CRIT-LINE: a noninvasive tool to monitor hemoglobin levels in pediatric hemodialysis patients.

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Garro, Rouba; Sutherland, Scott; Bayes, Liz; Alexander, Steven; Wong, Cynthia

2015-06-01

The national average for achieving the KDOQI-recommended hemoglobin (Hgb) target level of 11-12 g/dL is low with the current anemia management protocol of measuring Hgb levels every 2-4 weeks to guide intervention. The objective of this study was to correlate initial Hgb readings from the CRIT-LINE monitor with actual serum Hgb levels in pediatric patients on hemodialysis (HD). Data were collected from pediatric HD patients who had Hgb tests ordered for routine and/or clinical reasons. Hgb concentrations were read with the CRIT-LINE after 0.5 or 1 L of blood had been processed by HD in patients with a body weight of ≤20 or >20 kg, respectively. Ultrafiltration was kept at a minimum until the CRIT-LINE Hgb was read. In total, 217 Hgb readings from 23 HD patients were analyzed. Results showed a statistically significant correlation between CRIT-LINE readings and laboratory Hgb measurements (r = 0.94, p < 0.0001) using Pearson correlation coefficients for well-distributed data. The mean Hgb levels measured by CRIT-LINE and the laboratory were 11.12 ± 1.63 and 11.31 ± 1.69 g/dL, respectively. The CRIT-LINE monitor is an accurate instrument for monitoring Hgb levels in HD patients. Further studies will be needed to evaluate whether using CRIT-LINE Hgb levels to guide anemia management will improve the percentage of children with Hgb levels within target.

Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol.

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Klopčič, Ivana; Markovič, Tijana; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

2018-05-16

A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR). The endocrine disrupting effects were assessed in vitro in MDA-kb2 and GH3.TRE-Luc cell lines and by the XenoScreen YES/YAS assay. Moreover, binding affinity to nuclear receptors (GR and AR) was also measured. Immunomodulatory properties of the compounds were evaluated in lymphoblastoid cell lines. All the tested compounds showed endocrine disrupting and immunomodulatory activities. The results revealed that both DIC and its metabolite 4-HD exhibited significant estrogenic, anti-androgenic (in YAS assay), (anti)-androgenic, (anti)-glucocorticoid and anti-thyroid hormonal activities (in luciferase reporter gene assays). DIC showed direct binding to the GR, while its metabolite 4-HD to the GR and AR. Only metabolite 4-HD showed estrogenic, androgenic (in YAS assay) and thyroid-hormonal activities. PAR had anti-androgenic activity and anti-thyroid hormonal activity. PAR displayed GR agonist activity with competition to its receptor and agonistic activity to AR. All of the compounds significantly modulated pro-inflammatory and immunoregulatory cytokine production in lymphoblastoid cell lines and were thus proven immunomodulatory. The study is useful in determining toxicological effects and contributes to the knowledge of possible side effects of diclofenac, its metabolite and paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

Localization Microscopy Analyses of MRE11 Clusters in 3D-Conserved Cell Nuclei of Different Cell Lines.

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Eryilmaz, Marion; Schmitt, Eberhard; Krufczik, Matthias; Theda, Franziska; Lee, Jin-Ho; Cremer, Christoph; Bestvater, Felix; Schaufler, Wladimir; Hausmann, Michael; Hildenbrand, Georg

2018-01-22

In radiation biophysics, it is a subject of nowadays research to investigate DNA strand break repair in detail after damage induction by ionizing radiation. It is a subject of debate as to what makes up the cell's decision to use a certain repair pathway and how the repair machinery recruited in repair foci is spatially and temporarily organized. Single-molecule localization microscopy (SMLM) allows super-resolution analysis by precise localization of single fluorescent molecule tags, resulting in nuclear structure analysis with a spatial resolution in the 10 nm regime. Here, we used SMLM to study MRE11 foci. MRE11 is one of three proteins involved in the MRN-complex (MRE11-RAD50-NBS1 complex), a prominent DNA strand resection and broken end bridging component involved in homologous recombination repair (HRR) and alternative non-homologous end joining (a-NHEJ). We analyzed the spatial arrangements of antibody-labelled MRE11 proteins in the nuclei of a breast cancer and a skin fibroblast cell line along a time-course of repair (up to 48 h) after irradiation with a dose of 2 Gy. Different kinetics for cluster formation and relaxation were determined. Changes in the internal nano-scaled structure of the clusters were quantified and compared between the two cell types. The results indicate a cell type-dependent DNA damage response concerning MRE11 recruitment and cluster formation. The MRE11 data were compared to H2AX phosphorylation detected by γH2AX molecule distribution. These data suggested modulations of MRE11 signal frequencies that were not directly correlated to DNA damage induction. The application of SMLM in radiation biophysics offers new possibilities to investigate spatial foci organization after DNA damaging and during subsequent repair.

Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15.

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Artur Brandt

Full Text Available We describe a stromal predominant Wilms tumor with focal anaplasia and a complex, tumor specific chromosome 11 aberration: a homozygous deletion of the entire WT1 gene within a heterozygous 11p13 deletion and an additional region of uniparental disomy (UPD limited to 11p15.5-p15.2 including the IGF2 gene. The tumor carried a heterozygous p.T41A mutation in CTNNB1. Cells established from the tumor carried the same chromosome 11 aberration, but a different, homozygous p.S45Δ CTNNB1 mutation. Uniparental disomy (UPD 3p21.3pter lead to the homozygous CTNNB1 mutation. The tumor cell line was immortalized using the catalytic subunit of human telomerase (hTERT in conjunction with a novel thermolabile mutant (U19dl89-97tsA58 of SV40 large T antigen (LT. This cell line is cytogenetically stable and can be grown indefinitely representing a valuable tool to study the effect of a complete lack of WT1 in tumor cells. The origin/fate of Wilms tumors with WT1 mutations is currently poorly defined. Here we studied the expression of several genes expressed in early kidney development, e.g. FOXD1, PAX3, SIX1, OSR1, OSR2 and MEIS1 and show that these are expressed at similar levels in the parental and the immortalized Wilms10 cells. In addition the limited potential for muscle/ osteogenic/ adipogenic differentiation similar to all other WT1 mutant cell lines is also observed in the Wilms10 tumor cell line and this is retained in the immortalized cells. In summary these Wilms10 cells are a valuable model system for functional studies of WT1 mutant cells.

Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15

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Brandt, Artur; Löhers, Katharina; Beier, Manfred; Leube, Barbara; de Torres, Carmen; Mora, Jaume; Arora, Parineeta; Jat, Parmjit S.; Royer-Pokora, Brigitte

2016-01-01

We describe a stromal predominant Wilms tumor with focal anaplasia and a complex, tumor specific chromosome 11 aberration: a homozygous deletion of the entire WT1 gene within a heterozygous 11p13 deletion and an additional region of uniparental disomy (UPD) limited to 11p15.5-p15.2 including the IGF2 gene. The tumor carried a heterozygous p.T41A mutation in CTNNB1. Cells established from the tumor carried the same chromosome 11 aberration, but a different, homozygous p.S45Δ CTNNB1 mutation. Uniparental disomy (UPD) 3p21.3pter lead to the homozygous CTNNB1 mutation. The tumor cell line was immortalized using the catalytic subunit of human telomerase (hTERT) in conjunction with a novel thermolabile mutant (U19dl89-97tsA58) of SV40 large T antigen (LT). This cell line is cytogenetically stable and can be grown indefinitely representing a valuable tool to study the effect of a complete lack of WT1 in tumor cells. The origin/fate of Wilms tumors with WT1 mutations is currently poorly defined. Here we studied the expression of several genes expressed in early kidney development, e.g. FOXD1, PAX3, SIX1, OSR1, OSR2 and MEIS1 and show that these are expressed at similar levels in the parental and the immortalized Wilms10 cells. In addition the limited potential for muscle/ osteogenic/ adipogenic differentiation similar to all other WT1 mutant cell lines is also observed in the Wilms10 tumor cell line and this is retained in the immortalized cells. In summary these Wilms10 cells are a valuable model system for functional studies of WT1 mutant cells. PMID:27213811

Chromospherically active stars. 13: HD 30957: A double lined K dwarf binary

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Fekel, Francis C.; Dadonas, Virgilijus; Sperauskas, Julius; Vaccaro, Todd R.; Patterson, L. Ronald

1994-01-01

HD 30957 is a double-lined spectroscopic binary with a period of 44.395 days and a modest eccentricity of 0.09. The spectral types of the components are K2-3 V and K5 V. The measured v sin i for both components is less than or equal to 3 km/s and the orbital inclination is estimated to be 69 deg. The system is relatively nearby with a parallax of 0.025 sec or a distance of 40 pc. Space motions of the system indicate that it does not belong to any of the known moving groups. Absolute surface fluxes of the Ca II H and K lines have been recomputed and indicate only modest chromospheric activity. If the stars are rotating pseudosynchronously, the lack of light variability is consistent with the value of the critical Rossby number for starspot activity.

Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an oncolytic adenovirus that targets colon cancer cells

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Pittet Anne-Laure

2006-10-01

Full Text Available Abstract Background The Wnt signaling pathway is activated by mutations in the APC and β-catenin genes in many types of human cancer. β-catenin is stabilized by these mutations and activates transcription in part by acting as a bridge between Tcf/LEF proteins and the HD2 domain of the BCL9 coactivator. We have previously described oncolytic adenoviruses with binding sites for Tcf/LEF transcription factors inserted into the early viral promoters. These viruses replicate selectively in cells with activation of the Wnt pathway. To increase the activity of these viruses we have fused the viral transactivator E1A to the BCL9 HD2 domain. Methods Luciferase assays, co-immunoprecipitation and Western blotting, immunofluorescent cell staining and cytopathic effect assays were used to characterize the E1A-HD2 fusion protein and virus in vitro. Growth curves of subcutaneous SW620 colon cancer xenografts were used to characterize the virus in vivo. Results The E1A-HD2 fusion protein binds to β-catenin in vivo and activates a Tcf-regulated luciferase reporter better than wild-type E1A in cells with activated Wnt signaling. Expression of the E1A-HD2 protein promotes nuclear import of β-catenin, mediated by the strong nuclear localization signal in E1A. Tcf-regulated viruses expressing the fusion protein show increased expression of viral proteins and a five-fold increase in cytopathic effect (CPE in colorectal cancer cell lines. There was no change in viral protein expression or CPE in HeLa cells, indicating that E1A-HD2 viruses retain selectivity for cells with activation of the Wnt signaling pathway. Despite increasing the cytopathic effect of the virus in vitro, fusion of the HD2 domain to E1A did not increase the burst size of the virus in vitro or the anti-tumor effect of the virus in an SW620 xenograft model in vivo. Conclusion Despite an increase in the nuclear pool of β-catenin, the effects on viral activity in colon cancer cells were small

Genetic and Quantitative Trait Locus Analysis of Cell Wall Components and Forage Digestibility in the Zheng58 × HD568 Maize RIL Population at Anthesis Stage.

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Li, Kun; Wang, Hongwu; Hu, Xiaojiao; Ma, Feiqian; Wu, Yujin; Wang, Qi; Liu, Zhifang; Huang, Changling

2017-01-01

The plant cell wall plays vital roles in various aspects of the plant life cycle. It provides a basic structure for cells and gives mechanical rigidity to the whole plant. Some complex cell wall components are involved in signal transduction during pathogenic infection and pest infestations. Moreover, the lignification level of cell walls strongly influences the digestibility of forage plants. To determine the genetic bases of cell wall components and digestibility, quantitative trait locus (QTL) analyses for six related traits were performed using a recombinant inbred line (RIL) population from a cross between Zheng58 and HD568. Eight QTL for in vitro neutral detergent fiber (NDF) digestibility were observed, out of which only two increasing alleles came from HD568. Three QTL out of ten with alleles increasing in vitro dry matter digestibility also originated from HD568. Five-ten QTL were detected for lignin, cellulose content, acid detergent fiber, and NDF content. Among these results, 29.8% (14/47) of QTL explained >10% of the phenotypic variation in the RIL population, whereas 70.2% (33/47) explained ≤10%. These results revealed that in maize stalks, a few large-effect QTL and a number of minor-effect QTL contributed to most of the genetic components involved in cell wall biosynthesis and digestibility.

Localization Microscopy Analyses of MRE11 Clusters in 3D-Conserved Cell Nuclei of Different Cell Lines

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Marion Eryilmaz

2018-01-01

Full Text Available In radiation biophysics, it is a subject of nowadays research to investigate DNA strand break repair in detail after damage induction by ionizing radiation. It is a subject of debate as to what makes up the cell’s decision to use a certain repair pathway and how the repair machinery recruited in repair foci is spatially and temporarily organized. Single-molecule localization microscopy (SMLM allows super-resolution analysis by precise localization of single fluorescent molecule tags, resulting in nuclear structure analysis with a spatial resolution in the 10 nm regime. Here, we used SMLM to study MRE11 foci. MRE11 is one of three proteins involved in the MRN-complex (MRE11-RAD50-NBS1 complex, a prominent DNA strand resection and broken end bridging component involved in homologous recombination repair (HRR and alternative non-homologous end joining (a-NHEJ. We analyzed the spatial arrangements of antibody-labelled MRE11 proteins in the nuclei of a breast cancer and a skin fibroblast cell line along a time-course of repair (up to 48 h after irradiation with a dose of 2 Gy. Different kinetics for cluster formation and relaxation were determined. Changes in the internal nano-scaled structure of the clusters were quantified and compared between the two cell types. The results indicate a cell type-dependent DNA damage response concerning MRE11 recruitment and cluster formation. The MRE11 data were compared to H2AX phosphorylation detected by γH2AX molecule distribution. These data suggested modulations of MRE11 signal frequencies that were not directly correlated to DNA damage induction. The application of SMLM in radiation biophysics offers new possibilities to investigate spatial foci organization after DNA damaging and during subsequent repair.

NEW PRECISION ORBITS OF BRIGHT DOUBLE-LINED SPECTROSCOPIC BINARIES. III. HD 82191, ω DRACONIS, AND 108 HERCULIS

International Nuclear Information System (INIS)

Fekel, Francis C.; Williamson, Michael H.; Tomkin, Jocelyn

2009-01-01

We have determined improved spectroscopic orbits for three double-lined binaries, HD 82191 (Am), ω Dra (F5 V), and 108 Her (Am), using radial velocities from the 2.1 m telescope at McDonald Observatory, the coude feed telescope at Kitt Peak National Observatory, and 2 m telescope at Fairborn Observatory. The orbital periods range from 5.28 to 9.01 days, and all three systems have circular orbits. The new orbital dimensions (a 1 sin i and a 2 sin i) and minimum masses (m 1 sin 3 i and m 2 sin 3 i) have accuracies of 0.2% or better. Our improved results confirm the large minimum masses of HD 82191 and also agree with the values previously found for ω Dra. However, for the components of 108 Her our minimum masses are about 20% larger than the previous best values. We conclude that both components of HD 82191 as well as the primary of 108 Her are Am stars. However, the A9 secondary of 108 Her has normal abundances. We estimate spectral types of F4 dwarf and G0 dwarf for the components of ω Dra. The primaries of the three binaries are synchronously rotating as is the secondary of 108 Her. The secondaries of HD 82191 and ω Dra are possibly synchronously rotating.

Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines.

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Kopp, B; Zalko, D; Audebert, M

2018-04-01

Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants. Base on their lowest observed adverse effect concentration, the genotoxic potency of each heavy metal in each cell line was ranked in decreasing order, NaAsO 2  > CdCl 2  > PbCl 2 (only in LS-174T cells) > As 2 O 5  > SbCl 3  > K 2 TeO 3  > As 2 O 3 . No significant genotoxicity was observed with the other heavy metals tested. Cell viability data indicate that several heavy metals (As, Cd, Co, Ni, Sb, and Te) induce cytotoxicity at high concentrations, whereas an increase in the number of cells was observed for lead concentrations >100 µM in both cell lines tested, suggesting that lead stimulates cell growth. All these results highlight the possible human health hazards associated with the presence of heavy metals present in food. Environ. Mol. Mutagen. 59:202-210, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

TWO SMALL PLANETS TRANSITING HD 3167

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Vanderburg, Andrew; Bieryla, Allyson; Latham, David W.; Mayo, Andrew W.; Berlind, Perry; Duev, Dmitry A.; Jensen-Clem, Rebecca; Kulkarni, Shrinivas; Riddle, Reed; Baranec, Christoph; Law, Nicholas M.; Nieberding, Megan N.; Salama, Maïssa

2016-01-01

We report the discovery of two super-Earth-sized planets transiting the bright (V = 8.94, K = 7.07) nearby late G-dwarf HD 3167, using data collected by the K2 mission. The inner planet, HD 3167 b, has a radius of 1.6 R ⊕ and an ultra-short orbital period of only 0.96 days. The outer planet, HD 3167 c, has a radius of 2.9 R ⊕ and orbits its host star every 29.85 days. At a distance of just 45.8 ± 2.2 pc, HD 3167 is one of the closest and brightest stars hosting multiple transiting planets, making HD 3167 b and c well suited for follow-up observations. The star is chromospherically inactive with low rotational line-broadening, ideal for radial velocity observations to measure the planets’ masses. The outer planet is large enough that it likely has a thick gaseous envelope that could be studied via transmission spectroscopy. Planets transiting bright, nearby stars like HD 3167 are valuable objects to study leading up to the launch of the James Webb Space Telescope .

Effects of Hd2 in the presence of the photoperiod-insensitive functional allele of Hd1 in rice

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Zhen-Hua Zhang

2016-11-01

Full Text Available The role of photoperiod sensitivity (PS of flowering genes have become well recognized in rice, whereas little attention has been drawn to the non-PS component of these genes, especially to their influence on gene-by-gene interactions. Rice populations in which the photoperiod-sensitive allele at Hd1 has become insensitive to photoperiod but continued to affect heading date (HD were used in this study to fine-map a quantitative trait locus (QTL for HD and analyze its genetic relationship to Hd1. The QTL was delimitated to a 96.3-kb region on the distal end of the long arm of chromosome 7. Sequence comparison revealed that this QTL is identical to Hd2. In the near-isogenic line (NIL populations analyzed, Hd1 and Hd2 were shown to be photoperiod insensitive and have pleiotropic effects for HD, plant height and yield traits. The two genes were found to largely act additively in regulating HD and yield traits. The results indicate that non-PS components of flowering genes involved in photoperiod response play an important role in controlling flowering time and grain yield in rice, which should allow breeders to better manipulate pleiotropic genes for balancing adaptability and high-yielding accumulation.

Comparisons of amino acids, body constituents and antioxidative response between long-time HD and normal HD.

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Torigoe, Akira; Sato, Emiko; Mori, Takefumi; Ieiri, Norio; Takahashi, Chika; Ishida, Yoko; Hotta, Osamu; Ito, Sadayoshi

2016-10-01

Introduction Oxidative stress is one of the main mediators of progression of chronic kidney diseases (CKD). Nuclear factor E2-related factor 2 (Nrf2) is the transcription factor of antioxidant and detoxifying enzymes and related proteins which play an important role in cellular defense. Long-time hemodialysis (HD) therapy (8 hours) has been considered to be more beneficial compared to normal HD therapy (4 hours). We investigated oxidative response related to Nrf2 in peripheral blood mononuclear cells (PBMCs) of long-time HD and normal HD patients. Methods Eight adult long-time HD therapy patients (44.5 ± 3.0 years) and 10 normal HD therapy patients (68.1 ± 2.7 years) were enrolled. PBMCs were isolated and processed for expression of Nrf2 and its related genes by qRT-PCR. Plasma indoxyl sulfate, amino acids, and body constituents were measured. Findings Plasma indoxyl sulfate was significantly low after long-time HD therapy compare to that of normal HD therapy. Although, skeletal muscle mass, lean body mass, mineral and protein were significantly decreased 2 months in normal HD patients, those in long-time HD patients were significantly increased after 2 months. Almost of amino acids were significantly decreased after HD therapy in both HD therapies. Plasma amino acids were significantly low in long-time HD patients compared to normal HD patients. In PBMCs, the expression of Nrf2 was significantly decreased and hemooxygenase-1 expression was significantly increased in long-time HD compared to normal HD. Conclusion These observations indicate the beneficial effects of in long-time HD in improving oxidative stress in patients. © 2016 International Society for Hemodialysis.

TWO SMALL PLANETS TRANSITING HD 3167

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Vanderburg, Andrew; Bieryla, Allyson; Latham, David W.; Mayo, Andrew W.; Berlind, Perry [Harvard–Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Duev, Dmitry A.; Jensen-Clem, Rebecca; Kulkarni, Shrinivas; Riddle, Reed [California Institute of Technology, Pasadena, CA 91125 (United States); Baranec, Christoph [University of Hawai‘i at Mānoa, Hilo, HI 96720 (United States); Law, Nicholas M. [University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); Nieberding, Megan N. [National Optical Astronomy Observatory, 950 N. Cherry Avenue, Tucson, AZ 85719 (United States); Salama, Maïssa, E-mail: avanderburg@cfa.harvard.edu [University of Hawai‘i at Mānoa, Honolulu, HI 96822 (United States)

2016-09-20

We report the discovery of two super-Earth-sized planets transiting the bright (V = 8.94, K = 7.07) nearby late G-dwarf HD 3167, using data collected by the K2 mission. The inner planet, HD 3167 b, has a radius of 1.6 R {sub ⊕} and an ultra-short orbital period of only 0.96 days. The outer planet, HD 3167 c, has a radius of 2.9 R {sub ⊕} and orbits its host star every 29.85 days. At a distance of just 45.8 ± 2.2 pc, HD 3167 is one of the closest and brightest stars hosting multiple transiting planets, making HD 3167 b and c well suited for follow-up observations. The star is chromospherically inactive with low rotational line-broadening, ideal for radial velocity observations to measure the planets’ masses. The outer planet is large enough that it likely has a thick gaseous envelope that could be studied via transmission spectroscopy. Planets transiting bright, nearby stars like HD 3167 are valuable objects to study leading up to the launch of the James Webb Space Telescope .

Generation of induced pluripotent stem cell line, CSSi004-A (2962, from a patient diagnosed with Huntington's disease at the presymptomatic stage

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Eris Bidollari

2018-04-01

Full Text Available Huntington's disease (HD is an incurable, autosomal dominant, hereditary neurodegenerative disorder that typically manifests itself in midlife. This pathology is linked to the deregulation of multiple, as yet unknown, cellular processes starting before HD onset. A human iPS cell line was generated from skin fibroblasts of a subject at the presymptomatic life stage, carrying a polyglutamine expansion in HTT gene codifying Huntingtin protein. The iPSC line contained the expected CAG expansion, expressed the expected pluripotency markers, displayed in vivo differentiation potential to the three germ layers and had a normal karyotype.

Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of the literature and two pediatric cases

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Wernicke Caroline M

2011-08-01

Full Text Available Abstract Severe acute graft versus host disease (GvHD is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children. Our meta-analysis demonstrates that the overall response-rate is high (73.8% and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively. These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients.

Replication-competent human adenovirus 11p vectors can propagate in Vero cells

International Nuclear Information System (INIS)

Gokumakulapalle, Madhuri; Mei, Ya-Fang

2016-01-01

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

Replication-competent human adenovirus 11p vectors can propagate in Vero cells

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Gokumakulapalle, Madhuri; Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

2016-08-15

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel

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Eastman Alan

2011-05-01

Full Text Available Abstract Background The Mre11/Rad50/Nbs1 (MRN complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity. Methods We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes. Results HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells. Conclusions We have identified cells with possible defects in the MRN complex

Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel

International Nuclear Information System (INIS)

Garner, Kristen M; Eastman, Alan

2011-01-01

The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity. We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes. HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells. We have identified cells with possible defects in the MRN complex and S phase arrest, and a series of compounds that may

Genome-wide analysis of the HD-ZIP IV transcription factor family in Gossypium arboreum and GaHDG11 involved in osmotic tolerance in transgenic Arabidopsis.

Science.gov (United States)

Chen, Eryong; Zhang, Xueyan; Yang, Zhaoen; Wang, Xiaoqian; Yang, Zuoren; Zhang, Chaojun; Wu, Zhixia; Kong, Depei; Liu, Zhao; Zhao, Ge; Butt, Hamama Islam; Zhang, Xianlong; Li, Fuguang

2017-06-01

HD-ZIP IV proteins belong to the homeodomain-leucine zipper (HD-ZIP) transcription factor family and are involved in trichome development and drought stress in plants. Although some functions of the HD-ZIP IV group are well understood in Arabidopsis, little is known about their function in cotton. In this study, HD-ZIP genes were identified from three Gossypium species (G. arboreum, G. raimondii and G. hirsutum) and clustered into four families (HD-ZIP I, II, III and IV) to separate HD-ZIP IV from the other three families. Systematic analyses of phylogeny, gene structure, conserved domains, and expression profiles in different plant tissues and the expression patterns under osmotic stress in leaves were further conducted in G. arboreum. More importantly, ectopic overexpression of GaHDG11, a representative of the HD-ZIP IV family, confers enhanced osmotic tolerance in transgenic Arabidopsis plants, possibly due to elongated primary root length, lower water loss rates, high osmoprotectant proline levels, significant levels of antioxidants CAT, and/or SOD enzyme activity with reduced levels of MDA. Taken together, these observations may lay the foundation for future functional analysis of cotton HD-ZIP IV genes to unravel their biological roles in cotton.

Chemical analysis of three barium stars: HD 51959, HD 88035, and HD 121447

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Karinkuzhi, Drisya; Goswami, Aruna; Sridhar, Navin; Masseron, Thomas; Purandardas, Meenakshi

2018-05-01

We present elemental abundance results from high-resolution spectral analysis of three nitrogen-enhanced barium stars. The analysis is based on spectra obtained with the fibre-fed extended range optical spectrograph attached to 1.52 m telescope at European Southern Observatory, Chile. The spectral resolution is R ˜ 48,000 and the spectral coverage spans from 3500 to 9000Å . For the objects HD 51959 and HD 88035, we present the first-time abundance analyses results. Although a few studies are available in literature on the object HD 121447, the results are significantly different from each other. We have therefore carried out a detailed chemical composition study for this object based on a high-resolution spectrum with high S/N ratio, for a better understanding of the origin of the abundance patterns observed in this star. Stellar atmospheric parameters, the effective temperature, surface gravity, microturbulence, and metallicity of the stars are determined from the local thermodynamic equilibrium analysis using model atmospheres. The metallicities of HD 51959 and HD 88035 are found to be near-solar; they exhibit enhanced abundances of neutron-capture elements. HD 121447 is found to be moderately metal-poor with [Fe/H] = -0.65. While carbon is near-solar in the other two objects, HD 121447 shows carbon enhancement at a level, [C/Fe] = 0.82. Neutron-capture elements are highly enhanced with [X/Fe] > 2 (X: Ba, La, Pr, Nd, Sm) in this object. The α- and iron-peak elements show abundances very similar to field giants with the same metallicity. From kinematic analysis all the three objects are found to be members of thin disc population with a high probability of 0.99, 0.99, and 0.92 for HD 51959, HD 88035, and HD 121447, respectively.

NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

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Wei-Jan Huang

2012-01-01

Full Text Available HDAC inhibitors (HDACis have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP, and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231 and rat glioma cells (C6, with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1, gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1 gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo.

Low latency adaptive streaming of HD H.264 video over 802.11 wireless networks with cross-layer feedback

Science.gov (United States)

Patti, Andrew; Tan, Wai-tian; Shen, Bo

2007-09-01

Streaming video in consumer homes over wireless IEEE 802.11 networks is becoming commonplace. Wireless 802.11 networks pose unique difficulties for streaming high definition (HD), low latency video due to their error-prone physical layer and media access procedures which were not designed for real-time traffic. HD video streaming, even with sophisticated H.264 encoding, is particularly challenging due to the large number of packet fragments per slice. Cross-layer design strategies have been proposed to address the issues of video streaming over 802.11. These designs increase streaming robustness by imposing some degree of monitoring and control over 802.11 parameters from application level, or by making the 802.11 layer media-aware. Important contributions are made, but none of the existing approaches directly take the 802.11 queuing into account. In this paper we take a different approach and propose a cross-layer design allowing direct, expedient control over the wireless packet queue, while obtaining timely feedback on transmission status for each packet in a media flow. This method can be fully implemented on a media sender with no explicit support or changes required to the media client. We assume that due to congestion or deteriorating signal-to-noise levels, the available throughput may drop substantially for extended periods of time, and thus propose video source adaptation methods that allow matching the bit-rate to available throughput. A particular H.264 slice encoding is presented to enable seamless stream switching between streams at multiple bit-rates, and we explore using new computationally efficient transcoding methods when only a high bit-rate stream is available.

Automatic anterior chamber angle assessment for HD-OCT images.

Science.gov (United States)

Tian, Jing; Marziliano, Pina; Baskaran, Mani; Wong, Hong-Tym; Aung, Tin

2011-11-01

Angle-closure glaucoma is a major blinding eye disease and could be detected by measuring the anterior chamber angle in the human eyes. High-definition OCT (Cirrus HD-OCT) is an emerging noninvasive, high-speed, and high-resolution imaging modality for the anterior segment of the eye. Here, we propose a novel algorithm which automatically detects a new landmark, Schwalbe's line, and measures the anterior chamber angle in the HD-OCT images. The distortion caused by refraction is corrected by dewarping the HD-OCT images, and three biometric measurements are defined to quantitatively assess the anterior chamber angle. The proposed algorithm was tested on 40 HD-OCT images of the eye and provided accurate measurements in about 1 second.

Mouse DRG Cell Line with Properties of Nociceptors.

Science.gov (United States)

Doran, Ciara; Chetrit, Jonathan; Holley, Matthew C; Grundy, David; Nassar, Mohammed A

2015-01-01

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons.

Spectrum variability of the silicon Ap star HD 192913

International Nuclear Information System (INIS)

Riabchikova, T.A.; Davidova, E.S.; Adelman, S.J.

1990-01-01

The metal lines in the spectrum of the silicon Ap star HD 192913 are found to change with the photometric period. Many commonly found atomic species have lines which vary together in phase. The spectrum contains lines of most of the doubly ionized rare earth elements. 27 refs

Evidences of extragalactic origin and planet engulfment in the metal-poor twin pair HD 134439/HD 134440

Science.gov (United States)

Reggiani, Henrique; Meléndez, Jorge

2018-04-01

Recent studies of chemical abundances in metal-poor halo stars show the existence of different populations, which is important for studies of Galaxy formation and evolution. Here, we revisit the twin pair of chemically anomalous stars HD 134439 and HD 134440, using high resolution (R ˜ 72 000) and high S/N ratio (S/N ˜ 250) HDS/Subaru spectra. We compare them to the well-studied halo star HD 103095, using the line-by-line differential technique to estimate precise stellar parameters and LTE chemical abundances. We present the abundances of C, O, Na, Mg, Si, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, Sr, Y, Ba, La, Ce, Nd, and Sm. We compare our results to the precise abundance patterns of Nissen & Schuster (2010) and data from dwarf Spheroidal galaxies (dSphs). We show that the abundance pattern of these stars appears to be closely linked to that of dSphs with [α/Fe] knee below [Fe/H] < -1.5. We also find a systematic difference of 0.06 ± 0.01 dex between the abundances of these twin binary stars, which could be explained by the engulfment of a planet, thus suggesting that planet formation is possible at low metallicities ([Fe/H] = -1.4).

URG11 Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion

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Bin Pan

2018-01-01

Full Text Available Upregulated gene 11 (URG11, a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP, compared with human prostate epithelial cell line (RWPE-1. Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level of β-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression of β-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.

Infrared spectra of peculiar emission-line stars

International Nuclear Information System (INIS)

Andrillat, Yvette; Houziaux, Leo

1975-01-01

230A/mm spectra of HD51585, V1016Cyg, HBV475 and XXOph between 8,000 and 11,000A are described. Important spectral variations have been noted between 1974 and 1975. Satisfactory identifications cannot be proposed for lines at 9,180 and 9,204A [fr

Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells.

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Sook-Kyoung Heo

Full Text Available Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI, is approved for the second-line treatment of chronic myeloid leukemia (CML in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP-1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi-1 cells either in presence or absence of all trans-retinoic acid (ATRA. We found that radotinib promoted differentiation and induced CD11b expression in AML cells by downregulating LYN. However, CD11b expression induced by ATRA in HL60 cells was decreased by radotinib through upregulation of LYN. Furthermore, radotinib mainly induced apoptosis of CD11b+ cells in the total population of AML cells. Radotinib also increased apoptosis of CD11b+ HL60 cells when they were differentiated by ATRA/dasatinib treatment. We show that radotinib induced apoptosis via caspase-3 activation and the loss of mitochondrial membrane potential (ΔΨm in CD11b+ cells differentiated from AML cells. Our results suggest that radotinib may be used as a candidate drug in AML or a chemosensitizer for treatment of AML by other therapeutics.

Behavior of Abundances in Chemically Peculiar Dwarf and Subgiant A-Type Stars: HD 23193 and HD 170920

Science.gov (United States)

Kılıçoğlu, Tolgahan; Çalışkan, Şeyma; Ünal, Kübraözge

2018-01-01

To understand the origin of the abundance peculiarities of non-magnetic A-type stars, we present the first detailed chemical abundance analysis of a metallic line star HD 23193 (A2m) and an A-type subgiant HD 170920 (A5), which could have been a HgMn star on the main sequence. Our analysis is based on medium (R ∼ 14,000) and high (R ∼ 40,000) resolution spectroscopic data of the stars. The abundances of 18 elements are derived: C, O, Na, Mg, Al, Si, S, Ca, Sc, Ti, Cr, Mn, Fe, Ni, Zn, Sr, Y, and Ba. The masses of HD 23193 and HD 170920 are estimated from evolutionary tracks as 2.3 ± 0.1 M ⊙ and 2.9 ± 0.1 M ⊙. The ages are found to be 635 ± 33 Myr for HD 23193 and 480 ± 50 Myr for HD 170920 using isochrones. The abundance pattern of HD 23193 shows deviations from solar values in the iron-peak elements and indicates remarkable overabundances of Sr (1.16), Y (1.03), and Ba (1.24) with respect to the solar abundances. We compare the derived abundances of this moderately rotating (v\\sin i =37.5 km s‑1) Am star to the theoretical chemical evolution models including rotational mixing. The theoretically predicted abundances resemble our derived abundance pattern, except for a few elements (Si and Cr). For HD 170920, we find nearly solar abundances, except for C (‑0.43), S (0.16), Ti (0.15), Ni (0.16), Zn (0.41), Y (0.57), and Ba (0.97). Its low rotational velocity (v\\sin i=14.5 km s‑1), reduced carbon abundance, and enhanced heavy element abundances suggest that the star is most likely an evolved HgMn star. Based on observations made at the TÜBITAK National Observatory (Program ID 14BRTT150–671), and the Ankara University Observatory, Turkey.

Structure and function of homodomain-leucine zipper (HD-Zip) proteins.

Science.gov (United States)

Elhiti, Mohamed; Stasolla, Claudio

2009-02-01

Homeodomain-leucine zipper (HD-Zip) proteins are transcription factors unique to plants and are encoded by more than 25 genes in Arabidopsis thaliana. Based on sequence analyses these proteins have been classified into four distinct groups: HD-Zip I-IV. HD-Zip proteins are characterized by the presence of two functional domains; a homeodomain (HD) responsible for DNA binding and a leucine zipper domain (Zip) located immediately C-terminal to the homeodomain and involved in protein-protein interaction. Despite sequence similarities HD-ZIP proteins participate in a variety of processes during plant growth and development. HD-Zip I proteins are generally involved in responses related to abiotic stress, abscisic acid (ABA), blue light, de-etiolation and embryogenesis. HD-Zip II proteins participate in light response, shade avoidance and auxin signalling. Members of the third group (HD-Zip III) control embryogenesis, leaf polarity, lateral organ initiation and meristem function. HD-Zip IV proteins play significant roles during anthocyanin accumulation, differentiation of epidermal cells, trichome formation and root development.

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience.

Science.gov (United States)

Widmer, Fabienne; Balabanov, Stefan; Soldini, Davide; Samaras, Panagiotis; Gerber, Bernhard; Manz, Markus G; Goede, Jeroen S

2018-02-01

Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians' and patients' choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38-68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.

Antileukemic Effect of Tualang Honey on Acute and Chronic Leukemia Cell Lines

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Nik Muhd Khuzaimi Nik Man

2015-01-01

Full Text Available Complementary medicine using natural product as antitumor is on the rise. Much research has been performed on Tualang Honey and it was shown to have therapeutic potential in wound healing, and antimicrobial activity and be antiproliferative against several cancer models such as human osteosarcoma (HOS, human breast (MCF-7 and MDA-MB-231, and cervical (HeLa cancer cell lines. To date, there was limited study on antileukemic properties of Tualang (Koompassia excelsa Honey. The aim of this study was to evaluate the antileukemic effect of Tualang Honey on acute and chronic leukemia cell lines. Leukemia cell lines (K562 and MV4-11 and human mononuclear cell isolated from peripheral blood were grown in RPM1 1640 culture medium. The cells were incubated with increasing concentrations of Tualang Honey. After incubation, the evaluation of viability and apoptosis was performed. The morphological changes of leukemia cells were the presence of cytoplasmic blebs followed by apoptotic bodies and round shape of cells. IC50 against K562 and MV4-11 was determined. Tualang Honey gave 53.9% and 50.6% apoptosis activity on K562 and MV4-11, respectively, while on human mononuclear cell it was 37.4%. Tualang Honey has the apoptosis-inducing ability for acute and chronic myeloid leukemia (K562 and MV4-11 cell lines.

THE ROTATION PERIOD OF HD-77581 (VELA X-1)

NARCIS (Netherlands)

ZUIDERWIJK, EJ

The rotation period of HD 77581, supergiant primary in the X-ray binary Vela X-1, is determined from an analysis of selected absorption line profiles. The rotation rate determined from He I line profiles is 0.67 +/- 0.04 times that of the binary angular velocity, corresponding to a rotation velocity

The UV (IUE) spectrum of the planetary nebula PC 11 (HD 149427)

NARCIS (Netherlands)

Parthasarathy, M; Garcia-Lario, P; Pottasch, [No Value; de Martino, D; Surendiranath, R

The UV spectrum of PC 11 is found to show variations in the strength of the O III] 1666 Angstrom, N III] 1750 Angstrom and C III] 1909 Angstrom emission lines. The detection of continuum emission in the wavelength interval 2650 Angstrom to 3200 Angstrom indicates that the central star of PC 11 has

Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells

Science.gov (United States)

Takachi, Takayuki; Takahashi, Masahiko; Takahashi-Yoshita, Manami; Higuchi, Masaya; Obata, Miki; Mishima, Yukio; Okuda, Shujiro; Tanaka, Yuetsu; Matsuoka, Masao; Saitoh, Akihiko; Green, Patrick L; Fujii, Masahiro

2015-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells. PMID:25613934

Infrared absorption spectra of gaseous HD. II. Collision-induced fundamental band of HD in HD--Ne and HD--Ar mixtures at room temperature

International Nuclear Information System (INIS)

Prasad, R.D.G.; Reddy, S.P.

1976-01-01

The collision-induced infrared absorption spectra of the fundamental band of HD in binary mixtures of HD with Ne and Ar at room temperature have been studied with an absorption path length of 105.2 cm for different base densities of HD in the range 8--20 amagat and a number of total gas densities up to 175 amagat. The observed features of the profiles of the enhancement of absorption in these mixtures resemble closely those of the corresponding profiles of the fundamental band of H 2 in binary mixtures with Ne and Ar. The binary absorption coefficients of the band obtained from the measured integrated intensities are (1.84 +- 0.06) x 10 -35 and (4.41 +- 0.06) x 10 -35 cm 6 s -1 for HD--Ne and HD--Ar, respectively. The characteristic half-width parameters, delta/subd/ and delta/subc/ of the overlap transitions and delta/subq/ (and delta/subq//sub prime/) of the quadrupolar transitions, are obtained from an analysis of the profiles of the enhancement of absorption in both these mixtures. The quantity delta/subc/ which is the half-width of the intercollisional interference dip of the Q branch increases with the density of the perturbing gas Ne or Ar, and for HD--Ne it varies in a manner similar to that for HD--He as described in Paper I of this series

Accurate effective temperatures of the metal-poor benchmark stars HD 140283, HD 122563, and HD 103095 from CHARA interferometry

Science.gov (United States)

Karovicova, I.; White, T. R.; Nordlander, T.; Lind, K.; Casagrande, L.; Ireland, M. J.; Huber, D.; Creevey, O.; Mourard, D.; Schaefer, G. H.; Gilmore, G.; Chiavassa, A.; Wittkowski, M.; Jofré, P.; Heiter, U.; Thévenin, F.; Asplund, M.

