Expression of Osteopontin in oesophageal squamous cell carcinoma

Osteopontin is a multifunctional 34 kDa extracellular matrix protein with a cell-binding domain. It is involved cell adhesion and cell migration and is therefore considered to influence tumorigenesis and/or metastasis. The purpose of the present study was to evaluate the clinical significance of Osteopontin expression in oesophageal squamous cell carcinoma (ESCC). In the present study, we immunohistochemically investigated the relationship between Osteopontin expression and clinicopathological factors including prognosis in surgical specimens of primary tumours in 175 patients with ESCC. Osteopontin was expressed in 48% of 175 patients. Osteopontin expression was significantly correlated with lymph node metastasis, lymphatic invasion, and stage (P=0.0015, 0.037 and 0.033, respectively). Tumours with expressing Osteopontin exhibited more lymph node metastasis, lymphatic invasion and advanced stage than the tumour with negative Osteopontin expression. Five-year survival rate was better in patients with negative Osteopontin expression than in those with positive Osteopontin expression (P=0.035). However, multivariate analysis revealed that Osteopontin expression was not an independent prognostic factor. As our findings suggest that Osteopontin may play an important role in progress of ESCC, the evaluation of Osteopontin expression is useful for predicting the malignant properties of ESCC

Computational Modeling and Analysis of Insulin Induced Eukaryotic Translation Initiation

Insulin, the primary hormone regulating the level of glucose in the bloodstream, modulates a variety of cellular and enzymatic processes in normal and diseased cells. Insulin signals are processed by a complex network of biochemical interactions which ultimately induce gene expression programs or other processes such as translation initiation. Surprisingly, despite the wealth of literature on insulin signaling, the relative importance of the components linking insulin with translation initiation remains unclear. We addressed this question by developing and interrogating a family of mathematical models of insulin induced translation initiation. The insulin network was modeled using mass-action kinetics within an ordinary differential equation (ODE) framework. A family of model parameters was estimated, starting from an initial best fit parameter set, using 24 experimental data sets taken from literature. The residual between model simulations and each of the experimental constraints were simultaneously minimized using multiobjective optimization. Interrogation of the model population, using sensitivity and robustness analysis, identified an insulin-dependent switch that controlled translation initiation. Our analysis suggested that without insulin, a balance between the pro-initiation activity of the GTP-binding protein Rheb and anti-initiation activity of PTEN controlled basal initiation. On the other hand, in the presence of insulin a combination of PI3K and Rheb activity controlled inducible initiation, where PI3K was only critical in the presence of insulin. Other well known regulatory mechanisms governing insulin action, for example IRS-1 negative feedback, modulated the relative importance of PI3K and Rheb but did not fundamentally change the signal flow

Knocking out pain in livestock: Can technology succeed where morality has stalled?

Though the vegetarian movement sparked by Peter Singer’s book Animal Liberation has achieved some success, there is more animal suffering caused today due to factory farming than there was when the book was originally written. In this paper, I argue that there may be a technological solution to the problem of animal suffering in intensive factory farming operations. In particular, I suggest that recent research indicates that we may be very close to, if not already at, the point where we can genetically engineer factory-farmed livestock with a reduced or completely eliminated capacity to suffer. In as much as animal suffering is the principal concern that motivates the animal welfare movement, this development should be of central interest to its adherents. Moreover, I will argue that all people concerned with animal welfare should agree that we ought to replace the animals currently used in factory farming with animals whose ability to suffer is diminished if we are able to do so. </p

Erratum: Observational Constraints on the Ultrahigh Energy Cosmic Neutrino Flux from the Second Flight of the ANITA Experiment

This is an erratum to the original paper published in Physical Review D , 82 (2), article no. 022004, on 16 July 2010 (DOI: 10.1103/PhysRevD.82.022004)