Quantitative cell fusion: the fusion sensitivity (FS) potential

1981 ◽  
Vol 49 (1) ◽  
pp. 87-97
Author(s):  
D. Rohme
Keyword(s):  
Cell Line ◽  
Cell Fusion ◽  
Cell Lines ◽  
Dose Response ◽  
Sendai Virus ◽  
Biological Significance ◽  
Diploid Cell ◽  
Mammalian Cell Lines ◽  
Virus Dose ◽  
A Cell

The dose response of Sendai virus-induced cell fusion was studied in 10 mammalian cell lines, comprising 5 continuous and 5 diploid cell lines originating from 5 species. The extent of fusion was calculated using a parameter directly proportional to the number of fusion events (t-parameter). At lower levels of fusion the dose response was found to be based on the same simple kinetic rules in all cell lines and was defined by the formula: t = FS. FAU/(I + FS. FAU), where FS (fusion sensitivity) is a cell-specific constant of the fusion rate and FAU (fusion activity units) is the virus dose. The FS potential of a cell line was determined as the linear regression coefficient of the fusion index (t/(I - t)) on the virus dose. At higher levels of fusion, when the fusion extent reached cell-line-specific maximal levels, the dose response was not as uniform. In general, and particularly in the cases of the diploid cell lines, these maximal levels were directly proportional to the FS potentials. Thus, it was concluded that the FS potential is the basic quantitative feature, which expresses the cellular fusion efficiency. The fact that FS varied extensively between cell lines, but at the same time apparently followed certain patterns (being higher in continuous compared to diploid cell lines and being related to the species of origin of the cells), emphasizes it biological significance as well as its possible usefulness in studies of the efficiency of various molecular interactions in the cell membrane/cytoskeleton system.

Discrimination of Two Fusogenic Properties of Aqueous Polyethylene Glycol Solutions

1981 ◽  
Vol 36 (7-8) ◽  
pp. 593-596 ◽  
Author(s):  
Hermann Krähling
Keyword(s):  
Polyethylene Glycol ◽  
Cell Line ◽  
Cell Fusion ◽  
Mammalian Cell ◽  
Dose Response ◽  
Cell Contact ◽  
Cell Shrinkage ◽  
Mammalian Cell Lines ◽  
A Cell ◽  
Free Membrane

Abstract Investigations on the dose response of cell fusion, induced by ionfree aqueous polyethylene glycol (PEG) solutions, reveal distinct lowest fusogenic PEG concentrations for different permanently growing mammalian cell lines. Part of the requisite PEG can be replaced by carbo­ hydrates, preserving the fusogenity of the solutions. This discriminates two effects of PEG solutions causing cell fusion: a) cell shrinkage, the required hyperosmolality of the solutions may be provided by PEG or by carbohydrates, is supposed to cause intracellular processes necessary for consolidating polycaryons; b) membrane alterations, which can not be induced by carbo­ hydrates, enable intimate cell-cell contact via particle-free membrane areas. Depending on cell line salts can not only raise the osmolality of PEG solutions but are able to co-operate with PEG in generating membrane alterations.

lncLocator 2.0: a cell-line-specific subcellular localization predictor for long non-coding RNAs with interpretable deep learning

2021 ◽  
Author(s):  
Yang Lin ◽  
Xiaoyong Pan ◽  
Hong-Bin Shen
Keyword(s):  
Subcellular Localization ◽  
Cell Line ◽  
Cell Lines ◽  
Short Term Memory ◽  
Computational Method ◽  
Language Models ◽  
Supplementary Information ◽  
Deep Model ◽  
A Cell ◽  
Non Coding Rnas

