p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation.

p14ARF is a tumour suppressor which plays a critical role in p53-dependent or -independent cell growth control. Several studies have recently provided evidence that p14ARF can also interfere either directly or indirectly with some components of the RB signalling pathway to mediate its antiproliferative activity. The aim of this study was to explore the existence of direct relationships between p14ARF and RB proteins. We show that p14ARF promotes the accumulation of a hypoacetylated RB protein, when it is upregulated in a model of stable-inducible clones or physiologically induced following cell exposure to cytotoxic agents. Looking for the mechanisms involved in this process, we demonstrate that the histone acetyl transferase Tip60 directly interacts with RB and stimulates its degradation by the proteasome through acetylation of its C-terminus. Furthermore, and consistent with p14ARF-induced RB accumulation, we provide evidence that p14ARF prevents Tip60-mediated RB acetylation, therefore precluding its proteasomal degradation. Overall, our results identify a novel mechanism by which p14ARF controls the RB pathway to trigger its antiproliferative function.

Did psychrophilic enzymes really win the challenge?

Organisms living in permanently cold environments, which actually represent the greatest proportion of our planet, display at low temperatures metabolic fluxes comparable to those exhibited by mesophilic organisms at moderate temperatures. They produce cold-evolved enzymes partially able to cope with the reduction in chemical reaction rates and the increased viscosity of the medium induced by low temperatures. In most cases, the adaptation is achieved through a reduction in the activation energy, leading to a high catalytic efficiency, which possibly originates from an increased flexibility of either a selected area of or the overall protein structure. This enhanced plasticity seems in return to be responsible for the weak thermal stability of cold enzymes. These particular properties render cold enzymes particularly useful in investigating the possible relationships existing between stability, flexibility, and specific activity and make them potentially unrivaled for numerous biotechnological tasks. In most cases, however, the adaptation appears to be far from being fully achieved.

Cold-adapted enzymes: from fundamentals to biotechnology.

Psychrophilic enzymes produced by cold-adapted microorganisms display a high catalytic efficiency and are most often, if not always, associated with high thermosensitivity. Using X-ray crystallography, these properties are beginning to become understood, and the rules governing their adaptation to cold appear to be relatively diverse. The application of these enzymes offers considerable potential to the biotechnology industry, for example, in the detergent and food industries, for the production of fine chemicals and in bioremediation processes.

A rigorous mathematical treatment for the excluded volume effect in Monte Carlo simulations of polymeric chains.

In Monte Carlo simulations of polymeric chains, the chains are most often represented as spheres, or cylinders with flat ends. In this methodological paper, we adopt a representation of the chains as spherocylinders (continuous cylinders ending in semispheres). With such a representation the testing for chain overlap, which is the crucial step for the inclusion of the excluded volume effect in the simulations, can be defined in a rigorous geometrical framework. The treatment we then derive fulfills the following features: it allows a very simple, automatic, and exhaustive classification of all the possible configurations; and it provides a physical representation for steric hindrance effects more natural than the flat-ended cylinders. Notably, this representation avoids the introduction of artificial anisotropies in the treatments. This spherocylindrical representation is also well suited for several types of calculations that can be involved in elaborate Monte Carlo simulations.

Acetylcholine receptors are not functionally independent.

Analysis of current recordings from acetylcholine-activated channels has largely rested so far on the hypothesis of independence, which states that the opening of one channel does not influence that of its neighbors. We have submitted this assumption to several tests, using as experimental material single channel currents from rat myotubes. We found that, even though the distribution of multiple channel openings may be approximated by the Poisson law, openings are strongly coupled. This conclusion is derived from the analysis of two-time properties associated with patch-clamp data. We show how these properties, which contain more detailed information than the stationary probabilities, can be calculated in practice and why a Poisson analysis is misleading in the present case. The implications of our findings are finally discussed in terms of channel structure and function.

[Functional neurosurgery of cerebral palsy]. / La neurochirurgie fonctionnelle de l'infirmité motrice d'origine cérébrale.

In 1983, approximately 40 000 patients in France and 5 760 patients in Switzerland suffered from cerebral palsy, representing more than 0.1% of their respective populations. The functional disability of these patients is particularly impressive and emphasizes the medical, social and economic importance of this problem. The term cerebral palsy is restricted to non-progressive disorders of motor function, already observed at an early age and due to cerebral lesions. These motor disorders can be of paretic, dystonic and dyskinetic nature. Their epidemiology, classification, etiology, pathology, early diagnosis and evolution are extensively reviewed by Th. Deonna. The difficulty in evaluation of treatment is the absence of a generally accepted rating scale. G. Broggi has proposed one on the basis of a large experience which could serve in the future for more objective evaluation. This monograph is devoted to the functional neurosurgical treatment of cerebral palsy. Physiotherapy and rehabilitation are part of the basic treatment of cerebral palsy, and must be continued after any neurosurgical treatment. Various conservative methods of treatment and their neurophysiological rationale are mentioned by P. Claverie. Some technical devices which improve the neurological deficits and facilitate rehabilitation are presented. Radiculotomies and neurotomies are probably the oldest neurosurgical operations for the treatment of spasticity. The neurophysiological and neuroanatomical basis of this therapeutic approach are treated in the review of the material from the neurosurgical department of Montpellier. Sixty cases were collected and the results analysed according to the type of operation (posterior radiculotomy, anterior radiculotomy, mixed) performed. Stereotactic thalamotomies and subthalamotomies are believed to be the best neurosurgical method to treat the tremor and improve other dyskinesias and hyperkinesias. The technique and a personal review of 49 cases of cerebral palsy are presented. The long-term follow-up in this study demonstrates that this type of operation markedly improves the functional disability of patients with moderate hyperkinesias, moderately improves patients severely affected, but also demonstrates that possible side effects cannot be ignored. Review of the literature indicates the difficulty in interpretation of results due to a lack of objective evaluation. Nevertheless, stereotactic thalamotomy can still be recommended when tremor and rigidity are the most prominent symptoms. Stereotactic dentatotomies in the treatment of spasticity were very popular 20 years ago, but have been largely forgotten for nearly a decade.(ABSTRACT TRUNCATED AT 400 WORDS)

[Results and limitations of rehabilitation in cerebral palsy]. / Résultats et limites de la rééducation chez l'enfant infirme moteur d'origine cérébrale.

The authors have studied 1575 children treated by rehabilitation, splintage and eventually surgery. Some were followed up for 25 years and all were followed up for more than 4 years. The results are described for the upper limb in hemiplegics and quadriplegics and for the lower limb in paraplegics and quadriplegics. An analysis was made of the influence of I.Q., age at onset of treatment, and neurological features (spasticity, athetosis, sensory deficiency, anaesthesia). It is concluded that some attempts to treat must always be made. The authors describe the results that may be expected.