Cyclic helix B peptide inhibits ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway

Renal fibrosis is a main cause of end-stage renal disease. Clinically, there is no beneficial treatment that can effectively reverse the progressive loss of renal function. We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. In this study, we evaluated the effect of CHBP on renal fibrosis in an in vivo ischemia reperfusion injury (IRI) model and in vitro TGF-β-stimulated tubular epithelial cells (TCMK-1 and HK-2) model. In the IRI in vivo model, mice were randomly divided into sham (sham operation), IR and IR + CHBP groups (n = 6). CHBP (8 nmol/kg) was administered intraperitoneally at the onset of reperfusion, and renal fibrosis was evaluated at 12 weeks post-reperfusion. Our results showed that CHBP markedly attenuated the IRI-induced deposition of collagen I and vimentin. In the in vitro model, CHBP reversed the TGF-β-induced down-regulation of E-cadherin and up-regulation of α-SMA and vimentin. Furthermore, CHBP inhibited the phosphorylation of Akt and Forkhead box O 3a (FoxO3a), whose anti-fibrotic effect could be reversed by the 3-phosphoinositide-dependent kinase-1 (PI3K) inhibitor wortmannin as well as FoxO3a siRNA. These findings demonstrate that CHBP attenuates renal fibrosis and the epithelial-mesenchymal transition of tubular cells, possibly through suppression of the PI3K/Akt pathway and thereby the inhibition FoxO3a activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0699-2) contains supplementary material, which is available to authorized users

Reversals of impairment charges under IAS 36: evidence from Malaysia

We report that firms reversing impairments under IAS 36 are not more incentivized to engage in earnings management and do not actually engage in more earnings management than a control sample matched on size and industry. We observe that reversals are positively associated with stock market valuation changes but not with future operating performance. Bifurcating our reversal firms into earnings managers and other firms, we report that the impairment reversals of the latter are positively associated with future firm performance and current stock market returns, while those of the former are negatively associated with future operating performance and are unrelated to stock valuation. Thus, while on average impairment reversals are undertaken in an unbiased manner, a minority of firms exploit the latitude provided by this fair value accounting standard to manage earnings upward. This research provides useful information to accounting standard setters pertaining to the adoption of fair value accounting methods. It also assists investment analysts by demonstrating how to detect opportunistic reversals of impairments

Coffee: Cost-Effective Edge Caching for 360 Degree Live Video Streaming

While live 360 degree video streaming delivers immersive viewing experience, it poses significant bandwidth and latency challenges for content delivery networks. Edge servers are expected to play an important role in facilitating live streaming of 360 degree videos. In this paper, we propose a novel predictive edge caching algorithm (Coffee) for live 360 degree video that employ collaborative FoV prediction and predictive tile prefetching to reduce bandwidth consumption, streaming cost and improve the streaming quality and robustness. Our light-weight caching algorithms exploit the unique tile consumption patterns of live 360 degree video streaming to achieve high tile caching gains. Through extensive experiments driven by real 360 degree video streaming traces, we demonstrate that edge caching algorithms specifically designed for live 360 degree video streaming can achieve high streaming cost savings with small edge cache space consumption. Coffee, guided by viewer FoV predictions, significantly reduces back-haul traffic up to 76% compared to state-of-the-art edge caching algorithms. Furthermore, we develop a transcoding-aware variant (TransCoffee) and evaluate it using comprehensive experiments, which demonstrate that TransCoffee can achieve 63\% lower cost compared to state-of-the-art transcoding-aware approaches

Cloning and characterization of the mouse ret finger protein (rfp), a B box zinc finger protein

