Catherine Heusele

GTPase activity of the tubulin-colchicine in relation with tubulin-tubulin interactions.

Abstract The GTPase activity of the tubulin-colchicine complex has been studied at different tubulin-colchicine concentrations. The specific activity was found to decrease at low concentrations. Several hypothesis accounting for this observation have been discarded, and the activation via collisions between two molecules of tubulin has been considered as a possible model explaining the origin and observed concentration dependence of the GTPase activity. The activation of tubulin-colchicine by unliganded tubulin or tubulin-podophyllotoxin has been investigated within this model which emphasizes the connection between some specific tubulin-tubulin interactions and the conformation of the exchangeable nucleotide site on tubulin.

Modelling epidermis homoeostasis and psoriasis pathogenesis

We present a computational model to study the spatio-temporal dynamics of epidermis homoeostasis under normal and pathological conditions. The model consists of a population kinetics model of the central transition pathway of keratinocyte proliferation, differentiation and loss and an agent-based model that propagates cell movements and generates the stratified epidermis. The model recapitulates observed homoeostatic cell density distribution, the epidermal turnover time and the multilayered tissue structure. We extend the model to study the onset, recurrence and phototherapy-induced remission of psoriasis. The model considers psoriasis as a parallel homoeostasis of normal and psoriatic keratinocytes originated from a shared stem cell (SC) niche environment and predicts two homoeostatic modes of psoriasis: a disease mode and a quiescent mode. Interconversion between the two modes can be controlled by interactions between psoriatic SCs and the immune system and by normal and psoriatic SCs competing for growth niches. The prediction of a quiescent state potentially explains the efficacy of multi-episode UVB irradiation therapy and recurrence of psoriasis plaques, which can further guide designs of therapeutics that specifically target the immune system and/or the keratinocytes.

A photographic scale for the evaluation of facial skin aging in Indian women

The process of facial skin aging differs between different ethnic populations. Standardized tools to objectively evaluate facial skin aging in clinical and epidemiological studies in different ethnic populations are needed. We designed and validated a photonumeric scale for assessment of facial aging in the Indian population. A total of 149 subjects were selected from an electronic photographic database of 300 women from the Mumbai region. An expert consensus panel selected nine subjects representing a spectrum of skin damage from none to severe, on the basis of wrinkling and tissue slackening. The nine-point scale, composed of one face-on and one oblique photo of the same subject per grade, was validated by nine independent judges in 99 subjects with a repetition two weeks later. Inter-observer reliability and intra-observer reproducibility were calculated using Kappa coefficients. Validation of the scale showed a high level of inter-observer reliability between the consensus and independent panels, and intra-observer reproducibility between the two evaluations performed by the independent judges. In conclusion, this nine-point facial aging scale is a reliable tool for clinical evaluations of skin damage in Indian women, suitable for use in clinical and epidemiological studies.

Role of DAPI in microtubule reactions at steady-state

The new fluorophor for tubulin, DAPI, is shown to bind to a site different from the exchangeable nucleotide binding site (E site) and to inhibit GTP hydrolysis by the tubulin-colchicine complex within an uncompetitive scheme. Moreover the dissociation rate constant of tubulin for microtubule ends at 32 degrees C was found largely decreased in the presence of saturating amounts of the probe while the association rate constant was little affected. These data on the kinetic parameters of tubulin interactions in the presence of DAPI, together with the inhibition of GTP hydrolysis by microtubules at the steady state are understood as the main cause for microtubule stabilization at steady-state by DAPI.

Impact of exogenous stress on TGF-β inducible early gene 1 in human skin cells.

Keywords: oxidative stress; skin ageing; skin photoexposure; TGF-β; TGF-β inducible early gene-1