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Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. We investigated functional differences among three isoforms of A luciferase reporter gene assay using a 6XOSE2-SV40 promoter (6 tandem binding elements for Cbfa1 ligated in front of the SV40 promoter sequence), a mouse osteocalcin promoter, and a mouse osteopontin promoter revealed the differences in the transcriptional induction of target genes by each Cbfa1 isoform with or without its ␤-subunit. These results suggest that all three of the Cbfa1 isoforms used in the present study are involved in the stimulatory action of osteoblast differentiation, but they exert different functions in the process of osteoblast differentiation.

SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes cell growth, survival and migration, and is a key regulator of lymphocyte trafficking. Inhibition of S1P signalling has been proposed as a strategy for treatment of inflammatory diseases and cancer. In the present paper we describe the discovery and characterization of PF-543, a novel cell-permeant inhibitor of SphK1. PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform. In 1483 head and neck carcinoma cells, which are characterized by high levels of SphK1 expression and an unusually high rate of S1P production, PF-543 decreased the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. In contrast with past reports that show that the growth of many cancer cell lines is SphK1-dependent, specific inhibition of SphK1 had no effect on the proliferation and survival of 1483 cells, despite a dramatic change in the cellular S1P/sphingosine ratio. PF-543 was effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood. PF-543 is the most potent inhibitor of SphK1 described to date and it will be useful for dissecting specific roles of SphK1-driven S1P signalling.

The MEG experiment, designed to search for the µ + → e + γ decay at a 10 −13 sensitivity level, completed datataking in 2013. In order to increase the sensitivity reach of the experiment by an order of magnitude to the level of 6 × 10 −14 for the branching ratio, a total upgrade, involving substantial changes to the experiment, has been undertaken, known as MEG II. We present both the motivation for the upgrade and a detailed overview of the design of the experiment and of the expected detector performance.

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We present a measurement of angular observables and a test of lepton flavor universality in the B → K * + − decay, where is either e or µ. The analysis is performed on a data sample corresponding to an integrated luminosity of 711 fb −1 containing 772 × 10 6 B B pairs, collected at the Υ(4S) resonance with the Belle detector at the asymmetric-energy e + e − collider KEKB. The result is consistent with Standard Model (SM) expectations, where the largest discrepancy from a SM prediction is observed in the muon modes with a local significance of 2.6σ.

calcium and magnesium in stroke-prone spontaneously hypertensive rats and effects of blood pressure and various antihypertensive agents. Clinical and Experimental Pharmacology and Physiology, 20, 587-593.

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