Temperature sensitivity for conformation is an intrinsic property of wild-type p53.

The tumour-suppressor protein p53 is a metal-binding transcription factor with sequence-specific DNA-binding capacity. In cancer, mutation of p53 disrupts protein conformation with consequent loss of DNA binding and associated tumour-suppressor function. In vitro, the conformation and DNA-binding activity of wild-type p53 are subject to redox modulation and are abrogated by exposure to metal chelators. In the present study, we have used the chelator 1, 10-phenanthroline (OP) to probe the effect of temperature on the conformational stability of p53 translated in vitro. Whereas low temperature (30 degrees C) stabilised wild-type p53 conformation and protected against chelation, high temperature (41 degrees C) promoted destabilisation and enhanced chelation, indicating that temperature influences the folding of wild-type p53. Destabilisation of p53 tertiary structure induced protein aggregation through hydrophobic interactions, consistent with the notion that wild-type p53 contains a hydrophobic core which may become exposed by metal chelation. These results indicate that temperature sensitivity for conformation is an intrinsic property of wild-type p53 and suggests that small changes in temperature may directly affect p53 function

Assessment of Transformed Properties In Vitro and of Tumorigenicity In Vivo in Primary Keratinocytes Cultured for Epidermal Sheet Transplantation

Epidermal keratinocytes are used as a cell source for autologous and allogenic cell transplant therapy for skin burns. The question addressed here is to determine whether the culture process may induce cellular, molecular, or genetic alterations that might increase the risk of cellular transformation. Keratinocytes from four different human donors were investigated for molecular and cellular parameters indicative of transformation status, including (i) karyotype, (ii) telomere length, (iii) proliferation rate, (iv) epithelial-mesenchymal transition, (v) anchorage-independent growth potential, and (vi) tumorigenicity in nude mice. Results show that, despite increased cell survival in one keratinocyte strain, none of the cultures displayed characteristics of cell transformations, implying that the culture protocol does not generate artefacts leading to the selection of transformed cells. We conclude that the current protocol does not result in an increased risk of tumorigenicity of transplanted cells

Lightcurves of 20--100 kilometer Kuiper Belt Objects using the Hubble Space Telescope

We report high precision photometry of three small and one larger Kuiper Belt Objects (KBOs) obtained with the Advanced Camera for Surveys onboard the Hubble Space Telescope (ACS/HST). The three small bodies are the smallest KBOs for which lightcurve measurements are available. 2003 BF91 has a diameter of 20 kilometers (assuming 10% albedo) and a 1.09 magnitude, 9.1-hour lightcurve that is feasibly explained by the rotation of an elongated, coherent body that is supported by material strength and best imagined as an icy outer Solar System analog to asteroid (243) Ida. Two other small KBOs, 2003 BG91 and 2003 BH91 (diameters 31 and 18 km, with albedo 10%), exhibit an unremarkable lightcurve and no detectable photometric variation, respectively. For the larger KBO 2000 FV53 (116 km diameter, assuming 10% albedo) we strongly detect a non-sinusoidal periodic (7.5 hours) brightness variation with a very small amplitude (0.07 mag). This KBO may be nearly spherical, a result that might not be unusual in the Kuiper Belt but would be remarkable among outer Solar System satellites of similar size. We carry out a study of possible physical states and bulk densities under the assumptions of both fluid equilibrium and finite, non-zero internal friction. The densities for the these KBOs are likely to be in the range 1--2 g/cm3, and a plausible solution for 2000 FV53 is a rubble pile of this density that is held slightly out of the minimum-energy shape by internal friction among constituent blocks that are relatively small. Our interpretation of 2000 FV53 as a pulverized but essentially primordial object and 2003 BF91 as a collisional fragment is consistent with models of collisional timescales in the outer Solar System. We compile all published KBO lightcurve data and compare our results to the larger population. [abridged]Comment: AJ, in press. Tables 1-4 will be electronic only in published version but appear here in full. Figures 1,3,5 in colo