogenesis in the human RPE cell line ARPE-19. Methods The effect of pirfenidone on the TGF-β1-induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. Fibronectin and collagen production was measured with enzyme-linked immunosorbent assay, and cell migration activity was investigated using a scratch assay. Immunoblot analyses of cofilin, sma and mad protein (smad) 2/3, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and extracellular signal-related kinase expression were conducted to elucidate the cell signaling networks that contribute to the antifibrotic effect of pirfenidone. Results Treatment with TGF-β1 induced typical phenotypic changes such as formation of stress fiber running parallel to the long axis of cells and enhanced migration and production of extracellular matrix components such as collagen type I and fibronectin. This fibroblast-like phenotype induced by TGF-β1 was significantly inhibited by pretreatment with pirfenidone in a dose-dependent manner. We also elucidated the TGF-β signaling pathways as the target of the inhibitory effect of pirfenidone. Pirfenidone inhibited TGF-β signaling by preventing nuclear accumulation of active Smad2/3 complexes rather than phosphorylation of Smad2/3. Conclusions These results collectively provide a rational background for future evaluation of pirfenidone as a potential antifibrotic agent for treating proliferative vitreoretinopathy and other fibrotic retinal disorders. PMID:22550395

Ion-beam-induced magnetic and structural phase transformation of Ni-stabilized face-centered-cubic Fe films on Cu(100)

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

Gloss, Jonas; Institute of Physical Engineering, Faculty of Mechanical Engineering, Brno University of Technology, Technická 2, 616 69 Brno; Shah Zaman, Sameena

2013-12-23

Metastable face-centered cubic (fcc) Fe/Cu(100) thin films are good candidates for ion-beam magnetic patterning due to their magnetic transformation upon ion-beam irradiation. However, pure fcc Fe films undergo spontaneous transformation when their thickness exceeds 10 ML. This limit can be extended to approximately 22 ML by deposition of Fe at increased CO background pressures. We show that much thicker films can be grown by alloying with Ni for stabilizing the fcc γ phase. The amount of Ni necessary to stabilize nonmagnetic, transformable fcc Fe films in dependence on the residual background pressure during the deposition is determined and a phasemore » diagram revealing the transformable region is presented.« less

Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila

PubMed Central

2010-01-01

Background The TSC-22 domain family (TSC22DF) consists of putative transcription factors harboring a DNA-binding TSC-box and an adjacent leucine zipper at their carboxyl termini. Both short and long TSC22DF isoforms are conserved from flies to humans. Whereas the short isoforms include the tumor suppressor TSC-22 (Transforming growth factor-β1 stimulated clone-22), the long isoforms are largely uncharacterized. In Drosophila, the long isoform Bunched A (BunA) acts as a growth promoter, but how BunA controls growth has remained obscure. Results In order to test for functional conservation among TSC22DF members, we expressed the human TSC22DF proteins in the fly and found that all long isoforms can replace BunA function. Furthermore, we combined a proteomics-based approach with a genetic screen to identify proteins that interact with BunA. Madm (Mlf1 adapter molecule) physically associates with BunA via a conserved motif that is only contained in long TSC22DF proteins. Moreover, Drosophila Madm acts as a growth-promoting gene that displays growth phenotypes strikingly similar to bunA phenotypes. When overexpressed, Madm and BunA synergize to increase organ growth. Conclusions The growth-promoting potential of long TSC22DF proteins is evolutionarily conserved. Furthermore, we provide biochemical and genetic evidence for a growth-regulating complex involving the long TSC22DF protein BunA and the adapter molecule Madm. See minireview at http://jbiol.com/content/9/1/8. PMID:20149264

Modulated Fourier Transform Raman Fiber-Optic Spectroscopy

NASA Technical Reports Server (NTRS)

Jensen, Brian J. (Inventor); Cooper, John B. (Inventor); Wise, Kent L. (Inventor)

2000-01-01

A modification to a commercial Fourier Transform (FT) Raman spectrometer is presented for the elimination of thermal backgrounds in the FT Raman spectra. The modification involves the use of a mechanical optical chopper to modulate the continuous wave laser, remote collection of the signal via fiber optics, and connection of a dual-phase digital-signal-processor (DSP) lock-in amplifier between the detector and the spectrometer's collection electronics to demodulate and filter the optical signals. The resulting Modulated Fourier Transform Raman Fiber-Optic Spectrometer is capable of completely eliminating thermal backgrounds at temperatures exceeding 300 C.

Evaluation of TGF-β1 and MCP-1 expression and tubulointerstitial fibrosis in children with Henoch-Schönlein purpura nephritis and IgA nephropathy: A clinical correlation.

PubMed

Shuiai, Zhao; Huijun, Shen; Weizhong, Gu; Aimin, Liu; Jianhua, Mao

2017-02-01

Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are two diseases with similar clinical presentations but very different prognoses. Transforming growth factor β1 and monocyte chemoattractant protein-1 have been associated with the development of tissue fibrosis. We examined the development of tubulointerstitial fibrosis and its relationship with Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in these patients. Renal tissue samples were collected by renal biopsy from 50 children with Henoch-Schönlein purpura nephritis and 50 children with immunoglobulin A nephropathy. Hematoxylin and eosin and Masson's trichrome-stained tissues were examined using light microscopy. Tubulointerstitial fibrosis was graded using the method described by Bohle et al. (1). The immunohistochemical detection of Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was correlated with the tubulointerstitial fibrosis grade. Clinical Trial registration number: ZJCH-2012-0105. Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001). The immunoglobulin A nephropathy patients had a higher tubulointerstitial fibrosis grade than the Henoch-Schönlein purpura nephritis patients (p<0.001). The tubulointerstitial fibrosis grade was in accordance with the Transforming growth factor β1 and monocyte chemoattractant protein-1 expression levels in both diseases (both p<0.001). Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was associated with the development of immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis. Further studies are needed to better evaluate this association.

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

Chang, Yu-Tzu; Shu, Chung-Li; Lai, Jing-Yang

Mouse embryo fibroblasts (MEFs) grow slowly after cultivation from animals, however, after an extended period of cultivation, their growth accelerates. We found that SWAP-70 deficient MEFs failed to increase growth rates. They maintain normal growth rates and proliferation cycles for at least 5 years. Complementing SWAP-70 deficiency in one of these MEF clones, MEF1F2, by expressing human SWAP-70 resulted in fast growth of the cells after further cultivation for a long period. The resulting cells show a transformation phenotype, since they grow on top of each other and do not show contact inhibition. This phenotype was reverted when sanguinarine, amore » putative SWAP-70 inhibitor, was added. Two SWAP-70 expressing clones were examined in detail. Even after cell density became very high their cdc2 and NFκB were still activated suggesting that they do not stop growing. One of the clones formed colonies in soft agar and formed tumors in nude mice. Lately, one more clone became transformed being able to make colonies in soft agar. We maintain 4 human SWAP-70 expressing MEF1F2 cell lines. Three out of 4 clones exhibited transforming phenotypes. The mouse SWAP-70 gene also promoted transformation of MEFs. Taken together our data suggest that SWAP-70 is not a typical oncogene, but is required for spontaneous transformation of MEFs. - Highlights: • Mouse embryo fibroblasts (MEFs) lacking SWAP-70 do not cause spontaneous transform. • Adding back of SWAP-70 to SWAP-70-deficient MEFs induces spontaneous transformation. • SWAP-70 is required for spontaneous transformation of MEFs.« less

Stable Eutectoid Transformation in Nodular Cast Iron: Modeling and Validation

NASA Astrophysics Data System (ADS)

Carazo, Fernando D.; Dardati, Patricia M.; Celentano, Diego J.; Godoy, Luis A.

2017-01-01

This paper presents a new microstructural model of the stable eutectoid transformation in a spheroidal cast iron. The model takes into account the nucleation and growth of ferrite grains and the growth of graphite spheroids. Different laws are assumed for the growth of both phases during and below the intercritical stable eutectoid. At a microstructural level, the initial conditions for the phase transformations are obtained from the microstructural simulation of solidification of the material, which considers the divorced eutectic and the subsequent growth of graphite spheroids up to the initiation of the stable eutectoid transformation. The temperature field is obtained by solving the energy equation by means of finite elements. The microstructural (phase change) and macrostructural (energy balance) models are coupled by a sequential multiscale procedure. Experimental validation of the model is achieved by comparison with measured values of fractions and radius of 2D view of ferrite grains. Agreement with such experiments indicates that the present model is capable of predicting ferrite phase fraction and grain size with reasonable accuracy.

The effect of temperature and moisture on the amorphous-to-crystalline transformation of stavudine.

PubMed

Strydom, Schalk; Liebenberg, Wilna; Yu, Lian; de Villiers, Melgardt

2009-09-08

Stavudine is a nucleoside reverse transcriptase inhibitor active against HIV, and is known to exist in two polymorphic forms designated as forms I and II, and a hydrate form III. An amorphous solid of stavudine was successfully prepared and characterized during this investigation. A comprehensive evaluation of the stability of this amorphous solid showed that the amorphous solid transforms to either form II (anhydrous) or form III (hydrate) when exposed to temperature, in the absence or presence of moisture, respectively. The amorphous-to-hydrate transformation occurred at relatively low RH (>32%) and led to the formation of crystal aggregates of the hydrated form. Steady state growth rate analyses also showed that the amorphous-to-crystalline transformation occurs at a greater rate in the presence of moisture, compared to the transformation at the same temperature in a dry environment. Crystal growth studies showed that it is possible to stabilize the amorphous solid of stavudine against crystal transformations in the absence of moisture by coating it with poly(methyl methacrylate). However, this polymer coating could not prevent crystal growth from the amorphous solid during exposure to moisture.

In situ Observation of Phase Transformation in MnAl(C) Magnetic Materials

PubMed Central

Si, Ping-Zhan; Qian, Hui-Dong; Choi, Chul-Jin; Park, Jihoon; Han, Sangho; Ge, Hong-Liang; Shinde, Kiran P.

2017-01-01

The phase transformation in two modes, including both displacive and massive growth of τ-phase from ε-MnAl(C), was observed by in situ transmission electron microscopy. The exact temperature range for different phase transformation modes was determined by magnetic measurements. The displacive growth of ε→τ in Mn54Al46 (or Mn54Al46C2.44) occurs at temperatures below 650 K (or 766 K), above which both modes coexist. One-third or less of the ε-phase can be transformed into τ-phase via displacive mode while the remaining two-thirds or more via massive mode. In bulk τ-phase, most τ-nanocrystals formed via displacive mode are distributed in the matrix of large τ-grains that formed via massive mode. The typical massive growth rate of the τ-phase is 8–60 nm/s, while the displacive growth rate is low. A more complete understanding of the ε→τ phase transformations in the MnAl-based magnets was provided in this work, based on which the annealing process for ε→τ was optimized and thus high purity τ-phase with high saturation magnetization was obtained. PMID:28858231

Phase and microstructural development in alumina sol-gel coatings on CoCr alloy.

PubMed

Bae, I J; Standard, O C; Roger, G J; Brazil, D

2004-09-01

Phase transformation of gamma-Al(2)O(3) to alpha-Al(2)O(3) in alumina sol gel coatings on biomedical CoCr alloy was studied as function of heat treatment temperature and time. Transformation in unseeded coatings was significant only above approximately 1200 degrees C. Addition of alpha-Al(2)O(3) seed particles having an average size of approximately 40 nm lowered the phase transformation temperature to around 800 degrees C. These particles were considered to act as heterogeneous nucleation sites for epitaxial growth of the alpha-Al(2)O(3) phase. The kinetics and activation energy (420 kJ/mol) for the phase transformation in the seeded coatings were similar to those reported for seeded monolithic alumina gels indicating that the transformation mechanism is the same in the two material configurations. Avrami growth parameters indicated that the mechanism was diffusion controlled and invariant over the temperature range studied but that growth was possibly constrained by the finite size of the seed particles and/or coating thickness. The phase transformation occurred by the growth of alpha-Al(2)O(3) grains at the expense of the precursor fine-grained gamma-Al(2)O(3) matrix and near-complete transformation coincided with physical impingement of the growing grains. The grain size at impingement was approximately 100 nm which agreed well with that predicted from the theoretical linear spacing of seed particles in the initial sol.

A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

NASA Astrophysics Data System (ADS)

Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

1995-10-01

Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

Expression of PEP carboxylase from Escherichia coli complements the phenotypic effects of pyruvate carboxylase mutations in Saccharomyces cerevisiae.

PubMed

Flores, C L; Gancedo, C

1997-08-04

We investigated the effects of the expression of the Escherichia coli ppc gene encoding PEP carboxylase in Saccharomyces cerevisiae mutants devoid of pyruvate carboxylase. Functional expression of the ppc gene restored the ability of the yeast mutants to grow in glucose-ammonium medium. Growth yield in this medium was the same in the transformed yeast than in the wild type although the growth rate of the transformed yeast was slower. Growth in pyruvate was slowed down in the transformed strain, likely due to a futile cycle produced by the simultaneous action of PEP carboxykinase and PEP carboxylase.

Dynamical Instability Produces Transform Faults at Mid-Ocean Ridges

NASA Astrophysics Data System (ADS)

Gerya, Taras

2010-08-01

Transform faults at mid-ocean ridges—one of the most striking, yet enigmatic features of terrestrial plate tectonics—are considered to be the inherited product of preexisting fault structures. Ridge offsets along these faults therefore should remain constant with time. Here, numerical models suggest that transform faults are actively developing and result from dynamical instability of constructive plate boundaries, irrespective of previous structure. Boundary instability from asymmetric plate growth can spontaneously start in alternate directions along successive ridge sections; the resultant curved ridges become transform faults within a few million years. Fracture-related rheological weakening stabilizes ridge-parallel detachment faults. Offsets along the transform faults change continuously with time by asymmetric plate growth and discontinuously by ridge jumps.

Epidermal Growth Factor-Dependent Transformation by a Human EGF Receptor Proto-Oncogene

NASA Astrophysics Data System (ADS)

Velu, Thierry J.; Beguinot, Laura; Vass, William C.; Willingham, Mark C.; Merlino, Glenn T.; Pastan, Ira; Lowy, Douglas R.

1987-12-01

The epidermal growth factor (EGF) receptor gene EGFR has been placed in a retrovirus vector to examine the growth properties of cells that experimentally overproduce a full-length EGF receptor. NIH 3T3 cells transfected with the viral DNA or infected with the corresponding rescued retrovirus developed a fully transformed phenotype in vitro that required both functional EGFR expression and the presence of EGF in the growth medium. Cells expressing 4 × 105 EGF receptors formed tumors in nude mice, while control cells did not. Therefore, the EGFR retrovirus, which had a titer on NIH 3T3 cells that was greater than 107 focus-forming units per milliliter, can efficiently transfer and express this gene, and increased numbers of EGF receptors can contribute to the transformed phenotype.

The Role of Myoepithelial Maspin in Breast Carcinoma Progression Diagnosis and Screening

DTIC Science & Technology

2003-08-01

expression pro- xenografts, the tumors were essentially avascular and their filing (gene chip analysis) to see whether the different myo- 116 S.H. Barskv...factor; aFGF, acidic fibroblast growth factor; TFGa, transforming growth factor a; TGFP3. transforming growth factor 03; TNFa, tumor necrosis factor a...angiogenesis but containing bound angiogenic inhibitors. These myoepithelial xenografts exhibit only minimal hypoxia but extensive necrosis compared with their

Mesenchymal Stem Cells Suppress Chronic Rejection in Heterotopic Small Intestine Transplant Rat Models Via Inhibition of CD68, Transforming Growth Factor- β1, and Platelet-Derived Growth Factor Expression.

PubMed

Li, Fuxin; Cao, Jisen; Zhao, Zhicheng; Li, Chuan; Qi, Feng; Liu, Tong

2017-04-01

Mesenchymal stem cells are easy to obtain and expand, with characteristics of low immunogenicity and strong tissue repair capacity. In this study, our aim was to investigate the role of mesenchymal stem cells in chronic immune rejection of heterotopic small intestine transplant in rats. After successfully constructing a rat chronic immune rejection model of heterotopic small intestine transplant, we infused mesenchymal stem cells into the animal recipients. We observed mesenchymal stem cell location in the recipients, recipient survival, pathology changes, and the expression of CD68, transforming growth factor β1, and platelet-derived growth factor C in the donor intestine. Mesenchymal stem cells inhibited the lymphocyte proliferation caused by concanavalin A in vitro. After stem cells were infused into recipients, they were mainly located in the donor intestine, as well as in the spleen and thymus. Recovery after transplant and pathology changes of the donor intestine in rats with stem cell infusion were better than in the control group; however, we observed no differences in survival time, accompanied by downregulated expression of CD68, transforming growth factor β1, and platelet-derived growth factor C. Mesenchymal stem cells, to a certain extent, could inhibit the process of chronic rejection. The mechanisms may include the inhibited function of these cells on lymphocyte proliferation, reduced infiltration of macrophages, and reduced expression of transforming growth factor β1 and platelet-derived growth factor C.

Effects of nerve growth factor (NGF) on blood vessels area and expression of the angiogenic factors VEGF and TGFbeta1 in the rat ovary

PubMed Central

Julio-Pieper, Marcela; Lara, Hernán E; Bravo, Javier A; Romero, Carmen

2006-01-01

Background Angiogenesis is a crucial process in follicular development and luteogenesis. The nerve growth factor (NGF) promotes angiogenesis in various tissues. An impaired production of this neurotrophin has been associated with delayed wound healing. A variety of ovarian functions are regulated by NGF, but its effects on ovarian angiogenesis remain unknown. The aim of this study was to elucidate if NGF modulates 1) the amount of follicular blood vessels and 2) ovarian expression of two angiogenic factors: vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGFbeta1), in the rat ovary. Results In cultured neonatal rat ovaries, NGF increased VEGF mRNA and protein levels, whereas TGFbeta1 expression did not change. Sectioning of the superior ovarian nerve, which increases ovarian NGF protein content, augmented VEGF immunoreactivity and the area of capillary vessels in ovaries of prepubertal rats compared to control ovaries. Conclusion Results indicate that NGF may be important in the maintenance of the follicular and luteal vasculature in adult rodents, either indirectly, by increasing the expression of VEGF in the ovary, or directly via promoting the proliferation of vascular cells. This data suggests that a disruption on NGF regulation could be a component in ovarian disorders related with impaired angiogenesis. PMID:17096853

Improved electro-transformation of highly DNA-restrictive corynebacteria with DNA extracted from starved Escherichia coli.

PubMed

Ankri, S; Reyes, O; Leblon, G

1996-07-01

Differences of up to 33 000-fold in electro-transformability of highly DNA restrictive corynebacteria are observed in the DNA of a shuttle plasmid extracted from Escherichia coli hosts propagated in different nutritional conditions. Growth of the host in minimal medium increases plasmid transformability, whereas growth on rich media decreases it. In the E. coli DH5 alpha host, the starvation-dependent increase DNA transformability is reverted by supplementing with methionine, an obligate 5-adenosyl-methionine (SAM) precursor. This suggests that an E. coli nutritionally modulated SAM-dependent DNA-methyltransferase may be involved in this phenomenon.

A constitutive expression system for glycosyl hydrolase family 7 cellobiohydrolases in Hypocrea jecorina

DOE PAGES

Linger, Jeffrey G.; Taylor, II, Larry E.; Baker, John O.; ...

2015-03-18

One of the primary industrial-scale cellulase producers is the ascomycete fungus, Hypocrea jecorina, which produces and secretes large quantities of diverse cellulolytic enzymes. Perhaps the single most important biomass degrading enzyme is cellobiohydrolase I (cbh1or Cel7A) due to its enzymatic proficiency in cellulose depolymerization. However, production of Cel7A with native-like properties from heterologous expression systems has proven difficult. In this study, we develop a protein expression system in H. jecorina (Trichoderma reesei) useful for production and secretion of heterologous cellobiohydrolases from glycosyl hydrolase family 7. Building upon previous work in heterologous protein expression in filamentous fungi, we have integrated amore » native constitutive enolase promoter with the native cbh1 signal sequence. The results are the following: The constitutive eno promoter driving the expression of Cel7A allows growth on glucose and results in repression of the native cellulase system, severely reducing background endo- and other cellulase activity and greatly simplifying purification of the recombinant protein. Coupling this system to a Δcbh1 strain of H. jecorina ensures that only the recombinant Cel7A protein is produced. Two distinct transformant colony morphologies were observed and correlated with high and null protein production. Production levels in ‘fast’ transformants are roughly equivalent to those in the native QM6a strain of H. jecorina, typically in the range of 10 to 30 mg/L when grown in continuous stirred-tank fermenters. ‘Slow’ transformants showed no evidence of Cel7A production. Specific activity of the purified recombinant Cel7A protein is equivalent to that of native protein when assayed on pretreated corn stover, as is the thermal stability and glycosylation level. Purified Cel7A produced from growth on glucose demonstrated remarkably consistent specific activity. Purified Cel7A from the same strain grown on lactose demonstrated significantly higher variability in activity. In conclusion, he elimination of background cellulase induction provides much more consistent measured specific activity compared to a traditional cbh1 promoter system induced with lactose. This expression system provides a powerful tool for the expression and comparison of mutant and/or phylogenetically diverse cellobiohydrolases in the industrially relevant cellulase production host H. jecorina.« less

Broadband CARS spectral phase retrieval using a time-domain Kramers–Kronig transform

PubMed Central

Liu, Yuexin; Lee, Young Jong; Cicerone, Marcus T.

2014-01-01

We describe a closed-form approach for performing a Kramers–Kronig (KK) transform that can be used to rapidly and reliably retrieve the phase, and thus the resonant imaginary component, from a broadband coherent anti-Stokes Raman scattering (CARS) spectrum with a nonflat background. In this approach we transform the frequency-domain data to the time domain, perform an operation that ensures a causality criterion is met, then transform back to the frequency domain. The fact that this method handles causality in the time domain allows us to conveniently account for spectrally varying nonresonant background from CARS as a response function with a finite rise time. A phase error accompanies KK transform of data with finite frequency range. In examples shown here, that phase error leads to small (<1%) errors in the retrieved resonant spectra. PMID:19412273

Tax-dependent stimulation of G1 phase-specific cyclin-dependent kinases and increased expression of signal transduction genes characterize HTLV type 1-transformed T cells.

PubMed

Haller, K; Ruckes, T; Schmitt, I; Saul, D; Derow, E; Grassmann, R

2000-11-01

Human T cell leukemia virus protein induces T cells to permanent IL-2-dependent growth. These cells occasionally convert to factor independence. The viral oncoprotein Tax acts as an essential growth factor of transformed lymphocytes and stimulates the cell cycle in the G(1) phase. In T cells and fibroblasts Tax enhances the activity of the cyclin-dependent kinases (CDK) CDK4 and CDK6. These kinases, which require binding to cyclin D isotypes for their activity, control the G(1) phase. Coimmunoprecipitation from these cells revealed that Tax associates with cyclin D3/CDK6, suggesting a direct activation of this kinase. The CDK stimulation may account in part for the mitogenic Tax effect, which causes IL-2-dependent T cell growth by Tax. To address the conversion to IL-2-independent proliferation and to identify overexpressed genes, which contribute to the transformed growth, the gene expression patterns of HTLV-1-transformed T cells were compared with that of peripheral blood lymphocytes. Potentially overexpressed cDNAs were cloned, sequenced, and used to determine the RNA expression. Genes found to be up-regulated are involved in signal transduction (STAT5a, cyclin G(1), c-fgr, hPGT) and also glycoprotein synthesis (LDLC, ribophorin). Many of these are also activated during T cell activation and implicated in the regulation of growth and apoptosis. The transcription factor STAT5a, which is involved in IL-2 signaling, was strongly up-regulated only in IL-2-independent cells, thus suggesting that it contributes to factor-independent growth. Thus, the differentially expressed genes could cooperate with the Tax-induced cell cycle stimulation in the maintenance of IL-2-dependent and IL-2-independent growth of HTLV-transformed lymphocytes.

Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

PubMed

Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S P

2015-01-01

There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

Down-regulation of transforming growth factor beta-2 expression is associated with the reduction of cyclosporin induced gingival overgrowth in rats treated with roxithromycin: an experimental study

PubMed Central

2009-01-01

Background Gingival overgrowth (GO) is a common side effect of the chronic use of cyclosporine (CsA), an immunosuppressant widely used to prevent rejection in transplant patients. Recent studies have reported elevated levels of specific cytokines in gingival overgrowth tissue, particularly TGF-beta, suggesting that this growth factor plays a role in the accumulation of extracellular matrix materials. The effectiveness of azithromycin, a macrolide antibiotic, in the regression of this undesirable side effect has also been demonstrated. Methods In this study, we created an experimental model for assessing the therapeutic effect of roxithromycin in GO and the expression of transforming growth factor beta (TGF-beta2) through immunohistochemistry. We used four groups of rats totaling 32 individuals. GO was induced during five weeks and drug treatment was given on the 6th week as follows: group 1 received saline; group 2 received CsA and was treated with saline on the 6th week; group 3 received CsA and, on the 6th week, ampicilin; and group 4 received CsA during 5 weeks and, on the 6th week, was treated with roxithromycin. Results The results demonstrated that roxithromycin treatment was effective in reducing cyclosporine-induced GO in rats. Both epithelial and connective tissue showed a decrease in thickness and a significant reduction in TGF-beta2 expression, with a lower number of fibroblasts, reduction in fibrotic areas and decrease in inflammatory infiltrate. Conclusion The present data suggest that the down-regulation of TGF-beta2 expression may be an important mechanism of action by which roxithromycin inhibits GO. PMID:19995419

Development of an optimized tetracycline-inducible expression system to increase the accumulation of interleukin-10 in tobacco BY-2 suspension cells

PubMed Central

2012-01-01

Background Plant cell suspension cultures can be used for the production of valuable pharmaceutical and industrial proteins. When the recombinant protein is secreted into the culture medium, restricting expression to a defined growth phase can improve both the quality and quantity of the recovered product by minimizing proteolytic activity. Temporal restriction is also useful for recombinant proteins whose constitutive expression affects cell growth and viability, such as viral interleukin-10 (vIL-10). Results We have developed a novel, tetracycline-inducible system suitable for tobacco BY-2 suspension cells which increases the yields of vIL-10. The new system is based on a binary vector that is easier to handle than conventional vectors, contains an enhanced inducible promoter and 5′-UTR to improve yields, and incorporates a constitutively-expressed visible marker gene to allow the rapid and straightforward selection of the most promising transformed clones. Stable transformation of BY-2 cells with this vector, without extensive optimization of the induction conditions, led to a 3.5 fold increase in vIL-10 levels compared to constitutive expression in the same host. Conclusions We have developed an effective and straightforward molecular farming platform technology that improves both the quality and the quantity of recombinant proteins produced in plant cells, particularly those whose constitutive expression has a negative impact on plant growth and development. Although we tested the platform using vIL-10 produced in BY-2 cells, it can be applied to other host/product combinations and is also useful for basic research requiring strictly controlled transgene expression. PMID:22784336

FluG affects secretion in colonies of Aspergillus niger.

PubMed

Wang, Fengfeng; Krijgsheld, Pauline; Hulsman, Marc; de Bekker, Charissa; Müller, Wally H; Reinders, Marcel; de Vries, Ronald P; Wösten, Han A B

2015-01-01

Colonies of Aspergillus niger are characterized by zonal heterogeneity in growth, sporulation, gene expression and secretion. For instance, the glucoamylase gene glaA is more highly expressed at the periphery of colonies when compared to the center. As a consequence, its encoded protein GlaA is mainly secreted at the outer part of the colony. Here, multiple copies of amyR were introduced in A. niger. Most transformants over-expressing this regulatory gene of amylolytic genes still displayed heterogeneous glaA expression and GlaA secretion. However, heterogeneity was abolished in transformant UU-A001.13 by expressing glaA and secreting GlaA throughout the mycelium. Sequencing the genome of UU-A001.13 revealed that transformation had been accompanied by deletion of part of the fluG gene and disrupting its 3' end by integration of a transformation vector. Inactivation of fluG in the wild-type background of A. niger also resulted in breakdown of starch under the whole colony. Asexual development of the ∆fluG strain was not affected, unlike what was previously shown in Aspergillus nidulans. Genes encoding proteins with a signal sequence for secretion, including part of the amylolytic genes, were more often downregulated in the central zone of maltose-grown ∆fluG colonies and upregulated in the intermediate part and periphery when compared to the wild-type. Together, these data indicate that FluG of A. niger is a repressor of secretion.

View of transformer platform from Powerhouse roof showing oil tank ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of transformer platform from Powerhouse roof showing oil tank at original step-up transformer (center of foreground) and steel switchback (background), view to north-northeast - Morony Hydroelectric Facility, Dam and Powerhouse, Morony Dam Road, Great Falls, Cascade County, MT

From Winning-at-All-Costs to Give Us Back Our Game: Perspective Transformation in Youth Sport Coaches

ERIC Educational Resources Information Center

Fenoglio, Rick; Taylor, William

2014-01-01

Background: Drawing upon concepts from Mezirow's transformative learning theory, this research investigated the process of perspective transformation in three purposively sampled youth sport coaches in the UK. Perspective transformation is the process by which adults revise their culturally defined frames of reference which have arisen out of…

Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway

PubMed Central

He, Jun; Wang, Min; Jiang, Yue; Chen, Qiudan; Xu, Shaohua; Xu, Qing; Jiang, Bing-Hua

2014-01-01

Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood. Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth. Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis. Results: We found that miR-199a-5p expression levels were more than 100-fold lower in arsenic-transformed cells than parental cells. Re-expression of miR-199a-5p impaired arsenic-induced angiogenesis and tumor growth through its direct targets HIF-1α and COX-2. We further showed that arsenic induced COX-2 expression through HIF-1 regulation at the transcriptional level. In addition, we demonstrated that reactive oxygen species are an upstream event of miR-199a-5p/ HIF-1α/COX-2 pathway in arsenic-induced carcinogenesis. Conclusion: The findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis. Citation: He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH, Liu LZ. 2014. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environ Health Perspect 122:255–261; http://dx.doi.org/10.1289/ehp.1307545 PMID:24413338

Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-{beta} responsiveness

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

Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua

2008-03-10

Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-{beta} (TGF-{beta}) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-{beta}, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-{beta}. To explore this notion, we characterized TGF-{beta}-induced activation of fibroblasts from CCN2-null (CCN2{sup -/-}) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-{beta} signal transduction and regulation of collagen genemore » expression were examined in CCN2{sup -/-} MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2{sup -/-} MEFs was markedly reduced compared to wild type MEFs, TGF-{beta}-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2{sup -/-} MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-{beta}-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts.« less

A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

DTIC Science & Technology

2017-05-01

Transforming growth factor beta (TGFB) family members regulate multiple cellular functions and key reproductive processes in a contextually dependent manner...Appendices……………………………………………………………11 4 1. Introduction Transforming growth factor beta (TGFβ) family members regulate a myriad of cellular functions and... transformation 3. Accomplishments  What were the major goals of the project? The major goal during this reporting period is to identify the oncogenic

Principal component greenness transformation in multitemporal agricultural Landsat data

NASA Technical Reports Server (NTRS)

Abotteen, R. A.

1978-01-01

A data compression technique for multitemporal Landsat imagery which extracts phenological growth pattern information for agricultural crops is described. The principal component greenness transformation was applied to multitemporal agricultural Landsat data for information retrieval. The transformation was favorable for applications in agricultural Landsat data analysis because of its physical interpretability and its relation to the phenological growth of crops. It was also found that the first and second greenness eigenvector components define a temporal small-grain trajectory and nonsmall-grain trajectory, respectively.

The Effect of Nb Micro-alloying on the Bainitic Phase Transformation Under Strip Casting Conditions

NASA Astrophysics Data System (ADS)

Stanford, N.; Dorin, T.; Hodgson, P. D.

2018-04-01

The effect of Nb concentration on the transformation from austenite to bainitic ferrite has been examined under simulated strip casting conditions. Nb concentration was found to delay the nucleation of bainite, but accelerated its growth. It is suggested that the delay in nucleation increases the driving force for transformation, which results in an increase in the growth rate of the bainite. The bainite/austenite interfaces are proposed to move too quickly to suffer appreciable solute drag.

Cooperative transforming activities of ras, myc, and src viral oncogenes in nonestablished rat adrenocortical cells.

PubMed Central

MacAuley, A; Pawson, T

1988-01-01

Early-passage rat adrenocortical cells were infected with Kirsten murine sarcoma virus and MMCV mouse myc virus, two retroviruses carrying the v-Ki-ras and v-myc oncogenes, respectively. Efficient morphological transformation required coinfection with the two viruses, was dependent on the presence of high serum concentrations, and was not immediately accompanied by growth in soft agar. The doubly infected cells coordinately acquired the capacity for anchorage- and serum-independent growth during passage in culture. The appearance of such highly transformed cells was correlated with the emergence of a dominant clone, as suggested by an analysis of retrovirus integration sites. These results indicate that the concerted expression of v-Ki-ras and v-myc could induce rapid morphological transformation of nonestablished adrenocortical cells but that an additional genetic or epigenetic event was required to permit full transformation by these two oncogenes. In contrast, v-src, introduced by retrovirus infection in conjunction with v-myc, rapidly induced serum- and anchorage-independent growth. Therefore, the p60v-src protein-tyrosine kinase, unlike p21v-ras, is apparently not restricted in the induction of a highly transformed phenotype in adrenocortical cells. This system provides an in vitro model for the progressive transformation of epithelial cells by dominantly acting oncogenes. Images PMID:2846881

Transforming properties of the Huntingtin interacting protein 1/ platelet-derived growth factor beta receptor fusion protein.

PubMed

Ross, T S; Gilliland, D G

1999-08-06

We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor beta receptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFbetaR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3-independent growth. A kinase-inactive mutant is neither tyrosine-phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFbetaR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFbetaR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr --> Phe mutants of HIP1/PDGFbetaR in the known PDGFbetaR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFbetaR Tyr --> Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFbetaR.

Adaptive Filtering in the Wavelet Transform Domain Via Genetic Algorithms

DTIC Science & Technology

2004-08-01

inverse transform process. 2. BACKGROUND The image processing research conducted at the AFRL/IFTA Reconfigurable Computing Laboratory has been...coefficients from the wavelet domain back into the original signal domain. In other words, the inverse transform produces the original signal x(t) from the...coefficients for an inverse wavelet transform, such that the MSE of images reconstructed by this inverse transform is significantly less than the mean squared

Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation

DTIC Science & Technology

1999-10-01

deregulated cell mors and may eventually regress through growth (18). The importance of APC and 0- cat - apoptosis (25). enin in the development of colorectal...progression. In support of this idea, Torre Amione et al. [74] demonstrated that, unlike parental tumor cells, fibrosarcoma cells transfected to express 10

ALK and TGF-Beta Resistance in Breast Cancer

DTIC Science & Technology

2017-10-01

and H.F. Lodish, Role of transforming growth factor beta in human disease. N Engl J Med, 2000. 342(18): p. 1350-8. 3. Massague, J., S.W. Blain, and... Transforming growth factor-beta signaling in normal and malignant hematopoiesis. Leukemia, 2003. 17(9): p. 1731-7. 5. Lehman, H.L., et al., Modeling and

Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells.

PubMed Central

Shamah, S M; Stiles, C D; Guha, A

1993-01-01

Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas. Images PMID:8246942

Human Herpesvirus-8-Transformed Endothelial Cells Have Functionally Activated Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor

PubMed Central

Masood, Rizwan; Cesarman, Ethel; Smith, D. Lynne; Gill, Parkash S.; Flore, Ornella

2002-01-01

Kaposi’s sarcoma is a vascular tumor commonly associated with human immunodeficiency virus (HIV)-1 and human herpesvirus (HHV-8) also known as Kaposi’s sarcoma-associated herpesvirus. The principal features of this tumor are abnormal proliferation of vascular structures lined with spindle-shaped endothelial cells. HHV-8 may transform a subpopulation of endothelial cells in vitro via viral and cellular gene expression. We hypothesized that among the cellular genes, vascular endothelial growth factors (VEGFs) and their cognate receptors may be involved in viral-mediated transformation. We have shown that HHV-8-transformed endothelial cells (EC-HHV-8) express higher levels of VEGF, VEGF-C, VEGF-D, and PlGF in addition to VEGF receptors-1, -2, and -3. Furthermore, antibodies to VEGF receptor-2 inhibited cell proliferation and viability. Similarly, inhibition of VEGF gene expression with antisense oligonucleotides inhibited EC-HHV-8 cell proliferation/viability. The growth and viability of primary endothelial cells and a fibroblast cell line however were unaffected by either the VEGF receptor-2 antibody or the VEGF antisense oligodeoxynucleotides. VEGF and VEGF receptors are thus induced in EC-HHV-8 and participate in the transformation. Inhibitors of VEGF may thus modulate the disease process during development and progression. PMID:11786394

O(d,d)-duality in string theory

NASA Astrophysics Data System (ADS)

Rennecke, Felix

2014-10-01

A new method for obtaining dual string theory backgrounds is presented. Preservation of the Hamiltonian density and the energy momentum tensor induced by O( d, d)-transformations leads to a relation between dual sets of coordinate one-forms accompanied by a redefinition of the background fields and a shift of the dilaton. The necessity of isometric directions arises as integrability condition for this map. The isometry algebra is studied in detail using generalised geometry. In particular, non-abelian dualities and β-transformations are contained in this approach. The latter are exemplified by the construction of a new approximate non-geometric background.

The Potential Impact of CO2 and Air Temperature Increases on Krummholz's Transformation into Arborescent Form in the Southern Siberian Mountains

NASA Technical Reports Server (NTRS)

Kharuk, V. I.; Dvinskaya, M. L.; Im, S. T.; Ranson, K. J.

2011-01-01

Trees in the southern Siberian Mountains forest-tundra ecotone have considerably increased their radial and apical growth increments during the last few decades. This leads to the widespread vertical transformation of mat and prostrate krummholz forms of larch (Larix sibirica Ledeb) and Siberian pine (Pinus sibirica Du Tour). An analysis of the radial growth increments showed that these transformations began in the mid-1980s. Larch showed a greater resistance to the harsh alpine environment and attained a vertical growth form in areas where Siberian pine is still krummholz. Upper larch treeline is about 10 m higher than Siberian pine treeline. Observed apical and radial growth increment increases were correlated with CO2 concentration (r = 0.83-0.87), summer temperatures (r = 0.55-0.64), and "cold period" (i.e. September-May) air temperatures (r = 0.36-0.37). Positive correlation between growth increments and winter precipitation was attributed to snow cover protection for trees during wintertime.

Photonic Plasmid Stability of Transformed Salmonella Typhimurium: A Comparison of Three Unique Plasmids

USDA-ARS?s Scientific Manuscript database

Background: Acquiring a highly stable photonic plasmid in transformed Salmonella Typhimurium for use in biophotonic studies of bacterial tracking in vivo is critical to experimental paradigm development. The objective of this study was to determine stability of transformed Salmonella Typhimurium (S....

P01.29 Mutant (R132H) IDH1-driven cellular transformation makes cells dependent on continued wild type IDH1 expression in a model of in vitro gliomagenesis

PubMed Central

Johannessen, T.; Mukherjee, J.; Wood, M.; Viswanath, P.; Ohba, S.; Ronen, S.; Berkvig, R.; Pieper, R.

2017-01-01

Abstract Introduction: Missense R132H mutations in the active site of isocitrate dehydrogenase 1 (IDH1) biologically and diagnostically distinguish low-grade gliomas and secondary glioblastomas from primary glioblastomas. IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of α-ketoglutarate (α-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. We recently showed (Mol Cancer Res 14: 976–983, 2016) that although mutant IDH1 expression in hTERT-immortalized, p53/pRb-deficient astrocytes can drive cellular transformation and gliomagenesis, selective pharmacologic inhibition and elimination of 2-HG by the mutant IDH1 inhibitor AGI-5198 has little effect on the growth or clonagenicity of these transformed cells. To address the possible role of WT IDH1 in the growth of mutant IDH-driven tumor cells, we used a slightly different gliomagenesis model in which the transformation of TERT-deficient, p53/pRb-deficient astrocytes (pre-crisis cells) occurs only after prolonged expression of mutant IDH and passage through cellular crisis (post-crisis cells, Cancer Res 76:6680–6689, 2016). METHODS AND MATERIALS: Using this system we introduced AGI-5198, or siRNA targeting both WT and mutant forms of IDH1 into p53/pRb-deficient, mutant IDH1-expressing human astrocytes prior to or following their transformation, and compared the effects on cell growth and clonagenicity. Results: AGI-5198 exposure decreased levels of 2HG by greater than 90%, and as previously reported had no effect on the growth of either the pre-or post-crisis cell populations. A one-day exposure to a pan IDH1 siRNA resulted in a similar, prolonged (greater than 6 day), 80% inhibition of both WT and mutant IDH1 protein levels and 2HG in both cell groups. While the growth of the mutant IDH-expressing, non-transformed cells was similar to that of scramble siRNA controls, the growth of the mutant IDH-transformed cells was significantly reduced. This growth suppression was also accompanied by a four-fold increase in annexin V-positive apoptotic cells. Furthermore, the growth suppression in the cells transformed by mutant IDH1 expression could not be reversed by addition of a cell-permeable form of 2-HG. Conclusions: These results show that the in vitro transformative events driven by expression of mutant IDH1 make cells dependent not on continued mutant IDH1 expression, but rather on continued WT IDH1 expression. The data also support the development and testing of agents that can inhibit both the WT and mutant forms of IDH1.

The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells

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

Kim, Han-Soo; Kim, Ju Won; Gang, Jingu

2006-09-15

LB42708 (LB7) and LB42908 (LB9) are pyrrole-based orally active farnesyltransferase inhibitors (FTIs) that have similar structures. The in vitro potencies of these compounds against FTase and GGTase I are remarkably similar, and yet they display different activity in apoptosis induction and morphological reversion of ras-transformed rat intestinal epithelial (RIE) cells. Both FTIs induced cell death despite K-ras prenylation, implying the participation of Ras-independent mechanism(s). Growth inhibition by these two FTIs was accompanied by G1 and G2/M cell cycle arrests in H-ras and K-ras-transformed RIE cells, respectively. We identified three key markers, p21{sup CIP1/WAF1}, RhoB and EGFR, that can explain themore » differences in the molecular mechanism of action between two FTIs. Only LB7 induced the upregulation of p21{sup CIP1/WAF1} and RhoB above the basal level that led to the cell cycle arrest and to distinct morphological alterations of ras-transformed RIE cells. Both FTIs successfully inhibited the ERK and activated JNK in RIE/K-ras cells. While the addition of conditioned medium from RIE/K-ras reversed the growth inhibition of ras-transformed RIE cells by LB9, it failed to overcome the growth inhibitory effect of LB7 in both H-ras- and K-ras-transformed RIE cells. We found that LB7, but not LB9, decreased the expression of EGFRs that confers the cellular unresponsiveness to EGFR ligands. These results suggest that LB7 causes the induction of p21{sup CIP1/WAF1} and RhoB and downregulation of EGFR that may serve as critical steps in the mechanism by which FTIs trigger irreversible inhibitions on the cell growth and apoptosis in ras-transformed cells.« less

Poisson denoising on the sphere: application to the Fermi gamma ray space telescope

NASA Astrophysics Data System (ADS)

Schmitt, J.; Starck, J. L.; Casandjian, J. M.; Fadili, J.; Grenier, I.

2010-07-01

The Large Area Telescope (LAT), the main instrument of the Fermi gamma-ray Space telescope, detects high energy gamma rays with energies from 20 MeV to more than 300 GeV. The two main scientific objectives, the study of the Milky Way diffuse background and the detection of point sources, are complicated by the lack of photons. That is why we need a powerful Poisson noise removal method on the sphere which is efficient on low count Poisson data. This paper presents a new multiscale decomposition on the sphere for data with Poisson noise, called multi-scale variance stabilizing transform on the sphere (MS-VSTS). This method is based on a variance stabilizing transform (VST), a transform which aims to stabilize a Poisson data set such that each stabilized sample has a quasi constant variance. In addition, for the VST used in the method, the transformed data are asymptotically Gaussian. MS-VSTS consists of decomposing the data into a sparse multi-scale dictionary like wavelets or curvelets, and then applying a VST on the coefficients in order to get almost Gaussian stabilized coefficients. In this work, we use the isotropic undecimated wavelet transform (IUWT) and the curvelet transform as spherical multi-scale transforms. Then, binary hypothesis testing is carried out to detect significant coefficients, and the denoised image is reconstructed with an iterative algorithm based on hybrid steepest descent (HSD). To detect point sources, we have to extract the Galactic diffuse background: an extension of the method to background separation is then proposed. In contrary, to study the Milky Way diffuse background, we remove point sources with a binary mask. The gaps have to be interpolated: an extension to inpainting is then proposed. The method, applied on simulated Fermi LAT data, proves to be adaptive, fast and easy to implement.

Non-modal theory of the kinetic ion temperature gradient driven instability of plasma shear flows across the magnetic field

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

Mikhailenko, V. V., E-mail: vladimir@pusan.ac.kr; Mikhailenko, V. S.; Lee, Hae June, E-mail: haejune@pusan.ac.kr

2016-06-15

The temporal evolution of the kinetic ion temperature gradient driven instability and of the related anomalous transport of the ion thermal energy of plasma shear flow across the magnetic field is investigated analytically. This instability develops in a steady plasma due to the inverse ion Landau damping and has the growth rate of the order of the frequency when the ion temperature is equal to or above the electron temperature. The investigation is performed employing the non-modal methodology of the shearing modes which are the waves that have a static spatial structure in the frame of the background flow. Themore » solution of the governing linear integral equation for the perturbed potential displays that the instability experiences the non-modal temporal evolution in the shearing flow during which the unstable perturbation becomes very different from a canonical modal form. It transforms into the non-modal structure with vanishing frequency and growth rate with time. The obtained solution of the nonlinear integral equation, which accounts for the random scattering of the angle of the ion gyro-motion due to the interaction of ions with ensemble of shearing waves, reveals similar but accelerated process of the transformations of the perturbations into the zero frequency structures. It was obtained that in the shear flow the anomalous ion thermal conductivity decays with time. It is a strictly non-modal effect, which originates from the temporal evolution of the shearing modes turbulence.« less

Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease

PubMed Central

Curvo, Eduardo OV; Ferreira, Roberto R; Madeira, Fabiana S; Alves, Gabriel F; Chambela, Mayara C; Mendes, Veronica G; Sangenis, Luiz Henrique C; Waghabi, Mariana C; Saraiva, Roberto M

2018-01-01

BACKGROUND Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. OBJECTIVES We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. METHODS This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. FINDINGS TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. CONCLUSIONS TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients. PMID:29513876

Transforming Growth Factor-β1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study

PubMed Central

Talaat, Roba M.; Dondeti, Mahmoud F.; El-Shenawy, Soha Z.; Khamiss, Omaima A.

2013-01-01

The interindividual variations in the capacity of transforming growth factor-β1 (TGF-β1) production have been ascribed to genetic polymorphisms in TGF-β1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF-β1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. TGF-β1 plasma levels were measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC genotype was significantly higher (P < 0.05) in HBV patients compared to controls. On the contrary, TC genotype did not show significant difference in both groups. TT genotype was significantly higher (P < 0.01) in controls than HBV patients. Our current preliminary data revealed that the frequency of the genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the patients group was out of HWE (P < 0.01). TGF-β1 was significantly (r = −0.684; P < 0.001) deceased in the sera of patients as compared to normal subjects. Depending on our preliminary work, CC genotype may act as a host genetic factor in the susceptibility to HBV infection in Egyptians. Taken together, the current data pointed to the importance of polymorphism of TGF-β1 gene (T29C) in HBV infection. PMID:24455227

Arsenic uptake, transformation, and release by three freshwater algae under conditions with and without growth stress.

PubMed

Xie, Shaowen; Liu, Jinxin; Yang, Fen; Feng, Hanxiao; Wei, Chaoyang; Wu, Fengchang

2018-05-04

This study was carried out using indoor controlled experiments to study the arsenic (As) uptake, biotransformation, and release behaviors of freshwater algae under growth stress. Three freshwater algae, Microcystis aeruginosa, Anabaena flosaquae, and Chlorella sp., were chosen. Two types of inhibitors, e.g., Cu 2+ and isothiazolinone, were employed to inhibit the growth of the algae. The algae were cultivated to a logarithmic stage in growth media containing 0.1 mg/L P; then, 0.8 mg/L As in the form of arsenate (iAs V ) was added, while both inhibitors were simultaneously added at dosages of 0.1 and 0.3 mg/L, with no addition of inhibitors in the control. After 2 days of exposure, the average growth rate (μ 2d ) was measured to represent the growth rates of the algae cells; the extra- and intracellular As concentrations in various forms, i.e., arsenate, arsenite (iAs III ), monomethyl arsenic (MMA), and dimethyl arsenic (DMA), were also measured. Without inhibitors, the average growth rate followed the order of M. aeruginosa, Chlorella sp., and A. flosaquae, with the growth rate of M. aeruginosa significantly higher than that of the other two algae. However, when Cu 2+ was added as an external inhibitor, the order of the average growth rate for the three algae became partially reversed, suggesting differentiation of the algae in response to the inhibitor. This differentiation can be seen by the reduction in the average growth rate of M. aeruginosa, which was as high as 1730% at the 0.3-mg/L Cu 2+ dosage when compared with the control, while for the other two algae, much fewer changes were seen. The great reduction in M. aeruginosa growth rate was accompanied by increases in extracellular iAs V and iAs III and intracellular iAs V concentrations in the algae, indicating that As transformation is related to the growth of this algae. Much fewer or neglectable changes in growth were observed that were consistent with the few changes in the extra- and intracellular As speciation for the other two algae with Cu 2+ inhibition and all the three algae with isothiazolinone inhibition, corroborating the above hypothesis again. All the algae tested in this study demonstrated great abilities for As transformation and release, as seen by the much higher rates of 86.11-99.98% and 81.11-99.89% for transformation and release when compared to the control, respectively. When inhibitors were added, the transformation and release values of only A. flosaquae decreased remarkably down to 72.37-86.79% and 64.67-85.24%, respectively, while no changes were seen for these values in the other two algae, indicating that growth stress did not affect the As transformation and release of the other algae. The biological productivity of As by the three algae followed the order of M. aeruginosa, Chlorella sp., and A. flosaquae, which was generally consistent with the As transformation and release in conditions with and without inhibitors, suggesting that the As behavior in the algae that was related to growth stress largely differed among algae species.

SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

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

Wu, Feng; Jordan, Ashley; Kluz, Thomas

The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealedmore » the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.« less

Expression of transforming growth factor alpha and epidermal growth factor receptor messenger RNA in neoplastic and nonneoplastic human kidney tissue.

PubMed

Mydlo, J H; Michaeli, J; Cordon-Cardo, C; Goldenberg, A S; Heston, W D; Fair, W R

1989-06-15

Using Northern blot analysis, we have demonstrated that mRNA for transforming growth factor alpha (TGF-alpha) was expressed in five malignant kidney tissue specimens but was not detected in their autologous nonneoplastic homologues. In addition, the expression of epidermal growth factor (EGF) receptor mRNA in these malignant tissues was 2- to 3-fold greater than in nontransformed tissues. In two cases examined using immunohistochemistry, we were able to correlate the increased expression of the mRNA with an increase in protein expression. Since TGF-alpha is known to bind to the EGF receptor, the finding of an increased expression of both TGF-alpha and EGF receptor mRNA in kidney tumor tissue suggests that interaction between TGF-alpha and the EGF receptor may play a role in promoting transformation and/or proliferation of kidney neoplasms, perhaps by an autocrine mechanism.

Development of human epithelial cell systems for radiation risk assessment

NASA Astrophysics Data System (ADS)

Yang, C. H.; Craise, L. M.

1994-10-01

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene

PubMed Central

Domínguez, Sara; Rubio, M. Belén; Cardoza, Rosa E.; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

2016-01-01

Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in Trichoderma harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea, and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by (i) enhanced growth, (ii) increased carbon and nitrogen levels, and (iii) a higher sensitivity to B. cinerea infections in plants treated with amdS transformants as detected in greenhouse assays. These observations suggest that the increased plant development promoted by the amdS transformants was at expense of defenses. PMID:27536277

Requirement for the SnoN oncoprotein in transforming growth factor beta-induced oncogenic transformation of fibroblast cells.

PubMed

Zhu, Qingwei; Pearson-White, Sonia; Luo, Kunxin

2005-12-01

Transforming growth factor beta (TGF-beta) was originally identified by virtue of its ability to induce transformation of the AKR-2B and NRK fibroblasts but was later found to be a potent inhibitor of the growth of epithelial, endothelial, and lymphoid cells. Although the growth-inhibitory pathway of TGF-beta mediated by the Smad proteins is well studied, the signaling pathway leading to the transforming activity of TGF-beta in fibroblasts is not well understood. Here we show that SnoN, a member of the Ski family of oncoproteins, is required for TGF-beta-induced proliferation and transformation of AKR-2B and NRK fibroblasts. TGF-beta induces upregulation of snoN expression in both epithelial cells and fibroblasts through a common Smad-dependent mechanism. However, a strong and prolonged activation of snoN transcription that lasts for 8 to 24 h is detected only in these two fibroblast lines. This prolonged induction is mediated by Smad2 and appears to play an important role in the transformation of both AKR-2B and NRK cells. Reduction of snoN expression by small interfering RNA or shortening of the duration of snoN induction by a pharmacological inhibitor impaired TGF-beta-induced anchorage-independent growth of AKR-2B cells. Interestingly, Smad2 and Smad3 play opposite roles in regulating snoN expression in both fibroblasts and epithelial cells. The Smad2/Smad4 complex activates snoN transcription by direct binding to the TGF-beta-responsive element in the snoN promoter, while the Smad3/Smad4 complex inhibits it through a novel Smad inhibitory site. Mutations of Smad4 that render it defective in heterodimerization with Smad3, which are found in many human cancers, convert the activity of Smad3 on the snoN promoter from inhibitory to stimulatory, resulting in increased snoN expression in cancer cells. Thus, we demonstrate a novel role of SnoN in the transforming activity of TGF-beta in fibroblasts and also uncovered a mechanism for the elevated SnoN expression in some human cancer cells.

Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene.

PubMed

Domínguez, Sara; Rubio, M Belén; Cardoza, Rosa E; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

2016-01-01

Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in Trichoderma harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea, and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by (i) enhanced growth, (ii) increased carbon and nitrogen levels, and (iii) a higher sensitivity to B. cinerea infections in plants treated with amdS transformants as detected in greenhouse assays. These observations suggest that the increased plant development promoted by the amdS transformants was at expense of defenses.

Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

PubMed Central

Liu, C; Adamson, E; Mercola, D

1996-01-01

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1. Images Fig. 1 Fig. 5 PMID:8876223

Method for protecting bone marrow against chemotherapeutic drugs and radiation therapy using transforming growth factor beta 1

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

Keller, J.R.; Ruscetti, F.W.; Wiltrout, R.