An important question in biology is to understand the role of specific gene products in regulating embryogenesis and cellular differentiation. Many of the regulatory proteins possess specific motifs, such as the homeodomain, basic helix-loop-helix structure, zinc finger, and leucine zipper. These sequence motifs participate in specific protein-DNA, protein-RNA, and protein-protein interactions, and are important for the function of these regulatory proteins. The human rfp (ret finger protein) belongs to a novel zinc finger protein family, the B box zinc finger family. Most of the B box proteins, including rfp, have a conserved tripartite motif, consisting of two novel zinc fingers (the RING finger and the B box) and a coiled-coil domain. Interestingly, a fusion protein between the tripartite motif of rfp and the tyrosine kinase domain of c-ret has transforming activity. In this study, we examined the expression of rfp during mouse development, and characterized the role of the tripartite motif in rfp function. We cloned the mouse rfp cDNA, which shares a 98.4% homology with the human sequence at amino acid level. Such strikingly high degree of homology indicates the high evolutionary pressure on the conservation of the sequence, suggesting that rfp may have an important function. Using the somatic cell hybrid system, we assigned the rfp gene to mouse chromosome 13 and human chromosome 6. Rfp transcripts and protein were ubiquitous in day 10.5-13.5 mouse embryos; however, they were restricted in adult mice, with the highest level of expression in the testis. Rfp expression in the testis is detected only in late pachytene spermatocytes and round spermatids. In both embryos and spermatogenic cells, rfp protein was distributed within cell nuclei in a punctate pattern, similar to the PODs (PML oncogenic domains) observed with another B box protein, PML. In cultured mammalian cells, we found that rfp was indeed co-localized to the PODs with PML. Using the yeast two-hybrid system, we showed that the rfp could specifically interact with PML, and that the interaction was dependent on the distal portion of the rfp coiled-coil domain. We also showed that rfp could form homodimers, and both the B box and coiled-coil domain were required for proper dimerization. It seems that the proximal portion of the coiled-coil domain provides the interacting interface, while the B box zinc finger orients the coil and maintains the correct structure of the whole molecule. Our data are consistent with the zinc-binding property and structural analysis of the B box. The RING finger seems to be involved in rfp nuclear localization through interaction with other proteins. We believe that homodimerization and interaction with PML are important for the normal interaction of rfp during development and differentiation. In addition, rfp homodimerization may also be essential for the oncogenic activation of the rfp-ret fusion protein

Pay, Performance and Governance in Irish PLCs

This study finds that company size is a major determinant of chief executive officer (CEO) compensation in Ireland. There is little evidence of a relation between CEO remuneration and company performance. However, several corporate governance variables are related to remuneration in a manner that suggests that good governance reduces executive pay. There is also some evidence of a distinctive ‘US effect’, in that companies that are more exposed to business practices in the United States (US) have higher remuneration, particularly in the form of executive stock options.</jats:p

Impairment reversals: unbiased reporting or earnings management

Purpose This paper aims to provide evidence that will inform the convergence debate regarding accounting standards. The authors assess the ability of impairment reversals allowed under International Accounting Standard 36 but disallowed by the Financial Accounting Standards Board to provide useful information about a company. Design/methodology/approach The authors use a sample of 182 Malaysian firms that reversed impairment charges and a matched sample of firms which chose not to reverse their impairments. Further analysis examines if reversing an impairment charge is associated with motivations for and evidence of earnings management. Findings The authors find no evidence that the reversal of an impairment charge marks a company out as managing contemporaneous earnings. However, they document evidence that firms with high levels of abnormal accruals and weak corporate governance avoid earnings decline by reversing previously recognized impairments. In addition, companies that have engaged in big baths as evidenced by high accumulated impairment balances and prior changes in top management, use impairment reversals to avoid earnings declines. Research limitations/implications The results of this study support both the informative and opportunistic hypotheses of impairment reversal reporting using Financial Reporting Standard 136. Practical implications The results also demonstrate how companies that use impairment reversals opportunistically can be identified. Originality/value The results support IASB’s approach to the reversal of impairments. They also provide novel evidence as to how companies exploit a cookie-jar reserve created by a prior big bath opportunistically. </jats:sec