ASD: a bioinformatics resource on alternative splicing

Stamm, Stefan; Riethoven, Jean-Jack; Texier, Vincent Le; Gopalakrishnan, Chellappa; Kumanduri, Vasudev; Tang, Yesheng; Barbosa‐Morais, Nuno L.; Thanaraj, Thangavel Alphonse

doi:10.1093/nar/gkj031

Cited by 211 publications

(211 citation statements)

References 31 publications

(33 reference statements)

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“…Evaluation of these observations-and of ESR1-by quantitative reverse transcription polymerase chain reaction (quantitative reverse transcriptase (qRT)-PCR) and/or by western blotting assays corroborated the overexpression of ESR1 and RAF1 in MCF7-LTED cells (Figure 3d, left panel, and e, and Supplementary Table 2). Although a trend was observed, GATA3 expression change was not confirmed by qRT-PCR assays (Figure 3d, left panel), which might be because of alternative splicing patterns for this gene (Stamm et al, 2006) detected in MCF7 cells (Hoch et al, 1999). Finally, in accordance with the molecular characterization above (Figure 1b), EGFR also showed significant overexpression in the microarray dataset (Figure 3b).…”

Section: Resultssupporting

confidence: 51%

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

et al. 2010

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Endocrine therapies targeting the proliferative effect of 17b-estradiol through estrogen receptor a (ERa) are the most effective systemic treatment of ERa-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through molecular mechanisms that are not yet fully understood. The longterm estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERa. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were predicted to be influenced by transcription factors known to be involved in acquired resistance or cell proliferation (for example, interferon regulatory transcription factor 1 and E2F1, respectively) but, notably, not by canonical ERa transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)-to pS167-ERa were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERa-negative status, early response to letrozole and tamoxifen, and recurrence after tamoxifen treatment. In accordance with these profiles, MCF7-LTED cells showed increased sensitivity to inhibition of FGFR-mediated signaling with PD173074. This study provides mechanistic insight into acquired resistance to endocrine therapies of breast cancer and highlights a potential therapeutic strategy.

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Section: Resultssupporting

confidence: 51%

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

et al. 2010

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“…There are alternatively spliced isoforms of PKCδ, θ, η and ς predicted from EST databases [25][26][27]. The importance of these more recently described isoforms in insulin action has not been described, to date, but the fact that some of the isoforms can encode up to 12 different splice variants with potentially unique cell functions opens new options for PKC in signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Specific protein kinase C isoforms as transducers and modulators of insulin signaling

Sampson

Cooper

2006

Molecular Genetics and Metabolism

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Recent studies implicate specific PKC isoforms in the insulin-signaling cascade. Insulin activates PKCsα, βII, δ and ζ in several cell types. In addition, as will be documented in this review, certain members of the PKC family may also be activated and act upstream of PI3 and MAP kinases. Each of these isoforms has been shown one way or another either to mimic or to modify insulin-stimulated effects in one or all of the insulin-responsive tissues. Moreover, each of the isoforms has been shown to be activated by insulin stimulation or conditions important for effective insulin stimulation. Studies attempting to demonstrate a definitive role for any of the isoforms have been performed on different cells, ranging from appropriate model systems for skeletal muscle, liver and fat, such as primary cultures, and cell lines and even in vivo studies, including transgenic mice with selective deletion of specific PKC isoforms. In addition, studies have been done on certain expression systems such as CHO or HEK293 cells, which are far removed from the tissues themselves and serve mainly as vessels for potential protein-protein interactions. Thus, a clear picture for many of the isoforms remains elusive in spite of over two decades of intensive research. The recent intrusion of transgenic and precise molecular biology technologies into the research armamentarium has opened a wide range of additional possibilities for direct involvement of individual isoforms in the insulin signaling cascade. As we hope to discuss within the context of this review, whereas many of the long soughtafter answers to specific questions are not yet clear, major advances have been made in our understanding of precise roles for individual PKC isoforms in mediation of insulin effects. In this review, in which we shall focus our attention on isoforms in the conventional and novel categories, a clear case will be made to show that these isoforms are not only expressed but are importantly involved in regulation of insulin metabolic effects.

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“…The incident light can be modulated in different ways by their electro-optic effects depending on the voltage applied across the LC layer. Various types of LC electro-optic structures have been tested and investigated in LCOS devices, such as the twisted nematic, 38 hybrid field effect in nematic LC, 39 electrically controlled birefringence (ECB), 40,41 surface-stabilized ferroelectric LC (SSFLC) [42][43][44][45] and vertically aligned nematic (VAN), optical compensated birefringence (OCB). These devices have mostly been designed for light modulators by rotating the linear polarzation of light passing through polarizers.…”

Section: Lc Electro-optic Effects For Phase-only Lcos Devicesmentioning

confidence: 99%

Fundamentals of phase-only liquid crystal on silicon (LCOS) devices

2014

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This paper describes the fundamentals of phase-only liquid crystal on silicon (LCOS) technology, which have not been previously discussed in detail. This technology is widely utilized in high efficiency applications for real-time holography and diffractive optics. The paper begins with a brief introduction on the developmental trajectory of phase-only LCOS technology, followed by the correct selection of liquid crystal (LC) materials and corresponding electro-optic effects in such devices. Attention is focused on the essential requirements of the physical aspects of the LC layer as well as the indispensable parameters for the response time of the device. Furthermore, the basic functionalities embedded in the complementary metal oxide semiconductor (CMOS) silicon backplane for phase-only LCOS devices are illustrated, including two typical addressing schemes. Finally, the application of phase-only LCOS devices in real-time holography will be introduced in association with the use of cutting-edge computer-generated holograms. The architecture of LCOS devices is similar to conventional LC devices except that a silicon backplane constitutes one of the substrates (Figure 1). The silicon CMOS backplane consists of the electronic circuitry that is buried underneath pixel arrays to provide a high 'fill factor'. The pixels are aluminum mirrors deposited on the surface of the silicon backplane. The incident light is transmitted through the LC layer with almost zero absorption. The integration of high-performance driving circuitry allows the applied voltage to be changed on each pixel, thereby controlling the phase retardation of the incident wavefront across the device. Currently, there are two types of light modulation using LCOS devices, amplitude modulation and phase modulation. In the former case, the amplitude of the light signal is modulated 6,7 by varying the linear polarzation direction of the incident light passing through a linear polarizer, the same principle used in a standard LC television. In the latter case, the phase delay is accomplished by electrically adjusting the optical refractive index along the light path, which is possible because of the non-zero birefringence of the LC materials in use but should be carefully characterized. [8][9][10][11][12][13] In a phase-only LCOS SLM modulator, no light absorption by polarizers or other light-absorbing components will occur, such that the maximum light efficiency can be expected.Currently, most of the conventional LC devices are not able to efficiently modulate the phase of an incident wavefront. For instance, the LC device structure using thin film transistors is not suitable for phase modulation because an appropriate electro-optic effect has not been used (see the section on 'Twisted nematic (TN) configuration' and the section on 'VAN configuration' for details). Moreover, the pixels of this type of device are too large to provide acceptably large diffraction angles. In addition, the pixel circuitry and connection tracks are in the light path such that the ...

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ASD: a bioinformatics resource on alternative splicing

Cited by 211 publications

References 31 publications

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

Specific protein kinase C isoforms as transducers and modulators of insulin signaling

Fundamentals of phase-only liquid crystal on silicon (LCOS) devices

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