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.     

Conotoxins of the O-superfamily affecting voltage-gated sodium channels

The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized by a conserved cysteine knot pattern: C-C-CC-C-C. While ω-conotoxins and κ-conotoxins block Ca²⁺ and K⁺ channels, respectively, the closely related δ- and μO-conotoxins affect voltage-gated Na⁺ channels (Na_v channels). δ-conotoxins mainly remove the fast inactivation of Na_v channels and, thus, functionally resemble long-chain scorpion α-toxins. μO-conotoxins are functionally similar to μ-conotoxins, since they inhibit the ion flow through Na_v channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms. Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Na_v channels. Received 27 December 2006; received after revision 30 January 2007; accepted 19 February 2007     

Surface Waviness in Grinding of Thin Mould Insert Using Chilled Air as Coolant

On going trend of miniaturization in electronic rel at ed parts, which is an average of two times in every 5～7 years introduce grindin g challenges. In grinding process, the surface waviness control of thin parts is an ardent task due to its warpage, induced by the high specific grinding energy (2～10 J/mm 3). Therefore, coolant is often used to avoid thermal damage, obtai n better surface integrity and to prolong wheel life. However coolant, the incomp ressibility media introduce high forces at the gri...     

分子间作用力对制备含有机废弃之水泥浆体影响研究

研究以水泥处理固体有机物时，有机物对水泥水化的影响。以膜流模式说明水份在水泥浆体内传输的现象。水膜存在半干之水泥浆体，其厚度小于100nm，膜流由离分压所驱动，而离分压来自分子间作用力。膜拟结果发现，水泥浆体内局部位置可用以进行水化之水量为Q=-Aslv／6vπ。当有机物添加在水泥浆体内时，会影响Hamaker常数，Aslv因此可能使膜流不稳定或完全抑制膜流，因而使水泥浆体内局部缺水，影响水化进行，造成成品强度降低，影响品质。     

Regional distribution of thiamin pyrophosphokinase in rat brain

The highest specific activity of thiamin pyrophosphokinase was found in the cerebellum, and lower activity in cerebral cortex and midbrain. The regional difference in the enzyme activity was similar to that in thiamin content and the influx rate in rat brain, suggesting that the enzyme is involved in the thiamin transport.