scholarly journals A Cell Model for Conditional Profiling of Androgen-Receptor-Interacting Proteins

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
K. A. Mooslehner ◽  
J. D. Davies ◽  
I. A. Hughes
Keyword(s):  
Androgen Receptor ◽  
Protein Interactions ◽  
Cell Model ◽  
Mouse Cell ◽  
Interacting Proteins ◽  
Wild Type ◽  
Genital Development ◽  
A Cell ◽  
The Impact ◽  
Male Genital

Partial androgen insensitivity syndrome (PAIS) is associated with impaired male genital development and can be transmitted through mutations in the androgen receptor (AR). The aim of this study is to develop a cell model suitable for studying the impact AR mutations might have on AR interacting proteins. For this purpose, male genital development relevant mouse cell lines were genetically modified to express a tagged version of wild-type AR, allowing copurification of multiprotein complexes under native conditions followed by mass spectrometry. We report 57 known wild-type AR-interacting proteins identified in cells grown under proliferating and 65 under nonproliferating conditions. Of those, 47 were common to both samples suggesting different AR protein complex components in proliferating and proliferation-inhibited cells from the mouse proximal caput epididymus. These preliminary results now allow future studies to focus on replacing wild-type AR with mutant AR to uncover differences in protein interactions caused by AR mutations involved in PAIS.

scholarly journals A Cell-Based Method for Screening RNA-Protein Interactions: Identification of Constitutive Transport Element-Interacting Proteins

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48194 ◽  
Author(s):  
Robert L. Nakamura ◽  
Stephen G. Landt ◽  
Emily Mai ◽  
Jemiel Nejim ◽  
Lily Chen ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Interacting Proteins ◽  
Constitutive Transport Element ◽  
A Cell

scholarly journals A yeast-based functional assay for the detection of the mutant androgen receptor in prostate cancer

2003 ◽  
pp. 99-110 ◽  
Author(s):  
J Ceraline ◽  
E Erdmann ◽  
P Erbs ◽  
M Deslandres-Cruchant ◽  
D Jacqmin ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Expression Vector ◽  
Receptor Activation ◽  
Prostate Adenocarcinoma ◽  
Selective Medium ◽  
Functional Assay ◽  
Wild Type ◽  
Hormonal Therapies ◽  
The Impact ◽  
Human Androgen Receptor

OBJECTIVE: Mutations in the ligand-binding domain of the human androgen receptor (AR) figure among the ways used by prostate adenocarcinoma (PCa) cells to escape androgen dependence. These mutations may broaden the specificity and/or affinity of the AR to other hormones, resulting in inappropriate receptor activation and thus affecting the PCa response to physiological stimuli and hormonal therapies. DESIGN: In order to clarify the impact of these mutations on disease progression and treatment, we have developed a yeast-based functional assay that allows the detection of mutant ARs and the analysis of their transactivation capacities in response to different ligands. METHODS: AR cDNA was directly cloned into an expression vector in a yeast strain that carries a reporter gene (ADE2) linked to an androgen-dependent promoter. The expression of the ADE2 gene and consequently the yeast cell growth in a selective medium depleted in adenine depends on the specificity of the AR for the ligand added to the medium. RESULTS: By analysing the transactivation capacities of different AR molecules in response to a broad range of steroid and non-steroid ligands, we have demonstrated that this assay can discriminate among wild-type AR, T877A, C685Y and L701H mutant ARs and that at least 1% of mutant ARs could be detected when mutant and wild-type ARs were mixed at the cDNA level. CONCLUSIONS: The data presented here show that this simple AR assay is convenient for the routine detection of mutant ARs in PCa and is also suitable to evaluate the antagonist activities of anti-androgen molecules.

Regulation of stress-associated scaffold proteins JIP1 and JIP3 on the c-Jun NH2-terminal kinase in ischemia–reperfusion

2010 ◽  
Vol 88 (11) ◽  
pp. 1084-1092 ◽  
Author(s):  
Bing Xu ◽  
Yaling Zhou ◽  
Karmin O ◽  
Patrick C. Choy ◽  
Grant N. Pierce ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Scaffold Proteins ◽  
Signaling Cascade ◽  
Interacting Proteins ◽  
H9c2 Cells ◽  
Signaling Specificity ◽  
Sirna Treatment ◽  
A Cell

Ischemia–reperfusion (IR)-induced cell apoptosis involves the activation of c-Jun NH2-terminal kinase (JNK). The activation of JNK requires the presence of scaffold proteins called JNK-interacting proteins (JIP), which bind several members of a signaling cascade for proper signaling specificity. In this study, the expression of scaffold proteins JIP1 and JIP3 and their roles in the regulation of JNK activity were investigated in simulated IR in a cell model (H9c2). JIP1 protein expression was significantly decreased, whereas JIP3 protein expression was increased in IR H9c2 cells. Adenovirus-induced overexpression of JIP1 reduced IR-induced JNK activity and apoptosis. Conversely, overexpression of JIP3 increased JNK activity and apoptosis following IR. Depletion of endogenous JIP1 by siRNA treatment increased the IR-induced JNK activity, whereas siRNA-mediated depletion of endogenous JIP3 inhibited JNK activity. These results suggest that JIP1 and JIP3 play important roles in the activation of JNK during simulated IR challenge in H9c2 cells.

