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Abstract. In this paper, we propose a novel and efficient protocol for proving the correctness of a shuffle, without leaking how the shuffle was performed. Using this protocol, we can prove the correctness of a shuffle of n data with roughly 18n exponentiations, where as the protocol of Sako-Kilian[SK95] required 642n and that of Abe[Ab99] required 22n log n. The length of proof will be only 2 11 n bits in our protocol, opposed to 2 18 n bits and 2 14 n log n bits required by Sako-Kilian and Abe, respectively. The proposed protocol will be a building block of an efficient, universally verifiable mix-net, whose application to voting system is prominent.

Glycosylation is an essential post-translational modification that underlies many biological processes and diseases. α-dystroglycan (α-DG) is a receptor for matrix and synaptic proteins that causes muscular dystrophy and lissencephaly upon its abnormal glycosylation (α-dystroglycanopathies). Here we identify the glycan unit ribitol 5-phosphate (Rbo5P), a phosphoric ester of pentose alcohol, in α-DG. Rbo5P forms a tandem repeat and functions as a scaffold for the formation of the ligand-binding moiety. We show that enzyme activities of three major α-dystroglycanopathy-causing proteins are involved in the synthesis of tandem Rbo5P. Isoprenoid synthase domain-containing (ISPD) is cytidine diphosphate ribitol (CDP-Rbo) synthase. Fukutin and fukutin-related protein are sequentially acting Rbo5P transferases that use CDP-Rbo. Consequently, Rbo5P glycosylation is defective in α-dystroglycanopathy models. Supplementation of CDP-Rbo to ISPD-deficient cells restored α-DG glycosylation. These findings establish the molecular basis of mammalian Rbo5P glycosylation and provide insight into pathogenesis and therapeutic strategies in α-DG-associated diseases.

Background: Exosome, a type of extracellular vesicles, can associate with A␤ in vitro. Results: Intracerebrally injected exosomes trapped A␤ on surface glycosphingolipids and transported it into microglia in AD mouse brains, resulting in reductions in A␤ pathology. Conclusion: Exogenous exosomes act as potent scavengers for A␤ in mouse brains. Significance: The findings provide a novel therapeutic approach for AD.

a b s t r a c tElevated amyloid-b peptide (Ab) in brain contributes to Alzheimer's disease (AD) pathogenesis. We demonstrated the presence of exosome-associated Ab in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated Ab notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but not glial exosomes, had abundant glycosphingolipids and could capture Ab. Infusion of neuronal exosomes into brains of APP transgenic mice decreased Ab and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. These findings highlight the role of neuronal exosomes in Ab clearance, and suggest that their downregulation might relate to Ab accumulation and, ultimately, the development of AD pathology.

Changes in protein glycosylation profoundly affect protein function. To understand these effects of altered protein glycosylation, we urgently need high-throughput technologies to analyze glycan expression and glycan-protein interactions. Methods are not available for amplification of glycans; therefore, highly efficient sample preparation is a major issue. Here we present a novel strategy that allows flexible and sequential incorporation of various functional tags into oligosaccharides derived from biological samples in a practical manner. When combined with a chemoselective glycoblotting platform, our analysis enables us to complete sample preparation (from serum to released, purified, methyl-esterified, and labeled glycans) in 8 h from multiple serum samples (up to 96 samples) using a 96-well microplate format and a standard de-N-glycosylation protocol that requires reductive alkylation and tryptic digestion prior to PNGase F digestion to ensure maximal de-N-glycosylation efficiency. Using this technique, we quantitatively detected more than 120 glycans on human carcinoembryonic antigens for the first time. This approach was further developed to include a streamlined method of purification, chromatographic fractionation, and immobilization onto a solid support for interaction analysis. Since our approach enables rapid, flexible, and highly efficient tag conversion, it will contribute greatly to a variety of glycomic studies.

Sugars are essential molecules for all terrestrial biota working in many biological processes. Ribose is particularly essential as a building block of RNA, which could have both stored information and catalyzed reactions in primitive life on Earth. Meteorites contain a number of organic compounds including key building blocks of life, i.e., amino acids, nucleobases, and phosphate. An amino acid has also been identified in a cometary sample. However, the presence of extraterrestrial bioimportant sugars remains unclear. We analyzed sugars in 3 carbonaceous chondrites and show evidence of extraterrestrial ribose and other bioessential sugars in primitive meteorites. The 13C-enriched stable carbon isotope compositions (δ13C vs.VPDB) of the detected sugars show that the sugars are of extraterrestrial origin. We also conducted a laboratory simulation experiment of a potential sugar formation reaction in space. The compositions of pentoses in meteorites and the composition of the products of the laboratory simulation suggest that meteoritic sugars were formed by formose-like processes. The mineral compositions of these meteorites further suggest the formation of these sugars both before and after the accretion of their parent asteroids. Meteorites were carriers of prebiotic organic molecules to the early Earth; thus, the detection of extraterrestrial sugars in meteorites establishes the existence of natural geological routes to make and preserve them as well as raising the possibility that extraterrestrial sugars contributed to forming functional biopolymers like RNA on the early Earth or other primitive worlds.