2018-03-01

Large stellar surveys of the Milky Way require validation with reference to a set of `benchmark' stars whose fundamental properties are well determined. For metal-poor benchmark stars, disagreement between spectroscopic and interferometric effective temperatures has called the reliability of the temperature scale into question. We present new interferometric measurements of three metal-poor benchmark stars, HD 140283, HD 122563, and HD 103095, from which we determine their effective temperatures. The angular sizes of all the stars were determined from observations with the PAVO beam combiner at visible wavelengths at the CHARA array, with additional observations of HD 103095 made with the VEGA instrument, also at the CHARA array. Together with photometrically derived bolometric fluxes, the angular diameters give a direct measurement of the effective temperature. For HD 140283, we find θLD = 0.324 ± 0.005 mas, Teff = 5787 ± 48 K; for HD 122563, θLD = 0.926 ± 0.011 mas, Teff = 4636 ± 37 K; and for HD 103095, θLD = 0.595 ± 0.007 mas, Teff = 5140 ± 49 K. Our temperatures for HD 140283 and HD 103095 are hotter than the previous interferometric measurements by 253 and 322 K, respectively. We find good agreement between our temperatures and recent spectroscopic and photometric estimates. We conclude some previous interferometric measurements have been affected by systematic uncertainties larger than their quoted errors.

In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

DEFF Research Database (Denmark)

Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

1998-01-01

receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

Chromospherically active stars. IV - HD 178450 = V478 Lyr: An early-type BY Draconis type binary

Science.gov (United States)

Fekel, Francis C.

1988-01-01

It is shown that the variable star HD 178450 = V478 Lyr is a chromospherically active G8 V single-lined spectroscopic binary with a period of 2.130514 days. This star is characterized by strong UV emission features and a filled-in H-alpha absorption line which is variable in strength. Classified as an early-type BY Draconis system, it is similar to the BY Dra star HD 175742 = V775 Her. The unseen secondary of HD 178450 has a mass of about 0.3 solar masses and is believed to be an M2-M3 dwarf.

Distillation of hydrogen isotopes for polarized HD targets

Energy Technology Data Exchange (ETDEWEB)

Ohta, T., E-mail: takeshi@rcnp.osaka-u.ac.jp [Research Center for Nuclear Physics, Osaka University, Mihogaoka 10-1, Ibaraki, Osaka 567-0047 (Japan); Bouchigny, S. [IN2P3, Institut de Physique Nucleaire, F-91406 Orsay (France); CEA LIST, BP6-92265 Fontenay-aux-Roses, CEDEX (France); Didelez, J.-P. [IN2P3, Institut de Physique Nucleaire, F-91406 Orsay (France); Fujiwara, M. [Research Center for Nuclear Physics, Osaka University, Mihogaoka 10-1, Ibaraki, Osaka 567-0047 (Japan); Fukuda, K. [Kansai University of Nursing and Health Sciences, Shizuki Awaji 656-2131 (Japan); Kohri, H.; Kunimatsu, T.; Morisaki, C.; Ono, S. [Research Center for Nuclear Physics, Osaka University, Mihogaoka 10-1, Ibaraki, Osaka 567-0047 (Japan); Rouille, G. [IN2P3, Institut de Physique Nucleaire, F-91406 Orsay (France); Tanaka, M. [Kobe Tokiwa University, Ohtani-cho 2-6-2, Nagata, Kobe 653-0838 (Japan); Ueda, K.; Uraki, M.; Utsuro, M. [Research Center for Nuclear Physics, Osaka University, Mihogaoka 10-1, Ibaraki, Osaka 567-0047 (Japan); Wang, S.Y. [Institute of Physics, Academia Sinica, Taipei 11529, Taiwan (China); Department of Physics, National Kaohsiung Normal University, Kaohsiung 824, Taiwan (China); Yosoi, M. [Research Center for Nuclear Physics, Osaka University, Mihogaoka 10-1, Ibaraki, Osaka 567-0047 (Japan)

2012-02-01

We have developed a new cryogenic distillation system to purify Hydrogen-Deuteride (HD) gas for polarized HD targets in LEPS experiments at SPring-8. A small amount of ortho-H{sub 2} ({approx}0.01%) in the HD gas plays an important role in efficiently polarizing the HD target. Since there are 1-5% impurities of H{sub 2} and D{sub 2} in commercially available HD gases, it is necessary to purify the HD gas up to {approx}99.99%. The distillation system is equipped with a cryogenic distillation unit filled with many small stainless steel cells called 'Heli-pack'. The distillation unit consists of a condenser part, a rectification part, and a reboiler part. The unit is kept at the temperature of 17-21 K. The Heli-pack has a large surface area that makes a good contact between gases and liquids. An amount of 5.2 mol of commercial HD gas is fed into the distillation unit. Three trials were carried out to purify the HD gas by changing temperatures (17.5 K and 20.5 K) and gas extraction speeds (1.3 ml/min and 5.2 ml/min). The extracted gas was analyzed using a gas analyzer system combining a quadrupole mass spectrometer with a gas chromatograph. One mol of HD gas with a purity better than 99.99% has been successfully obtained for the first time. The effective NTP (Number of Theoretical Plates), which is an indication of the distillation performances, is obtained to be 37.2{+-}0.6. This value is in good agreement with a designed value of 37.9. The HD target is expected to be efficiently polarized under a well-controlled condition by adding an optimal amount of ortho-H{sub 2} to the purified HD gas.

Spectroscopic abundance analyses of the 3He stars HD 185330 and 3 Cen A

Science.gov (United States)

Sadakane, Kozo; Nishimura, Masayoshi

2018-04-01

Abundances of 21 elements in two 3He stars, HD 185330 and 3 Cen A, have been analysed relative to the well-studied sharp-lined B3 V star ι Her. Six elements (P, Ti, Mn, Fe, Ni, and Br) are over-abundant in these two peculiar stars, while six elements (C, O, Mg, Al, S, and Cl) are under-abundant. Absorption lines of the two rarely observed heavy elements Br II and Kr II are detected in both stars and these elements are both over-abundant. The centroid wavelengths of the Ca II infrared triplet lines in these stars are redshifted relative to those lines in ι Her and the presence of heavy isotopes of Ca (mass number 44-46) in these two stars is confirmed. In spite of these similarities, there are several remarkable differences in abundance pattern between these two stars. N is under-abundant in HD 185330, as in many Hg-Mn stars, while it is significantly over-abundant in 3 Cen A. P and Ga are both over-abundant in 3 Cen A, while only P is over-abundant and no trace of absorption line of Ga II can be found in HD 185330. Large over-abundances of Kr and Xe are found in both stars, while the abundance ratio Kr/Xe is significantly different between them (-1.4 dex in HD 185330 and +1.2 dex in 3 Cen A). Some physical explanations are needed to account for these qualitative differences.

NON-DETECTION OF L-BAND LINE EMISSION FROM THE EXOPLANET HD189733b

International Nuclear Information System (INIS)

Mandell, Avi M.; Deming, L. Drake; Mumma, Michael J.; Villanueva, Geronimo L.; Blake, Geoffrey A.; Knutson, Heather A.; Salyk, Colette

2011-01-01

We attempt to confirm bright non-local thermodynamic equilibrium (non-LTE) emission from the exoplanet HD 189733b at 3.25 μm, as recently reported by Swain et al. based on observations at low spectral resolving power (λ/δλ ∼ 30). Non-LTE emission lines from gas in an exoplanet atmosphere will not be significantly broadened by collisions, so the measured emission intensity per resolution element must be substantially brighter when observed at high spectral resolving power. We observed the planet before, during, and after a secondary eclipse event at a resolving power λ/δλ = 27, 000 using the NIRSPEC spectrometer on the Keck II telescope. Our spectra cover a spectral window near the peak found by Swain et al., and we compare emission cases that could account for the magnitude and wavelength dependence of the Swain et al. result with our final spectral residuals. To model the expected line emission, we use a general non-equilibrium formulation to synthesize emission features from all plausible molecules that emit in this spectral region. In every case, we detect no line emission to a high degree of confidence. After considering possible explanations for the Swain et al. results and the disparity with our own data, we conclude that an astrophysical source for the putative non-LTE emission is unlikely. We note that the wavelength dependence of the signal seen by Swain et al. closely matches the 2ν 2 band of water vapor at 300 K, and we suggest that an imperfect correction for telluric water is the source of the feature claimed by Swain et al.

Stimulation of MMP-11 (stromelysin-3) expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines

International Nuclear Information System (INIS)

Selvey, Saxon; Haupt, Larisa M; Thompson, Erik W; Matthaei, Klaus I; Irving, Michael G; Griffiths, Lyn R

2004-01-01

Matrix metalloproteinases (MMPs) are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14) and stromelysin-3 (MMP-11) are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs) were: a) treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b) grown on collagens I, IV and V; c) treated with fibronectin, con-A and matrigel; and d) co-cultured with a range of HBC (human breast cancer) cell lines of varied invasive and metastatic potential. Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms

Stimulation of MMP-11 (stromelysin-3 expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines

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Matthaei Klaus I

2004-07-01

Full Text Available Abstract Background Matrix metalloproteinases (MMPs are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14 and stromelysin-3 (MMP-11 are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. Methods To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs were: a treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b grown on collagens I, IV and V; c treated with fibronectin, con-A and matrigel; and d co-cultured with a range of HBC (human breast cancer cell lines of varied invasive and metastatic potential. Results Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. Conclusion We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms.

Detection of planet candidates around K giants. HD 40956, HD 111591, and HD 113996

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Jeong, G.; Lee, B.-C.; Han, I.; Omiya, M.; Izumiura, H.; Sato, B.; Harakawa, H.; Kambe, E.; Mkrtichian, D.

2018-02-01

Aims: The purpose of this paper is to detect and investigate the nature of long-term radial velocity (RV) variations of K-type giants and to confirm planetary companions around the stars. Methods: We have conducted two planet search programs by precise RV measurement using the 1.8 m telescope at Bohyunsan Optical Astronomy Observatory (BOAO) and the 1.88 m telescope at Okayama Astrophysical Observatory (OAO). The BOAO program searches for planets around 55 early K giants. The OAO program is looking for 190 G-K type giants. Results: In this paper, we report the detection of long-period RV variations of three K giant stars, HD 40956, HD 111591, and HD 113996. We investigated the cause of the observed RV variations and conclude the substellar companions are most likely the cause of the RV variations. The orbital analyses yield P = 578.6 ± 3.3 d, m sin i = 2.7 ± 0.6 MJ, a = 1.4 ± 0.1 AU for HD 40956; P = 1056.4 ± 14.3 d, m sin i = 4.4 ± 0.4 MJ, a = 2.5 ± 0.1 AU for HD 111591; P = 610.2 ± 3.8 d, m sin i = 6.3 ± 1.0 MJ, a = 1.6 ± 0.1 AU for HD 113996. Based on observations made with the BOES at BOAO in Korea and HIDES at OAO in Japan.Tables 3-5 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A3

Late Thyroid Sequlae after Treatment of Hodgkin's Disease (HD)

International Nuclear Information System (INIS)

Abaza, A.

2012-01-01

To identify the late effects of radio- chemotherapy (CTH) on thyroid gland in long-term survivors (LTS) HD patients regularly attending the pediatric oncology clinic of National Cancer Institute (NCI), 42 LTS (33 males and 9 females) were studied, together with 26 newly-diagnosed (ND) HD patients (15 males and 11 females) and 28 healthy controls. During 3 years period, all patients subjected to through clinical history/ examination. Files of LTS were revised for date of diagnoses, original site (s), stage, histopathological subtypes and dose/ duration of therapy. Clinical examination was done with laying stress on neck examination for thyroid swelling and lymphadenopathy. Lab investigations include hormonal assay of thyroid and parathyroid (T3, T4, TSH, Thyroglobin, and parathormone). In LTS the mean age was 14.9±3.4 yrs. versus 9.5±3.7 yrs. in ND patients. In LTS, treatment modalities included radiotherapy (RT) alone (2.4%), CTH alone (26.2%) or combination chemo-RT (71.4%). The mean followup time was 7.47±2.19 yrs. The incidence of hyper-/hypo-thyroidism was significantly higher in LTS. High TSH was found only among patients who received chemo-RT (11/26) with thyroid irradiation (IR) in the whole neck field. Finally, the study documented that the hyper-/hypo-thyroidism was one of the long-term complication of radio-CTH in HD patients. Recommendations regarding the follow-up of therapy for HD were discussed. New strategies and evidence based surveillance of the long-term effects are needed for dealing with HD, especially in children

Difference in membrane repair capacity between cancer cell lines and a normal cell line

DEFF Research Database (Denmark)

Frandsen, Stine Krog; McNeil, Anna K.; Novak, Ivana

2016-01-01

repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique...... cancer cell lines (p immortalized cell line (p

No hydrogen exosphere detected around the super-Earth HD 97658 b

Science.gov (United States)

Bourrier, V.; Ehrenreich, D.; King, G.; Lecavelier des Etangs, A.; Wheatley, P. J.; Vidal-Madjar, A.; Pepe, F.; Udry, S.

2017-01-01

The exoplanet HD 97658 b provides a rare opportunity to probe the atmospheric composition and evolution of moderately irradiated super-Earths. It transits a bright K star at a moderate orbital distance of 0.08 au. Its low density is compatible with a massive steam envelope that could photodissociate at high altitudes and become observable as escaping neutral hydrogen. Our analysis of three transits with HST/STIS at Lyman-α reveals no such signature, suggesting that the thermosphere of HD 97658 b is not hydrodynamically expanding and is subjected to a low escape of neutral hydrogen (soft X-ray source with signs of chromospheric variability in the Lyman-α line core. We determine an average reference for the intrinsic Lyman-α line and X-EUV (XUV) spectrum of the star, and show that HD 97658 b is in mild conditions of irradiation compared to other known evaporating exoplanets with an XUV irradiation about three times lower than the evaporating warm Neptune GJ436 b. This could be the reason why the thermosphere of HD 97658 b is not expanding: the low XUV irradiation prevents an efficient photodissociation of any putative steam envelope. Alternatively, it could be linked to a low hydrogen content or inefficient conversion of the stellar energy input. The HD 97658 system provides clues for understanding the stability of low-mass planet atmospheres in terms of composition, planetary density, and irradiation. Our study of HD 97658 b can be seen as a control experiment of our methodology, confirming that it does not bias detections of atmospheric escape and underlining its strength and reliability. Our results show that stellar activity can be efficiently discriminated from absorption signatures by a transiting exospheric cloud. They also highlight the potential of observing the upper atmosphere of small transiting planets to probe their physical and chemical properties.

HD 62542: Probing the Bare, Dense Core of an Interstellar Cloud

Science.gov (United States)

Welty, Daniel; Sonnentrucker, Paule G.; Rachford, Brian; Snow, Theodore; York, Donald G.

2018-01-01

We discuss the interstellar absorption from many atomic and molecular species seen in high-resolution HST/STIS UV spectra of the moderately reddened B3-5 V star HD 62542 [E(B-V) ~ 0.35; AV ~ 1.2]. This remarkable sight line exhibits both very steep far-UV extinction and a high fraction of hydrogen in molecular form -- with strong absorption from CH, C2, CN, and CO but weak absorption from CH+ and most of the commonly observed diffuse interstellar bands. Most of the material appears to reside in a single narrow velocity component -- thus offering a rare opportunity to probe the relatively dense, primarily molecular core of a single interstellar cloud, with little associated diffuse atomic gas.Detailed analyses of the absorption-line profiles seen in the UV spectra reveal a number of properties of the main diffuse molecular cloud toward HD 62542:1) The depletions of Mg, Si, and Fe are more severe than those seen in any other sight line, but the depletions of Cl and Kr are very mild; the overall pattern of depletions differs somewhat from those derived from larger samples of Galactic sight lines.2) The rotational excitation of H2 and C2 indicates that the gas is fairly cold (Tk = 40-45 K) and moderately dense (nH > 420 cm-3) somewhat higher densities are suggested by the fine-structure excitation of neutral carbon.3) The excitation temperatures characterizing the rotational populations of both 12CO (11.7 K) and 13CO (7.7 K) are higher than those typically found for Galactic diffuse molecular clouds.4) Carbon is primarily singly ionized -- N(C+) > N(CO) > N(C).5) The relative abundances of various trace neutral atomic species reflect the effects of both the steep far-UV extinction and the severe depletions of some elements.6) Differences in line widths for the various atomic and molecular species are suggestive of differences in spatial distribution within the main cloud.Support for this study was provided by NASA, via STScI grant GO-12277.008-A.

Gas Modelling in the Disc of HD 163296

Science.gov (United States)

Tilling, I.; Woitke, P.; Meeus, G.; Mora, A.; Montesinos, B.; Riviere-Marichalar, P.; Eiroa, C.; Thi, W. -F.; Isella, A.; Roberge, A.;

Production of Multiple Growth Factors by a Newly Established Human Thyroid Carcinoma Cell Line

Science.gov (United States)

Yoshida, Yataro; Ohashi, Kensaku; Sano, Emiko; Kobayashi, Hisataka; Endo, Keigo; Naruto, Masanobu; Nakamura, Toru

1992-01-01

A multiple growth factor‐producing tumor cell line (NIM‐1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM‐1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM‐1‐conditioned medium (NIM‐1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony‐stimulating factor (CSF)‐dependent cell lines, NFS60‐KX and TF‐1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte‐CSF (G‐CSF), granulocyte/macrophage‐CSF (GM‐CSF) and interleukin(IL)‐6 mRNAs in NIM‐1 cells. Enzyme‐linked immunosorbent assays (ELISA) using NIM‐1CM also confirmed the production of IL‐la and a small amount of IL‐1β besides G‐CSF, GM‐CSF and IL‐6 in NIM‐1 cells. In addition, unexpected production of IL‐11 in NIM‐1 cells was detected by northern blot hybridization analysis and by bioassay using an IL‐11‐dependent cell line. Therefore, NIM‐1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM‐CSF, IL‐6 and IL‐11. PMID:1372885

Skylab ultraviolet stellar spectra - A new white dwarf, HD 149499 B

Science.gov (United States)

Parsons, S. B.; Wray, J. D.; Benedict, G. F.; Henize, K. G.; Laget, M.

1976-01-01

The letter reports the discovery of a cool star with excess brightness in the vacuum ultraviolet on an objective-prism photograph obtained during the second Skylab mission. This star, HD 149499, is of type K0 V and has a companion with an apparent magnitude of about 11.8; the relatively flat UV spectrum observed at the position of HD 149499 is characteristic of a 10th or 11th magnitude unreddened O- or early B-type star. It is shown that the excess VUV brightness is due to the companion, HD 149499B, which probably lies in the region of the H-R diagram occupied by the hot white dwarfs. Inspection of white dwarf lists indicates that this star is the sixth or seventh brightest white dwarf known. A maximum orbital motion of 0.025 arcsec/yr is estimated along with a period of just under 500 yr.

Cell lines derived from the squash bug, Anasa tristis (Coreidae: Hemiptera).

Science.gov (United States)

Goodman, Cynthia L; Ringbauer, Joseph A; Li, Yao-Fa; Lincoln, Tamra Reall; Stanley, David

2017-05-01

The squash bug, Anasa tristis, is a pest of cucurbits that exerts direct damage on crops and is a vector of plant pathogens. We established cell lines from this insect to serve as tools for basic biology, including virology and immunology, as well as applied studies, such as insecticide development programs. We initiated 15 cell cultures, using nine media or combinations of media. The media yielding the best results were a modification of Kimura's medium and a combination of two commercially available cell culture media (EX-CELL 420 and L15). We designated the two cell lines as BCIRL-AtE-CLG11 and BCIRL-AtE-CLG15. From the AtE-CLG15 line, we isolated two sub-lines, A and B. Of these, the most consistently replicating line was AtE-CLG15A. We determined the doubling time of this line (190 h) and its mean cell diameter (14.5 ± 0.7 μm). We characterized the AtE-CLG15A line using DAF-PCR. The BCIRL-AtE-CLG15A cell line is now available for researchers world-wide.

Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.

Science.gov (United States)

Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y; Ito, C; Furukawa, H

2001-01-01

33 coumarins, mainly the simple isopentenylated coumarins and derived pyrano- and furanocoumarins, were examined for their antiproliferative activity towards several cancer and normal human cell lines. The pyrano- and furanocoumarins showed strong activity against the cancer cell lines, whereas they had weak antiproliferative activity against the normal human cell lines. The decreasing rank order of potency was osthenone (10), clausarin (25), clausenidin (26), dentatin (24), nordentatin (23), imperatorin (29), seselin (27), xanthyletin (21), suberosin (17), phebalosin (8) and osthol (12). The structure-activity relationship established from the results revealed that the 1,1-dimethylallyl and isopentenyl groups have an important role for antiproliferative activity.

SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

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Zaborski Margarete

2009-01-01

Full Text Available Abstract Background SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9(q34.11q34.13 has recently been described in T-cell acute lymphoblastic leukemia (T-ALL and in one case of acute myeloid leukemia (AML. The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene. Results Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Iβ-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Iα-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH and array-based copy number analysis were both consistent with del(9(q34.11q34.13 as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein. Conclusion Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells

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Xiaohong Xu

2017-03-01

Full Text Available Huntington disease (HD is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. Here we report correction of HD human induced pluripotent stem cells (hiPSCs using a CRISPR-Cas9 and piggyBac transposon-based approach. We show that both HD and corrected isogenic hiPSCs can be differentiated into excitable, synaptically active forebrain neurons. We further demonstrate that phenotypic abnormalities in HD hiPSC-derived neural cells, including impaired neural rosette formation, increased susceptibility to growth factor withdrawal, and deficits in mitochondrial respiration, are rescued in isogenic controls. Importantly, using genome-wide expression analysis, we show that a number of apparent gene expression differences detected between HD and non-related healthy control lines are absent between HD and corrected lines, suggesting that these differences are likely related to genetic background rather than HD-specific effects. Our study demonstrates correction of HD hiPSCs and associated phenotypic abnormalities, and the importance of isogenic controls for disease modeling using hiPSCs.

Radiosensitivity of mesothelioma cell lines

International Nuclear Information System (INIS)

Haekkinen, A.M.; Laasonen, A.; Linnainmaa, K.; Mattson, K.; Pyrhoenen, S.

1996-01-01

The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters α and β of the linear quadratic model (LQ-model) and mean inactivation dose (D MID ) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean α value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The α/β ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.)

Radiosensitivity of mesothelioma cell lines

Energy Technology Data Exchange (ETDEWEB)

Haekkinen, A.M. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland); Laasonen, A. [Dept. of Pathology, Central Hospital of Etelae-Pohjanmaa, Seinaejoki (Finland); Linnainmaa, K. [Dept. of Industrial Hygiene and Toxicology, Inst. of Occupational Health, Helsinki (Finland); Mattson, K. [Dept. Pulmonary Medicine, Univ. Central Hospital, Helsinki (Finland); Pyrhoenen, S. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland)

1996-10-01

The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters {alpha} and {beta} of the linear quadratic model (LQ-model) and mean inactivation dose (D{sub MID}) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean {alpha} value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The {alpha}/{beta} ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.).

In vitro Rb-1 gene transfer to retinoblastoma cell lines

International Nuclear Information System (INIS)

Choi, Sang Wook; Ham, Yong Hoh; Kim, Mee Heui

1994-04-01

After transfection of Rb-vector to packaging cell line (CRIP) by Ca-P precipitation method, we could select nineteen colonies of G-418 resistant clone by ring cloning. Each colony was transduced to NIH3T3 cells to select the one which produces high titer virus. After NIH3T3 cells transduction, we could get 28 colony counts for the high, 127 for the middle, and 6 for the low viral titer. With the supernatant of the high viral titer colony (CRIPRb 2-5). We transduct retinoblastoma cell lines. 5 figs, 11 refs. (Author)

The antiproliferative effect of acridone alkaloids on several cancer cell lines.

Science.gov (United States)

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H

1999-04-01

Fifteen acridone alkaloids were examined for their antiproliferative activity toward monolayers and suspension of several types of cancer and normal human cell lines. As a result, atalaphyllidine (9), 5-hydroxy-N-methylseverifoline (11), atalaphyllinine (12), and des-N-methylnoracronycine (13) showed potent antiproliferative activity against tumor cell lines, whereas they have weak cytotoxicity on normal human cell lines. The structure-activity relationship established from the results revealed that a secondary amine, hydroxyl groups at C-1 and C-5, and a prenyl group at C-2 played an important role for antiproliferative activities of the tetracyclic acridones.

IUE observations of an active region of HD206860

Energy Technology Data Exchange (ETDEWEB)

Blanco, C; Catalano, S; Marilli, E [Catania Univ. (Italy). Ist. di Astronomia

1979-08-23

The results of UV observations, with the IUE, of the Mg II H and k lines of HD206860, a GOV star, are reported. The aim of the observations was to search for short-term variability of the chromospheric emission connected with the rotation of the star.

Results of a Long-Term Spectral and Photometric Monitoring of the Herbig Ae Star HD 179218

Science.gov (United States)

Kozlova, O. V.; Alekseev, I. Yu.

2017-06-01

We present the results of the long-term spectroscopic and photometric monitoring of the Herbig Ae star HD 179218. The high-resolution spectra (R = 20000) were made on the 2.6-m telescope at the Crimean Astrophysical Observatory (CrAO) in the regions of Hα emission line. The photometric observations were obtained on 1.25-m telescope AZT-11 (CrAO) equipped with the UBVRI electrophotometer-polarimeter. Our results showed that Hα emission parameters demonstrate the long- term variability on the time scale about 4000 days. The same variability is observed in the change of the stellar brightness in V-band. The unusual behavior the V-I color index depending on the stellar brightness in the V-band can be concluded that around the star there is an additional source of IR-radiation. We believe that the obtained results can be explained by the presence in the vicinity of HD 179218 a low-mass component.

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

Science.gov (United States)

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

2014-01-01

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

FOXOs modulate proteasome activity in human-induced pluripotent stem cells of Huntington's disease and their derived neural cells.

Science.gov (United States)

Liu, Yanying; Qiao, Fangfang; Leiferman, Patricia C; Ross, Alan; Schlenker, Evelyn H; Wang, Hongmin

2017-11-15

Although it has been speculated that proteasome dysfunction may contribute to the pathogenesis of Huntington's disease (HD), a devastating neurodegenerative disorder, how proteasome activity is regulated in HD affected stem cells and somatic cells remains largely unclear. To better understand the pathogenesis of HD, we analyzed proteasome activity and the expression of FOXO transcription factors in three wild-type (WT) and three HD induced-pluripotent stem cell (iPSC) lines. HD iPSCs exhibited elevated proteasome activity and higher levels of FOXO1 and FOXO4 proteins. Knockdown of FOXO4 but not FOXO1 expression decreased proteasome activity. Following neural differentiation, the HD-iPSC-derived neural progenitor cells (NPCs) demonstrated lower levels of proteasome activity and FOXO expressions than their WT counterparts. More importantly, overexpression of FOXO4 but not FOXO1 in HD NPCs dramatically enhanced proteasome activity. When HD NPCs were further differentiated into DARPP32-positive neurons, these HD neurons were more susceptible to death than WT neurons and formed Htt aggregates under the condition of oxidative stress. Similar to HD NPCs, HD-iPSC-derived neurons showed reduced proteasome activity and diminished FOXO4 expression compared to WT-iPSC-derived neurons. Furthermore, HD iPSCs had lower AKT activities than WT iPSCs, whereas the neurons derived from HD iPSC had higher AKT activities than their WT counterparts. Inhibiting AKT activity increased both FOXO4 level and proteasome activity, indicating a potential role of AKT in regulating FOXO levels. These data suggest that FOXOs modulate proteasome activity, and thus represents a potentially valuable therapeutic target for HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

Science.gov (United States)

Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

2017-12-26

The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake

Directory of Open Access Journals (Sweden)

Xiao Chen

2017-08-01

Full Text Available Background: Andrographolide (ADR, the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.

Gene expression profiles in BCL11B-siRNA treated malignant T cells

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Grabarczyk Piotr

2011-05-01

Full Text Available Abstract Background Downregulation of the B-cell chronic lymphocytic leukemia (CLL/lymphoma11B (BCL11B gene by small interfering RNA (siRNA leads to growth inhibition and apoptosis of the human T-cell acute lymphoblastic leukemia (T-ALL cell line Molt-4. To further characterize the molecular mechanism, a global gene expression profile of BCL11B-siRNA -treated Molt-4 cells was established. The expression profiles of several genes were further validated in the BCL11B-siRNA -treated Molt-4 cells and primary T-ALL cells. Results 142 genes were found to be upregulated and 109 genes downregulated in the BCL11B-siRNA -treated Molt-4 cells by microarray analysis. Among apoptosis-related genes, three pro-apoptotic genes, TNFSF10, BIK, BNIP3, were upregulated and one anti-apoptotic gene, BCL2L1 was downregulated. Moreover, the expression of SPP1 and CREBBP genes involved in the transforming growth factor (TGF-β pathway was down 16-fold. Expression levels of TNFSF10, BCL2L1, SPP1, and CREBBP were also examined by real-time PCR. A similar expression pattern of TNFSF10, BCL2L1, and SPP1 was identified. However, CREBBP was not downregulated in the BLC11B-siRNA -treated Molt-4 cells. Conclusion BCL11B-siRNA treatment altered expression profiles of TNFSF10, BCL2L1, and SPP1 in both Molt-4 T cell line and primary T-ALL cells.

Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

International Nuclear Information System (INIS)

Hidalgo, Alfredo; Monroy, Alberto; Arana, Rosa Ma; Taja, Lucía; Vázquez, Guelaguetza; Salcedo, Mauricio

2003-01-01

Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation. We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients. All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma

Profile of He I lambda5876 in the P-Cygni-type of star HD 152408

International Nuclear Information System (INIS)

Walborn, N.R.

1975-01-01

The blue-shifted absorption component of the P-Cygni profile at He I lambda 5876 in HD 152408 (O8: Iafpe) has been found to be extremely broad, extending -1000 km sec -1 from the emission maximum. This unusual profile is probably due to overpopulation of the lower level of lambda 5876, which permits it to form throughout a greater extent of the expanding atmosphere than most other lines. This observation confirms Hutchings' identification of very large velocities in the blue-violet spectrum of HD 152408, and in particular his interpretation of a similar feature at He I lambda 3889, which is metastable. The lambda 5876 profile in HD 152408 is compared to those in the similar but less extreme P-Cygni star HD 151804 (O8 Iaf), and in the Wolf-Rayet star HD 151932 (WN7-A). The similarity between the absorption components in HD 152408 and the WN star is striking

Spectroscopic Variability of Supergiant Star HD14134, B3Ia

Indian Academy of Sciences (India)

Y. M. Maharramov

2017-06-19

Jun 19, 2017 ... the hot supergiant HD14134 studied in the present paper has a mass-loss rate of ...... tific program for the priority fields of research of the. National .... emission-line stars in the Large Magellanic Cloud, Astron. Astrophys., 158 ...

Cytogenetic Evolution of Human Ovarian Cell Lines Associated with Chemoresistance and Loss of Tumorigenicity

Directory of Open Access Journals (Sweden)

Stéphanie Struski

2003-01-01

Full Text Available In order to identify genomic changes associated with a resistant phenotype acquisition, we used comparative genomic hybridization (CGH to compare a human ovarian cell line, Igrov1, and four derived subcell lines, resistant to vincristine and presenting a reversion of malignant properties. Multicolor FISH (Multiplex‐FISH and Spectral Karyotype and conventional FISH are also used to elucidate the karyotype of parental cell line. The drug‐resistant subcell lines displayed many chromosomal abnormalities suggesting the implication of different pathways leading to a multidrug resistance phenotype. However, these cell lines shared two common rearrangements: an unbalanced translocation der(8t(8;13(p22;q? and a deletion of the 11p. These chromosomal imbalances could reflected the acquisition of the chemoresistance (der(8 or the loss of tumorigenicity properties (del(11p. Colour figure can be viewed on http://www.esacp.org/acp/2003/25‐3/struski.htm.

Dendritic cell fate is determined by BCL11A

Science.gov (United States)

Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.

2014-01-01

The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644

Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells.

Science.gov (United States)

Xu, Xiaohong; Tay, Yilin; Sim, Bernice; Yoon, Su-In; Huang, Yihui; Ooi, Jolene; Utami, Kagistia Hana; Ziaei, Amin; Ng, Bryan; Radulescu, Carola; Low, Donovan; Ng, Alvin Yu Jin; Loh, Marie; Venkatesh, Byrappa; Ginhoux, Florent; Augustine, George J; Pouladi, Mahmoud A

2017-03-14

Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. Here we report correction of HD human induced pluripotent stem cells (hiPSCs) using a CRISPR-Cas9 and piggyBac transposon-based approach. We show that both HD and corrected isogenic hiPSCs can be differentiated into excitable, synaptically active forebrain neurons. We further demonstrate that phenotypic abnormalities in HD hiPSC-derived neural cells, including impaired neural rosette formation, increased susceptibility to growth factor withdrawal, and deficits in mitochondrial respiration, are rescued in isogenic controls. Importantly, using genome-wide expression analysis, we show that a number of apparent gene expression differences detected between HD and non-related healthy control lines are absent between HD and corrected lines, suggesting that these differences are likely related to genetic background rather than HD-specific effects. Our study demonstrates correction of HD hiPSCs and associated phenotypic abnormalities, and the importance of isogenic controls for disease modeling using hiPSCs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

HD-DVD: the next consumer electronics revolution?

Science.gov (United States)

Topiwala, Pankaj N.

2003-11-01

The DVD is emerging as one of the world's favorite consumer electronics product, rapidly replacing analog videotape in the US and many other markets at prodigious rates. It is capable of offering a full feature-length, standard-definition movie in crisp rendition on TV. TV technology is itself in the midst of switching from analog to digital TV, with high-definition being the main draw. In fact, the US government has been advocating that switch over to digital TC, with both carrot and stick approaches, for nearly two decades, with only modest results--about 2% penetration. Under FCC herding, broadcasters are falling in the digital line--slowly, and sans profit. Meanwhile, delivery of HD content on portable media would be a great solution. Indeed, a new disk technology based on blue lasers is coming; but its widespread adoption may yet be four to five yeras away. But a promising new video codec--H.264/MPEG-4 AVC, the latest coding standard jointly developed by the Video Coding Experts Group (VCEG) of ITU-T and Moving Picture Experts Group (MPEG) of ISO/IEC, just might be the missing link. It offers substantial coding gains over MPEG-2, used in today's DVDs. With H.264, it appears possible to put HD movies on today's red-laser DVDs. Since consumers love DVDs, and HD--when they can see it, can H.264 and HD-DVD ignite a new revolution, now? It may have a huge impact on (H)DTV adoption rates.

Cell lines authentication and mycoplasma detection as minimun quality control of cell lines in biobanking.

Science.gov (United States)

Corral-Vázquez, C; Aguilar-Quesada, R; Catalina, P; Lucena-Aguilar, G; Ligero, G; Miranda, B; Carrillo-Ávila, J A

2017-06-01

Establishment of continuous cell lines from human normal and tumor tissues is an extended and useful methodology for molecular characterization of cancer pathophysiology and drug development in research laboratories. The exchange of these cell lines between different labs is a common practice that can compromise assays reliability due to contamination with microorganism such as mycoplasma or cells from different flasks that compromise experiment reproducibility and reliability. Great proportions of cell lines are contaminated with mycoplasma and/or are replaced by cells derived for a different origin during processing or distribution process. The scientific community has underestimated this problem and thousand of research experiment has been done with cell lines that are incorrectly identified and wrong scientific conclusions have been published. Regular contamination and authentication tests are necessary in order to avoid negative consequences of widespread misidentified and contaminated cell lines. Cell banks generate, store and distribute cell lines for research, being mandatory a consistent and continuous quality program. Methods implementation for guaranteeing both, the absence of mycoplasma and authentication in the supplied cell lines, has been performed in the Andalusian Health System Biobank. Specifically, precise results were obtained using real time PCR detection for mycoplasma and 10 STRs identification by capillary electrophoresis for cell line authentication. Advantages and disadvantages of these protocols are discussed.

Purinergic receptors and calcium signalling in human pancreatic duct cell lines

DEFF Research Database (Denmark)

Hansen, Mette R; Krabbe, Simon; Novak, Ivana

2008-01-01

pancreatic duct cell lines PANC-1 and CFPAC-1. Expression of P2 receptors was examined using RT-PCR and immunocytochemistry. Both cell lines, and also Capan-1 cells, express RNA transcripts for the following receptors: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11-14 and P2X1, P2X2, P2X4, P2X5, P2X6 and P2X7. Using Fura-2...... and single-cell imaging we tested effects of various nucleotide analogues on intracellular Ca(2+) signals in PANC-1 and CFPAC-1 cells. The cell lines responded to all nucleotides with the following efficiency: UTP >or= ATP = ATPgammaS > BzATP. ATP, UTP and ATPgammaS elicited oscillatory responses. Bz...

Hearily reddened Hg-Mn star HD 29647

International Nuclear Information System (INIS)

Strajzhis, V.; Glagolevskij, Yu.V.; Romanyuk, I.I.; Bychkov, V.D.; AN SSSR, Nizhnij Arkhyz. Spetsial'naya Astrofizicheskaya Observatoriya)

1982-01-01

A heavily reddened HD 29647 (V=8sup(m).4) star is investigated using the 6-meter telescope spectrograms with dispersions 9 and 28 A/mm and photometric observations in the Vilnius seven- color system. Parameters Tsub(e)=15600 K (corresponding spectral type B5) and log g=3.70 from hydrogen lines and Balmer jump were obtained. HD 29647 is a peculiar star of the Hg-Mn type. The radial velocity of the star is+14.1+-1.0 km/s, almost identical with that of the dark Taurus cloud and its T Tauri-type variables. If the star is near the front edge of the dark cloud at the distance of 165 pc and has Esub(B-V)=1.06, its visual absolute magnitude is - 0sup(m).9. Photometric observations permit to suspect a slight varia bility in the U, P, and X colors [ru

Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist

International Nuclear Information System (INIS)

Akech, Jacqueline; Roy, Somdutta Sinha; Das, Salil K.

2005-01-01

Changes in phospholipid and fatty acid profile are hallmarks of cancer progression. Increase in peripheral benzodiazepine receptor expression has been implicated in breast cancer. The benzodiazepine, Ro5-4864, increases cell proliferation in some breast cancer cell lines. Biosynthesis of phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates. Cholinephosphotransferase (CPT) is the terminal enzyme for the de novo biosynthesis of PC. We have addressed here whether Ro5-4864 facilitates some cancer causing mechanisms in breast cancer. We report that cell proliferation increases exponentially in aggressive breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells. Ro5-4864 also upregulates c-fos expression in breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the CPT gene is overexpressed in breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of CPT in forming PC is increased in the breast cancer cell lines cultured for 24 h. Additionally, we examined the CPT activity in the presence of nanomolar concentrations of Ro5-4864. Biosynthesis of PC was increased in breast cancer cell lines upon treatment. We therefore propose that Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells

Radiation sensitivity of Merkel cell carcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others

1995-07-30

Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

Radiation sensitivity of Merkell cell carcinoma cell lines

International Nuclear Information System (INIS)

Leonard, J. Helen; Ramsay, Jonathan R.; Kearsley, John H.; Birrell, Geoff W.