1989-06-29

Presented is a method for protecting hematopoietic stem cells from the myelotoxicity of chemotherapeutic drugs or radiation therapy, which comprises administering to a subject a therapeutically effective amount of transforming growth factor beta 1 for protecting bone marrow from the myelotoxicity of chemotherapeutic drugs or radiation therapy.

Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation

DTIC Science & Technology

2001-10-01

tu- vation of transcription and deregulated cell mors and may eventually regress through growth (18). The importance of APC and [- cat - apoptosis (25...receptors, fibrosarcoma cells transfected to express 10ng/ml TPRII [621, ALK-1 [63], and endoglin [64], and one of its TGF-131 in vitro are unable to

Increased susceptibility to atrial fibrillation secondary to atrial fibrosis in transgenic goats expressing transforming growth factor - B1

USDA-ARS?s Scientific Manuscript database

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in people with significant morbidity and mortality. There is a strong association between atrial fibrosis and AF. Transforming growth factor B1 (TGF-B1) is an essential mediator of atrial fibrosis in animal models and human pat...

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

PubMed

Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

2015-07-01

Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins.

PubMed

He, Jun; Tegen, Sarah B; Krawitz, Ariel R; Martin, G Steven; Luo, Kunxin

2003-08-15

The regulation of cell growth and differentiation by transforming growth factor-beta (TGF-beta) is mediated by the Smad proteins. In the nucleus, the Smad proteins are negatively regulated by two closely related nuclear proto-oncoproteins, Ski and SnoN. When overexpressed, Ski and SnoN induce oncogenic transformation of chicken embryo fibroblasts. However, the mechanism of transformation by Ski and SnoN has not been defined. We have previously reported that Ski and SnoN interact directly with Smad2, Smad3, and Smad4 and repress their ability to activate TGF-beta target genes through multiple mechanisms. Because Smad proteins are tumor suppressors, we hypothesized that the ability of Ski and SnoN to inactivate Smad function may be responsible for their transforming activity. Here, we show that the receptor regulated Smad proteins (Smad2 and Smad3) and common mediator Smad (Smad4) bind to different regions in Ski and SnoN. Mutation of both regions, but not each region alone, markedly impaired the ability of Ski and SnoN to repress TGF-beta-induced transcriptional activation and cell cycle arrest. Moreover, when expressed in chicken embryo fibroblasts, mutant Ski or SnoN defective in binding to the Smad proteins failed to induce oncogenic transformation. These results suggest that the ability of Ski and SnoN to repress the growth inhibitory function of the Smad proteins is required for their transforming activity. This may account for the resistance to TGF-beta-induced growth arrest in some human cancer cell lines that express high levels of Ski or SnoN.

Effect of Bromouracil-containing Deoxyribonucleic Acid on Bacillus subtilis

PubMed Central

Gimlin, Dixie M.; Hardman, Sue D.; Kelley, Betty N.; Butler, Grace C.; Leach, Franklin R.

1966-01-01

Gimlin, Dixie M. (Oklahoma State University, Stillwater), Sue D. Hardman, Betty N. Kelley, Grace C. Butler, and Franklin R. Leach. Effect of bromouracil-containing deoxyribonucleic acid on Bacillus subtilis. J. Bacteriol. 92:366–374. 1966.—Replacement of one-half of the thymine with bromouracil in Bacillus subtilis transforming deoxyribonucleic acid (DNA) resulted in a slight decrease in transforming activity, but, when used at high concentrations, this DNA preparation inhibited cell growth. Acid-hydrolyzed DNA, or addition of equivalent concentrations of the free base bromouracil in a transforming mixture, was without effect on cell growth. Treatment of the DNA preparation with deoxyribonuclease completely destroyed transforming activity and killing effect, whereas treatments with ribonuclease and trypsin were without effect on either transformation or killing activity. Growth of competent B. subtilis cells in test tubes was inhibited by high concentrations of both normal and bromouracil-containing DNA, with the bromouracil-containing DNA being significantly more inhibitory. This type of inhibition was also reflected in the time of division of the cells. The inhibitory effect was not due to viscosity, or to mutagenicity. The time course of killing paralleled transformation, and competency was required. These results can be interpreted as being due to uptake of homologous but imperfect DNA (containing bromouracil instead of thymine) by means of the systems involved in transformation, followed by either integration (resulting in lethal transformation, activation of a defective, nonlytic but lethal prophage) or interference with the recombination mechanism. PMID:16562122

Transformation of self-assembled InAs/InP quantum dots into quantum rings without capping.

PubMed

Sormunen, Jaakko; Riikonen, Juha; Mattila, Marco; Tiilikainen, Jouni; Sopanen, Markku; Lipsanen, Harri

2005-08-01

Transformation of self-assembled InAs quantum dots (QDs) on InP(100) into quantum rings (QRs) is studied. In contrast to the typical approach to III--V semiconductor QR growth, the QDs are not capped to form rings. Atomic force micrographs reveal a drastic change from InAs QDs into rings after a growth interruption in tertiarybutylphosphine ambient. Strain energy relief in the InAs QD is discussed and a mechanism for dot-to-ring transformation by As/P exchange reactions is proposed.

Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.

PubMed

Anan, K; Morisaki, T; Katano, M; Ikubo, A; Kitsuki, H; Uchiyama, A; Kuroki, S; Tanaka, M; Torisu, M

1996-03-01

Angiogenesis is a prerequisite for tumor growth and metastasis. Tumor angiogenesis may be mediated by several angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha, and basic fibroblast growth factor. Differential mRNA expressions of VEGF, PDGF (A chain), transforming growth factor-alpha and basic fibroblast growth factor in 32 primary invasive breast tumors were examined by reverse transcriptase-polymerase chain reaction. We analyzed relationships between mRNA expressions of these angiogenic factors and the degree of angiogenesis, tumor size, and metastasis. Quantification of angiogenesis was achieved by the immunohistochemical staining of endothelial cells with antibody to CD31. VEGF and PDGF-A mRNAs were expressed more frequently in breast tumors than in nontumor breast tissues, whereas no difference was found in expression frequency of either transforming growth factor-alpha or basic fibroblast growth factor mRNA. Vascular counts in tumors correlated with each expression frequency of VEGF and PDGF-A mRNA. PDGF-A mRNA was expressed more frequently in tumors with lymph node metastasis than in those without metastasis. Expression of VEGF and PDGF mRNAs detected by reverse transcriptase-polymerase chain reaction in breast tumors correlates with tumor-related characteristics of angiogenesis and metastatic potential. Analysis of these mRNAs by reverse transcriptase-polymerase chain reaction may be useful for assessing the biologic behavior of a breast tumor before surgical treatment.

Recombinational inactivation of the gene encoding nitrate reductase in Aspergillus parasiticus.

PubMed Central

Wu, T S; Linz, J E

1993-01-01

Functional disruption of the gene encoding nitrate reductase (niaD) in Aspergillus parasiticus was conducted by two strategies, one-step gene replacement and the integrative disruption. Plasmid pPN-1, in which an internal DNA fragment of the niaD gene was replaced by a functional gene encoding orotidine monophosphate decarboxylase (pyrG), was constructed. Plasmid pPN-1 was introduced in linear form into A. parasiticus CS10 (ver-1 wh-1 pyrG) by transformation. Approximately 25% of the uridine prototrophic transformants (pyrG+) were chlorate resistant (Chlr), demonstrating their inability to utilize nitrate as a sole nitrogen source. The genetic block in nitrate utilization was confirmed to occur in the niaD gene by the absence of growth of the A. parasiticus CS10 transformants on medium containing nitrate as the sole nitrogen source and the ability to grow on several alternative nitrogen sources. Southern hybridization analysis of Chlr transformants demonstrated that the resident niaD locus was replaced by the nonfunctional allele in pPN-1. To generate an integrative disruption vector (pSKPYRG), an internal fragment of the niaD gene was subcloned into a plasmid containing the pyrG gene as a selectable marker. Circular pSKPYRG was transformed into A. parasiticus CS10. Chlr pyrG+ transformants were screened for nitrate utilization and by Southern hybridization analysis. Integrative disruption of the genomic niaD gene occurred in less than 2% of the transformants. Three gene replacement disruption transformants and two integrative disruption transformants were tested for mitotic stability after growth under nonselective conditions. All five transformants were found to stably retain the Chlr phenotype after growth on nonselective medium.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8215371

Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling

PubMed Central

Jakobsen, Rune B.; Østrup, Esben; Zhang, Xiaolan; Mikkelsen, Tarjei S.; Brinchmann, Jan E.

2014-01-01

The in vitro process of chondrogenic differentiation of mesenchymal stem cells for tissue engineering has been shown to require three-dimensional culture along with the addition of differentiation factors to the culture medium. In general, this leads to a phenotype lacking some of the cardinal features of native articular chondrocytes and their extracellular matrix. The factors used vary, but regularly include members of the transforming growth factor β superfamily and dexamethasone, sometimes in conjunction with fibroblast growth factor 2 and insulin-like growth factor 1, however the use of soluble factors to induce chondrogenesis has largely been studied on a single factor basis. In the present study we combined a factorial quality-by-design experiment with high-throughput mRNA profiling of a customized chondrogenesis related gene set as a tool to study in vitro chondrogenesis of human bone marrow derived mesenchymal stem cells in alginate. 48 different conditions of transforming growth factor β 1, 2 and 3, bone morphogenetic protein 2, 4 and 6, dexamethasone, insulin-like growth factor 1, fibroblast growth factor 2 and cell seeding density were included in the experiment. The analysis revealed that the best of the tested differentiation cocktails included transforming growth factor β 1 and dexamethasone. Dexamethasone acted in synergy with transforming growth factor β 1 by increasing many chondrogenic markers while directly downregulating expression of the pro-osteogenic gene osteocalcin. However, all factors beneficial to the expression of desirable hyaline cartilage markers also induced undesirable molecules, indicating that perfect chondrogenic differentiation is not achievable with the current differentiation protocols. PMID:24816923

Transformation in Graduates of Hakomi Therapy Training: A Mindful, Body-Centered Approach

ERIC Educational Resources Information Center

Himanen, Caren

2015-01-01

Corrective experiences (CEs) in psychotherapy are important curative factors and clients who experience transformation post rapid gains and thrive as a result. Although transformations are important indicators of growth, less than half of clients experience them. This qualitative study explored the experience of transformation in graduates of a…

Chronic exposure to arsenic, estrogen, and their combination causes increased growth and transformation in human prostate epithelial cells potentially by hypermethylation-mediated silencing of MLH1.

PubMed

Treas, Justin; Tyagi, Tulika; Singh, Kamaleshwar P

2013-11-01

Chronic exposure to arsenic and estrogen is associated with risk of prostate cancer, but their mechanism is not fully understood. Additionally, the carcinogenic effects of their co-exposure are not known. Therefore, the objective of this study was to evaluate the effects of chronic exposure to arsenic, estrogen, and their combination, on cell growth and transformation, and identify the mechanism behind these effects. RWPE-1 human prostate epithelial cells were chronically exposed to arsenic and estrogen alone and in combination. Cell growth was measured by cell count and cell cycle, whereas cell transformation was evaluated by colony formation assay. Gene expression was measured by quantitative real-time PCR and confirmed at protein level by Western blot analysis. MLH1 promoter methylation was determined by pyrosequencing method. Exposure to arsenic, estrogen, and their combinations increases cell growth and transformation in RWPE-1 cells. Increased expression of Cyclin D1 and Bcl2, whereas decreased expression of mismatch repair genes MSH4, MSH6, and MLH1 was also observed. Hypermethylation of MLH1 promoter further suggested the epigenetic inactivation of MLH1 expression in arsenic and estrogen treated cells. Arsenic and estrogen combination caused greater changes than their individual treatments. Findings of this study for the first time suggest that arsenic and estrogen exposures cause increased cell growth and survival potentially through epigenetic inactivation of MLH1 resulting in decreased MLH1-mediated apoptotic response, and consequently increased cellular transformation. © 2013 Wiley Periodicals, Inc.

Comparing transformation methods for DNA microarray data

PubMed Central

Thygesen, Helene H; Zwinderman, Aeilko H

2004-01-01

Background When DNA microarray data are used for gene clustering, genotype/phenotype correlation studies, or tissue classification the signal intensities are usually transformed and normalized in several steps in order to improve comparability and signal/noise ratio. These steps may include subtraction of an estimated background signal, subtracting the reference signal, smoothing (to account for nonlinear measurement effects), and more. Different authors use different approaches, and it is generally not clear to users which method they should prefer. Results We used the ratio between biological variance and measurement variance (which is an F-like statistic) as a quality measure for transformation methods, and we demonstrate a method for maximizing that variance ratio on real data. We explore a number of transformations issues, including Box-Cox transformation, baseline shift, partial subtraction of the log-reference signal and smoothing. It appears that the optimal choice of parameters for the transformation methods depends on the data. Further, the behavior of the variance ratio, under the null hypothesis of zero biological variance, appears to depend on the choice of parameters. Conclusions The use of replicates in microarray experiments is important. Adjustment for the null-hypothesis behavior of the variance ratio is critical to the selection of transformation method. PMID:15202953

Transformation rules and degradation of CAHs by Fentonlike oxidation in growth ring of water distribution network-A review

NASA Astrophysics Data System (ADS)

Zhong, D.; Ma, W. C.; Jiang, X. Q.; Yuan, Y. X.; Yuan, Y.; Wang, Z. Q.; Fang, T. T.; Huang, W. Y.

2017-08-01

Chlorinated hydrocarbons are widely used as organic solvent and chemical raw materials. After treatment, water polluted with trichloroethylene (TCE)/tetrachloroethylene (PCE) can reach the water quality requirements, while water with trace amounts of TCE/PCE is still harmful to humans, which will cause cancers. Water distribution network is an extremely complicated system, in which adsorption, desorption, flocculation, movement, transformation and reduction will occur, leading to changes of TCE/PCE concentrations and products. Therefore, it is important to investigate the transformation rules of TCE/PCE in water distribution network. What’s more, growth-ring, including drinking water pipes deposits, can act as catalysts in Fenton-like reagent (H2O2). This review summarizes the status of transformation rules of CAHs in water distribution network. It also evaluates the effectiveness and fruit of CAHs degradation by Fenton-like reagent based on growth-ring. This review is important in solving the potential safety problems caused by TCE/PCE in water distribution network.

Mössbauer study of iron minerals transformations by Fuchsiella ferrireducens

NASA Astrophysics Data System (ADS)

Gracheva, M. A.; Chistyakova, N. I.; Antonova, A. V.; Rusakov, V. S.; Zhilina, T. N.; Zavarzina, D. G.

2017-11-01

Biogenic transformations of iron-containing minerals synthesized ferrihydrite, magnetite and hydrothermal siderite by anaerobic alkaliphilic bacterium Fuchsiella ferrireducens (strain Z-7101T) were studied by 57Fe Mössbauer spectroscopy. Mössbauer investigations of solid phase samples obtained after microbial transformation were carried out at room temperature and at 82 K. It was found that all tested minerals transformed during bacterial growth. In the presence of synthesized ferrihydrite, added as an electron acceptor, a mixture of large (more than 100 nm) and small (˜5 nm) particles of magnetically ordered phase and siderite was formed. Synthesized magnetite that contains both Fe3+ and Fe2+ forms could serve as electron acceptor as well as an electron donor for F.ferrireducens growth. As a result of its biotransformation, no siderite formation was observed while small particles of magnetite were formed. In the case of the addition of siderite as an electron donor formation of a small amount of a new phase containing Fe2+ caused by recrystallization of siderite during bacterial growth was detected.

Genetic transformation of tobacco NT1 cells with Agrobacterium tumefaciens.

PubMed

Mayo, Kristin J; Gonzales, Barbara J; Mason, Hugh S

2006-01-01

This protocol is used to produce stably transformed tobacco (Nicotiana tabacum) NT1 cell lines, using Agrobacterium tumefaciens-mediated DNA delivery of a binary vector containing a gene encoding hepatitis B surface antigen and a gene encoding the kanamycin selection marker. The NT1 cultures, at the appropriate stage of growth, are inoculated with A. tumefaciens containing the binary vector. A 3-day cocultivation period follows, after which the cultures are rinsed and placed on solid selective medium. Transformed colonies ('calli') appear in approximately 4 weeks; they are subcultured until adequate material is obtained for analysis of antigen production. 'Elite' lines are selected based on antigen expression and growth characteristics. The time required for the procedure from preparation of the plant cell materials to callus development is approximately 5 weeks. Growth of selected calli to sufficient quantities for antigen screening may require 4-6 weeks beyond the initial selection. Creation of the plasmid constructs, transformation of the A. tumefaciens line, and ELISA and Bradford assays to assess protein production require additional time.

A general method for baseline-removal in ultrafast electron powder diffraction data using the dual-tree complex wavelet transform.

PubMed

René de Cotret, Laurent P; Siwick, Bradley J

2017-07-01

The general problem of background subtraction in ultrafast electron powder diffraction (UEPD) is presented with a focus on the diffraction patterns obtained from materials of moderately complex structure which contain many overlapping peaks and effectively no scattering vector regions that can be considered exclusively background. We compare the performance of background subtraction algorithms based on discrete and dual-tree complex (DTCWT) wavelet transforms when applied to simulated UEPD data on the M1-R phase transition in VO 2 with a time-varying background. We find that the DTCWT approach is capable of extracting intensities that are accurate to better than 2% across the whole range of scattering vector simulated, effectively independent of delay time. A Python package is available.

SPARC Expression Is Selectively Suppressed in Tumor Initiating Urospheres Isolated from As+3- and Cd+2-Transformed Human Urothelial Cells (UROtsa) Stably Transfected with SPARC

PubMed Central

Slusser-Nore, Andrea; Larson-Casey, Jennifer L.; Zhang, Ruowen; Zhou, Xu Dong; Somji, Seema; Garrett, Scott H.; Sens, Donald A.; Dunlevy, Jane R.

2016-01-01

Background This laboratory previously analyzed the expression of SPARC in the parental UROtsa cells, their arsenite (As+3) and cadmium (Cd+2)-transformed cell lines, and tumor transplants generated from the transformed cells. It was demonstrated that SPARC expression was down-regulated to background levels in Cd+2-and As+3-transformed UROtsa cells and tumor transplants compared to parental cells. In the present study, the transformed cell lines were stably transfected with a SPARC expression vector to determine the effect of SPARC expression on the ability of the cells to form tumors in immune-compromised mice. Methods Real time PCR, western blotting, immunohistochemistry, and immunofluorescence were used to define the expression of SPARC in the As+3-and Cd+2-transformed cell lines, and urospheres isolated from these cell lines, following their stable transfection with an expression vector containing the SPARC open reading frame (ORF). Transplantation of the cultured cells into immune-compromised mice by subcutaneous injection was used to assess the effect of SPARC expression on tumors generated from the above cell lines and urospheres. Results It was shown that the As+3-and Cd+2-transformed UROtsa cells could undergo stable transfection with a SPARC expression vector and that the transfected cells expressed both SPARC mRNA and secreted protein. Tumors formed from these SPARC-transfected cells were shown to have no expression of SPARC. Urospheres isolated from cultures of the SPARC-transfected As+3-and Cd+2-transformed cell lines were shown to have only background expression of SPARC. Urospheres from both the non-transfected and SPARC-transfected cell lines were tumorigenic and thus fit the definition for a population of tumor initiating cells. Conclusions Tumor initiating cells isolated from SPARC-transfected As+3-and Cd+2-transformed cell lines have an inherent mechanism to suppress the expression of SPARC mRNA. PMID:26783756

Lithosperic rheology controls on oceanic spreading patterns

NASA Astrophysics Data System (ADS)

Gerya, T.

2012-04-01

Mid-ocean ridges sectioned by transform faults represent one of the most prominent surface expressions of terrestrial plate tectonics. A fundamental long standing problem of plate tectonics is how and why ridge-transform spreading patterns are formed and maintained. On the one hand, geometrical correspondence between mid-ocean ridges and respective rifted margins apparently suggests that many oceanic transform faults are inherited structures that persisted throughout the entire history of oceanic spreading. On the other hand, data from incipient oceanic spreading regions show that transform faults are not directly inherited from transverse rift structures and start to develop as or after oceanic spreading nucleate. Based on self-consistent 3D thermomechanical numerical model of oceanic spreading we demonstrate that only limited range of oceanic lithosphere rheologies can reproduce natural spreading patterns. In particular, spontaneous formation and long-term stability of orthogonal ridge-transform spreading pattern requires visco-brittle/plastic rheology of plates with strong dynamic weakening of spontaneously forming faults. Our, numerical models of incipient oceanic spreading demonstrate that one or several oceanic transform faults can form gradually within broad non-transform accommodation zones connecting initially offset spreading centers. Orientation of transform faults and spreading centers changes exponentially with time as the result of new oceanic crust growth. The resulting orthogonal ridge-transform system is established within few millions of years after the beginning of oceanic spreading. By its fundamental physical origin, this system is a crustal growth pattern governed by space accommodation and not a plate breakup pattern governed by stress distribution. It is demonstrated that the characteristic extension-parallel orientation of oceanic transform faults can be obtained from space accommodation criteria as a steady state orientation of a strike-slip fault sustaining in between simultaneously growing offset crustal segments. Numerical models also suggest that transform faults can develop at single straight ridge as the result of dynamical instability of constructive plate boundaries caused by weakening of forming brittle/plastic fractures. Boundary instability from asymmetric plate growth can spontaneously start in alternate directions along successive ridge sections; the resultant curved ridges become transform faults within a few million years. Offsets along the transform faults change continuously with time by asymmetric plate growth and discontinuously by ridge jumps. Degree of asymmetric plate accretion increases with increasing degree of brittle/plastic weakening. It is also strongly dependent on the brittle/plastic yielding criterion and is notably reduced in models with pressure-dependent brittle/plastic plate strength compared to models with pressure-independent strength.

Macropinocytosis of the PDGF β-receptor promotes fibroblast transformation by H-RasG12V

PubMed Central

Schmees, C.; Villaseñor, R.; Zheng, W.; Ma, H.; Zerial, M.; Heldin, C.-H.; Hellberg, C.

2012-01-01

Receptor tyrosine kinase (RTK) signaling is frequently increased in tumor cells, sometimes as a result of decreased receptor down-regulation. The extent to which the endocytic trafficking routes can contribute to such RTK hyperactivation is unclear. Here, we show for the first time that fibroblast transformation by H-RasG12V induces the internalization of platelet-derived growth factor β-receptor (PDGFRβ) by macropinocytosis, enhancing its signaling activity and increasing anchorage-independent proliferation. H-RasG12V transformation and PDGFRβ activation were synergistic in stimulating phosphatidylinositol (PI) 3-kinase activity, leading to receptor macropinocytosis. PDGFRβ macropinocytosis was both necessary and sufficient for enhanced receptor activation. Blocking macropinocytosis by inhibition of PI 3-kinase prevented the increase in receptor activity in transformed cells. Conversely, increasing macropinocytosis by Rabankyrin-5 overexpression was sufficient to enhance PDGFRβ activation in nontransformed cells. Simultaneous stimulation with PDGF-BB and epidermal growth factor promoted macropinocytosis of both receptors and increased their activation in nontransformed cells. We propose that H-Ras transformation promotes tumor progression by enhancing growth factor receptor signaling as a result of increased receptor macropinocytosis. PMID:22573884

Characterization of Antisense Transformed Plants Deficient in the Tobacco Anionic Peroxidase.

PubMed Central

Lagrimini, L. M.; Gingas, V.; Finger, F.; Rothstein, S.; Liu, TTY.

1997-01-01

On the basis of the biological compounds that they metabolize, plant peroxidases have long been implicated in plant growth, cell wall biogenesis, lignification, and host defenses. Transgenic tobacco (Nicotiana tabacum L.) plants that underexpress anionic peroxidase were generated using antisense RNA. The antisense RNA was found to be specific for the anionic isoenzyme and highly effective, reducing endogenous transcript levels and total peroxidase activity by as much as 1600-fold. Antisense-transformed plants appeared normal at initial observation; however, growth studies showed that plants with reduced peroxidase activity grow taller and flower sooner than control plants. In contrast, previously transformed plants overproducing anionic peroxidase were shorter and flowered later than controls. Axillary buds were more developed in antisense-transformed plants and less developed in plants overproducing this enzyme. It was found that the lignin content in leaf, stem, and root was unchanged in antisense-transformed plants, which does not support a role for anionic peroxidase in the lignification of secondary xylem vessels. However, studies of wounded tissue show some reduction in wound-induced deposition of lignin-like polymers. The data support a possible role for tobacco anionic peroxidase in host defenses but not without a reduction in growth potential. PMID:12223765

Characterization of Antisense Transformed Plants Deficient in the Tobacco Anionic Peroxidase.

PubMed

Lagrimini, L. M.; Gingas, V.; Finger, F.; Rothstein, S.; Liu, TTY.

1997-08-01

On the basis of the biological compounds that they metabolize, plant peroxidases have long been implicated in plant growth, cell wall biogenesis, lignification, and host defenses. Transgenic tobacco (Nicotiana tabacum L.) plants that underexpress anionic peroxidase were generated using antisense RNA. The antisense RNA was found to be specific for the anionic isoenzyme and highly effective, reducing endogenous transcript levels and total peroxidase activity by as much as 1600-fold. Antisense-transformed plants appeared normal at initial observation; however, growth studies showed that plants with reduced peroxidase activity grow taller and flower sooner than control plants. In contrast, previously transformed plants overproducing anionic peroxidase were shorter and flowered later than controls. Axillary buds were more developed in antisense-transformed plants and less developed in plants overproducing this enzyme. It was found that the lignin content in leaf, stem, and root was unchanged in antisense-transformed plants, which does not support a role for anionic peroxidase in the lignification of secondary xylem vessels. However, studies of wounded tissue show some reduction in wound-induced deposition of lignin-like polymers. The data support a possible role for tobacco anionic peroxidase in host defenses but not without a reduction in growth potential.

Intrinsic Astrocyte Heterogeneity Influences Tumor Growth in Glioma Mouse Models.

PubMed

Irvin, David M; McNeill, Robert S; Bash, Ryan E; Miller, C Ryan

2017-01-01

The influence of cellular origin on glioma pathogenesis remains elusive. We previously showed that mutations inactivating Rb and Pten and activating Kras transform astrocytes and induce tumorigenesis throughout the adult mouse brain. However, it remained unclear whether astrocyte subpopulations were susceptible to these mutations. We therefore used genetic lineage tracing and fate mapping in adult conditional, inducible genetically engineered mice to monitor transformation of glial fibrillary acidic protein (GFAP) and glutamate aspartate transporter (GLAST) astrocytes and immunofluorescence to monitor cellular composition of the tumor microenvironment over time. Because considerable regional heterogeneity exists among astrocytes, we also examined the influence of brain region on tumor growth. GFAP astrocyte transformation induced uniformly rapid, regionally independent tumor growth, but transformation of GLAST astrocytes induced slowly growing tumors with significant regional bias. Transformed GLAST astrocytes had reduced proliferative response in culture and in vivo and malignant progression was delayed in these tumors. Recruited glial cells, including proliferating astrocytes, oligodendrocyte progenitors and microglia, were the majority of GLAST, but not GFAP astrocyte-derived tumors and their abundance dynamically changed over time. These results suggest that intrinsic astrocyte heterogeneity, and perhaps regional brain microenvironment, significantly contributes to glioma pathogenesis. © 2016 International Society of Neuropathology.

Foxp3-dependent transformation of human primary CD4+ T lymphocytes by the retroviral protein tax.

PubMed

Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

2015-10-23

The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Foxp3-dependent Transformation of Human Primary CD4+ T Lymphocytes by the Retroviral Protein Tax

PubMed Central

Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

2015-01-01

The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells. PMID:26381169

24. Station Oil Tanks, view to the south. The four ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. Station Oil Tanks, view to the south. The four oil storage tanks located along the east wall (left side of photograph) are, from foreground to background: dirty transformer oil tank, clean transformer oil tank, dirty lubricating oil tank, and clean lubricating oil tank. An oil filter system is also visible in background along the far wall. - Washington Water Power Clark Fork River Noxon Rapids Hydroelectric Development, Powerhouse, South bank of Clark Fork River at Noxon Rapids, Noxon, Sanders County, MT

Effect of V-Nd co-doping on phase transformation and grain growth process of TiO2

NASA Astrophysics Data System (ADS)

Khatun, Nasima; Amin, Ruhul; Anita, Sen, Somaditya

2018-05-01

The pure and V-Nd co-doped TiO2 samples are prepared by the modified sol-gel process. The phase formation is confirmed by XRD spectrum. Phase transformation is delayed in V-Nd co-doped TiO2 (TVN) samples compared to pure TiO2. The particle size is comparatively small in TVN samples at both the temperature 450 °C and 900 °C. Hence the effect of Nd doping is dominated over V doping in both phase transformation and grain growth process of TiO2.

In vitro treatment with 17,20b-dihydroxy-4-pregnen-3-one regulates mRNA levels of transforming growth factor beta superfamily members in rainbow trout (Oncorhynchus mykiss) ovarian tissue

USDA-ARS?s Scientific Manuscript database

Transforming growth factor beta (TGFB) superfamily members are important paracrine/autocrine regulators of ovarian development and steroidogenesis in mammals, but their reproductive role in fishes is not well understood. Our objectives were 3-fold: to determine if key TGFB superfamily transcripts a...

Transforming Identities through Transforming Care: How People with Learning Disabilities Experience Moving out of Hospital

ERIC Educational Resources Information Center

Head, Annabel; Ellis-Caird, Helen; Rhodes, Louisa; Parkinson, Kathie

2018-01-01

Background: People with learning disabilities are moving out of hospitals as part of the Transforming Care programme, although thus far their views on how they have experienced this have not been researched. Materials and Methods: A qualitative design was used to explore how people with learning disabilities experienced moving as part of…

Impact of concurrent overexpression of cytosolic glutamine synthetase (GS1) and sucrose phosphate synthase (SPS) on growth and development in transgenic tobacco.

PubMed

Seger, Mark; Gebril, Sayed; Tabilona, Jules; Peel, Amanda; Sengupta-Gopalan, Champa

2015-01-01

The outcome of simultaneously increasing SPS and GS activities in transgenic tobacco, suggests that sucrose is the major determinant of growth and development, and is not affected by changes in N assimilation. Carbon (C) and nitrogen (N) are the major components required for plant growth and the metabolic pathways for C and N assimilation are very closely interlinked. Maintaining an appropriate balance or ratio of sugar to nitrogen metabolites in the cell, is important for the regulation of plant growth and development. To understand how C and N metabolism interact, we manipulated the expression of key genes in C and N metabolism individually and concurrently and checked for the repercussions. Transgenic tobacco plants with a cytosolic soybean glutamine synthetase (GS1) gene and a sucrose phosphate synthase (SPS) gene from maize, both driven by the CaMV 35S promoter were produced. Co-transformants, with both the transgenes were produced by sexual crosses. While GS is the key enzyme in N assimilation, involved in the synthesis of glutamine, SPS plays a key role in C metabolism by catalyzing the synthesis of sucrose. Moreover, to check if nitrate has any role in this interaction, the plants were grown under both low and high nitrogen. The SPS enzyme activity in the SPS and SPS/GS1 co-transformants were the same under both nitrogen regimens. However, the GS activity was lower in the co-transformants compared to the GS1 transformants, specifically under low nitrogen conditions. The GS1/SPS transformants showed a phenotype similar to the SPS transformants, suggesting that sucrose is the major determinant of growth and development in tobacco, and its effect is only marginally affected by increased N assimilation. Sucrose may be functioning in a metabolic capacity or as a signaling molecule.

Biochemical transformation of coals

DOEpatents

Lin, Mow S.; Premuzic, Eugene T.

1999-03-23

A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

Transpersonal Psychology: Facilitating Transformation in Outdoor Experiential Education.

ERIC Educational Resources Information Center

Brown, Michael H.

1989-01-01

Explores how outdoor experiential education can facilitate personal growth and transformation by balancing adventure-based activities with inner-directed processes. Discusses transpersonal psychology and research on consciousness and brain functions relevant to the process of transformation. Describes a specific technique to access deeper levels…

Metal-induced rapid transformation of diamond into single and multilayer graphene on wafer scale

DOE PAGES

Berman, Diana; Deshmukh, Sanket; Narayanan, Badri; ...

2016-07-04

The degradation of intrinsic properties of graphene during the transfer process constitutes a major challenge in graphene device fabrication, stimulating the need for direct growth of graphene on dielectric substrates. Previous attempts of metal-induced transformation of diamond and silicon carbide into graphene suffers from metal contamination and inability to scale graphene growth over large area. Here in this article, we introduce a direct approach to transform polycrystalline diamond into high-quality graphene layers on wafer scale (4 inch in diameter) using a rapid thermal annealing process facilitated by a nickel, Ni thin film catalyst on top. We show that the processmore » can be tuned to grow single or multilayer graphene with good electronic properties. Molecular dynamics simulations elucidate the mechanism of graphene growth on polycrystalline diamond. Additionally, we demonstrate the lateral growth of free-standing graphene over micron-sized pre-fabricated holes, opening exciting opportunities for future graphene/diamond-based electronics.« less

Metal-induced rapid transformation of diamond into single and multilayer graphene on wafer scale

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

Berman, Diana; Deshmukh, Sanket; Narayanan, Badri

The degradation of intrinsic properties of graphene during the transfer process constitutes a major challenge in graphene device fabrication, stimulating the need for direct growth of graphene on dielectric substrates. Previous attempts of metal-induced transformation of diamond and silicon carbide into graphene suffers from metal contamination and inability to scale graphene growth over large area. Here in this article, we introduce a direct approach to transform polycrystalline diamond into high-quality graphene layers on wafer scale (4 inch in diameter) using a rapid thermal annealing process facilitated by a nickel, Ni thin film catalyst on top. We show that the processmore » can be tuned to grow single or multilayer graphene with good electronic properties. Molecular dynamics simulations elucidate the mechanism of graphene growth on polycrystalline diamond. Additionally, we demonstrate the lateral growth of free-standing graphene over micron-sized pre-fabricated holes, opening exciting opportunities for future graphene/diamond-based electronics.« less

Agrobacterium-mediated transformation in Alpinia galanga (Linn.) Willd. for enhanced acetoxychavicol acetate production.

PubMed

Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Mangamoori, Lakshmi Narasu; Giri, Archana

2012-09-01

Agrobacterium-mediated transformations ensure elevated amounts of secondary metabolite accumulation with genetic and biosynthetic stability. In the present study, Alpinia galanga rich in bioactive compounds was genetically transformed using different strains of Agrobacterium rhizogenes viz. LBA 9402, A(4), 532, 2364 and PRTGus. Even though a higher growth rate was obtained with the LBA 9402 strain, maximum acetoxychavicol acetate accumulation (ACA) was seen in the PRTGus transformant. PRTGus root line has shown 10.1 fold higher ACA content in comparison to the control roots. The lowest ACA production was shown by the A(4) transformant (4.9 fold). The quantification of ACA in the transformed roots was carried out by using HPLC, which was found to be in the order of PRTGus > LBA 9402 > 2364 > 532 > A(4). The fast growth rate of hairy roots, genetic stability and their ability to synthesize more than one metabolite offer a promising system for the production of valuable secondary metabolites.

[Study of the phase transformation of TiO2 with in-situ XRD in different gas].

PubMed

Ma, Li-Jing; Guo, Lie-Jin

2011-04-01

TiO2 sample was prepared by sol-gel method from chloride titanium. The phase transformation of the prepared TiO2 sample was studied by in-situ XRD and normal XRD in different gas. The experimental results showed that the phase transformation temperatures of TiO2 were different under in-situ or normal XRD in different kinds of gas. The transformation of amorphous TiO2 to anatase was controlled by kinetics before 500 degrees C. In-situ XRD showed that the growth of anatase was inhibited, but the transformation of anatase to rutile was accelerated under inactive nitrogen in contrast to air. Also better crystal was obtained under hydrogen than in argon. These all showed that external oxygen might accelerate the growth of TiO2, but reduced gas might partly counteract the negative influence of lack of external oxygen. The mechanism of phase transformation of TiO2 was studied by in-situ XRD in order to control the structure in situ.

Cellular and molecular pathology of HTS: basis for treatment.

PubMed

Armour, Alexis; Scott, Paul G; Tredget, Edward E

2007-01-01

Hypertrophic scar and keloids are fibroproliferative disorders of the skin which occur often unpredictably, following trauma and inflammation that compromise cosmesis and function and commonly recur following surgical attempts for improvement. Despite decades of research in these fibrotic conditions, current non-surgical methods of treatment are slow, inconvenient and often only partially effective. Fibroblasts from these conditions are activated to produce extracellular matrix proteins such as collagen I and III, proteoglycans such as versican and biglycan and growth factors, including transforming growth factor-beta and insulin like growth factor I. However, more consistently these cells produce less remodeling enzymes including collagenase and other matrix metalloproteinases, as well as the small proteoglycan decorin which is important for normal collagen fibrillogenesis. Recently, the systemic response to injury appears to influence the local healing process whereby increases in Th2 and possibly Th3 cytokines such as IL-2, IL-4 and IL-10 and TGF-beta are present in the circulating lymphocytes in these fibrotic conditions. Finally, unique bone marrow derived cells including mesenchymal and endothelial stem cells as well as fibrocytes appear to traffic into healing wounds and influence the healing tissue. On this background, clinicians are faced with patients who require treatment and the pathophysiologic basis as currently understood is reviewed for a number of emerging modalities.

Kinetics of the coesite to quartz transformation

USGS Publications Warehouse

Mosenfelder, J.L.; Bohlen, S.R.

1997-01-01

The survival of coesite in ultrahigh-pressure (UHP) rocks has important implications for the exhumation of subducted crustal rocks. We have conducted experiments to study the mechanism and rate of the coesite ??? quartz transformation using polycrystalline coesite aggregates, fabricated by devitrifying silica glass cylinders containing 2850H/106 Si at 1000??C and 3.6 GPa for 24h. Conditions were adjusted following synthesis to transform the samples at 700-1000??C at pressures 190-410 MPa below the quartz-coesite equilibrium boundary. Reaction proceeds via grain-boundary nucleation and interface-controlled growth, with characteristic reaction textures remarkably similar to those seen in natural UHP rocks. We infer that the experimental reaction mechanism is identical to that in nature, a prerequisite for reliable extrapolation of the rate data. Growth rates obtained by direct measurement differ by up to two orders of magnitude from those estimated by fitting a rate equation to the transformation-time data. Fitting the rates to Turnbull's equation for growth therefore yields two distinct sets of parameters with similar activation energies (242 or 269 kJ/mol) but significantly different pre-exponential constants. Extrapolation based on either set of growth rates suggests that coesite should not be preserved on geologic time scales if it reaches the quartz stability field at temperatures above 375-400??C. The survival of coesite has previously been linked to its inclusion in strong phases, such as garnet, that can sustain a high internal pressure during decompression. Other factors that may play a crucial role in preservation are low fluid availability - possibly even less than that of our nominally "dry" experiments - and the development of transformation stress, which inhibits nucleation and growth. These issues are discussed in the context of our experiments as well as recent observations from natural rocks. ?? 1997 Elsevier Science B.V.

Role of activator protein-1 on the effect of arginine-glycine-aspartic acid containing peptides on transforming growth factor-beta1 promoter activity.

PubMed

Ruiz-Torres, M P; Perez-Rivero, G; Diez-Marques, M L; Griera, M; Ortega, R; Rodriguez-Puyol, M; Rodríguez-Puyol, D

2007-01-01

While arginine-glycine-aspartic acid-based peptidomimetics have been employed for the treatment of cardiovascular disorders and cancer, their use in other contexts remains to be explored. Arginine-glycine-aspartic acid-serine induces Transforming growth factor-beta1 transcription in human mesangial cells, but the molecular mechanisms involved have not been studied extensively. We explored whether this effect could be due to Activator protein-1 activation and studied the potential pathways involved. Addition of arginine-glycine-aspartic acid-serine promoted Activator protein-1 binding to its cognate sequence within the Transforming growth factor-beta1 promoter as well as c-jun and c-fos protein abundance. Moreover, this effect was suppressed by curcumin, a c-Jun N terminal kinase inhibitor, and was absent when the Activator protein-1 cis-regulatory element was deleted. Activator protein-1 binding was dependent on the activity of integrin linked kinase, as transfection with a dominant negative mutant suppressed both Activator protein-1 binding and c-jun and c-fos protein increment. Integrin linked kinase was, in turn, dependent on Phosphoinositol-3 kinase activity. Arginine-glycine-aspartic acid-serine stimulated Phosphoinositol-3 kinase activity, and Transforming growth factor-beta1 promoter activation was abrogated by the use of Phosphoinositol-3 kinase specific inhibitors. In summary, we propose that arginine-glycine-aspartic acid-serine activates Integrin linked kinase via the Phosphoinositol-3 kinase pathway and this leads to activation of c-jun and c-fos and increased Activator protein-1 binding and Transforming growth factor-beta1 promoter activity. These data may contribute to understand the molecular mechanisms involved in the cellular actions of arginine-glycine-aspartic acid-related peptides and enhance their relevance as these products evolve into clinical therapeutic use.

Multilingual Content Extraction Extended with Background Knowledge for Military Intelligence

DTIC Science & Technology

2011-06-01

extended with background knowledge (WordNet [Fel98], YAGO [SKW08]) so that new conclusions (logical inferences) can be drawn. For this purpose theorem...such formalized content is extended with background knowledge (WordNet, YAGO ) so that new conclusions (logical inferences) can be drawn. Our aim is to...External Knowledge Formulas Transformation FOLE MRS to FOLE WordNet OpenCyc ... YAGO Logical Calculation Knowledge Background Knowledge Axioms Background

Stability of pathogenic colony types of Neisseria gonorrhoeae in liquid culture by using the parameters of colonial morphology and deoxyribonucleic acid transformation.

PubMed Central

La Scolea, L J; Dul, M J; Young, F E

1975-01-01

This investigation describes the surveillance of the colonial stability of the pathogenic type 1 from the gonococcal strain F62 to the nonvirulent types 3 and 4 in different liquid media. The maintenance of the colony types was monitored by the parameters of colonial morphology and deoxyribonucleic acid-mediated transformation. During growth in a complex medium, Mueller-Hinton broth, only 46.7% of the gonococcal population remained as type 1 after 12 h. The greatest change in the type 1 colony-forming units correlated with the decline in viable count. The conversion process could not be prevented by the continual maintenance of the gonococcus in logarithmic growth. The frequency of transformation from PRO(minus) (proline) to PRO(plus) was proportional to this decrease in type 1 colony-forming units. In contrast to Mueller-Hinton medium, the chemically defined minimal medium Gonococcal Genetic Medium (GGM) was capable of maintaining approximately 90% of the gonococcal population in the type 1 colonial form after 16 h of growth, despite a decrease in the viable count. Although the percentage of type 1 appeared to remain constant in GGM, the apparent transformation frequency increased approximately 24-fold from 0 to 12 h of growth. GGM appears to stimulate or maintain competence, as evidenced by an eightfold increase in transformation when cells are exposed to deoxyribonucleic acid in GGM as compared to Mueller-Hinton. PMID:809469

Feature Transformation Detection Method with Best Spectral Band Selection Process for Hyper-spectral Imaging

NASA Astrophysics Data System (ADS)

Chen, Hai-Wen; McGurr, Mike; Brickhouse, Mark

2015-11-01

We present a newly developed feature transformation (FT) detection method for hyper-spectral imagery (HSI) sensors. In essence, the FT method, by transforming the original features (spectral bands) to a different feature domain, may considerably increase the statistical separation between the target and background probability density functions, and thus may significantly improve the target detection and identification performance, as evidenced by the test results in this paper. We show that by differentiating the original spectral, one can completely separate targets from the background using a single spectral band, leading to perfect detection results. In addition, we have proposed an automated best spectral band selection process with a double-threshold scheme that can rank the available spectral bands from the best to the worst for target detection. Finally, we have also proposed an automated cross-spectrum fusion process to further improve the detection performance in lower spectral range (<1000 nm) by selecting the best spectral band pair with multivariate analysis. Promising detection performance has been achieved using a small background material signature library for concept-proving, and has then been further evaluated and verified using a real background HSI scene collected by a HYDICE sensor.

Intrinsic noise analysis and stochastic simulation on transforming growth factor beta signal pathway

NASA Astrophysics Data System (ADS)

Wang, Lu; Ouyang, Qi

2010-10-01

A typical biological cell lives in a small volume at room temperature; the noise effect on the cell signal transduction pathway may play an important role in its dynamics. Here, using the transforming growth factor-β signal transduction pathway as an example, we report our stochastic simulations of the dynamics of the pathway and introduce a linear noise approximation method to calculate the transient intrinsic noise of pathway components. We compare the numerical solutions of the linear noise approximation with the statistic results of chemical Langevin equations, and find that they are quantitatively in agreement with the other. When transforming growth factor-β dose decreases to a low level, the time evolution of noise fluctuation of nuclear Smad2—Smad4 complex indicates the abnormal enhancement in the transient signal activation process.

Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

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

Isom, H.C.; Mummaw, J.; Kreider, J.W.

1983-04-30

Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virusmore » 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells.« less

Biochemical transformation of solid carbonaceous material

DOEpatents

Lin, Mow S.; Premuzic, Eugene T.

2001-09-25

A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

Biochemical transformation of coals

DOEpatents

Lin, M.S.; Premuzic, E.T.

1999-03-23

A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed. 7 figs.

The Role of Ect2 Nuclear RhoGEF Activity in Ovarian Cancer Cell Transformation

PubMed Central

Huff, Lauren P.; DeCristo, Molly J.; Trembath, Dimitri; Kuan, Pei Fen; Yim, Margaret; Liu, Jinsong; Cook, Danielle R.; Miller, C. Ryan; Der, Channing J.

2013-01-01

Ect2, a Rho guanine nucleotide exchange factor (RhoGEF), is atypical among RhoGEFs in its predominantly nuclear localization in interphase cells. One current model suggests that Ect2 mislocalization drives cellular transformation by promoting aberrant activation of cytoplasmic Rho family GTPase substrates. However, in ovarian cancers, where Ect2 is both amplified and overexpressed at the mRNA level, we observed that the protein is highly expressed and predominantly nuclear and that nuclear but not cytoplasmic Ect2 increases with advanced disease. Knockdown of Ect2 in ovarian cancer cell lines impaired their anchorage-independent growth without affecting their growth on plastic. Restoration of Ect2 expression rescued the anchorage-independent growth defect, but not if either the DH catalytic domain or the nuclear localization sequences of Ect2 were mutated. These results suggested a novel mechanism whereby Ect2 could drive transformation in ovarian cancer cells by acting as a RhoGEF specifically within the nucleus. Interestingly, Ect2 had an intrinsically distinct GTPase specificity profile in the nucleus versus the cytoplasm. Nuclear Ect2 bound preferentially to Rac1, while cytoplasmic Ect2 bound to RhoA but not Rac. Consistent with nuclear activation of endogenous Rac, Ect2 overexpression was sufficient to recruit Rac effectors to the nucleus, a process that required a functional Ect2 catalytic domain. Furthermore, expression of active nuclearly targeted Rac1 rescued the defect in transformed growth caused by Ect2 knockdown. Our work suggests a novel mechanism of Ect2-driven transformation, identifies subcellular localization as a regulator of GEF specificity, and implicates activation of nuclear Rac1 in cellular transformation. PMID:24386507

Mediation of wound-related Rous sarcoma virus tumorigenesis by TFG (transforming growth factor)-. beta

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

Sieweke, M.H.; Bissell, M.J.; Thompson, N.L.

1990-06-29

In Rous sarcoma virus (RSV)-infected chickens, wounding leads to tumor formation with nearly 100% frequency in tissues that would otherwise remain tumor-free. Identifying molecular mediators of this phenomenon should yield important clues to the mechanisms involved in RSV tumorigenesis. Immunohistochemical staining showed that TGF-{beta} is present locally shortly after wounding, but not in unwounded controls. In addition, subcutaneous administration of recombinant transforming growth factor {beta}1 (TGF-{beta}1) could substitute completely for wounding in tumor induction. A treatment protocol of four doses of 800 nanograms of TGF-{beta} resulted in v-src-expressing tumors with 100% frequency; four doses of only 10 nanograms still ledmore » to tumor formation in 80% of the animals. This effect was specific, as other growth factors with suggested roles in would healing did not elicit the same response. Epidermal growth factor (EGF) or TGF-{alpha} had no effect, and platelet-derived growth factor (PDGF) or insulin-like growth factor-1 (IGF-1) yielded only occasional tumors after longer latency. TGF-{beta} release during the would-healing response may thus be a critical event that creates a conducive environment for RSV tumorigenesis and may act as a cofactor for transformation in this system. 31 refs., 3 figs., 2 tabs.« less

Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22.

PubMed

Gupta, Rajnish A; Sarraf, Pasha; Brockman, Jeffrey A; Shappell, Scott B; Raftery, Laurel A; Willson, Timothy M; DuBois, Raymond N

2003-02-28

Peroxisome proliferator-activated receptor gamma (PPARgamma) and transforming growth factor-beta (TGF-beta) are key regulators of epithelial cell biology. However, the molecular mechanisms by which either pathway induces growth inhibition and differentiation are incompletely understood. We have identified transforming growth factor-simulated clone-22 (TSC-22) as a target gene of both pathways in intestinal epithelial cells. TSC-22 is member of a family of leucine zipper containing transcription factors with repressor activity. Although little is known regarding its function in mammals, the Drosophila homolog of TSC-22, bunched, plays an essential role in fly development. The ability of PPARgamma to induce TSC-22 was not dependent on an intact TGF-beta1 signaling pathway and was specific for the gamma isoform. Localization studies revealed that TSC-22 mRNA is enriched in the postmitotic epithelial compartment of the normal human colon. Cells transfected with wild-type TSC-22 exhibited reduced growth rates and increased levels of p21 compared with vector-transfected cells. Furthermore, transfection with a dominant negative TSC-22 in which both repressor domains were deleted was able to reverse the p21 induction and growth inhibition caused by activation of either the PPARgamma or TGF-beta pathways. These results place TSC-22 as an important downstream component of PPARgamma and TGF-beta signaling during intestinal epithelial cell differentiation.

Role of epidermal growth factor and transforming growth factor α in the developing stomach

PubMed Central

Kelly, E; Newell, S; Brownlee, K; Farmery, S; Cullinane, C; Reid, W; Jackson, P; Gray, S; Primrose, J; Lagopoulos, M

1997-01-01

AIMS—To determine whether epidermal growth factor (EGF) or the related transforming growth factor α (TGFα) may have a role in the developing human stomach; to substantiate the presence of EGF in human liquor in the non-stressed infant and whether EGF in amniotic fluid is maternally or fetally derived.
METHODS—The temporal expression and localisation of EGF, TGFα, and their receptors during fetal and neonatal life were examined in 20 fetal and five infant stomachs. Simultaneously, samples of amniotic fluid and fetal urine from 10 newborn infants were collected and assayed for EGF by radioimmunoassay.
RESULTS—EGF immunoreactivity was not noted in any of the specimens examined. In contrast, TGFα immunoreactivity was shown in mucous cells from 18 weeks of gestation onwards. EGF receptor immunoreactivity was seen on superficial mucous cells in gastric mucosa from 18 weeks of gestation onwards. The median concentration of EGF was 30 and 8.5 pg/ml in amniotic fluid and fetal urine, respectively, suggesting that EGF is not produced by the fetus.
CONCLUSIONS—This study adds weight to the hypothesis that swallowed EGF, probably produced by the amniotic membranes, and locally produced TGFα, may have a role in the growth and maturation of the human stomach.

 Keywords: epidermal growth factor; transforming growth factor α; EGF receptors; stomach PMID:9175944

Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats.

PubMed

Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Liou, Hung-Hsiang; Hsu, Bang-Gee

2014-01-01

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production. Copyright © 2013 Elsevier Ltd. All rights reserved.

v-Src-driven transformation is due to chromosome abnormalities but not Src-mediated growth signaling.

PubMed

Honda, Takuya; Morii, Mariko; Nakayama, Yuji; Suzuki, Ko; Yamaguchi, Noritaka; Yamaguchi, Naoto

2018-01-18

v-Src is the first identified oncogene product and has a strong tyrosine kinase activity. Much of the literature indicates that v-Src expression induces anchorage-independent and infinite cell proliferation through continuous stimulation of growth signaling by v-Src activity. Although all of v-Src-expressing cells are supposed to form transformed colonies, low frequencies of v-Src-induced colony formation have been observed so far. Using cells that exhibit high expression efficiencies of inducible v-Src, we show that v-Src expression causes cell-cycle arrest through p21 up-regulation despite ERK activation. v-Src expression also induces chromosome abnormalities and unexpected suppression of v-Src expression, leading to p21 down-regulation and ERK inactivation. Importantly, among v-Src-suppressed cells, only a limited number of cells gain the ability to re-proliferate and form transformed colonies. Our findings provide the first evidence that v-Src-driven transformation is attributed to chromosome abnormalities, but not continuous stimulation of growth signaling, possibly through stochastic genetic alterations.

Aggregation of the rhizospheric bacterium Azospirillum brasilense in response to oxygen

NASA Astrophysics Data System (ADS)

Abdoun, Hamid; McMillan, Mary; Pereg, Lily

2016-04-01

Azospirillum brasilense spp. have ecological, scientific and agricultural importance. As model plant growth promoting rhizobacteria they interact with a large variety of plants, including important food and cash crops. Azospirillum strains are known for their production of plant growth hormones that enhance root systems and for their ability to fix nitrogen. Azospirillum cells transform in response to environmental cues. The production of exopolysaccharides and cell aggregation during cellular transformation are important steps in the attachment of Azospirillum to roots. We investigate signals that induce cellular transformation and aggregation in the Azospirillum and report on the importance of oxygen to the process of aggregation in this rhizospheric bacterium.