Abstract Motivation Long non-coding RNAs (lncRNAs) are generally expressed in a tissue-specific way, and subcellular localizations of lncRNAs depend on the tissues or cell lines that they are expressed. Previous computational methods for predicting subcellular localizations of lncRNAs do not take this characteristic into account, they train a unified machine learning model for pooled lncRNAs from all available cell lines. It is of importance to develop a cell-line-specific computational method to predict lncRNA locations in different cell lines. Results In this study, we present an updated cell-line-specific predictor lncLocator 2.0, which trains an end-to-end deep model per cell line, for predicting lncRNA subcellular localization from sequences.We first construct benchmark datasets of lncRNA subcellular localizations for 15 cell lines. Then we learn word embeddings using natural language models, and these learned embeddings are fed into convolutional neural network, long short-term memory and multilayer perceptron to classify subcellular localizations. lncLocator 2.0 achieves varying effectiveness for different cell lines and demonstrates the necessity of training cell-line-specific models. Furthermore, we adopt Integrated Gradients to explain the proposed model in lncLocator 2.0, and find some potential patterns that determine the subcellular localizations of lncRNAs, suggesting that the subcellular localization of lncRNAs is linked to some specific nucleotides. Availability The lncLocator 2.0 is available at www.csbio.sjtu.edu.cn/bioinf/lncLocator2 and the source code can be found at https://github.com/Yang-J-LIN/lncLocator2. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals A Place for High-Throughput Electrophysiology in Cardiac Safety: Screening hERG Cell Lines and Novel Compounds with the Ion Works HTTM System

2005 ◽  
Vol 10 (8) ◽  
pp. 832-840 ◽  
Author(s):  
Heather Guthrie ◽  
Frederick S. Livingston ◽  
Ueli Gubler ◽  
Ralph Garippa
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Torsades De Pointes ◽  
Delayed Rectifier ◽  
Drug Candidates ◽  
Delayed Rectifier Potassium Channel ◽  
A Cell ◽  
Line Selection ◽  
Herg Channels ◽  
Cell Line Selection

Several commercially available pharmaceutical compounds have been shown to block the I Krcurrent of the cardiac action potential. This effect can cause a prolongation of the electrocardiogram QTinterval and a delay in ventricular repolarization. The Food and Drug Administration recommends that all new potential drug candidates be assessed for I Krblock to avoid a potentially lethal cardiac arrhythmia known as torsades de pointes. Direct compound interaction with the human ether-a-go-go– related gene (hERG) product, a delayed rectifier potassium channel, has been identified as a molecular mechanism of I Kr block. One strategy to identify compounds withh ERGliability is to monitor hERGcurrent inhibition using electrophysiology techniques. The authors describe the Ion Works HT ™instrument as a tool for screening cell lines expressing hERG channels. Based on current amplitude and stability criteria, a cell line was selected and used to perform a 300-compound screen. The screen was able to identify compounds with hERG activity within projects that spanned different therapeutic areas. The cell line selection and optimization, as well as the screening abilities of the Ion Works HT ™system, provide a powerful means of assessinghERGactive compounds early in the drug discovery pipeline.

scholarly journals Cell Line Classification Using Electric Cell-Substrate Impedance Sensing (ECIS)

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Megan L. Gelsinger ◽  
Laura L. Tupper ◽  
David S. Matteson
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Mammalian Cells ◽  
Statistical Tests ◽  
Classification Methods ◽  
Impedance Sensing ◽  
Mammalian Cell Lines ◽  
Cell Substrate ◽  
Multiple Cell ◽  
Line Classification

AbstractWe present new methods for cell line classification using multivariate time series bioimpedance data obtained from electric cell-substrate impedance sensing (ECIS) technology. The ECIS technology, which monitors the attachment and spreading of mammalian cells in real time through the collection of electrical impedance data, has historically been used to study one cell line at a time. However, we show that if applied to data from multiple cell lines, ECIS can be used to classify unknown or potentially mislabeled cells, factors which have previously been associated with the reproducibility crisis in the biological literature. We assess a range of approaches to this new problem, testing different classification methods and deriving a dictionary of 29 features to characterize ECIS data. Most notably, our analysis enriches the current field by making use of simultaneous multi-frequency ECIS data, where previous studies have focused on only one frequency; using classification methods to distinguish multiple cell lines, rather than simple statistical tests that compare only two cell lines; and assessing a range of features derived from ECIS data based on their classification performance. In classification tests on fifteen mammalian cell lines, we obtain very high out-of-sample predictive accuracy. These preliminary findings provide a baseline for future large-scale studies in this field.