1995-01-01

Purpose: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Methods and Materials: Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after γ irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. Results: We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to γ irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Conclusion: Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution

The TERMS Project: Improved Orbital Parameters and Photometry of HD168443 and the Photometry Pipeline

Science.gov (United States)

Pilyavsky, Genady; Mahadevan, S.; Kane, S. R.; Howard, A. W.; Ciardi, D. R.; de Pree, C.; Dragomir, D.; Fischer, D.; Henry, G. W.; Jensen, E. L. N.; Laughlin, G.; Marlowe, H.; Rabus, M.; von Braun, K.; Wright, J. T.; Wang, X.

2012-01-01

The discovery of transiting planets around bright stars holds the potential to greatly enhance our understanding of planetary atmospheres. The Transit Ephemeris Refinement and Monitoring Survey (TERMS) project focuses on updating the ephemerides of known exoplanets, put tighter constraints on the orbital parameters and shrink the large errors on the predicted transit windows, enabling photometric monitoring to search for a transit signature. Here, we present the revised orbital parameters and the photometric coverage during a predicted transit window of HD168443b, a massive planet orbiting the bright star HD 168443 (V = 6.92) with a period of 58.11 days. The high eccentricity of the planetary orbit (e = 0.53) significantly enhances the a-priori transit probability (3.7%) from what is expected for a circular orbit (2.5%). The transit ephemeris was updated using refined orbital parameters from additional Keck-HIRES radial velocities. The photometry obtained at the 1 m telescope in Cerro Tololo Inter-American Observatory (CTIO) and the T8 0.8 m Automated Photometric Telescope (APT) at Fairborn Observatory achieved the necessary millimag precision. The expected change in flux (0.5%) for HD168443 was not observed during the predicted transit window, thus allowing us to rule out the transit and put tighter constrains on the orbital inclination of HD168443b. Additionally, we present the software used to analyze the CTIO data. Developed by the TERMS team, this IDL based package is a fast, precise, and easy to use program which has eliminated the need for external software and command line prompts by utilizing the functionality of a graphical user interface (GUI).

Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines

Directory of Open Access Journals (Sweden)

M. Crescimanno

2009-01-01

Full Text Available The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance. Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At IC50 dose level (17 ug/ml and 32 ug/ml respectively for sensitive and resistant cell lines, the crude extract induced differentiation associated with the expression of CD14 monocytic cell lines but not that of CD11 granulocityc cell surface antigen. Further investigations are in progress to better clarify the mechanism by which olive oil phenols induce diffentiation on this cell line.

BCL11B is frequently downregulated in HTLV-1-infected T-cells through Tax-mediated proteasomal degradation.

Science.gov (United States)

Permatasari, Happy Kurnia; Nakahata, Shingo; Ichikawa, Tomonaga; Morishita, Kazuhiro

2017-08-26

Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia-lymphoma (ATLL). The HTLV-1-encoded protein Tax plays important roles in the proliferation of HTLV-1-infected T-cells by affecting cellular proteins. In this study, we showed that Tax transcriptionally and post-transcriptionally downregulates the expression of the tumor suppressor gene B-cell leukemia/lymphoma 11B (BCL11B), which encodes a lymphoid-related transcription factor. BCL11B expression was downregulated in HTLV-1-infected T-cell lines at the mRNA and protein levels, and forced expression of BCL11B suppressed the proliferation of these cells. The proteasomal inhibitor MG132 increased BCL11B expression in HTLV-1-infected cell lines, and colocalization of Tax with BCL11B was detected in the cytoplasm of HTLV-1-infected T-cells following MG132 treatment. shRNA knock-down of Tax expression also increased the expression of BCL11B in HTLV-1-infected cells. Moreover, we found that Tax physically binds to BCL11B protein and induces the polyubiquitination of BCL11B and proteasome-dependent degradation of BCL11B. Thus, inactivation of BCL11B by Tax protein may play an important role in the Tax-mediated leukemogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Nanodiamonds around HD 97048 and Elias 1

NARCIS (Netherlands)

Van Kerckhoven, C; Tielens, AGGM; Waelkens, C

We present an analysis of ISO-SWS observations of the Herbig Ae/Be stars HD 97048 and Elias 1. Besides the well-known family of IR emission bands at 3.3, 6.2, "7.7", 8.6 and 11.2 mum these objects show strong, peculiar emission features at 3.43 and 3.53 mum. The latter two features show pronounced

Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines.

Science.gov (United States)

Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

2009-01-01

The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines.

Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines

International Nuclear Information System (INIS)

Schröpfer, Andrea; Kammerer, Ulrike; Kapp, Michaela; Dietl, Johannes; Feix, Sonja; Anacker, Jelena

2010-01-01

Matrix metalloproteinases (MMPs) are involved in the degradation of protein components of the extracellular matrix and thus play an important role in tumor invasion and metastasis. Their expression is related to the progression of gynecological cancers (e.g. endometrial, cervical or ovarian carcinoma). In this study we investigated the expression pattern of the 23 MMPs, currently known in humans, in different gynecological cancer cell lines. In total, cell lines from three endometrium carcinomas (Ishikawa, HEC-1-A, AN3 CA), three cervical carcinomas (HeLa, Caski, SiHa), three chorioncarcinomas (JEG, JAR, BeWo), two ovarian cancers (BG-1, OAW-42) and one teratocarcinoma (PA-1) were examined. The expression of MMPs was analyzed by RT-PCR, Western blot and gelatin zymography. We demonstrated that the cell lines examined can constitutively express a wide variety of MMPs on mRNA and protein level. While MMP-2, -11, -14 and -24 were widely expressed, no expression was seen for MMP-12, -16, -20, -25, -26, -27 in any of the cell lines. A broad range of 16 MMPs could be found in the PA1 cells and thus this cell line could be used as a positive control for general MMP experiments. While the three cervical cancer cell lines expressed 10-14 different MMPs, the median expression in endometrial and choriocarcinoma cells was 7 different enzymes. The two investigated ovarian cancer cell lines showed a distinctive difference in the number of expressed MMPs (2 vs. 10). Ishikawa, Caski, OAW-42 and BeWo cell lines could be the best choice for all future experiments on MMP regulation and their role in endometrial, cervical, ovarian or choriocarcinoma development, whereas the teratocarcinoma cell line PA1 could be used as a positive control for general MMP experiments

On-line production of [11C]cyanogen bromide

International Nuclear Information System (INIS)

Westerberg, G.; Laangstroem, B.

1997-01-01

The electrophilic labelling precursor [ 11 C]cyanogen bromide was produced in 95% radiochemical yield (decay-corrected) from hydrogen [ 11 C]cyanide within 3 min from the end of bombardment using a simple and convenient solid-phase on-line procedure. The [ 11 C]cyanogen bromide has been used in the synthesis of a number of labelled compounds for use in positron emission tomography. (author)

Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).

Science.gov (United States)

Jager, Martine J; Magner, J Antonio Bermudez; Ksander, Bruce R; Dubovy, Sander R

2016-08-01

To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.

Search for Exoplanets around Northern Circumpolar Stars. II. The Detection of Radial Velocity Variations in M Giant Stars HD 36384, HD 52030, and HD 208742

Energy Technology Data Exchange (ETDEWEB)

Lee, Byeong-Cheol; Jeong, Gwanghui; Han, Inwoo; Lee, Sang-Min; Kim, Kang-Min [Korea Astronomy and Space Science Institute 776, Daedeokdae-ro, Yuseong-gu, Daejeon 305-348 (Korea, Republic of); Park, Myeong-Gu; Oh, Hyeong-Il [Department of Astronomy and Atmospheric Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Mkrtichian, David E. [National Astronomical Research Institute of Thailand, Chiang Mai 50200 (Thailand); Hatzes, Artie P. [Thüringer Landessternwarte Tautenburg (TLS), Sternwarte 5, D-07778 Tautenburg (Germany); Gu, Shenghong; Bai, Jinming, E-mail: bclee@kasi.re.kr [Yunnan Observatories, Chinese Academy of Sciences, Kunming 650011 (China)

2017-07-20

We present the detection of long-period RV variations in HD 36384, HD 52030, and HD 208742 by using the high-resolution, fiber-fed Bohyunsan Observatory Echelle Spectrograph (BOES) for the precise radial velocity (RV) survey of about 200 northern circumpolar stars. Analyses of RV data, chromospheric activity indicators, and bisector variations spanning about five years suggest that the RV variations are compatible with planet or brown dwarf companions in Keplerian motion. However, HD 36384 shows photometric variations with a period very close to that of RV variations as well as amplitude variations in the weighted wavelet Z-transform (WWZ) analysis, which argues that the RV variations in HD 36384 are from the stellar pulsations. Assuming that the companion hypothesis is correct, HD 52030 hosts a companion with minimum mass 13.3 M {sub Jup} orbiting in 484 days at a distance of 1.2 au. HD 208742 hosts a companion of 14.0 M {sub Jup} at 1.5 au with a period of 602 days. All stars are located at the asymptotic giant branch (AGB) stage on the H–R diagram after undergoing the helium flash and leaving the giant clump.With stellar radii of 53.0 R {sub ⊙} and 57.2 R {sub ⊙} for HD 52030 and HD 208742, respectively, these stars may be the largest yet, in terms of stellar radius, found to host substellar companions. However, given possible RV amplitude variations and the fact that these are highly evolved stars, the planet hypothesis is not yet certain.

Interaction between x-irradiated plateau-phase bone marrow stromal cell lines and co-cultivated factor-dependent cell lines leading to leukemogenesis in vitro

International Nuclear Information System (INIS)

Naparstek, E.; Anklesaria, P.; FitzGerald, T.J.; Sakakeeny, M.A.; Greenberger, J.S.

1987-01-01

Plateau-phase mouse clonal bone marrow stromal cell lines D2XRII and C3H cl 11 produce decreasing levels of M-CSF (CSF-1), a specific macrophage progenitor cell humoral regulator, following X-irradiation in vitro. The decrease did not go below 40% of control levels, even after irradiation doses of 50,000 rad (500 Gy). In contrast, a distinct humoral regulator stimulating growth of GM-CSF/IL-3 factor-dependent (FD) hematopoietic progenitor cell lines was detected following radiation to doses above 2000 rad. This humoral factor was not detectable in conditioned medium from irradiated cells, weakly detected using factor-dependent target cell populations in agar overlay, and was prominently detected by liquid co-cultivation of factor-dependent cells with irradiated stromal cell cultures. Subclonal lines of FD cells, derived after co-cultivation revealed karyotypic abnormalities and induced myeloblastic tumors in syngeneic mice. Five-eight weeks co-cultivation was required for induction of factor independence and malignancy and was associated with dense cell to cell contact between FD cells and stromal cells demonstrated by light and electron microscopy. Increases in hematopoietic to stromal cell surface area, total number of adherent cells per flask, total non-adherent cell colonies per flask, and cumulative non-adherent cell production were observed after irradiation. The present data may prove very relevant to an understanding of the cell to cell interactions during X-irradiation-induced leukemia

CLO : The cell line ontology

NARCIS (Netherlands)

Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Meehan, Terrence F.; Diehl, Alexander D.; Vempati, Uma D.; Schuerer, Stephan C.; Pang, Chao; Malone, James; Parkinson, Helen; Liu, Yue; Takatsuki, Terue; Saijo, Kaoru; Masuya, Hiroshi; Nakamura, Yukio; Brush, Matthew H.; Haendel, Melissa A.; Zheng, Jie; Stoeckert, Christian J.; Peters, Bjoern; Mungall, Christopher J.; Carey, Thomas E.; States, David J.; Athey, Brian D.; He, Yongqun

2014-01-01

Background: Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO

Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines.

Science.gov (United States)

Challier, C; Uphoff, C C; Janssen, J W; Drexler, H G

1996-05-01

The ufo protein (also termed axl) is a member of a new family of receptor tyrosine kinases and is encoded by a transforming gene that was initially isolated from primary human myeloid leukemia cells by DNA-mediated transformation of NIH/3T3 cells. The ligand, Gas6, a protein S-related molecule lacking any known function yet, has recently been identified. We report the expression pattern of ufo mRNA in a panel of 76 human continuous leukemia-lymphoma cell lines. The gene was not expressed in cell lines derived from lymphoid malignancies (n=28), but transcription was seen in 3/11 myeloid, 0/6 monocytic, 9/13 erythroid and 11/18 megakaryocytic cell lines. Several cell lines were treated with phorbol ester leading to significant upregulation of the ufo message in constitutively positive cells. An apparent ufo mRNA overexpression was not found in any of the positive leukemia cell lines, but was identified in the drug-resistant subclones of the cervix carcinoma cell line HeLa. Southern blot analysis of restriction enzyme-digested genomic DNA did not provide evidence for gene amplification, but the HeLa subclones showed banding patterns suggestive of gene rearrangement. Two main ufo mRNA bands of 3.2 and 5.0 kb were identified; no differences in the half-lives (t1/2 = 2.5 h) of these two mRNA species could be identified. In summary, ufo, representing a novel type of receptor tyrosine kinase, is expressed solely in myeloid and erythro-megakaryocytic leukemias but not in lymphoid malignancies. These and previous data suggest an involvement of the ufo receptor tyrosine kinase in normal and malignant myelopoiesis; however, its exact role, if any, and mode of operation in leukemogenesis remains to be determined.

BD+15 2940 AND HD 233604: TWO GIANTS WITH PLANETS CLOSE TO THE ENGULFMENT ZONE

International Nuclear Information System (INIS)

Nowak, G.; Niedzielski, A.; Adamów, M.; Maciejewski, G.; Wolszczan, A.

2013-01-01

We report the discovery of planetary-mass companions to two red giants by the ongoing Penn State-Toruń Planet Search (PTPS) conducted with the 9.2 m Hobby-Eberly Telescope. The 1.1 M ☉ K0-giant, BD+15 2940, has a 1.1 M J minimum mass companion orbiting the star at a 137.5 day period in a 0.54 AU orbit what makes it the closest—in planet around a giant and possible subject of engulfment as the consequence of stellar evolution. HD 233604, a 1.5 M ☉ K5-giant, is orbited by a 6.6 M J minimum mass planet which has a period of 192 days and a semi-major axis of only 0.75 AU making it one of the least distant planets to a giant star. The chemical composition analysis of HD 233604 reveals a relatively high 7 Li abundance which may be a sign of its early evolutionary stage or recent engulfment of another planet in the system. We also present independent detections of planetary-mass companions to HD 209458 and HD 88133, and stellar activity-induced radial velocity variations in HD 166435, as part of the discussion of the observing and data analysis methods used in the PTPS project.

Spectroscopic pulsational frequency identification and mode determination of γ Doradus star HD 12901

Science.gov (United States)

Brunsden, E.; Pollard, K. R.; Cottrell, P. L.; Wright, D. J.; De Cat, P.

2012-12-01

Using multisite spectroscopic data collected from three sites, the frequencies and pulsational modes of the γ Doradus star HD 12901 were identified. A total of six frequencies in the range 1-2 d-1 were observed, their identifications supported by multiple line-profile measurement techniques and previously published photometry. Five frequencies were of sufficient signal-to-noise ratio for mode identification, and all five displayed similar three-bump standard deviation profiles which were fitted well with (l,m) = (1,1) modes. These fits had reduced χ2 values of less than 18. We propose that this star is an excellent candidate to test models of non-radially pulsating γ Doradus stars as a result of the presence of multiple (1,1) modes. This paper includes data taken at the Mount John University Observatory of the University of Canterbury (New Zealand), the McDonald Observatory of the University of Texas at Austin (Texas, USA) and the European Southern Observatory at La Silla (Chile).

Claudin11 Promoter Hypermethylation Is Frequent in Malignant Melanoma of the Skin, but Uncommon in Nevus Cell Nevi

Energy Technology Data Exchange (ETDEWEB)

Walesch, Sara K.; Richter, Antje M. [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Helmbold, Peter [Department of Dermatology, University of Heidelberg, D-69120 Heidelberg (Germany); Dammann, Reinhard H., E-mail: reinhard.dammann@gen.bio.uni-giessen.de [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany)

2015-07-07

Epigenetic inactivation of tumor-related genes is an important characteristic in the pathology of human cancers, including melanomagenesis. We analyzed the epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the skin, including six melanoma cell lines, 39 primary melanoma, 41 metastases of MM and 52 nevus cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19 out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases, but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003, respectively). Moreover, a significant increase in the methylation level of CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003). Methylation of CLDN11 was significantly more frequent in skin metastases (79%) compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found in five out of six MM cell lines (83%) and its promoter hypermethylation correlated with a reduced expression. Treatment of MM cell lines with a DNA methylation inhibitor reactivated CLDN11 transcription by its promoter demethylation. In summary, CLDN11 proved to be an epigenetically inactivated tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level represents a potential tool for assisting in the discrimination between malignant melanoma and nevus cell nevi.

Authentication of M14 melanoma cell line proves misidentification of MDA‐MB‐435 breast cancer cell line

Science.gov (United States)

Korch, Christopher; Hall, Erin M.; Dirks, Wilhelm G.; Ewing, Margaret; Faries, Mark; Varella‐Garcia, Marileila; Robinson, Steven; Storts, Douglas; Turner, Jacqueline A.; Wang, Ying; Burnett, Edward C.; Healy, Lyn; Kniss, Douglas; Neve, Richard M.; Nims, Raymond W.; Reid, Yvonne A.; Robinson, William A.

2017-01-01

A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research. PMID:28940260

Characterization of Runella slithyformis HD-Pnk, a Bifunctional DNA/RNA End-Healing Enzyme Composed of an N-Terminal 2′,3′-Phosphoesterase HD Domain and a C-Terminal 5′-OH Polynucleotide Kinase Domain

Science.gov (United States)

Munir, Annum

2016-01-01

ABSTRACT 5′- and 3′-end-healing reactions are key steps in nucleic acid break repair in which 5′-OH ends are phosphorylated by a polynucleotide kinase (Pnk) and 3′-PO4 or 2′,3′-cyclic-PO4 ends are hydrolyzed by a phosphoesterase to generate the 5′-PO4 and 3′-OH termini required for sealing by classic polynucleotide ligases. End-healing and sealing enzymes are present in diverse bacterial taxa, often organized as modular units within a single multifunctional polypeptide or as subunits of a repair complex. Here we identify and characterize Runella slithyformis HD-Pnk as a novel bifunctional end-healing enzyme composed of an N-terminal 2′,3′-phosphoesterase HD domain and a C-terminal 5′-OH polynucleotide kinase P-loop domain. HD-Pnk phosphorylates 5′-OH polynucleotides (9-mers or longer) in the presence of magnesium and any nucleoside triphosphate donor. HD-Pnk dephosphorylates RNA 2′,3′-cyclic phosphate, RNA 3′-phosphate, RNA 2′-phosphate, and DNA 3′-phosphate ends in the presence of a transition metal cofactor, which can be nickel, copper, or cobalt. HD-Pnk homologs are present in genera from 11 bacterial phyla and are often encoded in an operon with a putative ATP-dependent polynucleotide ligase. IMPORTANCE The present study provides insights regarding the diversity of nucleic acid repair strategies via the characterization of Runella slithyformis HD-Pnk as the exemplar of a novel clade of dual 5′- and 3′-end-healing enzymes that phosphorylate 5′-OH termini and dephosphorylate 2′,3′-cyclic-PO4, 3′-PO4, and 2′-PO4 ends. The distinctive feature of HD-Pnk is its domain composition, i.e., a fusion of an N-terminal HD phosphohydrolase module and a C-terminal P-loop polynucleotide kinase module. Homologs of Runella HD-Pnk with the same domain composition, same domain order, and similar polypeptide sizes are distributed widely among genera from 11 bacterial phyla. PMID:27895092

Endogenous superoxide dismutase and catalase activities and radiation resistance in mouse cell lines

International Nuclear Information System (INIS)

Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Ostrand-Rosenberg, S.

1988-01-01

The relationship between the endogenous cytoplasmic levels of the enzymes superoxide dismutase and catalase and the inhibition of cell proliferation by γ-radiation has been studied in 11 mouse cell lines. The resistance of these mouse cell lines to radiation was found to vary by over 25-fold. No correlation was found between the cytoplasmic level of CuZn-superoxide dismutase or catalase and the resistance to radiation as measured by extrapolation number (EN), quasi-threshold dose (Dsub(q)), or Dsub(o). None of the cell lines had detectable cytoplasmic Mn-superoxide dismutase. The apparent Ksub(i) of potassium cyanide for mouse CuZn-superoxide dismutase was determined (Ksub(i) = 6.5 μmol dm -3 ). (author)

Cell lines radiosensitization of thyroid cancer by histone deacetylase inhibitors

International Nuclear Information System (INIS)

Perona, M; Dagrosa, M A; Rossich, L; Casal, M; Pisarev, M A; Thomasz, L; Juvenal G J

2012-01-01

Introduction: Thyroid cancer is the most common endocrine neoplasia. Surgical resection and radioactive iodine is an effective treatment for well-differentiated tumors. Histone deacetylase inhibitors (HDAC-I) are agents that cause hyperacetylation of histone proteins and as a consequence remodeling of chromatin structure. They can induce growth arrest, differentiation and apoptotic cell death in different tumor cells. The use of HDAC-I agents could be of utility to enhance the response to external radiation therapy of those thyroid cancers that are refractory to most conventional therapeutic treatments. Objective: To study the effect of HDAC-I as radiosensitizers for the treatment of thyroid cancer and their ability to induce differentiation of thyroid cancer cells. Materials and methods: The human thyroid follicular (WRO) and papillary (TPC-1) carcinoma cell lines were seeded and incubated with increasing doses (0, 0.3, 0.5, 1 and 1.5 mM) of the HDAC-I sodium butirate (NaB) and valproic acid (VA) to evaluate cell proliferation and iodide uptake. Cells were irradiated with a 60 Co γ-ray source (1 ± 5% Gy/min) and postirradiation survival was quantified with the colony formation assay. Survival fraction at 2 Gy (SF2) was calculated for each cell line. Cell cycle and cell death were evaluated at a dose of 3 Gy. Iodide uptake, PCR analysis and transient transfection studies were performed. Results: Cell proliferation was not significantly suppressed after 24 hours of incubation with both drugs at all assayed doses. Iodide uptake was not modified after incubation with HDAC-I of both cell lines. SF2 was reduced from 68 ± 1.6 % in the control WRO cells to 42 ± 3.8 % (P<0.001) in NaB-treated cells. In TPC-1 SF2 was reduced from 32 ± 1.1 % in the control cells to 24 ± 0.8 % (P<0.01). In VA-treated cells SF2 was reduced from 69 ± 0.02 % in control WRO cells to 56 ± 0.01 % (P<0.01) and from 31 ± 2 % in control TPC-1 cells to 11 ± 1 % (P<0.01). There was an arrest

Modified extracorporeal photopheresis with cells from a healthy donor for acute graft-versus-host disease in a mouse model.

Directory of Open Access Journals (Sweden)

Holger Budde

Full Text Available Graft-versus-host disease (GvHD is a major challenge after hematopoietic stem cell transplantation but treatment options for patients are still limited. In many cases first-line treatment with glucocorticoids is not successful. Among second-line therapies the extracorporeal photopheresis (ECP is frequently performed, due to induction of selective tolerance instead of general immunosuppression. However, for some patients with severe acute GvHD the leukapheresis step of the ECP procedure is physically exhausting and limits the number of ECP cycles.We hypothesized that leukocytes from healthy cell donors could be used as a replacement for ECP leukocytes gained from the GvHD patient. For this purpose we used a well established mouse model of acute GvHD. The ECP therapy was based on cells with the genetic background of the initial donor of the stem cell transplantation. As a precondition we developed a protocol representing conventional ECP in mice equivalent to clinical used ECP setup.We could demonstrate that conventional, clinically derived ECP setup is able to alleviate acute GvHD. By using leukocytes obtained from healthy mice with the bone marrow donor's genetic background we could not observe a statistically significant therapeutic effect.Conventional human ECP setup is effective in the mouse model of severe acute GvHD. In addition we could not prove that ECP cells from healthy mice with bone marrow donor's genetic background are as effective as ECP cells derived from GvHD mice. Based on our findings, new questions arise for further studies, in which the cellular characteristics for ECP mediated immune tolerance are a matter of investigation.

Two distinct affinity binding sites for IL-1 on human cell lines

International Nuclear Information System (INIS)

Bensimon, C.; Wakasugi, N.; Tagaya, Y.; Takakura, K.; Yodoi, J.; Tursz, T.; Wakasugi, H.

1989-01-01

We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125 I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.

Science.gov (United States)

Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A; Kim, Sungjoon; Wilson, Christopher J; Lehár, Joseph; Kryukov, Gregory V; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F; Monahan, John E; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H; Cheng, Jill; Yu, Guoying K; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P; Gabriel, Stacey B; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E; Weber, Barbara L; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L; Meyerson, Matthew; Golub, Todd R; Morrissey, Michael P; Sellers, William R; Schlegel, Robert; Garraway, Levi A

2012-03-28

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.

Prevalence and Distribution of Segmentation Errors in Macular Ganglion Cell Analysis of Healthy Eyes Using Cirrus HD-OCT.

Directory of Open Access Journals (Sweden)

Rayan A Alshareef

Full Text Available To determine the frequency of different types of spectral domain optical coherence tomography (SD-OCT scan artifacts and errors in ganglion cell algorithm (GCA in healthy eyes.Infrared image, color-coded map and each of the 128 horizontal b-scans acquired in the macular ganglion cell-inner plexiform layer scans using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA macular cube 512 × 128 protocol in 30 healthy normal eyes were evaluated. The frequency and pattern of each artifact was determined. Deviation of the segmentation line was classified into mild (less than 10 microns, moderate (10-50 microns and severe (more than 50 microns. Each deviation, if present, was noted as upward or downward deviation. Each artifact was further described as per location on the scan and zones in the total scan area.A total of 1029 (26.8% out of total 3840 scans had scan errors. The most common scan error was segmentation error (100%, followed by degraded images (6.70%, blink artifacts (0.09% and out of register artifacts (3.3%. Misidentification of the inner retinal layers was most frequent (62%. Upward Deviation of the segmentation line (47.91% and severe deviation (40.3% were more often noted. Artifacts were mostly located in the central scan area (16.8%. The average number of scans with artifacts per eye was 34.3% and was not related to signal strength on Spearman correlation (p = 0.36.This study reveals that image artifacts and scan errors in SD-OCT GCA analysis are common and frequently involve segmentation errors. These errors may affect inner retinal thickness measurements in a clinically significant manner. Careful review of scans for artifacts is important when using this feature of SD-OCT device.

Development of the HD-Teen Inventory.

Science.gov (United States)

Driessnack, Martha; Williams, Janet K; Barnette, J Jackson; Sparbel, Kathleen J; Paulsen, Jane S

2012-05-01

Adolescents, who have a parent with Huntington Disease (HD), not only are at genetic risk for HD but also are witness to its onset and devastating clinical progression as their parent declines. To date, no mechanism has been developed to direct health care providers to the atypical adolescent experiences of these teens. The purpose of this report is to describe the process of developing the HD-Teen Inventory clinical assessment tool. Forty-eight teens and young adults from 19 U.S. states participated in the evaluation of the HD-Teen Inventory tool. Following item analysis, the number of items was reduced and item frequency and reaction scales were combined, based on the strong correlation (r = .94). The resultant tool contains 15 inventory and 2 open-ended response items. The HD-Teen Inventory emerged as a more compact and efficient tool for identifying the most salient concerns of at-risk teens in HD families in research and/or clinical practice.

Spectrophotometry of peculiar B and A stars. XVIII - The helium rich variable stars HR 1890, Sigma Orionis E, and HD 37776

Science.gov (United States)

Adelman, S. J.; Pyper, D. M.

1985-01-01

Optical region spectrophotometry at 3300-7850 A has been obtained for three helium rich stars, HR 1890, Sigma Ori E, and HD 37776, of the Orion OB1 Association. New uvby-beta photometry of HR 1890 and HD 37776 as well as published data are also used to investigate the variability of these stars. A new period of 1.53862 days was determined for HD 37776. For all three stars H-beta varies in antiphase with strong He I lines. The spectrophotometric bandpass containing the strong He I line at 4471 A varies in phase with the R index of Pedersen and Thomsen (1977). Evidence is found for weak absorption features which appear to be an extension of the 5200 A feature seen in cooler CP stars.

Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington’s disease mice

International Nuclear Information System (INIS)

Li, Xueyi; Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B.; DiFiglia, Marian

2012-01-01

Highlights: ► Primary Huntington’s disease neurons are impaired in taking up glucose. ► Rab11 modulates glucose uptake in neurons. ► Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. ► We provide a novel mechanism for glucose hypometabolism in Huntington’s disease. -- Abstract: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD 140Q/140Q ). Primary HD 140Q/140Q cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD 140Q/140Q neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD 140Q/140Q neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

Analysis of spectra of V471 Tau and HD 115404

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Shimansky, V. V.; Bikmaev, I. F.; Shimanskaya, N. N.

2011-10-01

We analyze the chemical composition of the atmospheres of a single K-type star HD 115404 and the secondary component of the V471 Tau variable. We use the technique of modeling of synthetic spectra to analyze the high-resolution spectra of these stars, taken with the RTT 150 Russian-Turkish telescope and find the abundances of 23 and 17 elements in the atmospheres of HD 115404 and V471 Tau, respectively. We demonstrate the lack of composition anomalies in the HD 115404 and show it to be consistent with the published data, inferred from equivalent widths of spectral lines. We find the abundances of 15 elements from Na to Ba to be consistent with the metallicity of the atmosphere of V471 Tau ([Fe/H] = -0.22 ± 0.12dex), which differs significantly from the average metallicity of the Hyades cluster. We show the existence of strong carbon and oxygen overabundances (by more than 1dex) due to the enrichment of the secondary by the nucleosynthesis products during the common-envelope stage of the system. On the whole, we demonstrate that V471 Tau and the other precataclysmic variables share similar composition anomalies.

An SSH library responsive to azadirachtin A constructed in Spodoptera litura Fabricius cell lines.

Science.gov (United States)

Yan, Chao; Zhang, Zhi-Xiang; Xu, Han-Hong

2012-05-31

The present study revealed differentially expressed genes responsive to azadirachtin A (Aza) in Spodoptera litura cell line through suppression subtractive hybridization. In the Aza-responsive SSH library, approximately 270 sequences represent 53 different identified genes encoding proteins with various predicted functions, and the percentages of the gene clusters were 26.09% (genetic information processing), 11.41% (cell growth and death), 7.07% (metabolism), 6.52% (signal transduction/transport) and 2.72% (immunity), respectively. Eleven clones homologous to identified genes were selected to be confirmed through quantitative real time polymerase chain reaction. Among the eleven clones validated, all but one transcript of lipase showed an increase in SL cell line collected from ETA, whereas the transcripts of other genes were lower in the SL cell line collected from ETA compared with that of UETA. These genes were considered to be related to the response of SL cell line to Aza. These will provide a new clue to uncover the molecular mechanisms of Aza acting on SL cell line. Copyright © 2012 Elsevier B.V. All rights reserved.

The new Be-type star HD 147196 in the Rho Ophiuchi dark cloud region

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The, P. S.; Perez, M. R.; De Winter, D.; Van Den Ancker, M. E.

1993-01-01

The newly discovered hot-emission line star, HD 147196 in the Rho Oph dark cloud region was observed spectroscopically and photometrically and high and low resolution IUE spectra were obtained. The finding of Irvine (1990) that this relatively bright star show its H-alpha-line in emission is confirmed. Previous H-alpha-surveys of the Rho Oph star-forming region did not detect HD 147196 as an H-alpha-emission star, meaning that it must recently be very active and has perhaps transformed itself from a B-type star at shell phase to a Be-phase. The Mg II h + k resonance lines are in absorption and they appear to be interstellar in nature, which means that either the abundance of Mg in the extended atmosphere of the star is low or that the shell is not extended enough to produce emission lines of Mg II. Photometric observations of this B8 V type star do not show any variations during at least the years covered by our monitoring or any excess of NIR radiation in its spectral energy distribution up to the M-passband at 4.8 microns.

HD 179821 (V1427 Aql, IRAS 19114+0002) - a massive post-red supergiant star?

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Şahin, T.; Lambert, David L.; Klochkova, Valentina G.; Panchuk, Vladimir E.

2016-10-01

We have derived elemental abundances of a remarkable star, HD 179821, with unusual composition (e.g. [Na/Fe] = 1.0 ± 0.2 dex) and extra-ordinary spectral characteristics. Its metallicity at [Fe/H] = 0.4 dex places it among the most metal-rich stars yet analysed. The abundance analysis of this luminous star is based on high-resolution and high-quality (S/N ≈ 120-420) optical echelle spectra from McDonald Observatory and Special Astronomy Observatory. The data includes five years of observations over 21 epochs. Standard 1D local thermodynamic equilibrium analysis provides a fresh determination of the atmospheric parameters over all epochs: Teff = 7350 ± 200 K, log g= +0.6 ± 0.3, and a microturbulent velocity ξ = 6.6 ± 1.6 km s-1 and [Fe/H] = 0.4 ± 0.2, and a carbon abundance [C/Fe] = -0.19 ± 0.30. We find oxygen abundance [O/Fe] = -0.25 ± 0.28 and an enhancement of 0.9 dex in N. A supersonic macroturbulent velocity of 22.0 ± 2.0 km s-1 is determined from both strong and weak Fe I and Fe II lines. Elemental abundances are obtained for 22 elements. HD 179821 is not enriched in s-process products. Eu is overabundant relative to the anticipated [X/Fe] ≈ 0.0. Some peculiarities of its optical spectrum (e.g. variability in the spectral line shapes) is noticed. This includes the line profile variations for H α line. Based on its estimated luminosity, effective temperature and surface gravity, HD 179821 is a massive star evolving to become a red supergiant and finally a Type II supernova.

The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity

Science.gov (United States)

Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A.; Kim, Sungjoon; Wilson, Christopher J.; Lehár, Joseph; Kryukov, Gregory V.; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F.; Monahan, John E.; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A.; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H.; Cheng, Jill; Yu, Guoying K.; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D.; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C.; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P.; Gabriel, Stacey B.; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E.; Weber, Barbara L.; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L.; Meyerson, Matthew; Golub, Todd R.; Morrissey, Michael P.; Sellers, William R.; Schlegel, Robert; Garraway, Levi A.

2012-01-01

The systematic translation of cancer genomic data into knowledge of tumor biology and therapeutic avenues remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacologic annotation is available1. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacologic profiles for 24 anticancer drugs across 479 of the lines, this collection allowed identification of genetic, lineage, and gene expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Altogether, our results suggest that large, annotated cell line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of “personalized” therapeutic regimens2. PMID:22460905

High-definition optical coherence tomography enables visualization of individual cells in healthy skin

DEFF Research Database (Denmark)

Boone, Marc; Jemec, Gregor B E; Del Marmol, Véronique

2012-01-01

High-definition OCT (HD-OCT) is an innovative technique based on the principle of conventional OCT. Our objective was to test the resolution and image quality of HD-OCT in comparison with reflectance confocal microscopy (RCM) of healthy skin. Firstly, images have been made of a ultra-high-resolut......High-definition OCT (HD-OCT) is an innovative technique based on the principle of conventional OCT. Our objective was to test the resolution and image quality of HD-OCT in comparison with reflectance confocal microscopy (RCM) of healthy skin. Firstly, images have been made of a ultra......-high-resolution line-pair phantome with both systems. Secondly, we investigated 21 healthy volunteers of different phototypes with HD-OCT and RCM on volar forearm and compared the generated images. HD-OCT displays also differences depending on the skin phototype and anatomical site. The 3-μm lateral resolution...... of the HD-OCT could be confirmed by the phantom analysis. The identification of cells in the epidermis can be made by both techniques. RCM offers the best lateral resolution, and HD-OCT has the best penetration depth, providing images of individual cells deeper within the dermis. Eccrine ducts and hair...

16 CFR 1203.11 - Marking the impact test line.

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2010-01-01

... Section 1203.11 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT... (HPI), with the brow parallel to the basic plane. Place a 5-kg (11-lb) preload ballast on top of the... helmet coinciding with the intersection of the surface of the helmet with the impact line planes defined...

HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy

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Smeets, Cleo J. L. M.; Franklin, Sophie A.; Bondulich, Marie K.; Jolinon, Nelly; Muller, Thomas; Ahmed, Mhoriam; Dick, James R. T.; Piotrowska, Izabela; Greensmith, Linda; Smolenski, Ryszard T.; Bates, Gillian P.

2015-01-01

Skeletal muscle remodelling and contractile dysfunction occur through both acute and chronic disease processes. These include the accumulation of insoluble aggregates of misfolded amyloid proteins that is a pathological feature of Huntington’s disease (HD). While HD has been described primarily as a neurological disease, HD patients’ exhibit pronounced skeletal muscle atrophy. Given that huntingtin is a ubiquitously expressed protein, skeletal muscle fibres may be at risk of a cell autonomous HD-related dysfunction. However the mechanism leading to skeletal muscle abnormalities in the clinical and pre-clinical HD settings remains unknown. To unravel this mechanism, we employed the R6/2 transgenic and HdhQ150 knock-in mouse models of HD. We found that symptomatic animals developed a progressive impairment of the contractile characteristics of the hind limb muscles tibialis anterior (TA) and extensor digitorum longus (EDL), accompanied by a significant loss of motor units in the EDL. In symptomatic animals, these pronounced functional changes were accompanied by an aberrant deregulation of contractile protein transcripts and their up-stream transcriptional regulators. In addition, HD mouse models develop a significant reduction in muscle force, possibly as a result of a deterioration in energy metabolism and decreased oxidation that is accompanied by the re-expression of the HDAC4-DACH2-myogenin axis. These results show that muscle dysfunction is a key pathological feature of HD. PMID:25748626

The antiproliferative effect of coumarins on several cancer cell lines.

Science.gov (United States)

Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y

2001-01-01

Twenty-one coumarins were examined for their antiproliferative activity towards several cancer cell lines, namely lung carcinoma (A549), melanin pigment producing mouse melanoma (B16 melanoma 4A5), human T-cell leukemia (CCRF-HSB-2), and human gastric cancer, lymph node metastasized (TGBC11TKB). The structure-activity relationship established from the results revealed that the 6,7-dihydroxy moiety had an important role for their antiproliferative activity. Analysis of cell cycle distribution indicated that esculetin-treated cells accumulated in the G1 (at 400 microM) or in S phase (at 100 microM).

Spectral Evidence for an Inner Carbon-rich Circumstellar Belt in the Young HD 36546 A-star System

Energy Technology Data Exchange (ETDEWEB)

Lisse, C. M. [JHU-APL, 11100 Johns Hopkins Road, Laurel, MD 20723 (United States); Sitko, M. L. [Department of Physics, University of Cincinnati, Cincinnati, OH 45221-0011 and Space Science Institute, Boulder, CO 80301 (United States); Russell, R. W. [The Aerospace Corporation, Los Angeles, CA 90009 (United States); Marengo, M. [Department of Physics and Astronomy, 12 Physics Hall, Iowa State University, Ames, IA 50010 (United States); Currie, T. [Subaru Telescope, National Astronomical Observatory of Japan, National Institutes of Natural Sciences, Hilo, HI 96720 (United States); Melis, C. [Center for Astrophysics and Space Sciences, University of California, San Diego, CA 92093-0424 (United States); Mittal, T. [Department of Earth and Planetary Sciences, McCone Hall, University of California at Berkeley, Berkeley, CA 94720 (United States); Song, I., E-mail: carey.lisse@jhuapl.edu, E-mail: ron.vervack@jhuapl.edu, E-mail: sitkoml@ucmail.uc.edu, E-mail: ray.russell@aero.org, E-mail: mmarengo@iastate.edu, E-mail: currie@naoj.org, E-mail: cmelis@ucsd.edu, E-mail: tmittal2@berkeley.edu, E-mail: song@physast.uga.edu [Department of Physics and Astronomy, University of Georgia, Athens, GA 30602-2451 (United States)

2017-05-10

Using the NASA/IRTF SpeX and BASS spectrometers we have obtained 0.7–13 μ m observations of the newly imaged 3–10 Myr old HD 36546 disk system. The SpeX spectrum is most consistent with the photospheric emission expected from an L {sub *} ∼ 20 L {sub ⊙}, solar abundance A1.5V star with little to no extinction, and excess emission from circumstellar dust detectable beyond 4.5 μ m. Non-detections of CO emission lines and accretion signatures point to the gas-poor circumstellar environment of a very old transition disk. Combining the SpeX + BASS spectra with archival WISE / AKARI / IRAS / Herschel photometry, we find an outer cold dust belt at ∼135 K and 20–40 au from the primary, likely coincident with the disk imaged by Subaru, and a new second inner belt with a temperature ∼570 K and an unusual, broad SED maximum in the 6–9 μ m region, tracing dust at 1.1–2.2 au. An SED maximum at 6–9 μ m has been reported in just two other A-star systems, HD 131488 and HD 121191, both of ∼10 Myr age. From Spitzer , we have also identified the ∼12 Myr old A7V HD 148657 system as having similar 5–35 μ m excess spectral features. The Spitzer data allows us to rule out water emission and rule in carbonaceous materials—organics, carbonates, SiC—as the source of the 6–9 μ m excess. Assuming a common origin for the four young A-star systems’ disks, we suggest they are experiencing an early era of carbon-rich planetesimal processing.