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Science.gov Websites

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Growth kinetics of indium metal atoms on Si(1 1 2) surface

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

Raj, Vidur; Chauhan, Amit Kumar Singh; Gupta, Govind, E-mail: govind@nplindia.org

Graphical abstract: Controlled growth of indium atoms on Si(1 1 2) surface has been carried out systematically and the influence of substrate temperature on the kinetics is analysed under various growth conditions. Temperature induced anomalous layer-to-clusters transformation during thermal desorption has also been reported. - Highlights: • Controlled growth of indium atoms on Si(1 1 2) surface & their thermal stability. • Influence of substrate temperature on the kinetics under various growth conditions. • Temperature induced layer-to-clusters transformation during thermal desorption. - Abstract: The growth kinetics and desorption behavior of indium (In) atoms grown on high index Si(1 1 2)more » surface at different substrate temperatures has been studied. Auger electron spectroscopy analysis revealed that In growth at room temperature (RT) and high substrate temperature (HT) ∼250 °C follows Frank–van der Merve growth mode whereas at temperatures ≥450 °C, In growth evolves through Volmer–Weber growth mode. Thermal desorption studies of RT and 250 °C grown In/Si(1 1 2) systems show temperature induced rearrangement of In atoms over Si(1 1 2) surface leading to clusters to layer transformation. The monolayer and bilayer desorption energies for RT grown In/Si(1 1 2) system are calculated to be 2.5 eV and 1.52 eV, while for HT-250 °C the values are found to be 1.6 eV and 1.3 eV, respectively. This study demonstrates the effect of temperature on growth kinetics as well as on the multilayer/monolayer desorption pathway of In on Si(1 1 2) surface.« less

Effects of Non-Collagenous Proteins, TGF-β1, and PDGF-BB on Viability and Proliferation of Dental Pulp Stem Cells

PubMed Central

Tabatabaei, Fahimeh Sadat

2016-01-01

ABSTRACT Objectives The dentin matrix servers as a reservoir of growth factors, sequestered during dentinogenesis. The aim of this study was to assess the viability and proliferation of dental pulp stem cells in the presence of dentin matrix-derived non-collagenous proteins and two growth factors; platelet-derived growth factor BB and transforming growth factor beta 1. Material and Methods The dental pulp cells were isolated and cultured. The dentin proteins were extracted and purified. The MTT assay was performed for assessment of cell viability and proliferation in the presence of different concentrations of dentin proteins and growth factors during 24 - 72 h post-treatment. Results The cells treated with 250 ng/mL dentin proteins had the best viability and proliferation ability in comparison with other concentrations (P < 0.05). The MTT assay demonstrated that cells cultured with 5 ng/mL platelet-derived growth factor BB had the highest viability at each time point as compared to other groups (P < 0.05). However, in presence of platelet-derived growth factor BB alone and in combination with transforming growth factor beta 1 and dentin proteins (10 ng/mL), significant higher viability was seen at all time points (P < 0.05). The least viability and proliferation at each growth factor concentration was seen in cells treated with combination of transforming growth factor beta 1 and dentin proteins at 72 h (P < 0.05). Conclusions The results indicated that the triple combination of growth factors and matrix-derived non-collagenous proteins (especially at 10 ng/mL concentration) has mitogenic effect on dental pulp stem cells. PMID:27099698

Transgenic mimicry of pathogen attack stimulates growth and secondary metabolite accumulation.

PubMed

Chaudhuri, Kuntal; Das, Sudripta; Bandyopadhyay, Moumita; Zalar, Andreja; Kollmann, Albert; Jha, Sumita; Tepfer, David

2009-02-01

Plant secondary metabolites, including pharmaceuticals, flavorings and aromas, are often produced in response to stress. We used chemical inducers of the pathogen defense response (jasmonic acid, salicylate, killed fungi, oligosaccharides and the fungal elicitor protein, cryptogein) to increase metabolite and biomass production in transformed root cultures of the medicinal plant, Withania somnifera, and the weed, Convolvulus sepium. In an effort to genetically mimic the observed effects of cryptogein, we employed Agrobacterium rhizogenes to insert a synthetic gene encoding cryptogein into the roots of C. sepium, W. somnifera and Tylophora tanakae. This genetic transformation was associated with stimulation in both secondary metabolite production and growth in the first two species, and in growth in the third. In whole plants of Convolvulus arvensis and Arabidopsis thaliana, transformation with the cryptogein gene led, respectively, to increases in the calystegines and certain flavonoids. A similar transgenic mimicry of pathogen attack was previously employed to stimulate resistance to the pathogen and abiotic stress. In the present study of biochemical phenotype, we show that transgenic mimicry is correlated with increased secondary metabolite production in transformed root cultures and whole plants. We propose that natural transformation with genes encoding the production of microbial elicitors could influence interactions between plants and other organisms.

Constitutive expression of thymidylate synthase from LCDV-C induces a transformed phenotype in fish cells.

PubMed

Zhao, Zhe; Shi, Yan; Ke, Fei; Wei, Sun; Gui, Jianfang; Zhang, Qiya

2008-03-01

Thymidylate synthase (TS), an essential enzyme in DNA synthesis and repair, plays a key role in the events of cell cycle regulation and tumor formation. Here, an investigation was presented about subcellular location and biological function of viral TS from lymphocystis disease virus from China (LCDV-C) in fish cells. Fluorescence microscopy revealed that LCDV-C TS was predominantly localized in the cytoplasm in fish cells. Cell cycle analysis demonstrated that LCDV-C TS promoted cell cycle progression into S and G2/M phase in the constitutive expressed cells. As a result, the cells have a faster growth rate compared with the control cells as revealed by cell growth curves. For foci assay, the TS-expressed cells gave rise to foci 4-5 weeks after incubation. Microscopic examination of the TS-induced foci revealed multilayered growth and crisscross morphology characteristic of transformed cells. Moreover, LCDV-C TS predisposed the transfected cells to acquire an anchorage-independent phenotype and could grow in 0.3% soft agar. So the data reveal LCDV-C TS is sufficient to induce a transformed phenotype in fish cells in vitro and exhibits its potential ability in cell transformation. To our knowledge, it is the first report on viral TS sequences associated with transforming activity.

Contrasts between whole-plant and local nutrient levels determine root growth and death in Ailanthus altissima (Simaroubaceae).

PubMed

Hu, Fengqin; Mou, Paul P; Weiner, Jacob; Li, Shuo

2014-05-01

• There is an ongoing debate about the importance of whole-plant control vs. local modular mechanisms for root growth. We conducted a split-root experiment with different patch/background levels of nitrogen to examine whether local root growth and death are controlled by local resource levels or at the whole-plant level.• Three microrhizotrons with 0, 10, and 100 µg N/g growth medium levels (74 g growth medium each) were attached to pots of high or low soil N in which one Ailanthus altissima individual was growing. One fine root was guided into each of the microrhizotrons and photographed every 4 d. Plants were harvested after 28 d; root growth and mortality in the microrhizotrons were recorded. Changes in root length, number of laterals, and interlateral length were determined from the photos and analyzed.• While overall plant growth was influenced by background N level, both patch and background N levels influenced root growth and mortality in patches. Local roots proliferated most when the patch N level was high and background level low, and they proliferated least and showed highest mortality when patch N was low and the background level high.• The fate of roots growing in a patch is influenced by the resource environment of the plant's other roots as well as the resource levels in the patch itself. Thus, the growth and death of roots in patches is determined by both modular and whole-plant mechanisms. © 2014 Botanical Society of America, Inc.

Iterative Correction Scheme Based on Discrete Cosine Transform and L1 Regularization for Fluorescence Molecular Tomography With Background Fluorescence.

PubMed

Zhang, Jiulou; Shi, Junwei; Guang, Huizhi; Zuo, Simin; Liu, Fei; Bai, Jing; Luo, Jianwen

2016-06-01

High-intensity background fluorescence is generally encountered in fluorescence molecular tomography (FMT), because of the accumulation of fluorescent probes in nontarget tissues or the existence of autofluorescence in biological tissues. The reconstruction results are affected or even distorted by the background fluorescence, especially when the distribution of fluorescent targets is relatively sparse. The purpose of this paper is to reduce the negative effect of background fluorescence on FMT reconstruction. After each iteration of the Tikhonov regularization algorithm, 3-D discrete cosine transform is adopted to filter the intermediate results. And then, a sparsity constraint step based on L1 regularization is applied to restrain the energy of the objective function. Phantom experiments with different fluorescence intensities of homogeneous and heterogeneous background are carried out to validate the performance of the proposed scheme. The results show that the reconstruction quality can be improved with the proposed iterative correction scheme. The influence of background fluorescence in FMT can be reduced effectively because of the filtering of the intermediate results, the detail preservation, and noise suppression of L1 regularization.

The Synthesis of L-Alanyl and β-Alanyl Derivatives of 2-Aminoacridone and Their Application in the Detection of Clinically-Important Microorganisms.

PubMed

Cellier, Marie; James, Arthur L; Orenga, Sylvain; Perry, John D; Turnbull, Graeme; Stanforth, Stephen P

2016-01-01

In clinical microbiology the speed with which pathogenic microorganisms may be detected has a direct impact on patient health. One important strategy used in the laboratory is the growth of cultures in the presence of an enzymatic substrate which, once transformed by the appropriate microbial enzyme, generates a detectable colour or fluorescence output. Such substrates have previously been prepared by our group and others and are available as commercial diagnostic kits, however they all suffer from some degree of diffusion when used in a solid growth medium. This diffusion complicates the detection and differentiation of species in polymicrobial cultures and so we sought to improve on our previous work. In this work we have prepared and evaluated a series of novel fluorogenic enzyme substrates based on N-substituted-2-aminoacridones. All of the prepared substrates were found to be suitable for the detection and differentiation of certain microorganisms, however those based on the 2-amino-10-benzylacridone core in particular showed no apparent diffusion when incorporated into solid growth media. On transformation these substrates generated brightly fluorescent colonies that are clearly contrasted with the background medium due to the difference in emission wavelength (λem 445-450 nm for the substrate, λem 550 nm for the product). Here we have shown that our L-alanyl aminopeptidase substrate, 2-(N-L-alanylamino)-10-benzylacridone, is particularly suited to the detection of Gram-negative bacteria, and our β-alanyl aminopeptidase substrate, 2-(N- β-alanylamino)-10-benzylacridone, to the detection of Pseudomonas aeruginosa and Serratia marcescens when grown on solid media incorporating these substrates. The resulting fluorophore shows no apparent diffusion from the colonies of interest, and the enhanced sensitivity offered by fluorescent emission may allow for the detection of these organisms as microcolonies using automated fluorescence microscopy.

Increased expression of transforming growth factor beta s after acute oedematous pancreatitis in rats suggests a role in pancreatic repair.

PubMed Central

Riesle, E; Friess, H; Zhao, L; Wagner, M; Uhl, W; Baczako, K; Gold, L I; Korc, M; Büchler, M W

1997-01-01

BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. AIMS: To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using northern blot analysis and immunohistochemistry, the expression and localisation of TGF beta isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGF beta s was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the pancreatic parenchyma. Images PMID:9155579

Inertial Oscillations and the Galilean Transformation

NASA Astrophysics Data System (ADS)

Korotaev, G. K.

2018-03-01

This paper presents a general solution of shallow-water equations on the f-plane. The solution describes the generation of inertial oscillations by wind-pulse forcing over the background of currents arbitrarily changing in time and space in a homogeneous fluid. It is shown that the existence of such a complete solution of shallow-water equations on the f-plane is related to their invariance with respect to the generalized Galilean transformations. Examples of velocity hodographs of inertial oscillations developing over the background of a narrow jet are presented which explain the diversity in their forms.

Effect of Relaxin Expressing Adenovirus on Scar Remodeling: A Preliminary Study

PubMed Central

Jung, Bok Ki; Lee, Won Jai; Kang, Eunhye; Ahn, Hyo Min; Kim, Yong Oock; Rah, Dong Kyun; Yun, Chae-Ok

2017-01-01

Background Relaxin is a transforming growth factor β1 antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. Methods Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. Results Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. Conclusion Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated. PMID:28913296

Environmental Monitoring of Microbe Metabolic Transformation

NASA Technical Reports Server (NTRS)

Bebout, Brad (Inventor); Fleming, Erich (Inventor); Piccini, Matthew (Inventor); Beasley, Christopher (Inventor); Bebout, Leslie (Inventor)

2013-01-01

Mobile system and method for monitoring environmental parameters involved in growth or metabolic transformation of algae in a liquid. Each of one or more mobile apparati, suspended or partly or wholly submerged in the liquid, includes at least first and second environmental sensors that sense and transmit distinct first and second environmental, growth or transformation parameter values, such as liquid temperature, temperature of gas adjacent to and above the exposed surface, liquid pH, liquid salinity, liquid turbidity, O.sub.2 dissolved in the liquid, CO.sub.2 contained in the liquid, oxidization and reduction potential of the liquid, nutrient concentrations in the liquid, nitrate concentration in the liquid, ammonium concentration in the liquid, bicarbonate concentration in the liquid, phosphate concentration in the liquid, light intensity at the liquid surface, electrical conductivity of the liquid, and a parameter.alpha.(alga) associated with growth stage of the alga, using PAM fluorometry or other suitable parameter measurements.

Modeling solid-state transformations occurring in dissolution testing.

PubMed

Laaksonen, Timo; Aaltonen, Jaakko

2013-04-15

Changes in the solid-state form can occur during dissolution testing of drugs. This can often complicate interpretation of results. Additionally, there can be several mechanisms through which such a change proceeds, e.g. solvent-mediated transformation or crystal growth within the drug material itself. Here, a mathematical model was constructed to study the dissolution testing of a material, which undergoes such changes. The model consisted of two processes: the recrystallization of the drug from a supersaturated liquid state caused by the dissolution of the more soluble solid form and the crystal growth of the stable solid form at the surface of the drug formulation. Comparison to experimental data on theophylline dissolution showed that the results obtained with the model matched real solid-state changes and that it was able to distinguish between cases where the transformation was controlled either by solvent-mediated crystallization or solid-state crystal growth. Copyright © 2013 Elsevier B.V. All rights reserved.

Biofilm-induced bioclogging produces sharp interfaces in hyporheic flow, redox conditions, and microbial community structure

NASA Astrophysics Data System (ADS)

Caruso, Alice; Boano, Fulvio; Ridolfi, Luca; Chopp, David L.; Packman, Aaron

2017-05-01

Riverbed sediments host important biogeochemical processes that play a key role in nutrient dynamics. Sedimentary nutrient transformations are mediated by bacteria in the form of attached biofilms. The influence of microbial metabolic activity on the hydrochemical conditions within the hyporheic zone is poorly understood. We present a hydrobiogeochemical model to assess how the growth of heterotrophic and autotrophic biomass affects the transport and transformation of dissolved nitrogen compounds in bed form-induced hyporheic zones. Coupling between hyporheic exchange, nitrogen metabolism, and biomass growth leads to an equilibrium between permeability reduction and microbial metabolism that yields shallow hyporheic flows in a region with low permeability and high rates of microbial metabolism near the stream-sediment interface. The results show that the bioclogging caused by microbial growth can constrain rates and patterns of hyporheic fluxes and microbial transformation rate in many streams.

Over-expressing the C3 photosynthesis cycle enzyme Sedoheptulose-1-7 Bisphosphatase improves photosynthetic carbon gain and yield under fully open air CO2 fumigation (FACE)

PubMed Central

2011-01-01

Background Biochemical models predict that photosynthesis in C3 plants is most frequently limited by the slower of two processes, the maximum capacity of the enzyme Rubisco to carboxylate RuBP (Vc,max), or the regeneration of RuBP via electron transport (J). At current atmospheric [CO2] levels Rubisco is not saturated; consequently, elevating [CO2] increases the velocity of carboxylation and inhibits the competing oxygenation reaction which is also catalyzed by Rubisco. In the future, leaf photosynthesis (A) should be increasingly limited by RuBP regeneration, as [CO2] is predicted to exceed 550 ppm by 2050. The C3 cycle enzyme sedoheptulose-1,7 bisphosphatase (SBPase, EC 3.1.3.17) has been shown to exert strong metabolic control over RuBP regeneration at light saturation. Results We tested the hypothesis that tobacco transformed to overexpressing SBPase will exhibit greater stimulation of A than wild type (WT) tobacco when grown under field conditions at elevated [CO2] (585 ppm) under fully open air fumigation. Growth under elevated [CO2] stimulated instantaneous A and the diurnal photosynthetic integral (A') more in transformants than WT. There was evidence of photosynthetic acclimation to elevated [CO2] via downregulation of Vc,max in both WT and transformants. Nevertheless, greater carbon assimilation and electron transport rates (J and Jmax) for transformants led to greater yield increases than WT at elevated [CO2] compared to ambient grown plants. Conclusion These results provide proof of concept that increasing content and activity of a single photosynthesis enzyme can enhance carbon assimilation and yield of C3 crops grown at [CO2] expected by the middle of the 21st century. PMID:21884586

Acetylation at lysine 346 controls the transforming activity of the HTLV-1 Tax oncoprotein in the Rat-1 fibroblast model

PubMed Central

2013-01-01

Background Transformation by the Tax oncoprotein of the human T cell leukemia virus type 1 (HTLV-1) is governed by actions on cellular regulatory signals, including modulation of specific cellular gene expression via activation of signaling pathways, acceleration of cell cycle progression via stimulation of cyclin-dependent kinase activity leading to retinoblastoma protein (pRb) hyperphosphorylation and perturbation of survival signals. These actions control early steps in T cell transformation and development of Adult T cell leukemia (ATL), an aggressive malignancy of HTLV-1 infected T lymphocytes. Post-translational modifications of Tax by phosphorylation, ubiquitination, sumoylation and acetylation have been implicated in Tax-mediated activation of the NF-κB pathway, a key function associated with Tax transforming potential. Results In this study, we demonstrate that acetylation at lysine K346 in the carboxy-terminal domain of Tax is modulated in the Tax nuclear bodies by the acetyltransferase p300 and the deacetylases HDAC5/7 and controls phosphorylation of the tumor suppressor pRb by Tax-cyclin D3-CDK4-p21CIP complexes. This property correlates with the inability of the acetylation deficient K346R mutant, but not the acetylation mimetic K346Q mutant, to promote anchorage-independent growth of Rat-1 fibroblasts. By contrast, acetylation at lysine K346 had no effects on the ability of Tax carboxy-terminal PDZ-binding domain to interact with the tumor suppressor hDLG. Conclusions The identification of the acetyltransferase p300 and the deacetylase HDAC7 as enzymes modulating Tax acetylation points to new therapeutic targets for the treatment of HTLV-1 infected patients at risk of developing ATL. PMID:23880157

High performance microbiological transformation of L-tyrosine to L-dopa by Yarrowia lipolytica NRRL-143

PubMed Central

Ali, Sikander; Shultz, Jeffry L; Ikram-ul-Haq

2007-01-01

Background The 3,4-dihydroxy phenyl L-alanine (L-dopa) is a drug of choice for Parkinson's disease, controlling changes in energy metabolism enzymes of the myocardium following neurogenic injury. Aspergillus oryzae is commonly used for L-dopa production; however, potential improvements in ease of handling, growth rate and environmental impact have led to an interest in exploiting alternative yeasts. The two important elements required for L-dopa production are intracellular tyrosinases (thus pre-grown yeast cells are required for the transformation of L-tyrosine to L-dopa) and L-ascorbate, which acts as a reducing agent. Results Pre-grown cells of Yarrowia lipolytica NRRL-143 were used for the microbiological transformation of L-tyrosine to L-dopa. Different diatomite concentrations (0.5–3.0 mg/ml) were added to the acidic (pH 3.5) reaction mixture. Maximum L-dopa biosynthesis (2.96 mg/ml L-dopa from 2.68 mg/ml L-tyrosine) was obtained when 2.0 mg/ml diatomite was added 15 min after the start of the reaction. After optimizing reaction time (30 min), and yeast cell concentration (2.5 mg/ml), an overall 12.5 fold higher L-dopa production rate was observed when compared to the control. Significant enhancements in Yp/s, Qs and qs over the control were observed. Conclusion Diatomite (2.0 mg/ml) addition 15 min after reaction commencement improved microbiological transformation of L-tyrosine to L-dopa (3.48 mg/ml; p ≤ 0.05) by Y. lipolytica NRRL-143. A 35% higher substrate conversion rate was achieved when compared to the control. PMID:17705832

Use of ex vitro composite plants to study the interaction of cowpea (Vigna unguiculata L.) with the root parasitic angiosperm Striga gesnerioides

PubMed Central

2012-01-01

Background Cowpea (Vigna unguiculata L.) is an important grain and forage legume grown throughout sub-Saharan Africa primarily by subsistence farmers on poor, drought prone soils. Genetic improvement of the crop is being actively pursued and numerous functional genomics studies are underway aimed at characterizing gene controlling key agronomic characteristics for disease and pest resistances. Unfortunately, similar to other legumes, efficient plant transformation technology is a rate-limiting step in analysis of gene function in cowpea. Results Here we describe an optimized protocol for the rapid generation of transformed hairy roots on ex vitro composite plants of cowpea using Agrobacterium rhizogenes. We further demonstrate the applicability of cowpea composite plants to study gene expression involved in the resistance response of the plant roots to attack by the root parasitic weed, Striga gesnerioides. The utility of the new system and critical parameters of the method are described and discussed herein. Conclusions Cowpea composite plants offer a rapid alternative to methods requiring stable transformation and whole plant regeneration for studying gene expression in resistance or susceptibility responses to parasitic weeds. Their use can likely be readily adapted to look at the effects of both ectopic gene overexpression as well as gene knockdown of root associated defense responses and to the study of a broader range of root associated physiological and aphysiological processes including root growth and differentiation as well as interactions with other root pests, parasites, and symbionts. PMID:22741546

PGASO: A synthetic biology tool for engineering a cellulolytic yeast

PubMed Central

2012-01-01

Background To achieve an economical cellulosic ethanol production, a host that can do both cellulosic saccharification and ethanol fermentation is desirable. However, to engineer a non-cellulolytic yeast to be such a host requires synthetic biology techniques to transform multiple enzyme genes into its genome. Results A technique, named Promoter-based Gene Assembly and Simultaneous Overexpression (PGASO), that employs overlapping oligonucleotides for recombinatorial assembly of gene cassettes with individual promoters, was developed. PGASO was applied to engineer Kluyveromycesmarxianus KY3, which is a thermo- and toxin-tolerant yeast. We obtained a recombinant strain, called KR5, that is capable of simultaneously expressing exoglucanase and endoglucanase (both of Trichodermareesei), a beta-glucosidase (from a cow rumen fungus), a neomycin phosphotransferase, and a green fluorescent protein. High transformation efficiency and accuracy were achieved as ~63% of the transformants was confirmed to be correct. KR5 can utilize beta-glycan, cellobiose or CMC as the sole carbon source for growth and can directly convert cellobiose and beta-glycan to ethanol. Conclusions This study provides the first example of multi-gene assembly in a single step in a yeast species other than Saccharomyces cerevisiae. We successfully engineered a yeast host with a five-gene cassette assembly and the new host is capable of co-expressing three types of cellulase genes. Our study shows that PGASO is an efficient tool for simultaneous expression of multiple enzymes in the kefir yeast KY3 and that KY3 can serve as a host for developing synthetic biology tools. PMID:22839502

Effect of Isothermal Temperature on Growth Behavior of Nanostructured Bainite in Laser Cladded Coatings

PubMed Central

Guo, Yanbing; Yao, Chengwu; Feng, Kai; Li, Zhuguo; Chu, Paul K.; Wu, Yixiong

2017-01-01

The growth and propagation behavior of austenite-to-bainite isothermal transformation in laser-cladded, Si-rich, and Fe-based coatings is investigated. The crystallographic features, orientation relationship at different isothermal temperatures, and the morphology of the nanostructured bainite are determined. The Nishiyama-Wassermann type orientation relationship is observed at a high temperature and at a low temperature, and mixed Nishiyama-Wassermann and Kurdjumov-Sach mechanisms are seen. The growth direction is investigated by the partial dislocation theory and an extrapolated model based on the repeated formation of lenticular-shaped subunits and pile-up along the close-packed directions of the close-packed planes. The variants of the bainite growth directions would be more selective at the high transformation temperature. PMID:28773161

Role of Vascular Endothelial Growth Factor and Transforming Growth Factor-β2 in Rat Bone Tissue after Bone Fracture and Placement of Titanium Implants with Bioactive Bioresorbable Coatings.

PubMed

Kalinichenko, S G; Matveeva, N Yu; Kostiv, R E; Puz', A V

2017-03-01

The study established enhanced expression of vascular endothelial growth factor (VEGF) in the subpopulation of osteoblasts located in the regeneration region of femoral bone fracture near the titanium implants with bioactive calcium phosphate and hydroxyapatite coatings and suppressed activity of transforming growth factor-β2 (TGF-β2) in chondroblasts during the two weeks after surgery. In the delayed posttraumatic period, the distribution of TGF-β2 inversely related to its maximal activity. The data revealed the up-regulating effect of bioresorbable coatings on expression of VEGF and TGF-β2 and their implication in the control over various stages of reparative osteogenesis.

Clean Energy Policies Analysis: The Role of Policy in Clean Energy Market Transformation (Presentation)

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

Doris, E.

2010-11-01

This presentation was written and presented by Elizabeth Doris (NREL) at the November 17 TAP Webinar to provide background detail about how state policies are transforming the clean energy market in different regions of the country.

Reactivation of Embryonic Nodal Signaling is Associated with Tumor Progression and Promotes the Growth of Prostate Cancer Cells

PubMed Central

Lawrence, Mitchell G.; Margaryan, Naira V.; Loessner, Daniela; Collins, Angus; Kerr, Kris M.; Turner, Megan; Seftor, Elisabeth A.; Stephens, Carson R.; Lai, John; BioResource, APC; Postovit, Lynne-Marie; Clements, Judith A.; Hendrix, Mary J.C.

2011-01-01

Background Nodal is a member of the Transforming Growth Factor β (TGFβ) superfamily that directs embryonic patterning and promotes the plasticity and tumorigenicity of tumor cells, but its role in the prostate is unknown. The goal of this study was to characterize the expression and function of Nodal in prostate cancer and determine whether, like other TGFβ ligands, it modulates androgen receptor (AR) activity. Methods Nodal expression was investigated using immunohistochemistry of tissue microarrays and Western blots of prostate cell lines. The functional role of Nodal was examined using Matrigel and soft agar growth assays. Cross-talk between Nodal and AR signaling was assessed with luciferase reporter assays and expression of endogenous androgen regulated genes. Results Significantly increased Nodal expression was observed in cancer compared with benign prostate specimens. Nodal was only expressed by DU145 and PC3 cells. All cell lines expressed Nodal’s co-receptor, Cripto-1, but lacked Lefty, a critical negative regulator of Nodal signaling. Recombinant human Nodal triggered downstream Smad2 phosphorylation in DU145 and LNCaP cells, and stable transfection of pre-pro-Nodal enhanced the growth of LNCaP cells in Matrigel and soft agar. Finally, Nodal attenuated AR signaling, reducing the activity of a PSA promoter construct in luciferase assays and down-regulating the endogenous expression of androgen regulated genes. Conclusions An aberrant Nodal signaling pathway is re-expressed and functionally active in prostate cancer cells. PMID:21656830

Transformation of PRT6 RNAi construct into tomato (Solanum lycopersicum) cv. Micro-Tom

NASA Astrophysics Data System (ADS)

Suka, Intan Elya; Chew, Bee Lynn; Goh, Hoe-Han; Isa, Nurulhikma Md

2018-04-01

PROTEOLYSIS 6 plays major role in the N-end rule pathway as N-recognin which functions as E3 ligase enzyme. It mediates ubiquitin processes that lead to degradation of unstable substrate protein. The aim of the current study is to transform the PRT6 gene into tomato (Solanum lycopersicum) from the cultivar Micro-Tom and to investigate its function in regulating ripening in tomato fruits. The PRT6_RNAi construct was successfully transformed into Agrobacterium C58 via heat shock method and transformed into seven days old cotyledon explants. Factors affecting transformation efficiency such as co-cultivation time and type of plant growth regulator combination were evaluated. Results from this study found that pre-cultured cotyledons from seven days old seedlings incubated for 2 days in co-cultivation medium increased shoot regeneration. Plant growth hormones zeatin combine with auxin produced a higher number of callus formation but lower shoot proliferation and transformation frequency compared to treatments of single plant hormone in the selection medium. Polymerase chain reaction (PCR) was performed on the regenerated shoots to confirm the integration of PRT6 fragment into the genome of transgenic plants. Based on PCR analysis, all putative shoots were positive transformants.

In-situ laser ultrasonic measurement of the hcp to bcc transformation in commercially pure titanium

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

Shinbine, A., E-mail: alyssa.shinbine@gmail.com; Garcin, T.; Sinclair, C.

2016-07-15

Using a novel in-situ laser ultrasonic technique, the evolution of longitudinal velocity was used to measure the α − β transformation during cyclic heating and cooling in commercially pure titanium. In order to quantify the transformation kinetics, it is shown that changes in texture can not be ignored. This is particularly important in the case of titanium where significant grain growth occurs in the β-phase leading to the ultrasonic wave sampling a decreasing number of grains on each thermal treatment cycle. Electron backscatter diffraction measurements made postmortem in the region where the ultrasonic pulse traveled were used to obtain anmore » estimate of such local texture and grain size changes. An analysis technique for including the anisotropy of wave velocity depending on local texture is presented and shown to give self consistent results for the transformation kinetics. - Highlights: • Laser ultrasound and EBSD interpret the hcp/bcc phase transformation in cp-Ti. • Grain growth and texture produced variation in velocity during similar treatments. • Texture was deconvoluted from phase addition to obtain transformation kinetics.« less

Isolation and identification of Paenibacillus sp. FM-6, involved in the biotransformation of albendazole.

PubMed

Jin, Lei; Zhang, Xiaojun; Sun, Xiumei; Shi, Hui; Li, Tiejun

2014-10-01

A strain, designated as FM-6, was isolated from fish. Based on the results of phenotypic, physiological characteristics, genotypic and phylogenetic analysis, strain FM-6 was finally identified as Paenibacillus sp. When albendazole was provided as the sole carbon source, strain FM-6 could grow and transform albendazole. About 82.7 % albendazole (50 mg/L) was transformed by strain FM-6 after 5 days incubation at 30 °C, 160 rpm. With HPLC-MS method, the transforming product of albendazole was researched. Based on the molecular weight and the retention time, product was identified as albendazole sulfoxide and the transforming pathway of albendazole by strain FM-6 was proposed finally. The optimum temperature and pH for the bacterium growth and albendazole transformation by strain FM-6 were both 30 °C and 7.0. Moreover, the optimum concentration of albendazole for the bacterium growth was 50 mg/L. Coupled with practical production, 50 mg/L was the optimum concentration of albendazole transformation for strain FM-6. This study highlights an important potential use of strain FM-6 for producing albendazole sulfoxide.

Crystal grain growth at the α -uranium phase transformation in praseodymium

NASA Astrophysics Data System (ADS)

Cunningham, Nicholas C.; Velisavljevic, Nenad; Vohra, Yogesh K.

2005-01-01

Structural phase transformations under pressure are examined in praseodymium metal for the range 0-40GPa at ambient temperature. Pressure was generated with a diamond-anvil cell, and data were collected using high-resolution synchrotron x-ray diffraction and the image plate technique. The structural sequence double hexagonal close packed (dhcp)→face centered cubic (fcc)→distorted-fcc (d-fcc)→ α -uranium (α-U) is observed with increasing pressure. Rietveld refinement of all crystallographic phases provided confirmation of the hR24 structure for the d-fcc phase while the previously reported monoclinic phase between the d-fcc and the α-U phase was not confirmed. We observe dramatic crystal grain growth during the volume collapse concurrent with the symmetry-lowering transition to the α-U structure. No preferred orientation axis is observed, and the formation process for these large grains is expected to be via a nucleation and growth mechanism. An analogous effect in rare earth metal cerium suggests that the grain growth during transformation to the α-U structure is a common occurrence in f -electron metals at high pressures.

Impact of asymmetric martensite and austenite nucleation and growth behavior on the phase stability and hysteresis of freestanding shape-memory nanoparticles

NASA Astrophysics Data System (ADS)

Ko, Won-Seok; Grabowski, Blazej; Neugebauer, Jörg

2018-03-01

Martensitic transformations in nanoscaled shape-memory alloys exhibit characteristic features absent for the bulk counterparts. Detailed understanding is required for applications in micro- and nanoelectromechanical systems, and experimental limitations render atomistic simulation an important complementary approach. Using a recently developed, accurate potential we investigate the phase transformation in freestanding Ni-Ti shape-memory nanoparticles with molecular-dynamics simulations. The results confirm that the decrease in the transformation temperature with decreasing particle size is correlated with an overstabilization of the austenitic surface energy over the martensitic surface energy. However, a detailed atomistic analysis of the nucleation and growth behavior reveals an unexpected difference in the mechanisms determining the austenite finish and martensite start temperature. While the austenite finish temperature is directly affected by a contribution of the surface energy difference, the martensite start temperature is mostly affected by the transformation strain, contrary to general expectations. This insight not only explains the reduced transformation temperature but also the reduced thermal hysteresis in freestanding nanoparticles.

Increasing the quantitative credibility of open-path FT-IR spectroscopic data with focus on several properties of the background spectrum

USDA-ARS?s Scientific Manuscript database

The choice of the type of background spectrum affects the credibility of open-path Fourier transform infrared (OP/FT-IR) spectroscopic data, and consequently the quality of data analysis. We systematically investigated several properties of the background spectrum. The results show that a short-pa...

In Situ Monitoring and Modeling of the Solution-Mediated Polymorphic Transformation of Rifampicin: From Form II to Form I.

PubMed

Guo, Nannan; Hou, Baohong; Wang, Na; Xiao, Yan; Huang, Jingjing; Guo, Yanmei; Zong, Shuyi; Hao, Hongxun

2018-01-01

In this article, the solution-mediated polymorphic transformation of rifampicin was investigated and simulated in 3 solvents at 30°C. The solid-state form I and form II of rifampicin was characterized by powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR). To explore the relative stability, solubility data of form I and form II of rifampicin in butan-1-ol were determined using a dynamical method. In addition, Raman spectroscopy and focused beam reflectance measurement were used to in situ monitor the transformation of rifampicin from form II to form I. The liquid state concentration of rifampicin was measured by UV spectroscopic method. To investigate the effect of solvent on transformation, the transformation experiments were carried out in 3 solvents. Furthermore, a mathematical model was built to describe the kinetics of dissolution, nucleation, and growth processes during transformation by using experimental data. By combination of experimental and simulation results, it was found that the transformation process of rifampicin is controlled by dissolution of form II in heptane, whereas the transformation in hexane and octane was firstly controlled by dissolution of solid-state form and then controlled by growth of form I. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth.

PubMed

Soikkeli, Johanna; Podlasz, Piotr; Yin, Miao; Nummela, Pirjo; Jahkola, Tiina; Virolainen, Susanna; Krogerus, Leena; Heikkilä, Päivi; von Smitten, Karl; Saksela, Olli; Hölttä, Erkki

2010-07-01

Although the outgrowth of micrometastases into macrometastases is the rate-limiting step in metastatic progression and the main determinant of cancer fatality, the molecular mechanisms involved have been little studied. Here, we compared the gene expression profiles of melanoma lymph node micro- and macrometastases and unexpectedly found no common up-regulation of any single growth factor/cytokine, except for the cytokine-like SPP1. Importantly, metastatic outgrowth was found to be consistently associated with activation of the transforming growth factor-beta signaling pathway (confirmed by phospho-SMAD2 staining) and concerted up-regulation of POSTN, FN1, COL-I, and VCAN genes-all inducible by transforming growth factor-beta. The encoded extracellular matrix proteins were found to together form intricate fibrillar networks around tumor cell nests in melanoma and breast cancer metastases from various organs. Functional analyses suggested that these newly synthesized protein networks regulate adhesion, migration, and growth of tumor cells, fibroblasts, and endothelial cells. POSTN acted as an anti-adhesive molecule counteracting the adhesive functions of FN1 and COL-I. Further, cellular FN and POSTN were specifically overexpressed in the newly forming/formed tumor blood vessels. Transforming growth factor-beta receptors and the metastasis-related matrix proteins, POSTN and FN1, in particular, may thus provide attractive targets for development of new therapies against disseminated melanoma, breast cancer, and possibly other tumors, by affecting key processes of metastasis: tumor/stromal cell migration, growth, and angiogenesis.

Productive interaction between transmembrane mutants of the bovine papillomavirus E5 protein and the platelet-derived growth factor beta receptor.

PubMed

Lai, Char-Chang; Edwards, Anne P B; DiMaio, Daniel

2005-02-01

The bovine papillomavirus E5 protein is a 44-amino-acid transmembrane protein that transforms cells by binding to the transmembrane region of the cellular platelet-derived growth factor (PDGF) beta receptor, resulting in sustained receptor signaling. However, there are published reports that certain mutants with amino acid substitutions in the membrane-spanning segment of the E5 protein transform cells without activating the PDGF beta receptor. We re-examined several of these transmembrane mutants, and here we present five lines of evidence that these mutants do in fact activate the PDGF beta receptor, resulting in cellular signaling and transformation.

Crystalline phase transformation of colloidal cadmium sulfide nanocrystals

NASA Astrophysics Data System (ADS)

Ghali, M.; Eissa, A. M.; Mosaad, M. M.

2017-03-01

In this paper, we give a microscopic view concerning influence of the growth conditions on the physical properties of nanocrystals (NCs) thin films made of CdS, prepared using chemical bath deposition CBD technique. We show a crystalline phase transformation of CdS NCs from hexagonal wurtzite (W) structure to cubic zincblende (ZB) when the growth conditions change, particularly the solution pH values. This effect was confirmed using X-ray diffraction (XRD), transmission electron microscopy (TEM), optical absorption and photoluminescence (PL) measurements. The optical absorption spectra allow calculation of the bandgap value, Eg, where significant increase ˜200 meV in the CdS bandgap when transforming from Hexagonal to Cubic phase was found.

Urban transformation of a metropolis and its environmental impacts: a case study in Shanghai.

PubMed

Tian, Zhan; Cao, Guiying; Shi, Jun; McCallum, Ian; Cui, Linli; Fan, Dongli; Li, Xinhu

2012-06-01

The aim of this paper is to understand the sustainability of urban spatial transformation in the process of rapid urbanization, and calls for future research on the demographic and economic dimensions of climate change. Shanghai towards its transformation to a metropolis has experienced vast socioeconomic and ecological change and calls for future research on the impacts of demographic and economic dimensions on climate change. We look at the major questions (1) to explore economic and demographic growth, land use and land-cover changes in the context of rapid economic and city growth, and (2) to analyze how the demography and economic growth have been associated with the local air temperature and vegetation. We examine urban growth, land use and land-cover changes in the context of rapid economic development and urbanization. We assess the impact of urban expansion on local air temperature and vegetation. The analysis is based on time series data of land use, normalized difference vegetation index (NDVI), and meteorological, demographic and economic data. The results indicate that urban growth has been driven by mass immigration; as a consequence of economic growth and urban expansion, a large amount of farmland has been converted to paved road and residential buildings. Furthermore, the difference between air temperature in urban and exurban areas has increased rapidly. The decrease of high mean annual NDVI has mainly occurred around the dense urban areas.

Transformational Leadership in the Era of Change

DTIC Science & Technology

2003-05-22

16 1 CHAPTER I: INTRODUCTION AND BACKGROUND We are about leadership ; it is our stock in trade, and it is what makes us different. We take soldiers who... Northouse , another leading author on leadership styles, also states “transformational leadership is a process that changes and transforms individuals...Lawrence Erlbaum Associates, 1998), 3. 9 B. Bass, 4. 10 Paul Northouse , Leadership : Theory and Practice (Thousand Oaks, CA: Sage Publications, 2001

Deregulation of cell growth and malignant transformation.

PubMed

Sulić, Sanda; Panić, Linda; Dikić, Ivan; Volarević, Sinisa

2005-08-01

Cell growth and cell division are fundamental aspects of cell behavior in all organisms. Recent insights from many model organisms have shed light on the molecular mechanisms that control cell growth and cell division. A significant body of evidence has now been accumulated, showing a direct link between deregulation of components of cell cycle machinery and cancer. In addition, defects in one or more steps that control growth are important for malignant transformation, as many tumor suppressors and proto-oncogenes have been found to regulate cell growth. The importance of cell growth in tumor development is further supported by the discovery that rapamycin, an effective anticancer drug, inhibits a key regulator of protein synthetic machinery and cell growth, mammalian target of rapamycin (mTOR). In most cases, cell growth and cell division are coupled, thereby maintaining cell size within physiological limits. We believe that, in a long-term perspective, understanding how these two processes are coordinated in vivo and how their interplay is deregulated in a number of diseases, including cancer, may have a direct impact on the efficiency of modern therapeutics.

The molecular and cellular response of normal and progressed human bronchial epithelial cells to HZE particles

NASA Astrophysics Data System (ADS)

Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Larsen, Jill

We have used a model of non-oncogenically immortalized normal human bronchial epithelial cells to determine the response of such cells to particles found outside the protection of the earth’s electromagnetic field. We have identified an enhanced frequency of cellular transformation, as measured by growth in soft agar, for both 56Fe and 28Si (1 GeV/n) that is maximal (4-6 fold) at 0.25 Gy and 0.40 Gy, respectively. At 4 months post-irradiation 38 individual soft agar clones were isolated. These clones were characterized extensively for cellular and molecular changes. Gene expression analysis suggested that these clones had down-regulated several genes associated with anti-oxidant pathways including GLS2, GPX1 and 4, SOD2, PIG3, and NQO1 amongst others. As a result, many of these transformed clones were exposed to high levels of intracellular radical oxygen species (ROS), although there appeared not to be any enhanced mitochondrial ROS. DNA repair pathways associated with ATM/ATR signaling were also upregulated. However, these transformants do not develop into tumors when injected into immune-compromised mice, suggesting that they have not progressed sufficiently to become oncogenic. Therefore we chose 6 soft agar clones for continuous culture for an additional 14 months. Amongst the 6 clones, only one clone showed any significant change in phenotype. Clone 3kt-ff.2a, propagated for 18 months, were 2-fold more radioresistant, had a shortened doubling time and the background rate of transformation more than doubled. Furthermore, the morphology of transformed clones changed. Clones from this culture are being compared to the original clone as well as the parental HBEC3KT and will be injected into immune-compromised mice for oncogenic potential. Oncogenically progressed HBECs, HBEC3KT cells that overexpress a mutant RAS gene and where p53 has been knocked down, designated HBEC3KTR53, responded quite differently to HZE particle exposure. First, these cells are more radioresistant to all radiations used when compared to the parental cell line HBEC3KT. Furthermore, within days of their exposure to low and high LET radiations they exhibit enhanced cellular transformation over the parental cells. Moreover, HZE radiations are many fold more effective at initiating cellular transformation. Gene expression analysis identified several pathways that support oncogenic growth as overrepresented in the progressed cells. With continual culture some clones undergo epithelial to mesenchymal transition, change morphology and express markers associated with EMT. And, at least one clone is oncogenic forming highly aggressive tumors in an immune compromised mouse strain. It is important to note that HBEC3KTR53 cells will not form tumors in mice, however, this irradiated clone has moved through the multi-step process of carcinogenesis. We are now examining the molecular alterations that led to oncogenesis in this clone.

Physicochemical effects on sulfite transformation in a lipid-rich Chlorella sp. strain

NASA Astrophysics Data System (ADS)

Liang, Fang; Wen, Xiaobin; Luo, Liming; Geng, Yahong; Li, Yeguang

2014-11-01

SO2 is very rapidly hydrated to sulfurous acid in water solution at pH value above 6.0, whereby sulfite is yielded from the disassociation of protons. We aimed to improve the sulfite transformation efficiency and provide a basis for the direct utilization of SO2 from flue gas by a microalgal suspension. Chlorella sp. XQ-20044 was cultured in a medium with 20 mmol/L sodium sulfite under different physicochemical conditions. Under light conditions, sulfite concentration in the algal suspension reduced linearly over time, and was completely converted into sulfate within 8 h. The highest sulfite transformation rate (3.25 mmol/(L·h)) was obtained under the following conditions: 35°C, light intensity of 300 μmol/(m2·s), NaHCO3 concentration of 6 g/L, initial cell density (OD540) of 0.8 and pH of 9-10. There was a positive correlation between sulfite transformation rate and the growth of Chlorella, with the conditions favorable to algal growth giving better sulfite transformation. Although oxygen in the air plays a role in the transformation of SO2- 3 to SO2- 4, the transformation is mainly dependent on the metabolic activity of algal cells. Chlorella sp. XQ-20044 is capable of tolerating high sulfite concentration, and can utilize sulfite as the sole sulfur source for maintaining healthy growth. We found that sulfite ≤20 mmol/L had no obvious effect on the total lipid content and fatty acid profiles of the algae. Thus, the results suggest it is feasible to use flue gas for the mass production of feedstock for biodiesel using Chlorella sp. XQ-20044, without preliminary removal of SO2, assuming there is adequate control of the pH.

High-pressure deformation of calcite marble and its transformation to aragonite under non-hydrostatic conditions

USGS Publications Warehouse

Hacker, B.R.; Kirby, S.H.

1993-01-01

We conducted deformation experiments on Carrara marble in the aragonite and calcite stability fields to observe the synkinematic transformation of calcite to aragonite, and to identify any relationships between transformation and deformation or sample strength. Deformation-induced microstructures in calcite crystals varied most significantly with temperature, ranging from limited slip and twinning at 400??C, limited recrystallization at 500??C, widespread recrystallization at 600 and 700??C, to grain growth at 800-900??C. Variations in confining pressure from 0.3 to 2.0 GPa have no apparent effect on calcite deformation microstructures. Aragonite grew in 10-6-10-7 s-1strain rate tests conducted for 18-524 h at confining pressures of 1.7-2.0 GPa and temperatures of 500-600??C. As in our previously reported hydrostatic experiments on this same transformation, the aragonite nucleated on calcite grain boundaries. The extent of transformation varied from a few percent conversion near pistons at 400??C, 2.0 GPa and 10-4 s-1 strain rate in a 0.8 h long experiment, to 98% transformation in a 21-day test at a strain rate of 10-7 s-7, a temperature of 600??C and a pressure of 2.0 GPa. At 500??C, porphyroblastic 100-200 ??m aragonite crystals grew at a rate faster than 8 ?? 10-1m s-1. At 600??C, the growth of aragonite neoblasts was slower, ???6 ?? 10-1 m s -1, and formed 'glove-and-finger' cellularprecipitation-like textures identical to those observed in hydrostatic experiments. The transformation to aragonite is not accompanied by a shear instability or anisotropic aragonite growth, consistent with its relatively small volume change and latent heat in comparison with compounds that do display those features. ?? 1993.

Doctoral Education and Transformative Consumer Research

ERIC Educational Resources Information Center

Mari, Carlo

2008-01-01

This article examines why and how transformative consumer research (TCR) can become a relevant perspective in doctoral programs. The article draws selectively from studies published in consumer behavior, marketing, and marketing education that theoretically or empirically address this topic. It discusses the meaning and background of TCR together…

Growth of organic crystals via attachment and transformation of nanoscopic precursors

NASA Astrophysics Data System (ADS)

Jiang, Yuan; Kellermeier, Matthias; Gebaue, Denis; Lu, Zihao; Rosenberg, Rose; Moise, Adrian; Przybylski, Michael; Cölfen, Helmut

2017-06-01

A key requirement for the understanding of crystal growth is to detect how new layers form and grow at the nanoscale. Multistage crystallization pathways involving liquid-like, amorphous or metastable crystalline precursors have been predicted by theoretical work and have been observed experimentally. Nevertheless, there is no clear evidence that any of these precursors can also be relevant for the growth of crystals of organic compounds. Herein, we present a new growth mode for crystals of DL-glutamic acid monohydrate that proceeds through the attachment of preformed nanoscopic species from solution, their subsequent decrease in height at the surface and final transformation into crystalline 2D nuclei that eventually build new molecular layers by further monomer incorporation. This alternative mechanism provides a direct proof for the existence of multistage pathways in the crystallization of molecular compounds and the relevance of precursor units larger than the monomeric constituents in the actual stage of growth.

14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1.

PubMed

Hong, Hye-Young; Jeon, Woo-Kwang; Bae, Eun-Jin; Kim, Shin-Tae; Lee, Ho-Jae; Kim, Seong-Jin; Kim, Byung-Chul

2010-03-01

The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the effects of 14-3-3 zeta and 14-3-3 sigma on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-beta1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-beta1-mediated growth inhibition displayed increased expression of 14-3-3 zeta and decreased expression of 14-3-3 sigma compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 sigma or 14-3-3 zeta, we showed that 14-3-3 sigma is required for TGF-beta1-mediated growth inhibition whereas 14-3-3 zeta negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 zeta increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-beta1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 zeta phosphorylation sites in Smad3 markedly reduced the 14-3-3 zeta-mediated inhibition of TGF-beta1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3 zeta in the suppression of TGF-beta1-mediated growth. Taken together, our findings indicate that dysregulation of 14-3-3 sigma or 14-3-3 zeta contributes to TGF-beta1 resistance in cancer cells.

Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts

NASA Technical Reports Server (NTRS)

Ji, C.; Chen, Y.; McCarthy, T. L.; Centrella, M.

1999-01-01

Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

Estimation and Simulation of Slow Crack Growth Parameters from Constant Stress Rate Data

NASA Technical Reports Server (NTRS)

Salem, Jonathan A.; Weaver, Aaron S.

2003-01-01

Closed form, approximate functions for estimating the variances and degrees-of-freedom associated with the slow crack growth parameters n, D, B, and A(sup *) as measured using constant stress rate ('dynamic fatigue') testing were derived by using propagation of errors. Estimates made with the resulting functions and slow crack growth data for a sapphire window were compared to the results of Monte Carlo simulations. The functions for estimation of the variances of the parameters were derived both with and without logarithmic transformation of the initial slow crack growth equations. The transformation was performed to make the functions both more linear and more normal. Comparison of the Monte Carlo results and the closed form expressions derived with propagation of errors indicated that linearization is not required for good estimates of the variances of parameters n and D by the propagation of errors method. However, good estimates variances of the parameters B and A(sup *) could only be made when the starting slow crack growth equation was transformed and the coefficients of variation of the input parameters were not too large. This was partially a result of the skewered distributions of B and A(sup *). Parametric variation of the input parameters was used to determine an acceptable range for using closed form approximate equations derived from propagation of errors.

B-Transform and Its Application to a Fish-Hyacinth Model

ERIC Educational Resources Information Center

Oyelami, B. O.; Ale, S. O.

2002-01-01

A new transform proposed by Oyelami and Ale for impulsive systems is applied to an impulsive fish-hyacinth model. A biological policy regarding the growth of the fish and the hyacinth populations is formulated.

JS-K, a Nitric Oxide Prodrug, Has Enhanced Cytotoxicity in Colon Cancer Cells with Knockdown of Thioredoxin Reductase 1

PubMed Central

Edes, Kornelia; Cassidy, Pamela; Shami, Paul J.; Moos, Philip J.

2010-01-01

Background The selenoenzyme thioredoxin reductase 1 has a complex role relating to cell growth. It is induced as a component of the cellular response to potentially mutagenic oxidants, but also appears to provide growth advantages to transformed cells by inhibiting apoptosis. In addition, selenocysteine-deficient or alkylated forms of thioredoxin reductase 1 have also demonstrated oxidative, pro-apoptotic activity. Therefore, a greater understanding of the role of thioredoxin reductase in redox initiated apoptotic processes is warranted. Methodology The role of thioredoxin reductase 1 in RKO cells was evaluated by attenuating endogenous thioredoxin reductase 1 expression with siRNA and then either inducing a selenium-deficient thioredoxin reductase or treatment with distinct redox challenges including, hydrogen peroxide, an oxidized lipid, 4-hydroxy-2-nonenol, and a nitric oxide donating prodrug. Thioredoxin redox status, cellular viability, and effector caspase activity were measured. Conclusions/Significance In cells with attenuated endogenous thioredoxin reductase 1, a stably integrated selenocysteine-deficient form of the enzyme was induced but did not alter either the thioredoxin redox status or the cellular growth kinetics. The oxidized lipid and the nitric oxide donor demonstrated enhanced cytotoxicity when thioredoxin reductase 1 was knocked-down; however, the effect was more pronounced with the nitric oxide prodrug. These results are consistent with the hypothesis that attenuation of the thioredoxin-system can promote apoptosis in a nitric oxide-dependent manner. PMID:20098717

Validation of time and temperature values as critical limits for Salmonella and background flora growth during the production of fresh ground and boneless pork products.

PubMed

Mann, J E; Smith, L; Brashears, M M

2004-07-01

To provide pork processors with valuable data to validate the critical limits set for temperature during pork fabrication and grinding, a study was conducted to determine the growth of Salmonella serotypes and background flora at various temperatures. Growth of Salmonella Typhimurium and Salmonella Enteritidis and of background flora was monitored in ground pork and boneless pork chops held at various temperatures to determine growth patterns. Case-ready modified atmosphere packaged ground pork and fresh whole pork loins were obtained locally. Boneless chops and ground pork were inoculated with a cocktail mixture of streptomycin-resistant Salmonella to facilitate recovery in the presence of background flora. Samples were held at 4.4, 7.2C, and 10 degrees C and at room temperature (22.2 to 23.3 degrees C) to mimic typical processing and holding temperatures observed in pork processing environments. Salmonella counts were determined at regular intervals over 12 and 72 h for both room and refrigeration temperatures. No significant growth of Salmonella (P < 0.05) was observed in boneless pork chops held at refrigeration temperatures. However, Salmonella in boneless pork chops held at room temperature had grown significantly by 8 h. Salmonella grew at faster rates in ground pork. Significant growth was observed at 6, 24. and 72 h when samples were held at room temperature, 10 degrees C, and 7.2 degrees C, respectively. No significant growth was observed at 4.4 degrees C. Background flora in ground pork samples increased significantly after 10 h at room temperature and after 12 h for samples held at 10 and 7.2 degrees C. Background flora in samples held at refrigeration temperatures did not increase until 72 h. Background flora in the boneless chops increased significantly after 6 h at room temperature and after 24 h when held at 10 and 4.4 degrees C. These results illustrate that meat processors can utilize a variety of time and temperature combinations as critical limits to minimize Salmonella growth during production and storage of raw pork products.

Targeting Transforming Growth Factor Beta to Enhance the Fracture Resistance of Bone

DTIC Science & Technology

2013-01-01

Transforming Growth Factor Beta to Enhance the Fracture Resistance of Bone is to determine whether the suppression of TGF-β activity improves the fracture...effect primarily occurred in the old rats. Effect of TGF-β suppression on fracture resistance in female mice Since the suppression of TGF-β activity by...treated mice. This suggests that 1D11 treatment depleted the osteoprogenitor pool to some extent as inhibition of TGF-β activity in vivo may favor

Association between Plasma Levels of Transforming Growth Factor-beta1, IL-23 and IL-17 and the Severity of Autism in Egyptian Children

ERIC Educational Resources Information Center

Hashim, Haitham; Abdelrahman, Hadeel; Mohammed, Doaa; Karam, Rehab

2013-01-01

It has been recently shown that dysregulation of transforming growth factor-beta1 (TGF-beta1), IL-23 and IL-17 has been identified as a major factor involved in autoimmune disorders. Based on the increasing evidence of immune dysfunction in autism the aim of this study was to measure serum levels of TGF-beta1, IL-23 and IL-17 in relation to the…

Infrared small target enhancement: grey level mapping based on improved sigmoid transformation and saliency histogram

NASA Astrophysics Data System (ADS)

Wan, Minjie; Gu, Guohua; Qian, Weixian; Ren, Kan; Chen, Qian

2018-06-01

Infrared (IR) small target enhancement plays a significant role in modern infrared search and track (IRST) systems and is the basic technique of target detection and tracking. In this paper, a coarse-to-fine grey level mapping method using improved sigmoid transformation and saliency histogram is designed to enhance IR small targets under different backgrounds. For the stage of rough enhancement, the intensity histogram is modified via an improved sigmoid function so as to narrow the regular intensity range of background as much as possible. For the part of further enhancement, a linear transformation is accomplished based on a saliency histogram constructed by averaging the cumulative saliency values provided by a saliency map. Compared with other typical methods, the presented method can achieve both better visual performances and quantitative evaluations.

