다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Integrins: versatility, modulation, and signaling in cell adhesion.

Vertebrate sialic acids (Sias) display much diversity in modifications, linkages and underlying glycans. Slide microarrays allow high-throughput explorations of sialoglycan-protein interactions. A microarray presenting ~150 structurally-defined sialyltrisaccharides with various Sias linkages and modifications still poses challenges in planning, data sorting, visualization and analysis. To address these issues, we devised a simple 9-digit code for sialyltrisaccharides with terminal Sias and underlying two monosaccharides assigned from the non-reducing end, with three digits assigning a monosaccharide, its modifications, and linkage. Calculations based on the encoding system reveal >113,000 likely linear sialyltrisaccharides in nature. Notably a biantennary N-glycan with two terminal sialyltrisaccharides could thus have >1010 potential combinations and a triantennary N-glycan with three terminal sequences, >1015 potential combinations. While all possibilities likely do not exist in nature, sialoglycans encode enormous diversity. While glycomic approaches are used to probe such diverse sialomes, naturally-occurring bacterial AB5 toxin B subunits are simpler tools to track the dynamic sialome in biological systems. Sialoglycan microarray was utilized to compare sialoglycan-recognizing bacterial toxin B subunits. Unlike the poor correlation between B subunits and species phylogeny, there is stronger correlation with Sia-epitope preferences. Further supporting this pattern, we report a B subunit (YenB) from Yersinia enterocolitica (broad host range) recognizing almost all sialoglycans in the microarray, including 4-O-acetylated-Sias not recognized by a Y. pestis orthologue (YpeB). Differential Sia-binding patterns were also observed with phylogenetically-related B subunits from Escherichia coli (SubB), Salmonella Typhi (PltB), S. Typhimurium (ArtB), extra-intestinal E.coli (EcPltB), Vibrio cholera (CtxB), and cholera family homologue of E. coli (EcxB).

/pdf/simple-and-practical-sialoglycan-encoding-system-reveals-118guhuy.pdf

Simple and practical sialoglycan encoding system reveals vast diversity in nature and identifies a universal sialoglycan-recognizing probe derived from AB5 toxin B subunits.

17PUpregulation of self-associated molecular patterns and Siglec receptors on T cells facilitate cancer immune evasion

De-N-Acetyl Gangliosides: Do They Exist? If So, How Are They Made? What Do They Do?

Genetic Disorders of Glycosylation in Cultured Cells

Finding natural ligands involved in protein–protein interactions is relatively easy, and false-positives are rare. In contrast, the natural ligands for glycan-binding proteins (GBPs) can be quite elusive, and artifacts are common. For example, it took almost 10 years from the detection of P-selectin’s glycan binding properties (Moore et al. 1991) to reach the definitive conclusion that a certain specific posttranslationally modified form of the polypeptide PSGL-1 was the functionally relevant natural ligand for this GBP (Epperson et al. 2000). There are many reasons for such difficulties, including the fact that glycan binding is often of relatively low affinity and relies on multivalency to achieve adequate avidity, as well as the complexities of local rebinding effects such as the recently described “jump and bind” mechanisms for lectin–mucin interactions (Dam and Brewer 2008). Meanwhile, investigators continue to incorrectly state that “PSGL-1 is the ligand for P-selectin,” without realizing that while the PSGL-1 polypeptide backbone is expressed in many cell types (Laszik et al. 1996), it is only the correctly sialylated, fucosylated, and tyrosine-sulfated form found in certain cells that can function as a P-selectin ligand. In this regard, an excellent prior suggestion is to define the ligand as the glycan(s) bound by the GBP, the protein or lipid to which the glycan(s) are bound as the “carrier,” and the composite of the glycan and the carrier as the “counter–receptor” (Crocker and Feizi 1996) (see Notes). The Siglecs (Sialic acid-binding Ig super-family lectins) are a recently discovered family of GBPs (Crocker and Varki 2001; Varki and Angata 2006; Crocker et al. 2007). They are divided into two groups: the evolutionary conserved ones (Siglec-1, -2, -4, and -15) and the rapidly evolving CD33-related Siglecs (CD33rSiglecs, Siglec-3, 5–14, and -16 in primates, and Siglec-3 plus E-H in rodents). Within the first group there is evidence for specific sialylated ligands (for examples, see Sgroi et al. 1993; Schnaar et al. 1998; Nitschke et al. 1999; Van den Berg et al. 2001; Kimura et al. 2007). In contrast, it has been unclear what the natural ligands (or functions) of CD33-related Siglecs are. Based on the rapid evolution of their sialic acid-recognizing amino-terminal V-set domains, the inhibitory “ITIM” signaling motifs in their cytosolic tails, and the rapid evolving “sialome” of most vertebrate species, it was postulated that CD33rSiglecs function to recognize “self” in the

Ajit Varki

Papers

Simple and practical sialoglycan encoding system reveals vast diversity in nature and identifies a universal sialoglycan-recognizing probe derived from AB5 toxin B subunits.

17PUpregulation of self-associated molecular patterns and Siglec receptors on T cells facilitate cancer immune evasion

De-N-Acetyl Gangliosides: Do They Exist? If So, How Are They Made? What Do They Do?

Genetic Disorders of Glycosylation in Cultured Cells

Glyco-Forum section Natural ligands for CD33-related Siglecs?