828 research outputs found
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
Characterisation of candidate members of (136108) Haumea's family: II. Follow-up observations
From a dynamical analysis of the orbital elements of transneptunian objects
(TNOs), Ragozzine & Brown reported a list of candidate members of the first
collisional family found among this population, associated with (136108) Haumea
(a.k.a. 2003 EL61). We aim to distinguish the true members of the Haumea
collisional family from interlopers. We search for water ice on their surfaces,
which is a common characteristic of the known family members. The properties of
the confirmed family are used to constrain the formation mechanism of Haumea,
its satellites, and its family. Optical and near-infrared photometry is used to
identify water ice. We use in particular the CH4 filter of the Hawk-I
instrument at the European Southern Observatory Very Large Telescope as a short
H-band (Hs), the (J-Hs) colour being a sensitive measure of the water ice
absorption band at 1.6 {\mu}m. Continuing our previous study headed by
Snodgrass, we report colours for 8 candidate family members, including
near-infrared colours for 5. We confirm one object as a genuine member of the
collisional family (2003 UZ117), and reject 5 others. The lack of infrared data
for the two remaining objects prevent any conclusion from being drawn. The
total number of rejected members is therefore 17. The 11 confirmed members
represent only a third of the 36 candidates. The origin of Haumea's family is
likely to be related to an impact event. However, a scenario explaining all the
peculiarities of Haumea itself and its family remains elusive.Comment: 8 pages, 4 figures, accepted for publication in A&
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
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