Tuft (caveolated) cells in two human colon carcinoma cell lines.

OpenAIRE

Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

1988-01-01

The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

Three-dimensional (3D) structure prediction and function analysis of the chitin-binding domain 3 protein HD73_3189 from Bacillus thuringiensis HD73.

Science.gov (United States)

Zhan, Yiling; Guo, Shuyuan

2015-01-01

Bacillus thuringiensis (Bt) is capable of producing a chitin-binding protein believed to be functionally important to bacteria during the stationary phase of its growth cycle. In this paper, the chitin-binding domain 3 protein HD73_3189 from B. thuringiensis has been analyzed by computer technology. Primary and secondary structural analyses demonstrated that HD73_3189 is negatively charged and contains several α-helices, aperiodical coils and β-strands. Domain and motif analyses revealed that HD73_3189 contains a signal peptide, an N-terminal chitin binding 3 domains, two copies of a fibronectin-like domain 3 and a C-terminal carbohydrate binding domain classified as CBM_5_12. Moreover, analysis predicted the protein's associated localization site to be the cell wall. Ligand site prediction determined that amino acid residues GLU-312, TRP-334, ILE-341 and VAL-382 exposed on the surface of the target protein exhibit polar interactions with the substrate.

The far-UV spectrum of the low-excitation planetary nebula HD 138403

OpenAIRE

Surdej, Jean; Heck, A.

1982-01-01

Two high-resolution far-UV spectra of the low-excitation planetary nebula HD 138403 are analyzed which were obtained with the IUE satellite over the wavelength range from 1170 to 2070 A. It is shown that the nebula's far-UV spectrum comprises a stellar continuum on which are superimposed a few emission lines, numerous interstellar absorption lines, and various types of P Cygni profiles. Evidence is examined for substantial mass loss from the central nucleus, with terminal velocities of the or...

Study on diagnosis of HD

International Nuclear Information System (INIS)

Chen Shuran; Yang Yumei; Zhang Guangli

1994-01-01

The study suggests a three-step diagnostic method for diagnosing HD. The first step is to make TgA, TmA examination; the second step is to make differential diagnosis for the cases of negative TgA, TmA through FNAB examination; the third step is to make TgA, TmA and FNAB examination for dynamic observation of controversial cases left over in the former two steps to achieve accurate diagnosis. Differential diagnosis has been made with the method in 87 cases of HD (clinical diagnosis only). The result shows that 7 cases have been diagnosed as thyropathy through comprehensive evaluation; definite diagnosis of HD has been made in 62 cases through TgA, TmA and in 77 cases through FNAB; 3 cases of negative TgA and TmA failed to accept FNAB examination, and were later diagnosed as HD through operation pathology or clinical treatment

HD5980

Science.gov (United States)

Koenigsberger, C.

HD5980 is a multiple system containing at least 3 very massive and luminous stars. Located in the Small Magellanic Cloud, it is an ideal system for studying the massive star structure and evolutionary processes in low-metallicity environments. Intensely observed over the past few decades, HD5980 is a treasure trove of information on stellar wind structure, on wind-wind collisions and on the formation of wind-blown circumstellar structures. In addition, its characteristics suggest that the eclipsing WR+LBV stars of the system are the product of quasihomogeneous chemical evolution, thus making them candidate pair production supernovae or GRB progenitors. This paper summarizes some of the outstanding results derived from half a century of observations and recent theoretical studies.

Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.

Science.gov (United States)

Velásquez, Celestino; Amako, Yutaka; Harold, Alexis; Toptan, Tuna; Chang, Yuan; Shuda, Masahiro

2018-01-01

Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication. The N-terminal Rb binding domain remains intact. MCV-positive cell lines derived from MCC explants have been valuable tools to study the molecular mechanism of MCV-induced Merkel cell carcinogenesis. Although all cell lines have integrated MCV and express truncated LT antigens, the molecular sizes of the LT proteins differ between cell lines. The copy number of integrated viral genome also varies across cell lines, leading to significantly different levels of viral protein expression. Nevertheless, these cell lines share phenotypic similarities in cell morphology, growth characteristics, and neuroendocrine marker expression. Several low-passage MCV-positive MCC cell lines have been established since the identification of MCV. We describe a new MCV-positive MCV cell line, CVG-1, with features distinct from previously reported cell lines. CVG-1 tumor cells grow in more discohesive clusters in loose round cell suspension, and individual cells show dramatic size heterogeneity. It is the first cell line to encode an MCV sT polymorphism resulting in a unique leucine (L) to proline (P) substitution mutation at amino acid 144. CVG-1 possesses a LT truncation pattern near identical to that of MKL-1 cells differing by the last two C-terminal amino acids and also shows an LT protein expression level similar to MKL-1. Viral T antigen knockdown reveals that, like other MCV-positive MCC cell lines, CVG-1 requires T antigen expression for cell proliferation.

Isolation of Melittin from Iranian Honey Bee Venom and Investigation of Its Effect on Proliferation of Cervical Cancer- HeLa Cell Line

Directory of Open Access Journals (Sweden)

K Pooshang Bagheri

2013-06-01

Full Text Available Introduction: Cervical cancer is the second prevalent cancer in developing countries and the sixth prevalent cancer in USA. Since conventional treatment methods are associated with detrimental side effects, searching for new drugs using natural ingredients is very important. Previous studies have shown that melittin (main component of honey bee venom has anticancer properties along with the effect on cell membrane and activation of apoptosis. In this study, inhibitory effects of melittin on the viability and proliferation of cervical cancer cell line (HeLa was investigated. Methods: Melittin was purified from honeybee venom using reversed-phase HPLC method. Then, biological activity of melittin was examined by hemolytic activity analysis on the red blood cells. In order to investigate whether melittin inhibits proliferation of HeLa cell, MTT assay was performed. HeLa cells were plated in a 96-well plate and treated with serially diluted concentrations of melittin for 12 and 24 hours. The viability of the cells was measured via MTT assay at 540nm. Results: Melittin showed a strong hemolytic activity (HD50=0.5 µg/ml which can be reduced by FBS(HD50=2 µg/ml. Results of MTT assay indicated that melittin shows cytotoxic effect on cervical cancer cells with IC50 = 1.2 ug/ml at 12h incubation period. Conclusion: In this study, biological activity of melittin and inhibitory effect of FBS on hemolysis were determined via hemolytic activity analysis. MTT assay indicated that melittin induced cytotoxic effects in a dose dependent manner on cervical cancer cells and it also revealed dependence on incubation time as well.

Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines

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Anh Duc Truong

2018-06-01

Full Text Available Interleukin-34 (IL-34 is a newly recognized cytokine with functions similar to macrophage colony-stimulating factor 1. It is expressed in macrophages and fibroblasts, where it induces cytokine production; however, the mechanism of chicken IL-34 (chIL-34 signaling has not been identified to date. The aim of this study was to analyze the signal transduction pathways and specific biological functions associated with chIL-34 in chicken macrophage (HD11 and fibroblast (OU2 cell lines. We found that IL-34 is a functional ligand for the colony-stimulating factor receptor (CSF-1R in chicken cell lines. Treatment with chIL-34 increased the expression of Th1 and Th17 cytokines through phosphorylation of tyrosine and serine residues in Janus kinase (JAK 2, tyrosine kinase 2 (TYK2, signal transducer and activator of transcription (STAT 1, STAT3, and Src homology 2-containing tyrosine phosphatase 2 (SHP-2, which also led to phosphorylation of NF-κB1, p-mitogen-activated protein kinase kinase kinase 7 (TAK1, MyD88, suppressor of cytokine signaling 1 (SOCS1, and extracellular signal-regulated kinase 1 and 2 (ERK1/2. Taken together, these results suggest that chIL-34 functions by binding to CSF-1R and activating the JAK/STAT, nuclear factor κ B (NF-κB, and mitogen-activated protein kinase signaling pathways; these signaling events regulate cytokine expression and suggest roles for chIL-34 in innate and adaptive immunity.

"Osiris"(HD209458b), an evaporating planet

OpenAIRE

Vidal-Madjar, Alfred; Etangs, Alain Lecavelier des

2003-01-01

Three transits of the planet orbiting the solar type star HD209458 were observed in the far UV at the wavelength of the HI Ly-alpha line. The planet size at this wavelength is equal to 4.3 R_Jup, i.e. larger than the planet Roche radius (3.6 R_Jup). Absorbing hydrogen atoms were found to be blueshifted by up to -130 km/s, exceeding the planet escape velocity. This implies that hydrogen atoms are escaping this ``hot Jupiter'' planet. An escape flux of >~ 10^10g/s is needed to explain the obser...

Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

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Jack C. Reidling

2018-01-01

Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

Energy Technology Data Exchange (ETDEWEB)

Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

The Cellosaurus, a Cell-Line Knowledge Resource

Science.gov (United States)

Bairoch, Amos

2018-01-01

The Cellosaurus is a knowledge resource on cell lines. It aims to describe all cell lines used in biomedical research. Its scope encompasses both vertebrates and invertebrates. Currently, information for >100,000 cell lines is provided. For each cell line, it provides a wealth of information, cross-references, and literature citations. The Cellosaurus is available on the ExPASy server (https://web.expasy.org/cellosaurus/) and can be downloaded in a variety of formats. Among its many uses, the Cellosaurus is a key resource to help researchers identify potentially contaminated/misidentified cell lines, thus contributing to improving the quality of research in the life sciences. PMID:29805321

Anomalous H/D isotope effect on 35Cl NQR frequencies and H/D isotope effect on 1H MAS NMR spectra in pyrrolidinium p-chlorobenzoate

International Nuclear Information System (INIS)

Nakano, Ryo; Honda, Hisashi; Nakata, Eiichi; Takamizawa, Satoshi; Noro, Sumiko; Kimura, Taiki; Kyo, Shin-shin; Ishimaru, Shin'ichi; Miyake, Ryosuke

2010-01-01

An anomalous isotope effect was observed in the 35 Cl NQR frequency of pyrrolidinium p-chlorobenzoate (C 4 H 8 NH 2 + ·ClC 6 H 4 COO - ) by deuterium substitution of hydrogen atoms which form two kinds of N-H...O type hydrogen bonds. Large negative frequency shifts of the 35 Cl resonance lines, reaching 309 kHz at 77 K and 267 kHz at 293 K, were obtained upon deuteration, although the Cl atom in the molecule formed no hydrogen bonds in the crystal. 1 H MAS NMR lines showed significant changes by the deuterium substitution, while in contrast, small shifts of 13 C CP/MAS NMR signals were obtained. Our measurements of 1 H NMR spin-lattice relaxation times (T 1 ) suggested that the H/D isotope shifts detected from the 35 Cl NQR frequencies and 1 H NMR spectra are due to structural changes rather than molecular dynamics. Single-crystal X-ray diffraction measurements showed two remarkable H/D isotope differences in the molecular arrangements, (1) the N-H length along the crystallographic a axis became 1 pm shorter, and (2) the dihedral angle between benzene and the pyrrolidine ring changed by 1.1(2)deg upon deuteration. Using density functional theory estimations, the anomalous 35 Cl NQR frequency shifts and 1 H MAS NMR line-shape changes could be explained by the dihedral angle change rather than the N-H length difference. (author)

In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variants

International Nuclear Information System (INIS)

Carney, D.N.; Mitchell, J.B.; Kinsella, T.J.

1983-01-01

The in vitro response to radiation and chemotherapeutic drugs of cell lines established from 7 patients with small cell (SC) lung cancer were tested using a soft agarose clonogenic assay. Five cell lines retained the typical morphological and biochemical amine precursor uptake decarboxylation characteristics of SC, while two cell lines had undergone ''transformation'' to large cell (LC) morphological variants with loss of amine precursor uptake decarboxylation cell characteristics of SC. The radiation survival curves for the SC lines were characterized by D0 values ranging from 51 to 140 rads and extrapolation values (n) ranging from 1.0 to 3.3. While the D0 values of the radiation survival curves of the LC variants were similar (91 and 80 rads), the extrapolation values were 5.6 and 11.1 In vitro chemosensitivity testing of the cell lines revealed an excellent correlation between prior treatment status of the patient and in vitro sensitivity or resistance. No correlation was observed between in vitro chemosensitivity and radiation response. These data suggest that transformation of SC to LC with loss of amine precursor uptake and decarboxylation characteristics is associated with a marked increase in radiation resistance (n) in vitro. The observation of a 2- to 5-fold increase in survival of the LC compared to the SC lines following 200 rads suggests that the use of larger daily radiation fractions and/or radiation-sensitizing drugs might lead to a significantly greater clinical response in patients with LC morphology. This clinical approach may have a major impact on patient response and survival

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

DEFF Research Database (Denmark)

Netchiporouk, Elena; Gantchev, Jennifer; Tsang, Matthew

2017-01-01

HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome...... (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis......, TP53 sequencing in the 11 patient-derived HTLV- 1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors...

Interstellar gas and large grains toward HD 38087

International Nuclear Information System (INIS)

Snow, T.P.; Witt, A.

1989-01-01

High-dispersion IUE spectra have been obtained of HD 38087, a star associated with reflection nebulosity where 2175 A scattering has previously been observed. The presence of 2175 A in emission implies unusually large grains, an attempt was made to see how these unusual grains may have affected the depletions of gas-phase elements onto dust in the line of sight. Even though the observed scattering region constitutes only a fraction of the total column density of dust, it is expected that the present line-of-sight analysis provides useful information on the gas and dust in the scattering nebulosity. Somewhat larger overall depletions than normal are found, and it is found that the depletions of certain elements (manganese and zinc) are enhanced relative to the normal pattern of element-to-element depletions, suggesting that grain growth has occurred with some elements sticking to grains preferentially. The molecular fraction in the line of sight is low, in accord with similar lines of sight having low far-ultraviolet extinction and large depletions. 37 refs

The Danish HD Registrya nationwide family registry of HD families in Denmark

DEFF Research Database (Denmark)

Gilling, M.; Budtz-Jorgensen, E.; Boonen, S. E.

2017-01-01

-8:100 000. 1451 individuals in the DHR had the size of the HTT CAG repeat determined of which 975 had 36 CAG repeats or more (mean ± SD: 43,5 ± 4,8). Two unrelated individuals were compound heterozygous for alleles ≥36 CAGs, and 60 individuals from 34 independent families carried an intermediate allele.......The Danish Huntington's Disease Registry (DHR) is a nationwide family registry comprising 14 245 individuals from 445 Huntington's disease (HD) families of which the largest family includes 845 individuals in 8 generations. 1136 DNA and/or blood samples and 18 fibroblast cultures are stored...... in a local biobank. The birthplace of the oldest HD carrier in each of the 261 families of Danish origin was unevenly distributed across Denmark with a high number of families in the middle part of the peninsula Jutland and in Copenhagen, the capital. The prevalence of HD in Denmark was calculated to be 5...

The massive multiple system HD 64315

Science.gov (United States)

Lorenzo, J.; Simón-Díaz, S.; Negueruela, I.; Vilardell, F.; Garcia, M.; Evans, C. J.; Montes, D.

2017-10-01

Context. The O6 Vn star HD 64315 is believed to belong to the star-forming region known as NGC 2467, but previous distance estimates do not support this association. Moreover, it has been identified as a spectroscopic binary, but existing data support contradictory values for its orbital period. Aims: We explore the multiple nature of this star with the aim of determining its distance, and understanding its connection to NGC 2467. Methods: A total of 52 high-resolution spectra have been gathered over a decade. We use their analysis, in combination with the photometric data from All Sky Automated Survey and Hipparcos catalogues, to conclude that HD 64315 is composed of at least two spectroscopic binaries, one of which is an eclipsing binary. We have developed our own program to fit four components to the combined line shapes. Once the four radial velocities were derived, we obtained a model to fit the radial-velocity curves using the Spectroscopic Binary Orbit Program (SBOP). We then implemented the radial velocities of the eclipsing binary and the light curves in the Wilson-Devinney code iteratively to derive stellar parameters for its components. We were also able to analyse the non-eclipsing binary, and to derive minimum masses for its components which dominate the system flux. Results: HD 64315 contains two binary systems, one of which is an eclipsing binary. The two binaries are separated by 0.09 arcsec (or 500 AU) if the most likely distance to the system, 5 kpc, is considered. The presence of fainter companions is not excluded by current observations. The non-eclipsing binary (HD 64315 AaAb) has a period of 2.70962901 ± 0.00000021 d. Its components are hotter than those of the eclipsing binary, and dominate the appearance of the system. The eclipsing binary (HD 64315 BaBb) has a shorter period of 1.0189569 ± 0.0000008 d. We derive masses of 14.6 ± 2.3 M⊙ for both components of the BaBb system. They are almost identical; both stars are overfilling their

Spectral Variability of the Herbig Ae/Be Star HD 37806

Science.gov (United States)

Pogodin, M. A.; Pavlovskiy, S. E.; Kozlova, O. V.; Beskrovnaya, N. G.; Alekseev, I. Yu.; Valyavin, G. G.

2018-03-01

Results are reported from a spectroscopic study of the Herbig Ae/Be star HD 37806 from 2009 through 2017 using high resolution spectrographs at the Crimean Astrophysical Observatory and the OAN SPM Observatory in Mexico. 72 spectra of this object near the Hα, Hβ, HeI 5876 and D NaI lines are analyzed. The following results were obtained: 1. The type of spectral profile of the Hα line can change from P Cyg III to double emission and vice versa over a time scale on the order of a month. 2. Narrow absorption components are observed in the profiles of the Hα and D NaI lines with radial velocities that vary over a characteristic time on the order of a day. 3. On some days, the profiles of the Hβ, HeI 5876, and D NaI lines show signs of accretion of matter to the star with a characteristic lifetime of a few days. A possible interpretation of these phenomena was considered. The transformation of the Hα profile may be related to a change in the outer latitudinal width of the boundary of the wind zone. The narrow variable absorption lines may be caused by the rotation of local azimuthal inhomogeneities in the wind zone owing to the interaction of the disk with the star's magnetosphere in a propeller regime. Several current theoretical papers that predict the formation of similar inhomogeneous wind structures were examined. It is suggested that the episodes with signs of accretion in the spectral line profiles cannot be a consequence of the modulation of these profiles by the star's rotation but are more likely caused by sudden, brief changes in the accretion rate. These spectral observations of HD 37806 should be continued in a search for cyclical variability in the spectral parameters in order to identify direct signs of magnetospheric accretion and detect possible binary behavior in this object.

GRANULATION SIGNATURES IN THE SPECTRUM OF THE VERY METAL-POOR RED GIANT HD 122563

International Nuclear Information System (INIS)

RamIrez, I.; Collet, R.; Asplund, M.; Lambert, D. L.; Allende Prieto, C.

2010-01-01

A very high resolution (R = λ/Δλ = 200, 000), high signal-to-noise ratio (S/N ≅ 340) blue-green spectrum of the very metal-poor ([Fe/H] ≅ -2.6) red giant star HD 122563 has been obtained by us at McDonald Observatory. We measure the asymmetries and core wavelengths of a set of unblended Fe I lines covering a wide range of line strength. Line bisectors exhibit the characteristic C-shape signature of surface convection (granulation) and they span from about 100 m s -1 in the strongest Fe I features to 800 m s -1 in the weakest ones. Core wavelength shifts range from about -100 to -900 m s -1 , depending on line strength. In general, larger blueshifts are observed in weaker lines, but there is increasing scatter with increasing residual flux. Assuming local thermodynamic equilibrium (LTE), we synthesize the same set of spectral lines using a state-of-the-art three-dimensional (3D) hydrodynamic simulation for a stellar atmosphere of fundamental parameters similar to those of HD 122563. We find good agreement between model predictions and observations. This allows us to infer an absolute zero point for the line shifts and radial velocity. Moreover, it indicates that the structure and dynamics of the simulation are realistic, thus providing support to previous claims of large 3D-LTE corrections to elemental abundances and fundamental parameters of very metal-poor red giant stars obtained with standard 1D-LTE spectroscopic analyses, as suggested by the hydrodynamic model used here.

O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines.

OpenAIRE

Walker, M. C.; Masters, J. R.; Margison, G. P.

1992-01-01

The DNA repair enzyme, O6-alkylguanine-DNA-alkyltransferase (ATase), is thought to be the principal mechanism controlling resistance to nitrosoureas and related alkylating agents. We compared the sensitivities of five human testis and five bladder tumour cell lines to two nitrosoureas (N-nitroso-N-methylurea (MNU) and mitozolomide) with cellular levels of ATase. Enzyme levels ranged from 3 to 206 fmol mg-1 protein (0.1 x 10(4) to 5.1 x 10(4) molecules/cell) in the testis lines and from 11 to ...

Fundamental parameters of massive stars in multiple systems: The cases of HD 17505A and HD 206267A

Science.gov (United States)

Raucq, F.; Rauw, G.; Mahy, L.; Simón-Díaz, S.

2018-06-01

Context. Many massive stars are part of binary or higher multiplicity systems. The present work focusses on two higher multiplicity systems: HD 17505A and HD 206267A. Aims: Determining the fundamental parameters of the components of the inner binary of these systems is mandatory to quantify the impact of binary or triple interactions on their evolution. Methods: We analysed high-resolution optical spectra to determine new orbital solutions of the inner binary systems. After subtracting the spectrum of the tertiary component, a spectral disentangling code was applied to reconstruct the individual spectra of the primary and secondary. We then analysed these spectra with the non-LTE model atmosphere code CMFGEN to establish the stellar parameters and the CNO abundances of these stars. Results: The inner binaries of these systems have eccentric orbits with e 0.13 despite their relatively short orbital periods of 8.6 and 3.7 days for HD 17505Aa and HD 206267Aa, respectively. Slight modifications of the CNO abundances are found in both components of each system. The components of HD 17505Aa are both well inside their Roche lobe, whilst the primary of HD 206267Aa nearly fills its Roche lobe around periastron passage. Whilst the rotation of the primary of HD 206267Aa is in pseudo-synchronization with the orbital motion, the secondary displays a rotation rate that is higher. Conclusions: The CNO abundances and properties of HD 17505Aa can be explained by single star evolutionary models accounting for the effects of rotation, suggesting that this system has not yet experienced binary interaction. The properties of HD 206267Aa suggest that some intermittent binary interaction might have taken place during periastron passages, but is apparently not operating anymore. Based on observations collected with the TIGRE telescope (La Luz, Mexico), the 1.93 m telescope at Observatoire de Haute Provence (France), the Nordic Optical Telescope at the Observatorio del Roque de los

A SEARCH FOR THE TRANSIT OF HD 168443b: IMPROVED ORBITAL PARAMETERS AND PHOTOMETRY

Energy Technology Data Exchange (ETDEWEB)

Pilyavsky, Genady; Mahadevan, Suvrath; Wright, Jason T.; Wang, Xuesong X. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Kane, Stephen R.; Ciardi, David R.; Dragomir, Diana; Von Braun, Kaspar [NASA Exoplanet Science Institute, Caltech, MS 100-22, 770 South Wilson Avenue, Pasadena, CA 91125 (United States); Howard, Andrew W. [Department of Astronomy, University of California, Berkeley, CA 94720 (United States); De Pree, Chris; Marlowe, Hannah [Department of Physics and Astronomy, Agnes Scott College, 141 East College Avenue, Decatur, GA 30030 (United States); Fischer, Debra [Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Henry, Gregory W. [Center of Excellence in Information Systems, Tennessee State University, 3500 John A. Merritt Blvd., Box 9501, Nashville, TN 37209 (United States); Jensen, Eric L. N. [Department of Physics and Astronomy, Swarthmore College, Swarthmore, PA 19081 (United States); Laughlin, Gregory [UCO/Lick Observatory, University of California, Santa Cruz, CA 95064 (United States); Rabus, Markus, E-mail: gcp5017@psu.edu, E-mail: suvrath@astro.psu.edu [Departamento de Astonomia y Astrofisica, Pontificia Universidad Catolica de Chile, Casilla 306, Santiago 22 (Chile)

2011-12-20

The discovery of transiting planets around bright stars holds the potential to greatly enhance our understanding of planetary atmospheres. In this work we present the search for transits of HD 168443b, a massive planet orbiting the bright star HD 168443 (V = 6.92) with a period of 58.11 days. The high eccentricity of the planetary orbit (e = 0.53) significantly enhances the a priori transit probability beyond that expected for a circular orbit, making HD 168443 a candidate for our ongoing Transit Ephemeris Refinement and Monitoring Survey. Using additional radial velocities from Keck High Resolution Echelle Spectrometer, we refined the orbital parameters of this multi-planet system and derived a new transit ephemeris for HD 168443b. The reduced uncertainties in the transit window make a photometric transit search practicable. Photometric observations acquired during predicted transit windows were obtained on three nights. Cerro Tololo Inter-American Observatory 1.0 m photometry acquired on 2010 September 7 had the required precision to detect a transit but fell just outside of our final transit window. Nightly photometry from the T8 0.8 m automated photometric telescope at Fairborn Observatory, acquired over a span of 109 nights, demonstrates that HD 168443 is constant on a timescale of weeks. Higher-cadence photometry on 2011 April 28 and June 25 shows no evidence of a transit. We are able to rule out a non-grazing transit of HD 168443b.

A Search for the Transit of HD 168443b: Improved Orbital Parameters and Photometry

Science.gov (United States)

Pilyavsky, Genady; Mahadevan, Suvrath; Kane, Stephen R.; Howard, Andrew W.; Ciardi, David R.; de Pree, Chris; Dragomir, Diana; Fischer, Debra; Henry, Gregory W.; Jensen, Eric L. N.; Laughlin, Gregory; Marlowe, Hannah; Rabus, Markus; von Braun, Kaspar; Wright, Jason T.; Wang, Xuesong X.

2011-12-01

The discovery of transiting planets around bright stars holds the potential to greatly enhance our understanding of planetary atmospheres. In this work we present the search for transits of HD 168443b, a massive planet orbiting the bright star HD 168443 (V = 6.92) with a period of 58.11 days. The high eccentricity of the planetary orbit (e = 0.53) significantly enhances the a priori transit probability beyond that expected for a circular orbit, making HD 168443 a candidate for our ongoing Transit Ephemeris Refinement and Monitoring Survey. Using additional radial velocities from Keck High Resolution Echelle Spectrometer, we refined the orbital parameters of this multi-planet system and derived a new transit ephemeris for HD 168443b. The reduced uncertainties in the transit window make a photometric transit search practicable. Photometric observations acquired during predicted transit windows were obtained on three nights. Cerro Tololo Inter-American Observatory 1.0 m photometry acquired on 2010 September 7 had the required precision to detect a transit but fell just outside of our final transit window. Nightly photometry from the T8 0.8 m automated photometric telescope at Fairborn Observatory, acquired over a span of 109 nights, demonstrates that HD 168443 is constant on a timescale of weeks. Higher-cadence photometry on 2011 April 28 and June 25 shows no evidence of a transit. We are able to rule out a non-grazing transit of HD 168443b.

Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone.

Directory of Open Access Journals (Sweden)

Jinhu Xiong

Full Text Available The cytokine receptor activator of nuclear factor kappa B ligand (RANKL, encoded by the Tnfsf11 gene, is essential for osteoclastogenesis and previous studies have shown that deletion of the Tnfsf11 gene using a Dmp1-Cre transgene reduces osteoclast formation in cancellous bone by more than 70%. However, the Dmp1-Cre transgene used in those studies leads to recombination in osteocytes, osteoblasts, and lining cells making it unclear whether one or more of these cell types produce the RANKL required for osteoclast formation in cancellous bone. Because osteoblasts, osteocytes, and lining cells have distinct locations and functions, distinguishing which of these cell types are sources of RANKL is essential for understanding the orchestration of bone remodeling. To distinguish between these possibilities, we have now created transgenic mice expressing the Cre recombinase under the control of regulatory elements of the Sost gene, which is expressed in osteocytes but not osteoblasts or lining cells in murine bone. Activity of the Sost-Cre transgene in osteocytes, but not osteoblast or lining cells, was confirmed by crossing Sost-Cre transgenic mice with tdTomato and R26R Cre-reporter mice, which express tdTomato fluorescent protein or LacZ, respectively, only in cells expressing the Cre recombinase or their descendants. Deletion of the Tnfsf11 gene in Sost-Cre mice led to a threefold decrease in osteoclast number in cancellous bone and increased cancellous bone mass, mimicking the skeletal phenotype of mice in which the Tnfsf11 gene was deleted using the Dmp1-Cre transgene. These results demonstrate that osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling cancellous bone.

Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered

International Nuclear Information System (INIS)

Finver, S.N.; Nishikura, K.; Finger, L.R.; Haluska, F.G.; Finan, J.; Nowell, P.C.; Croce, C.M.

1988-01-01

The authors cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8; 14)(q24; q11) translocation, and determined the sequence of the MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments utilizing a MYC first exon probe demonstrated transcriptional deregulation of the MYC gene associated with the T-cell receptor α locus on the 8q + chromosome of SKW-3 cells. Nucleotide sequence analysis of the translocation-associated (8q +) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion. None of the deletions or substitutions localized to putative 5' regulatory regions. The MYC first exon sequence was germ line in both alleles. These results demonstrate that alterations within the putative 5' MYC regulatory regions are not necessarily involved in MYC deregulation in T-cell leukemias, and they show that juxtaposition of the T-cell receptor α locus to a germ-line MYC oncogene results in MYC deregulation

Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

Science.gov (United States)

Dörrie, J; Schuh, W; Keil, A; Bongards, E; Greil, J; Fey, G H; Zunino, S J

1999-10-01

The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

Cell Line Controls for the Genotyping of a Spectrum of Human Single Nucleotide Polymorphisms in the Clinical Laboratory.

Science.gov (United States)

Kimbacher, Christine; Paar, Christian; Freystetter, Andrea; Berg, Joerg

2018-05-01

Genotyping for clinically important single nucleotide polymorphisms (SNPs) is performed by many clinical routine laboratories. To support testing, quality controls and reference materials are needed. Those may be derived from residual patient samples, left over samples of external quality assurance schemes, plasmid DNA or DNA from cell lines. DNAs from cell lines are commutable and available in large amounts. DNA from 38 cell lines were examined for suitability as controls in 11 SNP assays that are frequently used in a clinical routine laboratory: FV (1691G>A), FII (20210G>A), PAI-1 4G/5G polymorphism, MTHFR (677C>T, 1298A>C), HFE (H63D, S65C, C282Y), APOE (E2, E3, E4), LPH (-13910C>T), UGT1A1 (*28, *36, *37), TPMT (*2, *3A, *3B, *3C), VKORC1 (-1639G>A, 1173C>T), CYP2C9 (*2, *3, *5). Genotyping was performed by real-time PCR with melting curve analysis and confirmed by bi-directional sequencing. We find an almost complete spectrum of genotypic constellations within these 38 cell lines. About 12 cell lines appear sufficient as genotypic controls for the 11 SNP assays by covering almost all of the genotypes. However, hetero- and homozygous genotypes for FII and the alleles TPMT*2, UGT1A1*37 and CYP2C9*5 were not detected in any of the cell lines. DNA from most of the examined cell lines appear suitable as quality controls for these SNP assays in the laboratory routine, as to the implementation of those assays or to prepare samples for quality assurance schemes. Our study may serve as a pilot to further characterize these cell lines to arrive at the status of reference materials.

Monitoring cell line identity in collections of human induced pluripotent stem cells

Directory of Open Access Journals (Sweden)

Raquel Sarafian

2018-04-01

Full Text Available The ability to reprogram somatic cells into induced pluripotent stem cells (hiPSCs has led to the generation of large collections of cell lines from thousands of individuals with specific phenotypes, many of which will be shared among different research groups as invaluable tools for biomedical research. As hiPSC-based research involves extensive culture of many cell lines, the issue periodic cell line identification is particularly important to ensure that cell line identity remains accurate. Here we analyzed the different commercially available genotyping methods considering ease of in-house genotyping, cost and informativeness, and applied one of them in our workflow for hiPSC generation. We show that the chosen STR method was able to establish a unique DNA profile for each of the 35 individuals/hiPSC lines at the examined sites, as well as identify two discrepancies resulting from inadvertently exchanged samples. Our results highlight the importance of hiPSC line genotyping by an in-house method that allows periodic cell line identification and demonstrate that STR is a useful approach to supplement less frequent karyotyping and epigenetic evaluations. Keywords: Induced pluripotent stem cells, Genotyping, Cell line identification, Short tandem repeats, Quality control

HD 30187 B and HD 39927 B: Two suspected nearby hot subdwarfs in resolved binaries (based on observations made with the ESA Hipparcos satellite)

DEFF Research Database (Denmark)

Makarov, V.V.; Fabricius, C.

1999-01-01

Stars: Individual: HD 30187 B -- Stars: Individual: HD 39927 B - Stars: White dwarfs - Stars: Binaries: Visual......Stars: Individual: HD 30187 B -- Stars: Individual: HD 39927 B - Stars: White dwarfs - Stars: Binaries: Visual...

HD 97658 and its super-Earth

Directory of Open Access Journals (Sweden)

Van Grootel V.

2015-01-01

Full Text Available Super-Earths transiting nearby bright stars are key objects that simultaneously allow for accurate measurements of both their mass and radius, providing essential constraints on their internal composition. We present the confirmation, based on Spitzer observations, that the super-Earth HD 97658 b transits its host star. HD 97658 is a low-mass (M* = 0.77 ± 0.05 M⊙ K1 dwarf, as determined from the Hipparcos parallax and stellar evolution modeling. To constrain the planet parameters, we carry out Bayesian global analyses of Keck-HIRES radial velocities, and MOST and Spitzer photometry. HD 97658 b is a massive (MP = 7.55−0.79+0.83 M⊕ and large (RP = 2.247−0.095+0.098 R⊕ at 4.5 μm super-Earth. We investigate the possible internal compositions for HD 97658 b. Our results indicate a large rocky component, by at least 60% by mass, and very little H-He components, at most 2% by mass. We also discuss how future asteroseismic observations can improve the knowledge of the HD 97658 system, in particular by constraining its age.

Sevelamer is cost effective versus calcium carbonate for the first-line treatment of hyperphosphatemia in new patients to hemodialysis: a patient-level economic evaluation of the INDEPENDENT-HD study.

Science.gov (United States)

Ruggeri, Matteo; Bellasi, Antonio; Cipriani, Filippo; Molony, Donald; Bell, Cynthia; Russo, Domenico; Di Iorio, Biagio

2015-10-01

The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study. Cost-effectiveness analysis. Adult patients new to HD in Italy. A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy's national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis. Sevelamer was compared to calcium carbonate. Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were €3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were €2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was €1,262, resulting in a cost per LY gained of €4,897. The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates, assuming a willingness-to-pay threshold of €20,000 per LY gained. Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study. Patient quality of life or health utility was not included in the analysis. Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy.

Establishment of cell lines with rat spermatogonial stem cell characteristics

NARCIS (Netherlands)

van Pelt, Ans M. M.; Roepers-Gajadien, Hermien L.; Gademan, Iris S.; Creemers, Laura B.; de Rooij, Dirk G.; van Dissel-Emiliani, Federica M. F.

2002-01-01

Spermatogonial cell lines were established by transfecting a mixed population of purified rat A(s) (stem cells), A(pr) and A(al) spermatogonia with SV40 large T antigen. Two cell lines were characterized and found to express Hsp90alpha and oct-4, specific markers for germ cells and A spermatogonia,

Functional somatostatin receptors on a rat pancreatic acinar cell line

International Nuclear Information System (INIS)

Viguerie, N.; Tahiri-Jouti, N.; Esteve, J.P.; Clerc, P.; Logsdon, C.; Svoboda, M.; Susini, C.; Vaysse, N.; Ribet, A.

1988-01-01

Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125 I-[Tyr 11 ]Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 ± 20 fmol/10 6 cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125 I-[Tyr 11 ]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein N i to inhibit adenylate cyclase

Comparison of steroid receptors from the androgen responsive DDT1 cell line and the nonresponsive HVP cell line.

Science.gov (United States)

Norris, J S; Kohler, P O

1978-01-01

Two hamster cell lines have been isolated from androgen target tissue. The DDT1 cells derived from ductus deferens tissue exhibit a growth response to androgens, while the HVP cells derived from ventral prostate are androgen unresponsive. Both cell lines contain androgen receptors, that are similar when compared by kinetic methods, sedimentation velocity, chromatographic procedures or nuclear translocation ability. The forms of the high salt extracted nuclear receptors are indistinguishable chromatographically. Therefore, we postulate that the lesion preventing androgen induced growth in the HVP cell line is subseqent to nuclear translocation of the steroid receptor complex.

Toward a Determination of the Proton-Electron Mass Ratio from the Lamb-Dip Measurement of HD

Science.gov (United States)

Tao, L.-G.; Liu, A.-W.; Pachucki, K.; Komasa, J.; Sun, Y. R.; Wang, J.; Hu, S.-M.

2018-04-01

Precision spectroscopy of the hydrogen molecule is a test ground of quantum electrodynamics (QED), and it may serve for the determination of fundamental constants. Using a comb-locked cavity ring-down spectrometer, for the first time, we observed the Lamb-dip spectrum of the R (1 ) line in the overtone of hydrogen deuteride (HD). The line position was determined to be 217 105 182.79 ±0.03stat±0.08syst MHz (δ ν /ν =4 ×10-10 ), which is the most accurate rovibrational transition ever measured in the ground electronic state of molecular hydrogen. Moreover, from calculations including QED effects up to the order meα6, we obtained predictions for this R (1 ) line as well as for the HD dissociation energy, which are less accurate but signaling the importance of the complete treatment of nonadiabatic effects. Provided that the theoretical calculation reaches the same accuracy, the present measurement will lead to a determination of the proton-to-electron mass ratio with a precision of 1.3 parts per billion.

Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie.

Science.gov (United States)

Lutz, Manfred P; Wilke, Hansjochen; Wagener, D J Theo; Vanhoefer, Udo; Jeziorski, Krzysztof; Hegewisch-Becker, Susanna; Balleisen, Leopold; Joossens, Eric; Jansen, Rob L; Debois, Muriel; Bethe, Ullrich; Praet, Michel; Wils, Jacques; Van Cutsem, Eric

2007-06-20

This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials. A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate. Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission [CR]) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively. Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.

