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.     

The material theory of induction and the epistemology of thought experiments

John D. Norton is responsible for a number of influential views in contemporary philosophy of science. This paper will discuss two of them. The material theory of induction claims that inductive arguments are ultimately justified by their material features, not their formal features. Thus, while a deductive argument can be valid irrespective of the content of the propositions that make up the argument, an inductive argument about, say, apples, will be justified (or not) depending on facts about apples. The argument view of thought experiments claims that thought experiments are arguments, and that they function epistemically however arguments do. These two views have generated a great deal of discussion, although there hasn't been much written about their combination. I argue that despite some interesting harmonies, there is a serious tension between them. I consider several options for easing this tension, before suggesting a set of changes to the argument view that I take to be consistent with Norton's fundamental philosophical commitments, and which retain what seems intuitively correct about the argument view. These changes require that we move away from a unitary epistemology of thought experiments and towards a more pluralist position.     

The origin of the instantaneous elasticity in single frog muscle fibres.

High-speed cinematographic recordings of single tetanized muscle fibres during a quick decrease in length revealed that the shortening was mostly localized at the fibre segment nearest the released end of the fibre, indicating that the instantaneous elasticity may not originate from the elasticity of the cross-bridges.     

Influences of temperature change on the relaxation and amplitude inhibition by noradrenaline in the rabbit jejunum.

In the rabbit jejunum, the elevation of temperature within the range of 25-37 degrees C diminished the sensitivity to noradrenaline (NA) for both the relaxation and amplitude inhibition. The relaxation by NA was mainly mediated via adrenergic beta-receptors at 25, 30 or 37 degrees C. The amplitude inhibition was mediated via alpha-receptors at 37 degrees C, and both alpha- and beta-receptors at 30 or 25 degrees C.     

The influence of insulin, cAMP and the calcium ionophore X 537 A on the growth of the cartilage analagen of limb buds in vitro.

Limb buds of 11-day-old mouse embryos were cultured for 6 days with insulin, dibutyryl cAMP and X 537 A. The cartilage anlage was reduced by insulin and enlarged by dibutyryl cAMP and X 537 A. The effects are due to changes in the amount of intercellular substance.     

Cytotoxicity of ethyl methanesulfonate in mice spermatogonia.

Enumeration of different types of spermatogonia, following a single i.p. administration of different doses of ethyl methanesulfonate in mice, showed a survival of A1-A4 and in spermatogonia is markedly reduced due to cell killing while the remaining types of spermatogonia were affected marginally. The cell killing effect was dose-dependent, and replenishment of these cells was observed by the end of one cycle of the seminiferous epithelium comprising of 8.5 days.     

Toxicity of Phytophthora infestans and Alternaria solani to chick embryos

None of the extracts and culture filtrates from growth of 9 races of Phytophthora infestans on living potato tissue and potato dextrose broth are toxic to chick embryos. Chloroform extracts of 4 out of 10 isolates of Alternaria solani grown on potato dextrose broth showed some toxicity to chick embryos.     

The effect of glycine on serum luteinizing hormone in adult female rats

The response of serum luteinizing hormone to glycine has been studied during the estrous cycle in adult female rats. I.p. administration of 200 mg of glycine significantly elevated serum luteinizing hormone levels at all stages of the estrous cycle.     

HCO-3-ATPase activity distribution in rat liver cell fractions prepared by zonal centrifugation.

Plasma membrane sheets prepared by zonal centrifugation of a premicrosomal pellet obtained from a rat liver homogenate are devoid of HCO-3-ATPase activity. Since the microsomal fraction is also lacking in this ATPase activity, it can be concluded that the HCO-3-ATPase is not involved in the secretion of HCO-3 into bile.