De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy

Early infantile epileptic encephalopathy with suppression-burst (EIEE), also known as Ohtahara syndrome, is one of the most severe and earliest forms of epilepsy. Using array-based comparative genomic hybridization, we found a de novo 2.0-Mb microdeletion at 9q33.3-q34.11 in a girl with EIEE. Mutation analysis of candidate genes mapped to the deletion revealed that four unrelated individuals with EIEE had heterozygous missense mutations in the gene encoding syntaxin binding protein 1 (STXBP1). STXBP1 (also known as MUNC18-1) is an evolutionally conserved neuronal Sec1/Munc-18 (SM) protein that is essential in synaptic vesicle release in several species. Circular dichroism melting experiments revealed that a mutant form of the protein was significantly thermolabile compared to wild type. Furthermore, binding of the mutant protein to syntaxin was impaired. These findings suggest that haploinsufficiency of STXBP1 causes EIEE.     

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.     

Grinding Characteristics Of Directionally Aligned SiC Whisker Wheel - Comparison With A12O3 Fiber Wheel

A unique SiC whisker wheel was invented, in which the whiskers were aligned normally to the grinding wheel surface. In this paper, grindabilities of the SiC whisker wheel are investigated and compared with those of other wheels of SiC grains, Al2O3 grains, as well as Al2O3 long and short fibres which were also aligned normally to the grinding wheel surface, respectively. The main research contents concern grinding characteristics of a directionally aligned SiC whisker wheel such as material-removal volume, wheel-wear rates, integrity of the ground surfaces, grinding ratios and grinding efficiency. Furthermore, grinding wheels of whiskers and fibres have a common disadvantage: they tend to load easily. The authors have proposed a simple method of loading-free grinding to overcome this propensity and investigate some related grinding characteristics under loading-free grinding conditions.     

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.     

Smart Processing in Materials Tectonics:Fabrication of Photonic Crystals for Terahertz Wave Control by Using Micro-Stereolithography

Photonic crystals with three-dimensional dielectric structures were fabricated to control terahertz waves effectively by using micro-stereolithography of a CAD/CAM process. The photonic crystals with a diamond structure composed of acrylic lattice with nanosized alumina particles were fabricated. Dense alumina structures were obtained by successive dewaxing and sintering in an air atmosphere. The electromagnetic wave properties of these samples were measured by using a terahertz spectroscopy device. The micro periodic structures exhibited perfect band gaps in the terahertz range. To control terahertz waves, micrometer sized electromagnetic devices for cavities, filters, and antennas will be necessary.     

The genome of Cryptosporidium hominis

Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They are members of the Apicomplexa--protozoan pathogens that invade host cells by using a specialized apical complex and are usually transmitted by an invertebrate vector or intermediate host. In contrast to other Apicomplexans, Cryptosporidium is transmitted by ingestion of oocysts and completes its life cycle in a single host. No therapy is available, and control focuses on eliminating oocysts in water supplies. Two species, C. hominis and C. parvum, which differ in host range, genotype and pathogenicity, are most relevant to humans. C. hominis is restricted to humans, whereas C. parvum also infects other mammals. Here we describe the eight-chromosome approximately 9.2-million-base genome of C. hominis. The complement of C. hominis protein-coding genes shows a striking concordance with the requirements imposed by the environmental niches the parasite inhabits. Energy metabolism is largely from glycolysis. Both aerobic and anaerobic metabolisms are available, the former requiring an alternative electron transport system in a simplified mitochondrion. Biosynthesis capabilities are limited, explaining an extensive array of transporters. Evidence of an apicoplast is absent, but genes associated with apical complex organelles are present. C. hominis and C. parvum exhibit very similar gene complements, and phenotypic differences between these parasites must be due to subtle sequence divergence.     

Tension directly stabilizes reconstituted kinetochore-microtubule attachments

Kinetochores are macromolecular machines that couple chromosomes to dynamic microtubule tips during cell division, thereby generating force to segregate the chromosomes. Accurate segregation depends on selective stabilization of correct 'bi-oriented' kinetochore-microtubule attachments, which come under tension as the result of opposing forces exerted by microtubules. Tension is thought to stabilize these bi-oriented attachments indirectly, by suppressing the destabilizing activity of a kinase, Aurora B. However, a complete mechanistic understanding of the role of tension requires reconstitution of kinetochore-microtubule attachments for biochemical and biophysical analyses in vitro. Here we show that native kinetochore particles retaining the majority of kinetochore proteins can be purified from budding yeast and used to reconstitute dynamic microtubule attachments. Individual kinetochore particles maintain load-bearing associations with assembling and disassembling ends of single microtubules for >30?min, providing a close match to the persistent coupling seen in vivo between budding yeast kinetochores and single microtubules. Moreover, tension increases the lifetimes of the reconstituted attachments directly, through a catch bond-like mechanism that does not require Aurora B. On the basis of these findings, we propose that tension selectively stabilizes proper kinetochore-microtubule attachments in vivo through a combination of direct mechanical stabilization and tension-dependent phosphoregulation.     

Novel wide band gap alloyed semiconductors,x(LiGaO_2)_(1/2)-(1-x)ZnO,and fabrication of their thin films

Oxide semiconductor alloys of x(LiGaO2) 1/2-(1-x) ZnO were fabricated by the solid state reaction betweenβ-LiGaO2 and ZnO and rf-magnetron sputtering.For the solid state reaction,the wurtzite-type single phases were obtained in the composition range of x≤0.38.The formation range of the alloys was wider than that of the(Mg1-xZnx) O system,because the β-LiGaO 2possesses a wurtzite-derived structure and approximately the same lattice constants with ZnO.The electrical resistivity and energy band gap of the 0.38(LiGaO2) 1/2-0.62ZnO alloyed ceramic were 0.45-cm and 3.7 eV,respectively,at room temperature.For the alloying by sputtering,the films consisting of the wurtzite-type single phase were obtained over the entire composition range of x(LiGaO2) 1/2-(1-x) ZnO.The energy band gap was controllable in the range from 3.3 to 5.6 eV.For the as-deposited film fabricated using the 0.4(LiGaO2) 1/2-0.6ZnO alloyed ceramic target,the energy band gap was 3.74 eV,and the electrical resistivity,carrier density and the Hall mobility at room temperature were 3.6-cm,3.4×1017 cm-3and 5.6 cm 2 V-1s-1,respectively.     

Square ZnO nano-column and its thermal evolution

Square ZnO nano-columns have been manufactured by molecular beam epitaxy on p-type Si (100) substrate. The morphology and the evolution sequences after thermal annealing were investigated by in-situ scanning tunneling microscopy. We associated the morphology and microstructure evolution with the cubic Si (100) substrate, large lattice mismatching, the coexistence of wurtzite and zincblende phases of ZnO, and the thermal effect.