Investigating The Role of AEG-1 in Mouse Models of Pain

Background: Astrocyte Elevated Gene 1 (AEG-1) is a multifunctional protein shown to be a regulator of transcription and multiple intracellular signaling pathways. The role of AEG-1 in cellular inflammation appears to be primarily facilitated by its direct interaction with the transcription factor NFκB, transcriptional regulator of inflammatory cytokines. May be have a potential role in models of pain, particularly chronic inflammatory and chemotherapy induced peripheral neuropathy (CIPN). Methods: C57BL6/J male and female mice, 8-14 weeks old. AEG-1 wild type (WT) and global knockout (KO) male and female mice, 8-14 weeks old. Chronic Inflammatory Pain induced via i.pl. injection of 50% Freund\u27s Complete Adjuvant (CFA) or vehicle into mouse right hind paw. CIPN induced via four 8 mg/kg, i.p. injections of Paclitaxel or vehicle (Toma, et. al). Mechanical hypersensitivity assessed via von frey filaments. Acetone Test was used to assess cold sensitivity. mRNA transcripts collected from tissues were measured via qRT-PCR. Results: AEG-1 KO mice displayed protection from CFA induced mechanical hypersensitivity, thermal sensitivity, and reduces paw edema compare to WT mice. AEG-1 KO mice displayed enhanced recovery from paclitaxel induced mechanical hypersensitivity and cold sensitivity compared to WT mice. AEG-1 expression levels in the periaqueductal grey, spinal cord, and L4-6 corresponding dorsal root ganglia collected from C57BL6/J mice treated with 8mg/Kg paclitaxel or 50% CFA (3 days post injection) showed no difference from control groups. Conclusions: Our data suggest that AEG-1 may be involved in inflammatory and CIPN related nociception in C57BL6/J mice.https://scholarscompass.vcu.edu/gradposters/1093/thumbnail.jp

A SEMIOLOGIC APPROACH TO AUDIT EXPECTATIONS GAP

Audit expectations gap (AEG) is one of the most debated phenomena animating the international scientific research scene. The volume of papers focused on defining the AEG concept, examining its determinants, implications, and mechanisms to minimize the gapaudit expectation gap, audit research, auditors, perceptions

Valuation Errors Caused by Conservative Accounting in Residual Income and Abnormal Earnings Growth Valuation Models

The impact of conservative accounting in residual income valuation (RIV) and abnormal earnings growth (AEG) valuation modeling is investigated in this paper. Unconstrained and two types of constrained model specifications are evaluated regarding their ability to withstand biases in book values and earnings due to accounting conservatism. Given that the “clean surplus relation” holds and that the precision of forecasted accounting numbers is unaffected by the type of accounting principles, the unconstrained valuation models are – not surprisingly – found to be immune to conservatism. This does not hold for the constrained models, even though conservatism can be accommodated in these if the time-series specification of the conservative bias fulfils certain conditions. In a comparison between terminal value constrained models, the AEG model is found to be superior to the RIV model if the growth of the conservative bias in the terminal period is not too extreme. Comparing the information dynamics constrained models being proposed in Ohlson (1995) and Ohlson & Juettner-Nauroth (2005), the AEG model is potentially more accurate than the RIV model. However, in a company steady state setting with constant growth, there is no comparative advantage for the AEG model. Also, using the same set of forecasted accounting numbers in the information dynamics constrained RIV model as in the corresponding AEG model, the two models cannot be ranked.Abnormal earnings growth model; Accounting-based valuation; Conservative accounting; Financial analysis; Residual income model

Astrocyte Elevated Gene-1 (AEG-1) Deletion Selectively Enhances the Antinociceptive Effects of Morphine

Background: Opioids are a class of drugs that are utilized in clinical settings to alleviate acute and chronic pain, but can often lead to development of tolerance, addiction and overdose following prolonged usage. Opioids such as morphine function by activating endogenous µ opioid receptors, which are located in various tissues throughout the body. Astrocyte Elevated Gene-1 (AEG-1) is a multifunctional protein that regulates inflammation, myeloid cell activity and lipid metabolism. Studies have shown interactions and overlaps in cellular signaling between the inflammatory/immune responses and the endogenous opioid system which could suggest a role for AEG-1 in opioids effects. Our goal is to investigate the role of AEG-1 in morphine mediated pharmacological effects including analgesia. Methods: Adult AEG-1 global knockout (KO) and wild-type (WT) male and female mice (C57BL/6J background) were utilized to assess morphine-induced thermal antinociception (The tail immersion assay test), hyperlocomotion, gastrointestinal (GI) transit inhibition, and tolerance. GI transit was assessed via charcoal transit assay. Locomotor boxes were used to assess spontaneous activity in mice. Results: AEG-1 KO mice displayed increased thermal antinociception following acute and repeated morphine administration compared to their WT counterparts. Pretreatment with naloxone blocked the enhancement of morphine thermal antinociception in AEG-1 KO mice. In addition, chronic morphine treated AEG-1 KO mice displayed reduced morphine tolerance development compared to their WT counterparts. No significant differences in morphine-induced hyperlocomotion or GI transit inhibition were observed between AEG-1 KO and WT mice. Conclusions: Our data suggest that AEG-1 deletion enhances the antinociceptive effects of morphine and reduces tolerance to chronic morphine treatment. However, AEG-1 deletion does not impact morphine-induced locomotor activity of GI transit inhibition. Overall, our results suggest that AEG-1 may function as a modulator of the endogenous opioid system.https://scholarscompass.vcu.edu/uresposters/1413/thumbnail.jp

