3D DNA origami designed with caDNAno

For about three decades, DNA-based nanotechnology has been undergoing development as an assembly method for nanostructured materials. The DNA origami method pioneered by Rothemund paved the way for the formation of 3D structures using DNA self assembly. The origami approach uses a long scaffold strand as the input for the self assembly of a few hundred staple strands into desired shapes. Herein, we present a 3D origami roller (75 nm in length) designed using caDNAno software. This has the potential to be used as a template to assemble nanoparticles into different pre-defined shapes. The roller was characterized with agarose gel electrophoresis, atomic force microscopy (AFM) and transmission electron microscopy (TEM).     

Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice

A fundamental question about the pathogenesis of spontaneous autoimmune diabetes is whether there are primary autoantigens. For type 1 diabetes it is clear that multiple islet molecules are the target of autoimmunity in man and animal models. It is not clear whether any of the target molecules are essential for the destruction of islet beta cells. Here we show that the proinsulin/insulin molecules have a sequence that is a primary target of the autoimmunity that causes diabetes of the non-obese diabetic (NOD) mouse. We created insulin 1 and insulin 2 gene knockouts combined with a mutated proinsulin transgene (in which residue 16 on the B chain was changed to alanine) in NOD mice. This mutation abrogated the T-cell stimulation of a series of the major insulin autoreactive NOD T-cell clones. Female mice with only the altered insulin did not develop insulin autoantibodies, insulitis or autoimmune diabetes, in contrast with mice containing at least one copy of the native insulin gene. We suggest that proinsulin is a primary autoantigen of the NOD mouse, and speculate that organ-restricted autoimmune disorders with marked major histocompatibility complex (MHC) restriction of disease are likely to have specific primary autoantigens.     

A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis

Genetic susceptibility to multiple sclerosis is associated with genes of the major histocompatibility complex (MHC), particularly HLA-DRB1 and HLA-DQB1 (ref. 1). Both locus and allelic heterogeneity have been reported in this genomic region. To clarify whether HLA-DRB1 itself, nearby genes in the region encoding the MHC or combinations of these loci underlie susceptibility to multiple sclerosis, we genotyped 1,185 Canadian and Finnish families with multiple sclerosis (n = 4,203 individuals) with a high-density SNP panel spanning the genes encoding the MHC and flanking genomic regions. Strong associations in Canadian and Finnish samples were observed with blocks in the HLA class II genomic region (P < 4.9 x 10(-13) and P < 2.0 x 10(-16), respectively), but the strongest association was with HLA-DRB1 (P < 4.4 x 10(-17)). Conditioning on either HLA-DRB1 or the most significant HLA class II haplotype block found no additional block or SNP association independent of the HLA class II genomic region. This study therefore indicates that MHC-associated susceptibility to multiple sclerosis is determined by HLA class II alleles, their interactions and closely neighboring variants.     

导弹制导和控制系统

虽然导弹制导和控制系统的出现源自军事目的，但是这项技术已经应用于很多领域，比如机器人、工业过程控制和全球定位系统（GPS，Global Positioning System）。本书详细的阐述了这项技术的最新幕后，战略和战术导弹及其对给定目标的制导、控制和采取的策略。     

Insect antifeedant properties of withanolides and related steroids from Solanaceae

Summary Physalis peruviana shrubs were not attacked by larvae ofSpodoptera littoralis. It was demonstrated that withanolide E, a steroid isolated fromP. peruviana, as well as several related steroids, have insect antifeedant properties.     

Effect of nitrate esters of androgen steroids on the succinate oxidase and NADH-Cytochrome C reductase activity of isolated rat liver mitochondria

Résumé Le testostérone et la 5-androstane-17-ol-3-one stimulent l'activité de la succinoxydase des mitochondries intactes et l'activité de la NADH-cytochrome-c-réductase des mitochondries à membranes lésées, extraites du foie du rat blanc. Les nitrates-esters des mÊmes stéroÏdes réduisent l'activité des deux enzymes.