Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.     

模糊性的度量及其应用

本文根据模糊度的一般定义及其充分必要条件，提出几种实用方便的模糊度定义，同时讨论模糊度准则在模糊神经网络分类器设计中的指导作用。     

弱智儿童肤纹特征的研究

在弱智儿童中，对有遗传倾向的２４１人（男１４１人，女１００人）进行了手纹调查，并与正常儿童２０２人（男１０２人，女１００人）的手纹进行了比较，发现在指端纹型百分频率、组合格局、ＴＦＲＣ值、ａ一ｂＲＣ值、花样强度和猿线出现率等多项肤纹指标，存在着显著差异或非常显著的差异，这说明有遗传倾向的弱智儿童的确有自己的肤纹特征。     

科举与社会流动性--看王安石论宋人"自进"

在宋人王安石看来,“自进”是“不得已”士人的合理选择,“自进”有“道”。同时,“自进”人存在身份和资格上的限制。首先,“自进”与庶民无关,平等有限;其次,它要限制“势家官户’’子弟,保护弱势地主子弟。所以,就王安石看来,北宋科举未能激起结构性的社会变动,科举“自进”只是一种必要但有限的士人流动方式。     

Role of plasminogen activator-plasmin system in tumor angiogenesis

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated with important extracellular remodeling involving different proteolytic systems among which the plasminogen system plays an essential role. It belongs to the large serine proteinase family and can act directly or indirectly by activating matrix metalloproteinases or by liberating growth factors and cytokines sequestered within the extracellular matrix. Migration of endothelial cells is associated with significant upregulation of proteolysis and, conversely, immunoneutralization or chemical inhibition of the system reduces angiogenesis in vitro. On the other hand, genetically altered mice developed normally without overt vascular anomalies indicating the possibility of compensation by other proteases in vivo. Nevertheless, they have in some experimental settings revealed unanticipated roles for previously characterized proteinases or their inhibitors. In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications.     

Evidence for co-evolution of gene order and recombination rate

There is increasing evidence in eukaryotic genomes that gene order is not random, even allowing for tandem duplication. Notably, in numerous genomes, genes of similar expression tend to be clustered. Are there other reasons for clustering of functionally similar genes? If genes are linked to enable genetic, rather than physical clustering, then we also expect that clusters of certain genes might be associated with blocks of reduced recombination rates. Here we show that, in yeast, essential genes are highly clustered and this clustering is independent of clustering of co-expressed genes and of tandem duplications. Adjacent pairs of essential genes are preferentially conserved through evolution. Notably, we also find that clusters of essential genes are in regions of low recombination and that larger clusters have lower recombination rates. These results suggest that selection acts to modify both the fine-scale intragenomic variation in the recombination rate and the distribution of genes and provide evidence for co-evolution of gene order and recombination rate.     

Cytosolic pH regulates root water transport during anoxic stress through gating of aquaporins

Flooding of soils results in acute oxygen deprivation (anoxia) of plant roots during winter in temperate latitudes, or after irrigation, and is a major problem for agriculture. One early response of plants to anoxia and other environmental stresses is downregulation of water uptake due to inhibition of the water permeability (hydraulic conductivity) of roots (Lp(r)). Root water uptake is mediated largely by water channel proteins (aquaporins) of the plasma membrane intrinsic protein (PIP) subgroup. These aquaporins may mediate stress-induced inhibition of Lp(r) but the mechanisms involved are unknown. Here we delineate the whole-root and cell bases for inhibition of water uptake by anoxia and link them to cytosol acidosis. We also uncover a molecular mechanism for aquaporin gating by cytosolic pH. Because it is conserved in all PIPs, this mechanism provides a basis for explaining the inhibition of Lp(r) by anoxia and possibly other stresses. More generally, our work opens new routes to explore pH-dependent cell signalling processes leading to regulation of water transport in plant tissues or in animal epithelia.     

HCN channels contribute to the intrinsic activity of cochlear pyramidal cells

A hyperpolarization-activated current recorded from the pyramidal cells of the dorsal cochlear nucleus was investigated in the present study by using 150- to 200-m-thick brain slices prepared from 6- to 14-day-old Wistar rats. The pyramidal neurones exhibited a slowly activating inward current on hyperpolarization. The reversal potential of this component was –32 ± 3 mV (mean ± SE, n = 6), while its half-activation voltage was –99 ± 1 mV with a slope factor of 10.9 ± 0.4 mV (n = 27). This current was highly sensitive to the extracellular application of both 1 mM Cs⁺ and 10 M ZD7288. The electrophysiological properties and the pharmacological sensitivity of this current indicated that it corresponded to a hyperpolarization-activated non-specific cationic current (I_h). Our experiments showed that there was a correlation between the availability of the h-current and the spontaneous activity of the pyramidal cells, suggesting that this conductance acts as a pacemaker current in these neurones. Immunocytochemical experiments were also conducted on freshly isolated pyramidal cells to demonstrate the possible subunit composition of the channels responsible for the genesis of the pyramidal h-current. These investigations indicated the presence of HCN1, HCN2 and HCN4 subunits in the pyramidal cells.Received 15 May 2003; received after revision 26 June 2003; accepted 21 July 2003     

离子膜法分离氨基乙酸的研究

设计探讨了离子膜法分离氨基乙酸新工艺,该分离新工艺不存在甲醇污染,使用洁净能源———电力,降低能耗５０％。新工艺操作方便,成本低,三废少,具有工业化前景。     

多重运输调度问题的分枝定界算法及界限估计

多重运输调度问题（ＭＶＲＰ）来源于大规模生产过程的运输组织与实施。本文建立了ＭＶＲＰ的数学规划模型,研究了模型的变形形式、结构特征及解的性质;基于ＭＶＲＰ的数学规划模型,提出了它的分枝定界算法;最后给出了ＭＶＲＰ的上、下界的两个估计式,获得了需求矩阵在平衡时解的精确表示。