Sequential interactions with Sec23 control the direction of vesicle traffic

How the directionality of vesicle traffic is achieved remains an important unanswered question in cell biology. The Sec23p/Sec24p coat complex sorts the fusion machinery (SNAREs) into vesicles as they bud from the endoplasmic reticulum (ER). Vesicle tethering to the Golgi begins when the tethering factor TRAPPI binds to Sec23p. Where the coat is released and how this event relates to membrane fusion is unknown. Here we use a yeast transport assay to demonstrate that an ER-derived vesicle retains its coat until it reaches the Golgi. A Golgi-associated kinase, Hrr25p (CK1δ orthologue), then phosphorylates the Sec23p/Sec24p complex. Coat phosphorylation and dephosphorylation are needed for vesicle fusion and budding, respectively. Additionally, we show that Sec23p interacts in a sequential manner with different binding partners, including TRAPPI and Hrr25p, to ensure the directionality of ER-Golgi traffic and prevent the back-fusion of a COPII vesicle with the ER. These events are conserved in mammalian cells.     

Expansion of amino acid homo-sequences in proteins: Insights into the role of amino acid homo-polymers and of the protein context in aggregation

Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines, in proteins has been directly implicated in various degenerative diseases through a mechanism of protein misfolding and aggregation. However, it is still unclear how the nature of the expansion and the protein context influence the tendency of a protein to aggregate. Here, we have addressed these questions using spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the polyglutamine proteins, chosen as a model system. Using a transfected mammalian cell line, we demonstrate that ATX3 aggregation is noticeably reduced by deletion or replacement of regions other than the polyglutamine tract. The nature of the amino acid homo-sequences also has a strong influence on aggregation. From our studies, we draw general conclusions on the effect of the protein architecture and of the amino acid homo-sequence on pathology. Received 3 March 2006; received after revision 19 April 2006; accepted 22 May 2006     

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.     

Widespread occurrence of inhibitors of melanoma tyrosinase in plant and mammalian tissues

Résumé Les inhibiteurs de tyrosinase ont été trouvés dans des extraits de foie, de rein, de rate et de cerveau de rats et de souris, ainsi que dans des tumeurs amélanotiques S91, des sérums humains, des extraits de foie, de rein, de rate, de sein, et de peau humaine. Il y a au moins deux inhibiteurs: le premier, stable à la chaleur et dialysable, tandis que le second est labile à la chaleur et non-dialysable.

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This investigation was supported by the Medical Research Council of Canada, and the Ontario Cancer Treatment and Research Foundation. One of us (H.F.H.) is a Fellow of the Ontario Cancer Treatment and Research Foundation. The authors thank Mrs.H. Li and MissE. Santos for their skilful technical assistance.     

Clara cell surface of the rat: scanning and transmission electron microscopic study

Summary In normal young rats, groups of Clara cells in the bronchioles showed the formation of many cytoplasmic blebs on their cytoplasmic domes. Detached blebs rested on the bronchiolar epithelial cells. The scanning (SEM) and transmision electron microscope (TEM) studies suggest localized changes of Clare cell surface activities by increased formation of cytoplasmic blebs which may represent the apocrine type of secretion.This project was supported by research grants from NIH HD-10139 and the American Heart Association, Kansas Affiliate. We used the Electron Microscope Research Service Laboratory of the University of Kansas Medical Center.     

On the multiple sex chromosome mechanism in a lygaeid,Oxycarenus hyalinipennis (Costa)

Résumé Oxycarenus hyalinipennis (Costa) possède vraisemblablement des chromosomes sexuels multiples du typeX ₁ X ₂ Y. Les métaphases diploïdes renferment, soit 17, soit 19 éléments. Les 2 éléments supplémentaires des cinèses à 19, bien que comparables auxm-chromosomes des autres Lygéides, diffèrent de ces derniers en certains points de leur comportement qui évoque celui des «surnuméraires» trouvés chez d'autres insectes. La méiose est du type habituel chez les Hétéroptères.     

小型无人直升机纵向和横向动力学的鲁棒反推控制(英文)

研究了阵风情况下悬停飞行模式中的无人直升机的纵向与横向位置的稳定性问题.由于通用的线性模型成功地描述了大多数小型直升机的行为,其被用来设计控制器.基于控制Lyapunov方法,一种递归(反推)设计流程被用来设计纵向和横向动力学的鲁棒控制器.为了比较,我们基于线性二次调节器(LQR)准则设计了另一种控制器.仿真结果表明,所提出的反馈控制器能有效地减弱阵风的影响,在阵风下能够实现纵向和横向位置的快速、准确跟踪.