A comment on the design of experiments to estimate the Michaelis-Menten parameters of enzyme-catalysed reactions

Summary Michaelis-Menten parameters can be estimated by measuring initial velocities (v) in replicate at 2 concentrations of substrate, one much lower than K_m and the other much higher than it. Analysis of simulated experimental data suggests that this design will probably give more precise estimates of K_m and V than the conventional design in which v is measured at several different concentrations of substrate.     

A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis

Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood. Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPARγ (peroxisome proliferator activated receptor γ), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs. FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes. Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions. We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPARγ acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPARγ–FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization.     

手性药物拆分方法的研究

本通过对几种拆分手性药物的方法的列举，比较几种方法，详细介绍了几种方法的特点，以及它们的不同作用。各个方法中又列出了不同的线索，根据这些线索来研究这几种拆分的方法，它们的优缺点以及针对这些缺点的解决方法，最后给出了几个典型的用该方法的实验，以辨别它们的效用。     

An unusual basement membrane underlying intestinal epithelium of the platypus (Ornithorhynchus anatinus)

Zusammenfassung Es werden die besonderen strukturellen Eigenschaften der Basalmembran beschrieben, die unter dem Mucosaepithel aller Darmregionen (Magen bis Rectum) des Schnabeltiers (Ornithorhynchus anatinus) liegt.