The celestial mechanics of Leibniz in the light of Newtonian criticism

By the middle of the nineteenth century science was developing into a profession demanding advanced training and devotion to research. American institutions, however, were still better suited to an earlier stage of popular science. Many of the difficulties and frustrations for would-be scientists created by the time lag in institutional change are illustrated in the career of Cleveland Abbe. In the fifteen years between 1856 and 1871 his attempts to become an astronomer touched upon many significant aspects of American science as a profession, including the American observatory movement, the creation of graduate education, government support for science, and the tension between the joint goals of the increase and the diffusion of knowledge.     

Christiaan Huygens: Aviation pioneer extraordinary

In the histories of science, technology and aviation Christiaan Huygens has been unjustly neglected. Documents in the corpus of his works show a life-long interest in the problem of human flight together with some considerable anticipations of, and contributions to, its solution. He was among the first, if not the first, in perceiving the potential of the heavier-than-air approach. He clearly recognized the need for a powerful, mechanical motive source. He stated the first laws of aerodynamics and conceived the modern propeller for propulsion. He was the first to conceive of the aeroplane. His approach to the problem of flying was both global and scientific.     

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.