Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.     

An intracellular P2X receptor required for osmoregulation in Dictyostelium discoideum

P2X receptors are membrane ion channels gated by extracellular ATP that are found widely in vertebrates, but not previously in microbes. Here we identify a weakly related gene in the genome of the social amoeba Dictyostelium discoideum, and show, with the use of heterologous expression in human embryonic kidney cells, that it encodes a membrane ion channel activated by ATP (30-100 muM). Site-directed mutagenesis revealed essential conservation of structure-function relations with P2X receptors of higher organisms. The receptor was insensitive to the usual P2X antagonists but was blocked by nanomolar concentrations of Cu2+ ions. In D. discoideum, the receptor was found on intracellular membranes, with prominent localization to an osmoregulatory organelle, the contractile vacuole. Targeted disruption of the gene in D. discoideum resulted in cells that were unable to regulate cell volume in hypotonic conditions. Cell swelling in these mutant cells was accompanied by a marked inhibition of contractile vacuole emptying. These findings demonstrate a new functional role for P2X receptors on intracellular organelles, in this case in osmoregulation.     

P2X receptors as cell-surface ATP sensors in health and disease

P2X receptors are membrane ion channels activated by the binding of extracellular adenosine triphosphate (ATP). For years their functional significance was consigned to distant regions of the autonomic nervous system, but recent work indicates several further key roles, such as afferent signalling, chronic pain, and in autocrine loops of endothelial and epithelial cells. P2X receptors have a molecular architecture distinct from other ion channel protein families, and have several unique functional properties.     

直流锅炉蒸发区域一种新的建模方法

对于电站直流锅炉蒸发区域提出一种新的建模方法，克服了以往方法遇到的问题，仿真结果表明，用这种方法建立的模型在大扰动的情况下能够正确反映对象各参数的响应特性，该建模方法同样适用于核电站直流蒸汽发生器。     

动态矩阵解耦控制及其应用

针对双输入双输出的多变量强耦合系统，首先将其分解为两个双输入单输出系统，并用动态矩阵控制原理设计了控制器。通过求解二元一次矩阵方程组，实现了多步预测的解耦控制。仿真研究结果证实了该算法的有效性。     

降雨入渗补给地下水的影响因素

选取汾河二坝灌区降雨量和地下水动态观测资料来计算该区降雨入渗补给系数α值，并对影响α值的各种因素进行分析。