AtHD2D gene plays a role in plant growth, development and response to abiotic stresses in Arabidopsis thaliana

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Zhaofen eHan

2016-03-01

Full Text Available Abstracts: The histone deacetylases play important roles in the regulation of gene expression and the subsequent control of a number of important biological processes, including those involved in the response to environmental stress. A specific group of histone deacetylase genes, HD2, is present in plants. In Arabidopsis, HD2s include HD2A, HD2B, HD2C and HD2D. Previous research showed that HD2A, HD2B and HD2C are more related in terms of expression and function, but not HD2D. In this report, we studied different aspects of AtHD2D in Arabidopsis with respect to plant response to drought and other abiotic stresses. Bioinformatics analysis indicates that HD2D is distantly related to other HD2 genes. Transient expression in Nicotiana benthamiana and stable expression in Arabidopsis of AtHD2D fused with gfp showed that AtHD2D was expressed in the nucleus. Overexpression of AtHD2D resulted in developmental changes including fewer main roots, more lateral roots, and a higher root:shoot ratio. Seed germination and plant flowering time were delayed in transgenic plants expressing AtHD2D, but these plants exhibited higher degrees of tolerance to abiotic stresses, including drought, salt and cold stresses. Physiological studies indicated that the malondialdehyde (MDA content was high in wild-type plants but in plants overexpressing HD2D the MDA level increased slowly in response to stress conditions of drought, cold, and salt stress. Furthermore, electrolyte leakage in leaf cells of wild type plants increased but remained stable in transgenic plants. Our results indicate that AtHD2D is unique among HD2 genes and it plays a role in plant growth and development regulation and these changes can modulate plant stress responses.

Evidence for a connection between photospheric and wind structure in HD 64760

Science.gov (United States)

Kaufer, A.; Prinja, R. K.; Stahl, O.

2002-02-01

We report on the results of an extended optical spectroscopic monitoring campaign on the early-type B supergiant HD 64760 (B0.5 Ib). The study is based on high-resolution echelle spectra obtained with the Landessternwarte Heidelberg's HEROS instrument at ESO La Silla. Ninety-nine spectra were collected over 103 nights between January 19 and May 1, 1996. The Hα line shows a characteristic profile with a central photospheric absorption superimposed by symmetrically blue- and red-shifted wind-emission humps. The time-averaged line profile is well described by a differentially rotating and expanding radiation-driven wind: the redistribution of the wind emission flux into a double peak profile is interpreted in terms of the resonance zone effect in rotating winds as first described by Petrenz & Puls (\\cite{Pet96}). Detailed time-series analyses of the line profile variations across the Hα profile reveal for the first time in an optical data set of HD 64760 a periodic 2.4-day modulation of the inner and outer flanks of the Hα emission humps. The stronger modulations of the inner flanks of the emission humps at photospheric velocities are due to complex width variations of the underlying photospheric Hα profile. The weaker variations of the outer flanks are in phase and reflect variations at the base of the stellar wind. The detected 2.4-day modulation period together with a second period of 1.2 days (in the red emission hump only) is in excellent agreement with the outer-wind modulation periods as reported by Fullerton et al. (\\cite{Ful97}) from intensive IUE UV time-series observations in 1993 and 1995. The 2.4-day period is further detected in the photospheric He I lambda4026 line as prograde traveling (pseudo-)absorption and emission features. The observed variability pattern is indicative for low-order non-radial pulsations in the photosphere of HD 64760. The non-radial pulsations are identified as the source of persistent, regularly spaced stellar surface

Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

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Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

Characterization of stem-like cells in a new astroblastoma cell line

Energy Technology Data Exchange (ETDEWEB)

Coban, Esra Aydemir; Kasikci, Ezgi [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul (Turkey); Karatas, Omer Faruk [Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum (Turkey); Suakar, Oznur; Kuskucu, Aysegul [Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul (Turkey); Altunbek, Mine [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul (Turkey); Türe, Uğur [Department of Neurosurgery, Yeditepe University School of Medicine, Istanbul (Turkey); Sahin, Fikrettin [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul (Turkey); Bayrak, Omer Faruk, E-mail: ofbayrak@yeditepe.edu.tr [Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul (Turkey)

2017-03-15

Cell lines established from tumors are the most commonly used models in cancer research, and their use in recent years has enabled a greater understanding of the biology of cancer and the means to develop effective treatment strategies. Astroblastomas are uncommon neuroepithelial tumors of glial origin, predominantly affecting young people, mainly teenagers and children, predominantly females. To date, only a single study has reported that astroblastomas contain a large number of neural stem-like cells, which had only a partial proliferation capacity and differentiation. Our objective was to establish an astroblastoma cell line to investigate the presence of astroblastic cells and cancer stem-like cells. The migratory and invasion abilities of the cells were quantified with invasion and migration assays and compared to a glioblastoma cell line. The presence of stem cells was detected with surface-marker analysis by using flow cytometry, and measuring the differentiation ability with a differentiation assay and the self-renewal capacity with a sphere-forming assay. These characteristics may determine whether this novel cell line is a model for astroblastomas that may have stem-cell characteristics. With this novel cell line, scientists can investigate the molecular pathways underlying astroblastomas and develop new therapeutic strategies for patients with these tumors. - Highlights: • An establishment of a novel astroblastoma cell line was proposed. • The presence of astroblastic cells and cancer stem-like cells was investigated. • The molecular pathways underlying astroblastomas may be investigated. • New therapeutic strategies for patients with astroblastoma may be developed.

Purification and characterization of antifungal compounds from Lactobacillus plantarum HD1 isolated from kimchi.

Science.gov (United States)

Ryu, Eun Hye; Yang, Eun Ju; Woo, Eun Rhan; Chang, Hae Choon

2014-08-01

Strain HD1 with antifungal activity was isolated from kimchi and identified as Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous fungi than yeast. Antifungal compounds were purified using solid phase extraction (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were elucidated by electrospray ionization-mass spectrometry and nuclear magnetic resonance. Active compounds from Lb. plantarum HD1 were identified as 5-oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5-dodecenoic acid (MW 214). To investigate the potential application of these antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice wine was used as a food model. White film-forming yeasts were observed in control draft rice wine after 11 days of incubation. However, film-forming yeasts were not observed in draft rice wine treated with SPE-prepared culture supernatant of Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27 days of incubation. The addition of antifungal compounds to Korean draft rice wine extended shelf-life up to 27 days at 10 °C without any sterilization process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the development of powerful biopreservative systems capable of preventing food- and feed-borne fungal spoilage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spectral analysis of the He-enriched sdO-star HD 127493

Science.gov (United States)

Dorsch, Matti; Latour, Marilyn; Heber, Ulrich

2018-02-01

The bright sdO star HD127493 is known to be of mixed H/He composition and excellent archival spectra covering both optical and ultraviolet ranges are available. UV spectra play a key role as they give access to many chemical species that do not show spectral lines in the optical, such as iron and nickel. This encouraged the quantitative spectral analysis of this prototypical mixed H/He composition sdO star. We determined atmospheric parameters for HD127493 in addition to the abundance of C, N, O, Si, S, Fe, and Ni in the atmosphere using non-LTE model atmospheres calculated with TLUSTY/SYNSPEC. A comparison between the parallax distance measured by Hipparcos and the derived spectroscopic distance indicate that the derived atmospheric parameters are realistic. From our metal abundance analysis, we find a strong CNO signature and enrichment in iron and nickel.

Detection of HD in the atmospheres of Uranus and Neptune : a new determination of the D/H ratio

NARCIS (Netherlands)

Feuchtgruber, H; Lellouch, E; Bezard, B; Encrenaz, T; de Graauw, T.; Davis, GR

Observations with the Short Wavelength Spectrometer (SWS) onboard the Infrared Space Observatory (ISO) have led to the first unambiguous detection of HD in the atmospheres of Uranus and Neptune, from its R(2) rotational line at 37.7 mu m Using S(0) and S(1) quadrupolar lines of H(2) at 28.2 and 17.0

Characterization of immortalized MARCO and SR-AI/II-deficient murine alveolar macrophage cell lines

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Imrich Amy

2008-05-01

Full Text Available Abstract Background Alveolar macrophages (AM avidly bind and ingest unopsonized inhaled particles and bacteria through class A scavenger receptors (SRAs MARCO and SR-AI/II. Studies to characterize the function of these SRAs have used AMs from MARCO or SR-AI/II null mice, but this approach is limited by the relatively low yield of AMs. Moreover, studies using both MARCO and SR-AI/II-deficient (MS-/- mice have not been reported yet. Hence, we sought to develop continuous cell lines from primary alveolar macrophages from MS-/- mice. Results We used in vitro infection of the primary AMs with the J2 retrovirus carrying the v-raf and v-myc oncogenes. Following initial isolation in media supplemented with murine macrophage colony-stimulating factor (M-CSF, we subcloned three AM cell lines, designated ZK-1, ZK-2 and ZK-6. These cell lines grow well in RPMI-1640-10% FBS in the absence of M-CSF. These adherent but trypsin-sensitive cell lines have a doubling time of approximately 14 hours, exhibit typical macrophage morphology, and express macrophage-associated cell surface Mac-1 (CD11b and F4/80 antigens. The cell lines show robust Fc-receptor dependent phagocytosis of opsonized red blood cells. Similar to freshly isolated AMs from MS-/- mice, the cell lines exhibit decreased phagocytosis of unopsonized titanium dioxide (TiO2, fluorescent latex beads and bacteria (Staphylococcus aureus compared with the primary AMs from wild type (WT C57BL/6 mice. Conclusion Our results indicated that three contiguous murine alveolar macrophage cell lines with MS-/- (ZK1, ZK2 and ZK6 were established successfully. These cell lines demonstrated macrophage morphology and functional activity. Interestingly, similar to freshly isolated AMs from MS-/- mice, the cell lines have a reduced, but not absent, ability to bind and ingest particles, with an altered pattern of blockade by scavenger receptor inhibitors. These cell lines will facilitate in vitro studies to further define

THE MASS OF HD 38529c FROM HUBBLE SPACE TELESCOPE ASTROMETRY AND HIGH-PRECISION RADIAL VELOCITIES

International Nuclear Information System (INIS)

Benedict, G. Fritz; McArthur, Barbara E.; Bean, Jacob L.; Barnes, Rory; Harrison, Thomas E.; Hatzes, Artie; Martioli, Eder; Nelan, Edmund P.

2010-01-01

Hubble Space Telescope Fine Guidance Sensor astrometric observations of the G4 IV star HD 38529 are combined with the results of the analysis of extensive ground-based radial velocity (RV) data to determine the mass of the outermost of two previously known companions. Our new RVs obtained with the Hobby-Eberly Telescope and velocities from the Carnegie-California group now span over 11 yr. With these data we obtain improved RV orbital elements for both the inner companion, HD 38529b, and the outer companion, HD 38529c. We identify a rotational period of HD 38529 (P rot = 31.65 ± 0fd17) with Fine Guidance Sensor photometry. The inferred star spot fraction is consistent with the remaining scatter in velocities being caused by spot-related stellar activity. We then model the combined astrometric and RV measurements to obtain the parallax, proper motion, perturbation period, perturbation inclination, and perturbation size due to HD 38529c. For HD 38529c we find P = 2136.1 ± 0.3 d, perturbation semimajor axis α = 1.05 ± 0.06 mas, and inclination i = 48. 0 3 ± 3. 0 7. Assuming a primary mass M * = 1.48 M sun , we obtain a companion mass M c = 17.6 +1.5 -1.2 M Jup , 3σ above a 13 M Jup deuterium burning, brown dwarf lower limit. Dynamical simulations incorporating this accurate mass for HD 38529c indicate that a near-Saturn mass planet could exist between the two known companions. We find weak evidence of an additional low amplitude signal that can be modeled as a planetary-mass (∼0.17 M Jup ) companion at P ∼194 days. Including this component in our modeling lowers the error of the mass determined for HD 38529c. Additional observations (RVs and/or Gaia astrometry) are required to validate an interpretation of HD 38529d as a planetary-mass companion. If confirmed, the resulting HD 38529 planetary system may be an example of a 'Packed Planetary System'.

In vitro oxygen-dependent survival of two human cell lines after combined radiations tirapazamin and cisplatin

International Nuclear Information System (INIS)

Lartigau, E.; Stern, S.; Guichard, M.

2000-01-01

Recent data have shown that the in vitro and in vivo cytotoxicity of bioreductive drugs could be significantly cytotoxicity of bioreductive drugs could be significantly increased by combination with ionising radiation or chemotherapy. Various parameters such as oxygen tension and timing of administration of the drugs could play a crucial role in the efficacy of combined treatment modalities. The aim of this study was to define the oxygen dependency of cell survival after in vitro irradiation and incubation with tirapazamin, a bioreductive drug, and cisplatin given alone or simultaneously. Two human cell lines were studied: one cell line sensitive to tirapazamin, Na11+, a pigmented melanoma with a high percentage of hypoxic cells, and a less sensitive cell line to tirapazamin, HRT18, a rectal adenocarcinoma. Gas changes were made to study cell survival at four different oxygen concentrations (pO 2 ): air (20.9 % O 2 ), 10.2 and 0.2 %. Cells were incubated with tirapazamin and cisplatin alone or combined for one hour at 37 deg C, then irradiated and cultured. For Na11+, cell survival after irradiation was comparable in air and at 10 % oxygen with the two drugs given alone or combined. At 2 and 0.2 % oxygen, cell killing was largely increased by tirapazamin and was not modified by the addition of cisplatin. For HRT18, cell survival was not modified when cisplatin was added to radiation, whatever the oxygen partial pressure. At low pO 2 (2 and 0.2 %) the cytotoxic effect of tirapazamin was not significantly decreased by the addition of cisplatin. When cytotoxic and bioreductive drugs are combined to radiation, the magnitude of the observed effect is highly dependent on the partial oxygen pressure and on the sensitivity of the cell line to the individual drugs. This has very important implications for clinical strategies based on combined chemo-radiotherapy. (authors)

Neurotensin is metabolized by endogenous proteases in prostate cancer cell lines.

Science.gov (United States)

Moody, T W; Mayr, C A; Gillespie, T J; Davis, T P

1998-01-01

The formation and processing of neurotensin (NT) by three prostate cancer cell lines was investigated. Neurotensin (NT) immunoreactivity was detected in conditioned media and extracts of LNCaP cells. Using HPLC techniques, the immunoreactivity extracted from LNCaP cells coeluted with synthetic NT standard. Metalloendopeptidase 3.4.24.15 activity was detected in PC-3, DU-145 and LNCaP cells, whereas high levels of neutral endopeptidase 3.4.24.1 1 activity was detected only in LNCaP cells. NT was relatively stable when incubated with PC-3 or D-145 cells but was rapidly degraded by LNCaP cells to NT1-11 and NT1-10. Phosphoramidon inhibited the metabolism of NT by LNCaP cells. These data suggest that NT is present in and metabolized by LNCaP cellular enzymes.

Cancer antigens are expressed in a carcinogen-transformed Bloom syndrome B-lymphoblastoid cell line

International Nuclear Information System (INIS)

Shiraishi, Yukimasa; Soma, Hiroaki

1988-01-01

The authors have cloned malignant cells carrying specific antigens associated with ovarian cancer (OVC) and malignant lymphoma (ML) from BS-SHI-4M cells, a line derived from a 1-methyl-3-nitro-1-nitrosoguanidine-treated B-lymphoblastoid cell line isolated from a patient with Bloom syndrome. Since BS-SHI-4M cells react with sera from various individual cancer patients at relatively low frequencies (2-9%), as detected by an indirect immunofluorescence technique, cell clones that specifically react with sera from patients with OVC and ML were separated by the panning method in which polystyrene dishes were coated with sera from OVC and ML patients and cells with the corresponding antigens bound to the dishes. Subsequent cloning by limiting dilution provided cell clones highly enriched for OVC- and ML-associated antigens. Karyotype analyses revealed that cell clones with OVC and ML antigens had common marker chromosomes. Interestingly, in cell clones with a strong OVC antigen response, the distal part of the Y chromosome (Yq11) was missing in 100% of the cells. Therefore the cell line BS-SHI-4M appears to be a reservoir of cell clones each of which carries a specific tumor antigen and thus provides a potential tool for rapid serological diagnosis of cancer

Cell fusion induced by ionizing radiation in various cell lines

International Nuclear Information System (INIS)

Khair, M.B.

1994-07-01

Cell fusion induced by ionizing radiation has been studied in rat's hepatocytes in vivo and in different cell lines in vitro. These cell lines were: Hela cells, V-79 fibroblasts, human and rat lymphocytes. For irradiation, 0.85 MeV fission neutrons and 14 MeV fast neutrons were used. Cell analyses were performed by fluorescent dyes using immunofluorescent microscope and flow cytometre. Our results in vivo showed that, regardless the dose-rate, a dose of 1 Gy approximately was enough to induce a significant level of cell fusion depending on neutron energy and the age of rats. The level of cell fusion was also significant in Hela cells at a dose of 0.5 Gy. Similar effect, but to a lesser extent, was observed in V-79 cells. Whereas, in lymphocytes insignificant cell fusion was noticed. The varying levels of cell-fusion in different cell lines could be attributed to the type of cells and mutual contact between cells. Furthermore irradiation did not show any influence on cell division ability in both hepatocytes and Hela cells and that fused cells were also able to divide forming a new generation of cells. (author). 36 refs., 8 figs., 10 tabs

New ALMA Images of the HD 32297 and HD 61005 Debris Disks

Science.gov (United States)

MacGregor, Meredith Ann; Weinberger, Alycia; Wilner, David; Hughes, A. Meredith; debes, John Henry; Redfield, Seth; Donaldson, Jessica; Nesvold, Erika; Schneider, Glenn; Currie, Thayne; Roberge, Aki; Rodriguez, David

2018-01-01

HD 61005 (G-type star, “The Moth") and HD 32297 (A-type star) host two of the most iconic debris disks. Scattered light images show that both disks are nearly edge-on with dramatic swept-back wings of dust. Previous studies have proposed a range of mechanisms to explain this distinctive morphology including interactions with the interstellar medium, secular perturbations of grains by low-density, neutral interstellar gas, and gravitational interactions with an inclined, eccentric companion. We present new observations from the Atacama Large Millimeter/submillimeter Array (ALMA) at 1.3 mm that provide the highest resolution images at millimeter wavelengths to date of both systems. Observations at millimeter wavelengths are especially critical to our understanding of the physical mechanisms shaping the structure of these disks, since the large grains that dominate emission at these wavelengths are less affected by stellar radiation and winds and more reliably trace the underlying planetesimal distribution. We fit models directly to the observed visibilities within a Markov Chain Monte Carlo (MCMC) framework to characterize the continuum emission and place constraints on the structure of these unique debris disks. Our new ALMA images reveal that despite differences in spectral type, both systems are best described by a two-component structure with (1) a parent body belt, and (2) an outer halo aligned with the scattered light disk. Such halos have typically been assumed to be composed of small grains visible in scattered light, so these images are some of the first observational evidence that larger grains may also populate extended halos. In addition, we detect significant 12CO gas emission from HD 32297, and determine a robust upper limit for HD 61005.

MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

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Kumar Smriti

2011-09-01

Full Text Available Abstract Background Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Methods The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs between cis-platin sensitive (A2780, and cis-platin resistant (A2780/CP70 cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. Results Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. Conclusions Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated

Relative survival of hybrid x-ray-resistant, and normally sensitive mammalian cells exposed to x rays and protons under aerobic and hypoxic conditions

International Nuclear Information System (INIS)

Williams, J.R.; Gould, R.G.; Flynn, D.; Robertson, J.B.; Little, J.B.

1978-01-01

Survival of an x-ray-resistant hybrid cell line (HD 1 ) and a normally responsive cell line (H 4 ) have been compared when irradiated under induced hypoxia by both protons and X rays. The two cell lines are similarly protected when irradiated under hypoxic conditions with oxygen enhancement ratios of 2.8 and 2.7, respectively. The protection is consistent with a dose-modifying factor. No statistically significant difference is observed between cell inactivation by x rays and protons in either cell line, whether irradiated under aerobic or hypoxic conditions

Epstein-Barr virus (EBV antibody in childhood Hodgkin's disease (HD at Imam khomeini Medical Complex

Directory of Open Access Journals (Sweden)

Nahid M

1998-08-01

Full Text Available Association of EBV with the tumor cells of HD has been proven by a variety of the methods, using serologic and immunohistochemical techniques and in the recent years with molecular biologic techniques which can detect EBV genome in tumor biopsies. In this regard we prompted to perform a case control study on 25 childhood HD cases with respected to their antibodies gainst EBNA and EBV-IgM antibodies in Imam Khomeini Hospital in Tehran. In our study the ratio of positive titers was significantly higher among HD patients compared with age and sex-matched healthy controls.

THE DISCOVERY OF HD 37605c AND A DISPOSITIVE NULL DETECTION OF TRANSITS OF HD 37605b

International Nuclear Information System (INIS)

Wang, Sharon Xuesong; Wright, Jason T.; Mahadevan, Suvrath; Cochran, William; Endl, Michael; MacQueen, Phillip J.; Kane, Stephen R.; Von Braun, Kaspar; Henry, Gregory W.; Payne, Matthew J.; Ford, Eric B.; Valenti, Jeff A.; Antoci, Victoria; Dragomir, Diana; Matthews, Jaymie M.; Howard, Andrew W.; Marcy, Geoffrey W.; Isaacson, Howard

2012-01-01

We report the radial velocity discovery of a second planetary mass companion to the K0 V star HD 37605, which was already known to host an eccentric, P ∼ 55 days Jovian planet, HD 37605b. This second planet, HD 37605c, has a period of ∼7.5 years with a low eccentricity and an Msin i of ∼3.4 M Jup . Our discovery was made with the nearly 8 years of radial velocity follow-up at the Hobby-Eberly Telescope and Keck Observatory, including observations made as part of the Transit Ephemeris Refinement and Monitoring Survey effort to provide precise ephemerides to long-period planets for transit follow-up. With a total of 137 radial velocity observations covering almost 8 years, we provide a good orbital solution of the HD 37605 system, and a precise transit ephemeris for HD 37605b. Our dynamic analysis reveals very minimal planet-planet interaction and an insignificant transit time variation. Using the predicted ephemeris, we performed a transit search for HD 37605b with the photometric data taken by the T12 0.8 m Automatic Photoelectric Telescope (APT) and the MOST satellite. Though the APT photometry did not capture the transit window, it characterized the stellar activity of HD 37605, which is consistent of it being an old, inactive star, with a tentative rotation period of 57.67 days. The MOST photometry enabled us to report a dispositive null detection of a non-grazing transit for this planet. Within the predicted transit window, we exclude an edge-on predicted depth of 1.9% at the >>10σ level, and exclude any transit with an impact parameter b > 0.951 at greater than 5σ. We present the BOOTTRAN package for calculating Keplerian orbital parameter uncertainties via bootstrapping. We made a comparison and found consistency between our orbital fit parameters calculated by the RVLIN package and error bars by BOOTTRAN with those produced by a Bayesian analysis using MCMC.

Cell line name recognition in support of the identification of synthetic lethality in cancer from text

Science.gov (United States)

Kaewphan, Suwisa; Van Landeghem, Sofie; Ohta, Tomoko; Van de Peer, Yves; Ginter, Filip; Pyysalo, Sampo

2016-01-01

Motivation: The recognition and normalization of cell line names in text is an important task in biomedical text mining research, facilitating for instance the identification of synthetically lethal genes from the literature. While several tools have previously been developed to address cell line recognition, it is unclear whether available systems can perform sufficiently well in realistic and broad-coverage applications such as extracting synthetically lethal genes from the cancer literature. In this study, we revisit the cell line name recognition task, evaluating both available systems and newly introduced methods on various resources to obtain a reliable tagger not tied to any specific subdomain. In support of this task, we introduce two text collections manually annotated for cell line names: the broad-coverage corpus Gellus and CLL, a focused target domain corpus. Results: We find that the best performance is achieved using NERsuite, a machine learning system based on Conditional Random Fields, trained on the Gellus corpus and supported with a dictionary of cell line names. The system achieves an F-score of 88.46% on the test set of Gellus and 85.98% on the independently annotated CLL corpus. It was further applied at large scale to 24 302 102 unannotated articles, resulting in the identification of 5 181 342 cell line mentions, normalized to 11 755 unique cell line database identifiers. Availability and implementation: The manually annotated datasets, the cell line dictionary, derived corpora, NERsuite models and the results of the large-scale run on unannotated texts are available under open licenses at http://turkunlp.github.io/Cell-line-recognition/. Contact: sukaew@utu.fi PMID:26428294

Studies on the effects of adriamycin-derivatives in combination with X-rays on MeWo- and Be11-cells

International Nuclear Information System (INIS)

Krueger, M.; Beuningen, D. van; Streffer, C.

1990-01-01

The survival rate of human melanoma cells after X-ray irradiation, treamtment with adriamycin derivatives and combined treatment with X-rays and adriamycin derivatives was measured by means of the colony formation test. After X-ray irradiation the melanoma cells showed a high resistance for cell survival. In all tests the Be11-cells were more resistant than MeWo-cells. On combined exposure especially with higher doses of adriamycin derivatives, both cell lines showed the interesting effect, that with increasing concentration the survival rate decreased whereas the D 0 increased. Aclacinomycin-A (ACM-A) and Pirarubicin reduced recovery processes after X-ray irradiation. Therefore Be11-cells showed a four times higher DMF (dosis modifying factor) after ACM-A-treatment than MeWo-cells. Low ACM-A-concentrations combined with low X-ray doses showed on both cell lines supraadditive effects. The effect of pirarubicin was in most of the tests only additive. Compared with ACM-A, pirarubicin was less cytotoxic, showed a larger therapeutic range, caused a smaller D 0 and D q and had a supraadditive effect in low concentrations on both cell lines. For clinical combined therapy with patients ACM-A is probably better suited than pirarubicin. (orig.) [de

Feeder-cell-independent culture of the pig-embryonic-stem-cell-derived exocrine pancreatic cell line, PICM-31

Science.gov (United States)

The adaptation to feeder-independent growth of a pig embryonic stem cell-derived pancreatic cell line is described. The parental PICM-31 cell line, previously characterized as an exocrine pancreas cell line, was colony-cloned two times in succession resulting in the subclonal cell line, PICM-31A1. P...

Application of DNA fingerprints for cell-line individualization.

Science.gov (United States)

Gilbert, D A; Reid, Y A; Gail, M H; Pee, D; White, C; Hay, R J; O'Brien, S J

1990-09-01

DNA fingerprints of 46 human cell lines were derived using minisatellite probes for hypervariable genetic loci. The incidence of 121 HaeIII DNA fragments among 33 cell lines derived from unrelated individuals was used to estimate allelic and genotypic frequencies for each fragment and for composite individual DNA fingerprints. We present a quantitative estimate of the extent of genetic difference between individuals, an estimate based on the percentage of restriction fragments at which they differ. The average percent difference (APD) among pairwise combinations from the population of 33 unrelated cell lines was 76.9%, compared with the APD in band sharing among cell lines derived from the same individual (less than or equal to 1.2%). Included in this survey were nine additional cell lines previously implicated as HeLa cell derivatives, and these lines were clearly confirmed as such by DNA fingerprints (APD less than or equal to 0.6%). On the basis of fragment frequencies in the tested cell line population, a simple genetic model was developed to estimate the frequencies of each DNA fingerprint in the population. The median incidence was 2.9 X 10(-17), and the range was 2.4 X 10(-21) to 6.6 X 10(-15). This value approximates the probability that a second cell line selected at random from unrelated individuals will match a given DNA fingerprint. Related calculations address the chance that any two DNA fingerprints would be identical among a large group of cell lines. This estimate is still very slight; for example, the chance of two or more common DNA fingerprints among 1 million distinct individuals is less than .001. The procedure provides a straightforward, easily interpreted, and statistically robust method for identification and individualization of human cells.

Catabolism of neurotensin by neural (neuroblastoma clone N1E115) and extraneural (HT29) cell lines

International Nuclear Information System (INIS)

Checler, F.; Amar, S.; Kitabgi, P.; Vincent, J.P.

1986-01-01

The mechanisms by which neurotensin (NT) was inactivated by differentiated neuroblastoma and HT29 cells were characterized. In both cell lines, the sites of primary cleavages of NT were Pro7-Arg8, Arg8-Arg9 and Pro10-Tyr11 bonds. The cleavage at the Pro7-Arg8 bond was totally inhibited by N-benzyloxycarbonyl-Prolyl-Prolinal and therefore resulted from the action of proline endopeptidase. This peptidase also contributed in a major way to the cleavage at the Pro10-Tyr11 bond. However the latter breakdown was partly due to an NT-degrading neutral metallopeptidase. Finally, we demonstrated the involvement of a recently purified rat brain soluble metalloendopeptidase at the Arg8-Arg9 site by the use of its specific inhibitor N-[1(R,S)-carboxy-2-Phenylethyl]-alanylalanylphenylalanine-p-amino benzoate. The secondary processing of NT degradation products revealed differences between HT29 and N1E115 cells. Angiotensin converting enzyme was shown to degrade NT1-10 and NT1-7 in N1E115 cells but was not detected in HT29 cells. A post-proline dipeptidyl aminopeptidase activity converted NT9-13 into NT11-13 in HT29 cells but not in N1E115 cells. Finally, bestatin-sensitive aminopeptidases rapidly broke down NT11-13 to Tyr in both cell lines. Models for the inactivation of NT in HT29 and N1E115 cells are proposed and compared to that previously described for purified rat brain synaptic membranes

Natural killer cells for immunotherapy – Advantages of cell lines over blood NK cells

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Hans eKlingemann

2016-03-01

Full Text Available Natural killer cells are potent cytotoxic effector cells for cancer therapy and potentially for severe viral infections. However, there are technical challenges to obtain sufficient numbers of functionally active NK cells form a patient’s blood since they represent only 10% of the lymphocytes. Especially, cancer patients are known to have dysfunctional NK cells. The alternative is to obtain cells from a healthy donor, which requires depletion of the allogeneic T-cells. Establishing cell lines from donor blood NK cells have not been successful, in contrast to blood NK cells obtained from patients with a clonal NK cell lymphoma. Those cells can be expanded in culture in the presence of IL-2. However, except for the NK-92 cell line none of the other six known cell lines has consistent and reproducibly high anti-tumor cytotoxicity, nor can they be easily genetically manipulated to recognize specific tumor antigens or to augment monoclonal antibody activity through ADCC. NK-92 is also the only cell line product that has been widely given to patients with advanced cancer with demonstrated efficiency and minimal side effects.

Susceptibility testing of fish cell lines for virus isolation

DEFF Research Database (Denmark)

Ariel, Ellen; Skall, Helle Frank; Olesen, Niels Jørgen

2009-01-01

and laboratories, but also between lineages of the same cell line. To minimise the occurrence of false negatives in a cell culture based surveillance system, we have investigated methods, to select cell lineages that are relatively superior in their susceptibility to a panel of virus isolates. The procedures...... cell lineages, we increased the number of isolates of each virus, propagated stocks in a given cell line and tested all lineages of that line in use in the laboratory. Testing of relative cell line susceptibility between laboratories is carried out annually via the Inter-laboratory Proficiency Test...... sensitivity for surveillance purposes within a cell line and between laboratories.In terms of economic and practical considerations as well as attempting to approach a realistic test system, we suggest the optimal procedure for susceptibility testing of fish cell lines for virus isolation to be a combination...

α-Defensin HD5 Inhibits Human Papillomavirus 16 Infection via Capsid Stabilization and Redirection to the Lysosome

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Mayim E. Wiens

2017-01-01

Full Text Available α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5 blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition. Instead, HD5 altered HPV trafficking in the cell. In the presence of an inhibitory concentration of HD5, HPV was internalized and reached the early endosome. The internalized capsid became permeable to antibodies and proteases; however, HD5 prevented dissociation of the viral capsid from the genome, reduced viral trafficking to the trans-Golgi network, redirected the incoming viral particle to the lysosome, and accelerated the degradation of internalized capsid proteins. This mechanism is equivalent to the mechanism by which HD5 inhibits human adenovirus. Thus, our data support capsid stabilization and redirection to the lysosome during infection as a general antiviral mechanism of α-defensins against nonenveloped viruses.

Effect of cisplatin on the clinically relevant radiosensitivity of human cervical carcinoma cell lines

International Nuclear Information System (INIS)

Britten, Richard A.; Evans, Andrew J.; Allalunis-Turner, M. Joan; Pearcey, Robert G.

1996-01-01

Purpose: To evaluate the effect of clinically relevant levels of cisplatin on the radiosensitivity of human cervical tumor cells, and to estimate what changes in local control rates might be expected to accrue from the concomitant use of cisplatin during fractionated radiotherapy. Methods and Materials: The effects of concomitant cisplatin (1 μg/ml, a typical intratumor concentration) on the clinically relevant radiosensitivity, i.e., surviving fraction after 2 G (SF 2 ) values, was determined in 19 cloned human cervical tumor cell lines. These early passage cell lines had SF 2 values ranging from 0.26 to 0.87. Results: The concomitant administration of cisplatin reduced the clinically relevant radiosensitivity in the majority (11 out of 19) of the human tumor cell lines investigated. In only 4 out of 19 was any radiosensitization observed, and in 4 out of 19 cell lines there was no significant change in radiosensitivity. However, the sum of the independent cell killing by radiation and cisplatin, was approximately twofold higher than after radiation alone. There was no apparent dependence of the cisplatin-induced changes in SF 2 values upon the level of cell killing by cisplatin. However, there is a suggestion that concomitant cisplatin administration may have a differential effect in inherently radiosensitive and resistant human tumor cell lines. Conclusions: Our data suggest that concomitant cisplatin/radiotherapy regimens may result in a higher level of local tumor control, but primarily through additive toxicity and not through radiosensitization. Future improvements in local tumor control may, thus, be derived by increasing the total dose of cisplatin

Efficient delivery and stable gene expression in a hematopoietic cell line using a chimeric serotype 35 fiber pseudotyped helper-dependent adenoviral vector

International Nuclear Information System (INIS)

Balamotis, Michael Andrew; Huang, Katie; Mitani, Kohnosuke

2004-01-01

Certain human cell populations have remained difficult to infect with human adenovirus (Ad) serotype 5 because of their lack of coxsackievirus B-adenovirus receptor (CAR). Native adenovirus fiber compositions, although diverse, cannot infect all tissue types. Recently, a chimeric Ad5/35 fiber was created, which displays an altered tropism from Ad5. We incorporated this chimeric fiber into a helper-dependent (HD) adenovirus vector system and compared HD to E1-deleted (E1Δ) vectors by transgene expression, cell transduction efficiency, and cytotoxicity. K562 cells were infected ∼50 times more efficiently with the chimeric Ad5/35 fiber compared with the Ad5 fiber. Short-term transgene expression was sustained longer from HD Ad5/35 than E1Δ Ad5/35 vector after in vitro infection of actively dividing K562 cells. Rapid loss of transgene expression from E1Δ Ad5/35 infection was not due to the loss of vector genomes, as determined by quantitative real-time PCR (QRT-PCR), or cytotoxicity, but rather through a putative silencing mechanism

HD 101065, the Most Peculiar Star

Indian Academy of Sciences (India)

2016-01-27

Jan 27, 2016 ... In this paper we discuss the prospects for asteroseismology with spatial resolution and motivate studies of the most chemically peculiar roAp star HD 101065. We present the first results from a high-precision radial velocity (RV) study of HD 101065 based on data spanning four nights that were acquired ...

Fourier-transform spectroscopy of HD in the vacuum ultraviolet at λ = 87-112 nm

Science.gov (United States)

Ivanov, T. I.; Dickenson, G. D.; Roudjane, M.; de Oliveira, N.; Joyeux, D.; Nahon, L.; Tchang-Brillet, W.-Ü. L.; Ubachs, W.

2010-03-01

Absorption spectroscopy in the vacuum ultraviolet (VUV) domain was performed on the hydrogen-deuteride molecule with a novel Fourier-transform spectrometer based upon wavefront division interferometry. This unique instrument, which is a permanent endstation of the undulator-based beamline DESIRS on the synchrotron SOLEIL facility, opens the way to Fourier-transform spectroscopy in the VUV range. The HD spectral lines in the Lyman and Werner bands were recorded in the 87-112 nm range from a quasi-static gas sample in a windowless configuration and with a Doppler-limited resolution. Line positions of some 268 transitions in the ? Lyman bands and 141 transitions in the ? Werner bands were deduced with uncertainties of 0.04 cm-1 (1σ) which correspond to Δλ/λ ∼ 4 × 10-7. This extensive laboratory database is of relevance for comparison with astronomical observations of H2 and HD spectra from highly redshifted objects, with the goal of extracting a possible variation of the proton-to-electron mass ratio (μ = m p /m e ) on a cosmological time scale. For this reason also calculations of the so-called sensitivity coefficients K i were performed in order to allow for deducing constraints on Δμ/μ. The K i coefficients, associated with the line shift that each spectral line undergoes as a result of a varying value for μ, were derived from calculations as a function of μ solving the Schrödinger equation using ab initio potentials.

3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Qin, J.-Z.; Xin, H. [Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University of Chicago Medical Center (United States); Nickoloff, B.J., E-mail: bnickol@lumc.edu [Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University of Chicago Medical Center (United States)

2010-05-28

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.

3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines.

Science.gov (United States)

Qin, J-Z; Xin, H; Nickoloff, B J

2010-05-28

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma. Copyright (c) 2010 Elsevier Inc. All rights reserved.

3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines

International Nuclear Information System (INIS)

Qin, J.-Z.; Xin, H.; Nickoloff, B.J.

2010-01-01

Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.

Tuft (caveolated) cells in two human colon carcinoma cell lines.

Science.gov (United States)

Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

1988-09-01

The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

Life without water: cross-resistance of anhydrobiotic cell line to abiotic stresses

Science.gov (United States)

Gusev, Oleg

2016-07-01

Anhydrobiosis is an intriguing phenomenon of natural ability of some organisms to resist water loss. The larvae of Polypedilum vanderplanki, the sleeping chironomid is the largest and most complex anhydrobionts known to date. The larvae showed ability to survive variety of abiotic stresses, including outer space environment. Recently cell line (Pv11) derived from the embryonic mass of the chironomid was established. Initially sensitive to desiccation cells, are capable to "induced" anhydrobiosis, when the resistance to desiccation can be developed by pre-treatment of the cells with trehalose followed by quick desiccation. We have further conducted complex analysis of the whole genome transcription response of Pv11 cells to different abiotic stresses, including oxidative stress and irradiation. Comparative analysis showed that the gene set, responsible for formation of desiccation resistance (ARID regions in the genome) is also activated in response to other types of stresses and likely to contribute to general enhancing of the resistance of the cells to harsh environment. We have further demonstrated that the cells are able to protect recombinant proteins from harmful effect of desiccation

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

International Nuclear Information System (INIS)

Ghislin, Stephanie; Obino, Dorian; Middendorp, Sandrine; Boggetto, Nicole; Alcaide-Loridan, Catherine; Deshayes, Frederique

2012-01-01

Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

Directory of Open Access Journals (Sweden)

Ghislin Stephanie

2012-10-01

Full Text Available Abstract Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18 expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration.

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

Directory of Open Access Journals (Sweden)

Marie-Theres Zeuner

2017-01-01

Full Text Available Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation, has been linked to autoimmune diseases, development and progression of cancer, and neurological disorders like Alzheimer’s disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of proinflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals. We used lentivirus to transduce the glioma cell line U251-MG with a tandem NF-κB reporter construct containing GFP and firefly luciferase allowing an assessment of NF-κB activity via fluorescence microscopy, flow cytometry, and luminometry. We observed a robust activation of NF-κB after exposure of the reporter cell line to tumour necrosis factor alpha (TNFα and amyloid-β peptide [1-42] as well as to LPS derived from Salmonella minnesota and Escherichia coli. Finally, we demonstrate that the U251-NF-κB-GFP-Luc reporter cells can be used for assessing the anti-inflammatory potential of pharmaceutical compounds using Bay11-7082 and IMD0354. In summary, our newly generated cell line is a robust and cost-efficient tool to study pro- and anti-inflammatory potential of drugs and biologics in neural cells.