Growth in Reading-Related Skills of Language Minority Learners and Their Classmates: More Evidence for Early Identification and Intervention

ERIC Educational Resources Information Center

Kieffer, Michael J.; Vukovic, Rose K.

2013-01-01

This longitudinal study investigated growth in reading-related skills between Grade 1 and 4 for language minority (LM) learners and their native English-speaking classmates from similarly low socioeconomic backgrounds (N = 166). Growth trajectories were compared by language background and by Grade 4 reading difficulties, with the goal of informing…

Graded inhibition of oncogenic Ras-signaling by multivalent Ras-binding domains

PubMed Central

2014-01-01

Background Ras is a membrane-associated small G-protein that funnels growth and differentiation signals into downstream signal transduction pathways by cycling between an inactive, GDP-bound and an active, GTP-bound state. Aberrant Ras activity as a result of oncogenic mutations causes de novo cell transformation and promotes tumor growth and progression. Results Here, we describe a novel strategy to block deregulated Ras activity by means of oligomerized cognate protein modules derived from the Ras-binding domain of c-Raf (RBD), which we named MSOR for multivalent scavengers of oncogenic Ras. The introduction of well-characterized mutations into RBD was used to adjust the affinity and hence the blocking potency of MSOR towards activated Ras. MSOR inhibited several oncogenic Ras-stimulated processes including downstream activation of Erk1/2, induction of matrix-degrading enzymes, cell motility and invasiveness in a graded fashion depending on the oligomerization grade and the nature of the individual RBD-modules. The amenability to accurate experimental regulation was further improved by engineering an inducible MSOR-expression system to render the reversal of oncogenic Ras effects controllable. Conclusion MSOR represent a new tool for the experimental and possibly therapeutic selective blockade of oncogenic Ras signals. PMID:24383791

NASA's Human Planetary Landing Systems Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Mueller, Rob

2005-01-01

General Background and Introduction of Capability Roadmaps Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date)

Transforming Growth Factor-β Signaling Pathway in Patients with Kawasaki Disease

PubMed Central

Shimizu, Chisato; Jain, Sonia; Lin, Kevin O.; Molkara, Delaram; Frazer, Jeffrey R.; Sun, Shelly; Baker, Annette L.; Newburger, Jane W.; Rowley, Anne H.; Shulman, Stanford T.; Davila, Sonia; Hibberd, Martin L.; Burgner, David; Breunis, Willemijn B.; Kuijpers, Taco W.; Wright, Victoria J.; Levin, Michael; Eleftherohorinou, Hariklia; Coin, Lachlan; Popper, Stephen J.; Relman, David A.; Fury, Wen; Lin, Calvin; Mellis, Scott; Tremoulet, Adriana H.; Burns, Jane C.

2011-01-01

Background Transforming growth factor (TGF)-β is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-β signaling might be important in KD susceptibility and disease outcome. Methods and Results We investigated genetic variation in 15 genes belonging to the TGF-β pathway in a total 771 KD subjects of mainly European descendent from the US, UK, Australia and the Netherlands. We analyzed transcript abundance patterns using microarray and RT-PCR for these same genes and measured TGF-β2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2 and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in two independent cohorts and an intronic SNP in a separate haplotype block was also strongly associated (A/G, rs4776338) (p=0.000022, OR 1.50, 95% CI 1.25-1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-β pathway in KD pathogenesis. Whole blood transcript abundance for these genes and TGF-β2 plasma protein levels changed dynamically over the course of the illness. Conclusions These studies suggest that genetic variation in the TGF-β pathway influences KD susceptibility, disease outcome, and response to therapy and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis. PMID:21127203

Evaluation of a topical treatment for the relief of sensitive skin

PubMed Central

Heinicke, Ingrid R; Adams, Damian H; Barnes, Tanya M; Greive, Kerryn A

2015-01-01

Background Approximately, 50% of the population claim to have sensitive skin, which has created an important challenge for dermatologists and the cosmetic industry. This study evaluates the properties of QV Face Rescue Gel (Rescue Gel) that contains a combination of moisturizing and anti-irritant ingredients, and which is used to relieve the symptoms of sensitive facial skin. Methods The ability of Rescue Gel to induce collagen types I and III in cultured neonatal human foreskin fibroblasts compared to transforming growth factor beta 1, a known potent inducer of collagen types I and III, was measured using immunofluorescence staining. Furthermore, healthy volunteers were recruited to measure the potential for Rescue Gel to reduce erythema induced by solar-simulated ultraviolet radiation on the skin compared to 0.5% hydrocortisone cream (positive control) as well as it’s ability to decrease transepidermal water loss compared to baseline levels. In addition, the formulation was tested for its potential to be 1) nonstinging using a facial sting/discomfort assay performed on volunteers who reacted positively to lactic acid, 2) nonirritating as determined by repeat insult patch tests, and 3) noncomedogenic. Results Rescue Gel significantly induced collagen types I and III in cultured human foreskin fibroblasts similarly to transforming growth factor beta 1. In volunteers, Rescue Gel was shown to significantly reduce erythema induced by solar-simulated ultraviolet radiation similarly to 0.5% hydrocortisone, and to significantly reduce transepidermal water loss compared to baseline levels. Further, the formulation was found to be nonstinging, nonirritating, and noncomedogenic. No adverse events were observed. Conclusion In this study, Rescue Gel has been shown to exhibit properties that make it effective for use on sensitive or irritated facial skin, without exacerbation of the symptoms associated with sensitive skin. PMID:26251625

Time indices of multiphasic development in genotypes of sweet cherry are similar from dormancy to cessation of pit growth

PubMed Central

Gibeaut, David M.; Whiting, Matthew D.; Einhorn, Todd

2017-01-01

Background and Aims The archetypical double sigmoid-shaped growth curve of the sweet cherry drupe (Prunus avium) does not address critical development from eco-dormancy to anthesis and has not been correlated to reproductive bud development. Accurate representation of the growth and development of post-anthesis ovaries is confounded by anthesis timing, fruiting-density and the presence of unfertilized and defective ovaries whose growth differs from those that persist to maturation. These factors were addressed to assess pre-anthesis and full-season growth and development of three sweet cherry cultivars, ‘Chelan’, ‘Bing’ and ‘Sweetheart’, differing primarily in seasonal duration and fruit size. Methods Volume was calculated from photographic measurements of reproductive buds, ovaries and pits at all phases of development. A population of unfertilized ovaries was produced using bee-exclusion netting to enable a statistical comparison with an open pollinated population to detect differences in size and shape between successful and failing fruit growth. Anthesis timing and fruiting-density were manipulated by floral extinction at the spur and whole-tree scales. Developmental time indices were analysed using polynomial curve fitting of log-transformed data supported by Richards and logistic functions of asymptotic growth of the pit and maturing fruit, respectively. Key Results Pre-anthesis growth began at the completion of eco-dormancy. A slight decline in relative growth rate (RGR) was observed during bud scale separation approx. −16 d from anthesis (DFA) before resumption of exponential growth to a maximum about 14 DFA. After anthesis, reduced growth of unfertilized or defective ovaries was partly discriminated from successful fruit at 5 DFA and completely at 25 DFA. Time indices of RGR inflections were similar among cultivars when adjusted for anthesis date alone, until the end of pit growth. Asymptotic growth of the pit underpinned the declining growth rate of fruit at the end of the first exponential growth phase. Duration of the subsequent expansive growth phase accounted for genotypic differences in seasonal duration and final size. Pit size and final fruit size were inversely related to fruiting-density. Conclusions Developmental differences among early, mid and late maturing cultivars were not detected until the final growth period. PMID:28064193

New Zealand and Queensland Teachers' Conceptions of Learning: Transforming More than Reproducing

ERIC Educational Resources Information Center

Brown, Gavin T. L.; Lake, Robert; Matters, Gabrielle

2008-01-01

Background: Two major conceptions of learning exist: reproducing new material and transforming material to make meaning. Teachers' understandings of what learning is probably influence their teaching practices and student academic performance. Aims: To validate a short scale derived from Tait, Entwistle, & McCune's (1998) ASSIST inventory and…

Beyond Passwords: Usage and Policy Transformation

DTIC Science & Technology

2007-03-01

case scenario for lost productivity due to users leaving their CAC at work, in their computer, is costing 261 work years per year with an estimated ...one for your CAC) are you currently using? ..................................................................................................... 43...PASSWORDS: USAGE AND POLICY TRANSFORMATION I. Introduction Background Currently , the primary method for network authentication on the

Synchronicity and Transformation in the Experience of Prison Educators

ERIC Educational Resources Information Center

Woods, Robert

2010-01-01

Many inmates arrive in prison with weak educational backgrounds and social skills as well as psychological problems and drug and alcohol addiction. The focus of this phenomenological study was to identify roles of prison educators in helping inmate students overcome their challenges through transformative experiences that motivate the students to…

Examining the Genetic Background of Porcine Muscle Growth and Development Based on Transcriptome and miRNAome Data.

PubMed

Ropka-Molik, Katarzyna; Pawlina-Tyszko, Klaudia; Żukowski, Kacper; Piórkowska, Katarzyna; Żak, Grzegorz; Gurgul, Artur; Derebecka, Natalia; Wesoły, Joanna

2018-04-16

Recently, selection in pigs has been focused on improving the lean meat content in carcasses; this focus has been most evident in breeds constituting a paternal component in breeding. Such sire-breeds are used to improve the meat quantity of cross-breed pig lines. However, even in one breed, a significant variation in the meatiness level can be observed. In the present study, the comprehensive analysis of genes and microRNA expression profiles in porcine muscle tissue was applied to identify the genetic background of meat content. The comparison was performed between whole gene expression and miRNA profiles of muscle tissue collected from two sire-line pig breeds (Pietrain, Hampshire). The RNA-seq approach allowed the identification of 627 and 416 differentially expressed genes (DEGs) between pig groups differing in terms of loin weight between Pietrain and Hampshire breeds, respectively. The comparison of miRNA profiles showed differential expression of 57 microRNAs for Hampshire and 34 miRNAs for Pietrain pigs. Next, 43 genes and 18 miRNAs were selected as differentially expressed in both breeds and potentially related to muscle development. According to Gene Ontology analysis, identified DEGs and microRNAs were involved in the regulation of the cell cycle, fatty acid biosynthesis and regulation of the actin cytoskeleton. The most deregulated pathways dependent on muscle mass were the Hippo signalling pathway connected with the TGF-β signalling pathway and controlling organ size via the regulation of ubiquitin-mediated proteolysis, cell proliferation and apoptosis. The identified target genes were also involved in pathways such as the FoxO signalling pathway, signalling pathways regulating pluripotency of stem cells and the PI3K-Akt signalling pathway. The obtained results indicate molecular mechanisms controlling porcine muscle growth and development. Identified genes ( SOX2 , SIRT1 , KLF4 , PAX6 and genes belonging to the transforming growth factor beta superfamily) could be considered candidate genes for determining muscle mass in pigs.

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

PubMed Central

2012-01-01

Background Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. Results Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2–5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1–7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. Conclusion Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs. PMID:23237028

Wheat (Triticum aestivum L.) transformation using mature embryos.

PubMed

Medvecká, Eva; Harwood, Wendy A

2015-01-01

In most protocols for the Agrobacterium-mediated transformation of wheat, the preferred target tissues are immature embryos. However, transformation methods relying on immature embryos require the growth of plants under controlled conditions to provide a continuous supply of good-quality target tissue. The use of mature embryos as a target tissue has the advantage of only requiring good-quality seed as the starting material. Here we describe a transformation method based on the Agrobacterium-mediated transformation of callus cultures derived from mature wheat embryos of the genotype Bobwhite S56.

Histological transformation after acquired resistance to epidermal growth factor tyrosine kinase inhibitors.

PubMed

Shao, Yi; Zhong, Dian-Sheng

2018-04-01

Non-small-cell lung cancer patients with sensitive epidermal growth factor receptor mutations generally respond well to tyrosine kinase inhibitors (TKIs). However, acquired resistance will eventually develop place after 8-16 months. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification, epithelial mesenchymal transformation and PIK3CA mutation; however, histological transformation is a rare mechanism. The patterns and mechanisms underlying histological transformation need to be explored. We searched PubMed, EMBASE and search engines Google Scholar, Medical Matrix for literature related to histological transformation. Case reports, cases series, and clinical and basic medical research articles were reviewed. Sixty-one articles were included in this review. Cases of transformation to small-cell lung cancer, squamous cell carcinoma, large-cell neuroendocrine carcinoma and sarcoma after TKI resistance have all been reported. As the clinical course differed dramatically between cases, a new treatment scheme needs to be recruited. The mechanisms underlying histological transformation have not been fully elucidated and probably relate to cancer stem cells, driver genetic alterations under selective pressure or the heterogeneity of the tumor. When TKI resistance develops, we recommend that patients undergo a second biopsy to determine the reason, guide the next treatment and predict the prognosis.

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.

Straw blood cell count, growth, inhibition and comparison to apoptotic bodies.

PubMed

Wu, Yonnie; Henry, David C; Heim, Kyle; Tomkins, Jeffrey P; Kuan, Cheng-Yi

2008-05-20

Mammalian cells transform into individual tubular straw cells naturally in tissues and in response to desiccation related stress in vitro. The transformation event is characterized by a dramatic cellular deformation process which includes: condensation of certain cellular materials into a much smaller tubular structure, synthesis of a tubular wall and growth of filamentous extensions. This study continues the characterization of straw cells in blood, as well as the mechanisms of tubular transformation in response to stress; with specific emphasis placed on investigating whether tubular transformation shares the same signaling pathway as apoptosis. There are approximately 100 billion, unconventional, tubular straw cells in human blood at any given time. The straw blood cell count (SBC) is 45 million/ml, which accounts for 6.9% of the bloods dry weight. Straw cells originating from the lungs, liver and lymphocytes have varying nodules, hairiness and dimensions. Lipid profiling reveals severe disruption of the plasma membrane in CACO cells during transformation. The growth rates for the elongation of filaments and enlargement of rabbit straw cells is 0.6 approximately 1.1 (microm/hr) and 3.8 (microm(3)/hr), respectively. Studies using apoptosis inhibitors and a tubular transformation inhibitor in CACO2 cells and in mice suggested apoptosis produced apoptotic bodies are mediated differently than tubular transformation produced straw cells. A single dose of 0.01 mg/kg/day of p38 MAPK inhibitor in wild type mice results in a 30% reduction in the SBC. In 9 domestic animals SBC appears to correlate inversely with an animal's average lifespan (R2 = 0.7). Straw cells are observed residing in the mammalian blood with large quantities. Production of SBC appears to be constant for a given animal and may involve a stress-inducible protein kinase (P38 MAPK). Tubular transformation is a programmed cell survival process that diverges from apoptosis. SBCs may be an important indicator of intrinsic aging-related stress.

Stimulation of the cell cycle and maize transformation by disruption of the plant retinoblastoma pathway

PubMed Central

Gordon-Kamm, William; Dilkes, Brian P.; Lowe, Keith; Hoerster, George; Sun, Xifan; Ross, Margit; Church, Laura; Bunde, Chris; Farrell, Jeff; Hill, Patrea; Maddock, Sheila; Snyder, Jane; Sykes, Louisa; Li, Zhongsen; Woo, Young-min; Bidney, Dennis; Larkins, Brian A.

2002-01-01

The genome of the Mastreviruses encodes a replication-associated protein (RepA) that interacts with members of the plant retinoblastoma-related protein family, which are putative cell cycle regulators. Expression of ZmRb1, a maize retinoblastoma-related gene, and RepA inhibited and stimulated, respectively, cell division in tobacco cell cultures. The effect of RepA was mitigated by over-expression of ZmRb1. RepA increased transformation frequency and callus growth rate of high type II maize germplasm. RepA-containing transgenic maize calli remained embryogenic, were readily regenerable, and produced fertile plants that transmitted transgene expression in a Mendelian fashion. In high type II, transformation frequency increased with the strength of the promoter driving RepA expression. When a construct in which RepA was expressed behind its native LIR promoter was used, primary transformation frequencies did not improve for two elite Pioneer maize inbreds. However, when LIR:RepA-containing transgenic embryos were used in subsequent rounds of transformation, frequencies were higher in the RepA+ embryos. These data demonstrate that RepA can stimulate cell division and callus growth in culture, and improve maize transformation. PMID:12185243

Middle Level Mathematics Teachers' Self-Efficacy Growth through Professional Development: Differences Based on Mathematical Background

ERIC Educational Resources Information Center

Stevens, Tara; Aguirre-Munoz, Zenaida; Harris, Gary; Higgins, Raegan; Liu, Xun

2013-01-01

growth of teachers with more and less mathematics background as the teachers participated in professional development across two summers. Professional development activities were associated with increases in teachers' self-efficacy; however, without considering mathematics…

Development paths of China's agricultural Pharmaceutical industry under Eco-agriculture background.

PubMed

Li, Jinkai; Gong, Liutang; Ji, Xi; Zhang, Jin; Miao, Pei

2014-07-01

Using pesticides has double effects. On one hand, it contributes to pests control and regulates the growth of crops; On the other hand, it does harm to the environment. To develop ecological agriculture should not only emphasize the output level of agriculture to pursuit of economic efficiency, but also need to keep the ecological environment protected and focus on the social benefits during the development of the industry. As a large agricultural country in the world, China is vigorously promoting the development of ecological agriculture, which is bound to put forward to developing the pesticide industry and green ecological development requirements to promote the transformation and upgrading of agricultural pharmaceutical industry. This paper discusses the mechanism of pesticide pollution on the ecological environment and analyzes China's agricultural problems in the pharmaceutical industry. Then study on the development of Chinese green pesticides and try to find the proper paths of agricultural pharmaceutical to achieve industrial upgrading.

Generation of astaxanthin mutants in Xanthophyllomyces dendrorhous using a double recombination method based on hygromycin resistance.

PubMed

Niklitschek, Mauricio; Baeza, Marcelo; Fernández-Lobato, María; Cifuentes, Víctor

2012-01-01

Generally two selection markers are required to obtain homozygous mutations in a diploid background, one for each gene copy that is interrupted. In this chapter is described a method that allows the double gene deletions of the two copies of a gene from a diploid organism, a wild-type strain of the Xanthophyllomyces dendrorhous yeast, using hygromycin B resistance as the only selection marker. To accomplish this, in a first step, a heterozygous hygromycin B-resistant strain is obtained by a single process of transformation (carrying the inserted hph gene). Following, the heterozygous mutant is grown in media with increasing concentrations of the antibiotic. In this way, the strains that became homozygous (by mitotic recombination) for the antibiotic marker would able to growth at higher concentration of the antibiotic than the heterozygous. The method can be potentially applied for obtaining double mutants of other diploid organisms.

MSX-1 gene expression and regulation in embryonic palatal tissue.

PubMed

Nugent, P; Greene, R M

1998-01-01

The palatal cleft seen in Msx-1 knock-out mice suggests a role for this gene in normal palate development. The cleft is presumed secondary to tooth and jaw malformations, since in situ hybridization suggests that Msx-1 mRNA is not highly expressed in developing palatal tissue. In this study we demonstrate, by Northern blot analysis, the expression of Msx-1, but not Msx-2, in the developing palate and in primary cultures of murine embryonic palate mesenchymal cells. Furthermore, we propose a role for Msx-1 in retinoic acid-induced cleft palate, since retinoic acid inhibits Msx-1 mRNA expression in palate mesenchymal cells. We also demonstrate that transforming growth factor beta inhibits Msx-1 mRNA expression in palate mesenchymal cells, with retinoic acid and transforming growth factor beta acting synergistically when added simultaneously to these cells. These data suggest a mechanistic interaction between retinoic acid, transforming growth factor beta, and Msx-1 in the etiology of retinoic acid-induced cleft palate.

Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

PubMed

Opgenorth, A; Nation, N; Graham, K; McFadden, G

1993-02-01

The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

Strain distribution of confined Ge/GeO2 core/shell nanoparticles engineered by growth environments

NASA Astrophysics Data System (ADS)

Wei, Wenyan; Yuan, Cailei; Luo, Xingfang; Yu, Ting; Wang, Gongping

2016-02-01

The strain distributions of Ge/GeO2 core/shell nanoparticles confined in different host matrix grown by surface oxidation are investigated. The simulated results by finite element method demonstrated that the strains of the Ge core and the GeO2 shell strongly depend on the growth environments of the nanoparticles. Moreover, it can be found that there is a transformation of the strain on Ge core from tensile to compressive strain during the growth of Ge/GeO2 core/shell nanoparticles. And, the transformation of the strain is closely related with the Young's modulus of surrounding materials of Ge/GeO2 core/shell nanoparticles.

Effect of phosphorus addition on the reductive transformation of pentachlorophenol (PCP) and iron reduction with microorganism involvement.

PubMed

Wang, Yongkui; Liu, Xianli; Huang, Jiexun; Xiao, Wensheng; Zhang, Jiaquan; Yin, Chunqin

2017-10-01

The transformation of phosphorus added to the soil environment has been proven to be influenced by the Fe biochemical process, which thereby may affect the transformation of organic chlorinated contaminants. However, the amount of related literatures regarding this topic is limited. This study aimed to determine the effects of phosphorus addition on pentachlorophenol (PCP) anaerobic transformation, iron reduction, and paddy soil microbial community structure. Results showed that the transformation of phosphorus, iron, and PCP were closely related to the microorganisms. Moreover, phosphorus addition significantly influenced PCP transformation and iron reduction, which promoted and inhibited these processes at low and high concentrations, respectively. Both the maximum reaction rate of PCP transformation and the maximum Fe(II) amount produced were obtained at 1 mmol/L phosphorus concentration. Among the various phosphorus species, dissolved P and NaOH-P considerably changed, whereas only slight changes were observed for the remaining phosphorus species. Microbial community structure analysis demonstrated that adding low concentration of phosphorus promoted the growth of Clostridium bowmanii, Clostridium hungatei, and Clostridium intestinale and Pseudomonas veronii. By contrast, high-concentration phosphorus inhibited growth of these microorganisms, similar to the curves of PCP transformation and iron reduction. These observations indicated that Clostridium and P. veronii, especially Clostridium, played a vital role in the transformation of related substances in the system. All these findings may serve as a reference for the complicated reactions among the multiple components of soils.

Scanning Thin-Sheet Laser Imaging Microscopy Elucidates Details on Mouse Ear Development

PubMed Central

Kopecky, Benjamin; Johnson, Shane; Schmitz, Heather; Santi, Peter; Fritzsch, Bernd

2016-01-01

Background The mammalian inner ear is transformed from a flat placode into a three-dimensional (3D) structure with six sensory epithelia that allow for the perception of sound and both linear and angular acceleration. While hearing and balance problems are typically considered to be adult onset diseases, they may arise as a developmental perturbation to the developing ear. Future prevention of hearing or balance loss requires an understanding of how closely genetic mutations in model organisms reflect the human case, necessitating an objective multidimensional comparison of mouse ears with human ears that have comparable mutations in the same gene. Results Here, we present improved 3D analyses of normal murine ears during embryonic development using optical sections obtained through Thin-Sheet Laser Imaging Microscopy. We chronicle the transformation of an undifferentiated otic vesicle between mouse embryonic day 11.5 to a fully differentiated inner ear at postnatal day 15. Conclusions Our analysis of ear development provides new insights into ear development, enables unique perspectives into the complex development of the ear, and allows for the first full quantification of volumetric and linear aspects of ear growth. Our data provide the framework for future analysis of mutant phenotypes that are currently under-appreciated using only two dimensional renderings. PMID:22271591

Intracellular mediators of transforming growth factor beta superfamily signaling localize to endosomes in chicken embryo and mouse lenses in vivo.

PubMed

Rajagopal, Ramya; Ishii, Shunsuke; Beebe, David C

2007-06-25

Endocytosis is a key regulator of growth factor signaling pathways. Recent studies showed that the localization to endosomes of intracellular mediators of growth factor signaling may be required for their function. Although there is substantial evidence linking endocytosis and growth factor signaling in cultured cells, there has been little study of the endosomal localization of signaling components in intact tissues or organs. Proteins that are downstream of the transforming growth factor-beta superfamily signaling pathway were found on endosomes in chicken embryo and postnatal mouse lenses, which depend on signaling by members of the TGFbeta superfamily for their normal development. Phosphorylated Smad1 (pSmad1), pSmad2, Smad4, Smad7, the transcriptional repressors c-Ski and TGIF and the adapter molecules Smad anchor for receptor activation (SARA) and C184M, localized to EEA-1- and Rab5-positive vesicles in chicken embryo and/or postnatal mouse lenses. pSmad1 and pSmad2 also localized to Rab7-positive late endosomes. Smad7 was found associated with endosomes, but not caveolae. Bmpr1a conditional knock-out lenses showed decreased nuclear and endosomal localization of pSmad1. Many of the effectors in this pathway were distributed differently in vivo from their reported distribution in cultured cells. Based on the findings reported here and data from other signaling systems, we suggest that the localization of activated intracellular mediators of the transforming growth factor-beta superfamily to endosomes is important for the regulation of growth factor signaling.

Pilot-scale cultivation of wall-deficient transgenic Chlamydomonas reinhardtii strains expressing recombinant proteins in the chloroplast.

PubMed

Zedler, Julie A Z; Gangl, Doris; Guerra, Tiago; Santos, Edgar; Verdelho, Vitor V; Robinson, Colin

2016-08-01

Microalgae have emerged as potentially powerful platforms for the production of recombinant proteins and high-value products. Chlamydomonas reinhardtii is a potentially important host species due to the range of genetic tools that have been developed for this unicellular green alga. Transformation of the chloroplast genome offers important advantages over nuclear transformation, and a wide range of recombinant proteins have now been expressed in the chloroplasts of C. reinhardtii strains. This is often done in cell wall-deficient mutants that are easier to transform. However, only a single study has reported growth data for C. reinhardtii grown at pilot scale, and the growth of cell wall-deficient strains has not been reported at all. Here, we report the first pilot-scale growth study for transgenic, cell wall-deficient C. reinhardtii strains. Strains expressing a cytochrome P450 (CYP79A1) or bifunctional diterpene synthase (cis-abienol synthase, TPS4) were grown for 7 days under mixotrophic conditions in a Tris-acetate-phosphate medium. The strains reached dry cell weights of 0.3 g/L within 3-4 days with stable expression levels of the recombinant proteins during the whole upscaling process. The strains proved to be generally robust, despite the cell wall-deficient phenotype, but grew poorly under phototrophic conditions. The data indicate that cell wall-deficient strains may be highly amenable for transformation and suitable for commercial-scale operations under mixotrophic growth regimes.

Phase Transformations and Microstructural Evolution: Part II

DOE PAGES

Clarke, Amy Jean

2015-10-30

The activities of the Phase Transformations Committee of the Materials Processing & Manufacturing Division (MPMD) of The Minerals, Metals & Materials Society (TMS) are oriented toward understanding the fundamental aspects of phase transformations. Emphasis is placed on the thermodynamic driving forces for phase transformations, the kinetics of nucleation and growth, interfacial structures and energies, transformation crystallography, surface reliefs, and, above all, the atomic mechanisms of phase transformations. Phase transformations and microstructural evolution are directly linked to materials processing, properties, and performance. In this issue, aspects of liquid–solid and solid-state phase transformations and microstructural evolution are highlighted. Many papers in thismore » issue are highlighted by this paper, giving a brief summary of what they bring to the scientific community.« less

BSC-1 growth inhibitor transforms a mitogenic stimulus into a hypertrophic stimulus for renal proximal tubular cells: relationship to Na/sup +//H/sup +/ antiport activity

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

Fine, L.G.; Holley, R.W.; Nasri, H.

Renal hypertrophy is characterized by an increase in cell size and protein content with minimal hyperplasia. The mechanisms of control of this pattern of cell growth have not been determined. The present studies examined whether the growth inhibitor elaborated by BSC-1 kidney epilethal cells (GI), which has nearly identical biological properties to transforming growth factor ..beta.. (TGF-..beta..), could transform a mitogenic stimulus into a hypertrophic stimulus for rabbit renal proximal tubular cells in primary culture. Insulin plus hydrocortisone increased the amount of protein per cell, cell volume, and (/sup 3/H)thymidine incorporation at 24 and 48 hr in these cells. Whenmore » added together with insulin plus hydrocortisone, GI/TGF-..beta.. inhibited the stimulatory effect of these mitogens on (/sup 3/H)thymidine incorporation but did not block the increase in protein per cell and cell volume - i.e., the cells underwent hypertrophy. The fact that this pattern persisted for 48 hr indicated that GI/TGF-..beta.. exerted a prolonged inhibitory effect on mitogenic-stimulated DNA synthesis rather than delaying its onset. Amiloride-sensitive Na/sup +/ uptake using /sup 22/Na/sup +/ as a tracer, correlated with protein per cell and cell volume rather than with DNA synthesis. These studies indicate that the control of cell size may be regulated by autocrine mechanisms mediated by the elaboration of growth inhibitory factors that alter the pattern of the growth response to mitogens.« less

Does the immune reaction cause malignant transformation by disrupting cell-to-cell or cell-to-matrix communications?

PubMed

Prehn, Richmond T

2007-05-04

TUMOR PROGRESSION: In many (perhaps in all) tumor systems, a malignant cancer is preceded by a benign lesion. Most benign lesions do not transform to malignancy and many regress. The final transformative step to malignancy differs from the preceding steps in, among other things, that it often occurs in the absence of the original carcinogenic stimulus. Relatively low titers of specific immune reactants are known to stimulate, but cell-to-cell or cell-to-matrix interactions appear to be major inhibitors of tumor-growth. Therefore, it seems reasonable to hypothesize that the mechanism of immunostimulation may be an interference with cell-to-cell or cell-to-matrix communication by a sub-lethal immune-reaction. While the above hypothesis remains unproven, some evidence suggests that immunity may have a major facilitating effect on tumor growth especially at the time of malignant transformation. There is even some evidence suggesting that transformation in vivo may seldom occur in the absence of immunostimulation of the premalignant lesion. Positive selection by the immune reaction may be the reason that tumors are immunogenic.

Activated platelet-derived growth factor autocrine pathway drives the transformed phenotype of a human glioblastoma cell line.

PubMed

Vassbotn, F S; Ostman, A; Langeland, N; Holmsen, H; Westermark, B; Heldin, C H; Nistér, M

1994-02-01

Human glioblastoma cells (A172) were found to concomitantly express PDGF-BB and PDGF beta-receptors. The receptors were constitutively autophosphorylated in the absence of exogenous ligand, suggesting the presence of an autocrine PDGF pathway. Neutralizing PDGF antibodies as well as suramin inhibited the autonomous PDGF receptor tyrosine kinase activity and resulted in up-regulation of receptor protein. The interruption of the autocrine loop by the PDGF antibodies reversed the transformed phenotype of the glioblastoma cell, as determined by (1) diminished DNA synthesis, (2) inhibition of tumor colony growth, and (3) reversion of the transformed morphology of the tumor cells. The PDGF antibodies showed no effect on the DNA synthesis of another glioblastoma cells line (U-343MGa 31L) or on Ki-ras-transformed fibroblasts. The present study demonstrates an endogenously activated PDGF pathway in a spontaneous human glioblastoma cell line. Furthermore, we provide evidence that the autocrine PDGF pathway drives the transformed phenotype of the tumor cells, a process that can be blocked by extracellular antagonists.

Succinate, iron chelation, and monovalent cations affect the transformation efficiency of Acinetobacter baylyi ATCC 33305 during growth in complex media.

PubMed

Leong, Colleen G; Boyd, Caroline M; Roush, Kaleb S; Tenente, Ricardo; Lang, Kristine M; Lostroh, C Phoebe

2017-10-01

Natural transformation is the acquisition of new genetic material via the uptake of exogenous DNA by competent bacteria. Acinetobacter baylyi is model for natural transformation. Here we focus on the natural transformation of A. baylyi ATCC 33305 grown in complex media and seek environmental conditions that appreciably affect transformation efficiency. We find that the transformation efficiency for A. baylyi is a resilient characteristic that remains high under most conditions tested. We do find several distinct conditions that alter natural transformation efficiency including addition of succinate, Fe 2+ (ferrous) iron chelation, and substitution of sodium ions with potassium ones. These distinct conditions could be useful to fine tune transformation efficiency for researchers using A. baylyi as a model organism to study natural transformation.

A Genetic Screen for Pathogenicity Genes in the Hemibiotrophic Fungus Colletotrichum higginsianum Identifies the Plasma Membrane Proton Pump Pma2 Required for Host Penetration

PubMed Central

Dahl, Marlis; Müller, Susanne; Voll, Lars M.; Koch, Christian

2015-01-01

We used insertional mutagenesis by Agrobacterium tumefaciens mediated transformation (ATMT) to isolate pathogenicity mutants of Colletotrichum higginsianum. From a collection of 7200 insertion mutants we isolated 75 mutants with reduced symptoms. 19 of these were affected in host penetration, while 17 were affected in later stages of infection, like switching to necrotrophic growth. For 16 mutants the location of T-DNA insertions could be identified by PCR. A potential plasma membrane H+-ATPase Pma2 was targeted in five independent insertion mutants. We genetically inactivated the Ku80 component of the non-homologous end-joining pathway in C. higginsianum to establish an efficient gene knockout protocol. Chpma2 deletion mutants generated by homologous recombination in the ΔChku80 background form fully melanized appressoria but entirely fail to penetrate the host tissue and are non-pathogenic. The ChPMA2 gene is induced upon appressoria formation and infection of A. thaliana. Pma2 activity is not important for vegetative growth of saprophytically growing mycelium, since the mutant shows no growth penalty under these conditions. Colletotrichum higginsianum codes for a closely related gene (ChPMA1), which is highly expressed under most growth conditions. ChPMA1 is more similar to the homologous yeast genes for plasma membrane pumps. We propose that expression of a specific proton pump early during infection may be common to many appressoria forming fungal pathogens as we found ChPMA2 orthologs in several plant pathogenic fungi. PMID:25992547

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies

PubMed Central

2011-01-01

Background Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains. Results The plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats. Conclusion Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I. PMID:21486461

Linear analysis on the growth of non-spherical perturbations in supersonic accretion flows

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

Takahashi, Kazuya; Yamada, Shoichi, E-mail: ktakahashi@heap.phys.waseda.ac.jp

We analyzed the growth of non-spherical perturbations in supersonic accretion flows. We have in mind an application to the post-bounce phase of core-collapse supernovae (CCSNe). Such non-spherical perturbations have been suggested by a series of papers by Arnett, who has numerically investigated violent convections in the outer layers of pre-collapse stars. Moreover, Couch and Ott demonstrated in their numerical simulations that such perturbations may lead to a successful supernova even for a progenitor that fails to explode without fluctuations. This study investigated the linear growth of perturbations during the infall onto a stalled shock wave. The linearized equations are solvedmore » as an initial and boundary value problem with the use of a Laplace transform. The background is a Bondi accretion flow whose parameters are chosen to mimic the 15 M {sub ☉} progenitor model by Woosley and Heger, which is supposed to be a typical progenitor of CCSNe. We found that the perturbations that are given at a large radius grow as they flow down to the shock radius; the density perturbations can be amplified by a factor of 30, for example. We analytically show that the growth rate is proportional to l, the index of the spherical harmonics. We also found that the perturbations oscillate in time with frequencies that are similar to those of the standing accretion shock instability. This may have an implication for shock revival in CCSNe, which will be investigated in our forthcoming paper in more detail.« less

Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease

PubMed Central

2012-01-01

Background In vitro exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new in vitro model of NASH. Methods HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured. Results FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species. Conclusions The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH. PMID:22380754

Optimization of conditions for transient Agrobacterium-mediated gene expression assays in Arabidopsis.

PubMed

Kim, Mi Jung; Baek, Kon; Park, Chung-Mo

2009-08-01

Transient genetic transformation of plant organs is an indispensable way of studying gene function in plants. This study was aimed to develop an optimized system for transient Agrobacterium-mediated transformation of the Arabidopsis leaves. The beta-glucuronidase (GUS) reporter gene was employed to evaluate growth and biochemical parameters that influence the levels of transient expression. The effects of plant culture conditions, Agrobacterial genetic backgrounds, densities of Agrobacterial cell suspensions, and of several detergents were analyzed. We found that optimization of plant culture conditions is the most critical factor among the parameters analyzed. Higher levels of transient expression were observed in plants grown under short day conditions (SDs) than in plants grown under long day conditions (LDs). Furthermore, incubation of the plants under SDs at high relative humidity (85-90%) for 24 h after infiltration greatly improved the levels of transient expression. Under the optimized culture conditions, expression of the reporter gene reached the peak 3 days after infiltration and was rapidly decreased after the peak. Among the five Agrobacterial strains examined, LAB4404 produced the highest levels of expression. We also examined the effects of detergents, including Triton X-100, Tween-20, and Silwet L-77. Supplementation of the infiltration media either with 0.01% Triton X-100 or 0.01% Tween-20 improved the levels of expression by approximately 1.6-fold. Our observations indicate that transient transformation of the Arabidopsis leaves in the infiltration media supplemented with 0.01% Triton X-100 and incubation of the infiltrated plants under SDs at high relative humidity are necessary for maximal levels of expression.

Microstructure of warm rolling and pearlitic transformation of ultrafine-grained GCr15 steel

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

Sun, Jun-Jie; Lian, Fu-Liang; Liu, Hong-Ji

2014-09-15

Pearlitic transformation mechanisms have been investigated in ultra-fine grained GCr15 steel. The ultrafine-grained steel, whose grain size was less than 1 μm, was prepared by thermo-mechanical treatment at 873 K and then annealing at 923 K for 2 h. Pearlitic transformation was conducted by reheating the ultra-fine grained samples at 1073 K and 1123 K for different periods of time and then cooling in air. Scanning electron microscope observation shows that normal lamellar pearlite, instead of granular cementite and ferrite, cannot be formed when the grain size is approximately less than 4(± 0.6) μm, which yields a critical grain sizemore » for normal lamellar pearlitic transformations in this chromium alloyed steel. The result confirms that grain size has a great influence on pearlitic transformation by increasing the diffusion rate of carbon atoms in the ultra-fine grained steel, and the addition of chromium element doesn't change this pearlitic phase transformation rule. Meanwhile, the grain growth rate is reduced by chromium alloying, which is beneficial to form fine grains during austenitizing, thus it facilitating pearlitic transformation by divorced eutectoid transformation. Moreover, chromium element can form a relatively high gradient in the frontier of the undissolved carbide, which promotes carbide formation in the frontier of the undissolved carbide, i.e., chromium promotes divorced eutectoid transformation. - Highlights: • Ultrafine-grained GCr15 steel was obtained by warm rolling and annealing technology. • Reduction of grain size makes pearlite morphology from lamellar to granular. • Adding Cr does not change normal pearlitic phase transformation rule in UFG steel. • Cr carbide resists grain growth and facilitates pearlitic transformation by DET.« less

In situ Observations of Magnetosonic Waves Modulated by Background Plasma Density

NASA Astrophysics Data System (ADS)

Yu, X.; Yuan, Z.; Huang, S.; Wang, D.; Funsten, H. O.

2017-12-01

We report in situ observations by the Van Allen Probe mission that magnetosonic (MS) waves are clearly relevant to appear relevant to the background plasma number density. As the satellite moved across dense and tenuous plasma alternatively, MS waves occurred only in lower density region. As the observed protons with 'ring' distributions provide free energy, local linear growth rates are calculated and show that magnetosonic waves can be locally excited in tenuous plasma. With variations of the background plasma density, the temporal variations of local wave growth rates calculated with the observed proton ring distributions, show a remarkable agreement with those of the observed wave amplitude. Therefore, the paper provides a direct proof that background plasma densities can modulate the amplitudes of magnetosonic waves through controlling the wave growth rates.

Structural Variability of Tropospheric Growth Factors Transforming Mid-latitude Cyclones to Severe Storms over the North Atlantic

NASA Astrophysics Data System (ADS)

Wild, Simon; Befort, Daniel J.; Leckebusch, Gregor C.

2015-04-01

The development of European surface wind storms out of normal mid-latitude cyclones is substantially influenced by upstream tropospheric growth factors over the Northern Atlantic. The main factors include divergence and vorticity advection in the upper troposphere, latent heat release and the presence of instabilities of short baroclinic waves of suitable wave lengths. In this study we examine a subset of these potential growth factors and their related influences on the transformation of extra-tropical cyclones into severe damage prone surface storm systems. Previous studies have shown links between specific growth factors and surface wind storms related to extreme cyclones. In our study we investigate in further detail spatial and temporal variability patterns of these upstream processes at different vertical levels of the troposphere. The analyses will comprise of the three growth factors baroclinicity, latent heat release and upper tropospheric divergence. Our definition of surface wind storms is based on the Storm Severity Index (SSI) alongside a wind tracking algorithm identifying areas of exceedances of the local 98th percentile of the 10m wind speed. We also make use of a well-established extra-tropical cyclone identification and tracking algorithm. These cyclone tracks form the base for a composite analysis of the aforementioned growth factors using ERA-Interim Reanalysis from 1979 - 2014 for the extended winter season (ONDJFM). Our composite analysis corroborates previous similar studies but extends them by using an impact based algorithm for the identification of strong wind systems. Based on this composite analysis we further identify variability patterns for each growth factor most important for the transformation of a cyclone into a surface wind storm. We thus also address the question whether the link between storm intensity and related growth factor anomaly taking into account its spatial variability is stable and can be quantified. While the robustness of our preliminary results is generally dependent on the growth factor investigated, some examples include i) the overall availability of latent heat seems to be less important than its spatial structure around the cyclone core and ii) the variability of upper-tropospheric baroclinicity appears to be highest north of the surface position of the cyclone, especially for those that transform into a surface storm.

Applications of FT-IR spectrophotometry in cancer diagnostics.

PubMed

Bunaciu, Andrei A; Hoang, Vu Dang; Aboul-Enein, Hassan Y

2015-01-01

This review provides a brief background to the application of infrared spectroscopy, including Fourier transform-infrared spectroscopy, in biological fluids. It is not meant to be complete or exhaustive but to provide the reader with sufficient background for selected applications in cancer diagnostics. Fourier transform-infrared spectroscopy (FT-IR) is a fast and nondestructive analytical method. The infrared spectrum of a mixture serves as the basis to quantitate its constituents, and a number of common clinical chemistry tests have proven to be feasible using this approach. This review focuses on biomedical FT-IR applications, published in the period 2009-2013, used for early detection of cancer through qualitative and quantitative analysis.

Association of p21ras with phosphatidylinositol 3-kinase.

PubMed Central

Sjölander, A; Yamamoto, K; Huber, B E; Lapetina, E G

1991-01-01

In mammalian cells, ras genes code for 21-kDa GTP-binding proteins. Increased expression and mutations in specific amino acids have been closely linked to alterations of normal cell morphology, growth, and differentiation and, in particular, to neoplastic transformation. The signal transduction induced by these p21ras proteins is largely unknown; however, the signaling pathways of several growth factors have been reported to involve phosphatidylinositol (PtdIns) 3-kinase. In the present study of a Ha-ras-transformed epithelial cell line, we demonstrated increased PtdIns 3-kinase activity in anti-phosphotyrosine and anti-receptor (insulin and hybrid insulin-like growth factor I) immunoprecipitates of cells that had been stimulated with insulin or insulin-like growth factor I. The PtdIns 3-kinase activity was also immunoprecipitated in these experiments by the anti-Ras monoclonal antibody Y13-259. The specificity of this association with p21ras was ascertained by the neutralizing effect of the antigen peptide and the absence of PtdIns 3-kinase activity in Y13-259 immunoprecipitates from cells in which the ras gene was turned off. These data indicate that PtdIns 3-kinase activity is an important step in the cascade of reactions in p21ras signal transduction, suggesting that the alterations of the cytoskeleton and growth in ras-transformed cells could be mediated by PtdIns 3-kinase activity. Images PMID:1716764

Transforming growth factor-alpha short-circuits downregulation of the epidermal growth factor receptor.

PubMed

Ouyang, X; Gulliford, T; Huang, G; Epstein, R J

1999-04-01

Transforming growth factor-alpha (TGFalpha) is an epidermal growth factor receptor (EGFR) ligand which is distinguished from EGF by its acid-labile structure and potent transforming function. We recently reported that TGFalpha induces less efficient EGFR heterodimerization and downregulation than does EGF (Gulliford et al., 1997, Oncogene, 15:2219-2223). Here we use isoform-specific EGFR and ErbB2 antibodies to show that the duration of EGFR signalling induced by a single TGFalpha exposure is less than that induced by equimolar EGF. The protein trafficking inhibitor brefeldin A (BFA) reduces the duration of EGF signalling to an extent similar to that seen with TGFalpha alone; the effects of TGFalpha and BFA on EGFR degradation are opposite, however, with TGFalpha sparing EGFR from downregulation but BFA accelerating EGF-dependent receptor loss. This suggests that BFA blocks EGFR recycling and thus shortens EGF-dependent receptor signalling, whereas TGFalpha shortens receptor signalling and thus blocks EGFR downregulation. Consistent with this, repeated application of TGFalpha is accompanied by prolonged EGFR expression and signalling, whereas similar application of EGF causes receptor downregulation and signal termination. These findings indicate that constitutive secretion of pH-labile TGFalpha may perpetuate EGFR signalling by permitting early oligomer dissociation and dephosphorylation within acidic endosomes, thereby extinguishing a phosphotyrosine-based downregulation signal and creating an irreversible autocrine growth loop.

Posttraumatic growth, depressive symptoms, posttraumatic stress symptoms, post-migration stressors and quality of life in multi-traumatized psychiatric outpatients with a refugee background in Norway

PubMed Central

2012-01-01

Background Psychiatric outpatients with a refugee background have often been exposed to a variety of potentially traumatizing events, with numerous negative consequences for their mental health and quality of life. However, some patients also report positive personal changes, posttraumatic growth, related to these potentially traumatic events. This study describes posttraumatic growth, posttraumatic stress symptoms, depressive symptoms, post-migration stressors, and their association with quality of life in an outpatient psychiatric population with a refugee background in Norway. Methods Fifty five psychiatric outpatients with a refugee background participated in a cross-sectional study using clinical interviews to measure psychopathology (SCID-PTSD, MINI), and four self-report instruments measuring posttraumatic growth, posttraumatic stress symptoms, depressive symptoms, and quality of life (PTGI-SF, IES-R, HSCL-25-depression scale, and WHOQOL-Bref) as well as measures of social integration, social network and employment status. Results All patients reported some degree of posttraumatic growth, while only 31% reported greater amounts of growth. Eighty percent of the patients had posttraumatic stress symptoms above the cut-off point, and 93% reported clinical levels of depressive symptoms. Quality of life in the four domains of the WHOQOL-Bref levels were low, well below the threshold for the’life satisfaction’ standard proposed by Cummins. A hierarchic regression model including depressive symptoms, posttraumatic stress symptoms, posttraumatic growth, and unemployment explained 56% of the total variance found in the psychological health domain of the WHOQOL-Bref scale. Posttraumatic growth made the strongest contribution to the model, greater than posttraumatic stress symptoms or depressive symptoms. Post-migration stressors like unemployment, weak social network and poor social integration were moderately negatively correlated with posttraumatic growth and quality of life, and positively correlated with psychopathological symptoms. Sixty percent of the outpatients were unemployed. Conclusions Multi-traumatized refugees in outpatient clinics reported both symptoms of psychopathology and posttraumatic growth after exposure to multiple traumatic events. Symptoms of psychopathology were negatively related to the quality of life, and positively related to post-migration stressors such as unemployment, weak social network and poor social integration. Posttraumatic growth was positively associated with quality of life, and negatively associated with post-migration stressors. Hierarchical regression modeling showed that posttraumatic growth explained more of the variance in quality of life than did posttraumatic stress symptoms, depressive symptoms or unemployment. It may therefore be necessary to address both positive changes and psychopathological symptoms when assessing and treating multi-traumatized outpatients with a refugee background. PMID:22824521

Oceanic transform faults: how and why do they form? (Invited)

NASA Astrophysics Data System (ADS)

Gerya, T.

2013-12-01

Oceanic transform faults at mid-ocean ridges are often considered to be the direct product of plate breakup process (cf. review by Gerya, 2012). In contrast, recent 3D thermomechanical numerical models suggest that transform faults are plate growth structures, which develop gradually on a timescale of few millions years (Gerya, 2010, 2013a,b). Four subsequent stages are predicted for the transition from rifting to spreading (Gerya, 2013b): (1) crustal rifting, (2) multiple spreading centers nucleation and propagation, (3) proto-transform faults initiation and rotation and (4) mature ridge-transform spreading. Geometry of the mature ridge-transform system is governed by geometrical requirements for simultaneous accretion and displacement of new plate material within two offset spreading centers connected by a sustaining rheologically weak transform fault. According to these requirements, the characteristic spreading-parallel orientation of oceanic transform faults is the only thermomechanically consistent steady state orientation. Comparison of modeling results with the Woodlark Basin suggests that the development of this incipient spreading region (Taylor et al., 2009) closely matches numerical predictions (Gerya, 2013b). Model reproduces well characteristic 'rounded' contours of the spreading centers as well as the presence of a remnant of the broken continental crustal bridge observed in the Woodlark basin. Similarly to the model, the Moresby (proto)transform terminates in the oceanic rather than in the continental crust. Transform margins and truncated tip of one spreading center present in the model are documented in nature. In addition, numerical experiments suggest that transform faults can develop gradually at mature linear mid-ocean ridges as the result of dynamical instability (Gerya, 2010). Boundary instability from asymmetric plate growth can spontaneously start in alternate directions along successive ridge sections; the resultant curved ridges become transform faults. Offsets along the transform faults change continuously with time by asymmetric plate growth and discontinuously by ridge jumps. The ridge instability is governed by rheological weakening of active fault structures. The instability is most efficient for slow to intermediate spreading rates, whereas ultraslow and (ultra)fast spreading rates tend to destabilize transform faults (Gerya, 2010; Püthe and Gerya, 2013) References Gerya, T. (2010) Dynamical instability produces transform faults at mid-ocean ridges. Science, 329, 1047-1050. Gerya, T. (2012) Origin and models of oceanic transform faults. Tectonophys., 522-523, 34-56 Gerya, T.V. (2013a) Three-dimensional thermomechanical modeling of oceanic spreading initiation and evolution. Phys. Earth Planet. Interiors, 214, 35-52. Gerya, T.V. (2013b) Initiation of transform faults at rifted continental margins: 3D petrological-thermomechanical modeling and comparison to the Woodlark Basin. Petrology, 21, 1-10. Püthe, C., Gerya, T.V. (2013) Dependence of mid-ocean ridge morphology on spreading rate in numerical 3-D models. Gondwana Res., DOI: http://dx.doi.org/10.1016/j.gr.2013.04.005 Taylor, B., Goodliffe, A., Martinez, F. (2009) Initiation of transform faults at rifted continental margins. Comptes Rendus Geosci., 341, 428-438.

Hydroxyl radical induced photo-transformation of single-walled carbon nanotubes in the aquatic environment

EPA Science Inventory

Inevitably, the growth in production of carbon nanotubes will translate into their release into our environment, yet existing information about their fate and persistence is limited. We hypothesize that indirect photochemical transformation of unfunctionalized carbon nanotubes is...

High Efficiency Transformation of Cultured Tobacco Cells 1

PubMed Central

An, Gynheung

1985-01-01

Tobacco calli were transformed at levels up to 50% by cocultivation of tobacco cultured cells with Agrobacterium tumefaciens harboring the binary transfer-DNA vector, pGA472, containing a kanamycin resistance marker. Transformation frequency was dependent on the physiological state of the tobacco cells, the nature of Agrobacterium strain and, less so, on the expression of the vir genes of the tumor-inducing plasmid. Maximum transformation frequency was obtained with exponentially growing plant cells, suggesting that rapid growth of plant cells is an essental factor for efficient transformation of higher plants. Images Fig. 1 PMID:16664453

Functional analysis of overexpressed PtDRS1 involved in abiotic stresses enhances growth in transgenic poplar.

PubMed

Mohammadi, Kourosh; Movahedi, Ali; Maleki, Samaneh Sadat; Sun, Weibo; Zhang, Jiaxin; Almasi Zadeh Yaghuti, Amir; Nourmohammadi, Saeed; Zhuge, Qiang

2018-05-01

Drought and salinity are two main abiotic stressors that can disrupt plant growth and survival. Various biotechnological approaches have been used to alleviate the problem of drought stress by improving water stress resistance in forestry and agriculture. The drought sensitive 1 (DRS1) gene acts as a regulator of drought stress, identified in human, yeast and some model plants, such as Arabidopsis thaliana, but there have been no reports of DRS1 transformation in poplar plants to date. In this study, we transformed the DRS1 gene from Populus trichocarpa into Populus deltoides × Populus euramericana 'Nanlin895' using Agrobacterium tumefaciens-mediated transformation. We confirmed that the DRS1 gene was transformed into 'Nanlin895' poplar genomes using reverse transcription polymerase chain reaction (PCR), multiplex PCR, real-time PCR, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All transformed and wild-type (WT) plants were then transferred into a greenhouse for complementary experiments. We analyzed the physiological and biochemical responses of transgenic plants under drought and salt stresses in the greenhouse, and the results were compared with control WT plants. Responses to abiotic stress were greater in transgenic plants compared with WT. Based on our results, introduction of the DRS1 gene into poplar 'Nanlin895' plants significantly enhanced the resistance of those plants to water deficit and high salinity, allowing higher growth rates of roots and shoots in those plants. Additionally, the clawed root rate increased in transformed poplars grown in culture media or in soil, and improved survival under drought and salt stress conditions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

National Research Council Dialogue to Assess Progress on NASA's Systems Engineering Cost/Risk Analysis Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Regenie, Victoria

2005-01-01

Contents include the following: General Background and Introduction of Capability. Roadmaps for Systems Engineering Cost/Risk Analysis. Agency Objectives. Strategic Planning Transformation. Review Capability Roadmaps and Schedule. Review Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

Effect of the theta-alpha-Al2O3 transformation on the oxidation behavior of beta-NiAl+Zr

NASA Technical Reports Server (NTRS)

Rybicki, George C.; Smialek, James L.

1989-01-01

Isothermal oxidation of NiAl+Zr has been performed over the temperature range of 800-1200 C and studied by TGA, XRD, and SEM. A discontinuous decrease in growth rate of two orders of magnitude was observed at 1000 C due to the formation of alpha-Al2O3 from theta-Al2O3. This transformation also resulted in a dramatic change in the surface morphology of the scales, as a whisker topography was changed into a weblike network of oxide ridges and radial transformation cracks. It is believed that the ridges are evidence for a short-circuit outward aluminum diffusion growth mechanism that has been documented in a number of O-18 tracer studies.