scholarly journals The Burkholderia pseudomallei ΔasdMutant Exhibits Attenuated Intracellular Infectivity and Imparts Protection against Acute Inhalation Melioidosis in Mice

2011 ◽  
Vol 79 (10) ◽  
pp. 4010-4018 ◽  
Author(s):  
Michael H. Norris ◽  
Katie L. Propst ◽  
Yun Kang ◽  
Steven W. Dow ◽  
Herbert P. Schweizer ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Cell Model ◽  
Single Copy ◽  
Wild Type ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Life Threatening ◽  
A Cell ◽  
Bioterrorism Agent

ABSTRACTBurkholderia pseudomallei, the cause of serious and life-threatening diseases in humans, is of national biodefense concern because of its potential use as a bioterrorism agent. This microbe is listed as a select agent by the CDC; therefore, development of vaccines is of significant importance. Here, we further investigated the growth characteristics of a recently createdB. pseudomallei1026b Δasdmutantin vitro, in a cell model, and in an animal model of infection. The mutant was typified by an inability to grow in the absence of exogenous diaminopimelate (DAP); upon single-copy complementation with a wild-type copy of theasdgene, growth was restored to wild-type levels. Further characterization of theB. pseudomalleiΔasdmutant revealed a marked decrease in RAW264.7 murine macrophage cytotoxicity compared to the wild type and the complemented Δasdmutant. RAW264.7 cells infected by the Δasdmutant did not exhibit signs of cytopathology or multinucleated giant cell (MNGC) formation, which were observed in wild-typeB. pseudomalleicell infections. The Δasdmutant was found to be avirulent in BALB/c mice, and mice vaccinated with the mutant were protected against acute inhalation melioidosis. Thus, theB. pseudomalleiΔasdmutant may be a promising live attenuated vaccine strain and a biosafe strain for consideration of exclusion from the select agent list.

scholarly journals FRAGMENTATION OF COLLIDING DISCS

1996 ◽  
Vol 07 (06) ◽  
pp. 837-855 ◽  
Author(s):  
FERENC KUN ◽  
HANS J. HERRMANN
Keyword(s):  
Mass Distribution ◽  
Initial Velocity ◽  
Cell Model ◽  
Low Velocity Impact ◽  
Anomalous Scaling ◽  
Low Velocity ◽  
Velocity Impact ◽  
Brittle Solids ◽  
A Cell ◽  
The Impact

We study the phenomena associated with the low-velocity impact of two solid discs of equal size using a cell model of brittle solids. The fragment ejection exhibits a jet-like structure the direction of which depends on the impact parameter. We obtain the velocity and the mass distribution of the debris. Varying the radius and the initial velocity of the colliding particles, the velocity components of the fragments show anomalous scaling. The mass distribution follows a power law in the region of intermediate masses.

scholarly journals The Impact of Cetuximab Plus AKT- or mTOR- Inhibitor in a Patient-Derived Colon Cancer Cell Model with Wild-Type RAS and PIK3CA Mutation

2017 ◽  
Vol 8 (14) ◽  
pp. 2713-2719 ◽  
Author(s):  
Ju Sun Kim ◽  
Jung Eun Kim ◽  
Kyung Kim ◽  
Jeeyun Lee ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cell ◽  
Mtor Inhibitor ◽  
Cell Model ◽  
Pik3ca Mutation ◽  
Colon Cancer Cell ◽  
Wild Type ◽  
The Impact

scholarly journals CREB5 reprograms nuclear interactions to promote resistance to androgen receptor targeting therapies

2021 ◽  
Author(s):  
Justin H Hwang ◽  
Rand Arafeh ◽  
Ji-Heui Seo ◽  
Sylvan C. Baca ◽  
Megan Ludwig ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Protein Interactions ◽  
Nuclear Protein ◽  
Regulatory Elements ◽  
Protein Protein Interactions ◽  
Castration Resistant ◽  
Nuclear Factors ◽  
Endogenous Proteins ◽  
Prostate Cancers ◽  
The Impact