Quality control of involved field radiotherapy in the HD 13 and HD 14 trials. Report of the radiotherapy panel of the German Hodgkin Study Group (GHSG)

Energy Technology Data Exchange (ETDEWEB)

Kriz, J.; Haverkamp, U.; Eich, H.T. [University of Muenster, Department of Radiation Oncology, Muenster (Germany); Baues, C. [University of Cologne, Department of Radiation Oncology, Cologne (Germany); Engenhart-Cabillic, R. [University of Marburg, Department of Radiation Oncology, Marburg (Germany); Herfarth, K. [University of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Lukas, P. [University of Innsbruck, Department of Radiation Oncology, Innsbruck (Austria); Pluetschow, A.; Fuchs, M.; Engert, A. [University of Cologne, Department of Internal Medicine, Cologne (Germany); Schmidberger, H. [University of Mainz, Department of Radiation Oncology, Mainz (Germany); Staar, S. [Bremen Mitte, Department of Radiation Oncology, Bremen (Germany)

2017-02-15

As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings. With the start of the fourth GHSG study generation (HD10-12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13-15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation. The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %). The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of ''modern RT'' in malignant lymphoma. (orig.) [German] Seit Gruendung der German Hodgkin Study Group (GHSG) im Jahr 1978 wurde ein zentrales Qualitaetssicherungsprogramm (QAP) der Radiotherapie (RT) etabliert, um die Qualitaet der RT sicherzustellen. Waehrend der fortlaufenden Studiengenerationen wurde dieses QAP kontinuierlich weiterentwickelt. In dieser Auswertung werden die Ergebnisse der fuenften Studiengeneration (HD13-15) praesentiert und mit frueheren Ergebnissen

RESOLVING THE HD 100546 PROTOPLANETARY SYSTEM WITH THE GEMINI PLANET IMAGER: EVIDENCE FOR MULTIPLE FORMING, ACCRETING PLANETS

Energy Technology Data Exchange (ETDEWEB)

Currie, Thayne [National Astronomical Observatory of Japan, Subaru Telescope (Japan); Cloutier, Ryan [Department of Astronomy and Astrophysics, University of Toronto, Toronto, ON (Canada); Brittain, Sean [Department of Physics and Astronomy, Clemson University, Clemson, SC (United States); Grady, Carol; Kuchner, Marc J. [Exoplanets and Stellar Astrophysics Laboratory, NASA Goddard Space Flight Center, Greenbelt, MD (United States); Burrows, Adam [Department of Astrophysics Sciences, Princeton University, Princeton, NJ (United States); Muto, Takayuki [Division of Liberal Arts, Kogakuin University, Tokyo (Japan); Kenyon, Scott J. [Smithsonian Astrophysical Observatory, Cambridge, MA (United States)

2015-12-01

We report Gemini Planet Imager H-band high-contrast imaging/integral field spectroscopy and polarimetry of the HD 100546, a 10 Myr old early-type star recently confirmed to host a thermal infrared (IR) bright (super-)Jovian protoplanet at wide separation, HD 100546 b. We resolve the inner disk cavity in polarized light, recover the thermal IR-bright arm, and identify one additional spiral arm. We easily recover HD 100546 b and show that much of its emission plausibly originates from an unresolved point source. The point-source component of HD 100546 b has extremely red IR colors compared to field brown dwarfs, qualitatively similar to young cloudy super-Jovian planets; however, these colors may instead indicate that HD 100546 b is still accreting material from a circumplanetary disk. Additionally, we identify a second point-source-like peak at r{sub proj} ∼ 14 AU, located just interior to or at the inner disk wall consistent with being a <10–20 M{sub J} candidate second protoplanet—“HD 100546 c”—and lying within a weakly polarized region of the disk but along an extension of the thermal IR-bright spiral arm. Alternatively, it is equally plausible that this feature is a weakly polarized but locally bright region of the inner disk wall. Astrometric monitoring of this feature over the next 2 years and emission line measurements could confirm its status as a protoplanet, rotating disk hot spot that is possibly a signpost of a protoplanet, or a stationary emission source from within the disk.

RESOLVING THE HD 100546 PROTOPLANETARY SYSTEM WITH THE GEMINI PLANET IMAGER: EVIDENCE FOR MULTIPLE FORMING, ACCRETING PLANETS

International Nuclear Information System (INIS)

Currie, Thayne; Cloutier, Ryan; Brittain, Sean; Grady, Carol; Kuchner, Marc J.; Burrows, Adam; Muto, Takayuki; Kenyon, Scott J.

2015-01-01

We report Gemini Planet Imager H-band high-contrast imaging/integral field spectroscopy and polarimetry of the HD 100546, a 10 Myr old early-type star recently confirmed to host a thermal infrared (IR) bright (super-)Jovian protoplanet at wide separation, HD 100546 b. We resolve the inner disk cavity in polarized light, recover the thermal IR-bright arm, and identify one additional spiral arm. We easily recover HD 100546 b and show that much of its emission plausibly originates from an unresolved point source. The point-source component of HD 100546 b has extremely red IR colors compared to field brown dwarfs, qualitatively similar to young cloudy super-Jovian planets; however, these colors may instead indicate that HD 100546 b is still accreting material from a circumplanetary disk. Additionally, we identify a second point-source-like peak at r proj ∼ 14 AU, located just interior to or at the inner disk wall consistent with being a <10–20 M J candidate second protoplanet—“HD 100546 c”—and lying within a weakly polarized region of the disk but along an extension of the thermal IR-bright spiral arm. Alternatively, it is equally plausible that this feature is a weakly polarized but locally bright region of the inner disk wall. Astrometric monitoring of this feature over the next 2 years and emission line measurements could confirm its status as a protoplanet, rotating disk hot spot that is possibly a signpost of a protoplanet, or a stationary emission source from within the disk

Design of a polarized target made of pure HD: analysis and distillation of HD, resonant virtual Compton scattering on the nucleon at TJNAF; Developpement d'une cible polarisee de pur HD: analyse et distillation du HD, diffusion compton virtuelle resonante sur le nucleon a TJNAF

Energy Technology Data Exchange (ETDEWEB)

Bouchigny, S

2004-04-01

The first part describe my work on the frozen spin target project HYDILE. This target has to be made of very pure HD (Hydrogen Deuterium), better than 99.95%. However, commercial HD is never found with a concentration better than 98%. The goal was, then, to build an HD distillation facility which could produce pure HD. We describe, in this thesis, the design of the distillator and the implementation of a quadrupole mass spectrometer to monitor the HD purity during the distillation process. The second part of the thesis concerns the analysis taken at the electron accelerator facility TJNAF (Virginia, USA). We look at the electroproduction of Delta resonances involving Deep Virtual Compton Scattering (DeltaVCS). The interpretation of this reaction in terms of GPDs (Generalized Parton Distribution) can provide new insights to the nucleon structure. We focus on the measurement of the beam spin asymmetry which comes from the interference of the Bethe Heitler process with the DeltaVCS. (author)

Elemental abundance studies of CP stars. II. The silicon stars HD 133029 and HD 192913

CERN Document Server

López-García, Z

1999-01-01

For pt.1 see ibid., vol.107, no.2, p.353-63 (1994). Fine analyses of the silicon stars HD 133029 and HD 192913 are presented using ATLAS9 model atmospheres whose predictions fit the optical region spectrophotometry and H gamma profiles and have the same bulk metallicity as the deduced abundances. Both are very He poor stars. The light elements are mostly solar except for silicon, and all the heavier elements, except nickel in HD 133029 which is solar, are greatly overabundant. The iron peak elements are typically 10 times overabundant. SrYZr are of order of 100 times solar. The rare earths are 1000 or more times overabundant. Table 4 is is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/Abstract.html. (50 refs).

Lines profile variations and binarity in Wolf-Rayet stars

International Nuclear Information System (INIS)

Bisiacchi, G.F.; Firmani, C.; Lara, E. de

1982-01-01

Recently, HD50896, a WN5 star, for a long time considered as isolated, has been demonstrated to be a binary. This star shows very small displacement of the lines due to orbital motion and no evidence of the secondary spectrum. Is HD50896 a rare system in which the profile variations are peculiarly strong and easy to be detected, or are there many of these undetected binaries for which the analysis of the profile variation may be a powerful method to determine the periodicity. With this problem in mind the authors have observed a sample of 17 WR stars during a week to analyze both profile and radial velocity variations. This sample includes all the WR stars with Msub(v) 0 0 except for five stars that are binaries with determined period. All the spectra have been taken with a dispersion of 1.1 A channel -1 using a SIT television camera and a low dispersion spectrograph attached to the 2-meter telescope of the Observatorio Astronomico Nacional in San Pedro Martir, Baja California (Mexico). (Auth.)

β-Caryophyllene, a Compound Isolated from the Biblical Balm of Gilead (Commiphora gileadensis, Is a Selective Apoptosis Inducer for Tumor Cell Lines

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Eitan Amiel

2012-01-01

Full Text Available The biblical balm of Gilead (Commiphora gileadensis was investigated in this study for anticancerous activity against tumor cell lines. The results obtained from ethanol-based extracts and from essential oils indicated that β-caryophyllene (trans-(1R,9S-8-methylene-4,11,11-trimethylbicyclo[7.2.0]undec-4-ene is a key component in essential oils extracted from the balm of Gilead. β-Caryophyllene can be found in spice blends, citrus flavors, soaps, detergents, creams, and lotions, as well as in a variety of food and beverage products, and it is known for its anti-inflammatory, local anaesthetic, and antifungal properties. It is also a potent cytotoxic compound over a wide range of cell lines. In the current paper, we found that Commiphora gileadensis stem extracts and essential oil have an antiproliferative proapoptotic effect against tumor cells and not against normal cells. β-caryophyllene caused a potent induction of apoptosis accompanied by DNA ladder and caspase-3 catalytic activity in tumor cell lines. In summary, we showed that C. gileadensis stems contain an apoptosis inducer that acts, in a selective manner, against tumor cell lines and not against normal cells.

Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

Energy Technology Data Exchange (ETDEWEB)

Henderson, R.F.; Waide, J.J.; Lechner, J.F.

1995-12-01

A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

International Nuclear Information System (INIS)

Arenz, Andrea; Ziemann, Frank; Wittig, Andrea; Preising, Stefanie; Engenhart-Cabillic, Rita; Mayer, Christina; Wagner, Steffen; Klussmann, Jens-Peter; Wittekindt, Claus; Dreffke, Kirstin

2014-01-01

Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair. (orig.) [de

Banana (Musa. spp.) strain HD-1 appraisal

International Nuclear Information System (INIS)

Longyan, G.; Xinguo, L.; Lingxia, W.; Xuefei, J.

2016-01-01

Being one of the important tropical and subtropical fruit trees, banana (Musa spp.) belongs to the family Musaceae and the order Scitaminae with two genera, Musa and Ensete. In a field survey, research team has discovered a potential banana mutant strain HD-1 with a sound economic value. The results of the finding are as follows: based on Simmonds classification, the pseudostem of banana strain HD-1 is relatively short and purplish red; its upright outward petiole groove has red edges and wraps its pseudostem loosely. Its ploidy is 3, AAA type. Karyotype analysis shows that the number of chromosomes is 33, the karyotype formula is 2n=3x=33=2L + 3 M2 + 4 M1 + 2 S, HD-1 is classified as 1B type. With the help of ISSR molecular markers, we find thatbanana HD-1 has the closest relationship with Pubei and Tianbao dwarf banana; the similarity coefficient is 0.81. In an artificial simulation tests of cold, drought and salt resistance environment changes of physiological and biochemical indexes indicate that HD-1 exhibits stronger defense capability than Brazil banana. By way of inoculation with injury of root dipping method, we respectively treat two kinds of banana seedlings inoculated Banana Fusarium wilt race 4 small species. The results show that their resistance evaluation scores are 3 and 4, disease levels are susceptible and high sensitivity respectively. We conclude that HD-1 has stronger resistance ability to Fusarium wilt than Brazil banana. (author)

Change of cell cycle arrest of tumor cell lines after 60Co γ-irradiation

International Nuclear Information System (INIS)

Tang Yi; Liu Wenli; Zhou Jianfeng; Gao Qinglei; Wu Jianhong

2003-01-01

Objective: To observe the cell cycle arrest changes in peripheral blood mononuclear cells (PBMNCs) of normal persons and several kinds of tumor cell lines after 60 Co γ-irradiation. Methods: PBMNCs of normal persons, HL-60, K562, SiHA and 113 tumor cell lines were irradiated with 60 Co γ-rays at the absorbed doses of 6, 10,15 Gy. Cell cycles changes were checked 6, 12, 24, 48 and 60 h after the irradiation. Results: A stasis state was observed in normal person PBMNCs, 95 percents of which were in G 1 phase, and they still remained stasis after the irradiation. Except the 113 cell line manifesting G 1 phase arrest, all other tumor cell lines showed G 2 /M phase arrest after irradiation. The radiation sensitivity of HL-60 was higher than that of SiHA cell line. Conclusion: Different cell lines have different cell cycle arrest reaction to radiation and their radiation sensitivity are also different

Combination therapy with vemurafenib (PLX4032/RG7204 and metformin in melanoma cell lines with distinct driver mutations

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Recio Juan A

2011-05-01

Full Text Available Abstract Background A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines. Materials and methods The combination of the BRAF inhibitor vemurafenib (formerly PLX4032 and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot. Results Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants, including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways. Conclusions The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.

Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes.

OpenAIRE

Taylor, G.M.; Gokhale, D.A.; Crowther, D.; Woll, P.J.; Harris, M.; Ryder, D.; Ayres, M.; Radford, J.A.

1999-01-01

It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS)...

Game-based combined cognitive and neurofeedback training using Focus Pocus reduces symptom severity in children with diagnosed AD/HD and subclinical AD/HD.

Science.gov (United States)

Johnstone, Stuart J; Roodenrys, Steven J; Johnson, Kirsten; Bonfield, Rebecca; Bennett, Susan J

2017-06-01

Previous studies report reductions in symptom severity after combined working memory (WM) and inhibitory control (IC) training in children with AD/HD. Based on theoretical accounts of the role of arousal/attention modulation problems in AD/HD, the current study examined the efficacy of combined WM, IC, and neurofeedback training in children with AD/HD and subclinical AD/HD. Using a randomized waitlist control design, 85 children were randomly allocated to a training or waitlist condition and completed pre- and post-training assessments of overt behavior, trained and untrained cognitive task performance, and resting and task-related EEG activity. The training group completed twenty-five sessions of training using Focus Pocus software at home over a 7 to 8-week period. Trainees improved at the trained tasks, while enjoyment and engagement declined across sessions. After training, AD/HD symptom severity was reduced in the AD/HD and subclinical groups according to parents, and in the former group only according to blinded teachers and significant-others. There were minor improvements in two of six near-transfer tasks, and evidence of far-transfer of training effects in four of five far-transfer tasks. Frontal region changes indicated normalization of atypical EEG features with reduced delta and increased alpha activity. It is concluded that technology developments provide an interesting a vehicle for delivering interventions and that, while further research is needed, combined WM, IC, and neurofeedback training can reduce AD/HD symptom severity in children with AD/HD and may also be beneficial to children with subclinical AD/HD. Copyright © 2017 Elsevier B.V. All rights reserved.

ACCRETION KINEMATICS THROUGH THE WARPED TRANSITION DISK IN HD 142527 FROM RESOLVED CO(6–5) OBSERVATIONS

Energy Technology Data Exchange (ETDEWEB)

Casassus, S.; Marino, S.; Pérez, S.; Plas, G. van der; Christiaens, V.; Montesinos, Matías [Departamento de Astronomía, Universidad de Chile, Casilla 36-D, Santiago (Chile); Roman, P.; Dunhill, A.; Cuadra, J.; Cieza, L.; Moral, Victor [Millennium Nucleus “Protoplanetary Disks,” Chile (Chile); Armitage, P. J. [JILA, University of Colorado and NIST, UCB 440, Boulder, CO 80309 (United States); Wootten, A., E-mail: scasassus@u.uchile.cl [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903-2475 (United States)

2015-10-01

The finding of residual gas in the large central cavity of the HD 142527 disk motivates questions regarding the origin of its non-Keplerian kinematics and possible connections with planet formation. We aim to understand the physical structure that underlies the intra-cavity gaseous flows, guided by new molecular-line data in CO(6–5) with unprecedented angular resolutions. Given the warped structure inferred from the identification of scattered-light shadows cast on the outer disk, the kinematics are consistent, to first order, with axisymmetric accretion onto the inner disk occurring at all azimuths. A steady-state accretion profile, fixed at the stellar accretion rate, explains the depth of the cavity as traced in CO isotopologues. The abrupt warp and evidence for near free-fall radial flows in HD 142527 resemble theoretical models for disk tearing, which could be driven by the reported low-mass companion, whose orbit may be contained in the plane of the inner disk. The companion’s high inclination with respect to the massive outer disk could drive Kozai oscillations over long timescales; high-eccentricity periods may perhaps account for the large cavity. While shadowing by the tilted disk could imprint an azimuthal modulation in the molecular-line maps, further observations are required to ascertain the significance of azimuthal structure in the density field inside the cavity of HD 142527.

Water line positions in the 782–840 nm region

International Nuclear Information System (INIS)

Hu, S.-M.; Chen, B.; Tan, Y.; Wang, J.; Cheng, C.-F.; Liu, A.-W.

2015-01-01

A set of water transitions in the 782–840 nm region, including 38 H 2 16 O lines, 12 HD 16 O lines, and 30 D 2 16 O lines, were recorded with a cavity ring-down spectrometer calibrated using precise atomic lines. Absolute frequencies of the lines were determined with an accuracy of about 5 MHz. Systematic shifts were found in the line positions given in the HITRAN database and the upper energy levels given in recent MARVEL studies. - Highlights: • Cavity ring-down spectra of H 2 16 O, HD 16 O, and D 2 16 O lines in the 782–840 nm region were measured. • Absolute line positions of 80 water lines were determined with an accuracy of about 5 MHz. • The H 2 16 O positions given in HITRAN have a systematic shift of 0.001 cm −1 in the 796–840 nm region. • MARVEL D 2 16 O energies have a systematic deviation of about −0.008 cm −1

Absolute parameters of southern detached eclipsing binary: HD 53570

Science.gov (United States)

Sürgit, D.

2018-05-01

In this study, we conducted the first analysis of spectroscopic and photometric observations of the eclipsing binary star HD 53570. Spectroscopic observations of HD 53570 were made at the Sutherland Station of the South African Astronomical Observatory in 2013 and 2014. The radial velocities of the components were determined using the cross-correlation technique. The spectroscopic mass ratio obtained for the system was 1.13 ( ± 0.07). The All Sky Automated Survey V light curve of HD 53570 was analyzed using the Wilson-Devinney code combined with the Monte Carlo search method. The final model showed that HD 53570 has a detached configuration. The mass and radii of the primary and secondary components of HD 53570 were derived as 1.06 ( ± 0.07) M⊙, 1.20 ( ± 0.16) M⊙, and 1.42 ( ± 0.14) R⊙, 2.07 ( ± 0.16) R⊙, respectively. The distance of HD 53570 was computed as 248 ( ± 38) pc considering interstellar extinction. The evolutionary status of the component stars was also investigated using Geneva evolutionary models.

Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Morling, N

1988-01-01

.01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P less than or equal to 0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data...... monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c...

Pulsed high-dose dexamethasone modulates Th1-/Th2-chemokine imbalance in immune thrombocytopenia.

Science.gov (United States)

Liu, Zongtang; Wang, Meiying; Zhou, Shufen; Ma, Ji; Shi, Yan; Peng, Jun; Hou, Ming; Guo, Chengshan

2016-10-24

Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways. Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied. Plasma levels of CCL5 and CXCL11 (Th1-associated) and of CCL11 (Th2-associated) were determined by ELISA. Gene expression of these three chemokines and their corresponding receptors CCR5, CXCR3, and CCR3, in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR. Thirty-three of the thirty-eight ITP patients responded effectively to HD-DXM (oral, 40 mg/day, 4 days). In ITP patients, plasma CXCL11 levels increased, while CCL11 and CCL5 decreased compared to controls (P Th1-/Th2-associated chemokines and chemokine receptors may play important roles in the pathogenesis of ITP. Importantly, regulating Th1 polarization by pulsed HD-DXM may represent a novel approach for immunoregulation in ITP.

Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and Thereof Derived Primary Cultures and Cell Lines

Directory of Open Access Journals (Sweden)

Susanne C. Hammer

2016-09-01

Full Text Available Human and canine mammary tumours show partial claudin expression deregulations. Further, claudins have been used for directed therapeutic approaches. However, the development of claudin targeting approaches requires stable claudin expressing cell lines. This study reports the establishment and characterisation of canine mammary tissue derived cell lines, analysing longitudinally the claudin-1, -3, -4 and -7 expressions in original tissue samples, primary cultures and developed cell lines. Primary cultures were derived from 17 canine mammary tissues: healthy, lobular hyperplasia, simple adenoma, complex adenoma, simple tubular carcinoma, complex carcinoma, carcinoma arising in a benign mixed tumour and benign mixed tissue. Cultivation was performed, if possible, until passage 30. Claudin mRNA and protein expressions were analysed by PCR, QuantiGene Plex Assay, immunocytochemistry and immunofluorescence. Further, cytokeratin expression was analysed immunocytochemically. Cultivation resulted in 11 established cell lines, eight showing epithelial character. In five of the early passages the claudin expressions decreased compared to the original tissues. In general, claudin expressions were diminished during cultivation. Three cell lines kept longitudinally claudin, as well as epithelial marker expressions, representing valuable tools for the development of claudin targeted anti-tumour therapies.

Studies on the potency of oral polio vaccine using RD cell line and ...

African Journals Online (AJOL)

Studies on the potency of oral polio vaccine using RD cell line and evaluation of growth using different serum concentration and volume of media. ... The culture flasks containing different volumes of growth medium with 10% serum concentration such as 8, 9, 10, 11 and 12 ml were added to a series of culture flasks. All the ...

Derivation and characterization of a pig embryonic stem cell-derived exocrine pancreatic cell line

Science.gov (United States)

The establishment and initial characterization of a pig embryonic stem cell-derived pancreatic cell line, PICM-31, and a colony-cloned derivative cell line, PICM-31A, is described. The cell lines were propagated for several months at split ratios of 1:3 or 1:5 at each passage on STO feeder cells af...

THREE-DIMENSIONAL ATMOSPHERIC CIRCULATION MODELS OF HD 189733b AND HD 209458b WITH CONSISTENT MAGNETIC DRAG AND OHMIC DISSIPATION

International Nuclear Information System (INIS)

Rauscher, Emily; Menou, Kristen

2013-01-01

We present the first three-dimensional circulation models for extrasolar gas giant atmospheres with geometrically and energetically consistent treatments of magnetic drag and ohmic dissipation. Atmospheric resistivities are continuously updated and calculated directly from the flow structure, strongly coupling the magnetic effects with the circulation pattern. We model the hot Jupiters HD 189733b (T eq ≈ 1200 K) and HD 209458b (T eq ≈ 1500 K) and test planetary magnetic field strengths from 0 to 30 G. We find that even at B = 3 G the atmospheric structure and circulation of HD 209458b are strongly influenced by magnetic effects, while the cooler HD 189733b remains largely unaffected, even in the case of B = 30 G and super-solar metallicities. Our models of HD 209458b indicate that magnetic effects can substantially slow down atmospheric winds, change circulation and temperature patterns, and alter observable properties. These models establish that longitudinal and latitudinal hot spot offsets, day-night flux contrasts, and planetary radius inflation are interrelated diagnostics of the magnetic induction process occurring in the atmospheres of hot Jupiters and other similarly forced exoplanets. Most of the ohmic heating occurs high in the atmosphere and on the dayside of the planet, while the heating at depth is strongly dependent on the internal heat flux assumed for the planet, with more heating when the deep atmosphere is hot. We compare the ohmic power at depth in our models, and estimates of the ohmic dissipation in the bulk interior (from general scaling laws), to evolutionary models that constrain the amount of heating necessary to explain the inflated radius of HD 209458b. Our results suggest that deep ohmic heating can successfully inflate the radius of HD 209458b for planetary magnetic field strengths of B ≥ 3-10 G.

Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

International Nuclear Information System (INIS)

Playle, L.C.

2001-03-01

The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

Polymer encapsulated dopaminergic cell lines as "alternative neural grafts".

Science.gov (United States)

Jaeger, C B; Greene, L A; Tresco, P A; Winn, S R; Aebischer, P

1990-01-01

Our preliminary findings (Jaeger et al., 1988; Aebischer et al., 1989; Tresco et al., 1989) and the studies in progress show that encapsulated dopaminergic cell lines survive enclosure within a semi-permeable membrane. The encapsulated cells remained viable for extended time periods when maintained in vitro. Moreover, encapsulated PC12 and T28 cells have the potential to survive following their implantation into the forebrain of rats. Cell lines are essentially "immortal" because they continue to divide indefinitely. This property allows perpetual "self-renewal" of a given cell population. However, the capacity of continuous uncontrolled cell division may also lead to tumor formation. This in fact is the case for unencapsulated PC12 cell implants placed into the brain of young Sprague Dawley rats (Jaeger, 1985). Cell line encapsulation has the potential to prevent tumor growth (Jaeger et al., 1988). Survival for 6 months in vitro suggests that encapsulation does not preclude long-term maintenance of an homogeneous cell line like PC12 cells. The presence of mitotic figures in the capsules further supports the likelihood of propagation and self renewal of the encapsulated population. Another significant property of cell lines is that they consist of a single, genetically homogeneous cell type. They do not require specific synaptic interactions for their survival. In the case of PC12 and T28 lines, the cells synthesize and release neurotransmitters. Our data show that PC12 and T28 cells continue to release dopamine spontaneously and to express specific transmitters and enzymes following encapsulation. Thus, cell lines such as these may constitute relatively simple "neural implants" exerting their function via humoral release.(ABSTRACT TRUNCATED AT 250 WORDS)

Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research.

Science.gov (United States)

Kniss, Douglas A; Summerfield, Taryn L

2014-08-01

Continuous cell lines are used frequently in reproductive biology research to study problems in early pregnancy events and parturition. It has been recognized for 50 years that many mammalian cell lines contain inter- or intraspecies contaminations with other cells. However, most investigators do not routinely test their culture systems for cross-contamination. The most frequent contributor to cross-contamination of cell lines is the HeLa cell isolated from an aggressive cervical adenocarcinoma. We report on the discovery of HeLa cell contamination of the human endometrial epithelial cell line HES isolated in our laboratory. Short tandem repeat analysis of 9 unique genetic loci demonstrated molecular identity between HES and HeLa cells. In addition, we verified that WISH cells, isolated originally from human amnion epithelium, were also contaminated with HeLa cells. Inasmuch as our laboratory did not culture HeLa cells at the time of HES cell derivations, the source of contamination was the WISH cell line. These data highlight the need for continued diligence in authenticating cell lines used in reproductive biology research. © The Author(s) 2014.

Variations of brightness and Ca 2 emission of the xi Boo AB and HD 1835 dWarf G stars

Energy Technology Data Exchange (ETDEWEB)

Chuganov, P.F.

1983-01-01

75 photoelectric UBV-observations of xi Boo AB were obtained during 45 nights in 1980. Real light variations of several thousandths of magnitude are revealed. Moreover, the variations observed in two nights were resembling flares. Both recent and published data on HD 1835 together with Wilson's observations of H and K Ca II lines in the spectra of xi Boo A, xi Boo B and HD 1835 are used for the search of periodicities. The periodicities are present in variations of light and Ca II -emission. Periodicities are more prominent in light variations (periods are 10 days for xi Boo AB and 7.66 days for HD 1835). In H and K Ca II lines the duration of cycles is different but the basic period is the same as in light variations. Therefore, the basic period (interpreted as the period of star roration) can be revealed only from a very long run of H and K Ca II observations (approximately 150). Light variations of xi Boo AB are probably due to the A-component since the basic period of Ca II-variations in xi Boo A is approximately the same (10 days). The basic period of Ca II-variations in xi Boo B is considerably larger.

Variations of brightness and Ca 2 emission of the xi Boo AB and HD 1835 dWarf G stars

International Nuclear Information System (INIS)

Chuganov, P.F.

1983-01-01

75 photoelectric UBV-observations of xi Boo AB were obtained during 45 nights in 1980. Real light variations of several thousandths of magnitude are revealed. Moreover, the variations observed in two nights were resembling flares. Both recent and published data on HD 1835 together with Wilson's observations of H and K Ca II lines in the spectra of xi Boo A, xi Boo B and HD 1835 are used for the search of periodicities. The periodicities are present in variations of light and Ca II -emission. Periodicities are more prominent in light variations (periods are 10 days for xi Boo AB and 7.66 days for HD 1835). In H and K Ca II lines the dura-- tion of cycles is different but the basic period is the same as in light variations. Therefore, the basic period (interpreted as the period of star roration) can be revealed only from a very long run of H and K Ca II observations (approximately 150). Light variations of xi Boo AB are probably due to the A-component since the basic period of Ca II-variations in xi Boo A is approximately the same (10 days). The basic period of Ca II-variations in xi Boo B is considerably larger;

Low-frequency photospheric and wind variability in the early-B supergiant HD2905

DEFF Research Database (Denmark)

Simon-Diaz, S.; Aerts, C.; Urbaneja, M. A.

2018-01-01

to the lack of adequate observations for a proper characterization of the complex spectroscopic and photometric variability occurring in these stars. Aims. Our goal is to detect, analyze, and interpret variability in the early-B-type supergiant HD2905 (kappa Cas, B1 Ia) using long-term, ground-based, high...... snapshot and time-dependent information about the stellar parameters and abundances by means of the FASTWIND stellar atmosphere code. Results. HD2905 is a spectroscopic variable with peak-to-peak amplitudes in the zero and first moments of the photospheric lines of up to 15% and 30 km s(-1), respectively....... Conclusions. Combined long-term uninterrupted space photometry with high-precision spectroscopy is the best strategy to unravel the complex low-frequency photospheric and wind variability of B supergiants. Three-dimensional (3D) simulations of waves and of convective motions in the sub-surface layers can shed...

THP-1 cell line: an in vitro cell model for immune modulation approach.

Science.gov (United States)

Chanput, Wasaporn; Mes, Jurriaan J; Wichers, Harry J

2014-11-01

THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. This cell line has become a common model to estimate modulation of monocyte and macrophage activities. This review attempts to summarize and discuss recent publications related to the THP-1 cell model. An overview on the biological similarities and dissimilarities between the THP-1 cell line and human peripheral blood mononuclear cell (PBMC) derived-monocytes and macrophages, as well as the advantages and disadvantages of the use of THP-1 cell line, is included. The review summarizes different published co-cultivation studies of THP-1 cells with other cell types, for instance, intestinal cells, adipocytes, T-lymphocytes, platelets, and vascular smooth muscle cells, which can be an option to study cell-cell interaction in vitro and can be an approach to better mimic in vivo conditions. Macrophage polarization is a relatively new topic which gains interest for which the THP-1 cell line also may be relevant. Besides that an overview of newly released commercial THP-1 engineered-reporter cells and THP-1 inflammasome test-cells is also given. Evaluation of recent papers leads to the conclusion that the THP-1 cell line has unique characteristics as a model to investigate/estimate immune-modulating effects of compounds in both activated and resting conditions of the cells. Although the THP-1 response can hint to potential responses that might occur ex vivo or in vivo, these should be, however, validated by in vivo studies to draw more definite conclusions. Copyright © 2013. Published by Elsevier B.V.

Chemical spots on the surface of the strongly magnetic Herbig Ae star HD 101412

DEFF Research Database (Denmark)

Järvinen, S. P.; Hubrig, S.; Schöller, M.

2016-01-01

Due to the knowledge of the rotation period and the presence of a rather strong surface magnetic field, the sharp-lined young Herbig Ae star HD 101412 with a rotation period of 42 d has become one of the most well-studied targets among the Herbig Ae stars. High-resolution HARPS polarimetric spectra...... that is opposite to the behaviour of the other elements studied. Since classical Ap stars usually show a relationship between the magnetic field geometry and the distribution of element spots, we used in our magnetic field measurements different line samples belonging to the three elements with the most numerous...

Differential heat shock response of primary human cell cultures and established cell lines

DEFF Research Database (Denmark)

Richter, W W; Issinger, O G

1986-01-01

degrees C treatment, whereas in immortalized cell lines usually 90% of the cells were found in suspension. Enhanced expression of the major heat shock protein (hsp 70) was found in all heat-treated cells. In contrast to the primary cell cultures, established and transformed cell lines synthesized...

Radiation response of haematopoietic cell lines of human origin

International Nuclear Information System (INIS)

Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.

1986-01-01

Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

Human rhabdomyosarcoma cell lines for rhabdomyosarcoma research: Utility and pitfalls

Directory of Open Access Journals (Sweden)

Ashley R.P. Hinson

2013-07-01

Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue sarcoma of childhood and adolescence. Despite intergroup clinical trials conducted in Europe and North America, outcomes for high risk patients with this disease have not significantly improved in the last several decades, and survival of metastatic or relapsed disease remains extremely poor. Accrual into new clinical trials is slow and difficult, so in vitro cell line research and in vivo xenograft models present an attractive alternative for preclinical research for this cancer type. Currently, 30 commonly used human RMS cell lines exist, with differing origins, karyotypes, histologies, and methods of validation. Selecting an appropriate cell line for RMS research has important implications for outcomes. There are also potential pitfalls in using certain cell lines including contamination with murine stromal cells, cross-contamination between cell lines, discordance between the cell line and its associated original tumor, imposter cell lines, and nomenclature errors that result in the circulation of two or more presumed unique cell lines that are actually from the same origin. These pitfalls can be avoided by testing for species-specific isoenzymes, microarray analysis, assays for subtype-specific fusion products, and short tandem repeat analysis.

Human Rhabdomyosarcoma Cell Lines for Rhabdomyosarcoma Research: Utility and Pitfalls

Science.gov (United States)

Hinson, Ashley R. P.; Jones, Rosanne; Crose, Lisa E. S.; Belyea, Brian C.; Barr, Frederic G.; Linardic, Corinne M.

2013-01-01

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Despite intergroup clinical trials conducted in Europe and North America, outcomes for high risk patients with this disease have not significantly improved in the last several decades, and survival of metastatic or relapsed disease remains extremely poor. Accrual into new clinical trials is slow and difficult, so in vitro cell-line research and in vivo xenograft models present an attractive alternative for preclinical research for this cancer type. Currently, 30 commonly used human RMS cell lines exist, with differing origins, karyotypes, histologies, and methods of validation. Selecting an appropriate cell line for RMS research has important implications for outcomes. There are also potential pitfalls in using certain cell lines including contamination with murine stromal cells, cross-contamination between cell lines, discordance between the cell line and its associated original tumor, imposter cell lines, and nomenclature errors that result in the circulation of two or more presumed unique cell lines that are actually from the same origin. These pitfalls can be avoided by testing for species-specific isoenzymes, microarray analysis, assays for subtype-specific fusion products, and short tandem repeat analysis. PMID:23882450

Radiation sensitivity of human lung cancer cell lines

International Nuclear Information System (INIS)

Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

1989-01-01

X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

Generation of genome-modified Drosophila cell lines using SwAP.

Science.gov (United States)

Franz, Alexandra; Brunner, Erich; Basler, Konrad

2017-10-02

The ease of generating genetically modified animals and cell lines has been markedly increased by the recent development of the versatile CRISPR/Cas9 tool. However, while the isolation of isogenic cell populations is usually straightforward for mammalian cell lines, the generation of clonal Drosophila cell lines has remained a longstanding challenge, hampered by the difficulty of getting Drosophila cells to grow at low densities. Here, we describe a highly efficient workflow to generate clonal Cas9-engineered Drosophila cell lines using a combination of cell pools, limiting dilution in conditioned medium and PCR with allele-specific primers, enabling the efficient selection of a clonal cell line with a suitable mutation profile. We validate the protocol by documenting the isolation, selection and verification of eight independently Cas9-edited armadillo mutant Drosophila cell lines. Our method provides a powerful and simple workflow that improves the utility of Drosophila cells for genetic studies with CRISPR/Cas9.

An explanation of the radio flux mystery of HD 192163 and empirical models for WN stars

International Nuclear Information System (INIS)

Nugis, T.

1982-01-01

The radio flux value of the star HD 192163 (WN6) measured by Dickel et al. (1980) imposes strong restrictions on the possible mass outflow region models of this star. Dickel et al. (1980) and also Barlow et al. (1980) suggested that the wind terminal velocity has not been reached in the IR emission region. But when taking into account the line spectrum data, it appears that the wind velocity must be comparatively close to the star already nearly constant. So it is necessary to search for some other explanation. The author has found that at reasonable values of density, electron and core (star) temperatures it is possible that helium becomes neutral at a comparatively large distance from the star and then the radio flux is mainly due to the f-f radiation of H + and N + . In the case of such an ionization structure there are no restrictions on the outflow velocity being already constant close to the star. Therefore it is now possible to explain the radio and IR fluxes as well as the line spectrum data of HD 192163. (Auth.)

Apoptosis induction in MV4-11 and K562 human leukemic cells by Pereskia sacharosa (Cactaceae) leaf crude extract.

Science.gov (United States)

Asmaa, Mat Jusoh Siti; Al-Jamal, Hamid Ali Nagi; Ang, Cheng Yong; Asan, Jamaruddin Mat; Seeni, Azman; Johan, Muhammad Farid

2014-01-01

Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia. Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. IC50 concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting. P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells. These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.

Peptidomic analysis of human cell lines

Science.gov (United States)

Gelman, Julia S.; Sironi, Juan; Castro, Leandro M.; Ferro, Emer S.; Fricker, Lloyd D.

2011-01-01

Peptides have been proposed to function in intracellular signaling within the cytosol. Although cytosolic peptides are considered to be highly unstable, a large number of peptides have been detected in mouse brain and other biological samples. In the present study, we evaluated the peptidome of three diverse cell lines: SH-SY5Y, MCF7, and HEK293 cells. A comparison of the peptidomes revealed considerable overlap in the identity of the peptides found in each cell line. The majority of the observed peptides are not derived from the most abundant or least stable proteins in the cell, and approximately half of the cellular peptides correspond to the N- or C- termini of the precursor proteins. Cleavage site analysis revealed a preference for hydrophobic residues in the P1 position. Quantitative peptidomic analysis indicated that the levels of most cellular peptides are not altered in response to elevated intracellular calcium, suggesting that calpain is not responsible for their production. The similarity of the peptidomes of the three cell lines and the lack of correlation with the predicted cellular degradome implies the selective formation or retention of these peptides, consistent with the hypothesis that they are functional in the cells. PMID:21204522

Quality control of involved field radiotherapy in the HD 13 and HD 14 trials. Report of the radiotherapy panel of the German Hodgkin Study Group (GHSG)

International Nuclear Information System (INIS)

Kriz, J.; Haverkamp, U.; Eich, H.T.; Baues, C.; Engenhart-Cabillic, R.; Herfarth, K.; Lukas, P.; Pluetschow, A.; Fuchs, M.; Engert, A.; Schmidberger, H.; Staar, S.

