Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer

The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2 60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate. Received 25 August 2006; received after revision 20 November 2006; accepted 20 December 2006     

A New Way of the Skeletal Metals Synthesis

1 Results Strongly disordered metals with the high chemical and catalytic activity are often called as skeletal metals.Usually for their preparation the metallides of d-metal (which afterwards will be left in the “skeleton“) and chemically active component(s) are firstly synthesized.Then the last one(s) is (are) removed by the leaching with aqueous solutions of alkalis or carbonates.However,this method sometime fails,first of all,for the reactions,which should be realized in non-aqueous conditions.In th...     

Structural Changes of Water Molecules Upon the Reduction of Quinones in The Reaction Center from Rhodobactery Sphaeroides

1 Results The photosynthetic bacterial reaction center (RC) is a membrane protein complex.The RC is composed of three protein subunits and redox components such as bacteriochlorophylls, bacteriopheophytins,and quinones.The RC performs the photochemical electron transfer from the bacteriochlorophyll dimer through a series of electron donor and acceptor molecules to a secondary quinone,QB.QB accepts electrons from a primary quinone,QA,in two sequential electron transfer reactions.The second electron trans...     

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

两种信令方式的转换及其实现

介绍了目前应用于我国长途电话交换局的两种主要的线路信令方式及其转换原理．分析了可能出现的“闭塞”现象，提出了解决方法，给出了实现方案和实际应用结果．     

插值Blaschke积的两个刻划定理

信据Ｂｌａｓｃｈｋｅ积在Ｈ＾∞的极大理想空间Ｍ上的零点分布，给出了Ｂｌａｓｃｈｋｅ积是插值Ｂｌａｓｃｈｋｅ积的两个刻划定理。     

织物设计中的色彩搭配

本文以色彩构成理论为依据，找出小配色模纹和较大配色模纹的不同配色所产生外观效应的规律，应用色彩构成规律使织物组织的设计尽可能符合美学观点。     

一种基于一元插值的网格化方法

针对地质数据点的空间分布特点，提出了一种一元网格化方法，探讨了几种常用一元插值方法的应用，并与Ｎ－Ｐ法进行了对比，说明了一元网格化方法的特点．