Eltrombopag, but Not Romiplostim or Thrombopoietin, Inhibits Growth of Thrombopoietin Receptor Positive and Negative Human Leukemia Cell Lines

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4726-4726
Author(s):  
David W. Rusnak ◽  
Sharon K. Rudolph ◽  
Afshin Safavi ◽  
Connie L. Erickson-Miller
Keyword(s):  
Clinical Trials ◽  
Cell Line ◽  
Cell Lines ◽  
Dose Response ◽  
Leukemia Cell ◽  
Cell Counts ◽  
Thrombopoietin Receptor ◽  
Ic50 Values ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 4726 The thrombopoietin receptor agonists (TPO-RA), romiplostim and eltrombopag, are presently indicated for the treatment of certain patient groups with immune thrombocytopenia purpura. In a clinical study with romiplostim in patients with low-/intermediate-1 risk myelodysplastic syndromes (MDS), cases of transient increases in blast cell counts were observed and cases of MDS disease progression to acute myeloid leukemia (AML) were reported. In the present study, we evaluated the impact of romiplostim, eltrombopag, and recombinant human thrombopoietin (TPO) on the proliferation of 5 human AML and 1 TPO-dependent megakaryoblastic cell line. The cell lines evaluated include the TPO-dependent cell line, N2C TPO; the TPO-R positive AML lines, HEL92.1.7 and OCI-AML-3; and the TPO-R negative AML cell lines, HL60, THP-1, and NOMO-1. All cells were exposed to 11-point dose response curves of the 3 agents at concentrations sufficient to generate a full stimulatory response in the N2C TPO cell line. Cells were exposed to concentrations of romiplostim and eltrombopag that met or exceeded the reported Cmax achieved for each agent in high-dose clinical trials and were 3- (eltrombopag) to 30-fold (romiplostim) above trough levels from the same clinical trials. Neither romiplostim nor TPO treatment resulted in detectable stimulation or inhibition of leukemia cell growth at concentrations up to 10 μg/mL. Treatment with eltrombopag up to 40 μg/mL caused inhibition of all AML cell lines with mean IC50 values ranging from 6.4 to 13.5 μg/mL. These IC50 values reflect concentrations that are 3- to 6-fold below the Cmax of a 300 qd dose of eltrombopag (40.5 μg/mL) and at concentrations as low as 2-fold below Ctau levels (12.4 μg/mL). Cmax exceeded the IC90 for these AML cell lines, which ranged from 18.5 to 27.9 μg/mL. No stimulation of AML growth was evident through the range of the eltrombopag dose response curve on any of the cell lines evaluated. The results of this study confirm earlier in vitro studies (Will 2009, Erickson-Miller 2010) showing inhibitory effects of eltrombopag on leukemic cell lines and support clinical studies to evaluate a potential anti-leukemic effect of higher doses of eltrombopag in patients with AML. Disclosures: Rusnak: GlaxoSmithKline: Consultancy, Equity Ownership, Patents & Royalties. Off Label Use: Eltrombopag is an oral TPO agonist indicated for chronic ITP being studied in MDS/AML. Rudolph:GlaxoSmithKline: Consultancy, Equity Ownership. Erickson-Miller:GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties, Research Funding.

scholarly journals MUTANTS OF NONPRODUCER CELL LINES TRANSFORMED BY MURINE SARCOMA VIRUS