Nanowire growth by an electron beam induced massive phase transformation

DOE PAGES

Sood, Shantanu; Kisslinger, Kim; Gouma, Perena

2014-11-15

Tungsten trioxide nanowires of a high aspect ratio have been synthesized in-situ in a TEM under an electron beam of current density 14A/cm² due to a massive polymorphic reaction. Sol-gel processed pseudocubic phase nanocrystals of tungsten trioxide were seen to rapidly transform to one dimensional monoclinic phase configurations, and this reaction was independent of the substrate on which the material was deposited. The mechanism of the self-catalyzed polymorphic transition and accompanying radical shape change is a typical characteristic of metastable to stable phase transformations in nanostructured polymorphic metal oxides. A heuristic model is used to confirm the metastable to stablemore » growth mechanism. The findings are important to the control electron beam deposition of nanowires for functional applications starting from colloidal precursors.« less

Phase Transformations and Microstructural Evolution: Part I

DOE PAGES

Clarke, Amy Jean

2015-08-29

The activities of the Phase Transformations Committee of the Materials Processing & Manufacturing Division (MPMD) of The Minerals, Metals & Materials Society (TMS) are oriented toward understanding the fundamental aspects of phase transformations. Emphasis is placed on the thermodynamic driving forces for phase transformations, the kinetics of nucleation and growth, interfacial structures and energies, transformation crystallography, surface reliefs, and, above all, the atomic mechanisms of phase transformations. Phase transformations and microstructural evolution are directly linked to materials processing, properties, and performance, including in extreme environments, of structural metal alloys. In this paper, aspects of phase transformations and microstructural evolution aremore » highlighted from the atomic to the microscopic scale for ferrous and non-ferrous alloys. Many papers from this issue are highlighted with small summaries of their scientific achievements given.« less

Structure evolution of zinc oxide thin films deposited by unbalance DC magnetron sputtering

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

Aryanto, Didik, E-mail: didi027@lipi.go.id; Materials Research Group, Physics Department, Universitas Negeri Semarang, Gunungpati, Semarang 50229 Jawa Tengah; Marwoto, Putut

Zinc oxide (ZnO) thin films are deposited on corning glass substrates using unbalanced DC magnetron sputtering. The effect of growth temperature on surface morphology and crystallographic orientation of ZnO thin film is studied using atomic force microscopy (AFM) and X-ray diffraction (XRD) techniques. The surface morphology and crystallographic orientation of ZnO thin film are transformed against the increasing of growth temperature. The mean grain size of film and the surface roughness are inversely and directly proportional towards the growth temperature from room temperature to 300 °C, respectively. The smaller grain size and finer roughness of ZnO thin film are obtainedmore » at growth temperature of 400 °C. The result of AFM analysis is in good agreement with the result of XRD analysis. ZnO thin films deposited in a series of growth temperatures have hexagonal wurtzite polycrystalline structures and they exhibit transformations in the crystallographic orientation. The results in this study reveal that the growth temperature strongly influences the surface morphology and crystallographic orientation of ZnO thin film.« less

Effects of medium and trace metals on kinetics of carbon tetrachloride transformation by Pseudomonas sp. strain KC.

PubMed Central

Tatara, G M; Dybas, M J; Criddle, C S

1993-01-01

Under denitrifying conditions, Pseudomonas sp. strain KC transforms carbon tetrachloride (CT) to carbon dioxide via a complex but as yet undetermined mechanism. Transformation rates were first order with respect to CT concentration over the CT concentration range examined (0 to 100 micrograms/liter) and proportional to protein concentration, giving pseudo-second-order kinetics overall. Addition of ferric iron (1 to 20 microM) to an actively transforming culture inhibited CT transformation, and the degree of inhibition increased with increasing iron concentration. By removing iron from the trace metals solution or by removing iron-containing precipitate from the growth medium, higher second-order rate coefficients were obtained. Copper also plays a role in CT transformation. Copper was toxic at neutral pH. By adjusting the medium pH to 8.2, soluble iron and copper levels decreased as a precipitate formed, and CT transformation rates increased. However, cultures grown at high pH without any added trace copper (1 microM) exhibited slower growth rates and greatly reduced rates of CT transformation, indicating that copper is required for CT transformation. The use of pH adjustment to decrease iron solubility, to avoid copper toxicity, and to provide a selective advantage for strain KC was evaluated by using soil slurries and groundwater containing high levels of iron. In samples adjusted to pH 8.2 and inoculated with strain KC, CT disappeared rapidly in the absence or presence of acetate or nitrate supplements. CT did not disappear in pH-adjusted controls that were not inoculated with strain KC. PMID:8357248

Accounting for inherent variability of growth in microbial risk assessment.

PubMed

Marks, H M; Coleman, M E

2005-04-15

Risk assessments of pathogens need to account for the growth of small number of cells under varying conditions. In order to determine the possible risks that occur when there are small numbers of cells, stochastic models of growth are needed that would capture the distribution of the number of cells over replicate trials of the same scenario or environmental conditions. This paper provides a simple stochastic growth model, accounting only for inherent cell-growth variability, assuming constant growth kinetic parameters, for an initial, small, numbers of cells assumed to be transforming from a stationary to an exponential phase. Two, basic, microbial sets of assumptions are considered: serial, where it is assume that cells transform through a lag phase before entering the exponential phase of growth; and parallel, where it is assumed that lag and exponential phases develop in parallel. The model is based on, first determining the distribution of the time when growth commences, and then modelling the conditional distribution of the number of cells. For the latter distribution, it is found that a Weibull distribution provides a simple approximation to the conditional distribution of the relative growth, so that the model developed in this paper can be easily implemented in risk assessments using commercial software packages.

Genetics Home Reference: Shprintzen-Goldberg syndrome

MedlinePlus

... the transforming growth factor beta (TGF-β) signaling pathway. The TGF-β pathway regulates many processes, including cell growth and division ( ... apoptosis ). By attaching to certain proteins in the pathway, the SKI protein blocks TGF-β signaling. The ...

The Spiritual Disciplines as Practices of Transformation

ERIC Educational Resources Information Center

Carr-Chellman, Davin J.; Kroth, Michael

2017-01-01

Spiritual disciplines are practices of transformation intentionally pursued through the day-to-day actions of deeper living. The spiritual disciplines are conceptualized here in their relationship to profound learning. The authors contend that profound learners exhibit certain dispositions, such as curiosity, that facilitate continual growth.…

Development of human epithelial cell systems for radiation risk assessment

NASA Technical Reports Server (NTRS)

Yang, C. H.; Craise, L. M.

1994-01-01

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

Down-regulation of Rab5 decreases characteristics associated with maintenance of cell transformation

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

Silva, Patricio; Soto, Nicolás; Díaz, Jorge

2015-08-21

The early endosomal protein Rab5 is highly expressed in tumor samples, although a causal relationship between Rab5 expression and cell transformation has not been established. Here, we report the functional effects of targeting endogenous Rab5 with specific shRNA sequences in different tumor cell lines. Rab5 down-regulation in B16-F10 cells decreased tumor formation by subcutaneous injection into C57/BL6 mice. Accordingly, Rab5 targeting in B16-F10 and A549, but not MDA-MB-231 cells was followed by decreased cell proliferation, increased apoptosis and decreased anchorage-independent growth. These findings suggest that Rab5 expression is required to maintain characteristics associated with cell transformation. - Highlights: • Rab5more » is important to the maintenance of cell transformation characteristics. • Down-regulation of Rab5 decreases cell proliferation and increases apoptosis in different cancer cells. • Rab5 is required for anchorage-independent growth and tumorigenicity in-vivo.« less

Step-scan differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS): a spectral deconvolution method for weak absorber detection in the presence of strongly overlapping background absorptions.

PubMed

Liu, Lixian; Mandelis, Andreas; Huan, Huiting; Michaelian, Kirk H

2017-04-01

The determination of small absorption coefficients of trace gases in the atmosphere constitutes a challenge for analytical air contaminant measurements, especially in the presence of strongly absorbing backgrounds. A step-scan differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) method was developed to suppress the coherent external noise and spurious photoacoustic (PA) signals caused by strongly absorbing backgrounds. The infrared absorption spectra of acetylene (C₂H₂) and local air were used to verify the performance of the step-scan DFTIR-PAS method. A linear amplitude response to C₂H₂ concentrations from 100 to 5000 ppmv was observed, leading to a theoretical detection limit of 5 ppmv. The differential mode was capable of eliminating the coherent noise and dominant background gas signals, thereby revealing the presence of the otherwise hidden C₂H₂ weak absorption. Thus, the step-scan DFTIR-PAS modality was demonstrated to be an effective approach for monitoring weakly absorbing gases with absorption bands overlapped by strongly absorbing background species.

End-of-Decade Survey Shows Academic Growth in Public Relations.

ERIC Educational Resources Information Center

Walker, Albert

1982-01-01

Compared surveys of public relations education (1970, 1975, 1980). Found, among other results, that (1) enrollment growth is the most significant change; (2) students are graduating with weak backgrounds in business; (3) teachers need stronger backgrounds, interest, and records in research. For journal availability, see CS 705 902. (PD)

Morphological transformation of soot: investigation of microphysical processes during the condensation of sulphuric acid and limonene ozonolysis products vapours

NASA Astrophysics Data System (ADS)

Pathak, R. K. P.; Pei, X.; Hallquist, M.; Pagels, J. H.

2017-12-01

Morphological transformation of soot particle by condensation of low volatility materials on it is a dominant atmospheric process with serious implications for its optical and hygroscopic properties, and atmospheric lifetime. In this study, the morphological transformation of soot agglomerate under the influence of condensation of vapours of sulphuric acid, and/or limonene ozonolysis products were investigated systematically using a Differential Mobility Analyser-Aerosol Particle Mass Analyser (DMA-APM) and the Tandem DMA techniques integrated with a laminar flow-tube system. We discovered that the morphology transformation of soot in general was a sequence of two-step process, i.e. (i) filling of void space within soot agglomerate; (ii) growth of particle diameter. These two steps followed and complimented each other. In the very beginning the filling was the dominant process followed by growth until it led to the accumulation of enough material that in turn exerted surface forces that eventually facilitated the further filling. The filling of void space was constrained by the initial morphology of fresh soot and the nature and amount of the material condensed. This process continued in several sequential steps until all void space within the soot agglomerate was filled completely and then growth of a spherical particle continued as long as mass was condensed on it. In this study, we developed a framework to quantify the microphysical transformation of soot upon the condensation of various materials. The framework utilized experimental data and hypothesis of ideal sphere growth and filling of voids to quantify the distribution of condensed materials in these two processes complimenting each other. Using this framework, we have quantified the percentage of material that went into processes of particle growth and void filling at each step. Using the same framework, we further estimated the fraction of internal voids and open voids and used this information to derive the volume equivalent diameter of soot agglomerate containing internal voids and calculated in-situ dynamic shape factor. Our study is the first study that tracks in situ microphysical changes in soot morphology quantitatively, providing the detailed status of both fresh and coated soot particles.

Protocol: optimising hydroponic growth systems for nutritional and physiological analysis of Arabidopsis thaliana and other plants

PubMed Central

2013-01-01

Background Hydroponic growth systems are a convenient platform for studying whole plant physiology. However, we found through trialling systems as they are described in the literature that our experiments were frequently confounded by factors that affected plant growth, including algal contamination and hypoxia. We also found the way in which the plants were grown made them poorly amenable to a number of common physiological assays. Results The drivers for the development of this hydroponic system were: 1) the exclusion of light from the growth solution; 2) to simplify the handling of individual plants, and 3) the growth of the plant to allow easy implementation of multiple assays. These aims were all met by the use of pierced lids of black microcentrifuge tubes. Seed was germinated on a lid filled with an agar-containing germination media immersed in the same solution. Following germination, the liquid growth media was exchanged with the experimental solution, and after 14-21 days seedlings were transferred to larger tanks with aerated solution where they remained until experimentation. We provide details of the protocol including composition of the basal growth solution, and separate solutions with altered calcium, magnesium, potassium or sodium supply whilst maintaining the activity of the majority of other ions. We demonstrate the adaptability of this system for: gas exchange measurement on single leaves and whole plants; qRT-PCR to probe the transcriptional response of roots or shoots to altered nutrient composition in the growth solution (we demonstrate this using high and low calcium supply); producing highly competent mesophyll protoplasts; and, accelerating the screening of Arabidopsis transformants. This system is also ideal for manipulating plants for micropipette techniques such as electrophysiology or SiCSA. Conclusions We present an optimised plant hydroponic culture system that can be quickly and cheaply constructed, and produces plants with similar growth kinetics to soil-grown plants, but with the advantage of being a versatile platform for a myriad of physiological and molecular biological measurements on all plant tissues at all developmental stages. We present ‘tips and tricks’ for the easy adoption of this hydroponic culture system. PMID:23379342

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration

PubMed Central

2014-01-01

Background Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Methods Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Results Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. Conclusions Taken together, these results demonstrate that dHACM grafts: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds. PMID:24817999

Solitons and rogue waves in spinor Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Li, Sitai; Prinari, Barbara; Biondini, Gino

2018-02-01

We present a general classification of one-soliton solutions as well as families of rogue-wave solutions for F =1 spinor Bose-Einstein condensates (BECs). These solutions are obtained from the inverse scattering transform for a focusing matrix nonlinear Schrödinger equation which models condensates in the case of attractive mean-field interactions and ferromagnetic spin-exchange interactions. In particular, we show that when no background is present, all one-soliton solutions are reducible via unitary transformations to a combination of oppositely polarized solitonic solutions of single-component BECs. On the other hand, we show that when a nonzero background is present, not all matrix one-soliton solutions are reducible to a simple combination of scalar solutions. Finally, by taking suitable limits of all the solutions on a nonzero background we also obtain three families of rogue-wave (i.e., rational) solutions.

Solitons and rogue waves in spinor Bose-Einstein condensates.

PubMed

Li, Sitai; Prinari, Barbara; Biondini, Gino

2018-02-01

We present a general classification of one-soliton solutions as well as families of rogue-wave solutions for F=1 spinor Bose-Einstein condensates (BECs). These solutions are obtained from the inverse scattering transform for a focusing matrix nonlinear Schrödinger equation which models condensates in the case of attractive mean-field interactions and ferromagnetic spin-exchange interactions. In particular, we show that when no background is present, all one-soliton solutions are reducible via unitary transformations to a combination of oppositely polarized solitonic solutions of single-component BECs. On the other hand, we show that when a nonzero background is present, not all matrix one-soliton solutions are reducible to a simple combination of scalar solutions. Finally, by taking suitable limits of all the solutions on a nonzero background we also obtain three families of rogue-wave (i.e., rational) solutions.

Application of point-to-point matching algorithms for background correction in on-line liquid chromatography-Fourier transform infrared spectrometry (LC-FTIR).

PubMed

Kuligowski, J; Quintás, G; Garrigues, S; de la Guardia, M

2010-03-15

A new background correction method for the on-line coupling of gradient liquid chromatography and Fourier transform infrared spectrometry has been developed. It is based on the use of a point-to-point matching algorithm that compares the absorption spectra of the sample data set with those of a previously recorded reference data set in order to select an appropriate reference spectrum. The spectral range used for the point-to-point comparison is selected with minimal user-interaction, thus facilitating considerably the application of the whole method. The background correction method has been successfully tested on a chromatographic separation of four nitrophenols running acetonitrile (0.08%, v/v TFA):water (0.08%, v/v TFA) gradients with compositions ranging from 35 to 85% (v/v) acetonitrile, giving accurate results for both, baseline resolved and overlapped peaks. Copyright (c) 2009 Elsevier B.V. All rights reserved.

The Nature and Effects of Transformational School Leadership: A Meta-Analytic Review of Unpublished Research

ERIC Educational Resources Information Center

Leithwood, Kenneth; Sun, Jingping

2012-01-01

Background: Using meta-analytic review techniques, this study synthesized the results of 79 unpublished studies about the nature of transformational school leadership (TSL) and its impact on the school organization, teachers, and students. This corpus of research associates TSL with 11 specific leadership practices. These practices, as a whole,…

Transformative Praxis in Teacher Practice: One Tauira Finds Her Place in Education

ERIC Educational Resources Information Center

Sexton, Steven S.

2011-01-01

This paper reports on an initial teacher education programme that has been designed to facilitate and support Maori student teachers in New Zealand. This paper highlights the ambiguity in New Zealand on the theoretical foundation of initial teacher education. Therefore a background on transformative praxis and how it has impacted on the education…

TPA induces a block of differentiation and increases the susceptibility to neoplastic transformation of a rat thyroid epithelial cell line.

PubMed

Portella, G; Vitagliano, D; Li, Z; Sferratore, F; Santoro, M; Vecchio, G; Fusco, A

1998-01-01

The PC Cl 3 cell line is a well-characterized epithelial cell line of rat thyroid origin. This cell line retains in vitro the typical markers of thyroid differentiation: thyroglobulin (TG) synthesis and secretion, iodide uptake, thyroperoxidase (TPO) expression, and dependency on TSH for growth. Although the differentiated phenotype of thyroid cells has been relatively well described, the molecular mechanisms that regulate both differentiation and neoplastic transformation of thyroid cells still need to be investigated in detail. Protein kinase C (PKC), the target of tetradecanoylphorbol acetate (TPA), regulates growth and differentiation of several cell types. Here we show that treatment of PC Cl 3 cells with TPA induces an acute block of thyroid differentiation. TPA-treated PC Cl 3 cells are unable to trap iodide and the expression levels of thyroglobulin, TSH receptor, and TPO genes are drastically reduced by TPA treatment. This differentiation block is not caused by a reduced expression of one of the master genes of thyroid differentiation, the thyroid transcription factor 1 (TTF-1). TPA-treated PC Cl 3 cells display an increased growth rate indicating that, in addition to the differentiation block, TPA also significantly affects the growth regulation of thyroid cells. Finally, TPA treatment dramatically increases the number of transformation foci induced in PC Cl 3 cells by retroviruses carrying v-Ki-ras, v-Ha-ras, and v-mos oncogenes. These findings support the notion that the PKC pathway can influence proliferation, differentiation, and neoplastic transformation of thyroid cells in culture.

Growth and element flux at fine taxonomic resolution in natural microbial communities

NASA Astrophysics Data System (ADS)

Hungate, Bruce; Mau, Rebecca; Schwartz, Egbert; Caporaso, J. Gregory; Dijkstra, Paul; van Gestel, Natasja; Koch, Benjamin J.; Liu, Cindy M.; McHugh, Theresa; Marks, Jane C.; Morrissey, Ember; Price, Lance B.

2015-04-01

Microorganisms are the engines of global biogeochemical cycles, driving half of all photosynthesis and nearly all decomposition. Yet, quantifying the rates at which uncultured microbial taxa grow and transform elements in intact and highly diverse natural communities in the environment remains among the most pressing challenges in microbial ecology today. Here, we show how shifts in the density of DNA caused by stable isotope incorporation can be used to estimate the growth rates of individual bacterial taxa in intact soil communities. We found that the distribution of growth rates followed the familiar lognormal distribution observed for the abundances, biomasses, and traits of many organisms. Growth rates of most bacterial taxa increased in response to glucose amendment, though the increase in growth observed for many taxa was larger than could be explained by direct utilization of the added glucose for growth, illustrating that glucose addition indirectly stimulated the utilization of other substrates. Variation in growth rates and phylogenetic distances were quantitatively related, connecting evolutionary history and biogeochemical function in intact soil microbial communities. Our approach has the potential to identify biogeochemically significant taxa in the microbial community and quantify their contributions to element transformations and ecosystem processes.

Induction of anchorage-independent growth in primary human cells exposed to protons or HZE ions separately or in dual exposures.

PubMed

Sutherland, B M; Cuomo, N C; Bennett, P V

2005-10-01

Travelers on space missions will be exposed to a complex radiation environment that includes protons and heavy charged particles. Since protons are present at much higher levels than are heavy ions, the most likely scenario for cellular radiation exposure will be proton exposure followed by a hit by a heavy ion. Although the effects of individual ion species on human cells are being investigated extensively, little is known about the effects of exposure to both radiation types. One useful measure of mammalian cell damage is induction of the ability to grow in a semi-solid agar medium highly inhibitory to the growth of normal human cells, termed neoplastic transformation. Using primary human cells, we evaluated induction of soft-agar growth and survival of cells exposed to protons only or to heavy charged particles (600 MeV/nucleon silicon) only as well as of cells exposed to protons followed after a 4-day interval by silicon ions. Both ions alone efficiently transformed the human cells to anchorage-independent growth. Initial experiments indicate that the dose responses for neoplastic transformation of cells exposed to protons and then after 4 days to silicon ions appear similar to that of cells exposed to silicon ions alone.

Multidisciplinary characterization of the long-bone cortex growth patterns through sheep's ontogeny.

PubMed

Cambra-Moo, Oscar; Nacarino-Meneses, Carmen; Díaz-Güemes, Idoia; Enciso, Silvia; García Gil, Orosia; Llorente Rodríguez, Laura; Rodríguez Barbero, Miguel Ángel; de Aza, Antonio H; González Martín, Armando

2015-07-01

Bone researches have studied extant and extinct taxa extensively trying to disclose a complete view of the complex structural and chemical transformations that model and remodel the macro and microstructure of bone during growth. However, to approach bone growth variations is not an easy task, and many aspects related with histological transformations during ontogeny remain unresolved. In the present study, we conduct a holistic approach using different techniques (polarized microscopy, Raman spectroscopy and X-ray diffraction) to examine the histomorphological and histochemical variations in the cortical bone of sheep specimens from intrauterine to adult stages, using environmentally controlled specimens from the same species. Our results suggest that during sheep bone development, the most important morphological (shape and size) and chemical transformations in the cortical bone occur during the first weeks of life; synchronized but dissimilar variations are established in the forelimb and hind limb cortical bone; and the patterns of bone tissue maturation in both extremities are differentiated in the adult stage. All of these results indicate that standardized histological models are useful not only for evaluating many aspects of normal bone growth but also to understand other important influences on the bones, such as pathologies that remain unknown. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidermal growth factor impairs palatal shelf adhesion and fusion in the Tgf-β 3 null mutant.

PubMed

Barrio, M Carmen; Del Río, Aurora; Murillo, Jorge; Maldonado, Estela; López-Gordillo, Yamila; Paradas-Lara, Irene; Hernandes, Luzmarina; Catón, Javier; Martínez-Álvarez, Concepción

2014-01-01

The cleft palate presented by transforming growth factor-β3 (Tgf-β3) null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-β1 (Tgf-β1) and muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in Tgf-β3 knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, Tgf-β1 and Msx-1 in Tgf-β3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-β3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal mesenchyme. Inhibition of TGF-β1 does not affect either EGF or Msx-1 expression. © 2014 S. Karger AG, Basel.

Infrared images target detection based on background modeling in the discrete cosine domain

NASA Astrophysics Data System (ADS)

Ye, Han; Pei, Jihong

2018-02-01

Background modeling is the critical technology to detect the moving target for video surveillance. Most background modeling techniques are aimed at land monitoring and operated in the spatial domain. A background establishment becomes difficult when the scene is a complex fluctuating sea surface. In this paper, the background stability and separability between target are analyzed deeply in the discrete cosine transform (DCT) domain, on this basis, we propose a background modeling method. The proposed method models each frequency point as a single Gaussian model to represent background, and the target is extracted by suppressing the background coefficients. Experimental results show that our approach can establish an accurate background model for seawater, and the detection results outperform other background modeling methods in the spatial domain.

Random T-DNA mutagenesis identifies a Cu-Zn-superoxide dismutase gene as a virulence factor of Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

Agrobacterium-mediated transformation (AMT) was used to identify potential virulence factors in Sclerotinia sclerotiorum. Screening AMT transformants identified two mutants showing significantly reduced virulence. The mutants showed similar growth rate, colony morphology, and sclerotial and oxalate ...

A critical role for transcription factor Smad4 in T cell function independent of transforming growth factor beta receptor signaling

PubMed Central

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A.; Wan, Yisong Y.

2014-01-01

Summary Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. While Smad4 was dispensable for T cell generation, homeostasis and effector function, it was essential for T cell proliferation following activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity and anti-tumor immunity. PMID:25577439

A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor β receptor signaling.

PubMed

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A; Wan, Yisong Y

2015-01-20

Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

PubMed Central

Maalouf, Katia; Baydoun, Elias; Rizk, Sandra

2011-01-01

Background: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer. Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes. Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry. Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 μg/μL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF-β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines. Conclusion: In conclusion, kefir is effective in inhibiting proliferation and inducing apoptosis of HTLV-1-negative malignant T-lymphocytes. Therefore, further in vivo investigation is highly recommended. PMID:21448298

Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy

PubMed Central

Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

2009-01-01

Background Insulin-like growth factor-1 (IGF-1), transforming growth factor β (TGFβ) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Methods Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFβ and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Results Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFβ, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. Conclusion These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies. PMID:19818143

Nasal bone length in human fetuses by X-ray.

PubMed

Moura, Felipe Nobre; Fernandes, Pablo Lourenco; de Oliveira Silva-Junior, Geraldo; Gomes de Souza, Margareth Maria; Mandarim-de-Lacerda, Carlos Alberto

2008-07-01

To construct a normal range for the prenatal nasal bone length (NBL) in Brazilians irrespective to the knowledge of the ethnic genetic background. We studied 35 human fetuses (20 males, 15 females) ranging from 14 to 22 weeks of gestation. Gestational age (GA), crown-rump length (CRL), foot length (FL) and body mass (BM) were measured. The X-ray of the head lateral view was made with the specimens placed directly on the film and the NBL was measured. The NBL was correlated with the GA, the CRL, the FL, and the BM using log-transformed data and the allometric model log y=log a+b log x. Correlations of the NBL growth with GA, CRL, FL, and BM were positive and significant (P<0.05), but NBL vs. BM showed the smallest R indicating this correlation as of little practical use. No sexual dimorphism in the NBL growth in the second trimester fetuses was observed. The NBL grew with positive allometry relative to GA, CRL and BM, but it was allometrically slightly negative relative to the FL in both genders. The NBL be allometrically positive against GA, CRL and BM means the bone grew with growth rates higher than those indices in the period analyzed, but not against FL. NBL could be considered an auxiliary measurement in the assessment of the 2nd trimester fetal development because its strong correlation with GA, CRL and FL, even when nothing is known about the ethnicity of the population.

Normal platelet function in platelet concentrates requires non-platelet cells: a comparative in vitro evaluation of leucocyte-rich (type 1a) and leucocyte-poor (type 3b) platelet concentrates

PubMed Central

Parrish, William R; Roides, Breana; Hwang, Julia; Mafilios, Michael; Story, Brooks; Bhattacharyya, Samir

2016-01-01

Background Therapeutic success of platelet-rich plasma (PRP) may vary based on the composition and preparation method. The objective of this study was to evaluate the cellular components of platelet concentrates produced by a leucocyte-rich (LR-PRP) and a leucocyte-poor PRP systems (LP-PRP). Methods Parameters evaluated included platelet recovery, platelet concentration, red blood cell (RBC) and white blood cell (WBC) composition, platelet growth factor release and stimulation of human tendon cell proliferation in vitro. Results Platelet recoveries were 52% for LP-PRP and 89% for LR-PRP. LR-PRP demonstrated greater reproducibility with a 4.2% coefficient of variation (CV) compared with 19.4% for LP-PRP (p<0.001). LR-PRP demonstrated a greater increase in platelet concentration (7.9-fold) than LP-PRP (2.2-fold; p<0.001). LP-PRP showed 5.0-fold reductions in WBCs, while LR-PRP showed a 4.0-fold increase (p<0.001). LP-PRP reduced RBCs to a haematocrit of 0.25, while LR-PRP reduced haematocrit to 11.8. LP-PRP did not coagulate robustly on reactivation with CaCl2, and released significantly lower levels of epidermal growth factor (EGF) and transforming growth factor β1 (TGF-β1) than whole blood (p<0.03). LP-PRP also did not stimulate tendon cell proliferation greater than whole blood. In contrast, LR-PRP showed increases in each growth factor on activation with CaCl2 (p<0.01) and stimulated greater proliferation (p<0.05) compared with whole blood. Forced activation of LP-PRP with exogenous thrombin rescued the coagulation deficiency and induced greater growth factor release than comparable whole blood (p<0.03). Conclusions These data suggest that non-platelet cellular components in platelet concentrates are important for proper platelet function, including thrombin generation, growth factor release and clot retraction. PMID:27900155

Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components

PubMed Central

Fekete, Natalie; Gadelorge, Mélanie; Fürst, Daniel; Maurer, Caroline; Dausend, Julia; Fleury-Cappellesso, Sandrine; Mailänder, Volker; Lotfi, Ramin; Ignatius, Anita; Sensebé, Luc; Bourin, Philippe; Schrezenmeier, Hubert; Rojewski, Markus Thomas

2012-01-01

Background aims The clinical use of human mesenchymal stromal cells (MSC) requires ex vivo expansion in media containing supplements such as fetal bovine serum or, alternatively, human platelet lysate (PL). Methods Platelet concentrates were frozen, quarantine stored, thawed and sterile filtered to obtain PL. PL content and its effect on fibroblast-colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied. Results PL contained high levels of basic fibroblast growth factor (bFGF), soluble CD40L (sCD40L), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor AB/BB (PDGF-AB/BB), chemokine (C-C) ligand 5 (CCL5; RANTES) transforming growth factor-β1 (TGF-β1) and chemokine (C-X-C) ligand 1/2/3 (GRO), with low batch-to-batch variability, and most were stable for up to 14 days. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. The strongest inhibition (about 75%) was observed with a combination of anti-bFGF + anti-PDGF-BB and anti-bFGF + anti-TGF-β1 + anti-PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF-β1 were not sufficient to promote cell proliferation. PL from whole blood-derived pooled platelet concentrates and apheresis platelet concentrates did not differ significantly in their growth-promoting activity on MSC. Conclusions PL enhances MSC proliferation and can be regarded as a safe tool for MSC expansion for clinical purposes. \\in particular, PDGF-BB and bFGF are essential components for the growth-promoting effect of PL, but are not sufficient for MSC proliferation. PMID:22296115

Does the immune reaction cause malignant transformation by disrupting cell-to-cell or cell-to-matrix communications?

PubMed Central

Prehn, Richmond T

2007-01-01

Tumor progression In many (perhaps in all) tumor systems, a malignant cancer is preceded by a benign lesion. Most benign lesions do not transform to malignancy and many regress. The final transformative step to malignancy differs from the preceding steps in, among other things, that it often occurs in the absence of the original carcinogenic stimulus. Mechanism of immunostimulation Relatively low titers of specific immune reactants are known to stimulate, but cell-to-cell or cell-to-matrix interactions appear to be major inhibitors of tumor-growth. Therefore, it seems reasonable to hypothesize that the mechanism of immunostimulation may be an interference with cell-to-cell or cell-to-matrix communication by a sub-lethal immune-reaction. Discussion While the above hypothesis remains unproven, some evidence suggests that immunity may have a major facilitating effect on tumor growth especially at the time of malignant transformation. There is even some evidence suggesting that transformation in vivo may seldom occur in the absence of immunostimulation of the premalignant lesion. Positive selection by the immune reaction may be the reason that tumors are immunogenic. PMID:17480231

'I learned to accept every part of myself': the transformative impact of a theatre-based sexual health and HIV prevention programme.

PubMed

Grewe, Mary E; Taboada, Arianna; Dennis, Alexis; Chen, Elizabeth; Stein, Kathryn; Watson, Sable; Barrington, Clare; Lightfoot, Alexandra F

Theatre-based interventions have been used in health promotion activities among young people to address HIV and sexual health. In this study, we explored the experience of undergraduate student performers participating in a theatre-based HIV prevention and sexual health education intervention for high school students in the USA. Undergraduate students enrolled in a credit-bearing course to learn about HIV and sexual health, participatory theatre and health education techniques. We analysed students' reflective essays written throughout the semester to identify any changes and the intervention processes that promoted these changes. Students experienced five interrelated forms of transformation: (1) increased knowledge about HIV and sexual health; (2) changes in attitude and communication about sex; (3) artistic growth; (4) emotional growth; and (5) clarification of career goals and future plans. Intervention processes that contributed to these transformations included improvisation, guided writing exercises, the creation of a close-knit cohesive group, and interactions with a group of HIV-positive speakers. Theatre-based, peer-led sexual health programmes can provide a transformative experience for undergraduate student performers. The transformative effects are linked to specific activities and processes of the intervention and require examination in future research.

Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

PubMed

Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

2012-10-01

For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.

The importance of chorismate mutase in the biocontrol potential of Trichoderma parareesei

PubMed Central

Pérez, Esclaudys; Rubio, M. Belén; Cardoza, Rosa E.; Gutiérrez, Santiago; Bettiol, Wagner; Monte, Enrique; Hermosa, Rosa

2015-01-01

Species of Trichoderma exert direct biocontrol activity against soil-borne plant pathogens due to their ability to compete for nutrients and to inhibit or kill their targets through the production of antibiotics and/or hydrolytic enzymes. In addition to these abilities, Trichoderma spp. have beneficial effects for plants, including the stimulation of defenses and the promotion of growth. Here we study the role in biocontrol of the T. parareesei Tparo7 gene, encoding a chorismate mutase (CM), a shikimate pathway branch point leading to the production of aromatic amino acids, which are not only essential components of protein synthesis but also the precursors of a wide range of secondary metabolites. We isolated T. parareesei transformants with the Tparo7 gene silenced. Compared with the wild-type, decreased levels of Tparo7 expression in the silenced transformants were accompanied by reduced CM activity, lower growth rates on different culture media, and reduced mycoparasitic behavior against the phytopathogenic fungi Rhizoctonia solani, Fusarium oxysporum and Botrytis cinerea in dual cultures. By contrast, higher amounts of the aromatic metabolites tyrosol, 2-phenylethanol and salicylic acid were detected in supernatants from the silenced transformants, which were able to inhibit the growth of F. oxysporum and B. cinerea. In in vitro plant assays, Tparo7-silenced transformants also showed a reduced capacity to colonize tomato roots. The effect of Tparo7-silencing on tomato plant responses was examined in greenhouse assays. The growth of plants colonized by the silenced transformants was reduced and the plants exhibited an increased susceptibility to B. cinerea in comparison with the responses observed for control plants. In addition, the plants turned yellowish and were defective in jasmonic acid- and ethylene-regulated signaling pathways which was seen by expression analysis of lipoxygenase 1 (LOX1), ethylene-insensitive protein 2 (EIN2) and pathogenesis-related protein 1 (PR-1) genes. PMID:26579090

Acoustic invisibility cloaks of arbitrary shapes for complex background media

NASA Astrophysics Data System (ADS)

Zhu, Jian; Chen, Tianning; Liang, Qingxuan; Wang, Xiaopeng; Xiong, Jie; Jiang, Ping

2016-04-01

We report on the theoretical investigation of the acoustic cloaks working in complex background media in this paper. The constitutive parameters of arbitrary-shape cloaks are derived based on the transformation acoustic theory and coordinate transformation technique. The detailed analysis of boundaries conditions and potential applications of the cloaks are also presented in our work. To overcome the difficulty of achieving the materials with ideal parameters in nature, concentric alternating layered isotropic materials is adopted to approximate the required properties of the cloak. Theoretical design and excellent invisibility are demonstrated by numerical simulations. The inhomogeneous medium and arbitrary-shape acoustic cloaks grow closer to real application and may be a new hot spot in future.

The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K-AKT-NFκB cascade.

PubMed

Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon; Satapathy, Shakti Ranjan; Siddharth, Sumit; Choudhuri, Tathagata; Wyatt, Michael D; Kundu, Chanakya Nath

2014-01-01

Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011μg Cd per cigarette equivalent, and Cd (0.0003μg Cd/1×10(7) cells) was also detected in the lysates from MCF-10A cells treated with 25μg/mL CSC. In similar manner to CSC, CdCl2 treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K-AKT-NFκB protein expression. An increase in the expression of PI3K-AKT-NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl2 treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. © 2013.

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

PubMed

Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

2016-01-01

The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under environmental stresses. This is the first report on the successful improvement of a rhizobium with a chaperone gene.

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene

PubMed Central

Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F.; Oliveira, Solange

2016-01-01

The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under environmental stresses. This is the first report on the successful improvement of a rhizobium with a chaperone gene. PMID:26845770

National Research Council Dialogue to Assess Progress on NASA's Title of CRM Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Crooke, Julie A.

2005-01-01

Contents include the following: General Background and Introduction of Capability Roadmaps "Title." Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

National Research Council Dialogue to Assess Progress on NASA's Human Health & Support Systems Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Aikins, Jan

2005-01-01

Contents include the following: General Background and Introduction of Capability Roadmaps. Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

--No Title--

Science.gov Websites

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Dim target trajectory-associated detection in bright earth limb background

NASA Astrophysics Data System (ADS)

Chen, Penghui; Xu, Xiaojian; He, Xiaoyu; Jiang, Yuesong

2015-09-01

The intensive emission of earth limb in the field of view of sensors contributes much to the observation images. Due to the low signal-to-noise ratio (SNR), it is a challenge to detect small targets in earth limb background, especially for the detection of point-like targets from a single frame. To improve the target detection, track before detection (TBD) based on the frame sequence is performed. In this paper, a new technique is proposed to determine the target associated trajectories, which jointly carries out background removing, maximum value projection (MVP) and Hough transform. The background of the bright earth limb in the observation images is removed according to the profile characteristics. For a moving target, the corresponding pixels in the MVP image are shifting approximately regularly in time sequence. And the target trajectory is determined by Hough transform according to the pixel characteristics of the target and the clutter and noise. Comparing with traditional frame-by-frame methods, determining associated trajectories from MVP reduces the computation load. Numerical simulations are presented to demonstrate the effectiveness of the approach proposed.

Epithelial to mesenchymal transition in arsenic-transformed cells promotes angiogenesis through activating β-catenin–vascular endothelial growth factor pathway

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

Wang, Zhishan; Humphries, Brock; Xiao, Hua

2013-08-15

Arsenic exposure represents a major health concern increasing cancer risks, yet the mechanism of arsenic carcinogenesis has not been elucidated. We and others recently reported that cell malignant transformation by arsenic is accompanied by epithelial to mesenchymal transition (EMT). However, the role of EMT in arsenic carcinogenesis is not well understood. Although previous studies showed that short term exposure of endothelial cells to arsenic stimulated angiogenesis, it remains to be determined whether cells that were malignantly transformed by long term arsenic exposure have a pro-angiogenic effect. The objective of this study was to investigate the effect of arsenic-transformed human bronchialmore » epithelial cells that underwent EMT on angiogenesis and the underlying mechanism. It was found that the conditioned medium from arsenic-transformed cells strongly stimulated tube formation by human umbilical vein endothelial cells (HUVECs). Moreover, enhanced angiogenesis was detected in mouse xenograft tumor tissues resulting from inoculation of arsenic-transformed cells. Mechanistic studies revealed that β-catenin was activated in arsenic-transformed cells up-regulating its target gene expression including angiogenic-stimulating vascular endothelial growth factor (VEGF). Stably expressing microRNA-200b in arsenic-transformed cells that reversed EMT inhibited β-catenin activation, decreased VEGF expression and reduced tube formation by HUVECs. SiRNA knockdown β-catenin decreased VEGF expression. Adding a VEGF neutralizing antibody into the conditioned medium from arsenic-transformed cells impaired tube formation by HUVECs. Reverse transcriptase-PCR analysis revealed that the mRNA levels of canonical Wnt ligands were not increased in arsenic-transformed cells. These findings suggest that EMT in arsenic-transformed cells promotes angiogenesis through activating β-catenin–VEGF pathway. - Highlights: • Arsenic-transformed cells that underwent EMT displayed a pro-angiogenic effect. • EMT in arsenic-transformed cells activates β-catenin. • β-Catenin activation increases VEGF expression in arsenic-transformed cells. • β-Catenin activation is likely independent of canonical Wnt signaling. • EMT in arsenic-transformed cells promotes angiogenesis via β-catenin–VEGF pathway.« less

Agrobacterium-mediated transformation of lipomyces

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

Dai, Ziyu; Magnuson, Jon K.; Deng, Shuang

This disclosure provides Agrobacterium-mediated transformation methods for the oil-producing (oleaginous) yeast Lipomyces sp., as well as yeast produced by the method. Such methods utilize Agrobacterium sp. cells that have a T-DNA binary plasmid, wherein the T-DNA binary plasmid comprises a first nucleic acid molecule encoding a first protein and a second nucleic acid molecule encoding a selective marker that permits growth of transformed Lipomyces sp. cells in selective culture media comprising an antibiotic.

Transforming your professional self: encouraging lifelong personal and professional growth.

PubMed

Rodts, Mary F; Lamb, Karen V

2008-01-01

Transforming from student nurse to registered nurse is often discussed in a capstone class or a hospital orientation program. Changes in professional plans later in the career continuum often occur, but are not always planned. This article discusses the challenges of change, the need for career planning, stages of role acquisition, role socialization, and role transformation. In addition, it outlines the importance of creating a career plan to meet future career goals.

Stabilization of growth of a pearlite colony because of interaction between carbon and lattice dilatations

NASA Astrophysics Data System (ADS)

Razumov, I. K.

2017-10-01

The previously proposed model of pearlite transformation develops taking into account the possible interaction between carbon and lattice dilatations arising in austenite near the pearlite colony. The normal stresses caused by the colony stimulate autocatalysis of plates, and tangential stresses promote the stabilization of the transformation front. The mechanism of ferrite branching, which can play an important role in the kinetics of pearlite and bainite transformations, is discussed.

Leadership Development of Rehabilitation Professionals in a Low-Resource Country: A Transformational Leadership, Project-Based Model.

PubMed

Pascal, Maureen Romanow; Mann, Monika; Dunleavy, Kim; Chevan, Julia; Kirenga, Liliane; Nuhu, Assuman

2017-01-01

This paper presents an overview of the activities and outcomes of the Leadership Institute (LI), a short-term leadership development professional development course offered to physiotherapists in a low-resource country. Previous studies have provided examples of the benefits of such programs in medicine and nursing, but this has yet to be documented in the rehabilitation literature. The prototype of leadership development presented may provide guidance for similar trainings in other low-resource countries and offer the rehabilitation community an opportunity to build on the model to construct a research agenda around rehabilitation leadership development. The course used a constructivist approach to integrate participants' experiences, background, beliefs, and prior knowledge into the content. Transformational leadership development theory was emphasized with the generation of active learning projects, a key component of the training. Positive changes after the course included an increase in the number of community outreach activities completed by participants and increased involvement with their professional organization. Thirteen leadership projects were proposed and presented. The LI provided present and future leaders throughout Rwanda with exposure to transformative leadership concepts and offered them the opportunity to work together on projects that enhanced their profession and met the needs of underserved communities. Challenges included limited funding for physiotherapy positions allocated to hospitals in Rwanda, particularly in the rural areas. Participants experienced difficulties in carrying out leadership projects without additional funding to support them. While the emphasis on group projects to foster local advocacy and community education is highly recommended, the projects would benefit from a strong long-term mentorship program and further budgeting considerations. The LI can serve as a model to develop leadership skills and spur professional growth in low-resource settings. Leadership development is necessary to address worldwide inequities in health care. The LI model presents a method to cultivate transformational leadership and work toward improvements in health care and delivery of service.

Development of an efficient regeneration and transformation method for the new potential oilseed crop Lepidium campestre

PubMed Central

2013-01-01

Background Lepidium campestre is an undomesticated oilseed species with a great potential to become a new crop for both food and industrial feedstocks production. Genetic modification is needed for further improving the oil quantity and quality of Lepidium. Studies on in vitro shoot regeneration of Lepidium are very limited and there is no transformation protocol available. Results We have investigated the effects of different factors, especially the type, concentration and combination of plant growth regulators (PGRs) on in vitro shoot regeneration of Lepidium. The results showed that the 2,4-D treatment was crucial to shoot regeneration from different explants. The duration of 2,4-D exposure between 2-4 days did not show significant difference in shoot regeneration, while the effect of 2,4-D concentration varied greatly depending on the type of explants and cytokinins used, for example, the low concentration of 2,4-D combined with TDZ significantly increased the regeneration frequency of hypocotyls. Cotyledon and hypocotyl explants responded differently to cytokinin, for example, TDZ was more effective than zeatin in promoting shoot regeneration from hypocotyls, but did not affect the regeneration of cotyledons which was more affected by high concentration of zeatin. The results also showed that NAA was not effective for shoot regeneration. Germination in light increased the regeneration frequency compared to that in dark. After optimization of the different conditions, an efficient regeneration protocol was developed with the regeneration efficiency of 92.7%. Using this protocol, the transformation frequency of 6% in average was achieved. The presence of transgenes in the transgenic lines was confirmed by GUS staining, PCR and Southern blot analyses. Conclusion Through systematic investigation of important factors affecting in vitro shoot regeneration, we have developed an efficient regeneration and transformation protocol for the genetic modification of Lepidium campestre. The method may also be applied to the related species. PMID:23937221

Quantitative 3D evolution of colloidal nanoparticle oxidation in solution

DOE PAGES

Sun, Yugang; Zuo, Xiaobing; Sankaranarayanan, Subramanian K. R. S.; ...

2017-04-21

Real-time tracking three-dimensional (3D) evolution of colloidal nanoparticles in solution is essential for understanding complex mechanisms involved in nanoparticle growth and transformation. We simultaneously use time-resolved small-angle and wide-angle x-ray scattering to monitor oxidation of highly uniform colloidal iron nanoparticles, enabling the reconstruction of intermediate 3D morphologies of the nanoparticles with a spatial resolution of ~5 Å. The in-situ probing combined with large-scale reactive molecular dynamics simulations reveals the transformational details from the solid metal nanoparticles to hollow metal oxide nanoshells via nanoscale Kirkendall process, for example, coalescence of voids upon their growth, reversing of mass diffusion direction depending onmore » crystallinity, and so forth. In conclusion, our results highlight the complex interplay between defect chemistry and defect dynamics in determining nanoparticle transformation and formation.« less

Adenovirus E1A and E1B-19K Proteins Protect Human Hepatoma Cells from Transforming Growth Factor β1-induced Apoptosis

PubMed Central

Tarakanova, Vera L.; Wold, William S. M.

2009-01-01

Primary and some transformed hepatocytes undergo apoptosis in response to transforming growth factor β1 (TGFβ). We report that infection with species C human adenovirus conferred resistance to TGFβ-induced apoptosis in human hepatocellular carcinoma cells (Huh-7). Protection against TGFβ-mediated cell death in adenovirus-infected cells correlated with the maintenance of normal nuclear morphology, lack of pro-caspases 8 and 3 processing, maintenance of the mitochondrial membrane potential, and lack of cellular DNA degradation. The TGFβ pro-apoptotic signaling pathway was blocked upstream of mitochondria in adenovirus-infected cells. Both the N-terminal sequences of the E1A proteins and the E1B-19K protein were necessary to protect infected cells against TGFβ-induced apoptosis. PMID:19854227

Quantitative 3D evolution of colloidal nanoparticle oxidation in solution

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

Sun, Yugang; Zuo, Xiaobing; Sankaranarayanan, Subramanian K. R. S.

Real-time tracking three-dimensional (3D) evolution of colloidal nanoparticles in solution is essential for understanding complex mechanisms involved in nanoparticle growth and transformation. We simultaneously use time-resolved small-angle and wide-angle x-ray scattering to monitor oxidation of highly uniform colloidal iron nanoparticles, enabling the reconstruction of intermediate 3D morphologies of the nanoparticles with a spatial resolution of ~5 Å. The in-situ probing combined with large-scale reactive molecular dynamics simulations reveals the transformational details from the solid metal nanoparticles to hollow metal oxide nanoshells via nanoscale Kirkendall process, for example, coalescence of voids upon their growth, reversing of mass diffusion direction depending onmore » crystallinity, and so forth. In conclusion, our results highlight the complex interplay between defect chemistry and defect dynamics in determining nanoparticle transformation and formation.« less

Autophagy in Ras-induced malignant transformation: fatal or vital?

PubMed

Mariño, Guillermo; Martins, Isabelle; Kroemer, Guido

2011-04-08

In this issue of Molecular Cell, Elgendy et al. suggest that Ras-induced autophagy may kill tumor cells on the verge of oncogenic transformation, providing a contrast to recent reports indicating that autophagy is required for optimal growth of Ras-driven cancers. Copyright © 2011 Elsevier Inc. All rights reserved.

Setaria viridis floral-dip: A simple and rapid Agrobacterium-medicated transformation method

USDA-ARS?s Scientific Manuscript database

Setaria viridis was recently described as a new monocotyledonous model species for C4 photosynthesis research and genetic transformation. It has biological attributes (rapid life cycle, small genome, diploid, short stature and simple growth requirements) that make it suitable for use as a model plan...

Transforming Knowledge into Wealth in a New Zealand Research University

ERIC Educational Resources Information Center

Spicer, Barry; Dunn, Wendell; Whitcher, Geoff

2006-01-01

This paper describes how New Zealand's leading research university, the University of Auckland, dealt with the issue of transforming knowledge into wealth using a "whole of institution" approach. The context of New Zealand's growth and innovation initiatives is outlined and the University of Auckland's engagement with and institutional…

Secondary Students' Accounts of Carbon-Transforming Processes before and after Instruction

ERIC Educational Resources Information Center

Onyancha, Kennedy M.; Anderson, Charles W.

2012-01-01

The purpose of this study is to examine the extent to which more targeted instruction is helpful in eliciting students' scientific explanations of six selected carbon-transforming processes of combustion, cross processes, decomposition, growth, photosynthesis and respiration. We also examined these students' accounts regarding the corresponding…

Influence of phase transformation on stress evolution during growth of metal thin films on silicon.

PubMed

Fillon, A; Abadias, G; Michel, A; Jaouen, C; Villechaise, P

2010-03-05

In situ stress measurements during two-dimensional growth of low mobility metal films on amorphous Si were used to demonstrate the impact of interface reactivity and phase transformation on stress evolution. Using Mo1-xSix films as examples, the results show that the tensile stress rise, which develops after the film has become crystalline, is correlated with an increase in lateral grain size. The origin of the tensile stress is attributed to the volume change resulting from the alloy crystallization, which occurs at a concentration-dependent critical thickness.

Retail growth and consumer changes in a declining urban economy: Antwerp (1650-1750).

PubMed

Blondé, Bruno; van Damme, Ilja

2010-01-01

This article examines the interplay between retail changes and transformations in the material culture of Antwerp, a provincial town in the southern Netherlands. We argue that major changes in the eighteenth-century material culture and retail sector were not significantly linked to preconditions of economic growth and urbanization. The Antwerp 'retail paradox' is that of a shrinking economic horizon running parallel to material culture and retail transformations, usually connected to expanding urban economies and societies. Changing retail and consumer practices explain the growing and prospering retail sector, rather than a growing economy.

Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers.

PubMed

Tanimoto, Ryuta; Lu, Kuojung G; Xu, Shi-Qiong; Buraschi, Simone; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2016-01-01

The growth factor progranulin has emerged in recent years as a critical regulator of transformation in several cancer models, including breast cancer, glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories, including ours, have also demonstrated an important role of progranulin in several genitourinary cancers, including ovarian, endometrial, cervical, prostate, and bladder tumors, where progranulin acts as an autocrine growth factor thereby modulating motility and invasion of transformed cells. In this review, we will focus on the mechanisms of action and regulation of progranulin signaling in genitourinary cancers with a special emphasis on prostate and bladder tumors.

Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers

PubMed Central

Tanimoto, Ryuta; Lu, Kuojung G.; Xu, Shi-Qiong; Buraschi, Simone; Belfiore, Antonino; Iozzo, Renato V.; Morrione, Andrea

2016-01-01

The growth factor progranulin has emerged in recent years as a critical regulator of transformation in several cancer models, including breast cancer, glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories, including ours, have also demonstrated an important role of progranulin in several genitourinary cancers, including ovarian, endometrial, cervical, prostate, and bladder tumors, where progranulin acts as an autocrine growth factor thereby modulating motility and invasion of transformed cells. In this review, we will focus on the mechanisms of action and regulation of progranulin signaling in genitourinary cancers with a special emphasis on prostate and bladder tumors. PMID:27512385

Phase transformations during the growth of paracetamol crystals from the vapor phase

NASA Astrophysics Data System (ADS)

Belyaev, A. P.; Rubets, V. P.; Antipov, V. V.; Bordei, N. S.

2014-07-01

Phase transformations during the growth of paracetamol crystals from the vapor phase are studied by differential scanning calorimetry. It is found that the vapor-crystal phase transition is actually a superposition of two phase transitions: a first-order phase transition with variable density and a second-order phase transition with variable ordering. The latter, being a diffuse phase transition, results in the formation of a new, "pretransition," phase irreversibly spent in the course of the transition, which ends in the appearance of orthorhombic crystals. X-ray diffraction data and micrograph are presented.

Teaching to Transform, Transforming to Teach: Exploring the Role of Teachers in Human Rights Education in India

ERIC Educational Resources Information Center

Bajaj, Monisha

2011-01-01

Background: Human rights education initiatives have proliferated in the past three decades and can be found in policy discussions, textbook reforms and grassroots initiatives across the globe. This article specifically explores the role of teachers in human rights education (HRE) by focusing on a case study of one non-governmental organisation's…

Acceptance and Transformation of English Educational Theory in Japan: On Student-Centered Education

ERIC Educational Resources Information Center

Kuwamura, Teresa

2014-01-01

In Japan, various theories and methodologies of English education born in other countries have been practiced, but the result has left a lot to be desired. Still, each theory has its own sociocultural background. When theory goes beyond its culture and locality, it transforms by losing its originality and absorbing new elements from a different…

Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling

PubMed Central

Archibald, Andrew; Al-Masri, Maia; Liew-Spilger, Alyson; McCaffrey, Luke

2015-01-01

Epithelial cells are major sites of malignant transformation. Atypical protein kinase C (aPKC) isoforms are overexpressed and activated in many cancer types. Using normal, highly polarized epithelial cells (MDCK and NMuMG), we report that aPKC gain of function overcomes contact inhibited growth and is sufficient for a transformed epithelial phenotype. In 2D cultures, aPKC induced cells to grow as stratified epithelia, whereas cells grew as solid spheres of nonpolarized cells in 3D culture. aPKC associated with Mst1/2, which uncoupled Mst1/2 from Lats1/2 and promoted nuclear accumulation of Yap1. Of importance, Yap1 was necessary for aPKC-mediated overgrowth but did not restore cell polarity defects, indicating that the two are separable events. In MDCK cells, Yap1 was sequestered to cell–cell junctions by Amot, and aPKC overexpression resulted in loss of Amot expression and a spindle-like cell phenotype. Reexpression of Amot was sufficient to restore an epithelial cobblestone appearance, Yap1 localization, and growth control. In contrast, the effect of aPKC on Hippo/Yap signaling and overgrowth in NMuMG cells was independent of Amot. Finally, increased expression of aPKC in human cancers strongly correlated with increased nuclear accumulation of Yap1, indicating that the effect of aPKC on transformed growth by deregulating Hippo/Yap1 signaling may be clinically relevant. PMID:26269582

Real-time video signal processing by generalized DDA and control memories: three-dimensional rotation and mapping

NASA Astrophysics Data System (ADS)

Hama, Hiromitsu; Yamashita, Kazumi

1991-11-01

A new method for video signal processing is described in this paper. The purpose is real-time image transformations at low cost, low power, and small size hardware. This is impossible without special hardware. Here generalized digital differential analyzer (DDA) and control memory (CM) play a very important role. Then indentation, which is called jaggy, is caused on the boundary of a background and a foreground accompanied with the processing. Jaggy does not occur inside the transformed image because of adopting linear interpretation. But it does occur inherently on the boundary of the background and the transformed images. It causes deterioration of image quality, and must be avoided. There are two well-know ways to improve image quality, blurring and supersampling. The former does not have much effect, and the latter has the much higher cost of computing. As a means of settling such a trouble, a method is proposed, which searches for positions that may arise jaggy and smooths such points. Computer simulations based on the real data from VTR, one scene of a movie, are presented to demonstrate our proposed scheme using DDA and CMs and to confirm the effectiveness on various transformations.

