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.     

Avian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus

From the complete nucleotide sequence of the genome of the avian sarcoma virus Y73, we have predicted amino acid sequence of p90 gag-yes, the product of the transforming gene. Contrary to previous evidence from molecular hybridization studies p90 gag-yes was found to have much homology with the transforming gene product p60 src of Rous sarcoma virus, suggesting that the cellular counterparts of the two (c-yes and c-src) originated from a common prototype sequence.     

Nuclear cataract caused by a lack of DNA degradation in the mouse eye lens

The eye lens is composed of fibre cells, which develop from the epithelial cells on the anterior surface of the lens. Differentiation into a lens fibre cell is accompanied by changes in cell shape, the expression of crystallins and the degradation of cellular organelles. The loss of organelles is believed to ensure the transparency of the lens, but the molecular mechanism behind this process is not known. Here we show that DLAD ('DNase II-like acid DNase', also called DNase IIbeta) is expressed in human and murine lens cells, and that mice deficient in the DLAD gene are incapable of degrading DNA during lens cell differentiation--the undigested DNA accumulates in the fibre cells. The DLAD-/- mice develop cataracts of the nucleus lentis, and their response to light on electroretinograms is severely reduced. These results indicate that DLAD is responsible for the degradation of nuclear DNA during lens cell differentiation, and that if DNA is left undigested in the lens, it causes cataracts of the nucleus lentis, blocking the light path.     

利用激光莫尔信号精密定位的复合控制研究

在分析利用激光干涉莫尔信号的精密定位方法的基础上，提出了精密定位的粗控、微控两段复合式控制方法，实现了装置宽范围控制的精密定位高业度及精密定位时间的缩短，对加快集成电路制造技术的进步有重要的参考价值。     

HLA-DQ is epistatic to HLA-DR in controlling the immune response to schistosomal antigen in humans

Antigens that produce an antibody response in some members of a species may fail to do so in others. The response to an antigen is controlled by a gene termed the immune response (Ir) gene, which is transmitted as a single dominant trait. We have provided evidence for similar immune suppression (Is) genes which control non-responsiveness through the antigen specific suppressor T cell. The non-responsiveness is also dominantly inherited and the Is genes are linked to the histocompatibility (HLA) antigen system. Here we report that the HLA-DR2 molecule from a non-responder haplotype (HLA-Dw12-DR2-DQwl) is required for the proliferative T cell response to schistosoma japonicum (Sj) antigen, as a restriction element, indicating that the HLA-DR2 is the product of the Ir gene, and that the HLA-DQwl molecule of the non-responder haplotype is important in the antigen-specific suppression of the response to this antigen, suggesting that it is the product of the Is gene. We therefore conclude that the HLA-DR and DQ molecules, which are controlled by the distinct genes in the MHC multigene family, regulate immune response and immune suppression and that the gene for HLA-DQ is epistatic to that for HLA-DR in controlling the immune response to schistosomal antigen in humans.     

Making continental crust: The sanukitoid connection

The average continental crust possesses intermediate compositions that typify arc magmatism and as a result it is believed to have been created at ancient convergent plate boundaries. One possible mechanism for intermediate continental crust formation is the direct production of andesitic melts in the upper mantle. Sanukitoids, which characterize the Setouchi volcanic belt, SW Japan, include unusually high-Mg andesites （HMA）. They were generated by slab melting and subsequent melt-mantle interactions under unusual tectonic settings such as where warm lithosphere subducts into hot upper mantle. Such conditions would have existed in the Archean. Hydrous HMA magmas are likely to have solidified within the crust to form HMA plutons, which were then remelted to produce differentiated sanukitoids. At present, generation and differentiation of HMA magmas may be taking place in the Izu-Bonin-Mariana arc-trench system （IBM）, because （1） HMA magmatism characterizes the initial stages of the IBM evolution and （2） the IBM middle crust exhibits Vp identical to that of the bulk conti- nental crust. Vp estimates for plutonic rocks with HMA compositions support this. However tonalitic composition for middle-crust-forming rocks cannot be ruled out, suggesting an alternative possibility that the continental crust has been created by differentiation of mantle-derived basaltic magmas.