2017-01-01

As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings. With the start of the fourth GHSG study generation (HD10-12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13-15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation. The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %). The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of ''modern RT'' in malignant lymphoma. (orig.) [de

The transcriptional diversity of 25 Drosophila cell lines

Energy Technology Data Exchange (ETDEWEB)

Cherbas, Lucy [Indiana Univ., Bloomington, IN (United States); Willingham, Aarron [Affymetrix Inc., Santa Clara, CA (United States); Zhang, Dayu [Indiana Univ., Bloomington, IN (United States); Yang, Li [University of Connecticut Health Center, Farmington, Connecticut (United States); Zou, Yi [Indiana Univ., Bloomington, IN (United States); Eads, Brian D. [Indiana Univ., Bloomington, IN (United States); Carlson, Joseph W. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Landolin, Jane M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kapranov, Philipp [Affymetrix Inc., Santa Clara, CA (United States); Dumais, Jacqueline [Affymetrix Inc., Santa Clara, CA (United States); Samsonova, Anastasia [Harvard Medical School, Boston, MA (United States); Choi, Jeong-Hyeon [Indiana Univ., Bloomington, IN (United States); Roberts, Johnny [Indiana Univ., Bloomington, IN (United States); Davis, Carrie A. [Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (United States); Tang, Haixu [Indiana Univ., Bloomington, IN (United States); van Baren, Marijke J. [Washington Univ., St. Louis, MO (United States); Ghosh, Srinka [Affymetrix Inc., Santa Clara, CA (United States); Dobin, Alexander [Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (United States); Bell, Kim [Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (United States); Lin, Wei [Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (United States); Langton, Laura [Washington Univ., St. Louis, MO (United States); Duff, Michael O. [University of Connecticut Health Center, Farmington, Connecticut (United States); Tenney, Aaron E. [Washington Univ., St. Louis, MO (United States); Zaleski, Chris [Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (United States); Brent, Michael R. [Washington Univ., St. Louis, MO (United States); Hoskins, Roger A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kaufman, Thomas C. [Indiana University, Bloomington, Indiana (United States); Andrews, Justen [Indiana University, Bloomington, Indiana (United States); Graveley, Brenton R. [University of Connecticut Health Center, Farmington, Connecticut (United States); Perrimon, Norbert [Harvard Medical School, Boston, MA (United States); Howard Hughes Medical Institute, Boston, MA (United States); Celniker, Susan E. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gingeras, Thomas R. [Affymetrix Inc., Santa Clara, CA (United States); Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (United States); Cherbas, Peter [Indiana Univ., Bloomington, IN (United States)

2010-12-22

Drosophila melanogaster cell lines are important resources for cell biologists. In this article, we catalog the expression of exons, genes, and unannotated transcriptional signals for 25 lines. Unannotated transcription is substantial (typically 19% of euchromatic signal). Conservatively, we identify 1405 novel transcribed regions; 684 of these appear to be new exons of neighboring, often distant, genes. Sixty-four percent of genes are expressed detectably in at least one line, but only 21% are detected in all lines. Each cell line expresses, on average, 5885 genes, including a common set of 3109. Expression levels vary over several orders of magnitude. Major signaling pathways are well represented: most differentiation pathways are ‘‘off’’ and survival/growth pathways ‘‘on.’’ Roughly 50% of the genes expressed by each line are not part of the common set, and these show considerable individuality. Thirty-one percent are expressed at a higher level in at least one cell line than in any single developmental stage, suggesting that each line is enriched for genes characteristic of small sets of cells. Most remarkable is that imaginal disc-derived lines can generally be assigned, on the basis of expression, to small territories within developing discs. These mappings reveal unexpected stability of even fine-grained spatial determination. No two cell lines show identical transcription factor expression. We conclude that each line has retained features of an individual founder cell superimposed on a common ‘‘cell line‘‘ gene expression pattern. We report the transcriptional profiles of 25 Drosophila melanogaster cell lines, principally by whole-genome tiling microarray analysis of total RNA, carried out as part of the modENCODE project. The data produced in this study add to our knowledge of the cell lines and of the Drosophila transcriptome in several ways. We summarize the expression of previously annotated genes in each of the 25

HD 285507b

DEFF Research Database (Denmark)

Quinn, Samuel N.; White, Russel J.; Latham, David W.

2014-01-01

We report the discovery of the first hot Jupiter in the Hyades open cluster. HD 285507b orbits a V = 10.47 K4.5V dwarf (M * = 0.734 M ☉; R * = 0.656 R ☉) in a slightly eccentric () orbit with a period of days. The induced stellar radial velocity corresponds to a minimum companion mass of M Psin i...... timescale for HD 285507b to be larger than the age of the Hyades, which may indicate that this planet's non-zero eccentricity is the result of migration via interactions with a third body. We also demonstrate a significant difference between the eccentricity distributions of hot Jupiters that have had time...... to tidally circularize and those that have not, which we interpret as evidence against Type II migration in the final stages of hot Jupiter formation. Finally, the dependence of the circularization timescale on the planetary tidal quality factor, Q P, allows us to constrain the average value for hot Jupiters to be ....

DISEQUILIBRIUM CARBON, OXYGEN, AND NITROGEN CHEMISTRY IN THE ATMOSPHERES OF HD 189733b AND HD 209458b

International Nuclear Information System (INIS)

Moses, Julianne I.; Visscher, C.; Fortney, J. J.; Showman, A. P.; Lewis, N. K.; Griffith, C. A.; Klippenstein, S. J.; Shabram, M.; Friedson, A. J.; Marley, M. S.; Freedman, R. S.

2011-01-01

We have developed a one-dimensional photochemical and thermochemical kinetics and diffusion model to study the effects of disequilibrium chemistry on the atmospheric composition of 'hot-Jupiter' exoplanets. Here we investigate the coupled chemistry of neutral carbon, hydrogen, oxygen, and nitrogen species on HD 189733b and HD 209458b and we compare the model results with existing transit and eclipse observations. We find that the vertical profiles of molecular constituents are significantly affected by transport-induced quenching and photochemistry, particularly on the cooler HD 189733b; however, the warmer stratospheric temperatures on HD 209458b help maintain thermochemical equilibrium and reduce the effects of disequilibrium chemistry. For both planets, the methane and ammonia mole fractions are found to be enhanced over their equilibrium values at pressures of a few bar to less than an mbar due to transport-induced quenching, but CH 4 and NH 3 are photochemically removed at higher altitudes. Disequilibrium chemistry also enhances atomic species, unsaturated hydrocarbons (particularly C 2 H 2 ), some nitriles (particularly HCN), and radicals like OH, CH 3 , and NH 2 . In contrast, CO, H 2 O, N 2 , and CO 2 more closely follow their equilibrium profiles, except at pressures ∼ 2 O, and N 2 are photochemically destroyed and CO 2 is produced before its eventual high-altitude destruction. The enhanced abundances of CH 4 , NH 3 , and HCN are expected to affect the spectral signatures and thermal profiles of HD 189733b and other relatively cool, transiting exoplanets. We examine the sensitivity of our results to the assumed temperature structure and eddy diffusion coefficients and discuss further observational consequences of these models.

Analysis of DNA repair in XP-HeLa hybrids; lack of correlation between excision repair of u.v. damage and adenovirus reactivation in an XP(D)-like cell line

International Nuclear Information System (INIS)

Johnson, R.Y.; Squires, S.; Elliott, G.C.

1986-01-01

Hybrids formed between HeLa cells and fibroblasts from xeroderma pigmentosum group D show either HeLa sensitivity or XPD-like hypersensitivity to u.v. radiation and corresponding high or low excision repair capability. Hybrids with low repair are presumed to have lost, via chromosome segregation, the HeLa wild type D alleles. The u.v. sensitivity and excision repair capability of another hybrid, HD1A, derived spontaneously from the normally sensitive hybrid HD1 are analyzed. While HD1A closely resembles the XPD phenotype in terms of u.v. sensitivity and excision repair it differs from XPD because of its ability to reactivate u.v.-irradiated adenovirus 2 to an extent similar to that of its HeLa parent. This capacity functionally dissociates excision repair of chromatin-based damage from damage in a viral environment. Moreover, on the basis of complementation studies the excision repair of genomic damage by HD1A is subtly different from that of a true XPD-like hybrid, HD2. The data are discussed in terms of a second change in the defective D allele of the HD1A cell. (author)

ROVIBRATIONAL QUENCHING RATE COEFFICIENTS OF HD IN COLLISIONS WITH He

International Nuclear Information System (INIS)

Nolte, J. L.; Stancil, P. C.; Lee, T.-G.; Balakrishnan, N.; Forrey, R. C.

2012-01-01

Along with H 2 , HD has been found to play an important role in the cooling of the primordial gas for the formation of the first stars and galaxies. It has also been observed in a variety of cool molecular astrophysical environments. The rate of cooling by HD molecules requires knowledge of collisional rate coefficients with the primary impactors, H, He, and H 2 . To improve knowledge of the collisional properties of HD, we present rate coefficients for the He-HD collision system over a range of collision energies from 10 –5 to 5 × 10 3 cm –1 . Fully quantum mechanical scattering calculations were performed for initial HD rovibrational states of j = 0 and 1 for v = 0-17 which utilized accurate diatom rovibrational wave functions. Rate coefficients of all Δv = 0, –1, and –2 transitions are reported. Significant discrepancies with previous calculations, which adopted a small basis and harmonic HD wave functions for excited vibrational levels, were found for the highest previously considered vibrational state of v = 3. Applications of the He-HD rate coefficients in various astrophysical environments are briefly discussed.

Which Executive Functioning Deficits Are Associated with AD/HD, ODD/CD and Comorbid AD/HD+ODD/CD? (Attention Deficit/hyperactivity Disorder)(Oppositional Defiant Disorder)

Science.gov (United States)

Oosterlaan, Jaap; Scheres, Anouk; Sergeant, Joseph A.

2005-01-01

This study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3) whether a combination of AD/HD and ODD/CD…

Investigation of the selenium metabolism in cancer cell lines

DEFF Research Database (Denmark)

Lunøe, Kristoffer; Gabel-Jensen, Charlotte; Stürup, Stefan

2011-01-01

The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line...... (Jurkat E6-1) were incubated with five selenium compounds representing inorganic as well as organic Se compounds in different oxidation states. Selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), methylseleninic acid (MeSeA), selenite and selenate in the concentration range 5-100 mu M were...... incubated with cells for 24 h and the induction of cell death was measured using flow cytometry. The amounts of total selenium in cell medium, cell lysate and the insoluble fractions was determined by ICP-MS. Speciation analysis of cellular fractions was performed by reversed phase, anion exchange and size...

HD271791: dynamical versus binary-supernova ejection scenario

Science.gov (United States)

Gvaramadze, V. V.

2009-05-01

The atmosphere of the extremely high-velocity (530-920kms-1) early B-type star HD271791 is enriched in α-process elements, which suggests that this star is a former secondary component of a massive tight binary system and that its surface was polluted by the nucleosynthetic products after the primary star exploded in a supernova. It was proposed that the (asymmetric) supernova explosion unbind the system and that the secondary star (HD271791) was released at its orbital velocity in the direction of Galactic rotation. In this Letter, we show that to explain the Galactic rest-frame velocity of HD271791 within the framework of the binary-supernova scenario, the stellar remnant of the supernova explosion (a =750-1200kms-1. We therefore consider the binary-supernova scenario as highly unlikely and instead propose that HD271791 attained its peculiar velocity in the course of a strong dynamical three- or four-body encounter in the dense core of the parent star cluster. Our proposal implies that by the moment of encounter HD271791 was a member of a massive post-supernova binary.

Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia-lymphoma.

Science.gov (United States)

Drexler, H G; Matsuo, Y

2000-05-01

Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias-lymphomas. Continuous NK leukemia-lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not immortalized, non-malignant, non-NK, or plain false cell lines, six bona fide malignant NK cell lines have been established and are sufficiently well characterized: HANK1, KHYG-1, NK-92, NKL, NK-YS and YT. Except for YT which was derived from a not further defined acute lymphoblastic lymphoma, these cell lines were established from patients with various NK cell malignancies. Five of the six cell lines are constitutively interleukin-2-dependent. Their immunoprofile is remarkably similar: CD1-, CD2+, surface CD3 (but cytoplasmic CD3epsilon+), CD4-, CD5-, CD7+, CD8-, CD16-, CD56+, CD57-, TCRalphabeta-, TCRgammadelta-, negative for B cell and myelomonocytic markers. The immunoglobulin heavy chain and T cell receptor genes are all in germline configuration. All six lines show complex chromosomal alterations, with both numerical and structural aberrations, attesting to their malignant and monoclonal nature. Functionally, these cells which contain azurophilic granules in their cytoplasm are nearly universally positive in NK activity assays. Three of five cell lines are Epstein-Barr virus-positive (type II latency). The composite data on these six cell lines allow for the operational definition of a typical malignant NK cell line profile. NK leukemia-lymphoma cell lines will prove invaluable for studies of normal and malignant NK cell biology.

HD 143418: an unusual light variable and a double-lined spectroscopic binary with a CP primary

Czech Academy of Sciences Publication Activity Database

Božić, H.; Wolf, M.; Harmanec, P.; Prša, A.; Percy, J. R.; Ruždjak, D.; Sudar, D.; Šlechta, Miroslav; Ak, H.; Eenens, P.

2007-01-01

Roč. 464, č. 1 (2007), s. 263-275 ISSN 0004-6361 R&D Projects: GA AV ČR KSK2043105; GA ČR GA205/03/0788 Grant - others:GA ČR(CZ) GA205/06/0304 Institutional research plan: CEZ:AV0Z10030501 Source of funding: V - iné verejné zdroje Keywords : binaries spectroscopis * individual star HD 143418 * chemically peculiar Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.259, year: 2007

High-resolution H-band spectroscopy of Be stars with SDSS-III/apogee. I. New Be stars, line identifications, and line profiles

International Nuclear Information System (INIS)

Chojnowski, S. Drew; Majewski, Steven R.; Hall, Matthew; Beaton, Rachael; Burton, Adam; Damke, Guillermo; Wilson, John; Whelan, David G.; Wisniewski, John P.; Shetrone, Matthew; Eikenberry, Steve; Hasselquist, Sten; Holtzman, Jon A.; Brewington, Howard; Brinkmann, J.; Mészáros, Szabolcs; Nidever, David; Schneider, Donald P.; Zasowski, Gail; Bizyaev, Dmitry

2015-01-01

shell absorption, even when the H i lines are clearly shell-dominated. The first known example of a quasi-triple-peaked Br11 line profile is reported for HD 253659, one of several stars exhibiting intra- and/or extra-species V/R and radial velocity variation within individual spectra. Br11 profiles are presented for all discussed stars, as are full APOGEE spectra for a portion of the sample.

Menadione inhibits MIBG uptake in two neuroendocrine cell lines

NARCIS (Netherlands)

Cornelissen, J.; Tytgat, G. A.; van den Brug, M.; van Kuilenburg, A. B.; Voûte, P. A.; van Gennip, A. H.

1997-01-01

In this paper we report on our studies of the effect of menadione on the uptake of MIBG in the neuroendocrine cell lines PC12 and SK-N-SH. Menadione inhibits the uptake of MIBG in both cell lines in a dose-dependent manner. Inhibition of MIBG uptake is most pronounced in the PC12 cell line.

Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines

Directory of Open Access Journals (Sweden)

Ismail Noorliza M

2010-09-01

Full Text Available Abstract Background The treatment of oral squamous cell carcinomas (OSCC and human osteosarcoma (HOS includes surgery and/or radiotherapy which often lead to reduced quality of life. This study was aimed to study the antiproliferative activity of local honey (Tualang on OSCC and HOS cell lines. Methods Several concentrations of Tualang honey (1% - 20% were applied on OSCC and HOS cell lines for 3, 6, 12, 24, 48 and 72 hours. Morphological characteristics were observed under light and fluorescent microscope. Cell viability was assessed using MTT assay and the optical density for absorbance values in each experiment was measured at 570 nm by an ELISA reader. Detection of cellular apoptosis was done using the Annexin V-FITC Apoptosis Detection Kit. Results Morphological appearance showed apoptotic cellular changes like becoming rounded, reduction in cell number, blebbed membrane and apoptotic nuclear changes like nuclear shrinkage, chromatin condensation and fragmented nucleus on OSCC and HOS cell lines. Cell viability assay showed a time and dose-dependent inhibitory effect of honey on both cell lines. The 50% inhibitory concentration (IC50 for OSCC and HOS cell lines was found to be 4% and 3.5% respectively. The maximum inhibition of cell growth of ≥80% was obtained at 15% for both cell lines. Early apoptosis was evident by flow cytometry where percentage of early apoptotic cells increased in dose and time dependent manner. Conclusion Tualang honey showed antiproliferative effect on OSCC and HOS cell lines by inducing early apoptosis.

Huntington's disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database.

Science.gov (United States)

Kalathur, Ravi Kiran Reddy; Hernández-Prieto, Miguel A; Futschik, Matthias E

2012-06-28

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally

Huntington's Disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database

Directory of Open Access Journals (Sweden)

Kalathur Ravi Kiran

2012-06-01

Full Text Available Abstract Background Huntington’s disease (HD is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. Methods To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. Results Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling, but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling. For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are

The Phosphoinositide 3-Kinaseα Selective Inhibitor, BYL719, Enhances the Effect of the Protein Kinase C Inhibitor, AEB071, in GNAQ/GNA11 Mutant Uveal Melanoma Cells

Science.gov (United States)

Musi, Elgilda; Ambrosini, Grazia; de Stanchina, Elisa; Schwartz, Gary K.

2014-01-01

G-protein mutations are one of the most common mutations occurring in uveal melanoma activating the protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-Kinase (PI3K)/AKT pathways. In this study, we described the effect of dual pathway inhibition in uveal melanoma harboring GNAQ and GNA11 mutations via PKC inhibition with AEB071 (Sotrastaurin) and PI3k/AKT inhibition with BYL719, a selective PI3Kα inhibitor. Growth inhibition was observed in GNAQ/GNA11 mutant cells with AEB071 versus no activity in WT cells. In the GNAQ-mutant cells, AEB071 decreased phosphorylation of MARCKS, a substrate of PKC, along with ERK1/2 and ribosomal S6, but persistent AKT activation was present. BYL719 had minimal anti-proliferative activity in all uveal melanoma cell lines, and inhibited phosphorylation of AKT in most cell lines. In the GNA11 mutant cell line, similar effects were observed with ERK1/2 inhibition, mostly inhibited by BYL719. With the combination treatment, both GNAQ and GNA11 mutant cell lines showed synergistic inhibition of cell proliferation and apoptotic cell death. In vivo studies correlated with in vitro findings showing reduced xenograft tumor growth with the combination therapy in a GNAQ mutant model. These findings suggest a new therapy treatment option for G-protein mutant uveal melanoma with a focus on specific targeting of multiple downstream pathways as part of combination therapy. PMID:24563540

The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells.

Science.gov (United States)

Musi, Elgilda; Ambrosini, Grazia; de Stanchina, Elisa; Schwartz, Gary K

2014-05-01

G-protein mutations are one of the most common mutations occurring in uveal melanoma activating the protein kinase C (PKC)/mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K)/AKT pathways. In this study, we described the effect of dual pathway inhibition in uveal melanoma harboring GNAQ and GNA11 mutations via PKC inhibition with AEB071 (sotrastaurin) and PI3K/AKT inhibition with BYL719, a selective PI3Kα inhibitor. Growth inhibition was observed in GNAQ/GNA11-mutant cells with AEB071 versus no activity in wild-type cells. In the GNAQ-mutant cells, AEB071 decreased phosphorylation of myristoylated alanine-rich C-kinase substrate, a substrate of PKC, along with ERK1/2 and ribosomal S6, but persistent AKT activation was present. BYL719 had minimal antiproliferative activity in all uveal melanoma cell lines, and inhibited phosphorylation of AKT in most cell lines. In the GNA11-mutant cell line, similar effects were observed with ERK1/2 inhibition, mostly inhibited by BYL719. With the combination treatment, both GNAQ- and GNA11-mutant cell lines showed synergistic inhibition of cell proliferation and apoptotic cell death. In vivo studies correlated with in vitro findings showing reduced xenograft tumor growth with the combination therapy in a GNAQ-mutant model. These findings suggest a new therapy treatment option for G-protein-mutant uveal melanoma with a focus on specific targeting of multiple downstream pathways as part of combination therapy.

Thermodynamics of dinonylnaphthalene sulfonic acid (HD)

International Nuclear Information System (INIS)

Raieh, M.A.; Aly, H.F.

1980-01-01

The effect of temperature on the extraction of the trivalent actinides Am 3+ , Cm 3+ and Cf 3+ with the liquid cation exchanger dinonylnaphtalenesulphonic acid (HD) in toluene is studied. The different thermodynamic functions of this system are determined from the experimental results. It is found that the free energy variation for the extraction of these metal ions by HD is mainly determined by the entropic terms arising from the hydration-dehydration process of the exchanged ions. (author)

HD 66051: the first eclipsing binary hosting an early-type magnetic star

Science.gov (United States)

Kochukhov, O.; Johnston, C.; Alecian, E.; Wade, G. A.

2018-05-01

Early-type magnetic stars are rarely found in close binary systems. No such objects were known in eclipsing binaries prior to this study. Here we investigated the eclipsing, spectroscopic double-lined binary HD 66051, which exhibits out-of-eclipse photometric variations suggestive of surface brightness inhomogeneities typical of early-type magnetic stars. Using a new set of high-resolution spectropolarimetric observations, we discovered a weak magnetic field on the primary and found intrinsic, element-dependent variability in its spectral lines. The magnetic field structure of the primary is dominated by a nearly axisymmetric dipolar component with a polar field strength Bd ≈ 600 G and an inclination with respect to the rotation axis of βd = 13°. A weaker quadrupolar component is also likely to be present. We combined the radial velocity measurements derived from our spectra with archival optical photometry to determine fundamental masses (3.16 and 1.75 M⊙) and radii (2.78 and 1.39 R⊙) with a 1-3% precision. We also obtained a refined estimate of the effective temperatures (13000 and 9000 K) and studied chemical abundances for both components with the help of disentangled spectra. We demonstrate that the primary component of HD 66051 is a typical late-B magnetic chemically peculiar star with a non-uniform surface chemical abundance distribution. It is not an HgMn-type star as suggested by recent studies. The secondary is a metallic-line star showing neither a strong, global magnetic field nor intrinsic spectral variability. Fundamental parameters provided by our work for this interesting system open unique possibilities for probing interior structure, studying atomic diffusion, and constraining binary star evolution.

Establishment and characterization of rat portal myofibroblast cell lines.

Directory of Open Access Journals (Sweden)

Michel Fausther

Full Text Available The major sources of scar-forming myofibroblasts during liver fibrosis are activated hepatic stellate cells (HSC and portal fibroblasts (PF. In contrast to well-characterized HSC, PF remain understudied and poorly defined. This is largely due to the facts that isolation of rodent PF for functional studies is technically challenging and that PF cell lines had not been established. To address this, we have generated two polyclonal portal myofibroblast cell lines, RGF and RGF-N2. RGF and RGF-N2 were established from primary PF isolated from adult rat livers that underwent culture activation and subsequent SV40-mediated immortalization. Specifically, Ntpdase2/Cd39l1-sorted primary PF were used to generate the RGF-N2 cell line. Both cell lines were functionally characterized by RT-PCR, immunofluorescence, immunoblot and bromodeoxyuridine-based proliferation assay. First, immortalized RGF and RGF-N2 cells are positive for phenotypic myofibroblast markers alpha smooth muscle actin, type I collagen alpha-1, tissue inhibitor of metalloproteinases-1, PF-specific markers elastin, type XV collagen alpha-1 and Ntpdase2/Cd39l1, and mesenchymal cell marker ecto-5'-nucleotidase/Cd73, while negative for HSC-specific markers desmin and lecithin retinol acyltransferase. Second, both RGF and RGF-N2 cell lines are readily transfectable using standard methods. Finally, RGF and RGF-N2 cells attenuate the growth of Mz-ChA-1 cholangiocarcinoma cells in co-culture, as previously demonstrated for primary PF. Immortalized rat portal myofibroblast RGF and RGF-N2 cell lines express typical markers of activated PF-derived myofibroblasts, are suitable for DNA transfection, and can effectively inhibit cholangiocyte proliferation. Both RGF and RGF-N2 cell lines represent novel in vitro cellular models for the functional studies of portal (myofibroblasts and their contribution to the progression of liver fibrosis.

A Decade of H α Transits for HD 189733 b: Stellar Activity versus Absorption in the Extended Atmosphere

Energy Technology Data Exchange (ETDEWEB)

Cauley, P. Wilson; Redfield, Seth [Wesleyan University, Astronomy Department, Van Vleck Observatory, 96 Foss Hill Drive, Middletown, CT 06459 (United States); Jensen, Adam G., E-mail: pcauley@wesleyan.edu [University of Nebraska-Kearney, Department of Physics and Astronomy, 24011 11th Avenue, Kearney, NE 68849 (United States)

2017-05-01

HD 189733 b is one of the most well studied exoplanets due to its large transit depth and host star brightness. The focus on this object has produced a number of high-cadence transit observations using high-resolution optical spectrographs. Here we present an analysis of seven full H α transits of HD 189733 b using HARPS on the 3.6 meter La Silla telescope and HIRES on Keck I, taken over the course of nine years from 2006 to 2015. H α transmission signals are analyzed as a function of the stellar activity level, as measured using the normalized core flux of the Ca ii H and K lines. We find strong variations in the strength of the H α transmission spectrum from epoch to epoch. However, there is no clear trend between the Ca ii core emission and the strength of the in-transit H α signal, although the transit showing the largest absorption value also occurs when the star is the most active. We present simulations of the in-transit contrast effect and find that the planet must consistently transit active latitudes with very strong facular and plage emission regions in order to reproduce the observed line strengths. We also investigate the measured velocity centroids with models of planetary rotation and show that the small line profile velocities could be due to large velocities in the upper atmosphere of the planet. Overall, we find it more likely that the measured H α signals arise in the extended planetary atmosphere, although a better understanding of active region emission for active stars such as HD 189733 is needed.

Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

DEFF Research Database (Denmark)

Odum, Niels; Ledbetter, J A; Martin, P

1991-01-01

Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce...... adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human...... class II-positive monocytic (I937) and T leukemic (HUT78) tumor cell lines and Epstein-Barr virus (EBV) transformed B-lymphoid cell lines (EBV-LCL). Class II-negative cell lines (U-937 and the EBV-LCL mutant line 616) were not induced to aggregate. An HLA-G-transfected EBV-LCL, 221-AGN...

Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

International Nuclear Information System (INIS)

Medina, D.; Oborn, C.J.; Li, M.L.; Bissell, M.J.

1987-01-01

The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appeared to represent myoepithelial cells. The cell lines were examined for expression of β-casein mRNA in the presence or absence of prolactin. The inducibility of β-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types

[Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro].

Science.gov (United States)

Ying, Zhi-Tao; Guo, Jun; Ren, Jun; Kong, Yan; Yuan, Zhi-Hong; Liu, Xi-Juan; Zhang, Chen; Zheng, Wen; Song, Yu-Qin; Zhang, Yun-Tao; Zhu, Jun

2009-06-01

This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.

9-β-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

International Nuclear Information System (INIS)

Heaton, D.

1992-06-01

The effect of 9-β-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D 0 values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D 0 values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 μM) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 μM were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo

9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

Energy Technology Data Exchange (ETDEWEB)

Heaton, D. [Rush Univ. Medical Center, Chicago, IL (United States). Therapeutic Radiology; Mustafi, R. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Schwartz, J.L. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology]|[Argonne National Lab., IL (United States)

1992-06-01

The effect of 9-{beta}-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D{sub 0} values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D{sub 0} values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 {mu}M) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 {mu}M were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo.

NV-CMOS HD camera for day/night imaging

Science.gov (United States)

Vogelsong, T.; Tower, J.; Sudol, Thomas; Senko, T.; Chodelka, D.

2014-06-01

SRI International (SRI) has developed a new multi-purpose day/night video camera with low-light imaging performance comparable to an image intensifier, while offering the size, weight, ruggedness, and cost advantages enabled by the use of SRI's NV-CMOS HD digital image sensor chip. The digital video output is ideal for image enhancement, sharing with others through networking, video capture for data analysis, or fusion with thermal cameras. The camera provides Camera Link output with HD/WUXGA resolution of 1920 x 1200 pixels operating at 60 Hz. Windowing to smaller sizes enables operation at higher frame rates. High sensitivity is achieved through use of backside illumination, providing high Quantum Efficiency (QE) across the visible and near infrared (NIR) bands (peak QE camera, which operates from a single 5V supply. The NVCMOS HD camera provides a substantial reduction in size, weight, and power (SWaP) , ideal for SWaP-constrained day/night imaging platforms such as UAVs, ground vehicles, fixed mount surveillance, and may be reconfigured for mobile soldier operations such as night vision goggles and weapon sights. In addition the camera with the NV-CMOS HD imager is suitable for high performance digital cinematography/broadcast systems, biofluorescence/microscopy imaging, day/night security and surveillance, and other high-end applications which require HD video imaging with high sensitivity and wide dynamic range. The camera comes with an array of lens mounts including C-mount and F-mount. The latest test data from the NV-CMOS HD camera will be presented.

Polarized proton and deuteron solid HD targets

International Nuclear Information System (INIS)

Honig, A.

1977-01-01

A decade has now elapsed since HD was proposed as a polarized proton and deuteron target with exceptionally desirable properties. These include a very high free proton proportion, independently polarizable proton and deuteron systems, and a ''frozen-spin'' mode of operation which allows separation of the functions of production and utilization of the highly polarized target. A discussion is given of what can be expected of the polarized HD system right now, without further research. The basic features of solid HD pertinent to its use as a ''frozen-spin'' target are outlined, then a summary is given of the particular experimental results which support the contention that the target will perform successfully, and finally, some feasible operating modes and the expected performances from them are presented

Fed-batch bioreactor performance and cell line stability evaluation of the artificial chromosome expression technology expressing an IgG1 in Chinese hamster ovary cells.

Science.gov (United States)

Combs, Rodney G; Yu, Erwin; Roe, Susanna; Piatchek, Michele Bailey; Jones, Heather L; Mott, John; Kennard, Malcolm L; Goosney, Danika L; Monteith, Diane

2011-01-01

The artificial chromosome expression (ACE) technology system uses an engineered artificial chromosome containing multiple site-specific recombination acceptor sites for the rapid and efficient construction of stable cell lines. The construction of Chinese hamster ovary(CHO) cell lines expressing an IgG1 monoclonal antibody (MAb) using the ACE system has been previously described (Kennard et al., Biotechnol Bioeng. 2009;104:540-553). To further demonstrate the manufacturing feasibility of the ACE system, four CHO cell lines expressing the human IgG1 MAb 4A1 were evaluated in batch and fed-batch shake flasks and in a 2-L fed-batch bioreactor. The batch shake flasks achieved titers between 0.7 and 1.1 g/L, whereas the fed-batch shake flask process improved titers to 2.5–3.0 g/L. The lead 4A1 ACE cell line achieved titers of 4.0 g/L with an average specific productivity of 40 pg/(cell day) when cultured in a non optimized 2-L fed-batch bioreactor using a completely chemically defined process. Generational stability characterization of the lead 4A1-expressing cell line demonstrated that the cell line was stable for up to 75 days in culture. Product quality attributes of the 4A1 MAb produced by the ACE system during the stability evaluation period were unchanged and also comparable to existing expression technologies such as the CHO-dhfr system. The results of this evaluation demonstrate that a clonal, stable MAb-expressing CHO cell line can be produced using ACE technology that performs competitively using a chemically defined fed-batch bioreactor process with comparable product quality attributes to cell lines generated by existing technologies.

Project VeSElkA: a search for the vertical stratification of element abundances in HD 157087

Science.gov (United States)

Khalack, V.

2018-06-01

The new spectropolarimetric spectra of HD 157087 obtained recently with ESPaDOnS (Echelle SpectroPolarimetric Device for Observations of Stars) at the Canada-France-Hawaii Telescope are analysed to verify the nature of this object. The fundamental stellar parameters Teff = 8882 K, log g = 3.57 were obtained for HD 157087 from the analysis of nine Balmer line profiles in two available spectra. A comparison of the results of our abundance analysis with previously published data shows a variability of the average abundance with time for some chemical species, while the abundances of other elements remain almost constant. The abundance analysis also reveals evidence of a significant abundance increase towards the deeper atmospheric layers for C, S, Ca, Sc, V, Cr, Mn, Co, Ni and Zr. Together with the discovered enhanced abundance of Ca and Sc, this finding contradicts the classification of HD 157087 as a marginal Am star. An analysis of the available measurements of radial velocity revealed long- and short-period variations. The long-period variation supports the idea that HD 157087 is an astrometric binary system with a period longer than 6 yr. The presence of the short-period variation of Vr, as well as the detection of the temporal variation of the average abundance, suggests that HD 157087 may be a triple system, in which a short-period binary rotates around a third star. In this case, the short-period binary may consist of slowly rotating Am and A (or Ap with a weak magnetic field) stars that have similar effective temperatures and surface gravities, but different abundance peculiarities.

Spectroscopic Peculiarity of the Herbig Be Star HD 259431

Science.gov (United States)

Pogodin, M. A.; Pavlovskij, S. E.; Drake, N. A.; Beskrovnaya, N. G.; Kozlova, O. V.; Alekseev, I. Yu.; Borges Fernandes, M.; Pereira, C. B.; Valyavin, G.

2017-06-01

High-resolution spectra of the Herbig Be star HD 259431 obtained in 2010-2016 at three observatories (Crimean AO, ESO in Chile, and OAN SPN in Mexico) are analysed. The object demonstrates a very rich emission line profile spectrum. The bulk of the lines exhibit double-peaked emission profiles and originate in the gaseous disk. The atmospheric lines are unusually shallow, and majority of them are distorted by the circumstellar (CS) contribution. Moreover, we have revealed that they are overlapped with an additional continuum emission. Using the observed ratio of the equivalent widths of two He I λ 4009 and 4026 lines, we estimated the spectral type of the object as B5 V. We also constructed the spectral energy distribution of the additional continuum using wide wings of the atmospheric Hβ-Hɛ lines free of the CS contribution. The continuum corresponds to the blue part of the black body spectrum. The Hβ - Hɛ Balmer emission lines show very variable profiles looking as either of P Cyg-type or a double-peaked emission line with a depression of the red wing. We found the period of this variability P = 2.630d and interpreted it as a sign of a rotating magnetosphere of the star with the magnetic axis inclined to the rotation axis. At different phases of rotation, the observer can see either an accretion flow at high magnetic latitudes or a wind zone at lower latitudes. We also estimated the inclination of the rotation axis i = 52°±1°.

Mosaicism for r(X and der(Xdel(X(p11.23dup(X(p11.21p11.22 provides insight into the possible mechanism of rearrangement

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Fang Ping

2008-07-01

Full Text Available Abstract We report a patient with a unique and complex cytogenetic abnormality involving mosaicism for a small ring X and deleted Xp derivative chromosome with tandem duplication at the break point. The patient presented with failure to thrive, muscular hypotonia, and minor facial anatomic anomalies, all concerning for Turner syndrome. Brain MRI revealed mild thinning of the corpus callosum, an apparent decrease in ventricular white matter volume, and an asymmetric myelination pattern. Array comparative genome hybridization analysis revealed mosaicism for the X chromosome, deletion of the short arm of an X chromosome, and a duplication of chromosome region Xp11.21-p11.22. G-banded chromosome and FISH analyses revealed three abnormal cell lines: 46,X,der(Xdel(X(p11.23dup(X(p11.21p11.22/46,X,r(X(q11.1q13.1/45,X. The small ring X chromosome was estimated to be 5.2 Mb in size and encompassed the centromere and Xq pericentromeric region. X chromosome inactivation (XCI studies demonstrated a skewed pattern suggesting that the ring X remained active, likely contributing to the observed clinical features of brain dysmyelination. We hypothesize that a prezygotic asymmetric crossing over within a loop formed during meiosis in an X chromosome with a paracentric inversion resulted in an intermediate dicentric chromosome. An uneven breakage of the dicentric chromosome in the early postzygotic period might have resulted in the formation of one cell line with the X chromosome carrying a terminal deletion and pericentromeric duplication of the short arm and the second cell line with the X chromosome carrying a complete deletion of Xp. The cell line carrying the deletion of Xp could have then stabilized through self-circularization and formation of the ring X chromosome.

In vitro culture of human osteosarcoma cell lines: a comparison of functional characteristics for cell lines cultured in medium without and with fetal calf serum.

Science.gov (United States)

Bruserud, Oystein; Tronstad, Karl Johan; Berge, Rolf

2005-06-01

Experimental in vitro models including well-characterised cell lines can be used to identify possible new therapeutic targets for the treatment of osteosarcoma. Culture media including inactivated serum is often recommended for in vitro culture of osteosarcoma cells, but the serum component then represents a nonstandardised parameter including a wide range of unidentified mediators. To improve the standardisation we have investigated whether serum-free culture media can be used in experimental in vitro studies of osteosarcoma cell lines. The seven osteosarcoma cell lines Cal72, SJSA-1, Saos-2, SK-ES-1, U2OS, 143.98.2, and KHOS-32IH were cultured in vitro in various serum-free media and media supplemented with 10% heat-inactivated fetal calf serum (FCS). Although proliferation often was relatively low in serum-free media (X-vivo 10, X-vivo 15, X-vivo 20, Stem Span SFEM), some cell lines (Cal72, KHOS-32IH, Saos-2) showed proliferation comparable with the recommended FCS-containing media even when using serum-free conditions. The optimal serum-free medium then varied between cell lines. We also compared 6 different FCS-containing media (including Stem Span with 10% FCS) and the optimal FCS-containing medium varied between cell lines. However, all cell lines proliferated well in Stem Span with FCS, and this medium was regarded as optimal for four of the lines. FCS could not be replaced by fatty acids or low density lipoprotein when testing the Stem Span medium. The release of a wide range of soluble mediators showed only minor differences when using serum-free and FCS-containing media (including Stem Span with and without FCS), and serum-free Stem Span could also be used for in vitro studies of mitogen-stimulated T cell activation in the presence of accessory osteosarcoma cells. The use of Stem Span with 10% FCS allowed the release of a wide range of chemokines by osteosarcoma cell lines (Cal72, SJSA-1), and the chemokine release profile was very similar to the

Clonogenic cell line survival of a human liver cancer cell line SMMC-7721 after carbon ion irradiation with different LET

International Nuclear Information System (INIS)

Lei Suwen; Su Xu; Wang Jifang; Li Wenjian

2003-01-01

Objective: To investigate the survival fraction of a human liver cancer cell line SMMC-7721 following irradiation with carbon ions with different LET. Methods: cells of the human liver cancer cell line SMMC-7721 were irradiated with carbon ions (LET=30 and 70 keV/μm). The survival fraction was determined with clonogenic assay after 9 days incubation in a 5% CO 2 incubator at 37 degree C. Results: When the survival fractions of 70 keV/μm were D s = 0.1 and D s=0.01 absorption dose were 2.94 and 5.88 Gy respectively, and those of 30 keV/μm were 4.00 and 8.00 Gy respectively. Conclusion: For the SMMC-7721 cell line, 70 keV/μm is more effective for cell killing than 30 keV/μm

Datablock: hd141

Indian Academy of Sciences (India)

2016-01-15

Jan 15, 2016 ... checkCIF/PLATON page 2 http://checkcif.iucr.org/cgibin/checkcif_hkl.pl. 1/3. checkCIF (basic structural check) running. checkCIF/PLATON (basic structural check). Structure factors have been supplied for datablock(s) hd141. THIS REPORT IS FOR GUIDANCE ONLY. IF USED AS PART OF A REVIEW.

Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

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Eva eRettinger

2012-04-01

Full Text Available Allogeneic stem cell transplantation (allo-SCT has become an important treatment modality for patients with high risk acute myeloid leukemia (AML and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions (DLI based on MRD status using IL-15-expanded cytokine-induced killer (CIK cells may prevent relapse without causing graft-versus-host-disease (GvHD. To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL2Rγc-, NSG were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction (qPCR for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow (BM followed by liver, lung, spleen, peripheral blood (PB, and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at an effector to target cell (E:T ratio of 1:1 were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells an E:T ratio of 250:1 was needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliably 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells

Establishment of a common acute lymphoblastic leukemia cell line (LC4-1) and effects of phorbol myristate acetate (PMA) on the surface antigen expression of the cell line.

Science.gov (United States)

Yoshimura, T; Mayumi, M; Yorifuji, T; Kim, K M; Heike, T; Miyanomae, T; Shinomiya, K; Mikawa, H

1987-09-01

A common acute lymphoblastic leukemia (ALL) cell line, designated LC4-1, was established from peripheral blood mononuclear cells of a patient with acute non-T-cell ALL. LC4-1 cells were characteristically positive for Ia, B4, and common ALL antigens (CALLA), but negative for B2, Tac, T3, T4, T8, T11, and M1 antigens and E-rosette formation. Approximately 30% of LC4-1 cells expressed detectable amounts of B1 antigens. LC4-1 cells expressed neither Epstein-Barr-virus-associated nuclear antigen (EBNA), cytoplasmic immunoglobulins (cIg) nor surface immunoglobulins (sIg). Gene rearrangements had already occurred in LC4-1 in the D-J region of immunoglobulin heavy chain genes, but not in T-cell receptor (beta-chain) genes, suggesting that LC4-1 is a progenitor cell line of B-cell lineage earlier than pre-B-cells. The expression of cell surface antigens of LC4-1 was changed by treatment with 4-phorbol 12-myristate 13-acetate (PMA) (0.1 ng/ml) for 2 days. Before treatment with PMA, about 98% of LC4-1 cells were positive for B4, CALLA, and Ia. However, following treatment they lost CALLA expression without any change in expression of Ia and B4. There was no change in B1-positive population. The change in surface antigens on LC4-1 cells seems to be due to differentiation induced in the cells by PMA. These results support the hypothesis that CALLA is a differentiation antigen and suggest one possible differentiation pathway for pre-B-cells.

