The Advantages of Obscurity: Charles Darwin's Negative Inference from the Histories of Domestic Breeds

In The Origin of Species, Charles Darwin famously accounted for the lack of fossil evidence in support of species evolution on the grounds that the fossil record is naturally incomplete. This essay examines a similar argument that Darwin applied to his analogy between natural and artificial selection: the scarcity of data about the historical backgrounds of domestic breeds was the natural by-product of an extremely gradual change process. The point was to enhance the ability of the artificial selection analogy to suggest that nature's species had undergone a similar transformation. Darwin did not depend on this negative inference alone, however, for in his writings he included whatever information he could find about the actual histories of particular breeds. A comparison with Darwin's treatment of the fossil record suggests the reasonableness of this combined use of opposite kinds of evidence to establish a single point. The comparison also suggests the unique qualities of negative inference as applied to the breeding analogy.     

Physical,Human and Divine attraction in the life and thought of George Cheyne

This paper is a study of the mental environment of the Newtonian conception of attraction in the case of George Cheyne, M.D. (1671–1743), physician of the early 18th century and author of a number of popular medical works. It traces the growth of his notions of a spiritual attraction between God and his creatures and between the creatures themselves, and the relation of these ideas both to his use of the Newtonian model of short-range attraction, and to his conception of the creatures as reflections of the divine essence. The paper contends that the development of these aspects of Cheyne's thought harmonizes with the changing pattern of his life, and that this harmony is expressed by his general technique of reasoning by analogy between the various spheres of experience.     

Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.