With the centenary of the first descriptions of 'hypersensitiveness' following pathogenic challenge upon us, it is appropriate to assess our current understanding of the hypersensitive response (HR) form of cell death. In recent decades our understanding of the initiation, associated signalling, and some important proteolytic events linked to the HR has dramatically increased. Genetic approaches are increasingly elucidating the function of the HR initiating resistance genes and there have been extensive analyses of death-associated signals, calcium, reactive oxygen species (ROS), nitric oxide, salicylic acid, and now sphingolipids. At the same time, attempts to draw parallels between mammalian apoptosis and the HR have been largely unsuccessful and it may be better to consider the HR to be a distinctive form of plant cell death. We will consider if the HR form of cell death may occur through metabolic dysfunction in which malfunctioning organelles may play a major role. This review will highlight that although our knowledge of parts of the HR is excellent, a comprehensive molecular model is still to be attained.

The lack of robust measures of dietary exposure hinders a quantitative understanding of causal relationships between diet and health. Non-targeted metabolite fingerprinting was used to explore the relationships between citrus exposure in free-living human subjects, estimated by a FFQ, and the chemical content of urine. Volunteers (study 1, n 12; study 2, n 11) were classified into high-, mediumand low-frequency citrus consumption groups. Overnight and spot fasting urine samples were obtained after exposure to a standardised citrus-free evening meal. The urine samples were analysed by flow injection electrospray-ionisation MS followed by supervised multivariate data classification analysis to discover discriminatory features associated with the level of citrus exposure. Good separation of high and low citrus consumption classes was achieved. Deeper exploration of high-ranked explanatory mass signals revealed several correlated signals derived from proline betaine. Targeted analysis of the relative levels of proline betaine in both fasting and overnight urine samples demonstrated good correlation with FFQ exposure data. Acute exposure of volunteers to orange juice resulted in the appearance of proline betaine and several biotransformed products in postprandial urine samples. Biomarker validation showed sensitivities of 80·8 -92·2 % and specificities of 74·2 -94·1 % (false discovery rate-adjusted P values ,0·05) for elevated proline betaine in participants who reported high citrus consumption. Proline betaine biotransformation products displayed weaker quantitative relationships with habitual citrus exposure. Targeted screening for the presence of biotransformation products of hesperidin and narirutin, known to be abundant in oranges, revealed that they were relatively poor indicators of citrus exposure.

Background: The lack of robust biological markers of dietary exposure hinders the quantitative understanding of causal relations between diet and health. Objective: We aimed to develop an efficient procedure to discover metabolites in urine that may have future potential as biomarkers of acute exposure to foods of high public health importance. Design: Twenty-four participants were provided with a test breakfast in which the cereal component of a standardized breakfast was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5-h postprandial urine samples were collected. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to discover signals resulting from consumption of each test food. Results: Fasted-state urine samples provided a universal comparator for food biomarker lead discovery in postprandial urine. The filtering of data features associated with consumption of the common components of the standardized breakfast improved discrimination models and readily identified metabolites that showed consumption of specific test foods. A combination of trimethylamine-N-oxide and 1-methylhistidine was associated with salmon consumption. Novel ascorbate derivatives were discovered in urine after consumption of either broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl-epicatechin concentrations increased dramatically after consumption of raspberries. Conclusions: This biomarker lead discovery strategy can identify urinary metabolites associated with acute exposure to individual foods. Future studies are required to validate the specificity and utility of potential biomarkers in an epidemiologic context. Am J Clin Nutr 2011;94:981-91.