1973 ◽  
Vol 138 (2) ◽  
pp. 364-372 ◽  
Author(s):  
M. Hatanaka ◽  
R. Klein ◽  
C. W. Long ◽  
R. Gilden
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
In Vitro Cultivation ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
A Cell ◽  
Phenotypic Reversion

Tumorigenic and nontumorigenic mutants induced by a single 5'-bromodeoxyuridine (BrdU) treatment of a nonproducer (NP) tumorigenic cell line were isolated and characterized. Among the cloned derivatives were examples of virus-free and sarcoma virus-producing cell lines. Oncogenicity did not correlate with production of virus or ease of rescue of the sarcoma genome. All lines, including nononcogenic derivatives, retained the sarcoma genome. Phenotypic reversion of some cell mutants was observed after in vivo inoculation or long term in vitro cultivation. The M-50T cell line, obtained from a tumor induced by M-50 cells, had a sarcoma genome rescuable by direct superinfection; this was only achieved with parental M-50 cells by a cell fusion rescue technique. The M-43-2T cell, obtained from a single small static tumor induced by otherwise nononcogenic M-43-2 cells, shed sarcoma virus and became tumorigenic. M-58-4-48 became tumorigenic after passage 48 of the M-58-4 line, which was originally nontumorigenic. These observations of phenotypic reversion demonstrate that the presence of the sarcoma gene in cells is an essential but not sufficient condition of tumorigenesis.

scholarly journals Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c)

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Warren Fiskus ◽  
Steffen Boettcher ◽  
Naval Daver ◽  
Christopher P. Mill ◽  
Koji Sasaki ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Cell Line ◽  
Cell Lines ◽  
Clinical Studies ◽  
Combined Therapy ◽  
Npm1 Mutation ◽  
In Vivo Efficacy ◽  
Clinical Responses ◽  
A Cell

AbstractTreatment with Menin inhibitor (MI) disrupts the interaction between Menin and MLL1 or MLL1-fusion protein (FP), inhibits HOXA9/MEIS1, induces differentiation and loss of survival of AML harboring MLL1 re-arrangement (r) and FP, or expressing mutant (mt)-NPM1. Following MI treatment, although clinical responses are common, the majority of patients with AML with MLL1-r or mt-NPM1 succumb to their disease. Pre-clinical studies presented here demonstrate that genetic knockout or degradation of Menin or treatment with the MI SNDX-50469 reduces MLL1/MLL1-FP targets, associated with MI-induced differentiation and loss of viability. MI treatment also attenuates BCL2 and CDK6 levels. Co-treatment with SNDX-50469 and BCL2 inhibitor (venetoclax), or CDK6 inhibitor (abemaciclib) induces synergistic lethality in cell lines and patient-derived AML cells harboring MLL1-r or mtNPM1. Combined therapy with SNDX-5613 and venetoclax exerts superior in vivo efficacy in a cell line or PD AML cell xenografts harboring MLL1-r or mt-NPM1. Synergy with the MI-based combinations is preserved against MLL1-r AML cells expressing FLT3 mutation, also CRISPR-edited to introduce mtTP53. These findings highlight the promise of clinically testing these MI-based combinations against AML harboring MLL1-r or mtNPM1.

scholarly journals Cell-Line Annotation on Europe PubMed Central

2014 ◽  
Author(s):  
Jee-Hyub Kim
Keyword(s):  
Cell Culture ◽  
Single Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Biomedical Literature ◽  
Pubmed Central ◽  
Preliminary Results ◽  
Data Citation ◽  
A Cell

A cell line is a cell culture developed from a single cell and therefore consisting of cells with a uniform genetic make-up. A cell line has an important role as a research resource such as organisms, antibodies, constructs, knockdown reagents, etc. Unique identification of cell lines in the biomedical literature is important for the reproducibility of science. As data citation, resource citation is also important for resource re-use. In this paper, we mention the challenges of identifying cell lines and describe a system for cell line annotation with preliminary results.

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