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The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles. Heart and soleus muscle are unaffected, indicating that muscles undergoing regular contractions, and therefore with a continuous mitochondrial ATP production, are protected. In contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass and a fast to slow shift in fiber types promoting mainly IIa and IIx fibers at the expense of fastest and glycolytic type IIb fibers. These observations are interpreted as a consequence of the strong potential dependence of the UCP1 protonophoric activity, which ensures a negligible proton leak at the membrane potential observed when mitochondrial ATP production is intense. Therefore UCP1 is not deleterious for an intense mitochondrial ATP production and this explains the tolerance of the heart to a high expression level of UCP1. In muscles at rest, where ATP production is low, the rise in membrane potential enhances UCP1 activity. The proton return through UCP1 mimics the effect of a sustained ATP production, permanently lowering mitochondrial membrane potential. This very likely constitutes the origin of the signal leading to the transition in fiber types at rest. Uncoupling protein 1 (UCP1)1 is expressed exclusively in brown adipose tissue (reviewed in Refs. 1 and 2). Its presence in brown fat mitochondria is responsible for heat production by the mitochondria in brown adipocytes. UCP1 allows return of protons into the matrix without ATP synthesis, and therefore dissipates the proton electrochemical gradient built up after proton pumping by the respiratory complexes. When this gradient reaches high values this makes proton pumping and thus substrate oxidation less easy and therefore slows down respiration. Activity of UCP1 prevents this rise of the proton gradient and therefore allows respiration to occur at a high rate, without phosphorylation of ADP into ATP, and therefore energy is instantaneously released as heat. The essential role of the UCP1 in thermogenesis is illustrated by the cold intolerance of mice whose ucp1 gene has been disrupted (3). Recently, two genes coding for proteins highly homologous to UCP1 have been described (reviewed in Refs. 4 -6). Although there are experimental evidence supporting the hypothesis of an uncoupling activity of these proteins (7,8), their physiological relevance is still incompletely resolved (9 -11). We intended to obtain transgenic mice overexpressing the UCP1 in skeletal muscles, with the aim of examining the effects of the presence of this uncoupling protein on the pattern of myosin expression and metabolic characteristics of locomotor muscles. Two other reports pub...

c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src.

Venous insufficiency is a multifactorial pathology that has an important impact on the quality of life of the patients. The primary factor of venous disease is an abnormal wall distensibility, which seems to be correlated with genetic factors. Facilitating factors include hormonal impregnation and prolonged hydrostatic load, particularly under conditions where the control of the sympathetic nervous system is reduced by an increase in local temperature. The resulting valvular incompetence, combined with the augmented hydrostatic load, leads to varicosis and venous stasis. The ensuing tissue hypoxia and local edema favor inflammation and infection, which ultimately favor the occurrence of ulcers. The available data on the impact of the disease suggest a relation between the physiopathological phenomena and some parameters of health-related quality of life.