A Case for Caution: An Evaluation of Calabrese and Baldwin\u27s Studies of Chemical Hormesis

Suggesting a need for more research, Mr. Elliott argues that it is too soon for risk-assessment policy to account for recent challenges to a toxicological linear dose-response assumption

Exercise epigenetics and the foetal origins of disease

Exercise epigenetics is a nascent area of research with vast health implications (e.g., from the treatment of obesity-related diseases to beneficially decoupling epigenetic and chronological age). Evidence is accumulating [1] that exercise can acutely modify the epigenome (e.g., via DNA methylation) for short-term regulatory purposes (e.g., mRNA expression). More speculatively perhaps, maternal exercise during the pre and post–partum period could cause epigenetic changes in offspring. It is generally believed that there are benefits of regular moderate exercise during pregnancy [2]. The phenotypic benefits of maternal exercise notwithstanding, exercise can be viewed as a type of organismal stressor [1]. There are a myriad of ways in which environmental perturbations can affect foetal development. For example gestational stress could alter the epigenome and subsequent physical development. We suggest that maternal exercise -- like most gestational stressors -- will have a dose-response relationship on an offspring’s epigenome (i.e., negative effects at high doses), akin to the phenomenon of hormesis. Interestingly there is no research investigating the epigenetic effects of maternal exercise in humans. This editorial is a call for research on the subject

Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

Software that Learns from its Own Failures

All non-trivial software systems suffer from unanticipated production failures. However, those systems are passive with respect to failures and do not take advantage of them in order to improve their future behavior: they simply wait for them to happen and trigger hard-coded failure recovery strategies. Instead, I propose a new paradigm in which software systems learn from their own failures. By using an advanced monitoring system they have a constant awareness of their own state and health. They are designed in order to automatically explore alternative recovery strategies inferred from past successful and failed executions. Their recovery capabilities are assessed by self-injection of controlled failures; this process produces knowledge in prevision of future unanticipated failures