NanoLuc reporter for dual luciferase imaging in living animals.

PubMed

Stacer, Amanda C; Nyati, Shyam; Moudgil, Pranav; Iyengar, Rahul; Luker, Kathryn E; Rehemtulla, Alnawaz; Luker, Gary D

2013-10-01

Bioluminescence imaging is widely used for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on the high signal to background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events, as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, adenosine triphosphate–independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc [NL]) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although the detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in transforming growth factor β signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as a new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development.

Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer.

PubMed

Bradley, Sarah V; Oravecz-Wilson, Katherine I; Bougeard, Gaelle; Mizukami, Ikuko; Li, Lina; Munaco, Anthony J; Sreekumar, Arun; Corradetti, Michael N; Chinnaiyan, Arul M; Sanda, Martin G; Ross, Theodora S

2005-05-15

Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-alpha-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer.

Genetic changes in mammalian cells transformed by helium ions

NASA Astrophysics Data System (ADS)

Durante, M.; Grossi, G.; Yang, T. C.; Roots, R.

Midterm Syrian Hamster embryo (SHE) cells were employed to study high LET-radiation induced tumorigenesis. Normal SHE cells (secondary passage) were irradiated with accelerated helium ions at an incident energy of 22 MeV/u (9-10 keV/μm). Transformed clones were isolated after growth in soft agar of cells obtained from the foci of the initial monolayer plated postirradiation. To study the progression process of malignant transformation, the transformed clones were followed by monolayer subculturing for prolonged periods of time. Subsequently, neoplasia tests in nude mice were done. In this work, however, we have focused on karyotypic changes in the banding patterns of the chromosomes during the early part of the progressive process of cell transformation for helium ion-induced transformed cells.

Effect of transforming growth factor-beta1 on decorin expression and muscle morphology during chicken embryonic and posthatch growth and development.

PubMed

Li, X; Velleman, S G

2009-02-01

During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation, as well as a regulator of extracellular matrix (ECM) production. Decorin, a member of the small leucine-rich ECM proteoglycans, binds to TGF-beta1 and modulates TGF-beta1-dependent cell growth stimulation or inhibition. The expression of decorin can be regulated by TGF-beta1 during muscle proliferation and differentiation. How TGF-beta1 affects decorin and muscle growth, however, has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on decorin expression and intracellular connective tissue development during skeletal muscle growth. Exogenous TGF-beta1 significantly decreased the number of myofibers in a given area at both 1 d and 6 wk posthatch. The TGF-beta1-treated muscle had a significant decrease in decorin mRNA expression at embryonic day (ED) 10, whereas protein amounts decreased at 17 ED and 1 d posthatch compared to the control muscle. Decorin was localized in both the endomysium and perimysium in the control pectoralis major muscle. Transforming growth factor-beta1 reduced decorin in both the endomysium and perimysium from 17 ED to 6 wk posthatch. Compared to the control muscle, the perimysium space in the pectoralis major muscle was dramatically decreased by TGF-beta1 during embryonic development through posthatch growth. Because decorin regulates collagen fibrillogenesis, a major component of the ECM, the reduction of decorin by TGF-beta1 treatment may cause the irregular formation of collagen fibrils, leading to the decrease in endomysium and perimysium space. The results from the current study suggest that the effect of TGF-beta1 on decorin expression and localization was likely associated with altered development of the perimysium and the regulation of muscle fiber development.

Accelerated Stem Growth Rates and Improved Fiber Properties of Loblolly Pine: Functional Analysis Of CyclinD from Pinus taeda

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

Dr. John Cairney, School of Biology and Institute of Paper Science and Technology @ Georgia Tech, Georgia Institute of Technology; Dr. Gary Peter, University of Florida; Dr. Ulrika Egertsdotter, Dept. of Forestry, Virgina Tech

A sustained supply of low-cost, high quality raw materials is essential for the future success of the U.S. forest products industry. To maximize stem (trunk) growth, a fundamental understanding of the molecular mechanisms that regulate cell divisions within the cambial meristem is essential. We hypothesize that auxin levels within the cambial meristem regulate cyclin gene expression and this in turn controls cell cycle progression as occurs in all eukaryotic cells. Work with model plant species has shown that ectopic overexpression of cyclins promotes cell division thereby increasing root growth > five times. We intended to test whether ectopic overexpression ofmore » cambial cyclins in the cambial zone of loblolly pine also promotes cell division rates that enhance stem growth rates. Results generated in model annual angiosperm systems cannot be reliably extrapolated to perennial gymnosperms, thus while the generation and development of transgenic pine is time consuming, this is the necessary approach for meaningful data. We succeeded in isolating a cyclin D gene and Clustal analysis to the Arabidopsis cyclin D gene family indicates that it is more closely related to cyclin D2 than D1 or D3 Using this gene as a probe we observed a small stimulation of cyclin D expression in somatic embryo culture upon addition of auxin. We hypothesized that trees with more cells in the vascular cambial and expansion zones will have higher cyclin mRNA levels. We demonstrated that in trees under compressive stress where the rates of cambial divisions are increased on the underside of the stem relative to the top or opposite side, there was a 20 fold increase in the level of PtcyclinD1 mRNA on the compressed side of the stem relative to the opposite. This suggests that higher secondary growth rates correlate with PtcyclinD1 expression. We showed that larger diameter trees show more growth during each year and that the increased growth in loblolly pine trees correlates with more cell divisions in the cambial meristem as expected. We isolated a promoter from a cambial specific gene and commenced development of transformation protocols for loblolly pine. Since our results show that cyclin D expression correlates with increased growth we continued with experiments to demonstrate the effect of cyclin overexpression upon tree growth. Vectors which constitutively express the cyclin D cDNA were constructed and transformed into a transgenic pine system through the collaboration with Forest Research, New Zealand. The transformation system for Pinus radiata is well established and we hoped to gain phenotypic information in a closely related pine, rather than await development of a robust loblolly pine transformation method. Transformation experiments were conducted by a biolistic method developed at Forest Research, NZ. A total of 78 transgenic embryogenic lines were generated and bulked up with a good representation of transgenic lines per construct. Transformed calli were originally identified by resistance to the antibiotic Geneticin contained in the medium. The transgenic nature of the selected lines was subsequently confirmed using histochemical GUS staining. To date, 10 out of 13 selected transgenic lines have produced embryos and we are currently harvesting the first transgenic plantlets. At present time 22 of those plantlets have been moved to GMO facilities. We will soon develop a strategy for assessing potential phenotypic differences between the transclones and non-transformed controls. Transgenic plants are being grown to a stage (approx. 1 year) when meaningful phenotypic evaluation can be conducted. The recent availability of 10,000 element loblolly pine cDNA microarray will permit the evaluation of cyclinD overexpression upon gene expression in transgenic Pinus.« less

SPARC Expression Is Selectively Suppressed in Tumor Initiating Urospheres Isolated from As+3- and Cd+2-Transformed Human Urothelial Cells (UROtsa) Stably Transfected with SPARC.

PubMed

Slusser-Nore, Andrea; Larson-Casey, Jennifer L; Zhang, Ruowen; Zhou, Xu Dong; Somji, Seema; Garrett, Scott H; Sens, Donald A; Dunlevy, Jane R

2016-01-01

This laboratory previously analyzed the expression of SPARC in the parental UROtsa cells, their arsenite (As(+3)) and cadmium (Cd(+2))-transformed cell lines, and tumor transplants generated from the transformed cells. It was demonstrated that SPARC expression was down-regulated to background levels in Cd(+2)-and As(+3)-transformed UROtsa cells and tumor transplants compared to parental cells. In the present study, the transformed cell lines were stably transfected with a SPARC expression vector to determine the effect of SPARC expression on the ability of the cells to form tumors in immune-compromised mice. Real time PCR, western blotting, immunohistochemistry, and immunofluorescence were used to define the expression of SPARC in the As(+3)-and Cd(+2)-transformed cell lines, and urospheres isolated from these cell lines, following their stable transfection with an expression vector containing the SPARC open reading frame (ORF). Transplantation of the cultured cells into immune-compromised mice by subcutaneous injection was used to assess the effect of SPARC expression on tumors generated from the above cell lines and urospheres. It was shown that the As(+3)-and Cd(+2)-transformed UROtsa cells could undergo stable transfection with a SPARC expression vector and that the transfected cells expressed both SPARC mRNA and secreted protein. Tumors formed from these SPARC-transfected cells were shown to have no expression of SPARC. Urospheres isolated from cultures of the SPARC-transfected As(+3)-and Cd(+2)-transformed cell lines were shown to have only background expression of SPARC. Urospheres from both the non-transfected and SPARC-transfected cell lines were tumorigenic and thus fit the definition for a population of tumor initiating cells. Tumor initiating cells isolated from SPARC-transfected As(+3)-and Cd(+2)-transformed cell lines have an inherent mechanism to suppress the expression of SPARC mRNA.

Is cancer a pure growth curve or does it follow a kinetics of dynamical structural transformation?

PubMed

González, Maraelys Morales; Joa, Javier Antonio González; Cabrales, Luis Enrique Bergues; Pupo, Ana Elisa Bergues; Schneider, Baruch; Kondakci, Suleyman; Ciria, Héctor Manuel Camué; Reyes, Juan Bory; Jarque, Manuel Verdecia; Mateus, Miguel Angel O'Farril; González, Tamara Rubio; Brooks, Soraida Candida Acosta; Cáceres, José Luis Hernández; González, Gustavo Victoriano Sierra

2017-03-07

Unperturbed tumor growth kinetics is one of the more studied cancer topics; however, it is poorly understood. Mathematical modeling is a useful tool to elucidate new mechanisms involved in tumor growth kinetics, which can be relevant to understand cancer genesis and select the most suitable treatment. The classical Kolmogorov-Johnson-Mehl-Avrami as well as the modified Kolmogorov-Johnson-Mehl-Avrami models to describe unperturbed fibrosarcoma Sa-37 tumor growth are used and compared with the Gompertz modified and Logistic models. Viable tumor cells (1×10 5 ) are inoculated to 28 BALB/c male mice. Modified Gompertz, Logistic, Kolmogorov-Johnson-Mehl-Avrami classical and modified Kolmogorov-Johnson-Mehl-Avrami models fit well to the experimental data and agree with one another. A jump in the time behaviors of the instantaneous slopes of classical and modified Kolmogorov-Johnson-Mehl-Avrami models and high values of these instantaneous slopes at very early stages of tumor growth kinetics are observed. The modified Kolmogorov-Johnson-Mehl-Avrami equation can be used to describe unperturbed fibrosarcoma Sa-37 tumor growth. It reveals that diffusion-controlled nucleation/growth and impingement mechanisms are involved in tumor growth kinetics. On the other hand, tumor development kinetics reveals dynamical structural transformations rather than a pure growth curve. Tumor fractal property prevails during entire TGK.

Efficient Agrobacterium-mediated transformation of the liverwort Marchantia polymorpha using regenerating thalli.

PubMed

Kubota, Akane; Ishizaki, Kimitsune; Hosaka, Masashi; Kohchi, Takayuki

2013-01-01

The thallus, the gametophyte body of the liverwort Marchantia polymorpha, develops clonal progenies called gemmae that are useful in the isolation and propagation of isogenic plants. Developmental timing is critical to Agrobacterium-mediated transformation, and high transformation efficiency has been achieved only with sporelings. Here we report an Agrobacterium-mediated transformation system for M. polymorpha using regenerating thalli. Thallus regeneration was induced by cutting the mature thallus across the apical-basal axis and incubating the basal portion of the thallus for 3 d. Regenerating thalli were infected with Agrobacterium carrying binary vector that contained a selection marker, the hygromycin phosphotransferase gene, and hygromycin-resistant transformants were obtained with an efficiency of over 60%. Southern blot analysis verified random integration of 1 to 4 copies of the T-DNA into the M. polymorpha genome. This Agrobacterium-mediated transformation system for M. polymorpha should provide opportunities to perform genetic transformation without preparing spores and to generate a sufficient number of transformants with isogenic background.

Rolling Bearing Fault Diagnosis Based on an Improved HTT Transform

PubMed Central

Tang, Guiji; Tian, Tian; Zhou, Chong

2018-01-01

When rolling bearing failure occurs, vibration signals generally contain different signal components, such as impulsive fault feature signals, background noise and harmonic interference signals. One of the most challenging aspects of rolling bearing fault diagnosis is how to inhibit noise and harmonic interference signals, while enhancing impulsive fault feature signals. This paper presents a novel bearing fault diagnosis method, namely an improved Hilbert time–time (IHTT) transform, by combining a Hilbert time–time (HTT) transform with principal component analysis (PCA). Firstly, the HTT transform was performed on vibration signals to derive a HTT transform matrix. Then, PCA was employed to de-noise the HTT transform matrix in order to improve the robustness of the HTT transform. Finally, the diagonal time series of the de-noised HTT transform matrix was extracted as the enhanced impulsive fault feature signal and the contained fault characteristic information was identified through further analyses of amplitude and envelope spectrums. Both simulated and experimental analyses validated the superiority of the presented method for detecting bearing failures. PMID:29662013

Evaluate the growth and adhesion of osteoblast cells on nanocomposite scaffold of hydroxyapatite/titania coated with poly hydroxybutyrate

PubMed Central

Pourmollaabbassi, Babak; Karbasi, Saeed; Hashemibeni, Batool

2016-01-01

Background: The generation of bioartificial bone tissues may help to overcome the problems related to donor site morbidity and size limitations. Materials and Methods: In this paper, hydroxyapatite (HA) powder was made out of bovine bone by thermal analysis at 900°C and first, and then, porous HA (50 weight percentage) was produced by polyurethane sponge replication method. In order to improve the scaffold mechanical properties, they have been coated with poly hydroxybutyrate. In terms of phase studies, morphology, and specifying agent groups, the specific characterization devices such as X-ray diffraction and Fourier transform infrared, were employed. To compare the behavior of cellular scaffolds, they were divided into four groups of scaffolds. The osteoblast cells were cultured. To perform phase studies, analysis of Methylthiazole tetrazolium (MTT) and Trypan blue were carried out for the viability and attachment on the surface of the scaffold, and the specification of Scanning electron microscopy was employed for the morphology of the cells. Results: The results of MTT analysis performed on four groups of scaffolds have shown that Titanium oxide (Tio2) had no effect on cell growth alone and HA was the main factor of growth and cell osteoblast adhesion on the scaffold. Moreover, the results showed that the use of coating with poly-3-hydroxybutyrate saved the factors and placed the osteoblasts within the pore. Since the main part of bone consists of HA, the TiO2 accelerates the formation of apatite crystals at the scaffold surface which is the evidence for bone tissue regeneration. Conclusions: It is likely that the relation between HA and TiO2 leads to an increase in osteoblast adhesion and growth of cells on the scaffold surface. PMID:27761431

Hair growth-promoting effect of Geranium sibiricum extract in human dermal papilla cells and C57BL/6 mice.

PubMed

Boisvert, William A; Yu, Miri; Choi, Youngbin; Jeong, Gi Hee; Zhang, Yi-Lin; Cho, Sunghun; Choi, Changsun; Lee, Sanghyun; Lee, Bog-Hieu

2017-02-13

Geranium sibiricum L. has been used as a medicinal plant to treat diarrhea, bacterial infection, and cancer in Bulgaria, Peru, and Korea. However, its hair growth-promoting effect was not investigated so far. This study examined the effects of Geranium sibiricum L. extract (GSE) on hair growth, using in vitro and in vivo models. Antioxidant, proliferation and migration assay of GSE was performed with human dermal papilla cells (hDPCs). Hair-growth promoting effect was measured in animal model. Relative expression of interleukin-1, vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor beta 1 was determined by real time RT-PCR. Expression of Ki-67 and stem cell factor were analyzed by immunohistochemistry. GSE treatment proliferated and migrated human dermal papilla cells (hDPCs) more than treatment of 10 μM minoxidil. GSE significantly stimulated the expression of Ki-67 protein and the mRNA levels of hepatocyte growth factor and vascular endothelial growth factor in hDPCs. Topical application of 1,000 ppm GSE for 3 weeks promoted more significant hair growth on shaved C57BL/6 mice than did 5% minoxidil. The histological morphology of hair follicles demonstrated an active anagen phase with the induction of stem cell factor. GSE treatment significantly reduced the number of mast cells and the expression of transforming growth factor beta 1 in mouse skin tissues. These results demonstrated that GSE promotes hair growth in vitro and in vivo by regulating growth factors and the cellular response.

Evaluation of Phytate-Degrading Lactobacillus Culture Administration to Broiler Chickens

PubMed Central

Askelson, Tyler E.; Campasino, Ashley; Lee, Jason T.

2014-01-01

Probiotics have been demonstrated to promote growth, stimulate immune responses, and improve food safety of poultry. While widely used, their effectiveness is mixed, and the mechanisms through which they contribute to poultry production are not well understood. Microbial phytases are increasingly supplemented in feed to improve digestibility and reduce antinutritive effects of phytate. The microbial origin of these exogenous enzymes suggests a potentially important mechanism of probiotic functionality. We investigated phytate degradation as a novel probiotic mechanism using recombinant Lactobacillus cultures expressing Bacillus subtilis phytase. B. subtilis phyA was codon optimized for expression in Lactobacillus and cloned into the expression vector pTRK882. The resulting plasmid, pTD003, was transformed into Lactobacillus acidophilus, Lactobacillus gallinarum, and Lactobacillus gasseri. SDS-PAGE revealed a protein in the culture supernatants of Lactobacillus pTD003 transformants with a molecular weight similar to that of the B. subtilis phytase. Expression of B. subtilis phytase increased phytate degradation of L. acidophilus, L. gasseri, and L. gallinarum approximately 4-, 10-, and 18-fold over the background activity of empty-vector transformants, respectively. Phytase-expressing L. gallinarum and L. gasseri were administered to broiler chicks fed a phosphorus-deficient diet. Phytase-expressing L. gasseri improved weight gain of broiler chickens to a level comparable to that for chickens fed a control diet adequate in phosphorus, demonstrating proof of principle that administration of phytate-degrading probiotic cultures can improve performance of livestock animals. This will inform future studies investigating whether probiotic cultures are able to provide both the performance benefits of feed enzymes and the animal health and food safety benefits traditionally associated with probiotics. PMID:24271165

Evaluation of phytate-degrading Lactobacillus culture administration to broiler chickens.

PubMed

Askelson, Tyler E; Campasino, Ashley; Lee, Jason T; Duong, Tri

2014-02-01

Probiotics have been demonstrated to promote growth, stimulate immune responses, and improve food safety of poultry. While widely used, their effectiveness is mixed, and the mechanisms through which they contribute to poultry production are not well understood. Microbial phytases are increasingly supplemented in feed to improve digestibility and reduce antinutritive effects of phytate. The microbial origin of these exogenous enzymes suggests a potentially important mechanism of probiotic functionality. We investigated phytate degradation as a novel probiotic mechanism using recombinant Lactobacillus cultures expressing Bacillus subtilis phytase. B. subtilis phyA was codon optimized for expression in Lactobacillus and cloned into the expression vector pTRK882. The resulting plasmid, pTD003, was transformed into Lactobacillus acidophilus, Lactobacillus gallinarum, and Lactobacillus gasseri. SDS-PAGE revealed a protein in the culture supernatants of Lactobacillus pTD003 transformants with a molecular weight similar to that of the B. subtilis phytase. Expression of B. subtilis phytase increased phytate degradation of L. acidophilus, L. gasseri, and L. gallinarum approximately 4-, 10-, and 18-fold over the background activity of empty-vector transformants, respectively. Phytase-expressing L. gallinarum and L. gasseri were administered to broiler chicks fed a phosphorus-deficient diet. Phytase-expressing L. gasseri improved weight gain of broiler chickens to a level comparable to that for chickens fed a control diet adequate in phosphorus, demonstrating proof of principle that administration of phytate-degrading probiotic cultures can improve performance of livestock animals. This will inform future studies investigating whether probiotic cultures are able to provide both the performance benefits of feed enzymes and the animal health and food safety benefits traditionally associated with probiotics.

Upregulation of Monocyte/Macrophage HGFIN (Gpnmb/Osteoactivin) Expression in End-Stage Renal Disease

PubMed Central

Vaziri, Nosratola D.; Yuan, Jun; Adler, Sharon G.

2010-01-01

Background and objectives: Hematopoietic growth factor–inducible neurokinin 1 (HGFIN), also known as Gpnmb and osteoactivin, is a transmembrane glycoprotein that is expressed in numerous cells, including osteoclasts, macrophages, and dendritic cells. It serves as an osteoblast differentiation factor, participates in bone mineralization, and functions as a negative regulator of inflammation in macrophages. Although measurable at low levels in monocytes, monocyte-to-macrophage transformation causes substantial increase in HGFIN expression. HGFIN is involved in systemic inflammation, bone demineralization, and soft tissue vascular calcification. Design, setting, participants, & measurements: We explored HGFIN expression in monocytes and monocyte-derived macrophages in 21 stable hemodialysis patients and 22 control subjects. Results: Dialysis patients exhibited marked upregulation of colony-stimulating factor and IL-6 and significant downregulation of IL-10 in intact monocytes and transformed macrophages. HGFIN expression in intact monocytes was negligible in control subjects but conspicuously elevated (8.6-fold) in dialysis patients. As expected, in vitro monocyte-to-macrophage transformation resulted in marked upregulation of HGFIN in cells obtained from both groups but much more so in dialysis patients (17.5-fold higher). Upregulation of HGFIN and inflammatory cytokines in the uremic monocyte-derived macrophages occurred when grown in the presence of either normal or uremic serum, suggesting the enduring effect of the in vivo uremic milieu on monocyte/macrophage phenotype and function. Conclusions: Uremic macrophages exhibit increased HGFIN gene and protein expression and heightened expression of proinflammatory and a suppressed expression of anti-inflammatory cytokines. Further studies are needed to determine the role of heightened monocyte/macrophage HGFIN expression in the pathogenesis of ESRD-induced inflammation and vascular and soft tissue calcification. PMID:19833906

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

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

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.

PubMed Central

Ferrara, N; Winer, J; Burton, T; Rowland, A; Siegel, M; Phillips, H S; Terrell, T; Keller, G A; Levinson, A D

1993-01-01

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes. Images PMID:8423215

Balance of antiangiogenic and angiogenic factors in the context of the etiology of preeclampsia.

PubMed

Seki, Hiroyuki

2014-10-01

The "two-stage disorder" theory that is assumed for the etiology of preeclampsia hypothesizes that antiangiogenic and angiogenic factors and/or placental debris play an important role in this disorder. The physiological actions of placental debris occur via the balance between antiangiogenic and angiogenic factors. Accordingly, this balance between antiangiogenic and angiogenic factors should be investigated to elucidate the various pathological features of preeclampsia. Their accurate evaluation is needed to investigate not only antiangiogenic factors (such as sFlt-1 and sEng) and angiogenic factors (such as vascular endothelial growth factor, placental growth factor and transforming growth factor-β) but also the expression level of their receptors such as Flt-1 and Eng. However, it is ethically and technically difficult to investigate the above-mentioned factors at antepartum in human patients. The examination of the ratios of sFlt-1/vascular endothelial growth factor receptor ligands and sEng/transforming vascular endothelial growth factor-β and the use of experimental animal models may help in elucidating various unresolved issues in preeclampsia. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Friend spleen focus-forming virus transforms rodent fibroblasts in cooperation with a short form of the receptor tyrosine kinase Stk

PubMed Central

Nishigaki, Kazuo; Hanson, Charlotte; Jelacic, Tanya; Thompson, Delores; Ruscetti, Sandra

2005-01-01

Friend spleen focus-forming virus (SFFV) causes rapid erythroleukemia in mice due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator erythropoietin (Epo) because of constitutive activation of Epo signal transduction pathways. Although SFFV infects many cell types, deregulation of cell growth occurs only when SFFV infects erythroid cells, suggesting that these cells express unique proteins that the virus requires to mediate its biological effects. Not only do erythroid cells express the Epo receptor (EpoR), but those from mice susceptible to SFFV-induced erythroleukemia also express a short form of the receptor tyrosine kinase Stk (sf-Stk). In erythroid cells, SFFV gp55 interacts with the EpoR complex and sf-Stk, leading to activation of the kinase and constitutive activation of signal transducing molecules. In this study, we demonstrate that SFFV gp55 can also deregulate the growth of nonerythroid cells when it is coexpressed with sf-Stk. Expression of SFFV gp55 in rodent fibroblasts engineered to express sf-Stk induced their transformation, as demonstrated by focus formation and anchorage-independent growth in vitro. This transformation by SFFV gp55 requires the kinase activity of sf-Stk and the presence of its extracellular domain but not expression of the EpoR or the tyrosine kinase Jak2, which is required for activation of signal transduction pathways through the EpoR. Thus, expression of SFFV gp55 in nonerythroid cells coexpressing sf-Stk results in their uncontrolled growth, demonstrating a previously unrecognized mechanism for retrovirus transformation of rodent fibroblasts and providing insight into SFFV-induced disease. PMID:16223879

Roles of Ring-Hydroxylating Dioxygenases in Styrene and Benzene Catabolism in Rhodococcus jostii RHA1▿ †

PubMed Central

Patrauchan, Marianna A.; Florizone, Christine; Eapen, Shawn; Gómez-Gil, Leticia; Sethuraman, Bhanu; Fukuda, Masao; Davies, Julian; Mohn, William W.; Eltis, Lindsay D.

2008-01-01

Proteomics and targeted gene disruption were used to investigate the catabolism of benzene, styrene, biphenyl, and ethylbenzene in Rhodococcus jostii RHA1, a well-studied soil bacterium whose potent polychlorinated biphenyl (PCB)-transforming properties are partly due to the presence of the related Bph and Etb pathways. Of 151 identified proteins, 22 Bph/Etb proteins were among the most abundant in biphenyl-, ethylbenzene-, benzene-, and styrene-grown cells. Cells grown on biphenyl, ethylbenzene, or benzene contained both Bph and Etb enzymes and at least two sets of lower Bph pathway enzymes. By contrast, styrene-grown cells contained no Etb enzymes and only one set of lower Bph pathway enzymes. Gene disruption established that biphenyl dioxygenase (BPDO) was essential for growth of RHA1 on benzene or styrene but that ethylbenzene dioxygenase (EBDO) was not required for growth on any of the tested substrates. Moreover, whole-cell assays of the ΔbphAa and etbAa1::cmrA etbAa2::aphII mutants demonstrated that while both dioxygenases preferentially transformed biphenyl, only BPDO transformed styrene. Deletion of pcaL of the β-ketoadipate pathway disrupted growth on benzene but not other substrates. Thus, styrene and benzene are degraded via meta- and ortho-cleavage, respectively. Finally, catalases were more abundant during growth on nonpolar aromatic compounds than on aromatic acids. This suggests that the relaxed specificities of BPDO and EBDO that enable RHA1 to grow on a range of compounds come at the cost of increased uncoupling during the latter's initial transformation. The stress response may augment RHA1's ability to degrade PCBs and other pollutants that induce similar uncoupling. PMID:17965160

Regulatory T cells protect mice against coxsackievirus-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway.

PubMed

Shi, Yu; Fukuoka, Masahiro; Li, Guohua; Liu, Youan; Chen, Manyin; Konviser, Michael; Chen, Xin; Opavsky, Mary Anne; Liu, Peter P

2010-06-22

Coxsackievirus B3 infection is an excellent model of human myocarditis and dilated cardiomyopathy. Cardiac injury is caused either by a direct cytopathic effect of the virus or through immune-mediated mechanisms. Regulatory T cells (Tregs) play an important role in the negative modulation of host immune responses and set the threshold of autoimmune activation. This study was designed to test the protective effects of Tregs and to determine the underlying mechanisms. Carboxyfluorescein diacetate succinimidyl ester-labeled Tregs or naïve CD4(+) T cells were injected intravenously once every 2 weeks 3 times into mice. The mice were then challenged with intraperitoneal coxsackievirus B3 immediately after the last cell transfer. Transfer of Tregs showed higher survival rates than transfer of CD4(+) T cells (P=0.0136) but not compared with the PBS injection group (P=0.0589). Interestingly, Tregs also significantly decreased virus titers and inflammatory scores in the heart. Transforming growth factor-beta and phosphorylated AKT were upregulated in Tregs-transferred mice and coxsackie-adenovirus receptor expression was decreased in the heart compared with control groups. Transforming growth factor-beta decreased coxsackie-adenovirus receptor expression and inhibited coxsackievirus B3 infection in HL-1 cells and neonatal cardiac myocytes. Splenocytes collected from Treg-, CD4(+) T-cell-, and PBS-treated mice proliferated equally when stimulated with heat-inactivated virus, whereas in the Treg group, the proliferation rate was reduced significantly when stimulated with noninfected heart tissue homogenate. Adoptive transfer of Tregs protected mice from coxsackievirus B3-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway and thus suppresses the immune response to cardiac tissue, maintaining the antiviral immune response.

Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor β.

PubMed

Rawal, S Y; Dabbous, M Kh; Tipton, D A

2012-06-01

Marijuana (Cannabis sativa) use may be associated with gingival enlargement, resembling that caused by phenytoin. Cannabidiol (CBD), a nonpsychotropic Cannabis derivative, is structurally similar to phenytoin. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis components on these cells. The objective of this study was to determine effects of CBD on human gingival fibroblast fibrogenic and matrix-degrading activities. Fibroblasts were incubated with CBD in serum-free medium for 1-6 d. The effect of CBD on cell viability was determined by measuring activity of a mitochondrial enzyme. The fibrogenic molecule transforming growth factor β and the extracellular matrix molecule fibronectin were measured by ELISA. Pro-MMP-1 and total MMP-2 were measured by ELISA. Activity of MMP-2 was determined via a colorimetric assay in which a detection enzyme is activated by active MMP-2. Data were analysed using ANOVA and Scheffe's F procedure for post hoc comparisons. Cannabidiol had little or no significant effect on cell viability. Low CBD concentrations increased transforming growth factor β production by as much as 40% (p < 0.001), while higher concentrations decreased it by as much as 40% (p < 0.0001). Cannabidiol increased fibronectin production by as much as approximately 100% (p < 0.001). Lower CBD concentrations increased MMP production, but the highest concentrations decreased production of both MMPs (p < 0.05) and decreased MMP-2 activity (p < 0.02). The data suggest that the CBD may promote fibrotic gingival enlargement by increasing gingival fibroblast production of transforming growth factor β and fibronectin, while decreasing MMP production and activity. © 2011 John Wiley & Sons A/S.

Activation of the JNK pathway is essential for transformation by the Met oncogene.

PubMed

Rodrigues, G A; Park, M; Schlessinger, J

1997-05-15

The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically activated through a rearrangement that creates a hybrid gene Tpr-Met. The resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH2-containing signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor protein, which couples receptor tyrosine kinases to the Ras signaling pathway. Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase signaling pathway through Grb2 may be essential for cellular transformation. To test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3 domains were introduced into Tpr-Met transformed fibroblasts. Cells overexpressing the mutants were found to be morphologically reverted and exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both Tpr-Met-induced transformation and activation of JNK. These experiments reveal a novel link between Met and the JNK pathway, which is essential for transformation by this oncogene.

Transformation and Sorption of Illicit Drug Biomarkers in Sewer Systems: Understanding the Role of Suspended Solids in Raw Wastewater.

PubMed

Ramin, Pedram; Libonati Brock, Andreas; Polesel, Fabio; Causanilles, Ana; Emke, Erik; de Voogt, Pim; Plósz, Benedek Gy

2016-12-20

Sewer pipelines, although primarily designed for sewage transport, can also be considered as bioreactors. In-sewer processes may lead to significant variations of chemical loadings from source release points to the treatment plant influent. In this study, we assessed in-sewer utilization of growth substrates (primary metabolic processes) and transformation of illicit drug biomarkers (secondary metabolic processes) by suspended biomass. Sixteen drug biomarkers were targeted, including mephedrone, methadone, cocaine, heroin, codeine, and tetrahydrocannabinol (THC) and their major human metabolites. Batch experiments were performed under aerobic and anaerobic conditions using raw wastewater. Abiotic biomarker transformation and partitioning to suspended solids and reactor wall were separately investigated under both redox conditions. A process model was identified by combining and extending the Wastewater Aerobic/anaerobic Transformations in Sewers (WATS) model and Activated Sludge Model for Xenobiotics (ASM-X). Kinetic and stoichiometric model parameters were estimated using experimental data via the Bayesian optimization method DREAM (ZS) . Results suggest that biomarker transformation significantly differs from aerobic to anaerobic conditions, and abiotic conversion is the dominant mechanism for many of the selected substances. Notably, an explicit description of biomass growth during batch experiments was crucial to avoid significant overestimation (up to 385%) of aerobic biotransformation rate constants. Predictions of in-sewer transformation provided here can reduce the uncertainty in the estimation of drug consumption as part of wastewater-based epidemiological studies.

Arsenic transformation and plant growth promotion characteristics of As-resistant endophytic bacteria from As-hyperaccumulator Pteris vittata.

PubMed

Xu, Jia-Yi; Han, Yong-He; Chen, Yanshan; Zhu, Ling-Jia; Ma, Lena Q

2016-02-01

The ability of As-resistant endophytic bacteria in As transformation and plant growth promotion was determined. The endophytes were isolated from As-hyperaccumulator Pteris vittata (PV) after growing for 60 d in a soil containing 200 mg kg(-1) arsenate (AsV). They were isolated in presence of 10 mM AsV from PV roots, stems, and leaflets, representing 4 phyla and 17 genera. All endophytes showed at least one plant growth promoting characteristics including IAA synthesis, siderophore production and P solubilization. The root endophytes had higher P solubilization ability than the leaflet (60.0 vs. 18.3 mg L(-1)). In presence of 10 mM AsV, 6 endophytes had greater growth than the control, suggesting As-stimulated growth. Furthermore, root endophytes were more resistant to AsV while the leaflet endophytes were more tolerant to arsenite (AsIII), which corresponded to the dominant As species in PV tissues. Bacterial As resistance was positively correlated to their ability in AsV reduction but not AsIII oxidation. The roles of those endophytes in promoting plant growth and As resistance in P. vittata warrant further investigation. Published by Elsevier Ltd.

Measuring Attitude towards RE: Factoring Pupil Experience and Home Faith Background into Assessment

ERIC Educational Resources Information Center

Thanissaro, Phra Nicholas

2012-01-01

Recent studies have increasingly favoured contextualisation of religious education (RE) to pupils' home faith background in spite of current assessment methods that might hinder this. For a multi-religious, multi-ethnic sample of 369 London school pupils aged from 13 to 15 years, this study found that the participatory, transformative and…

Interdisciplinary Education--A Predator-Prey Model for Developing a Skill Set in Mathematics, Biology and Technology

ERIC Educational Resources Information Center

van der Hoff, Quay

2017-01-01

The science of biology has been transforming dramatically and so the need for a stronger mathematical background for biology students has increased. Biological students reaching the senior or post-graduate level often come to realize that their mathematical background is insufficient. Similarly, students in a mathematics programme, interested in…

Implicit Theories about Intelligence and Growth (Personal Best) Goals: Exploring Reciprocal Relationships

ERIC Educational Resources Information Center

Martin, Andrew J.

2015-01-01

Background: There has been increasing interest in growth approaches to students' academic development, including value-added models, modelling of academic trajectories, growth motivation orientations, growth mindsets, and growth goals. Aims: This study sought to investigate the relationships between implicit theories about intelligence…

Future Climate Prediction of Urban Atmosphere in A Tropical Megacity: Utilization of RCP/SSP Scenarios with an Urban Growth Model

NASA Astrophysics Data System (ADS)

Darmanto, N. S.; Varquez, A. C. G.; Kanda, M.; Takakuwa, S.

2016-12-01

Economic development in Southeast Asia megacities leads to rapid transformation into more complicated urban configurations. These configurations, including building geometry, enhance aerodynamic drag thus reducing near-surface wind speeds. Roughness parameters representing building geometry, along with anthropogenic heat emissions, contribute to the formation of urban heat islands (UHI). All these have been reproduced successfully in the Weather Research and Forecasting (WRF) Model coupled with an improved single-layer urban canopy model incorporating a realistic distribution of urban parameters and anthropogenic heat emission in the Jakarta Greater Area. We apply this technology to climate change studies by introducing future urbanization defined by urban sprawl, vertical rise in buildings, and increase anthropogenic heat emission (AHE) due to population changes, into futuristic climate modelling. To simulate 2050s future climate, pseudo-global warming method was used which relied on current and ensembles of 5 CMIP5 GCMs for 2 representative concentration pathways (RCP), 2.6 and 8.5. To determine future urbanization level, 2050 population growth and energy consumption were estimated from shared socioeconomic pathways (SSP). This allows the estimation of future urban sprawl, building geometry, and AHE using the SLEUTH urban growth model and spatial growth assumptions. Two cases representing combinations of RCP and SSP were simulated in WRF: RCP2.6-SSP1 and RCP8.5-SSP3. Each case corresponds to best and worst-case scenarios of implementing adaptation and mitigation strategies, respectively. It was found that 2-m temperature of Jakarta will increase by 0.62°C (RCP2.6) and 1.44°C (RCP8.5) solely from background climate change; almost on the same magnitude as the background temperature increase of RCP2.6 (0.5°C) and RCP8.5 (1.2°C). Compared with previous studies, the result indicates that the effect of climate change on UHI in tropical cities may be lesser than cities located in the mid-latitudes. However, it is expected that the combined effect of urbanization and climate change will result to significant changes on future urban temperature. ACK: This research was supported by the Environment Research and Technology Development Fund (S-14) of the Ministry of the Environment, Japan.

Learning and Refugees: Recognizing the Darker Side of Transformative Learning

ERIC Educational Resources Information Center

Morrice, Linda

2013-01-01

Learning is generally viewed as a positive process bringing benefits to the individual, leading to growth and self-development. But is this always the case? This article draws on empirical research with refugees and considers the processes of transforming experience and learning that accompanies transition to life in the United Kingdom. I will…

Jack Mezirow's Conceptualisation of Adult Transformative Learning: A Review

ERIC Educational Resources Information Center

Calleja, Colin

2014-01-01

This paper traces the evolution of Jack Mezirow's transformative learning theory and its conceptualisation. It discusses the three major influences, namely Thomas Khun's philosophical conception of paradigm, Freire's conception of conscientisation and consciousness growth, and Habermas' domains of learning and the discussion of…

Midlife Awakening: An Emergent Transformation of the Self

ERIC Educational Resources Information Center

Lear, Glenna

2017-01-01

This article explores women's midlife learning as an awakening of the self in the process of being in the world and interacting with others and uses the author's personal experience of transformation as a developmental change with the emergence of personal growth and self-realization of a more complete, balanced, and fulfilled self. In the…

Outdoor Adventure Education: Applying Transformative Learning Theory to Understanding Instrumental Learning and Personal Growth in Environmental Education

ERIC Educational Resources Information Center

D'Amato, Laura Galen; Krasny, Marianne E.

2011-01-01

We conducted a qualitative study of the experiences of 23 Outdoor Adventure Education (OAE) participants to determine what participants found significant about their course and to what course elements they attributed this significance. Participants experienced personal transformations, which they attributed to spending extended time in pristine…

Unleashing Waves of Innovation: Transformative Broadband for America's Future. Version 18

ERIC Educational Resources Information Center

Western Interstate Commission for Higher Education, 2009

2009-01-01

A forward-thinking National Broadband Strategy should focus on the transformative power of advanced networks to unleash new waves of innovation, jobs, economic growth, and national competitiveness. Such a strategy should create new tools to deliver health care, education, and a low carbon economy. The American Recovery and Reinvestment Act…

Creating Sacred Experiences for Children as Pathways to Healing, Growth and Transformation

ERIC Educational Resources Information Center

Bhagwan, Raisuyah

2009-01-01

Spiritual well-being forms an important dimension of children's lives globally. They are vulnerable to a range of difficulties as they grow and develop. Recently there has been a strong awareness that spirituality not only enables their healing but is critical to spiritual transformation. This paper briefly explores children's spirituality and…

Key Enzymes Enabling the Growth of Arthrobacter sp. Strain JBH1 with Nitroglycerin as the Sole Source of Carbon and Nitrogen

PubMed Central

Husserl, Johana; Hughes, Joseph B.

2012-01-01

Flavoprotein reductases that catalyze the transformation of nitroglycerin (NG) to dinitro- or mononitroglycerols enable bacteria containing such enzymes to use NG as the nitrogen source. The inability to use the resulting mononitroglycerols limits most strains to incomplete denitration of NG. Recently, Arthrobacter strain JBH1 was isolated for the ability to grow on NG as the sole source of carbon and nitrogen, but the enzymes and mechanisms involved were not established. Here, the enzymes that enable the Arthrobacter strain to incorporate NG into a productive pathway were identified. Enzyme assays indicated that the transformation of nitroglycerin to mononitroglycerol is NADPH dependent and that the subsequent transformation of mononitroglycerol is ATP dependent. Cloning and heterologous expression revealed that a flavoprotein catalyzes selective denitration of NG to 1-mononitroglycerol (1-MNG) and that 1-MNG is transformed to 1-nitro-3-phosphoglycerol by a glycerol kinase homolog. Phosphorylation of the nitroester intermediate enables the subsequent denitration of 1-MNG in a productive pathway that supports the growth of the isolate and mineralization of NG. PMID:22427495

Key enzymes enabling the growth of Arthrobacter sp. strain JBH1 with nitroglycerin as the sole source of carbon and nitrogen.

PubMed

Husserl, Johana; Hughes, Joseph B; Spain, Jim C

2012-05-01

Flavoprotein reductases that catalyze the transformation of nitroglycerin (NG) to dinitro- or mononitroglycerols enable bacteria containing such enzymes to use NG as the nitrogen source. The inability to use the resulting mononitroglycerols limits most strains to incomplete denitration of NG. Recently, Arthrobacter strain JBH1 was isolated for the ability to grow on NG as the sole source of carbon and nitrogen, but the enzymes and mechanisms involved were not established. Here, the enzymes that enable the Arthrobacter strain to incorporate NG into a productive pathway were identified. Enzyme assays indicated that the transformation of nitroglycerin to mononitroglycerol is NADPH dependent and that the subsequent transformation of mononitroglycerol is ATP dependent. Cloning and heterologous expression revealed that a flavoprotein catalyzes selective denitration of NG to 1-mononitroglycerol (1-MNG) and that 1-MNG is transformed to 1-nitro-3-phosphoglycerol by a glycerol kinase homolog. Phosphorylation of the nitroester intermediate enables the subsequent denitration of 1-MNG in a productive pathway that supports the growth of the isolate and mineralization of NG.

Colour preferences of juvenile turbot (Scophthalmus maximus).

PubMed

Li, Xian; Chi, Liang; Tian, Huiqin; Meng, Lingjie; Zheng, Jimeng; Gao, Xiaolong; Liu, Ying

2016-03-15

The background colour of aquaculture tanks is normally chosen based on practical experience and/or observations of fish behaviour and the growth rates achieved. However, some farmed species, including turbot, are sentient and can show a preference for a particular environment. In the current study, a self-referent colour preference device was developed and the self-referent colour preference of farmed fish investigated. In experiment 1, the background colour preference of juvenile turbot cultured under a grey background for >3months post-incubation was evaluated. Based on these results, in experiment 2, juvenile turbot were adapted to blue, pink, white, or black backgrounds for 50days and their preferences established. Meanwhile, the growth rates, feed intake, and metabolic rates (including oxygen consumption rate, and ammonia excretion rate) of the turbot were evaluated. The results showed that turbot farmed under a grey background, or after long-term white, blue, pink and black colour adaptation, always displayed a preference for a white background and a dislike for black, red, or brown backgrounds, although their body colour was greyish. Long-term adaptation influenced the frequency of juveniles selecting white, black, pink or blue backgrounds. They showed the highest growth rate, feed intake, and metabolic rates under blue and white backgrounds, and the lowest under a black background in accordance with their preferences shown in experiment 1. Although it is unclear how turbot determine their self-referent colour preferences over such a short period of time, these results indicate that dark colours are unsuitable for the aquaculture of turbot culture in terms of the welfare of the fish. Copyright © 2016 Elsevier Inc. All rights reserved.

Posttraumatic growth, depressive symptoms, posttraumatic stress symptoms, post-migration stressors and quality of life in multi-traumatized psychiatric outpatients with a refugee background in Norway.

PubMed

Teodorescu, Dinu-Stefan; Siqveland, Johan; Heir, Trond; Hauff, Edvard; Wentzel-Larsen, Tore; Lien, Lars

2012-07-23

Psychiatric outpatients with a refugee background have often been exposed to a variety of potentially traumatizing events, with numerous negative consequences for their mental health and quality of life. However, some patients also report positive personal changes, posttraumatic growth, related to these potentially traumatic events. This study describes posttraumatic growth, posttraumatic stress symptoms, depressive symptoms, post-migration stressors, and their association with quality of life in an outpatient psychiatric population with a refugee background in Norway. Fifty five psychiatric outpatients with a refugee background participated in a cross-sectional study using clinical interviews to measure psychopathology (SCID-PTSD, MINI), and four self-report instruments measuring posttraumatic growth, posttraumatic stress symptoms, depressive symptoms, and quality of life (PTGI-SF, IES-R, HSCL-25-depression scale, and WHOQOL-Bref) as well as measures of social integration, social network and employment status. All patients reported some degree of posttraumatic growth, while only 31% reported greater amounts of growth. Eighty percent of the patients had posttraumatic stress symptoms above the cut-off point, and 93% reported clinical levels of depressive symptoms. Quality of life in the four domains of the WHOQOL-Bref levels were low, well below the threshold for the'life satisfaction' standard proposed by Cummins. A hierarchic regression model including depressive symptoms, posttraumatic stress symptoms, posttraumatic growth, and unemployment explained 56% of the total variance found in the psychological health domain of the WHOQOL-Bref scale. Posttraumatic growth made the strongest contribution to the model, greater than posttraumatic stress symptoms or depressive symptoms. Post-migration stressors like unemployment, weak social network and poor social integration were moderately negatively correlated with posttraumatic growth and quality of life, and positively correlated with psychopathological symptoms. Sixty percent of the outpatients were unemployed. Multi-traumatized refugees in outpatient clinics reported both symptoms of psychopathology and posttraumatic growth after exposure to multiple traumatic events. Symptoms of psychopathology were negatively related to the quality of life, and positively related to post-migration stressors such as unemployment, weak social network and poor social integration. Posttraumatic growth was positively associated with quality of life, and negatively associated with post-migration stressors. Hierarchical regression modeling showed that posttraumatic growth explained more of the variance in quality of life than did posttraumatic stress symptoms, depressive symptoms or unemployment. It may therefore be necessary to address both positive changes and psychopathological symptoms when assessing and treating multi-traumatized outpatients with a refugee background.

Overexpression of a glutamine synthetase gene affects growth and development in sorghum.

PubMed

Urriola, Jazmina; Rathore, Keerti S

2015-06-01

Nitrogen is a primary macronutrient in plants, and nitrogen fertilizers play a critical role in crop production and yield. In this study, we investigated the effects of overexpressing a glutamine synthetase (GS) gene on nitrogen metabolism, and plant growth and development in sorghum (Sorghum bicolor L., Moench). GS catalyzes the ATP dependent reaction between ammonia and glutamate to produce glutamine. A 1,071 bp long coding sequence of a sorghum cytosolic GS gene (Gln1) under the control of the maize ubiquitin (Ubq) promoter was introduced into sorghum immature embryos by Agrobacterium-mediated transformation. Progeny of the transformants exhibited higher accumulation of the Gln1 transcripts and up to 2.2-fold higher GS activity compared to the non-transgenic controls. When grown under optimal nitrogen conditions, these Gln1 transgenic lines showed greater tillering and up to 2.1-fold increase in shoot vegetative biomass. Interestingly, even under greenhouse conditions, we observed a seasonal component to both these parameters and the grain yield. Our results, showing that the growth and development of sorghum Gln1 transformants are also affected by N availability and other environmental factors, suggest complexity of the relationship between GS activity and plant growth and development. A better understanding of other control points and the ability to manipulate these will be needed to utilize the transgenic technology to improve nitrogen use efficiency of crop plants.

Establishment and characterization of a new marine fish cell line from ovary of barfin flounder ( Verasper moseri)

NASA Astrophysics Data System (ADS)

Xu, Xiaohui; Fan, Tingjun; Jiang, Guojian; Yang, Xiuxia

2015-12-01

A novel continuous ovary cell line from barfin flounder ( Verasper moseri) (BFO cell line) was established with its primitive application in transgenic expression demonstrated in this study. Primarily cultured cells grew well at 22°C in Dulbecco's modified Eagle medium/F12 medium (DMEM/F12, 1:1; pH 7.2) supplemented with 20% fetal bovine serum (FBS), carboxymethyl chitooligosaccharide, basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I). The primary BFO cells in fibroblastic morphology proliferated into a confluent monolayer about 2 weeks later, and were able to be subcultured. Impacts of medium and temperature on the growth of the cells were examined. The optimum growth was found in DMEM/F12 with 20% FBS and at 22°C. The BFO cells can be continuously subcultured to Passage 120 steadily with a population doubling time of 32.7 h at Passage 60. Chromosome analysis revealed that 72% of BFO cells at Passage 60 maintained the normal diploid chromosome number (46) with a normal karyotype of 2st+44t. The results of gene transformation indicated that green fluorescence protein (GFP) positively expressed in these cells after being transformed with pcDNA3.1-GFP. Therefore, a continuous and transformable BFO cell line was successfully established, which may serve as a useful tool for cytotechnological manipulation and transgenic modification of this fish.

Antisense suppression of violaxanthin de-epoxidase in tobacco does not affect plant performance in controlled growth conditions.

PubMed

Chang, S H; Bugos, R C; Sun, W H; Yamamoto, H Y

2000-01-01

Violaxanthin de-epoxidase (VDE) catalyzes the de-epoxidation of violaxanthin to antheraxanthin and zeaxanthin in the xanthophyll cycle. Tobacco was transformed with an antisense VDE construct under control of the cauliflower mosaic virus 35S promoter to determine the effect of reduced levels of VDE on plant growth. Screening of 40 independent transformants revealed 18 antisense lines with reduced levels of VDE activity with two in particular (TAS32 and TAS39) having greater than 95% reduction in VDE activity. Northern analysis demonstrated that these transformants had greatly suppressed levels of VDE mRNA. De-epoxidation of violaxanthin was inhibited to such an extent that no zeaxanthin and only very low levels of antheraxanthin could be detected after exposure of leaves to high light (2000 mumol m(-2) s(-1) for 20 min) with no observable effect on levels of other carotenoids and chlorophyll. Non-photochemical quenching was greatly reduced in the antisense VDE tobacco, demonstrating that a significant level of the non-photochemical quenching in tobacco requires de-epoxidation of violaxanthin. Although the antisense plants demonstrated a greatly impaired de-epoxidation of violaxanthin, no effect on plant growth or photosynthetic rate was found when plants were grown at a photon flux density of 500 or 1000 mumol m(-2) s(-1) under controlled growth conditions as compared to wild-type tobacco.

Abrogation of both short and long forms of latent transforming growth factor-β binding protein-1 causes defective cardiovascular development and is perinatally lethal.

PubMed

Horiguchi, Masahito; Todorovic, Vesna; Hadjiolova, Krassimira; Weiskirchen, Ralf; Rifkin, Daniel B

2015-04-01

Latent transforming growth factor-β binding protein-1 (LTBP-1) is an extracellular protein that is structurally similar to fibrillin and has an important role in controlling transforming growth factor-β (TGF-β) signaling by storing the cytokine in the extracellular matrix and by being involved in the conversion of the latent growth factor to its active form. LTBP-1 is found as both short (LTBP-1S) and long (LTBP-1L) forms, which are derived through the use of separate promoters. There is controversy regarding the importance of LTBP-1L, as Ltbp1L knockout mice showed multiple cardiovascular defects but the complete null mice did not. Here, we describe a third line of Ltbp1 knockout mice generated utilizing a conditional knockout strategy that ablated expression of both L and S forms of LTBP-1. These mice show severe developmental cardiovascular abnormalities and die perinatally; thus these animals display a phenotype similar to previously reported Ltbp1L knockout mice. We reinvestigated the other "complete" knockout line and found that these mice express a splice variant of LTBP-1L and, therefore, are not complete Ltbp1 knockouts. Our results clarify the phenotypes of Ltbp1 null mice and re-emphasize the importance of LTBP-1 in vivo. Copyright © 2015. Published by Elsevier B.V.

Emerging Definition of Next-Generation of Aeronautical Communications

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.

2006-01-01

Aviation continues to experience rapid growth. In regions such as the United States and Europe air traffic congestion is constraining operations, leading to major new efforts to develop methodologies and infrastructures to enable continued aviation growth through transformational air traffic management systems. Such a transformation requires better communications linking airborne and ground-based elements. Technologies for next-generation communications, the required capacities, frequency spectrum of operation, network interconnectivity, and global interoperability are now receiving increased attention. A number of major planning and development efforts have taken place or are in process now to define the transformed airspace of the future. These activities include government and industry led efforts in the United States and Europe, and by international organizations. This paper will review the features, approaches, and activities of several representative planning and development efforts, and identify the emerging global consensus on requirements of next generation aeronautical communications systems for air traffic control.

An in situ X ray diffraction study of the kinetics of the Ni2SiO4 olivine-spinel transformation

NASA Technical Reports Server (NTRS)

Rubie, D. C.; Tsuchida, Y.; Yagi, T.; Utsumi, W.; Kikegawa, T.

1990-01-01

The kinetics of the olivine-spinel transformation in Ni2SiO4 were investigated in an in situ X-ray diffraction experiments in which synchrotron radiation was used as an X-ray source. The starting material was Ni2SO4 olivine which was hot-pressed in situ at 980 C and 2.5 GPa; during the transformation, X-ray diffraction patterns were collected at intervals of 30 or 120 sec. The kinetic data were analyzed using Cahn's (1956) model. The activation energy for growth at 3.6-3.7 GPa was estimated as 438 + or - 199 kJ/mol. It is shown that, in order to make significant extrapolations of the kinetic data to a geological scale, the dependence of the rates of both nucleation and growth on temperature and pressure must be evaluated separately.

Anaerobic Transformation of Furfural by Methanococcus deltae (Delta)LH

PubMed Central

Belay, N.; Boopathy, R.; Voskuilen, G.

