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Download:*smooth midi audio*TGF-beta1 alters cell cycle regulation in murine fibroblasts: effect on cyclin-dependent kinases and transcriptional induction of p15(Ink4b) and p21(Cip1). Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of the proliferation of fibroblasts and has been shown to induce the expression of the cell cycle inhibitor p15(Ink4b). In the present study, we examined the effects of TGF-beta1 on the cell cycle regulatory proteins cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. In quiescent 3T6 murine fibroblasts, TGF-beta1 treatment for 24 hours induced a nearly two-fold increase in the expression of cyclin D1. In contrast, the expression of CDKs 2, 4, and 6 was not altered by TGF-beta1 treatment, except for a modest reduction in the expression of CDK4 at late time points. In serum-starved Swiss 3T3 fibroblasts, TGF-beta1 treatment for 24 hours inhibited the progression of cells through S phase by two to three hours. To understand further the mechanism of the inhibition of cell cycle progression, we examined the induction of p15(Ink4b) and p21(Cip1) and the effect of TGF-beta1 on the activity of CDKs 4 and 6. TGF-beta1 induced the transcription of the p15(Ink4b) gene, but not p21(Cip1). However, the induction of p15(Ink4b) was accompanied by a decrease in the activity of CDK4, but not of CDK6. These results suggest that TGF-beta1 alters the expression of cyclin D1, which is required for the induction of p15(Ink4b) expression by TGF-beta1, and may also involve the inhibition of CDK4 activity, which is required for the expression of p15(Ink4b).The CIA began using drones in 2002, shortly after the Sept. 11, 2001, terror attacks. But the agency has been flying the unmanned aerial vehicles (UAVs) mostly in Afghanistan and Pakistan, where al-Qaida and the Taliban are headquartered. But the U




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