Oxidative damage of cells and tissues is broadly implicated in human pathophysiology, including cardiometabolic diseases. Polyphenols, as important constituents of the human diet and potent in vitro free radical scavengers, have been extensively studied for their beneficial effects on cardiometabolic health. However, it has been demonstrated that the in vivo antioxidant activity of polyphenols is distinct from their in vitro free radical-scavenging capacity. Indeed, bioavailability of nutritional polyphenols is low and conditioned by complex mechanisms of absorption, distribution, metabolism and excretion. Nowadays, it is commonly accepted that the cellular antioxidant activity of polyphenols is mainly carried out via modification of transcription of genes involved in antioxidant defence. Importantly, polyphenols also contribute to cardiometabolic health by modulation of a plethora of cellular processes that are not directly associated with antioxidant enzymes, through nutri(epi)genomic mechanisms. Numerous human intervention studies have demonstrated beneficial effects of polyphenols on the key cardiometabolic risk factors. However, inconsistency of the results of some studies led to identification of the inter-individual variability in response to consumption of polyphenols. In perspective, a detailed investigation of the determinants of this inter-individual variability will potentially lead us towards personalised dietary recommendations. The phenomenon of inter-individual variability is also of relevance for supplementation with antioxidant (pro)vitamins.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

Emerging evidence suggests that dietary phytochemicals, in particular flavonoids, may exert beneficial effects on the central nervous system by protecting neurons against stress-induced injury, by suppressing neuroinflammation and by improving cognitive function. It is likely that flavonoids exert such effects, through selective actions on different components of a number of protein kinase and lipid kinase signalling cascades, such as the phosphatidylinositol-3 kinase (PI3K)/Akt, protein kinase C and mitogen-activated protein kinase (MAPK) pathways. This review explores the potential inhibitory or stimulatory actions of flavonoids within these pathways, and describes how such interactions are likely to underlie neurological effects through their ability to affect the activation state of target molecules and/or by modulating gene expression. Future research directions are outlined in relation to the precise site(s) of action of flavonoids within signalling pathways and the sequence of events that allow them to regulate neuronal function.

Recently, adult stem cells have become a focus of intensive biomedical research, but thecomplex regulation that allows a small population of stem cells to replenish depleted tissues is stillunknown. It has been suggested that specific tissue structures delimit the spaces where stem cellsundergo unlimited proliferation (stem cell niche). In contrast, mathematical analysis suggests thata feedback control of stem cells on their own proliferation and differentiation (denoted QuorumSensing) suffices for preserving homeostasis in developing tissues. In the present work we examinethis discrepancy by analyzing a mathematical model of signalling pathways in a mammary stemcell. Our work shows that the model has a unique equilibrium depending on the environmentalconditions, which is stable for appropriate parameter values. We show how this dependence onthe micro-environment can control the cell decision to either proliferate or differentiate. Our workfurther suggests that this description is sufficient for the creation of niche conditions, with no needof additional structures. The analysis also pinpoints the pathways that may serve as the QuorumSensing mechanism.

Résumé

La vitamine E, l'antioxydant liposoluble le plus important, fut découverte à l'Université de Californie à Berkeley en 1922. Depuis sa découverte, les études sur les tocophérols et les tocotrienols que constitue cette vitamine, ont été centrées pour la plupart sur leurs propriétés antioxydantes. En 1991, le groupe de Angelo Azzi (Boscoboinik et al. 1991a,b) fut le premier à décrire les fonctions autres que les antioxydantes et de transmission de signaux de l'α-tocophérol, en démontrant la régulation par la vitamine E de l'activité de la protéine kinase C dans les cellules de muscle lisse. Au niveau de la transcription, l'²-tocophérol module l'expression de la protéine de transfert hépatique de l'α-tocophérol, ainsi que l'expression du ge`ne alpha1 du collage`ne du foie, du ge`ne de la collagénase et du ge`ne de l'α-tropomyosine. Récemment, un facteur de transcription dépendant du tocophérol (la protéine associée au tocophérol) a été découvert. Il a été démontré sur des cellules cultivées que la vitamine E inhibe l'inflammation, l'adhésion cellulaire, l'agrégation des plaquettes et la prolifération des cellules de muscle lisse. Les avancées récentes de la biologie moléculaire et des techniques génomiques ont conduit à la découverte de nouveaux ge`nes et des mécanismes de transduction des signaux sensibles à la vitamine E.

Active oxygen species (AOS) are involved in various aspects of seed physiology. Their generation, which occurs during seed desiccation, germination and ageing, may lead to oxidative stress and cellular damage, resulting in seed deterioration. However, cells are endowed with detoxifying enzymes and antioxidant compounds that scavenge AOS and participate in seed survival. The detoxifying mechanisms play a key role in acquisition of desiccation tolerance of developing seeds, completion of seed germination and seed storability. However, AOS must also be regarded as molecules intervening in cellular signalling. They are involved in growth processes occurring at early embryogenesis during seed development, and participate in the mechanisms underlying radicle protrusion during seed germination. AOS might also have a regulatory function in the changes in gene expression during seed development, dormancy and germination. Their interplay with other molecules, particularly with hormones such as abscisic acid, suggests that they should be considered as key components of an integrated signalling network involved in many aspects of seed physiology.

The formation of crossveins in Drosophila was an important early case study in understanding the role of the environment in the development and evolution of morphological structures. More recent work has shown that signalling processes play a crucial role in the formation of crossveins in Drosophila and that the interaction of a heat shock factor, Hsp90, with components of signal transduction pathways may account for the sensitivity of these structures to environmental perturbations. A new model for the development of crossveins is presented that divides the formation of crossveins into 3 separate stages. First, the number and placement of the crossveins is determined by signalling along the proximal-distal axis of the wing. This signal may involve the cdc42 gene product and the Jun-N-terminal Kinase signal transduction pathway. Then, during the second stage, an inductive signal from the dorsal wing epithelium is sent to the ventral wing epithelium at locations specified by the first signal. The second signal appears to involve the BMP-like signalling pathway. Finally, in the third stage, a domain of vein competent cells is defined by the signalling from the EGF-receptor-Map Kinase signal transduction pathway, and the exact location of the veins is eventually determined within that domain by Notch-Delta signalling interactions. By altering components of these 3 stages, insects can independently regulate the presence or absence, the number and placement, and the thickness and flexibility of the crossveins. This capacity for the modulation of crossvein structure in many different ways may have contributed to the evolution of different modes of insect flight.

This paper discusses ways in which plant metabolism, development and survival influence, and are influenced by, gaseous pollutants. When amino acids are used as carbon and energy sources by plants and other organisms, reduced inorganic nitrogen is released, with wide-ranging implications for the N cycle. Plants can detect the presence and amounts of deposited N and ozone in the environment, not only by direct metabolic incorporation but probably also via distinct signalling systems. Low-nutrient communities and ecosystems, such as temperate conifer forest, are often protected against N overnutrition by adaptations that insulate plant metabolism and growth from the fertilizing effects of deposited pollutant N. Changes in ecosystem balance and biodiversity are not related in any simple way to differential injury responses of constituent species. The question of what happens when a particular component of a changing plant community fails is considered in terms of the relationship between phases of development and the turnover of tissues and organisms.