1997-01-01

Methanococcus deltae (Delta)LH was grown on H(inf2)-CO(inf2) in the presence of various concentrations of furfural. Furfural at higher concentrations, namely, 20 and 25 mM, inhibited growth of this organism. At concentration of 5 and 10 mM, no inhibition of growth was observed. The other methanogens in this study were not inhibited by 10 mM furfural. Among the methanogens tested, M. deltae was capable of transforming furfural, whereas Methanobacterium thermoautotrophicum Marburg, Methanosarcina barkeri 227, Methanococcus thermolithotrophicus, and Methanobrevibacter ruminantium lacked this capability. One hundred percent removal of furfural was observed within 48 h of incubation in M. deltae cultures. The end product observed during furfural metabolism was furfuryl alcohol. An almost stoichiometric amount of furfuryl alcohol was produced by M. deltae. This transformation is likely to be of value in the detoxification of furfural and in its ultimate conversion to methane and CO(inf2) by anaerobic digestion. PMID:16535618

Diffusive and martensitic nucleation kinetics in solid-solid transitions of colloidal crystals

NASA Astrophysics Data System (ADS)

Peng, Yi; Li, Wei; Wang, Feng; Still, Tim; Yodh, Arjun G.; Han, Yilong

2017-05-01

Solid-solid transitions between crystals follow diffusive nucleation, or various diffusionless transitions, but these kinetics are difficult to predict and observe. Here we observed the rich kinetics of transitions from square lattices to triangular lattices in tunable colloidal thin films with single-particle dynamics by video microscopy. Applying a small pressure gradient in defect-free regions or near dislocations markedly transform the diffusive nucleation with an intermediate-stage liquid into a martensitic generation and oscillation of dislocation pairs followed by a diffusive nucleus growth. This transformation is neither purely diffusive nor purely martensitic as conventionally assumed but a combination thereof, and thus presents new challenges to both theory and the empirical criterion of martensitic transformations. We studied how pressure, density, grain boundary, triple junction and interface coherency affect the nucleus growth, shape and kinetic pathways. These novel microscopic kinetics cast new light on control solid-solid transitions and microstructural evolutions in polycrystals.

Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.

PubMed

Tarte, Karin; Gaillard, Julien; Lataillade, Jean-Jacques; Fouillard, Loic; Becker, Martine; Mossafa, Hossein; Tchirkov, Andrei; Rouard, Hélène; Henry, Catherine; Splingard, Marie; Dulong, Joelle; Monnier, Delphine; Gourmelon, Patrick; Gorin, Norbert-Claude; Sensebé, Luc

2010-02-25

Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.

Optimal mode transformations for linear-optical cluster-state generation

DOE PAGES

Uskov, Dmitry B.; Lougovski, Pavel; Alsing, Paul M.; ...

2015-06-15

In this paper, we analyze the generation of linear-optical cluster states (LOCSs) via sequential addition of one and two qubits. Existing approaches employ the stochastic linear-optical two-qubit controlled-Z (CZ) gate with success rate of 1/9 per operation. The question of optimality of the CZ gate with respect to LOCS generation has remained open. We report that there are alternative schemes to the CZ gate that are exponentially more efficient and show that sequential LOCS growth is indeed globally optimal. We find that the optimal cluster growth operation is a state transformation on a subspace of the full Hilbert space. Finally,more » we show that the maximal success rate of postselected entangling n photonic qubits or m Bell pairs into a cluster is (1/2) n-1 and (1/4) m-1, respectively, with no ancilla photons, and we give an explicit optical description of the optimal mode transformations.« less

Diffusive and martensitic nucleation kinetics in solid-solid transitions of colloidal crystals

PubMed Central

Peng, Yi; Li, Wei; Wang, Feng; Still, Tim; Yodh, Arjun G.; Han, Yilong

2017-01-01

Solid–solid transitions between crystals follow diffusive nucleation, or various diffusionless transitions, but these kinetics are difficult to predict and observe. Here we observed the rich kinetics of transitions from square lattices to triangular lattices in tunable colloidal thin films with single-particle dynamics by video microscopy. Applying a small pressure gradient in defect-free regions or near dislocations markedly transform the diffusive nucleation with an intermediate-stage liquid into a martensitic generation and oscillation of dislocation pairs followed by a diffusive nucleus growth. This transformation is neither purely diffusive nor purely martensitic as conventionally assumed but a combination thereof, and thus presents new challenges to both theory and the empirical criterion of martensitic transformations. We studied how pressure, density, grain boundary, triple junction and interface coherency affect the nucleus growth, shape and kinetic pathways. These novel microscopic kinetics cast new light on control solid–solid transitions and microstructural evolutions in polycrystals. PMID:28504246

A numerical study of steady crystal growth in a vertical Bridgman device

NASA Astrophysics Data System (ADS)

Jalics, Miklos Kalman

Electronics based on semiconductors creates an enormous demand for high quality semiconductor single crystals. The vertical Bridgman device is commonly used for growing single crystals for a variety of materials such as GaAs, InP and HgCdTe. A mathematical model is presented for steady crystal growth under conditions where crystal growth is determined strictly by heat transfer. The ends of the ampoule are chosen far away from the insulation zone to allow for steady growth. A numerical solution is sought for this mathematical model. The equations are transformed into a rectangular geometry and appropriate finite difference techniques are applied on the transformed equations. Newton's method solves the nonlinear problem. To improve efficiency GMRES with preconditioning is used to compute the Newton iterates. The numerical results are used to compare with two current asymptotic theories that assume small Biot numbers. Results indicate that one of the asymptotic theories is accurate for even moderate Biot numbers.

Enhancement of microalgal growth and biocomponent-based transformations for improved biofuel recovery: A review.

PubMed

Salama, El-Sayed; Hwang, Jae-Hoon; El-Dalatony, Marwa M; Kurade, Mayur B; Kabra, Akhil N; Abou-Shanab, Reda A I; Kim, Ki-Hyun; Yang, Il-Seung; Govindwar, Sanjay P; Kim, Sunjoon; Jeon, Byong-Hun

2018-06-01

Microalgal biomass has received much attention as feedstock for biofuel production due to its capacity to accumulate a substantial amount of biocomponents (including lipid, carbohydrate, and protein), high growth rate, and environmental benefit. However, commercial realization of microalgal biofuel is a challenge due to its low biomass production and insufficient technology for complete utilization of biomass. Recently, advanced strategies have been explored to overcome the challenges of conventional approaches and to achieve maximum possible outcomes in terms of growth. These strategies include a combination of stress factors; co-culturing with other microorganisms; and addition of salts, flue gases, and phytohormones. This review summarizes the recent progress in the application of single and combined abiotic stress conditions to stimulate microalgal growth and its biocomponents. An innovative schematic model is presented of the biomass-energy conversion pathway that proposes the transformation of all potential biocomponents of microalgae into biofuels. Copyright © 2018 Elsevier Ltd. All rights reserved.

Wound Healing and Cancer Stem Cells: Inflammation as a Driver of Treatment Resistance in Breast Cancer

PubMed Central

Arnold, Kimberly M; Opdenaker, Lynn M; Flynn, Daniel; Sims-Mourtada, Jennifer

2015-01-01

The relationship between wound healing and cancer has long been recognized. The mechanisms that regulate wound healing have been shown to promote transformation and growth of malignant cells. In addition, chronic inflammation has been associated with malignant transformation in many tissues. Recently, pathways involved in inflammation and wound healing have been reported to enhance cancer stem cell (CSC) populations. These cells, which are highly resistant to current treatments, are capable of repopulating the tumor after treatment, causing local and systemic recurrences. In this review, we highlight proinflammatory cytokines and developmental pathways involved in tissue repair, whose deregulation in the tumor microenvironment may promote growth and survival of CSCs. We propose that the addition of anti-inflammatory agents to current treatment regimens may slow the growth of CSCs and improve therapeutic outcomes. PMID:25674014

Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene.

PubMed

Reznikoff, C A; Loretz, L J; Christian, B J; Wu, S Q; Meisner, L F

1988-08-01

Normal human urinary tract epithelial cells (HUC) were neoplastically transformed in vitro using a step-wise strategy. First, a partially transformed non-virus-producing cell line was obtained after infection of HUC with simian virus 40 (SV40). This cell line (SV-HUC-1) was demonstrated to be clonal in origin, as 100% of cells contained at least five of seven marker chromosomes. Marker chromosomes were formed by balanced translocations resulting in a 'pseudodiploid' cell line. SV-HUC-1 showed altered growth properties in vitro (e.g. anchorage independent growth) but failed to form tumors in athymic nude mice, even after 3 years in culture (80 passages). In the studies reported here, SV-HUC-1 at early passages (P15-P19) were exposed to 3-methylcholanthrene (MCA) in three separate experiments. After a six-week post-treatment period of cell culture, cells were inoculated s.c. into athymic nude mice. In all experiments, MCA-treated SV-HUC-1 formed carcinomas in mice usually with a latent period of 5-8 weeks. These carcinomas showed heterogeneity with respect to histopathologies and growth properties in the mice and karyotypes. All the tumors retained SV-HUC-1 chromosome markers, but each independent transformant was aneuploid and contained unique new marker chromosomes. Chromosomes usually altered in tumor cells included numbers 3, 5, 6, 9, 11 and 13. Mutations in the ras family of cellular proto-oncogenes resulting in altered mobility of the p21 protein product were not detected in six cell lines established from independently derived tumors. It is not yet known whether other cellular proto-oncogenes are activated in these tumorigenic transformants. Neither control SV-HUC-1 (which were not exposed to MCA), nor early passage HUC exposed to MCA formed tumors when inoculated into mice. Thus, the tumorigenic transformation of HUC resulted from the combined actions of SV40 and MCA.

Transforming han: a correlational method for psychology and religion.

PubMed

Oh, Whachul

2015-06-01

Han is a destructive feeling in Korea. Although Korea accomplished significant exterior growth, Korean society is still experiencing the dark aspects of transforming han as evidenced by having the highest suicide rate in Asia. Some reasons for this may be the fragmentation between North and South Korea. If we can transform han then it can become constructive. I was challenged to think of possibilities for transforming han internally; this brings me to the correlational method through psychological and religious interpretation. This study is to challenge and encourage many han-ridden people in Korean society. Through the psychological and religious understanding of han, people suffering can positively transform their han. They can relate to han more subjectively, and this means the han-ridden psyche has an innate sacredness of potential to transform.

Transformation of the diamond /110/ surface

NASA Technical Reports Server (NTRS)

Pepper, S. V.

1982-01-01

The diamond surface undergoes a transformation in its electronic structure by a vacuum anneal at approximately 900 C. This transformation is characterized by the appearance of a feature in the band gap region of the energy loss spectrum. The kinetics of the transformation on the (110) surface is studied by observing the growth of this feature with time and temperature. The transformation is found to be consistent with first-order kinetics with an activation energy of 4.8 eV. It is also found that the band gap feature could be removed by exposure of the transformed surface to excited hydrogen. The results are consistent with the polished diamond (110) surface being covered with hydrogen which removes the band gap states and can be thermally desorbed at approximately 900 C.

Growth and stress-induced transformation of zinc blende AlN layers in Al-AlN-TiN multilayers

DOE PAGES

Li, Nan; Yadav, Satyesh K.; Wang, Jian; ...

2015-12-18

We report that AlN nanolayers in sputter deposited {111}Al/AlN/TiN multilayers exhibit the metastable zinc-blende-structure (z-AlN). Based on density function theory calculations, the growth of the z-AlN is ascribed to the kinetically and energetically favored nitridation of the deposited aluminium layer. In situ nanoindentation of the as-deposited {111}Al/AlN/TiN multilayers in a high-resolution transmission electron microscope revealed the z-AlN to wurzite AlN phase transformation through collective glide of Shockley partial dislocations on every two {111} planes of the z-AlN.

Transforming growth factor β as regulator of cancer stemness and metastasis

PubMed Central

Bellomo, Claudia; Caja, Laia; Moustakas, Aristidis

2016-01-01

Key elements of cancer progression towards metastasis are the biological actions of cancer stem cells and stromal cells in the tumour microenvironment. Cross-communication between tumour and stromal cells is mediated by secreted cytokines, one of which, the transforming growth factor β (TGFβ), regulates essentially every cell within the malignant tissue. In this article, we focus on the actions of TGFβ on cancer stem cells, cancer-associated fibroblasts and immune cells that assist the overall process of metastatic dissemination. We aim at illustrating intricate connections made by various cells in the tumour tissue and which depend on the action of TGFβ. PMID:27537386

Transforming growth factor β: a master regulator of the gut microbiota and immune cell interactions.

PubMed

Bauché, David; Marie, Julien C

2017-04-01

The relationship between host organisms and their microbiota has co-evolved towards an inter-dependent network of mutualistic interactions. This interplay is particularly well studied in the gastrointestinal tract, where microbiota and host immune cells can modulate each other directly, as well as indirectly, through the production and release of chemical molecules and signals. In this review, we define the functional impact of transforming growth factor-beta (TGF-β) on this complex interplay, especially through its modulation of the activity of local regulatory T cells (Tregs), type 17 helper (Th17) cells, innate lymphoid cells (ILCs) and B cells.

Effect of the cancer specific shorter form of human 6-phosphofructo-1-kinase on the metabolism of the yeast Saccharomyces cerevisiae.

PubMed

Andrejc, Darjan; Možir, Alenka; Legiša, Matic

2017-05-08

At first glance, there appears to be a high degree of similarity between the metabolism of yeast (the Crabtree effect) and human cancer cells (the Warburg effect). At the root of both effects is accelerated metabolic flow through glycolysis which leads to overflows of ethanol and lactic acid, respectively. It has been proposed that enhanced glycolytic flow in cancer cells is triggered by the altered kinetic characteristics of the key glycolytic regulatory enzyme 6-phosphofructo-1-kinase (Pfk). Through a posttranslational modification, highly active shorter Pfk-M fragments, which are resistant to feedback inhibition, are formed after the proteolytic cleavage of the C-terminus of the native human Pfk-M. Alternatively, enhanced glycolysis is triggered by optimal growth conditions in the yeast Saccharomyces cerevisiae. To assess the deregulation of glycolysis in yeast cells, the sfPFKM gene encoding highly active human shorter Pfk-M fragments was introduced into pfk-null S. cerevisiae. No growth of the transformants with the sfPFKM gene was observed on glucose and fructose. Glucose even induced rapid deactivation of Pfk1 activities in such transformants. However, Pfk1 activities of the sfPFKM transformants were detected in maltose medium, but the growth in maltose was possible only after the addition of 10 mM of ethanol to the medium. Ethanol seemed to alleviate the severely unbalanced NADH/NADPH ratio in the sfPFKM cells. However, the transformants carrying modified Pfk-M enzymes grew faster than the transformants with the human native human Pfk-M enzyme in a narrow ecological niche with a low maltose concentration medium that was further improved by additional modifications. Interestingly, periodic extracellular accumulation of phenylacetaldehyde was detected during the growth of the strain with modified Pfk-M but not with the strain encoding the human native enzyme. Highly active cancer-specific shorter Pfk-M fragments appear to trigger several controlling mechanisms in the primary metabolism of yeast S. cerevisiae cells. These results suggest more complex metabolic regulation is present in S. cerevisiae as free living unicellular eukaryotic organisms in comparison to metazoan human cells. However, increased productivity under broader growth conditions may be achieved if more gene engineering is performed to reduce or omit several controlling mechanisms.

Expansion and redifferentiation of chondrocytes from osteoarthritic cartilage: cells for human cartilage tissue engineering.

PubMed

Hsieh-Bonassera, Nancy D; Wu, Iwen; Lin, Jonathan K; Schumacher, Barbara L; Chen, Albert C; Masuda, Koichi; Bugbee, William D; Sah, Robert L

2009-11-01

To determine if selected culture conditions enhance the expansion and redifferentiation of chondrocytes isolated from human osteoarthritic cartilage with yields appropriate for creation of constructs for treatment of joint-scale cartilage defects, damage, or osteoarthritis. Chondrocytes isolated from osteoarthritic cartilage were analyzed to determine the effects of medium supplement on cell expansion in monolayer and then cell redifferentiation in alginate beads. Expansion was assessed as cell number estimated from DNA, growth rate, and day of maximal growth. Redifferentiation was evaluated quantitatively from proteoglycan and collagen type II content, and qualitatively by histology and immunohistochemistry. Using either serum or a growth factor cocktail (TFP: transforming growth factor beta1, fibroblast growth factor 2, and platelet-derived growth factor type bb), cell growth rate in monolayer was increased to 5.5x that of corresponding conditions without TFP, and cell number increased 100-fold within 17 days. In subsequent alginate bead culture with human serum or transforming growth factor beta1 and insulin-transferrin-selenium-linoleic acid-bovine serum albumin, redifferentiation was enhanced with increased proteoglycan and collagen type II production. Effects of human serum were dose dependent, and 5% or higher induced formation of chondron-like structures with abundant proteoglycan-rich matrix. Chondrocytes from osteoarthritic cartilage can be stimulated to undergo 100-fold expansion and then redifferentiation, suggesting that they may be useful as a cell source for joint-scale cartilage tissue engineering.

Tanzania at the Turn of the Century: Background Papers and Statistics. A World Bank Country Study.

ERIC Educational Resources Information Center

World Bank, Washington, DC.

This report presents lessons from Tanzania's development experience of the past four decades, with emphasis on the period since the last report (1996), and assesses the imperatives for higher sustained growth and better livelihood for its citizens in the future. The background papers review and assess Tanzania's actual growth and poverty reduction…

Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor.

PubMed

Chesney, Jason; Clark, Jennifer; Lanceta, Lilibeth; Trent, John O; Telang, Sucheta

2015-07-20

Human tumors exhibit increased glucose uptake and metabolism as a result of high demand for ATP and anabolic substrates and this metabolotype is a negative prognostic indicator for survival. Recent studies have demonstrated that cancer cells from several tissue origins and genetic backgrounds require the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4), a regulatory enzyme that synthesizes an allosteric activator of glycolysis, fructose-2,6-bisphosphate. We report the discovery of a first-in-class PFKFB4 inhibitor, 5-(n-(8-methoxy-4-quinolyl)amino)pentyl nitrate (5MPN), using structure-based virtual computational screening. We find that 5MPN is a selective inhibitor of PFKFB4 that suppresses the glycolysis and proliferation of multiple human cancer cell lines but not non-transformed epithelial cells in vitro. Importantly, 5MPN has high oral bioavailability and per os administration of a non-toxic dose of 5MPN suppresses the glucose metabolism and growth of tumors in mice.

Do spatial patterns of urbanization and land consumption reflect different socioeconomic contexts in Europe?

PubMed

Salvati, Luca; Zambon, Ilaria; Chelli, Francesco Maria; Serra, Pere

2018-06-01

Land-use changes and urban sprawl have transformed European cities, with a direct impact on both metropolitan structures and socioeconomic functions. However, these processes tend to be relatively different across countries, being influenced by place-specific factors associated to socioeconomic, historical, political and cultural factors that influence decisions on the use of land. Considering 155 metropolitan areas in 6 European macro-regions, the present study investigates spatial patterns of land consumption profiling cities according to a large set of territorial variables, with the final objective to identify relevant socioeconomic dimensions characteristic of recent processes of urban growth. Investigating the socioeconomic background underlying land-use changes in metropolitan regions allows identification of place-specific factors improving the design of effective strategies containing land consumption in different European urban typologies. An exhaustive analysis of land-use changes at regional and local spatial scales contributes to find alternative policies for land-use efficiency and long-term environmental sustainability. Copyright © 2018 Elsevier B.V. All rights reserved.

Anomaly-corrected supersymmetry algebra and supersymmetric holographic renormalization

NASA Astrophysics Data System (ADS)

An, Ok Song

2017-12-01

We present a systematic approach to supersymmetric holographic renormalization for a generic 5D N=2 gauged supergravity theory with matter multiplets, including its fermionic sector, with all gauge fields consistently set to zero. We determine the complete set of supersymmetric local boundary counterterms, including the finite counterterms that parameterize the choice of supersymmetric renormalization scheme. This allows us to derive holographically the superconformal Ward identities of a 4D superconformal field theory on a generic background, including the Weyl and super-Weyl anomalies. Moreover, we show that these anomalies satisfy the Wess-Zumino consistency condition. The super-Weyl anomaly implies that the fermionic operators of the dual field theory, such as the supercurrent, do not transform as tensors under rigid supersymmetry on backgrounds that admit a conformal Killing spinor, and their anticommutator with the conserved supercharge contains anomalous terms. This property is explicitly checked for a toy model. Finally, using the anomalous transformation of the supercurrent, we obtain the anomaly-corrected supersymmetry algebra on curved backgrounds admitting a conformal Killing spinor.

Supervised target detection in hyperspectral images using one-class Fukunaga-Koontz Transform

NASA Astrophysics Data System (ADS)

Binol, Hamidullah; Bal, Abdullah

2016-05-01

A novel hyperspectral target detection technique based on Fukunaga-Koontz transform (FKT) is presented. FKT offers significant properties for feature selection and ordering. However, it can only be used to solve multi-pattern classification problems. Target detection may be considered as a two-class classification problem, i.e., target versus background clutter. Nevertheless, background clutter typically contains different types of materials. That's why; target detection techniques are different than classification methods by way of modeling clutter. To avoid the modeling of the background clutter, we have improved one-class FKT (OC-FKT) for target detection. The statistical properties of target training samples are used to define tunnel-like boundary of the target class. Non-target samples are then created synthetically as to be outside of the boundary. Thus, only limited target samples become adequate for training of FKT. The hyperspectral image experiments confirm that the proposed OC-FKT technique provides an effective means for target detection.

Novel symmetries in Weyl-invariant gravity with massive gauge field

NASA Astrophysics Data System (ADS)

Abhinav, K.; Shukla, A.; Panigrahi, P. K.

2016-11-01

The background field method is used to linearize the Weyl-invariant scalar-tensor gravity, coupled with a Stückelberg field. For a generic background metric, this action is found not to be invariant, under both a diffeomorphism and generalized Weyl symmetry, the latter being a combination of gauge and Weyl transformations. Interestingly, the quadratic Lagrangian, emerging from a background of Minkowski metric, respects both transformations independently. The Becchi-Rouet-Stora-Tyutin symmetry of scalar-tensor gravity coupled with a Stückelberg-like massive gauge particle, possessing a diffeomorphism and generalized Weyl symmetry, reveals that in both cases negative-norm states with unphysical degrees of freedom do exist. We then show that, by combining diffeomorphism and generalized Weyl symmetries, all the ghost states decouple, thereby removing the unphysical redundancies of the theory. During this process, the scalar field does not represent any dynamic mode, yet modifies the usual harmonic gauge condition through non-minimal coupling with gravity.

Loss of Robustness and Addiction to IGF1 during Early Keratinocyte Transformation by Human Papilloma Virus 16

PubMed Central

Geiger, Tamar; Levitzki, Alexander

2007-01-01

Infection of keratinocytes with high risk human Papilloma virus causes immortalization, and when followed by further mutations, leads to cervical cancer and other anogenital tumors. Here we monitor the progressive loss of robustness in an in vitro model of the early stages of transformation that comprises normal keratinocytes and progressive passages of HPV16 immortalized cells. As transformation progresses, the cells acquire higher proliferation rates and gain the ability to grow in soft agar. Concurrently, the cells lose robustness, becoming more sensitive to serum starvation and DNA damage by Cisplatin. Loss of robustness in the course of transformation correlates with significant reductions in the activities of the anti-apoptotic proteins PKB/Akt, Erk, Jnk and p38 both under normal growth conditions and upon stress. In parallel, loss of robustness is manifested by the shrinkage of the number of growth factors that can rescue starving cells from apoptosis, with the emergence of dependence solely on IGF1. Treatment with IGF1 activates PKB/Akt and Jnk and through them inhibits p53, rescuing the cells from starvation. We conclude that transformation in this model induces higher susceptibility of cells to stress due to reduced anti-apoptotic signaling and hyper-activation of p53 upon stress. PMID:17622350

Hypoxia induces hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

PubMed

Xiao, Zhengzheng; Liu, Qin; Zhao, Boxi; Wu, Jun; Lei, Ting

2011-12-01

The hypoxia inducible factor 1 α (HIF-1α) activity has been associated with various hemorrhagic events. The biological role of HIF-1α in the hemorrhagic transformation of pituitary adenomas remains unknown. We hypothesized that fast growing tumor cells tend to predispose themselves to sublethal hypoxia and activate the HIF-1α signaling pathway, leading to hemorrhagic transformation in pituitary adenomas. Here, we used apoplectic and non-apoplectic pituitary adenomas to determine the involvement of HIF-1α signaling in intratumoral hemorrhage. We employed HIF-1α overexpression/knockdown strategies to examine the association between HIF-1α signaling and hemorrhagic presentation in vitro and in vivo. In support of our hypothesis, compared with non-hemorrhagic pituitary adenomas, higher cellular proliferation was observed in hemorrhagic ones and it correlated with increased HIF-1α signaling. HIF-1α overexpression activated its downstream genes, vascular endothelial growth factor and the proapoptotic BNIP3, in MMQ pituitary adenoma cells and this up-regulation was attenuated by HIF-1 siRNA. In vivo studies using MMQ cell xenografts in nude mice showed that HIF-1α overexpression significantly promoted hemorrhagic transformation. Our study indicates that tumor hypoxia, following rapid tumor growth, may promote hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

‘I learned to accept every part of myself’: the transformative impact of a theatre-based sexual health and HIV prevention programme

PubMed Central

Grewe, Mary E.; Taboada, Arianna; Dennis, Alexis; Chen, Elizabeth; Stein, Kathryn; Watson, Sable; Barrington, Clare; Lightfoot, Alexandra F.

2015-01-01

Theatre-based interventions have been used in health promotion activities among young people to address HIV and sexual health. In this study, we explored the experience of undergraduate student performers participating in a theatre-based HIV prevention and sexual health education intervention for high school students in the USA. Undergraduate students enrolled in a credit-bearing course to learn about HIV and sexual health, participatory theatre and health education techniques. We analysed students’ reflective essays written throughout the semester to identify any changes and the intervention processes that promoted these changes. Students experienced five interrelated forms of transformation: (1) increased knowledge about HIV and sexual health; (2) changes in attitude and communication about sex; (3) artistic growth; (4) emotional growth; and (5) clarification of career goals and future plans. Intervention processes that contributed to these transformations included improvisation, guided writing exercises, the creation of a close-knit cohesive group, and interactions with a group of HIV-positive speakers. Theatre-based, peer-led sexual health programmes can provide a transformative experience for undergraduate student performers. The transformative effects are linked to specific activities and processes of the intervention and require examination in future research. PMID:26085813

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1986-01-01

Background information, list of materials needed, and procedures used are provided for a demonstration involving the transformation of a hydrophobic liquid to a partially hydrophobic semisolid. Safety considerations are noted. (JN)

Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

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

Carpenter, Richard L.; Jiang, Yue; Jing, Yi

2011-10-28

Highlights: Black-Right-Pointing-Pointer Chronic exposure to arsenite induces cell proliferation and transformation. Black-Right-Pointing-Pointer Arsenite-induced transformation increases ROS production and downstream signalings. Black-Right-Pointing-Pointer Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. Black-Right-Pointing-Pointer Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidencemore » suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.« less

Ringwoodite rim around olivine core in shock-induced melt veins of Antarctic chondrite : Mechanisms of transformation and Fe-Mg diffusion

NASA Astrophysics Data System (ADS)

Xie, Z.; Li, X.; Sharp, T. G.; de Carli, P. S.

2009-12-01

Introduction: High-pressure minerals, produced by shock metamorphism, are common in and around melt veins in highly shocked chondrites. The shock duration can be constrained by using transformation kinetics, such as the crystallization rate of the melt-vein matrix[1-2], or growth rate of the high-pressure minerals [3-4], or using elements diffusion rate between two minerals [5]. Using transformation kinetics to constrain shock duration de-pend on the details of the transformation mechanism. For example, growth of topotaxial ringwoodite in olivine with coherent interfaces is slower than growth of inclusions with incoherent interfaces [4-5]. Similarly, diffusion-controlled growth, where rates are determined by long-range diffusion, is generally much slower than interface-controlled growth, which is only dependent on diffusion across the interface [6-8]. The occurrences of the high-pressure mineral rims were recently reported in shock-induced melt veins in several heavily shocked (S6) chondrites, ALH78003, Peace River and GRV052049 [9-11]. Here we report EMAP and Raman results of the ringwoodite rims around olivine cores in shock veins of the Antarctic chondrites GRV 022321, and to elucidate the mechanisms of transformation and Mg-Fe diffusion of the olivine to ringwoodite. Results: GRV022321 has a network of black veins which enclose abundant host-rock fragments. The enclosed fragments have sizes ranging from 5 µm to 30 µm, with a brighter rim up to several µm wide and a dark core in reflected light and BSE image. The Raman data reveal that the rim mineral is ringwoodite signature, and the core minerals are dominated by olivine and mixed minor ringwoodite. EMAP data confirm that the ringwoodite in rim is richer in faylite (Fa) than the olivine core. The Fa values range from 50 to 10 with the outer rim having highest Fa value, and the inside darker area with a lower value. Discussion: The occurrence of the rounded shape grains with smooth edges embedded in the fine matrix in shock-induced melt veins suggest that they are enclosed host-rock fragments and that the ringwoodite in the rim was transformed by solid-state transformation from previous olivine. The variable extent of transformation is likely a result of temperature variations during shock, with the hottest outer olivine forming the ringwoodite rim. The outer hotter ringwoodite attract more Fe than inside cooler olivine, and Mg-Fe diffusion occurs in rapid transformation at high pressure and temperature over up to 10 µm distance. The sample is unique because we can test and double check different shock duration constraints in future work. References: [1] Langenhorst and Poirier (2000) EPSL 184, 37-55. [2] Xie, Z. et al. (2006) GCA, 70. 504-515. [3] Ohtani et al. (2004) EPSL 227(3-4), 505-515. [4] Xie and Sharp (2007), EPLS, 433-445. [5] Beck, et al. (2005) Nature 435, 1071-1074. [6] Kerschhofer et al. (1996) Science 274 (5284), 79-81. [7] Kerschhofer et al. (2000) PEPI 121, 59-76. [8] Sharp and DeCarli (2006) MESS II, 653-677. [9] Ohtani et al. (2006), Shock Waves, 16:45-52. [10] Miyahara et al. (2008) Proceedings. of NAS 105,8542-8547. [11] Feng et al. (2007), MAPS 42, A45.

Bearing Restoration by Grinding

DTIC Science & Technology

1976-05-21

lIng of bearings prior to installation, installing a contaminated bearing, manufacturing defects, ring growth in service, and corrosion. Nonmetallic...operation of rolling-elemsnt bearings is growth of the bearing race rings. As an example, the inner or outer races, can grow due to metallurgical...transformations or due to hoop stresses during operation This growth results in the bearing being not reusable after removal from its application. For aircraft

Transposon mutagenesis to improve the growth of recombinant Saccharomyces cerevisiae on D-xylose

Treesearch

Haiying Ni; Jose M. Laplaza; Thomas W. Jeffries

2007-01-01

Saccharomyces cerevisiae L2612 transformed with genes for xylose reductase and xylitol dehydrogenase (XYL1 and XYL2) grows well on glucose but very poorly on D-xylose. When a gene for D-xylulokinase (XYL3 or XKS1) is overexpressed, growth on glucose is unaffected, but growth on xylose is blocked. Spontaneous or chemically induced mutants of this engineered yeast that...

Charter School Innovations: A Teacher Growth Model

ERIC Educational Resources Information Center

Radoslovich, Julie; Roberts, Shelley; Plaza, Andres

2014-01-01

Committed to being a charter school with a professional learning community that empowers teachers, New Mexico's South Valley Academy (SVA) staff transformed its state evaluation process into a practitioner action research process (Anderson, Herr, & Nihlen, 2007). While teachers self-diagnose growth needs and play active roles in improving…

Diet and growth in infancy: relationship to socioeconomic background and to health and development in the Avon Longitudinal Study of Parents and Children.

PubMed

Emmett, Pauline M; Jones, Louise R

2014-08-01

To assess the relationship between diet and growth in infancy and socioeconomic background, all publications from the Avon Longitudinal Study of Parents and Children (ALSPAC) covering breastfeeding, diet and growth in infancy, and the associations of these factors with socioeconomic background and later health and developmental outcomes were reviewed. Diet was assessed by parent-completed food records and parent-completed food frequency questionnaires covering infant feeding practices. Infancy growth was monitored through routine screening and by standardized measurements. Indicators of socioeconomic background were obtained by parent-completed questionnaires. Childhood outcomes were measured by standardized procedures. Rapid early weight gain was associated with later obesity. Longer breastfeeding duration was associated with lower body fat, but not lower body mass index, and with higher IQ in mid-childhood. Breastfed infants were better at regulating their energy intake than bottle-fed infants. In bottle-fed infants, energy intake at 4 months was associated with greater weight gain up to 5 years of age. Feeding cow's milk as a main drink in infancy was associated with anemia and high salt intake. Maternal education was a strong determinant of dietary differences: low education was associated with never breastfeeding and not following feeding guidelines. ALSPAC has provided unique insights into the relationship between diet and growth in infancy and later developmental outcomes. © 2014 International Life Sciences Institute.

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

PubMed Central

2011-01-01

Background Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. PMID:21864401

Breathers and solitons on two different backgrounds in a generalized coupled Hirota system with four wave mixing

NASA Astrophysics Data System (ADS)

Xu, Han-Xiang; Yang, Zhan-Ying; Zhao, Li-Chen; Duan, Liang; Yang, Wen-Li

2018-07-01

We study breathers and solitons on different backgrounds in optical fiber system, which is governed by generalized coupled Hirota equations with four wave mixing effect. On plane wave background, a transformation between different types of solitons is discovered. Then, on periodic wave background, we find breather-like nonlinear localized waves of which formation mechanism are related to the energy conversion between two components. The energy conversion results from four wave mixing. Furthermore, we prove that this energy conversion is controlled by amplitude and period of backgrounds. Finally, solitons on periodic wave background are also exhibited. These results would enrich our knowledge of nonlinear localized waves' excitation in coupled system with four wave mixing effect.

National Research Council Dialogue to Assess Progesss on NASA's Human Exploration Systems and Mobility Capability Roadmap Development: General Background and Introduction

NASA Technical Reports Server (NTRS)

Inman, Thomas

2005-01-01

General Background and Introduction of Capability Roadmaps: Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Technology and Capability Readiness Levels. Relationships Between Roadmaps. Purpose of NRC Review. Capability Roadmap Development (Team Progress to Date).

Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

PubMed Central

Nahta, Rita; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Andrade-Vieira, Rafaela; Bay, Sarah; G. Brown, Dustin; Calaf, Gloria M.; Castellino, Robert C.; Cohen-Solal, Karine A.; Colacci, Annamaria; Cruickshanks, Nichola; Dent, Paul; Di Fiore, Riccardo; Forte, Stefano; Goldberg, Gary S.; Hamid, Roslida A.; Krishnan, Harini; Laird, Dale W.; Lasfar, Ahmed; Marignani, Paola A.; Memeo, Lorenzo; Mondello, Chiara; Naus, Christian C.; Ponce-Cusi, Richard; Raju, Jayadev; Roy, Debasish; Roy, Rabindra; P. Ryan, Elizabeth; Salem, Hosni K.; Scovassi, A. Ivana; Singh, Neetu; Vaccari, Monica; Vento, Renza; Vondráček, Jan; Wade, Mark; Woodrick, Jordan; Bisson, William H.

2015-01-01

As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks. PMID:26106139

Initial Growth of Single-Crystalline Nanowires: From 3D Nucleation to 2D Growth.

PubMed

Huang, Xh; Li, Gh; Sun, Gz; Dou, Xc; Li, L; Zheng, Lx

2010-04-17

The initial growth stage of the single-crystalline Sb and Co nanowires with preferential orientation was studied, which were synthesized in porous anodic alumina membranes by the pulsed electrodeposition technique. It was revealed that the initial growth of the nanowires is a three-dimensional nucleation process, and then gradually transforms to two-dimensional growth via progressive nucleation mechanism, which resulting in a structure transition from polycrystalline to single crystalline. The competition among the nuclei inside the nanoscaled-confined channel and the growth kinetics is responsible for the structure transition of the initial grown nanowires.

Thermal stability of the microstructure of silver films

NASA Astrophysics Data System (ADS)

Sursaeva, V. G.; Straumal, A. B.

2017-04-01

The thermal stability of freely suspended silver films 100 nm thick is studied during isothermal annealing at temperatures of 350-600°C for different times. At temperatures of 350-450°C, only grain growth is observed. Above 450°C, along with grain growth, the formation and growth of hillocks and holes take place; in this case, grain boundaries are essential in the processes. A continuous film transforms into a cellular one. At 500°C, the growth processes of both grains and holes have the same incubation period, during which no grain growth, hole formation, and hole growth take place.

Librarians Lead the Growth of Information Literacy and Global Digital Citizens

ERIC Educational Resources Information Center

Crockett, Lee Watanabe

2018-01-01

Librarians are leaders in growing global digital citizens. The libraries of the future are more than just housing centers for books and media. They are invigorating meeting places and communities where truly meaningful learning and discovery take place. As technology has transformed reading and learning, it has also transformed the vision of the…

Stress induction in the bacteria Shewanella oneidensis and Deinococcus radiodurans in response to below-background ionizing radiation.

PubMed

Castillo, Hugo; Schoderbek, Donald; Dulal, Santosh; Escobar, Gabriela; Wood, Jeffrey; Nelson, Roger; Smith, Geoffrey

2015-01-01

The 'Linear no-threshold' (LNT) model predicts that any amount of radiation increases the risk of organisms to accumulate negative effects. Several studies at below background radiation levels (4.5-11.4 nGy h(-1)) show decreased growth rates and an increased susceptibility to oxidative stress. The purpose of our study is to obtain molecular evidence of a stress response in Shewanella oneidensis and Deinococcus radiodurans grown at a gamma dose rate of 0.16 nGy h(-1), about 400 times less than normal background radiation. Bacteria cultures were grown at a dose rate of 0.16 or 71.3 nGy h(-1) gamma irradiation. Total RNA was extracted from samples at early-exponential and stationary phases for the rt-PCR relative quantification (radiation-deprived treatment/background radiation control) of the stress-related genes katB (catalase), recA (recombinase), oxyR (oxidative stress transcriptional regulator), lexA (SOS regulon transcriptional repressor), dnaK (heat shock protein 70) and SOA0154 (putative heavy metal efflux pump). Deprivation of normal levels of radiation caused a reduction in growth of both bacterial species, accompanied by the upregulation of katB, recA, SOA0154 genes in S. oneidensis and the upregulation of dnaK in D. radiodurans. When cells were returned to background radiation levels, growth rates recovered and the stress response dissipated. Our results indicate that below-background levels of radiation inhibited growth and elicited a stress response in two species of bacteria, contrary to the LNT model prediction.

Stability of an ion-ring distribution in a multi-ion component plasma

NASA Astrophysics Data System (ADS)

Mithaiwala, Manish; Rudakov, Leonid; Ganguli, Gurudas

2010-04-01

The stability of a cold ion-ring velocity distribution in a thermal plasma is analyzed. In particular, the effect of plasma temperature and density on the instability is considered. A high ring density (compared to the background plasma) neutralizes the stabilizing effect of the warm background plasma and the ring is unstable to the generation of waves below the lower-hybrid frequency even for a very high temperature plasma. For ring densities lower than the background plasma density, there is a slow instability where the growth rate is less than the background-ion cyclotron frequency and, consequently, the background-ion response is magnetized. This is in addition to the widely discussed fast instability where the wave growth rate exceeds the background-ion cyclotron frequency and hence the background ions are effectively unmagnetized. Thus, even a low density ring is unstable to waves around the lower-hybrid frequency range for any ring speed. This implies that effectively there is no velocity threshold for a sufficiently cold ring.

Transformation and precipitation in vanadium treated steels

NASA Astrophysics Data System (ADS)

Vassiliou, Andreas D.

A series of carbon manganese steels containing varying amounts of carbon, vanadium and nitrogen was investigated in relation to the solubility of VC and VN in austenite, the grain coarsening characteristics of austenite, the tempering of martensite and other structures, the transformation during continuous cooling, the effect of vanadium addition and increasing nitrogen content on the thermo-mechanical processing of austenite, and the transformation of various morphologies of austenite to ferrite.The sites for preferential nucleation and growth of ferrite were identified and the effect of ferrite grain size inhomogeneity was investigated with a view to minimising it.The C/N ratio in the V(CN) precipitates was largely controlled by C/N ratio in the steel and it was also influenced by the austenitising treatment. As expected, the solubility of VN was less than that of VC.A systematic investigation of austenitising time and temperature on the grain coarsening characteristics was carried out showing the effects of vanadium, carbon and nitrogen. It was tentatively suggested that C-C and N-N clustering in the vanadium free steels controlled the grain growth whereas in the presence of vanadium, it was shown that VN and VC pinned the austenite grain boundaries and restricted grain growth. However coarsening or solution of VC and VN allowed the grain bondaries to migrate and grain coarsening occurred. The grain coarsening temperature was controlled predominantly by VN, whilst the VC dissolved frequently below the grain coarsening temperature.In the as quenched martensite, increasing nitrogen progressively increased the as quenched hardness, and the hardness also greatly increased with increasing carbon and vanadium added together. Examining the precipitation strengthening in tempered martensite showed that in the absence of vanadium, martensite softened progressively with increasing temperature and time. Vanadium additions increased the hardness level during low temperature tempering and at higher tempering temperature introduced secondary hardening. The intensity of secondary hardening increased with increasing vanadium, whereas austenitising temperature had little or no effect. The softening after the secondary hardening was faster after austenitising at the higher temperature and when recrystallisation occurred at the highest tempering temperatures, the hardness was lower due to coarse recrystallised ferrite.Isothermal transformation studies showed that vanadium additions raised the Ar3 temperature and accelerated ferrite nucleation, whilst the growth of ferrite was delayed due to the formation of V(CN) interphase and general precipitation pinning, of the transformation front. Increasing nitrogen content in the V-steel increased the incubation period for ferrite nucleation and increasingly reduced the ferrite growth by increasing V(CN) precipitation pinning of the transformation front.Transformation during continuous cooling was examined in relation to the effect of vanadium, carbon and nitrogen together with the effect of austenitising temperature. Increasing austenitising temperature increased the austenite grain size, and it then became apparent that increasing vanadium, carbon and nitrogen increased the hardenability and raised the hardness level of the jominy curve for the non-martensitic products. (Abstract shortened by ProQuest.).

Angiotensin II Receptor Antagonism Reduces Transforming Growth Factor Beta and Smad Signaling in Thoracic Aortic Aneurysm

PubMed Central

Nataatmadja, Maria; West, Jennifer; Prabowo, Sulistiana; West, Malcolm

2013-01-01

ABSTRACT Background The expression of transforming growth factor beta (TGF-β) and Smad3 regulates extracellular matrix homeostasis and inflammation in aortic aneurysms. The expression of Smad3 depends on signaling by angiotensin II (AngII) receptor pathways through TGF-β receptor–dependent and –independent pathways. Methods To determine the expression of AngII type 1 (AT1R) and type 2 receptors (AT2R), TGF-β, and Smad3 in thoracic aortic aneurysms, we performed immunohistochemistry testing on tissue and cultured cells derived from subjects with Marfan syndrome (MFS) and bicuspid aortic valve (BAV) malformation and from normal aortas of subjects who were organ donors. Results MFS and BAV aneurysm tissue showed enhanced accumulation of TGF-β and Smad3 in vascular smooth muscle cells (VSMCs) and in inflammatory cells in the subintimal layer and tunica media. The normal aortic wall exhibited minimal TGF-β and Smad3 staining. Cultured VSMCs from MFS and BAV samples showed nuclear Smad3 and strong cytoplasmic TGF-β expression in the cytoplasmic vesicles. In control cells, Smad3 was located mainly in the cytoplasm, and weak cytoplasmic TGF-β was distributed with a pattern similar to that of the aneurysm-derived cells. Compared to normal aorta cells, AT1R and AT2R expression was increased in both aneurysm types. Treatment of cultured VSMCs with the AT1R antagonist losartan caused both reduced TGF-β vesicle localization and nuclear expression of Smad3. Conclusions Increased TGF-β and Smad3 expression in aneurysm tissue and cultured VSMCs is consistent with aberrant TGF-β expression and the activation of Smad3 signaling. Losartan-mediated reduction in TGF-β expression and the cytoplasmic localization of Smad3 support a role for AT1R antagonism in the inhibition of aneurysm progression. PMID:23532685

Multidrug resistance protein MdtM adds to the repertoire of antiporters involved in alkaline pH homeostasis in Escherichia coli

PubMed Central

2013-01-01

Background In neutralophilic bacteria, monovalent metal cation/H+ antiporters play a key role in pH homeostasis. In Escherichia coli, only four antiporters (NhaA, NhaB, MdfA and ChaA) are identified to function in maintenance of a stable cytoplasmic pH under conditions of alkaline stress. We hypothesised that the multidrug resistance protein MdtM, a recently characterised homologue of MdfA and a member of the major facilitator superfamily, also functions in alkaline pH homeostasis. Results Assays that compared the growth of an E. coli ΔmdtM deletion mutant transformed with a plasmid encoding wild-type MdtM or the dysfunctional MdtM D22A mutant at different external alkaline pH values (ranging from pH 8.5 to 10) revealed a potential contribution by MdtM to alkaline pH tolerance, but only when millimolar concentrations of sodium or potassium was present in the growth medium. Fluorescence-based activity assays using inverted vesicles generated from transformants of antiporter-deficient (ΔnhaA, ΔnhaB, ΔchaA) E. coli TO114 cells defined MdtM as a low-affinity antiporter that catalysed electrogenic exchange of Na+, K+, Rb+ or Li+ for H+. The K+/H+ antiport reaction had a pH optimum at 9.0, whereas the Na+/H+ exchange activity was optimum at pH 9.25. Measurement of internal cellular pH confirmed MdtM as contributing to maintenance of a stable cytoplasmic pH, acid relative to the external pH, under conditions of alkaline stress. Conclusions Taken together, the results support a role for MdtM in alkaline pH tolerance. MdtM can therefore be added to the currently limited list of antiporters known to function in pH homeostasis in the model organism E. coli. PMID:23701827

LLNL compiled first pages ordered by ascending B&R code

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

Campbell, G; Kumar, M; Tobin, J

We aim to develop a fundamental understanding of materials dynamics (from {micro}s to ns) in systems where the required combination of spatial and temporal resolution can only be reached by the dynamic transmission electron microscope (DTEM). In this regime, the DTEM is capable of studying complex transient phenomena with several orders of magnitude time resolution advantage over any existing in-situ TEM. Using the unique in situ capabilities and the nanosecond time resolution of the DTEM, we seek to study complex transient phenomena associated with rapid processes in materials, such as active sites on nanoscale catalysts and the atomic level mechanismsmore » and microstructural features for nucleation and growth associated with phase transformations in materials, specifically in martensite formation and crystallization reactions from the amorphous phase. We also will study the transient phase evolution in rapid solid-state reactions, such as those occurring in reactive multilayer foils (RMLF). Program Impact: The LLNL DTEM possesses unique capabilities for capturing time resolved images and diffraction patterns of rapidly evolving materials microstructure under strongly driven conditions. No other instrument in the world can capture images with <10 nm spatial resolution of interesting irreversible materials processes such as phase transformations, plasticity, or morphology changes with 15 ns time resolution. The development of this innovative capability requires the continuing collaboration of laser scientists, electron microscopists, and materials scientists experienced in time resolved observations of materials that exist with particularly relevant backgrounds at LLNL. The research team has made observations of materials processes that are possible by no other method, such as the rapid crystallization of thin film NiTi that identified a change in mechanism at high heating rates as compared to isothermal anneals through changes in nucleation and growth rates of the crystalline phase. The project is designed to reveal these fundamental processes and mechanisms in rapid microstructure evolution that form the foundation of understanding that is an integral part of the DOE-BES mission.« less

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

PubMed Central

KURTZBERG, JOANNE; BUNTZ, SUSAN; GENTRY, TRACY; NOELDNER, PAMELA; OZAMIZ, APRIL; RUSCHE, BENJAMIN; STORMS, ROBERT W.; WOLLISH, AMY; WENGER, DAVID A.; BALBER, ANDREW E.

2016-01-01

Background aims Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. Methods DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays. Results DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-β, IL-1β, interferon-γ and TNF-α in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-β and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC. Conclusions DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases. PMID:25770677

Experimental Study on Effects of Adipose-Derived Stem Cell–Seeded Silk Fibroin Chitosan Film on Wound Healing of a Diabetic Rat Model

PubMed Central

Wu, Yan-Yun; Jiao, Yan-Peng; Xiao, Li-Ling; Li, Min-Min; Liu, Hong-Wei; Li, Sheng-Hong; Liao, Xuan; Chen, Yong-Tian; Li, Jiang-Xuan; Zhang, Yang

2018-01-01

Background Wound healing is a complex process that relies on growth factors and stimulation of angiogenesis. Tissue engineering materials composed of adipose-derived stem cells (ADSCs) and silk fibroin (SF)/chitosan (CS) may be able to solve this problem. The aim of this study was to investigate the wound-healing potential of ADSC-seeded SF/CS in streptozotocin-induced diabetic rats. Materials and Methods Thirty-six male Sprague-Dawley rats were purchased and randomly assigned into 3 groups: a control group (no graft), a group treated with SF/CS film graft, and a group treated with ADSC-seeded SF/CS graft. The number of animals in each group was 12. Diabetes was induced by an intraperitoneal injection of streptozotocin. A cutaneous wound was incised at the dorsal region of all the experimental animals. The ADSCs were labeled with CM-Dil fluorescent staining. Wound healing was assessed for all animal groups by observing the rate of wound closure and hematoxylin and eosin staining. The expression of epidermal growth factor, transforming growth factor-β, and vascular endothelial growth factor at the wound sites was studied by enzyme-linked immunosorbent assay to evaluate the effect of growth factors secreted by ADSCs. The differentiation of ADSCs was analyzed by immunofluorescence staining. Results The ADSC-seeded SF/CS film treatment significantly increased the rates of wound closure in treated animals, and hence wound healing was drastically enhanced for ADSC-SF/CS treatment groups compared with control groups and SF/CS film treatment group. Histological observations showed the condition of wound healing. Enzyme-linked immunosorbent assay and immunofluorescence staining observations showed the secretion and differentiation of ADSCs, respectively. Conclusions Our analyses clearly suggested that it is feasible and effective to enhance wound healing in a diabetic rat model with ADSC-seeded SF/CS film. PMID:29443833

Coloured computational imaging with single-pixel detectors based on a 2D discrete cosine transform

NASA Astrophysics Data System (ADS)

Liu, Bao-Lei; Yang, Zhao-Hua; Liu, Xia; Wu, Ling-An

2017-02-01

We propose and demonstrate a computational imaging technique that uses structured illumination based on a two-dimensional discrete cosine transform to perform imaging with a single-pixel detector. A scene is illuminated by a projector with two sets of orthogonal patterns, then by applying an inverse cosine transform to the spectra obtained from the single-pixel detector a full-colour image is retrieved. This technique can retrieve an image from sub-Nyquist measurements, and the background noise is easily cancelled to give excellent image quality. Moreover, the experimental set-up is very simple.

Passive Standoff Detection of Chemical Vapors by Differential FTIR Radiometry

DTIC Science & Technology

2001-01-01

8217 utilisation d’un interferometre infrarouge a transformation de Fourier (FTIR) a double entree optimise pour la soustraction optique. En vue de sa mise...Valcartier (DREV) is currently developing a passive Fourier Transform InfraRed (FTIR) technique for the standoff detection and identification of...chemical vapors. A well-known difficulty associated with this technique is that the recorded signal also contains a large amount of unwanted background

Survey of digital filtering

NASA Technical Reports Server (NTRS)

Nagle, H. T., Jr.

1972-01-01

A three part survey is made of the state-of-the-art in digital filtering. Part one presents background material including sampled data transformations and the discrete Fourier transform. Part two, digital filter theory, gives an in-depth coverage of filter categories, transfer function synthesis, quantization and other nonlinear errors, filter structures and computer aided design. Part three presents hardware mechanization techniques. Implementations by general purpose, mini-, and special-purpose computers are presented.

Evolutionary transgenomics: prospects and challenges.

PubMed

Correa, Raul; Baum, David A

2015-01-01

Many advances in our understanding of the genetic basis of species differences have arisen from transformation experiments, which allow us to study the effect of genes from one species (the donor) when placed in the genetic background of another species (the recipient). Such interspecies transformation experiments are usually focused on candidate genes - genes that, based on work in model systems, are suspected to be responsible for certain phenotypic differences between the donor and recipient species. We suggest that the high efficiency of transformation in a few plant species, most notably Arabidopsis thaliana, combined with the small size of typical plant genes and their cis-regulatory regions allow implementation of a screening strategy that does not depend upon a priori candidate gene identification. This approach, transgenomics, entails moving many large genomic inserts of a donor species into the wild type background of a recipient species and then screening for dominant phenotypic effects. As a proof of concept, we recently conducted a transgenomic screen that analyzed more than 1100 random, large genomic inserts of the Alabama gladecress Leavenworthia alabamica for dominant phenotypic effects in the A. thaliana background. This screen identified one insert that shortens fruit and decreases A. thaliana fertility. In this paper we discuss the principles of transgenomic screens and suggest methods to help minimize the frequencies of false positive and false negative results. We argue that, because transgenomics avoids committing in advance to candidate genes it has the potential to help us identify truly novel genes or cryptic functions of known genes. Given the valuable knowledge that is likely to be gained, we believe the time is ripe for the plant evolutionary community to invest in transgenomic screens, at least in the mustard family Brassicaceae where many species are amenable to efficient transformation.

STEM Career Changers' Transformation into Science Teachers

NASA Astrophysics Data System (ADS)

Snyder, Catherine; Oliveira, Alandeom W.; Paska, Lawrence M.

2013-06-01

This study examines the transformation (professional growth) of career-changing women scientists who decided to become teachers. Drawing upon Mezirow's Transformative Learning Theory, we tracked their transformation for 3 years. Our findings revealed multiple identities, disorientation, a perceived sense of meaninglessness, loss and eventual regain in confidence, gain in pedagogical knowledge and skill, and changed perceptions of the social roles of science teachers and scientists. Driven by personal choice or need (financial, intellectual), such transformations were achieved through active pursuit of meaning in one's work, critical assessment of assumptions, planning, and trying on the unfamiliar role of a science teacher. It is argued that such transition entails complex changes in thinking about science teaching and identifying oneself as a science teacher.

Altered receptor trafficking in Huntingtin Interacting Protein 1-transformed cells.