Astrocyte elevated gene 1: biological functions and molecular mechanism in cancer and beyond

Since its discovery, nearly one decade of research on astrocyte elevated gene 1 (AEG-1) has witnessed expanding knowledge of this molecule, ranging from its role in cancer biology to molecular mechanisms underlying the biological functions. As a multifunctional oncoprotein, AEG-1 has been shown to overexpress in multiple types of human cancer, and the elevation of AEG-1 in tumor cells leads to enhanced phenotypes characteristic of malignant aggressiveness, including increased abilities to proliferate robustly, to invade surrounding tissues, to migrate, to induce neovascularization, and to enhance chemoresistance. The multifunctional role of AEG-1 in tumor development and progression has been found to be associated with several signaling cascades, namely, 1) activation of NF-kappa B, partially through direct interaction with p65; 2) PI3K/AKT signaling triggered by AEG-1 indirectly; 3) enhancement of the transcriptional activity of beta-catenin by indirect activation of MAPK and induction of LEF1; 4) regulation of mi/siRNA-mediated gene silencing by interacting with SND1; and 5) promotion of protective autophagy; in addition to possibly unknown mechanisms. Elevated AEG-1 expression is seen in nearly all tumor types, and in most cases AEG-1 positively correlates with tumor progression and poorer patient survival. Taken together, AEG-1 might represent a potential prognostic biomarker and therapeutic target

Affective Music Information Retrieval

Much of the appeal of music lies in its power to convey emotions/moods and to evoke them in listeners. In consequence, the past decade witnessed a growing interest in modeling emotions from musical signals in the music information retrieval (MIR) community. In this article, we present a novel generative approach to music emotion modeling, with a specific focus on the valence-arousal (VA) dimension model of emotion. The presented generative model, called \emph{acoustic emotion Gaussians} (AEG), better accounts for the subjectivity of emotion perception by the use of probability distributions. Specifically, it learns from the emotion annotations of multiple subjects a Gaussian mixture model in the VA space with prior constraints on the corresponding acoustic features of the training music pieces. Such a computational framework is technically sound, capable of learning in an online fashion, and thus applicable to a variety of applications, including user-independent (general) and user-dependent (personalized) emotion recognition and emotion-based music retrieval. We report evaluations of the aforementioned applications of AEG on a larger-scale emotion-annotated corpora, AMG1608, to demonstrate the effectiveness of AEG and to showcase how evaluations are conducted for research on emotion-based MIR. Directions of future work are also discussed.Comment: 40 pages, 18 figures, 5 tables, author versio

Astrocyte elevated gene-1 (AEG-1) is a marker for aggressive salivary gland carcinoma

<p>Abstract</p> <p>Background</p> <p>Astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression in diverse human cancers. The present study was aimed to investigate the clinical and prognostic significance of AEG-1 in salivary gland carcinomas (SGC).</p> <p>Methods</p> <p>Real-time PCR and western blot analyses were employed to examine AEG-1 expression in two normal salivary gland tissues, eight SGC tissues of various clinical stages, and five pairs of primary SGC and adjacent salivary gland tissues from the same patient. Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in paraffin-embedded tissues from 141 SGC patients. Statistical analyses was applies to evaluate the diagnostic value and associations of AEG-1 expression with clinical parameters.</p> <p>Results</p> <p>AEG-1 expression was evidently up-regulated in SGC tissues compared with that in the normal salivary gland tissues and in matched adjacent salivary gland tissues. AEG-1 protein level was positively correlated with clinical stage (<it>P </it>< 0.001), T classification (<it>P </it>= 0.008), N classification (<it>P </it>= 0.008) and M classifications (<it>P </it>= 0.006). Patients with higher AEG-1 expression had shorter overall survival time, whereas those with lower tumor AEG-1 expression had longer survival time.</p> <p>Conclusions</p> <p>Our results suggest that AEG-1 expression is associated with SGC progression and may represent a novel and valuable predictor for prognostic evaluation of SGC patients.</p

Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells

<p>Abstract</p> <p>Background</p> <p><it>Astrocyte elevated gene-1 </it>(<it>AEG</it>-<it>1</it>) was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of <it>AEG-1 </it>in promoting tumor progression and metastasis. The aim of this study was to investigate if <it>AEG-1 </it>serves as a potential therapeutic target of human neuroblastoma.</p> <p>Methods</p> <p>We employed RNA interference to reduce <it>AEG-1 </it>expression in human neuroblastoma cell lines and analyzed their phenotypic changes.</p> <p>Results</p> <p>We found that the knockdown of <it>AEG-1 </it>expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G₀/G₁phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of <it>AEG-1</it>.</p> <p>Conclusion</p> <p>Our study suggests that overexpressed <it>AEG-1 </it>enhance the tumorogenic properties of neuroblastoma cells. The inhibition of <it>AEG-1 </it>expression could be a new adjuvant therapy for neuroblastoma.</p

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial–mesenchymal transition in proximal tubular epithelial cells

AbstractObjectiveTo prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial–mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells.MethodsThe protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot.ResultsAEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT.ConclusionsOur results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells