Drugs of the future: the hormone relaxin

The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis, inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions, and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin. The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight its potential as a drug of the future. Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007     

How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity. Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007     

Podocalyxin enhances the adherence of cells to platelets

Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium, progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed in glycomutant CHO cells deficient in sialic acid. Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007     

Regulation of insulin receptor function

Resistance to the biological actions of insulin contributes to the development of type 2 diabetes and risk of cardiovascular disease. A reduced biological response to insulin by tissues results from an impairment in the cascade of phosphorylation events within cells that regulate the activity of enzymes comprising the insulin signaling pathway. In most models of insulin resistance, there is evidence that this decrement in insulin signaling begins with either the activation or substrate kinase activity of the insulin receptor (IR), which is the only component of the pathway that is unique to insulin action. Activation of the IR can be impaired by post-translational modifications of the protein involving serine phosphorylation, or by binding to inhibiting proteins such as PC-1 or members of the SOCS or Grb protein families. The impact of these processes on the conformational changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human disease, is reviewed in this article. Received 3 August 2006; received after revision 1 December 2006; accepted 8 January 2007     

双面吸声板:KD-1的研制

针对商品吸声材料吸声特性的不足与实际工程的需要,介绍了KD-1研制的出发点、特点、效果与构造.经过实验室的检测,可认为KD-1是一种用于厅堂声学设计的新型吸声装置.     

三类分块矩阵的群逆

设Cm×n为复数域上m×n阵的集合.如果A∈Cn×n,则称满足如下条件AXA=AXAX=XAX=XA的矩阵X为A的群逆,记为A#.它若存在则是唯一的.给出了一些特殊形式的分块矩阵群逆存在的充分必要条件及其具体表达式.     

钆基无机纳米粒子磁共振造影剂设计的研究进展

磁共振成像(MRI)技术是常见的临床医学影像学的检测手段之一.在临床诊断中使用最多的是纵向弛豫(T₁)造影剂：马根维显(Gd-DTPA).自其正式商用化后,人们对钆基造影剂进行了大量研究.文章介绍了钆基无机纳米粒子(Gd IONPs)造影剂的作用原理,阐述了无机纳米粒子的形貌、尺寸、表面修饰、氧空位等因素的影响,并对Gd IONPs造影剂的设计做了展望.     

耐高浓度甘油的1,3-丙二醇生产菌的诱变选育

利用紫外线对克雷伯杆菌进行诱变,筛选出耐高浓度甘油且1,3-丙二醇(1,3-PD)产量较高的突变株KpⅥ.实验结果表明,在距离34 cm,功率30 W的紫外灯垂直照射下,最佳紫外诱变时间为6 min,此时,致死率为90.9%.克雷伯杆菌经过紫外诱变后,菌落明显增大,是原始菌株的2~4倍;变异菌株KpⅥ经过6代遗传稳定性考察,甘油消耗率和1,3-PD产量稳定,且保持了较高水平.在甘油质量浓度为90 g.L-1的条件下,变异菌株KpⅥ的甘油消耗率为98.3%,甘油转化率为50.4%,1,3-PD产量为44.81 g.L-1,生产能力达到0.75 g.(L.h)-1.     

几种高分子微球与兔免疫球蛋白的偶联及偶联条件的优化

利用化学偶联法,将8种不同性质的高分子微球与自制的兔免疫球蛋白偶联,根据偶联量大小,考虑微球的性价比,选择出合适的高分子微球产品.实验对200目的氨基硅胶微球的偶联条件作进一步摸索.结果表明,当偶联时间6~8 h,EDC浓度10 g/L,反应pH为5.0,温度为4℃,蛋白质初始浓度为0.7 g/L时,兔免疫球蛋白的偶联量达到6 mg蛋白/g微球,黄曲酶毒素B1的柱回收率在90%以上,达到放大生产要求.