The extreme-ultraviolet structure and properties of a newly emerged active region

The structure and properties of a newly emerged solar active region (NOAA Active Region 7985) are discussed using the Coronal Diagnostic Spectrometer (CDS) and the Extreme- Ultraviolet Imaging Telescope (EIT) on board the Solar and Heliospheric Observatory. CDS obtained high-resolution EUV spectra in the 308-381 Angstrom and 513-633 Angstrom wavelength ranges, while EIT recorded full-disk EUV images in the He II (304 Angstrom), Fe IX/X (171 Angstrom), Fe xii (195 Angstrom), and Fe XV (284 Angstrom) bandpasses. Electron density measurements from Si rx, Si X, Fe xii, Fe XIII, and Fe xiv line ratios indicate that the region consists of a central high- density core with peak densities of the order of 1.2 x 10(10) cm(-3), which decrease monotonically to similar to5.0 X 10(8) cm(-3) at the active region boundary. The derived electron densities also vary systematically with temperature. Electron pressures as a function of both active region position and temperature were estimated using the derived electron densities and ion formation temperatures, and the constant pressure assumption was found to be an unrealistic simplification. Indeed, the active region is found to have a high-pressure core (1.3 x 10(16) cm(-3) K) that falls to 6.0 x 10(14) cm(-3) K just outside the region. CDS line ratios from different ionization stages of iron, specifically Fe xvi (335.4 Angstrom) and Fe xiv (334.4 Angstrom), were used to diagnose plasma temperatures within the active region. Using this method, peak temperatures of 2.1 x 10(6) K were identified. This is in good agreement with electron temperatures derived using EIT filter ratios and the two-temperature model of Zhang et al. The high- temperature emission is confined to the active region core, while emission from cooler (1-1.6) x 10(6) K lines originates in a system of loops visible in EIT 171 and 195 X images. Finally, the three-dimensional geometry of the active region is investigated using potential field extrapolations from a Kitt Peak magnetogram. The combination of EUV and magnetic field extrapolations extends the "core-halo" picture of active region structure to one in which the core is composed of a number of compact coronal loops that confine the hot, dense, high- pressure core plasma while the halo emission emerges from a system of cooler and more extended loops.

Human Papillomavirus Type 16 E6 and E7 Cause Polyploidy in Human Keratinocytes and Up-Regulation of G2-M-phase Proteins

Human papillomavirus type 16 proteins E6 and E7 have been shown to cause centrosome amplification and lagging chromosomes during mitosis. These abnormalities during mitosis can result in missegregation of the chromosomes, leading to chromosomal instability. Genomic instability is thought to be an essential part of the conversion of a normal cell to a cancer cell. We now show that E6 and E7 together cause polyploidy in primary human keratinocytes soon after these genes are introduced into the cells. Polyploidy seems to result from a spindle checkpoint failure arising from abrogation of the normal functions of p53 and retinoblastoma family members by E6 and E7, respectively. In addition, E6 and E7 cause deregulation of cellular genes such as Plk1, Aurora-A, cdk1, and Nek2, which are known to control the G2-M-phase transition and the ordered progression through mitosis.

Induction of tetraploidy through loss of p53 and upregulation of Plk1 by Human Papillomavirus type-16 E6

Cancer cells are insensitive to many signals that inhibit growth of untransformed cells. Here, we show that primary human epithelial cells expressing human papillomavirus (HPV) type-16 E6/E7 bypass arrest caused by the DNA-damaging drug adriamycin and become tetraploid. To determine the contribution of E6 in the context of E7 to the resistance of arrest and induction of tetraploidy, we used an E6 mutant unable to degrade p53 or RNAi targeting p53 for knockdown. The E6 mutant fails to generate tetraploidy; however, the presence of E7 is sufficient to bypass arrest while the p53 RNAi permits both arrest insensitivity and tetraploidy. We published previously that polo-like kinase 1 (Plk1) is upregulated in E6/E7-expressing cells. We observe here that abnormal expression of Plk1 protein correlates with tetraploidy. Using the p53 binding-defective mutant of E6 and p53 RNAi, we show that p53 represses Plk1, suggesting that loss of p53 results in tetraploidy through upregulation of Plk1. Consistent with this hypothesis, overexpression of Plk1 in cells generates tetraploidy but does not confer resistance to arrest. These results support a model for transformation caused by HPV-16 where bypass of arrest and tetraploidy are separable consequences of p53 loss with Plk1 required only for the latter effect.

Antagonistic effects of two novel GIP analogs, (Hyp(3))GIP and (Hyp(3)) GIPLys(16)PAL, on the biological actions of GIP and longer-term effects in diabetic ob/ob mice

This study examines the actions of the novel enzyme- resistant, NH2- terminally modified GIP analog ( Hyp(3)) GIP and its fatty acid- derivatized analog ( Hyp(3)) GIPLys(16)PAL. Acute effects are compared with the established GIP receptor antagonist ( Pro(3)) GIP. All three peptides exhibited DPP IV resistance, and significantly inhibited GIP stimulated cAMP formation and insulin secretion in GIP receptor- transfected fibroblasts and in clonal pancreatic BRIN- BD11 cells, respectively. Likewise, in obese diabetic ob/ob mice, intraperitoneal administration of GIP analogs significantly inhibited the acute antihyperglycemic and insulinreleasing effects of native GIP. Administration of once daily injections of ( Hyp(3)) GIP or ( Hyp(3)) GIPLys(16)PAL for 14 days resulted in significantly lower plasma glucose levels ( P <0.05) after ( Hyp3) GIP on days 12 and 14 and enhanced glucose tolerance ( P <0.05) and insulin sensitivity ( P <0.05 to P <0.001) in both groups by day 14. Both ( Hyp(3)) GIP and ( Hyp(3)) GIPLys(16)PAL treatment also reduced pancreatic insulin ( P <0.05 to P <0.01) without affecting islet number. These data indicate that ( Hyp3) GIP and ( Hyp(3)) GIPLys(16)PAL function as GIP receptor antagonists with potential for ameliorating obesity- related diabetes. Acylation of ( Hyp(3)) GIP to extend bioactivity does not appear to be of any additional benefit.