PubMed

Rao, Dinesh S; Bradley, Sarah V; Kumar, Priti D; Hyun, Teresa S; Saint-Dic, Djenann; Oravecz-Wilson, Katherine; Kleer, Celina G; Ross, Theodora S

2003-05-01

The clathrin-associated protein, Huntingtin Interacting Protein 1 (HIP1), is overexpressed in multiple human epithelial tumors. Here, we report that HIP1 is a novel oncoprotein that transforms cells. HIP1-transformed cells, in contrast to RasV12-transformed cells, have dysregulation of multiple receptors involved in clathrin trafficking. Examples include upregulation of the epidermal growth factor receptor (EGFR) and the transferrin receptor. Furthermore, accumulation of transferrin and EGF in the HIP1-transformed cells was increased, and breast tumors that had EGFR expressed also had HIP1 upregulated. Thus, HIP1 overexpression promotes tumor formation and is associated with a general alteration in receptor trafficking. HIP1 is the first endocytic protein to be directly implicated in tumor formation.

Motivating and Evaluating Growth in Ballet Technique

ERIC Educational Resources Information Center

White, Julie Hammond

2012-01-01

In teaching young dancers ballet, the utilization of effective assessments in partnership with supportive and creative teaching strategies can transform not only the learning experience, but the dancer as well. In this article, the author shares a "growth grade rubric" that specifically addresses three areas in ballet training: (1) skills and…

ROLE OF TRANSFORMING GROWTH FACTOR- AND THE EPIDERMAL GROWTH FACTOR RECEPTOR IN EMBRYONIC RAT TESTIS DEVELOPMENT. (R827405)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Initial growth of vertically aligned carbon nanofibers

NASA Astrophysics Data System (ADS)

Cui, Hongtao; Yang, Xiaojing; Simpson, Michael L.; Lowndes, Douglas H.; Varela, Maria

2004-05-01

Samples of vertically aligned carbon nanofibers (VACNFs) were viewed transverse to the growth direction and studied using both scanning and transmission electron microscopy. The VACNFs are composed of graphite layers nearly parallel to the substrate at their bottom end, gradually formed graphite "cups" in the main body, and a catalyst particle on the tip. The formation of such structure is due to the corresponding transformation of the shape of the catalyst particle during initial VACNF growth. A model for their initial growth is proposed.

Quantification and Discrimination of in Vitro Regeneration Swertia nervosa at Different Growth Periods using the UPLC/UV Coupled with Chemometric Method.

PubMed

Li, Jie; Zhang, Ji; Zuo, Zhitian; Huang, Hengyu; Wang, Yuanzhong

2018-05-09

Background : Swertia nervosa (Wall. ex G. Don) C. B. Clarke, a promising traditional herbal medicine for the treatment of liver disorders, is endangered due to its extensive collection and unsustainable harvesting practices. Objective : The aim of this study is to discuss the diversity of metabolites (loganic acid, sweroside, swertiamarin, and gentiopicroside) at different growth stages and organs of Swertia nervosa using the ultra-high-performance LC (UPLC)/UV coupled with chemometric method. Methods : UPLC data, UV data, and data fusion were treated separately to find more useful information by partial least-squares discriminant analysis (PLS-DA). Hierarchical cluster analysis (HCA), an unsupervised method, was then employed for validating the results from PLS-DA. Results : Three strategies displayed different chemical information associated with the sample discrimination. UV information mainly contributed to the classification of different organs; UPLC information was prominently responsible for both organs and growth periods; the data fusion did not perform with apparent superiority compared with single data analysis, although it provided useful information to differentiate leaves that could not be recognized by UPLC. The quantification result showed that the content of swertiamarin was the highest compared with the other three metabolites, especially in leaves at the rooted stage (19.57 ± 5.34 mg/g). Therefore, we speculated that interactive transformations occurred among these four metabolites, facilitated by root formation. Conclusions : This work will contribute to exploitation of bioactive compounds of S. nervosa , as well as its large-scale propagation. Highlights : The roots formation may influence the distribution and accumulation of metabolites.

Allometries of maximum growth rate versus body mass at maximum growth indicate that non-avian dinosaurs had growth rates typical of fast growing ectothermic sauropsids.

PubMed

Werner, Jan; Griebeler, Eva Maria

2014-01-01

We tested if growth rates of recent taxa are unequivocally separated between endotherms and ectotherms, and compared these to dinosaurian growth rates. We therefore performed linear regression analyses on the log-transformed maximum growth rate against log-transformed body mass at maximum growth for extant altricial birds, precocial birds, eutherians, marsupials, reptiles, fishes and dinosaurs. Regression models of precocial birds (and fishes) strongly differed from Case's study (1978), which is often used to compare dinosaurian growth rates to those of extant vertebrates. For all taxonomic groups, the slope of 0.75 expected from the Metabolic Theory of Ecology was statistically supported. To compare growth rates between taxonomic groups we therefore used regressions with this fixed slope and group-specific intercepts. On average, maximum growth rates of ectotherms were about 10 (reptiles) to 20 (fishes) times (in comparison to mammals) or even 45 (reptiles) to 100 (fishes) times (in comparison to birds) lower than in endotherms. While on average all taxa were clearly separated from each other, individual growth rates overlapped between several taxa and even between endotherms and ectotherms. Dinosaurs had growth rates intermediate between similar sized/scaled-up reptiles and mammals, but a much lower rate than scaled-up birds. All dinosaurian growth rates were within the range of extant reptiles and mammals, and were lower than those of birds. Under the assumption that growth rate and metabolic rate are indeed linked, our results suggest two alternative interpretations. Compared to other sauropsids, the growth rates of studied dinosaurs clearly indicate that they had an ectothermic rather than an endothermic metabolic rate. Compared to other vertebrate growth rates, the overall high variability in growth rates of extant groups and the high overlap between individual growth rates of endothermic and ectothermic extant species make it impossible to rule out either of the two thermoregulation strategies for studied dinosaurs.

Allometries of Maximum Growth Rate versus Body Mass at Maximum Growth Indicate That Non-Avian Dinosaurs Had Growth Rates Typical of Fast Growing Ectothermic Sauropsids

PubMed Central

Werner, Jan; Griebeler, Eva Maria

2014-01-01

We tested if growth rates of recent taxa are unequivocally separated between endotherms and ectotherms, and compared these to dinosaurian growth rates. We therefore performed linear regression analyses on the log-transformed maximum growth rate against log-transformed body mass at maximum growth for extant altricial birds, precocial birds, eutherians, marsupials, reptiles, fishes and dinosaurs. Regression models of precocial birds (and fishes) strongly differed from Case’s study (1978), which is often used to compare dinosaurian growth rates to those of extant vertebrates. For all taxonomic groups, the slope of 0.75 expected from the Metabolic Theory of Ecology was statistically supported. To compare growth rates between taxonomic groups we therefore used regressions with this fixed slope and group-specific intercepts. On average, maximum growth rates of ectotherms were about 10 (reptiles) to 20 (fishes) times (in comparison to mammals) or even 45 (reptiles) to 100 (fishes) times (in comparison to birds) lower than in endotherms. While on average all taxa were clearly separated from each other, individual growth rates overlapped between several taxa and even between endotherms and ectotherms. Dinosaurs had growth rates intermediate between similar sized/scaled-up reptiles and mammals, but a much lower rate than scaled-up birds. All dinosaurian growth rates were within the range of extant reptiles and mammals, and were lower than those of birds. Under the assumption that growth rate and metabolic rate are indeed linked, our results suggest two alternative interpretations. Compared to other sauropsids, the growth rates of studied dinosaurs clearly indicate that they had an ectothermic rather than an endothermic metabolic rate. Compared to other vertebrate growth rates, the overall high variability in growth rates of extant groups and the high overlap between individual growth rates of endothermic and ectothermic extant species make it impossible to rule out either of the two thermoregulation strategies for studied dinosaurs. PMID:24586409

Phase competition in the growth of SrCoOx/LaAlO3 thin films

NASA Astrophysics Data System (ADS)

Zhang, Jie; Meng, Dechao; Huang, Haoliang; Cai, Honglei; Huang, Qiuping; Wang, Jianlin; Yang, Yuanjun; Zhai, Xiaofang; Fu, Zhengping; Lu, Yalin

2018-02-01

The reversible topotactic phase transformation between brownmillerite SrCoO2.5 to perovskite SrCoO3 has attracted more and more attention for potential applications as solid oxide fuels and electrolysis cells. However, the relatively easy transformation result from small thermal stable energy barriers between the two phases leads to unstable the structures. In the paper, amounts of SrCoO3-δ films have been prepared by pulsed laser deposition at optimized growth conditions with the temperature range of 590-720°C. The X-ray diffraction (XRD) results demonstrated that a phase competition emerged around 650°C. The Gibbs free energies of two phases at high temperature revealed the difference of stability of these two phases under different growth temperature. The optical spectroscopies and X-ray photoelectron spectroscopies were used to verify the electronic structure and chemical state differences between the two phases with distinct crystal structures.

Smolt physiology and endocrinology: Chapter 5

USGS Publications Warehouse

McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

2012-01-01

The parr-smolt transformation of anadromous salmonids is a suite of behavioral, morphological, and physiological changes that are preparatory for downstream migration and seawater entry. The timing of smolt development varies among species, occurring soon after hatching in pink and chum salmon and after one to several years in Atlantic salmon. In many species the transformation is size dependent and occurs in spring, mediated through photoperiod and temperature cues. Smolt development is stimulated by several hormones including growth hormone, insulin-like growth factor-1, cortisol, and thyroid hormones, whereas prolactin is generally inhibitory. Increased salinity tolerance is one of the most important and tractable changes, and is caused by alteration in the function of the major osmoregulatory organs, the gill, gut, and kidney. Increased abundance of specific ion transporters (Na+/K+-ATPase, Na+/K+/Cl− cotransporter and apical Cl− channel) in gill ionocytes results in increased salt secretory capacity, increased growth and swimming performance in seawater, and higher marine survival.

Impact of accelerated plant growth on seed variety development

NASA Astrophysics Data System (ADS)

Christophersen, Eric

1998-01-01

The commercial lives of agricultural seed products have steadily declined in recent years. The introduction of genetically engineered crop seeds in 1966 has accentuated that trend. Widespread grower demand for genetically engineered seed requires competitive response by industry followers in order to avert market share losses to the industry leaders. Limitations on plant transformation technology, regulatory requirements and patent impediments require companies to rapidly convert transformed lines into elite commercial products. Massive multigenerational backcrossing efforts are required to distribute genetically engineered traits into a broad product mix. Significant incidents of expression failures, or ``gene silencing,'' have occurred unexpectedly, requiring product substitution strategies. First-to-market strategies, competitive response, broad germplasm conversion and rescue of product failures all share the element of urgency. Technologies which reliably accelerate product development rates can expect favorable reception by commercial seed developers. A growth chamber which dramatically accelerates the rate of plant growth is described.

Cdk5 is required for the neuroprotective effect of transforming growth factor-β1 against cerebral ischemia-reperfusion

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

Zhao, Wenhui; Yan, Jing; Sino-UK Joint Laboratory of Brain Functions and Injury, Science and Technology Department of Henan Province

Transforming Growth Factor β1 (TGF-β1), a well-known neuroprotective and neurotrophic factor in the central nervous system, is also involved in the repair process responses after ischemia-reperfusion injury. Herein, we found that TGF-β1 enhanced Cdk5 expression while decreased Tunel-positive cells compared with the ischemia group, and roscovitine(Cdk5 inhibitor) treatment could blunt these effects. In vitro study, TGF-β1 facilitated Cdk5/p35 complex, the proliferation, neurite growth and differentiation of PC12 cells, effects of which could be blunted by roscovitine and Cdk5 silencing. Moreover, ERK1/2 inhibitor SCH772984 abrogated the effects of TGF- β1 on Cdk5 and Bax levels. Taken together, we conclude that Cdk5 contributes tomore » the neuroprotective function of TGF- β1 via ERK1/2 signaling.« less

Spatially covariant theories of gravity: disformal transformation, cosmological perturbations and the Einstein frame

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

Fujita, Tomohiro; Gao, Xian; Yokoyama, Jun'ichi, E-mail: tomofuji@stanford.edu, E-mail: gao@th.phys.titech.ac.jp, E-mail: yokoyama@resceu.s.u-tokyo.ac.jp

We investigate the cosmological background evolution and perturbations in a general class of spatially covariant theories of gravity, which propagates two tensor modes and one scalar mode. We show that the structure of the theory is preserved under the disformal transformation. We also evaluate the primordial spectra for both the gravitational waves and the curvature perturbation, which are invariant under the disformal transformation. Due to the existence of higher spatial derivatives, the quadratic Lagrangian for the tensor modes itself cannot be transformed to the form in the Einstein frame. Nevertheless, there exists a one-parameter family of frames in which themore » spectrum of the gravitational waves takes the standard form in the Einstein frame.« less

Role of transforming growth factor-β2 in, and apossible transforming growth factor-β2 gene polymorphism as a marker of, renal dysfunction in essential hypertension: A study in Turkish patients

PubMed Central

Bicik, Zerrin; Gönen, Sevim; Bahçebasi, Talat; Reis, Kadriye; Arinsoy, Turgay; Sindel, Sükrü

2005-01-01

Background: Many studies have shown that transforming growth factor(TGF)-β has a major role in renal scarring in many renal diseases and hypertension. Objectives: The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-β2 (a more sensitive isoform for glomeruli than TGF-β1), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-β2 levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-β2 gene polymorphism and essential hypertension. Methods: This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged ≥18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] >120/>80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage lI hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-β2 and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-β2 primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-β2 kit. Results: Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-β2 levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-β2 level did not change significantly. Three patients, all of whom were found to have TGF-β2 gene mutations, had increased urinary TGF-β2 levels despite good blood pressure control. Conclusions: The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-β2 levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-β2 locus should be kept in mind. PMID:24672129

Flooding event impacts soil pH, Ca, and P concentration distribution in a cattle backgrounding site on karst topography.

USDA-ARS?s Scientific Manuscript database

Beef cattle backgrounding in US, function as an intermediate between cow-calf enterprises and feedlot finishing. Beef cattle backgrounding receives weaned calves of different growth stages from cow-calf operations and prepare them ready for feed lot finishing. Many beef cattle backgrounding operati...

Discrimination of malignant lymphomas and leukemia using Radon transform based-higher order spectra

NASA Astrophysics Data System (ADS)

Luo, Yi; Celenk, Mehmet; Bejai, Prashanth

2006-03-01

A new algorithm that can be used to automatically recognize and classify malignant lymphomas and leukemia is proposed in this paper. The algorithm utilizes the morphological watersheds to obtain boundaries of cells from cell images and isolate them from the surrounding background. The areas of cells are extracted from cell images after background subtraction. The Radon transform and higher-order spectra (HOS) analysis are utilized as an image processing tool to generate class feature vectors of different type cells and to extract testing cells' feature vectors. The testing cells' feature vectors are then compared with the known class feature vectors for a possible match by computing the Euclidean distances. The cell in question is classified as belonging to one of the existing cell classes in the least Euclidean distance sense.

Discrete rational and breather solution in the spatial discrete complex modified Korteweg-de Vries equation and continuous counterparts.

PubMed

Zhao, Hai-Qiong; Yu, Guo-Fu

2017-04-01

In this paper, a spatial discrete complex modified Korteweg-de Vries equation is investigated. The Lax pair, conservation laws, Darboux transformations, and breather and rational wave solutions to the semi-discrete system are presented. The distinguished feature of the model is that the discrete rational solution can possess new W-shape rational periodic-solitary waves that were not reported before. In addition, the first-order rogue waves reach peak amplitudes which are at least three times of the background amplitude, whereas their continuous counterparts are exactly three times the constant background. Finally, the integrability of the discrete system, including Lax pair, conservation laws, Darboux transformations, and explicit solutions, yields the counterparts of the continuous system in the continuum limit.

The topological structure of supergravity: an application to supersymmetric localization

NASA Astrophysics Data System (ADS)

Imbimbo, Camillo; Rosa, Dario

2018-05-01

The BRST algebra of supergravity is characterized by two different bilinears of the commuting supersymmetry ghosts: a vector γ μ and a scalar ϕ, the latter valued in the Yang-Mills Lie algebra. We observe that under BRST transformations γ and ϕ transform as the superghosts of, respectively, topological gravity and topological Yang-Mills coupled to topological gravity. This topological structure sitting inside any supergravity leads to universal equivariant cohomological equations for the curvatures 2-forms which hold on supersymmetric bosonic backgrounds. Additional equivariant cohomological equations can be derived for supersymmetric backgrounds of supergravities for which certain gauge invariant scalar bilinears of the commuting ghosts exist. Among those, N = (2 , 2) in d = 2, which we discuss in detail in this paper, and N = 2 in d = 4.

Agrobacterium tumefaciens-mediated transformation of Campanula carpatica: factors affecting transformation and regeneration of transgenic shoots.

PubMed

Sriskandarajah, Sridevy; Frello, Stefan; Jørgensen, Kirsten; Serek, Margrethe

2004-08-01

An efficient transformation system for Campanula carpatica was developed using Agrobacterium tumefaciens strains LBA4404 (harbouring the plasmid pBI121), and AGL0 (harbouring the plasmid pBEO210). This is the first report on the transformation of C. carpatica. Various factors affecting the transformation efficiency and subsequent regeneration were identified. The age of seedlings from which the explants for transformation studies were taken, and the growth conditions under which the seedlings were grown had a significant influence on the production of transformed shoots. Hypocotyls taken from 12-day-old seedlings grown in the dark were the most productive, with up to 25% of hypocotyls producing transformed shoots. Explants taken from 5-week-old seedlings produced only transformed callus. The medium used for co-cultivation and incubation also had a significant influence on transformation frequency and shoot regeneration. The cultivar "Blue Uniform" was more responsive than "White Uniform". Both bacterial strains and plasmids were equally effective in producing transformed tissue. Transformed shoots were selected on kanamycin medium, and the presence of the uidA and nptII genes in those selected shoots was confirmed by beta-glucuronidase and ELISA analyses, respectively.

Bioactive molecules in milk and their role in health and disease: the role of transforming growth factor-beta.

PubMed

Donnet-Hughes, A; Duc, N; Serrant, P; Vidal, K; Schiffrin, E J

2000-02-01

Human breast milk is rich in nutrients, hormones, growth factors and immunoactive molecules, which influence the growth, development and immune status of the newborn infant. Although several of these factors are also present in bovine milk, the greater susceptibility of the formula-fed infant to infection and disease and the development of allergy is often attributed to the reduced level of protective factors in milk formulas. Nevertheless, modifying manufacturing processes may preserve the biological activity of some bioactive molecules in end products. Transforming growth factor (TGF)-beta is one such molecule. TGF-beta is a polypeptide, which has been described in both human and bovine milk. It is implicated in many processes, including epithelial cell growth and differentiation, development, carcinogenesis and immune regulation. The present article discusses the biological activity of TGF-beta2 that has been preserved and activated in a cow's milk-based product. More specifically, it addresses possible mechanisms of action in the intestinal lumen and speculates on how milk products containing naturally occurring TGF-beta2 could be exploited in functional foods for the infant or as therapies for specific intestinal diseases.

Aberrant Receptor Internalization and Enhanced FRS2-dependent Signaling Contribute to the Transforming Activity of the Fibroblast Growth Factor Receptor 2 IIIb C3 Isoform*

PubMed Central

Cha, Jiyoung Y.; Maddileti, Savitri; Mitin, Natalia; Harden, T. Kendall; Der, Channing J.

2009-01-01

Alternative splice variants of fibroblast growth factor receptor 2 (FGFR2) IIIb, designated C1, C2, and C3, possess progressive reduction in their cytoplasmic carboxyl termini (822, 788, and 769 residues, respectively), with preferential expression of the C2 and C3 isoforms in human cancers. We determined that the progressive deletion of carboxyl-terminal sequences correlated with increasing transforming potency. The highly transforming C3 variant lacks five tyrosine residues present in C1, and we determined that the loss of Tyr-770 alone enhanced FGFR2 IIIb C1 transforming activity. Because Tyr-770 may compose a putative YXXL sorting motif, we hypothesized that loss of Tyr-770 in the 770YXXL motif may cause disruption of FGFR2 IIIb C1 internalization and enhance transforming activity. Surprisingly, we found that mutation of Leu-773 but not Tyr-770 impaired receptor internalization and increased receptor stability and activation. Interestingly, concurrent mutations of Tyr-770 and Leu-773 caused 2-fold higher transforming activity than caused by the Y770F or L773A single mutations, suggesting loss of Tyr and Leu residues of the 770YXXL773 motif enhances FGFR2 IIIb transforming activity by distinct mechanisms. We also determined that loss of Tyr-770 caused persistent activation of FRS2 by enhancing FRS2 binding to FGFR2 IIIb. Furthermore, we found that FRS2 binding to FGFR2 IIIb is required for increased FRS2 tyrosine phosphorylation and enhanced transforming activity by Y770F mutation. Our data support a dual mechanism where deletion of the 770YXXL773 motif promotes FGFR2 IIIb C3 transforming activity by causing aberrant receptor recycling and stability and persistent FRS2-dependent signaling. PMID:19103595

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

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

Ebi, Masahide; Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp; Shimura, Takaya

2010-11-19

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cellmore » growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF{beta} enhanced gastric cancer cell growth and ADAM inhibitors suppressed this effect. EGFR phosphorylation, HB-EGF-CTF nuclear translocation, and cell growth were suppressed in ADAM17 knockdown cells. Conclusion: HB-EGF-CTF nuclear translocation and EGFR transactivation from proHB-EGF shedding mediated by ADAM17 activated by TGF{beta} might be an important pathway of gastric cancer cell proliferation by TGF{beta}.« less

Economic Growth and Landscape Change

USGS Publications Warehouse

Prato, Tony; Fagre, Dan

2007-01-01

Sustaining Rocky Mountain Landscapes provides a scientific basis for communities to develop policies for managing the growth and economic transformation of the CCE without sacrificing the quality of life and environment for which the land is renowned. This forthcoming edited volume focuses on five aspects of sustaining mountain landscapes in the CCE and similar regions in the Rocky Mountains. The five aspects are: 1) how social, economic, demographic and environmental forces are transforming ecosystem structure and function, 2) trends in use and conditions for human and environmental resources, 3) activating science, policy and education to enhance sustainable landscape management, 4) challenges to sustainable management of public and private lands, and 5) future prospects for achieving sustainable landscapes.

Transforming Growth Factor Beta-2 Mutations in Barlow's Disease and Aortic Dilatation.

PubMed

Disha, Kushtrim; Schulz, Solveig; Kuntze, Thomas; Girdauskas, Evaldas

2017-07-01

We report on a patient operated on for degenerative myxomatous mitral and tricuspid valve disease (Barlow's disease) and aortic root dilatation. A valve repair operation and the postoperative course were uneventful. Multigenerational genetic analyses revealed two different mutations in the transforming growth factor beta-2 gene in the same patient. The two mutations in different exons were inherited from both parents each. None of the parents presented with either valve dysfunction or aortic root dilatation. This rare case illustrates potentially common genetic and signaling pathways of concomitant myxomatous valve disease and aortic root dilatation. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Education, Skills and Industrial Development in the Structural Transformation of Africa. Innocenti Occasional Papers Number 3. Special Subseries: Structural Adjustment in Sub-Saharan Africa.

ERIC Educational Resources Information Center

Lall, Sanjaya

Industrial expansion remains essential for the development and structural transformation of most sub-Saharan African economies. The advantages of industrialization go beyond the provision of manufactured goods and the diversification of exports to the modernization of society. Growth rates in formal manufacturing tell little about the economic…

Grand challenges in evolutionary and population genetics: The importance of integrating epigenetics, genomics, modeling, and experimentation

Treesearch

Samuel A. Cushman

2014-01-01

This is a time of explosive growth in the fields of evolutionary and population genetics, with whole genome sequencing and bioinformatics driving a transformative paradigm shift (Morozova and Marra, 2008). At the same time, advances in epigenetics are thoroughly transforming our understanding of evolutionary processes and their implications for populations, species and...

Plankton Dynamics and Mesoscale Turbulence

DTIC Science & Technology

2010-06-29

transformation of inorganic materials and light into living matter by photosynthesis ) is operated mainly by small, unicellular algae that float freely in the...ecosystems, primary production (the transformation of inorganic materials and light into living matter by photosynthesis ) is operated mainly by small...them into biomass via photosynthesis . The main limiting factors for phytoplankton growth are light and nutrient availability; for this reason

Reversible Smad-dependent signaling between tumor suppression and oncogenesis.

PubMed

Sekimoto, Go; Matsuzaki, Koichi; Yoshida, Katsunori; Mori, Shigeo; Murata, Miki; Seki, Toshihito; Matsui, Hirofumi; Fujisawa, Jun-ichi; Okazaki, Kazuichi

2007-06-01

Cancer cells often gain advantage by reducing the tumor-suppressive activity of transforming growth factor-beta (TGF-beta) together with stimulation of its oncogenic activity as in Ras-transformed cells; however, molecular mechanisms remain largely unknown. TGF-beta activates both its type I receptor (TbetaRI) and c-Jun NH2-terminal kinase (JNK), which phosphorylate Smad2 and Smad3 at the COOH-terminal (pSmad2/3C) and linker regions (pSmad2/3L). Here, we report that Ras transformation suppresses TbetaRI-mediated pSmad3C signaling, which involves growth inhibition by down-regulating c-Myc. Instead, hyperactive Ras constitutively stimulates JNK-mediated pSmad2/3L signaling, which fosters tumor invasion by up-regulating plasminogen activator inhibitor-1 and matrix metalloproteinase-1 (MMP-1), MMP-2, and MMP-9. Conversely, selective blockade of linker phosphorylation by a mutant Smad3 lacking JNK-dependent phosphorylation sites results in preserved tumor-suppressive function via pSmad3C in Ras-transformed cells while eliminating pSmad2/3L-mediated invasive capacity. Thus, specific inhibition of the JNK/pSmad2/3L pathway should suppress cancer progression by shifting Smad-dependent signaling from oncogenesis to tumor suppression.

Growth and development of Colorado potato beetle larvae, Leptinotarsa decemlineata, on potato plants expressing the oryzacystatin II proteinase inhibitor.

PubMed

Cingel, Aleksandar; Savić, Jelena; Vinterhalter, Branka; Vinterhalter, Dragan; Kostić, Miroslav; Jovanović, Darka Šešlija; Smigocki, Ann; Ninković, Slavica

2015-08-01

Plant proteinase inhibitors (PIs) are attractive tools for crop improvement and their heterologous expression can enhance insect resistance in transgenic plants. PI oryzacystatin II (OCII), isolated from rice, showed potential in controlling pests that utilize cysteine proteinases for protein digestion. To evaluate the applicability of the OCII gene in enhancing plant defence, OCII-transformed potatoes were bioassayed for resistance to Colorado potato beetle (Leptinotarsa decemlineata Say). Feeding on transformed leaves of potato cultivars Desiree and Jelica significantly affected larval growth and development, but did not change mortality rates. During the L2 and L3 developmental stages larvae consumed the OCII-transformed foliage faster as compared to the nontransformed control. Also these larvae reached the prepupal stage (end of L4 stage) 2 days earlier than those fed on control leaves. However, the total amounts of consumed OCII-transformed leaves were up to 23% lower than of control, and the maximal weights of prepupal larvae were reduced by up to 18% as compared to larvae fed on nontransformed leaves. The reduction in insect fitness reported in this study in combination with other control measures, could lead to improved CPB resistance management in potato.

Growth factors and chronic wound healing: past, present, and future.

PubMed

Goldman, Robert

2004-01-01

Growth substances (cytokines and growth factors) are soluble signaling proteins affecting the process of normal wound healing. Cytokines govern the inflammatory phase that clears cellular and extracellular matrix debris. Wound repair is controlled by growth factors (platelet-derived growth factor [PDGF], keratinocyte growth factor, and transforming growth factor beta). Endogenous growth factors communicate across the dermal-epidermal interface. PDGF is important for most phases of wound healing. Becaplermin (PDGF-BB), the only growth factor approved by the Food and Drug Administration, requires daily application for neuropathic wound healing. Gene therapy is under development for more efficient growth factor delivery; a single application will induce constitutive growth factor expression for weeks. Based on dramatic preclinical animal studies, a phase 1 clinical trial planned on a PDGF genetic construct appears promising.

Managing diversity and enhancing team outcomes: the promise of transformational leadership.

PubMed

Kearney, Eric; Gebert, Diether

2009-01-01

In a sample of 62 research and development (R&D) teams, the authors examined transformational leadership as a moderator of the relationship of age, nationality, and educational background diversity with team outcomes. When levels of transformational leadership were high, nationality and educational diversity were positively related to team leaders' longitudinal ratings of team performance. These relationships were nonsignificant when transformational leadership was low. Age diversity was not related to team performance when transformational leadership was high, and it was negatively related to team performance when transformational leadership was low. Two mediated moderation effects help explain these findings. Transformational leadership moderated the relationship of the 3 examined diversity dimensions with the elaboration of task-relevant information, which in turn was positively associated with team performance. Moreover, transformational leadership moderated the relationship of the 3 diversity types with collective team identification, which in turn was positively related to the elaboration of task-relevant information. The authors discuss the theoretical and practical implications of these results. Overall, this study suggests that transformational leadership can foster the utilization of the potential, but frequently untapped, benefits entailed by both demographic and informational/cognitive team diversity. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Surface-mediated nucleation in the solid-state polymorph transformation of terephthalic acid.

PubMed

Beckham, Gregg T; Peters, Baron; Starbuck, Cindy; Variankaval, Narayan; Trout, Bernhardt L

2007-04-18

A molecular mechanism for nucleation for the solid-state polymorph transformation of terephthalic acid is presented. New methods recently developed in our group, aimless shooting and likelihood maximization, are employed to construct a model for the reaction coordinate for the two system sizes studied. The reaction coordinate approximation is validated using the committor probability analysis. The transformation proceeds via a localized, elongated nucleus along the crystal edge formed by fluctuations in the supramolecular synthons, suggesting a nucleation and growth mechanism in the macroscopic system.

Information Age Transformation: Getting to a 21st Century Military (revised)

DTIC Science & Technology

2002-06-01

strategy for transformation is built around experimentation with network- centric concepts designed to leverage the power of Information Age technologies and...Edward A. Smith: From Network- Centric to Effects-Based Operations. 7 CHAPTER 2 Background and Purpose DoD is fully committed to taking advantage...Network Centric Warfare3 (NCW) translates these broad vision statements into a way ahead. NCW is a set of warfighting concepts4 designed to create and

Role of the XIAP-Cooper Axis in Prostate Cancer

DTIC Science & Technology

2011-04-01

growing yeast transformed with a plasmid encoding human XIAP in Cu-free selective medium. Supplemental Cu was added to the medium 1-2 hours before...human XIAP into yeast deletion strains. We selected 16 deletion strains from the same background as our wild-type control (BY4741) for analysis. These...transformed with the XIAP expression plasmid. This objective is complete. Assess yeast deletion mutants for delivery of copper to XIAP. After

Growth of children living in the outskirts of Ankara: impact of low socio-economic status.

PubMed

Gültekin, Timur; Hauspie, Roland; Susanne, Charles; Güleç, Erksin

2006-01-01

Most studies of the growth of Turkish schoolchildren are limited to large cities and to subjects from high socio-economic background. Very little is known about growth and development of rural, suburban and low socio-economic children in Turkey. The purpose of this study is to compare height and weight of school-aged children of low socio-economic background with available growth data from high socio-economic strata, and to verify the possible influences of three socio-demographic parameters on their growth. The sample consisted of 1,052 girls and 1,223 boys, aged between 7-17 years, living in the outskirts of Ankara, a suburban area of poor socio-economic background. Centile distributions for height and weight were estimated by the LMS-method. ANOVA and Student's t-test were used to compare mean z-scores for height and weight among the various categories of the socio-demographic parameters. Children living in the outskirts of Ankara have lower mean values for height and weight when compared with growth data of upper socio-economic strata children. The differences were most pronounced during adolescence. Skinfolds were higher in girls than in boys at all ages (largest p = 0.007). There was no clear relationship between growth and the number of siblings, the number of rooms in the house, the mother's and father's education, and the father's professional status (p > 0.05), except for the height of girls (p < 0.05). It is suggested that the lower growth status of children living in the outskirts of Ankara is attributable to the poor socio-economic status of this suburban population, which has not changed over the past decades. It is postulated that the growth impairment during adolescence might be due to a reduced tempo of growth in these children.

Homogeneous Yang-Baxter deformations as generalized diffeomorphisms

NASA Astrophysics Data System (ADS)

Sakamoto, Jun-ichi; Sakatani, Yuho; Yoshida, Kentaroh

2017-10-01

Yang-Baxter (YB) deformations of string sigma model provide deformed target spaces. We propose that homogeneous YB deformations always lead to a certain class of β-twisted backgrounds and represent the bosonic part of the supergravity fields in terms of the classical r-matrix associated with the YB deformation. We then show that various β-twisted backgrounds can be realized by considering generalized diffeomorphisms in the undeformed background. Our result extends the notable relation between the YB deformations and (non-commuting) TsT transformations. We also discuss more general deformations beyond the YB deformations.

The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K–AKT–NFκB cascade

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

Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon

Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in themore » MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 × 10{sup 7} cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl{sub 2} treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K–AKT–NFκB protein expression. An increase in the expression of PI3K–AKT–NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl{sub 2} treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. - Highlights: • Repeated exposure of CSC causes malignant transformation in MCF-10A. • MCF-10A-Tr cells showed a distinct STR profile and tumor inducing characteristics. • Increased expression of PI3K, AKT, and NFκB protein in MCF-10A-Tr and solid tumor. • Increased ROS and PI3K-AKT-NFκB proteins in smoke carcinogen exposed MCF-10A cells. • Cadmium may be a strong contributor to the transformation of MCF-10A cells.« less

Beta-type transforming growth factor specifies organizational behavior in vascular smooth muscle cell cultures

PubMed Central

1987-01-01

In culture, vascular smooth muscle cells (SMC) grow in a "hill-and- valley" (multilayered) pattern of organization. We have studied the growth, behavioral organization, and biosynthetic phenotype of rat aortic SMC exposed to purified platelet-derived growth regulatory molecules. We show that multilayered growth is not a constitutive feature of cultured SMC, and that beta-type transforming growth factor (TGF-beta) is the primary determinant of multilayered growth and the hill-and-valley pattern of organization diagnostic for SMC in culture. TGF-beta inhibited, in a dose-dependent manner, the serum- or platelet- derived growth factor-mediated proliferation of these cells in two- dimensional culture, but only when cells were plated at subconfluent densities. The ability of TGF-beta to inhibit SMC growth was inversely correlated to plating cell density. When SMC were plated at monolayer density (5 X 10(4) cells/cm2) to allow maximal cell-to-cell contact, TGF-beta potentiated cell growth. This differential response of SMC to TGF-beta may contribute to the hill-and-valley pattern of organization. Unlike its effect on other cell types, TGF-beta did not enhance the synthesis of fibronectin or its incorporation into the extracellular matrix. However, the synthesis of a number of other secreted proteins was altered by TGF-beta treatment. SMC treated with TGF-beta for 4 or 8 h secreted markedly enhanced amounts of an Mr 38,000-D protein doublet whose synthesis is known to be increased by heparin (another inhibitor of SMC growth), suggesting metabolic similarities between heparin- and TGF-beta-mediated SMC growth inhibition. The data suggest that TGF-beta may play an important and complex regulatory role in SMC proliferation and organization during development and after vascular injury. PMID:3475277

Generation of Trichoderma atroviride mutants with constitutively activated G protein signaling by using geneticin resistance as selection marker.

PubMed

Gruber, Sabine; Omann, Markus; Rodrìguez, Carolina Escobar; Radebner, Theresa; Zeilinger, Susanne

2012-11-17

Species of the fungal genus Trichoderma are important industrial producers of cellulases and hemicellulases, but also widely used as biocontrol agents (BCAs) in agriculture. In the latter function Trichoderma species stimulate plant growth, induce plant defense and directly antagonize plant pathogenic fungi through their mycoparasitic capabilities. The recent release of the genome sequences of four mycoparasitic Trichoderma species now forms the basis for large-scale genetic manipulations of these important BCAs. Thus far, only a limited number of dominant selection markers, including Hygromycin B resistance (hph) and the acetamidase-encoding amdS gene, have been available for transformation of Trichoderma spp. For more extensive functional genomics studies the utilization of additional dominant markers will be essential. We established the Escherichia coli neomycin phosphotransferase II-encoding nptII gene as a novel selectable marker for the transformation of Trichoderma atroviride conferring geneticin resistance. The nptII marker cassette was stably integrated into the fungal genome and transformants exhibited unaltered phenotypes compared to the wild-type. Co-transformation of T. atroviride with nptII and a constitutively activated version of the Gα subunit-encoding tga3 gene (tga3Q207L) resulted in a high number of mitotically stable, geneticin-resistant transformants. Further analyses revealed a co-transformation frequency of 68% with 15 transformants having additionally integrated tga3Q207L into their genome. Constitutive activation of the Tga3-mediated signaling pathway resulted in increased vegetative growth and an enhanced ability to antagonize plant pathogenic host fungi. The neomycin phosphotransferase II-encoding nptII gene from Escherichia coli proved to be a valuable tool for conferring geneticin resistance to the filamentous fungus T. atroviride thereby contributing to an enhanced genetic tractability of these important BCAs.

The bovine papillomavirus E5 protein requires a juxtamembrane negative charge for activation of the platelet-derived growth factor beta receptor and transformation of C127 cells.

PubMed

Klein, O; Kegler-Ebo, D; Su, J; Smith, S; DiMaio, D

1999-04-01

The bovine papillomavirus E5 gene encodes a 44-amino-acid, homodimeric transmembrane protein that is the smallest known transforming protein. The E5 protein transforms cultured fibroblasts by forming a stable complex with the endogenous platelet-derived growth factor (PDGF) beta receptor through transmembrane and juxtamembrane interactions, leading to sustained receptor activation. Aspartic acid 33 in the extracellular juxtamembrane region of the E5 protein is important for cell transformation and interaction with the PDGF beta receptor. A. N. Meyer et al. (Proc. Natl. Acad. Sci USA 91:4634-4638, 1994) speculated that this residue interacted with lysine 499 on the receptor. We constructed E5 mutants containing all possible substitutions at position 33, as well as several double mutants containing substitutions at aspartic acid 33 and at glutamic acid 36, and we examined the ability of these mutants to transform C127 mouse fibroblasts and to bind to and induce activation of the PDGF beta receptor. There was an excellent correlation between the transformation activities of the various mutants and their ability to bind to and activate the PDGF beta receptor. Analysis of the mutants demonstrated that a juxtamembrane negative charge on the E5 protein was required for cell transformation and for productive interaction with the PDGF beta receptor and indicated that aspartic acid 33 was more important for these activities than was glutamic acid 36. These results are consistent with the existence of an essential juxtamembrane salt bridge between lysine 499 on the PDGF beta receptor and an acidic residue in the C terminus of the E5 protein and lend support to our proposed model for the complex between the E5 dimer and the PDGF beta receptor.

The PDZ domain binding motif (PBM) of human T-cell leukemia virus type 1 Tax can be substituted by heterologous PBMs from viral oncoproteins during T-cell transformation.

PubMed

Aoyagi, Tomoya; Takahashi, Masahiko; Higuchi, Masaya; Oie, Masayasu; Tanaka, Yuetsu; Kiyono, Tohru; Aoyagi, Yutaka; Fujii, Masahiro

2010-04-01

Several tumor viruses, such as human T-cell leukemia virus (HTLV), human papilloma virus (HPV), human adenovirus, have high-oncogenic and low-oncogenic subtypes, and such subtype-specific oncogenesis is associated with the PDZ-domain binding motif (PBM) in their transforming proteins. HTLV-1, the causative agent of adult T-cell leukemia, encodes Tax1 with PBM as a transforming protein. The Tax1 PBM was substituted with those from other oncoviruses, and the transforming activity was examined. Tax1 mutants with PBM from either HPV-16 E6 or adenovirus type 9 E4ORF1 are fully active in the transformation of a mouse T-cell line from interleukin-2-dependent growth into independent growth. Interestingly, one such Tax1 PBM mutant had an extra amino acid insertion derived from E6 between PBM and the rest of Tax1, thus suggesting that the amino acid sequences of the peptides between PBM and the rest of Tax1 and the numbers only slightly affect the function of PBM in the transformation. Tax1 and Tax1 PBM mutants interacted with tumor suppressors Dlg1 and Scribble with PDZ-domains. Unlike E6, Tax1 PBM mutants as well as Tax1 did not or minimally induced the degradations of Dlg1 and Scribble, but instead induced their subcellular translocation from the detergent-soluble fraction into the insoluble fraction, thus suggesting that the inactivation mechanism of these tumor suppressor proteins is distinct. The present results suggest that PBMs of high-risk oncoviruses have a common function(s) required for these three tumor viruses to transform cells, which is likely associated with the subtype-specific oncogenesis of these tumor viruses.

Poorer detection rates of severe fetal growth restriction in women of likely refugee background: A case for re-focusing pregnancy care.

PubMed

Biro, Mary Anne; East, Christine

2017-04-01

Severe fetal growth restriction (FGR) (< third centile) in a singleton pregnancy undelivered by 40 weeks is one of a number of Victorian Perinatal Services Performance Indicators, which aim to provide a measure of the quality and safety of maternity care. Women of refugee background have been found to have poorer perinatal outcomes compared to others and these outcomes can in part be explained by previous history. However, less access to and engagement with pregnancy care may also be contributing factors. This study examined the impact of likely refugee background on severe FGR in a singleton pregnancy undelivered by 40 weeks. A retrospective study was undertaken utilising data on women who gave birth to a severely growth-restricted infant at Monash Health during January 2013-July 2015. Unadjusted and adjusted analyses were undertaken to examine the association between the mother being of likely refugee background and severe FGR in singletons delivered after 40 weeks. There was an association between the mother being of likely refugee background and giving birth to a severely growth-restricted baby after 40 weeks with these mothers at two and half times the odds compared to mothers of non-refugee background (adjusted odds ratio 2.52; 95% confidence interval: 1.44-4.42). While detecting FGR is clinically challenging, our findings suggest that maternity services need to be supported to offer care tailored to the specific needs of vulnerable and disadvantaged populations. Providing quality, culturally responsive and accessible care is fundamental to addressing refugee maternal and perinatal health inequalities. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Insights from Breast Cancer Survivors: The Interplay between Context, Epistemology, and Change

ERIC Educational Resources Information Center

Hoggan, Chad

2014-01-01

This study explored the processes by which a group of breast cancer survivors experienced positive learning and growth from their cancer experiences. The author argues that such learning and growth can be considered transformative learning, especially from ontological perspectives of the theory. The participants' change process consisted of…

Marketing Education for the next Four Billion: Challenges and Innovations

ERIC Educational Resources Information Center

Rosa, Jose Antonio

2012-01-01

This article argues for a third transformation in marketing pedagogy, one made necessary by the emergence of subsistence consumers as a high-growth market segment. Continued double-digit growth in buying power and consumption among the world's poor appear certain, provided that the subsistence merchants serving such markets are effective. Ensuring…

TERATOGENICITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN MICE LACKING THE EXPRESSION OF EGF AND/OR TGFALPHA

EPA Science Inventory

Abstract
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure produces hydronephrosis and cleft palate in mice. These responses are correlated with disruption of expression of epidermal growth factor (EGF) receptor ligands, primarily EGF and transforming growth factor-alpha ...

Monitoring wheat mitochondrial compositional and respiratory changes using Fourier transform mid-infrared spectroscopy in response to agrochemical treatments

USDA-ARS?s Scientific Manuscript database

Fungicides and plant growth regulators can impact plant growth outside of their effects on fungal pathogens. Although many of these chemicals are inhibitors of mitochondrial oxygen uptake, information remains limited as to whether they are able tomodify other mitochondrial constituents. Fourier tran...

Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.

PubMed

Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash

2012-04-01

The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. Copyright © 2011 Wiley Periodicals, Inc.

Agrobacterium-mediated genetic transformation of pineapple (Ananas comosus L., Merr.).

PubMed

Mhatre, Minal

2013-01-01

Pineapple (Ananas comosus L., Merr.) is a commercially important crop, grown in the tropical and subtropical regions. However, the crop is faced with postharvest damage and poor varietal and nutritional improvement. Being a vegetatively propagated crop, conventional breeding programs take longer time for genetic improvement, which may not necessarily successfully develop an improved cultivar. Hence, the genetic modification of pineapple is an alternative handy approach to improve pineapple. We have established an Agrobacterium-mediated transformation system using leaf bases from in vitro-grown pineapple plants. Being a monocot, acetosyringone is added to the culture medium for overnight growth of Agrobacterium and transformation to transfer a gene of interest MSI99 soybean ferritin. Leaf bases isolated from in vitro shoot cultures are treated with Agrobacterium suspension at two dilutions, 10× and 20×, for 30 min. Explants are subsequently blot dried and cultured on gelrite solidified hormone-free Pin1 medium for 2 days (cocultivation). Periodic transfer is first done to the regeneration medium (Pin1) containing cefotaxime for the suppression of Agrobacterium growth. The transformants are selected by culturing on Pin1 medium containing cefotaxime and kanamycin. Multiple shoots, regenerated in leaf bases, are further multiplied and individually rooted in the liquid RM medium amended with antibiotics to recover plants. Putative transformants are analyzed for transgene integration and expression using standard molecular biological methods of PCR, RT-PCR, and genomic Southern.

Mycoplasmal Infections Prevent Apoptosis and Induce Malignant Transformation of Interleukin-3-Dependent 32D Hematopoietic Cells

PubMed Central

Feng, Shaw-Huey; Tsai, Shien; Rodriguez, Jose; Lo, Shyh-Ching

1999-01-01

32D cells, a murine myeloid cell line, rapidly undergo apoptosis upon withdrawal of interleukin-3 (IL-3) supplement in culture. We found that 32D cells, if infected by several species of human mycoplasmas that rapidly activated NF-κB, would live and continue to grow in IL-3-depleted culture. Mycoplasma-infected cells showed no evidence of autocrine production of IL-3. Pyrrolidine dithiocarbamate (PDTC) blocked activation of NF-κB and led to prominent cell death. Heat-killed mycoplasmas or mycoplasmal membrane preparations alone could support continued growth of 32D cells in culture without IL-3 supplement for a substantial period of time. However, upon removal of heat-inactivated mycoplasmas, 32D cells quickly became apoptotic. In comparison, live Mycoplasma fermentans or M. penetrans infection for 4 to 5 weeks induced malignant transformation of 32D cells. Transformed 32D cells grew autonomously and no longer required support of growth-stimulating factors including IL-3 and mycoplasmas. The transformed 32D cells quickly formed tumors when injected into nude mice. Karyotyping showed that development of chromosomal changes and trisomy 19 was often associated with malignant transformation and tumorigenicity of 32D cells. Mycoplasmal infections apparently affected the fidelity of genomic transmission in cell division as well as checkpoints coordinating the progression of cell cycle events. PMID:10567525

RNAi-mediated silencing of MAP kinase signalling genes (Fmk1, Hog1, and Pbs2) in Fusarium oxysporum reduces pathogenesis on tomato plants.

PubMed

Pareek, Manish; Rajam, Manchikatla Venkat

2017-09-01

Fusarium oxysporum is a soil-borne plant fungal pathogen, and causes colossal losses in several crop plants including tomato. Effective control measures include the use of harmful fungicides and resistant cultivars, but these methods have shown limited success. Conventional methods to validate fungal pathogenic genes are labour intensive. Therefore, an alternative strategy is required to efficiently characterize unknown pathogenic genes. RNA interference (RNAi) has emerged as a potential tool to functionally characterize novel fungal pathogenic genes and also to control fungal diseases. Here, we report an efficient method to produce stable RNAi transformants of F. oxysporum using Agrobacterium-mediated transformation (AMT). We have transformed F. oxysporum spores using RNAi constructs of Fmk1, Hog1, and Pbs2 MAP kinase signalling genes. Fmk1 RNAi fungal transformants showed loss of surface hydrophobicity, reduced invasive growth on tomato fruits and hypo-virulence on tomato seedlings. Hog1 and Pbs2 RNAi transformants showed altered conidial size, and reduced invasive growth and pathogenesis. These results showed that AMT using RNAi constructs is an effective approach for dissecting the role of genes involved in pathogenesis in F. oxysporum and this could be extended for other fungal systems. The obtained knowledge can be easily translated for developing fungal resistant crops by RNAi. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

PubMed Central

Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

2017-01-01

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent. PMID:29340097

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells.

PubMed

Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

2017-12-19

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent.

Recruitment and retention: factors that affect pericyte migration

PubMed Central

Aguilera, Kristina Y.

2013-01-01

Pericytes are critical for vascular morphogenesis and contribute to several pathologies, including cancer development and progression. The mechanisms governing pericyte migration and differentiation are complex and have not been fully established. Current literature suggests that platelet-derived growth factor/platelet-derived growth factor receptor-β, sphingosine 1-phosphate/endothelial differentiation gene-1, angiopoietin-1/tyrosine kinase with immunoglobulin-like and EGF-like domains 2, angiopoietin-2/tyros-ine kinase with immunoglobulin-like and EGF-like domains 2, transforming growth factor β/activin receptor-like kinase 1, transforming growth factor β/activin receptor-like kinase 5, Semaphorin-3A/Neuropilin, and matrix metalloproteinase activity regulate the recruitment of pericytes to nascent vessels. Interestingly, many of these pathways are directly affected by secreted protein acidic and rich in cysteine (SPARC). Here, we summarize the function of these factors in pericyte migration and discuss if and how SPARC might infuence these activities and thus provide an additional layer of control for the recruitment of vascular support cells. Additionally, the consequences of targeted inhibition of pericytes in tumors and the current understanding of pericyte recruitment in pathological environments are discussed. PMID:23912898

Effects of inhalational anaesthetics in experimental allergic asthma.

PubMed

Burburan, S M; Silva, J D; Abreu, S C; Samary, C S; Guimarães, I H L; Xisto, D G; Morales, M M; Rocco, P R M

2014-06-01

We evaluated whether isoflurane, halothane and sevoflurane attenuate the inflammatory response and improve lung morphofunction in experimental asthma. Fifty-six BALB/c mice were sensitised and challenged with ovalbumin and anaesthetised with isoflurane, halothane, sevoflurane or pentobarbital sodium for one hour. Lung mechanics and histology were evaluated. Gene expression of pro-inflammatory (tumour necrosis factor-α), pro-fibrogenic (transforming growth factor-β) and pro-angiogenic (vascular endothelial growth factor) mediators, as well as oxidative process modulators, were analysed. These modulators included nuclear factor erythroid-2 related factor 2, sirtuin, catalase and glutathione peroxidase. Isoflurane, halothane and sevoflurane reduced airway resistance, static lung elastance and atelectasis when compared with pentobarbital sodium. Sevoflurane minimised bronchoconstriction and cell infiltration, and decreased tumour necrosis factor-α, transforming growth factor-β, vascular endothelial growth factor, sirtuin, catalase and glutathione peroxidase, while increasing nuclear factor erythroid-2-related factor 2 expression. Sevoflurane down-regulated inflammatory, fibrogenic and angiogenic mediators, and modulated oxidant-antioxidant imbalance, improving lung function in this model of asthma. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression.

PubMed

He, C; Lv, X; Hua, G; Lele, S M; Remmenga, S; Dong, J; Davis, J S; Wang, C

2015-12-10

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces the expression of epidermal growth factor (EGF) receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, whereas knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF & NRGs/ERBBs/YAP/HBEGF & NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression.

Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor Alpha in Cancer Bladder: Schistosomal and Non-Schistosomal

PubMed Central

Badawy, Afkar A.; El-Hindawi, Ali; Hammam, Olfat; Moussa, Mona; Helal, Noha S.; Kamel, Amira

2017-01-01

Introduction Overexpression of epidermal growth factor receptor (EGFR) has been described in several solid tumors including bladder cancer. Transforming growth factor alpha (TGFα) is frequently deregulated in neoplastic cells and plays a role in the development of bladder cancer. TGFα-EGFR ligand-receptor combination constitutes an important event in multistep tumorigenesis. Methods This study was done on 30 bladder biopsies from patients with urothelial carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control bladder specimens. All were immuohistochemically stained with EGFR and TGFα antibodies. Results EGFR and TGFα were over-expressed in higher grades and late stages of bladder cancer. Moreover, they show higher expression in squamous cell carcinoma compared to urothelial carcinoma and in schistosomal associated lesions than in non-schistosomal associated lesions. Conclusion EGFR and TGFα could be used as prognostic predictors in early stage and grade of bladder cancer cases, especially those with schistosomal association. In addition they can help in selecting patients who can get benefit from anti-EGFR molecular targeted therapy. PMID:28413380

Fungal endophytes and their interactions with plants in phytoremediation: A review.

PubMed

Deng, Zujun; Cao, Lixiang

2017-02-01

Endophytic microorganisms (including bacteria and fungi) are likely to interact closely with their hosts and are more protected from adverse changes in the environment. The microbiota contribute to plant growth, productivity, carbon sequestration, and phytoremediation. Elevated levels of contaminants (i.e. metals) are toxic to most plants, the plant's metabolism and growth were impaired and their potential for metal phytoextraction is highly restricted. Exploiting endophytic microorganisms to reduce metal toxicity to plants have been investigated to improve phytoremediation efficiencies. Fungi play an important role in organic and inorganic transformation, element cycling, rock and mineral transformations, bioweathering, mycogenic mineral formation, fungal-clay interactions, and metal-fungal interactions. Endophytic fungi also showed potentials to enhance phytoremediation. Compared to bacteria, most fungi exhibit a filamentous growth habit, which provides the ability to adopt both explorative or exploitative growth strategies and form linear organs of aggregated hyphae to protect fungal translocation. However, the information regarding the role of endophytic fungi in phytoremediation are incomplete, this review highlights the taxa, physiological properties, and interaction of endophytic fungi with plants in phytoremediation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Galangin inhibits human osteosarcoma cells growth by inducing transforming growth factor-β1-dependent osteogenic differentiation.

PubMed

Liu, Chunhong; Ma, Mingming; Zhang, Junde; Gui, Shaoliu; Zhang, Xiaohai; Xue, Shuangtao

2017-05-01

Osteosarcoma is the most common primary malignancy of the musculoskeletal system, and is associated with excessive proliferation and poor differentiation of osteoblasts. Currently, despite the use of traditional chemotherapy and radiotherapy, no satisfactory and effective agent has been developed to treat the disease. Herein, we found that a flavonoid natural product, galangin, could significantly attenuate human osteosarcoma cells proliferation, without causing obvious cell apoptosis. Moreover, galangin enhanced the expression of osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin and osteopontin) remarkably and elevated the alkaline phosphatase activity in human osteosarcoma cells. And galangin could also attenuated osteosarcoma growth in vivo. These bioactivities of galangin resulted from its selective activation of the transforming growth factor (TGF)-β1/Smad2/3 signaling pathway, which was demonstrated by pathway blocking experiments. These findings suggested that galangin could be a promising agent to treat osteosarcoma. In addition, targeting TGF-β1 to induce osteogenic differentiation might represent a novel therapeutic strategy to treat osteosarcoma with minimal side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.