Metastatic castration resistant prostate cancers (mCRPC) are treated with therapies that antagonize the androgen receptor (AR). Nearly all patients develop resistance to AR-targeted therapies (ART). Our previous work identified CREB5 as an upregulated target gene in human mCRPC that promoted resistance to all clinically-approved ART. The mechanisms by which CREB5 promotes progression of mCRPC or other cancers remains elusive. Integrating ChIP-seq and rapid immunoprecipitation and mass spectroscopy of endogenous proteins (RIME), we report that cells overexpressing CREB5 demonstrate extensive reprogramming of nuclear protein-protein interactions in response to the ART agent enzalutamide. Specifically, CREB5 physically interacts with AR, the pioneering actor FOXA1, and other known co-factors of AR and FOXA1 at transcription regulatory elements recently found to be active in mCRPC patients. We identified a subset of CREB5/FOXA1 co-interacting nuclear factors that have critical functions for AR transcription (GRHL2, HOXB13) while others (TBX3, NFIC) regulated cell viability and ART resistance and were amplified or overexpressed in mCRPC. Upon examining the nuclear protein interactions and the impact of CREB5 expression on the mCRPC patient transcriptome, we found CREB5 was associated with TGF-beta; and Wnt signaling and epithelial to mesenchymal transitions, implicating these pathways in ART resistance. Overall, these observations define the molecular interactions among CREB5, FOXA1, and pathways that promote ART resistance.

scholarly journals A quantitative high-resolution computational mechanics cell model for growing and regenerating tissues

2019 ◽  
Vol 19 (1) ◽  
pp. 189-220 ◽  
Author(s):  
Paul Van Liedekerke ◽  
Johannes Neitsch ◽  
Tim Johann ◽  
Enrico Warmt ◽  
Ismael Gonzàlez-Valverde ◽  
...  
Keyword(s):  
High Resolution ◽  
Blood Vessels ◽  
Cell Model ◽  
Medical Decision ◽  
Drug Induced ◽  
Tissue Organization ◽  
A Cell ◽  
Mechanical Elements ◽  
Scalable Network ◽  
The Impact

AbstractMathematical models are increasingly designed to guide experiments in biology, biotechnology, as well as to assist in medical decision making. They are in particular important to understand emergent collective cell behavior. For this purpose, the models, despite still abstractions of reality, need to be quantitative in all aspects relevant for the question of interest. This paper considers as showcase example the regeneration of liver after drug-induced depletion of hepatocytes, in which the surviving and dividing hepatocytes must squeeze in between the blood vessels of a network to refill the emerged lesions. Here, the cells’ response to mechanical stress might significantly impact the regeneration process. We present a 3D high-resolution cell-based model integrating information from measurements in order to obtain a refined and quantitative understanding of the impact of cell-biomechanical effects on the closure of drug-induced lesions in liver. Our model represents each cell individually and is constructed by a discrete, physically scalable network of viscoelastic elements, capable of mimicking realistic cell deformation and supplying information at subcellular scales. The cells have the capability to migrate, grow, and divide, and the nature and parameters of their mechanical elements can be inferred from comparisons with optical stretcher experiments. Due to triangulation of the cell surface, interactions of cells with arbitrarily shaped (triangulated) structures such as blood vessels can be captured naturally. Comparing our simulations with those of so-called center-based models, in which cells have a largely rigid shape and forces are exerted between cell centers, we find that the migration forces a cell needs to exert on its environment to close a tissue lesion, is much smaller than predicted by center-based models. To stress generality of the approach, the liver simulations were complemented by monolayer and multicellular spheroid growth simulations. In summary, our model can give quantitative insight in many tissue organization processes, permits hypothesis testing in silico, and guide experiments in situations in which cell mechanics is considered important.

scholarly journals Insert Switches Inside to Increase Battery Lifespan

2020 ◽  
Vol 5 (2) ◽  
pp. 201-209
Author(s):  
Christophe Savard ◽  
Pascal Venet ◽  
Eric Niel ◽  
Laurent Pietrac ◽  
Ali Sari
Keyword(s):  
Formal Model ◽  
Cell Model ◽  
Electrical Energy ◽  
Cell Aging ◽  
Fundamental Parameters ◽  
Electric Model ◽  
Behavioral Parameters ◽  
A Cell ◽  
The Impact ◽  
First Time

This paper shows the possible gain on time before the end of useful time brought by switches addition in a multicell battery. In a first time, it presents a battery electric model. A battery includes many identical electrical energy cells that electrically interact. From a behavioral standpoint, cell performance is measured by fundamental parameters: State of Charge (SoC) and State of Health (SoH). To simulate cell electrical behavior, the Thevenin model or the Nernst model are often used. However, these models do not take into account the cells aging or the possible interactions on aging. A cell ages mainly in two ways: cyclic and calendar. This aging impacts both the elements of the equivalent electrical model and the fundamental parameters (SoC and SoH). Thus, the conventional electric model of a cell does not accurately reflect the cell aging. In this paper, another formal model based on the fundamental curve that relates electrical and behavioral parameters is proposed. It integrates aging into the equivalent electric model estimation. In a second time, in order to validate this model, this cell model is used to simulate parallel-series association. To improve battery lifespan, in addition to the usual balancing techniques, it may be relevant to require some traditional reliability and operating safety solutions. This requires to add switches inside battery. The presented simulation shows adding switches solution is currently not deployed. This is justified in this paper by examining the impact provide on lifespan improvement on an example, which is pretty weak. But it also shows that however, by managing active cells in a different way, adding switches and spare cells can really reach this improvement.

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