Dosimetry during mango irradiation using Gafchromic HD-810 film

International Nuclear Information System (INIS)

Sharma, S. D.; Chilkulwar, R. H.; Kumar, R.

2009-01-01

The dosimetric characteristics of Gafchromic HD-810 film were evaluated for its possible use as a high-dose dosemeter for routine dosimetry during mango irradiation. The film dosemeter sample of size 2 x 2 cm 2 was used throughout the course of this work. The irradiation of the film dosemeter for characterisation and calibration purposes was carried out in a gamma irradiator. The dose-response of the Gafchromic HD-810 film dosemeter at 550 nm was found to be linear in the dose range 50-1000 Gy, which indicates the feasibility of using this film for dosimetry up to 1000 Gy. The mean inter-dosemeter variation was within 2%, which gives better dose-response consistency of the HD-810 film. The radiation absorbed dose measured by the Gafchromic HD-810 film dosemeter during mango irradiation was compared with that measured by a standard Ceric-cerous dosemeter. This study establishes the Gafchromic HD-810 film as a convenient and technically suitable dosemeter for high-dose dosimetry up to 1.0 kGy during mango irradiation. (authors)

Identification of a novel rhabdovirus in Spodoptera frugiperda cell lines.

Science.gov (United States)

Ma, Hailun; Galvin, Teresa A; Glasner, Dustin R; Shaheduzzaman, Syed; Khan, Arifa S

2014-06-01

The Sf9 cell line, derived from Spodoptera frugiperda, is used as a cell substrate for biological products, and no viruses have been reported in this cell line after extensive testing. We used degenerate PCR assays and massively parallel sequencing (MPS) to identify a novel RNA virus belonging to the order Mononegavirales in Sf9 cells. Sequence analysis of the assembled virus genome showed the presence of five open reading frames (ORFs) corresponding to the genes for the N, P, M, G, and L proteins in other rhabdoviruses and an unknown ORF of 111 amino acids located between the G- and L-protein genes. BLAST searches indicated that the S. frugiperda rhabdovirus (Sf-rhabdovirus) was related in a limited region of the L-protein gene to Taastrup virus, a newly discovered member of the Mononegavirales from a leafhopper (Hemiptera), and also to plant rhabdoviruses, particularly in the genus Cytorhabdovirus. Phylogenetic analysis of sequences in the L-protein gene indicated that Sf-rhabdovirus is a novel virus that branched with Taastrup virus. Rhabdovirus morphology was confirmed by transmission electron microscopy of filtered supernatant samples from Sf9 cells. Infectivity studies indicated potential transient infection by Sf-rhabdovirus in other insect cell lines, but there was no evidence of entry or virus replication in human cell lines. Sf-rhabdovirus sequences were also found in the Sf21 parental cell line of Sf9 cells but not in other insect cell lines, such as BT1-TN-5B1-4 (Tn5; High Five) cells and Schneider's Drosophila line 2 [D.Mel.(2); SL2] cells, indicating a species-specific infection. The results indicate that conventional methods may be complemented by state-of-the-art technologies with extensive bioinformatics analysis for identification of novel viruses. The Spodoptera frugiperda Sf9 cell line is used as a cell substrate for the development and manufacture of biological products. Extensive testing has not previously identified any viruses in this cell

Constitutive mRNA expression and protein activity levels of nine ABC efflux transporters in seven permanent cell lines derived from different tissues of rainbow trout (Oncorhynchus mykiss).

Science.gov (United States)

Fischer, Stephan; Loncar, Jovica; Zaja, Roko; Schnell, Sabine; Schirmer, Kristin; Smital, Tvrtko; Luckenbach, Till

2011-01-25

Permanent fish cell lines have become common model systems for determining ecotoxicological effects of pollutants. For these cell lines little is known on the cellular active transport mechanisms that control the amount of a compound entering the cell, such as the MXR (multixenobiotic resistance) system mediated by ATP binding cassette (ABC) transport proteins. Therefore, for toxic evaluation of chemicals with those cells information on MXR is important. We here present data on constitutive mRNA expression and protein activity levels of a series of ABC efflux transporters in seven permanent cell lines derived from liver (RTL-W1; R1) and liver hepatoma (RTH-149), gill (RTgill-W1), gonad (RTG-2), gut (RTgutGC) and brain (RTbrain) of rainbow trout (Oncorhynchus mykiss). In addition to known transporters abcb1 (designated here abcb1a), abcb11, abcc1-3, abcc5 and abcg2, we quantified expression levels of a newly identified abcb1 isoform (abcb1b) and abcc4, previously unknown in trout. Quantitative real time PCR (qPCR) indicated that mRNA of the examined ABC transporters was constitutively expressed in all cell lines. Transporter mRNA expression patterns were similar in all cell lines, with expression levels of abcc transporters being 80 to over 1000 fold higher than for abcg2, abcb1a/b and abcb11 (abcc1-5>abcg2>abcb1a/b, 11). Transporter activity in the cell lines was determined by measuring uptake of transporter type specific fluorescent substrates in the presence of activity inhibitors. The combination of the ABCB1 and ABCC transporter substrate calcein-AM with inhibitors cyclosporine A, PSC833 and MK571 resulted in a concentration-dependent fluorescence increase of up to 3-fold, whereas reversin 205 caused a slight, but not concentration-dependent fluorescence increase. Accumulation of the dyes Hoechst 33342 and 2',7'-dichlorodihydrofluorescein diacetate was basically unchanged in the presence of Ko134 and taurocholate, respectively, indicating low Abcg2 and Abcb11

Phenomena of g-u symmetry-breakdown in HD

NARCIS (Netherlands)

de Lange, A.; Reinhold, E.M.; Ubachs, W.M.G.

2002-01-01

Phenomena associated with the breakdown of inversion symmetry in the HD molecule are reviewed and discussed. A distinction is made between three kinds of physical effects observed in HD spectra. The existence of a small electric dipole moment in the ground state gives rise to vibrational and pure

Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines

International Nuclear Information System (INIS)

Hata, H.; Numata, M.; Tohda, H.; Yasui, A.; Oikawa, A.

1991-01-01

1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links

Lining cells on normal human vertebral bone surfaces

International Nuclear Information System (INIS)

Henning, C.B.; Lloyd, E.L.

1982-01-01

Thoracic vertebrae from two individuals with no bone disease were studied with the electron microscope to determine cell morphology in relation to bone mineral. The work was undertaken to determine if cell morphology or spatial relationships between the bone lining cells and bone mineral could account for the relative infrequency of bone tumors which arise at this site following radium intake, when compared with other sites, such as the head of the femur. Cells lining the vertebral mineral were found to be generally rounded in appearance with varied numbers of cytoplasmic granules, and they appeared to have a high density per unit of surface area. These features contrasted with the single layer of flattened cells characteristic of the bone lining cells of the femur. A tentative discussion of the reasons for the relative infrequency of tumors in the vertebrae following radium acquisition is presented

Susceptibility of various cell lines to Neospora caninum tachyzoites cultivation

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Khordadmehr, M.,

2014-05-01

Full Text Available Neospora caninum is a coccidian protozoan parasite which is a major cause of bovine abortions and neonatal mortality in cattle, sheep, goat and horse. Occasionally, cultured cells are used for isolation and multiplication of the agent in vitro with several purposes. In this study the tachyzoite yields of N. caninum were compared in various cell cultures as the host cell lines. Among the cell cultures tested, two presented good susceptibility to the agent: cell lines Vero and MA-104. SW742 and TLI (in vitro suspension culture of lymphoid cells infected with Theileria lestoquardi showed moderate sensitivity. No viable tachyzoite were detected in the culture of MDCK and McCoy cell lines. These results demonstrate that MA-104 and SW742 cells present adequate susceptibility to N. caninum compared to Vero cells, which have been largely used to multiply the parasite in vitro. Moreover, these have easy manipulation, fast multiplication and relatively low nutritional requirements. In addition, the result of this study showed that TLI cell line as a suspension cell culture is susceptible to Nc-1 tachyzoites infection and could be used as an alternative host cell line for tachyzoites culture in vitro studies.

HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor.

Science.gov (United States)

Nowak, Jacek; Nestorowicz, Klaudia; Graczyk-Pol, Elzbieta; Mika-Witkowska, Renata; Rogatko-Koros, Marta; Jaskula, Emilia; Koscinska, Katarzyna; Madej, Sylwia; Tomaszewska, Agnieszka; Nasilowska-Adamska, Barbara; Szczepinski, Andrzej; Halaburda, Kazimierz; Dybko, Jaroslaw; Kuliczkowski, Kazimierz; Czerw, Tomasz; Giebel, Sebastian; Holowiecki, Jerzy; Baranska, Malgorzata; Pieczonka, Anna; Wachowiak, Jacek; Czyz, Anna; Gil, Lidia; Lojko-Dankowska, Anna; Komarnicki, Mieczyslaw; Bieniaszewska, Maria; Kucharska, Agnieszka; Hellmann, Andrzej; Gronkowska, Anna; Jedrzejczak, Wieslaw W; Markiewicz, Miroslaw; Koclega, Anna; Kyrcz-Krzemien, Slawomira; Mielcarek, Monika; Kalwak, Krzysztof; Styczynski, Jan; Wysocki, Mariusz; Drabko, Katarzyna; Wojcik, Beata; Kowalczyk, Jerzy; Gozdzik, Jolanta; Pawliczak, Daria; Gwozdowicz, Slawomir; Dziopa, Joanna; Szlendak, Urszula; Witkowska, Agnieszka; Zubala, Marta; Gawron, Agnieszka; Warzocha, Krzysztof; Lange, Andrzej

2018-06-01

Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N = 889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p = 0.000037, HR = 10.68, 95%CI 5.50-32.5) and extended chronic GvHD (p < 0.000001, HR = 15.51, CI95% 5.36-44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p = 0.00065, HR = 4.05, CI95% 1.69-9.71) and non-relapse mortality (40% vs. 31%, p = 0.00037, HR = 5.63, CI95% 2.04-15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT. Copyright © 2018. Published by Elsevier Inc.

Enterovirus Species B Bias of RD Cell Line and Its Influence on Enterovirus Diversity Landscape.

Science.gov (United States)

Faleye, Temitope Oluwasegun Cephas; Adeniji, Johnson Adekunle

2015-12-01

Despite its widespread use in poliovirus isolation, studies show that most RD cell line isolates are species B enteroviruses (EB), it was therefore employed to further catalogue the EB diversity in two different regions of Nigeria. Concentrates of 18 environmental samples were inoculated into RD cell line. Isolates were subjected to PCR assays to detect enteroviruses, species C and B members and partial VP1 gene which was subsequently sequenced and used for identification and phylogenetic analysis. Isolates were further passaged in L20B cell line to detect polioviruses. Sixty-eight isolates were recovered from the 18 concentrates, all of which were positive for the enterovirus 5'-UTR screen. Thirteen of the 68 isolates were positive for the species C screen and replicated in L20B cell line, eleven of which also contained species B enteroviruses. Some of the mixed isolates were successfully typed, but as species B members. In all, isolates recovered in this study were identified as CVB5, E6, E7, E11, E13, E19, E20, E33, EVB75 and WPV3, while some could not be typed. Alongside the ten different enterovirus serotypes confirmed, results of this study document for the first time in Nigeria, EVB75. It showed the EB bias of RD cell line might indicate something much more fundamental in its biology. Finally, the finding of WPV3 in a region considered low risk for poliovirus emphasizes the need to expand poliovirus environmental surveillance to enable early detection of poliovirus silent circulation before occurrence of clinical manifestations.

Study of the adhesion interaction using 51Cr labelling method between the myeloma cell lines and the endothelial cells

International Nuclear Information System (INIS)

Zhang Xueguang; Wang Jiangfang; Mao Zijun

1995-06-01

Using 51 Cr labelled multiple myeloma (MM) cell lines U266/XG-7, the regulatory effect of cytokines on the adhesive interaction between myeloma-cell lines U266/XG-7 and the endothelial cells, and the effects of these cytokines on expression of adhesion molecules and secretion of other cytokines were studied. The experimental results were as follows: (1) IL-6 and IL-6 Rgp 130-associated growth factors (such as GM-CSF) are not only myeloma cell growth factors, but also can enhance the adhesion between MM cells and endothelial cells and thus facilitated the metastasis of tumor cells. (2) Cytokines could induce increase in the expression of CD54 and CD44 on the endothelial cells and the secretion of IL-6 and TNF by the endothelial cells. On the other hand, the adhesion could also cause the change of CD11a, CD54, CD44 and VLA-4 on surface of myeloma cells XG-7. Finally, the interaction between MM cells and stromal cells from murine bone marrow could rapidly induce autocrine of IL-6 in human IL-6-dependent MM cells. (3) The interaction between stromal cells and tumor cells regulated by the cytokines and adhesion molecules was a key element in the pathogenesis and development of human MM. Among these factors, VLA-4 might be one of the molecules involved in U266/XG-7-EC interaction. (5 tabs., 8 figs.)

[Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions and activities of matrix metalloproteinases in human skin fibroblasts and human leukemia cell line THP-1].

Science.gov (United States)

Liang, Ya-hui; Li, Ping; Zhao, Jing-xia; Liu, Xin; Huang, Qi-fu

2010-11-01

In order to reveal the treatment mechanism of Chinese medicine with the effect of activating blood and resolving putridity, we selected acetyl-11-keto-beta-boswellic acid (AKBA) and arsenic trioxide (ATO), the main monomeric components of frankincense and arsenolite which are two most commonly used Chinese medicine with effect of activating blood and resolving putridity. We combined AKBA and ATO as a compound, and explored its regulatory role in productions and activities of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 in human skin fibroblasts (HSFbs) and human acute monocytic leukemia cell line THP-1 in inflammatory state. In order to simulate the inflammatory micro-environment of chronic wounds, we established 3 cell models: HSFb model activated by tumor necrosis factor-alpha (TNF-α), THP-1 cell model activated by phorbol-12-myristate-13-acetate (PMA) and HSFb-THP-1 cell coculture system. AKBA and ATO were cocultured with these cell models. Enzyme-linked immunosorbent assay (ELISA), gelatin zymography assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to test the secretions, activities and mRNA expressions of MMP-1, MMP-2 and MMP-9. In the study of the regulatory mechanism of AKBA and ATO on MMPs, AKBA and ATO were cocultured with the cell models. ELISA was used to test the secretions of TNF-α and interleukin-1beta (IL-β) and Western blot was used to test the phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated proteinkinase (p38MAPK). Compound of AKBA and ATO inhibited MMP-1, MMP-2 and MMP-9 mRNA expressions, secretions and activities respectively in HSFbs and THP-1 cells in inflammatory state (PTHP-1 cells and cell coculture system (PTHP-1 cells (P<0.05, P<0.01). The combined use of AKBA and ATO which in line with the rule of activating blood and resolving putridity inhibits fibroblasts and inflammatory cells in producing MMPs in inflammatory state through inhibiting the

Molecular characterization of breast cancer cell lines through multiple omic approaches.

Science.gov (United States)

Smith, Shari E; Mellor, Paul; Ward, Alison K; Kendall, Stephanie; McDonald, Megan; Vizeacoumar, Frederick S; Vizeacoumar, Franco J; Napper, Scott; Anderson, Deborah H

2017-06-05

Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated. We determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer. The cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated

Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

Science.gov (United States)

Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

2014-01-01

Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation

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Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

2017-01-01

Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram. PMID:28467792

Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation.

Science.gov (United States)

Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

2017-06-27

Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram.

The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

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Cheng CHEN

2009-08-01

Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

Water vapor in the spectrum of the extrasolar planet HD 189733b. I. The transit

International Nuclear Information System (INIS)

McCullough, P. R.; Crouzet, N.; Deming, D.; Madhusudhan, N.

2014-01-01

We report near-infrared spectroscopy of the gas giant planet HD 189733b in transit. We used the Hubble Space Telescope Wide Field Camera 3 (HST WFC3) with its G141 grism covering 1.1 μm to 1.7 μm and spatially scanned the image across the detector at 2'' s –1 . When smoothed to 75 nm bins, the local maxima of the transit depths in the 1.15 μm and 1.4 μm water vapor features are, respectively, 83 ± 53 ppm and 200 ± 47 ppm greater than the local minimum at 1.3 μm. We compare the WFC3 spectrum with the composite transit spectrum of HD 189733b assembled by Pont et al., extending from 0.3 μm to 24 μm. Although the water vapor features in the WFC3 spectrum are compatible with the model of non-absorbing, Rayleigh-scattering dust in the planetary atmosphere, we also re-interpret the available data with a clear planetary atmosphere. In the latter interpretation, the slope of increasing transit depth with shorter wavelengths from the near infrared, through the visible, and into the ultraviolet is caused by unocculted star spots, with a smaller contribution of Rayleigh scattering by molecular hydrogen in the planet's atmosphere. At relevant pressures along the terminator, our model planetary atmosphere's temperature is ∼700 K, which is below the condensation temperatures of sodium- and potassium-bearing molecules, causing the broad wings of the spectral lines of Na I and K I at 0.589 μm and 0.769 μm to be weak.

Water vapor in the spectrum of the extrasolar planet HD 189733b. I. The transit

Energy Technology Data Exchange (ETDEWEB)

McCullough, P. R.; Crouzet, N. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Deming, D. [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Madhusudhan, N., E-mail: pmcc@stsci.edu [Yale Center for Astronomy and Astrophysics, Yale University, New Haven, CT 06511 (United States)

2014-08-10

We report near-infrared spectroscopy of the gas giant planet HD 189733b in transit. We used the Hubble Space Telescope Wide Field Camera 3 (HST WFC3) with its G141 grism covering 1.1 μm to 1.7 μm and spatially scanned the image across the detector at 2'' s{sup –1}. When smoothed to 75 nm bins, the local maxima of the transit depths in the 1.15 μm and 1.4 μm water vapor features are, respectively, 83 ± 53 ppm and 200 ± 47 ppm greater than the local minimum at 1.3 μm. We compare the WFC3 spectrum with the composite transit spectrum of HD 189733b assembled by Pont et al., extending from 0.3 μm to 24 μm. Although the water vapor features in the WFC3 spectrum are compatible with the model of non-absorbing, Rayleigh-scattering dust in the planetary atmosphere, we also re-interpret the available data with a clear planetary atmosphere. In the latter interpretation, the slope of increasing transit depth with shorter wavelengths from the near infrared, through the visible, and into the ultraviolet is caused by unocculted star spots, with a smaller contribution of Rayleigh scattering by molecular hydrogen in the planet's atmosphere. At relevant pressures along the terminator, our model planetary atmosphere's temperature is ∼700 K, which is below the condensation temperatures of sodium- and potassium-bearing molecules, causing the broad wings of the spectral lines of Na I and K I at 0.589 μm and 0.769 μm to be weak.

Establishment and conventional cytogenetic characterization of three gastric cancer cell lines.

Science.gov (United States)

Leal, Mariana Ferreira; Martins do Nascimento, José Luiz; da Silva, Carla Elvira Araújo; Vita Lamarão, Maria Fernanda; Calcagno, Danielle Queiroz; Khayat, André Salim; Assumpção, Paulo Pimentel; Cabral, Isabel Rosa; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

2009-11-01

Gastric cancer is the fourth most frequent type of cancer and the second most frequent cause of cancer mortality worldwide. Only a modest number of gastric carcinoma cell lines have been isolated thus far. Here we describe the establishment and cytogenetic characterization of three new gastric cancer cell lines obtained from primary gastric adenocarcinoma (ACP02 and ACP03) and cancerous ascitic fluid (AGP01) of individuals from northern Brazil. ACP02, ACP03, and AGP01 cell lines are presently in the 60th passage. The cell lines grew in a disorganized single layer with some agglomerations and heterogeneous divisions (bipolar and multipolar). All cell lines exhibited a composite karyotype with several clonal chromosome alterations. Trisomy 8 was the most frequent alteration. Chromosome 8 aneusomy was confirmed by fluorescence in situ hybridization. All cell lines also exhibited trisomy 7 and deletion of chromosome arm 17p. These results suggest that, although frequent chromosome alterations are commonly observed due to culture process, the ACP02, ACP03, and AGP01 cell lines and primary gastric cancer from individuals of northern Brazil share genetic alterations, supporting use of these cell lines as a model of gastric carcinogenesis in this population.

DNA fingerprinting of the NCI-60 cell line panel.

Science.gov (United States)

Lorenzi, Philip L; Reinhold, William C; Varma, Sudhir; Hutchinson, Amy A; Pommier, Yves; Chanock, Stephen J; Weinstein, John N

2009-04-01

The National Cancer Institute's NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as a screening tool for drug discovery. Because many laboratories around the world rely on data from the NCI-60 cells, confirmation of their genetic identities represents an essential step in validating results from them. Given the consequences of cell line contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have, therefore, used standard DNA microsatellite short tandem repeats to profile the NCI-60, and the resulting DNA fingerprints are provided here as a reference. Consistent with previous reports, the fingerprints suggest that several NCI-60 lines have common origins: the melanoma lines MDA-MB-435, MDA-N, and M14; the central nervous system lines U251 and SNB-19; the ovarian lines OVCAR-8 and OVCAR-8/ADR (also called NCI/ADR); and the prostate lines DU-145, DU-145 (ATCC), and RC0.1. Those lines also show that the ability to connect two fingerprints to the same origin is not affected by stable transfection or by the development of multidrug resistance. As expected, DNA fingerprints were not able to distinguish different tissues-of-origin. The fingerprints serve principally as a barcodes.

Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

International Nuclear Information System (INIS)

Cherubini, Marta; Ginés, Silvia

2017-01-01

Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

Down-regulation of HSP40 gene family following OCT4B1 suppression in human tumor cell lines

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Mohammad Reza Mirzaei

2016-02-01

Full Text Available Objective(s: The OCT4B1, as one of OCT4 variants, is expressed in cancer cell lines and tissues more than other variants and plays an important role in apoptosis and stress (heat shock protein pathways. The present study was designed to determine the effects of OCT4B1 silencing on expressional profile of HSP40 gene family expression in three different human tumor cell lines. Materials and Methods: The OCT4B1 expression was suppressed by specific siRNA transfection in AGS (gastric adenocarcinoma, 5637 (bladder tumor and U-87MG (brain tumor cell lines employing Lipofectamine reagent. Real-time PCR array technique was employed for RNA qualification. The fold changes were calculated using RT2 Profiler PCR array data analysis software version 3.5. Results: Our results indicated that fifteen genes (from 36 studied genes were down-regulated and two genes (DNAJC11 and DNAJC5B were up-regulated in all three studied tumor cell lines by approximately more than two folds. The result of other studied genes (19 genes showed different expressional pattern (up or down-expression based on tumor cell lines. Conclusion: According to the findings of the present study, we may suggest that there is a direct correlation between OCT4B1 expression in tumor cell lines (and tissues and HSP40 family gene expressions to escape from apoptosis and cancer expansion.

The 4.5 μm full-orbit phase curve of the hot Jupiter HD 209458b

International Nuclear Information System (INIS)

Zellem, Robert T.; Griffith, Caitlin A.; Showman, Adam P.; Lewis, Nikole K.; Knutson, Heather A.; Fortney, Jonathan J.; Laughlin, Gregory; Cowan, Nicolas B.; Agol, Eric; Burrows, Adam; Charbonneau, David; Deming, Drake; Langton, Jonathan

2014-01-01

The hot Jupiter HD 209458b is particularly amenable to detailed study as it is among the brightest transiting exoplanet systems currently known (V-mag = 7.65; K-mag = 6.308) and has a large planet-to-star contrast ratio. HD 209458b is predicted to be in synchronous rotation about its host star with a hot spot that is shifted eastward of the substellar point by superrotating equatorial winds. Here we present the first full-orbit observations of HD 209458b, in which its 4.5 μm emission was recorded with Spitzer/IRAC. Our study revises the previous 4.5 μm measurement of HD 209458b's secondary eclipse emission downward by ∼35% to 0.1391% −0.0069% +0.0072% , changing our interpretation of the properties of its dayside atmosphere. We find that the hot spot on the planet's dayside is shifted eastward of the substellar point by 40.°9 ± 6.°0, in agreement with circulation models predicting equatorial superrotation. HD 209458b's dayside (T bright = 1499 ± 15 K) and nightside (T bright = 972 ± 44 K) emission indicate a day-to-night brightness temperature contrast smaller than that observed for more highly irradiated exoplanets, suggesting that the day-to-night temperature contrast may be partially a function of the incident stellar radiation. The observed phase curve shape deviates modestly from global circulation model predictions potentially due to disequilibrium chemistry or deficiencies in the current hot CH 4 line lists used in these models. Observations of the phase curve at additional wavelengths are needed in order to determine the possible presence and spatial extent of a dayside temperature inversion, as well as to improve our overall understanding of this planet's atmospheric circulation.

The 4.5 μm full-orbit phase curve of the hot Jupiter HD 209458b

Energy Technology Data Exchange (ETDEWEB)

Zellem, Robert T.; Griffith, Caitlin A.; Showman, Adam P. [Lunar and Planetary Laboratory, University of Arizona, 1629 East University Boulevard, Tucson, AZ 85721 (United States); Lewis, Nikole K. [Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, MC 170-25 1200 East California Boulevard, Pasadena, CA 91125 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (United States); Cowan, Nicolas B. [Department of Earth and Planetary Sciences, Northwestern University, Technological Institute, 2145 Sheridan Road, Evanston, IL 60208 (United States); Agol, Eric [Astronomy Department, University of Washington, Physics-Astronomy Building, 3910 15th Avenue NE, Seattle, WA 98195 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, 4 Ivy Lane, Peyton Hall, Princeton University, Princeton, NJ 08544 (United States); Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street MS-16, Cambridge, MA 02138 (United States); Deming, Drake [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Langton, Jonathan, E-mail: rzellem@lpl.arizona.edu [Physics Department, Principia College, 1 Maybeck Place, Elsah, IL 62028 (United States)

2014-07-20

The hot Jupiter HD 209458b is particularly amenable to detailed study as it is among the brightest transiting exoplanet systems currently known (V-mag = 7.65; K-mag = 6.308) and has a large planet-to-star contrast ratio. HD 209458b is predicted to be in synchronous rotation about its host star with a hot spot that is shifted eastward of the substellar point by superrotating equatorial winds. Here we present the first full-orbit observations of HD 209458b, in which its 4.5 μm emission was recorded with Spitzer/IRAC. Our study revises the previous 4.5 μm measurement of HD 209458b's secondary eclipse emission downward by ∼35% to 0.1391%{sub −0.0069%}{sup +0.0072%}, changing our interpretation of the properties of its dayside atmosphere. We find that the hot spot on the planet's dayside is shifted eastward of the substellar point by 40.°9 ± 6.°0, in agreement with circulation models predicting equatorial superrotation. HD 209458b's dayside (T{sub bright} = 1499 ± 15 K) and nightside (T{sub bright} = 972 ± 44 K) emission indicate a day-to-night brightness temperature contrast smaller than that observed for more highly irradiated exoplanets, suggesting that the day-to-night temperature contrast may be partially a function of the incident stellar radiation. The observed phase curve shape deviates modestly from global circulation model predictions potentially due to disequilibrium chemistry or deficiencies in the current hot CH{sub 4} line lists used in these models. Observations of the phase curve at additional wavelengths are needed in order to determine the possible presence and spatial extent of a dayside temperature inversion, as well as to improve our overall understanding of this planet's atmospheric circulation.

Peroxisomal abnormalities in the immortalized human hepatocyte (IHH) cell line.

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Klouwer, Femke C C; Koster, Janet; Ferdinandusse, Sacha; Waterham, Hans R

2017-04-01

The immortalized human hepatocyte (IHH) cell line is increasingly used for studies related to liver metabolism, including hepatic glucose, lipid, lipoprotein and triglyceride metabolism, and the effect of therapeutic interventions. To determine whether the IHH cell line is a good model to investigate hepatic peroxisomal metabolism, we measured several peroxisomal parameters in IHH cells and, for comparison, HepG2 cells and primary skin fibroblasts. This revealed a marked plasmalogen deficiency and a deficient fatty acid α-oxidation in the IHH cells, due to a defect of PEX7, a cytosolic receptor protein required for peroxisomal import of a subset of peroxisomal proteins. These abnormalities have consequences for the lipid homeostasis of these cells and thus should be taken into account for the interpretation of data previously generated by using this cell line and when considering using this cell line for future research.

Zingiber officinale, Piper retrofractum and Combination Induced Apoptosis and p53 Expression in Myeloma and WiDr Cell Lines

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HENY EKOWATI

2012-09-01

Full Text Available In previous studies, Zingiber officinale, Piper retrofractum, and the combination showed cytotoxic activity, induced apoptosis, and p53 expression of HeLa, T47D, and MCF-7 cell lines. This study was conducted to investigate the cytotoxic and apoptotic activity of Zingiber officinale (ZO, Piper retrofractum (PR, and the combination as well as their effect to p53 expression on Myeloma and WiDr cells. The powder of ZO, PR, and ZO + PR combination (1:1 were macerated with 96% ethanol for 3 x 24 hours. MTT cytotoxic assay was performed on Myeloma and WiDr cell lines. Apoptotic cells were stained with ethidium bromide and acridine orange. Imunohistochemical expression of p53 was examined on Myeloma and WiDr cell lines. Doxorubicin was used as positive control in all assays. Results showed that ZO, PR, and ZO + PR combination had cytotoxic activity on Myeloma cells with IC50 of 28, 36, and 55 mg/ml respectively and WiDr cell lines with IC50 of 74, 158, and 64 mg/ml respectively, induced apoptotic activity, and increased p53 expression on Myeloma and WiDr cells. These results suggest that ZO, PR, and their combination induced Myeloma and WiDr cells in apoptosis through p53 expression.

Cellular radiosensitivity of small-cell lung cancer cell lines

DEFF Research Database (Denmark)

Krarup, M; Poulsen, H S; Spang-Thomsen, M

1997-01-01

PURPOSE: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based...

Establishment and Identification of Chinese Hamster Ovary Cell Lines with Stable Expression of Soluble CD40 Ligands

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JIANG Hua-wei

2014-09-01

Full Text Available Objective: To establish the Chinese Hamster Ovary (CHO cell lines with stable expression of soluble CD40 ligands (sCD40L. Methods: Recombinant plasmid pIRES2-EGFP-sCD40L, enzyme digestion and sequencing identification were obtained by cloning sCD40L coding sequences into eukaryotic expression vector pIRES2-EGFP from carrier pDC316-sCD40 containing sCD40L. CHO cells were transfected by electroporation, followed by screening of resistant clones with G418, after which monoclones were obtained by limited dilution assay and multiply cultured. Flow cytometer and reverted fluorescence microscope were applied to observe the expression of green fluorescent protein, while sCD40L expression was detected by polymerase chain reaction (PCR, reverse transcription-polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA from aspects of deoxyribose nucleic acid (DNA, messenger ribonucleic acid (mRNA and protein, respectively. CHO-sCD40L was cultured together with MDA-MB-231 cells to compare the expression changes of surface molecule fatty acid synthase (Fas by flow cytometer and observe the apoptosis of MDA-MB-231 cells after Fas activated antibodies (CH-11 were added 24 h later. Results: Plasmid pIRES2-EGFP-sCD40L was successfully established, and cell lines with stable expression of sCD40L were obtained with cloned culture after CHO cell transfection, which was named as B11. Flow cytometer and reverted fluorescence microscope showed ＞90% expression of green fluorescent protein, while PCR, RT-PCR and ELISA suggested integration of sCD40L genes into cell genome DNA, transcription of sCD40L mRNA and sCD40L protein expression being (4.5±2.1 ng/mL in the supernatant of cell culture, respectively. After co-culture of B11 and MDA-MB-231 cells, the surface Fas expression of MDA-MB-231 cells was increased from (3±1.02 % to (34.8±8.75%, while the apoptosis rate 24 h after addition of CH11 from (5.4±1.32% to (20.7±5.24%, and the differences

CO Gas Inside the Protoplanetary Disk Cavity in HD 142527: Disk Structure from ALMA

OpenAIRE

Perez, S.; Casassus, S.; Ménard, F.; Roman, P.; van der Plas, G.; Cieza, L.; Pinte, C.; Christiaens, Valentin; Hales, A. S.

2014-01-01

Inner cavities and annular gaps in circumstellar disks are possible signposts of giant planet formation. The young star HD 142527 hosts a massive protoplanetary disk with a large cavity that extends up to 140 AU from the central star, as seen in continuum images at infrared and millimeter wavelengths. Estimates of the survival of gas inside disk cavities are needed to discriminate between clearing scenarios. We present a spatially and spectrally resolved carbon monoxide isotopologue 2-1 line ...

C22:0- and C24:0-dihydroceramides confer mixed cytotoxicity in T-cell acute lymphoblastic leukemia cell lines.

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Michael W Holliday

Full Text Available We previously reported that fenretinide (4-HPR was cytotoxic to acute lymphoblastic leukemia (ALL cell lines in vitro in association with increased levels of de novo synthesized dihydroceramides, the immediate precursors of ceramides. However, the cytotoxic potentials of native dihydroceramides have not been defined. Therefore, we determined the cytotoxic effects of increasing dihydroceramide levels via de novo synthesis in T-cell ALL cell lines and whether such cytotoxicity was dependent on an absolute increase in total dihydroceramide mass versus an increase of certain specific dihydroceramides. A novel method employing supplementation of individual fatty acids, sphinganine, and the dihydroceramide desaturase-1 (DES inhibitor, GT-11, was used to increase de novo dihydroceramide synthesis and absolute levels of specific dihydroceramides and ceramides. Sphingolipidomic analyses of four T-cell ALL cell lines revealed strong positive correlations between cytotoxicity and levels of C22:0-dihydroceramide (ρ = 0.74-0.81, P ≤ 0.04 and C24:0-dihydroceramide (ρ = 0.84-0.90, P ≤ 0.004, but not between total or other individual dihydroceramides, ceramides, or sphingoid bases or phosphorylated derivatives. Selective increase of C22:0- and C24:0-dihydroceramide increased level and flux of autophagy marker, LC3B-II, and increased DNA fragmentation (TUNEL assay in the absence of an increase of reactive oxygen species; pan-caspase inhibition blocked DNA fragmentation but not cell death. C22:0-fatty acid supplemented to 4-HPR treated cells further increased C22:0-dihydroceramide levels (P ≤ 0.001 and cytotoxicity (P ≤ 0.001. These data demonstrate that increases of specific dihydroceramides are cytotoxic to T-cell ALL cells by a caspase-independent, mixed cell death mechanism associated with increased autophagy and suggest that dihydroceramides may contribute to 4-HPR-induced cytotoxicity. The targeted increase of specific acyl chain dihydroceramides

Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines.

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Van Roy, N; Van Limbergen, H; Vandesompele, J; Van Gele, M; Poppe, B; Salwen, H; Laureys, G; Manoel, N; De Paepe, A; Speleman, F

2001-10-01

Cancer cell lines are essential gene discovery tools and have often served as models in genetic and functional studies of particular tumor types. One of the future challenges is comparison and interpretation of gene expression data with the available knowledge on the genomic abnormalities in these cell lines. In this context, accurate description of these genomic abnormalities is required. Here, we show that a combination of M-FISH with banding analysis, standard FISH, and CGH allowed a detailed description of the genetic alterations in 16 neuroblastoma cell lines. In total, 14 cryptic chromosome rearrangements were detected, including a balanced t(2;4)(p24.3;q34.3) translocation in cell line NBL-S, with the 2p24 breakpoint located at about 40 kb from MYCN. The chromosomal origin of 22 marker chromosomes and 41 cytogenetically undefined translocated segments was determined. Chromosome arm 2 short arm translocations were observed in six cell lines (38%) with and five (31%) without MYCN amplification, leading to partial chromosome arm 2p gain in all but one cell line and loss of material in the various partner chromosomes, including 1p and 11q. These 2p gains were often masked in the GGH profiles due to MYCN amplification. The commonly overrepresented region was chromosome segment 2pter-2p22, which contains the MYCN gene, and five out of eleven 2p breakpoints clustered to the interface of chromosome bands 2p16 and 2p21. In neuroblastoma cell line SJNB-12, with double minutes (dmins) but no MYCN amplification, the dmins were shown to be derived from 16q22-q23 sequences. The ATBF1 gene, an AT-binding transcription factor involved in normal neurogenesis and located at 16q22.2, was shown to be present in the amplicon. This is the first report describing the possible implication of ATBF1 in neuroblastoma cells. We conclude that a combined approach of M-FISH, cytogenetics, and CGH allowed a more complete and accurate description of the genetic alterations occurring in the

Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells.

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Fan, Lianchun; Kadura, Ibrahim; Krebs, Lara E; Hatfield, Christopher C; Shaw, Margaret M; Frye, Christopher C

2012-04-01

Although Chinese hamster ovary (CHO) cells, with their unique characteristics, have become a major workhorse for the manufacture of therapeutic recombinant proteins, one of the major challenges in CHO cell line generation (CLG) is how to efficiently identify those rare, high-producing clones among a large population of low- and non-productive clones. It is not unusual that several hundred individual clones need to be screened for the identification of a commercial clonal cell line with acceptable productivity and growth profile making the cell line appropriate for commercial application. This inefficiency makes the process of CLG both time consuming and laborious. Currently, there are two main CHO expression systems, dihydrofolate reductase (DHFR)-based methotrexate (MTX) selection and glutamine synthetase (GS)-based methionine sulfoximine (MSX) selection, that have been in wide industrial use. Since selection of recombinant cell lines in the GS-CHO system is based on the balance between the expression of the GS gene introduced by the expression plasmid and the addition of the GS inhibitor, L-MSX, the expression of GS from the endogenous GS gene in parental CHOK1SV cells will likely interfere with the selection process. To study endogenous GS expression's potential impact on selection efficiency, GS-knockout CHOK1SV cell lines were generated using the zinc finger nuclease (ZFN) technology designed to specifically target the endogenous CHO GS gene. The high efficiency (∼2%) of bi-allelic modification on the CHO GS gene supports the unique advantages of the ZFN technology, especially in CHO cells. GS enzyme function disruption was confirmed by the observation of glutamine-dependent growth of all GS-knockout cell lines. Full evaluation of the GS-knockout cell lines in a standard industrial cell culture process was performed. Bulk culture productivity improved two- to three-fold through the use of GS-knockout cells as parent cells. The selection stringency was

Impurity profiling of liothyronine sodium by means of reversed phase HPLC, high resolution mass spectrometry, on-line H/D exchange and UV/Vis absorption.

Science.gov (United States)

Ruggenthaler, M; Grass, J; Schuh, W; Huber, C G; Reischl, R J

2017-09-05

For the first time, a comprehensive investigation of the impurity profile of the synthetic thyroid API (active pharmaceutical ingredient) liothyronine sodium (LT 3 Na) was performed by using reversed phase HPLC and advanced structural elucidation techniques including high resolution tandem mass spectrometry (HRMS/MS) and on-line hydrogen-deuterium (H/D) exchange. Overall, 39 compounds were characterized and 25 of these related substances were previously unknown to literature. The impurity classification system recently developed for the closely related API levothyroxine sodium (LT 4 Na) could be applied to the newly characterized liothyronine sodium impurities resulting in a wholistic thyroid API impurity classification system. Furthermore, the mass-spectrometric CID-fragmentation of specific related substances was discussed and rationalized by detailed fragmentation pathways. Moreover, the UV/Vis absorption characteristics of the API and selected impurities were investigated to corroborate chemical structure assignments derived from MS data. Copyright © 2017 Elsevier B.V. All rights reserved.

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