Hormonal control of p53 and chemoprevention

Improvements in the detection and treatment of breast cancer have dramatically altered its clinical course and outcome. However, prevention of breast cancer remains an elusive goal. Parity, age of menarche, and age at menopause are major risk factors drawing attention to the important role of the endocrine system in determining the risk of breast cancer, while heritable breast cancer susceptibility syndromes have implicated tumor suppressor genes as important targets. Recent work demonstrating hormonal modulation of the p53 tumor suppressor pathway draws together these established determinants of risk to provide a model of developmental susceptibility to breast cancer. In this model, the mammary epithelium is rendered susceptible due to impaired p53 activity during specific periods of mammary gland development, but specific endocrine stimuli serve to activate p53 function and to mitigate this risk. The results focus attention on p53 as a molecular target for therapies to reduce the risk of breast cancer

BDI logics for BDI architectures: old problems, new perspectives

International audienceThe mental attitudes of belief, desire, and intention play a central role in the design and implementation of autonomous agents. In 1987 Bratman proposed their integration into a belief-desire-intention (BDI) theory that was seminal in AI. Since then numerous approaches were built on the BDI paradigm, both practical (BDI architectures and BDI agents) and formal (BDI logics). The logical approaches that were most influential are due to Cohen&Levesque and to Rao&Georgeff. However, three fundamental problems remain up to now. First, the practical and the formal approaches evolved separately and neither fertilized the other. Second, only few formal approaches addressed some important issues such as the revision of intentions or the fundamentally paraconsistent nature of desires, and it seems fair to say that there is currently no consensual logical account of intentions. Finally, only few publications study the interaction between intention and other concepts that are naturally connected to intention, such as actions, planning, and the revision of beliefs and intentions. Our paper summarizes the state of the art, discusses the main open problems, and sketches how they can be addressed. We argue in particular that research on intention should be better connected to fields such as reasoning about actions, automated planning, and belief revision and update

Differentiation, growth and morphogenesis: Acetabularia as a model system

The aim of this paper is to review the present knowledge of the main aspects of differentiation of Acetabularia, a unicellular, eukaryotic organism, and to underline the multiple control pathways modulated by circadian rhythmicity. Growth and morphogenesis are sequentially programmed. Timing of cap differentiation is highly dependent on external conditions. The importance of the sequence of processes is shown by experimental disregulation. The alga is a highly polarized cell, both in morphology and in the relative concentrations of a number of the molecules it contains. Apical cap differentiation is regulated at the post-transcriptional level and could also depend in part on polyamines and on proteolytic activity. Acetabularia displays a number of circadian rhythms (CR). These rhythms form an elaborate biological time structure (also called temporal morphology, or morphology in time as opposed to morphology in space): the distribution in the 24 h cycle of the peaks and troughs of the oscillating functions. The oscillations display fixed relations both with the other functions and with external conditions (such as the transition from dark to light). Interestingly, the CR modulate Acetabularia's development, which is influenced by photoperiod; we present preliminary experiments suggesting that disruption of temporal morphology is deleterious to morphogenesis. Induction of growth and of morphogenesis are totally dependent on blue light. However, blue light receptors in plants are probably multiple, but we present arguments suggesting that flavin-cytochrome b and the associated SHAM-sensitive molecule are present in Acetabularia plasma membrane and are involved in blue light perception. Agents interfering with different steps of signal perception and transduction show that at least some of these steps are temporally regulated. According to recent experiments from our laboratory, the existence of a redox signalling mechanism appears to be highly probable. The phytohormones (or plant regulators), auxin (indole acetic acid), abscisic acid and ethylene, exert cell-regulatory functions and are involved in Acetabularia differentiation. They also modulate at least some circadian rhythms. Finally, circadian rhythms intervene in differentiation and are proposed to have an integrative function.SCOPUS: re.jFLWINinfo:eu-repo/semantics/publishe