Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOKexpressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.

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BackgroundLipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD). Ginkgo biloba extract (GBE) and its flavonoid ingredients (quercetin, kaempferol, and isorhamnetin) could lessen the lipid accumulation associated with up-regulation of the rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), in the β-oxidation of long-chain fatty acids. In this study, we investigated the mechanisms by which GBE and its flavonoids induced expression of CPT1A.ResultsCPT1A inhibition with RNAi resulted in triglyceride accumulation in HepG2 cells. Through deletion and mutation analysis of CPT1A’s promoter combined with electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments, the CPT1A promoter region (−50 to −5 nt) was determined to contain two putative Sp1 binding sites, namely Sp1a and Sp1b, which might act as the GBE regulation response DNA element. Sp1 might be induced to transfer from cytoplasma to nucleus to bind the promoter region of −50 to −5 nt by GBE. The regulatory effects of GBE on CPT1A were also verified on the flavonoid ingredients quercetin, kaempferol, and isorhamnetin.ConclusionSp1 was crucial in regulating CPT1A expression with GBE and its flavonoid ingredients, and the −50 to −5 nt region of CPT1A promoter played important roles in Sp1 binding.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-014-0087-x) contains supplementary material, which is available to authorized users.

The triglyceride-lowering effect of GBE on the HFD rat liver is closely associated with the increased expression and activity of CPT1A, and the flavonoid ingredients are the major contributors of GBE.

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An experimental study of the dynamics and droplet production in three mechanically generated plunging breaking waves is presented in this two-part paper. In the present paper (Part 1), the dynamics of the three breakers are studied through measurements of the evolution of their free surface profiles during 10 repeated breaking events for each wave. The waves are created from dispersively focused wave packets generated with three wave maker motions that differ primarily by small changes in their overall amplitude. Breaker profiles are measured with a cinematic laser-induced fluorescence technique covering a streamwise region of approximately one breaker wavelength and over a time of 3.4 breaker periods. The aligned profile data is used to create spatio-temporal maps of the ensemble average surface height and the standard deviation of both the local normal distance and the local arc length relative to the instantaneous mean profile. It is found that the mean and standard deviation maps contain strongly correlated localized features and indicate that the transition from laminar to turbulent flow is a highly repeatable process. Regions of high standard deviation include the splash created by the plunging jet impact and subsequent splash impacts at the front of the breaking region as well as the site where the air pocket entrained under the plunging jet at the moment of jet tip impact comes to the surface and pops. In Part 2 (Erinin et al., J. Fluid Mech., vol. 967, 2023, A36), these features are used to interpret various features of the distributions of droplet number, diameter and velocity.