CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium

Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein. We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme. Depletion of CEP41 causes ciliopathy-related phenotypes in zebrafish and mice and results in glutamylation defects in the ciliary axoneme. Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction.     

Variant between CPT1B and CHKB associated with susceptibility to narcolepsy

Narcolepsy (hypocretin deficiency), a sleep disorder characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities, is tightly associated with HLA-DRB1*1501 (M17378) and HLA-DQB1*0602 (M20432). Susceptibility genes other than those in the HLA region are also likely involved. We conducted a genome-wide association study using 500K SNP microarrays in 222 Japanese individuals with narcolepsy and 389 Japanese controls, with replication of top hits in 159 Japanese individuals with narcolepsy and 190 Japanese controls, followed by the testing of 424 Koreans, 785 individuals of European descent and 184 African Americans. rs5770917, a SNP located between CPT1B and CHKB, was associated with narcolepsy in Japanese (rs5770917[C], odds ratio (OR) = 1.79, combined P = 4.4 x 10(-7)) and other ancestry groups (OR = 1.40, P = 0.02). Real-time quantitative PCR assays in white blood cells indicated decreased CPT1B and CHKB expression in subjects with the C allele, suggesting that a genetic variant regulating CPT1B or CHKB expression is associated with narcolepsy. Either of these genes is a plausible candidate, as CPT1B regulates beta-oxidation, a pathway involved in regulating theta frequency during REM sleep, and CHKB is an enzyme involved in the metabolism of choline, a precursor of the REM- and wake-regulating neurotransmitter acetylcholine.     

The large-scale organization of metabolic networks

In a cell or microorganism, the processes that generate mass, energy, information transfer and cell-fate specification are seamlessly integrated through a complex network of cellular constituents and reactions. However, despite the key role of these networks in sustaining cellular functions, their large-scale structure is essentially unknown. Here we present a systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems. This may indicate that metabolic organization is not only identical for all living organisms, but also complies with the design principles of robust and error-tolerant scale-free networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.     

An overview of marine & utility system for offshore platform

Main marine & utility (M & U) systems are essential to the routine operation of offshore units,and are extremely important as they are the system that will ensure the basic safety of offshore platforms. This paper gave a general explanation and guideline of the marine & utility systems in offshore projects including their interface with topside,M & U engineering,equipment sizing operation and control.     

点阵中平均覆盖概率的模拟研究

首先对Ｗｏｅｄｒｏｏｆｅ和Ｊｈｕｎ（１９８９）中的结果在简单点阵中进行了模拟研究，然后通过模拟对靴带法与通常的近似值法进行了比较，揭示了采用平均覆盖概率的靴带法的优越性．     

Mechanical, deformation and fracture behaviors of bulk metallic glass composites reinforced by spherical B2 particles

Ti_(45)Cu_(40)Ni_7Zr_5Sn_(2.5)Si_(0.5) alloys were prepared under various cooling rate conditions during solidification.The alloys exhibited different volume fractions of B2 particles with 0～40 vol%in an amorphous matrix.Monolithic bulk metallic glass of 1 mm diameter showed no macroscopic plasticity and exhibited the typical vein patterns in a maximum shear stress plane on the fracture surface.However,a bulk metallic glass composite containing the B2 particles revealed obvious plasticity(～5.6%)with a remarkable work-hardening behavior that resulted from a stress-induced martensitic transformation of the B2 particles.Moreover,the composite displayed the complicated fracture morphologies containing of three types of fracture features.Through detailed investigations on the microstructural evolution,mechanical,deformation and fracture characteristics,the influence of B2 particle on overall behavior of the TiCu-based bulk metallic glass composites was elucidated.     

Development of a hybrid scaffold and a bioreactor for cartilage regeneration

We developed a hybrid scaffold and a bioreactor for cartilage regeneration. The hybrid scaffold was developed as combination of two components： a biodegradable framework and hydrogel-containing chondrocytes. We performed the MTT cell proliferation assay to compare the proliferation and viability of chondrocytes on three types of scaffolds： an aiginate gel, the hybrid scaffold, and an alginate sponge. Cells were encapsulated in 2% agarose gel. The bioreactor consisted of a circulation system and a compression system. We performed dynamic cell culture on these agarose gels in the bioreactor for 3 days.