The Rab8 GTPase regulates apical protein localization in intestinal cells

A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine.     

Correlation between the glass-forming ability and activation energy of crystallization for Zr75−x Ni25Al x metallic glasses

The thermal stability and the kinetics of glass transition and crystallization for Zr_75?x Ni₂₅Al _x (x = 8–15) metallic glasses were investigated using differential scanning calorimetry (DSC) under continuous heating conditions. The apparent activation energy of glass transition rises monotonously with the Al content increasing; the activation energy of crystallization increases with Al changing from 8at% to 15at%, and then decreases with Al further up to 24at%, which exhibits a good correlation to the thermal stability and the glass-forming ability (GFA). The Zr₆₀Ni₂₅Al₁₅ metallic glass with the largest supercooled liquid region and GFA possesses the highest activation energy of crystallization. The relation between the thermal stability, GFA and activation energy of crystallization was discussed in terms of the primary precipitated phases.     

The Novel Semiconductor Nanowire Heterostructures

1 Results If one-dimensional heterostructures with a well-defined compositional profile along the wire radial or axial direction can be realized within semiconductor nanowires, new nano-electronic devices,such as nano-waveguide and nano-capcipator, might be obtained. Here,we report the novel semiconducting nanowire heterostructures:(1) Si/ZnS side-to-side biaxial nanowires and ZnS/Si/ZnS sandwich-like triaxial nanowires[1],(2) Ga-Mg3N2 and Ga-ZnS metal-semiconductor nanowire heterojunctions[2-3]and (3) ...     

Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

DNA damage checkpoint genes, such as p53, are frequently mutated in human cancer, but the selective pressure for their inactivation remains elusive. We analysed a panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis. Progression to carcinoma was associated with p53 or 53BP1 inactivation and decreased apoptosis. A DNA damage response was also observed in dysplastic nevi and in human skin xenografts, in which hyperplasia was induced by overexpression of growth factors. Both lung and experimentally-induced skin hyperplasias showed allelic imbalance at loci that are prone to DNA double-strand break formation when DNA replication is compromised (common fragile sites). We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.     

Room-temperature fabrication of transparent flexible thin-film transistors using amorphous oxide semiconductors

Transparent electronic devices formed on flexible substrates are expected to meet emerging technological demands where silicon-based electronics cannot provide a solution. Examples of active flexible applications include paper displays and wearable computers. So far, mainly flexible devices based on hydrogenated amorphous silicon (a-Si:H) and organic semiconductors have been investigated. However, the performance of these devices has been insufficient for use as transistors in practical computers and current-driven organic light-emitting diode displays. Fabricating high-performance devices is challenging, owing to a trade-off between processing temperature and device performance. Here, we propose to solve this problem by using a novel semiconducting material--namely, a transparent amorphous oxide semiconductor from the In-Ga-Zn-O system (a-IGZO)--for the active channel in transparent thin-film transistors (TTFTs). The a-IGZO is deposited on polyethylene terephthalate at room temperature and exhibits Hall effect mobilities exceeding 10 cm2 V(-1) s(-1), which is an order of magnitude larger than for hydrogenated amorphous silicon. TTFTs fabricated on polyethylene terephthalate sheets exhibit saturation mobilities of 6-9 cm2 V(-1) s(-1), and device characteristics are stable during repetitive bending of the TTFT sheet.     

Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ～50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Nymphs of hemimetabolous insects such as cockroaches and crickets exhibit a remarkable capacity for regenerating complex structures from damaged legs. Until recent years, however, approaches to elucidate the molecular mechanisms underlying the leg regeneration process have been lacking. Taking the cricket Gryllus bimaculatus as a model, we found that a phenotype related to regeneration frequently appears during leg regeneration, even though no phenotype is induced by RNA interference (RNAi) in the cricket nymph, designated as regeneration-dependent RNAi. Since then, we have investigated the functions of various genes encoding signaling factors and cellular adhesion proteins like Fat and Dachsous during leg regeneration. In this review, we summarize the classical knowledge about insect leg regeneration and introduce recent advances concerning the signaling cascades required for regenerating a leg. Our results provide clues to the mechanisms of regeneration which are relevant to vertebrate systems.