John Harris' argument for a duty to research

John Harris suggests that partcipation in or support research, particularly medical research, is a moral duty. One kind of defence of this position rests on an appeal to the past, and produces two arguments. The first of these arguments is that it is unfair to accept the benefits of research without contributing something back in the form of support for, or participation in, research. A second argument is that we have a social duty to maintain those practices and institutions that sustain us, such as those which contribute to medical knowledge. This argument is related to the first, but it does not rely so heavily on fairness. Another kind of defence of the duty to research rests on an appeal to the future benefits of research: research is an effective way to discharge a duty to rescue others from serious illness or death, therefore we have a duty to research. I suggest that all three of Harris' lines fail to provide a compelling duty to research and spell out why. Moreover, not only do the lines of argument fail in their own terms: in combination, they turn out to be antagonistic to the very position that Harris wants to defend. While it is not my intention here to deny that there might be a duty to research, I claim that Harris' argument for the existence of such a duty is not the best way to establish it.     

Myosin X is a high duty ratio motor

Myosin X is expressed in a variety of cell types and plays a role in cargo movement and filopodia extension, but its mechanoenzymatic characteristics are not fully understood. Here we analyzed the kinetic mechanism of the ATP hydrolysis cycle of acto-myosin X using a single-headed construct (M10IQ1). Myosin X was unique for the weak "strong actin binding state" (AMD) with a K(d) of 1.6 microm attributed to the large dissociation rate constant (2.1 s(-1)). V(max) and K(ATPase) of the actin-activated ATPase activity of M10IQ1 were 13.5 s(-1) and 17.4 mum, respectively. The ATP hydrolysis rate (>100 s(-1)) and the phosphate release rate from acto-myosin X (>100 s(-1)) were much faster than the entire ATPase cycle rate and, thus, not rate-limiting. The ADP off-rate from acto-myosin X was 23 s(-1), which was two times larger than the V(max). The P(i)-burst size was low (0.46 mol/mol), indicating that the equilibrium is significantly shifted toward the prehydrolysis intermediate. The steady-state ATPase rate can be explained by a combination of the unfavorable equilibrium constant of the hydrolysis step and the relatively slow ADP off-rate. The duty ratio calculated from our kinetic model, 0.6, was consistent with the duty ratio, 0.7, obtained from comparison of K(m ATPase) and K(m motility). Our results suggest that myosin X is a high duty ratio motor.     

Use or abuse of bioinformatic tools: a response to Samach

In a recent paper, we described for the first time the effects of fruit on the expression of putative homologues of genes involved in flowering pathways. It was our aim to provide insight into the molecular mechanisms underlying alternate bearing in citrus. However, a bioinformatics-based critique of our and other related papers has been given by Samach in the preceding Viewpoint article in this issue of Annals of Botany. The use of certain bioinformatic tools in a context of structural rather than functional genomics can cast doubts about the veracity of a large amount of data published in recent years. In this response, the contentions raised by Samach are analysed, and rebuttals of his criticisms are presented.