Origination of New Immunological Functions in the Costimulatory Molecule B7-H3: The Role of Exon Duplication in Evolution of the Immune System

B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication. Further sequence analysis indicated that this duplication generated a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presented both membrane and soluble forms. Through three-dimensional (3D) structure modeling and fusion-protein binding assays, we discovered that the duplicated isoform had a different structure and might bind to another potential receptor on activated T cells. In T cell proliferation assay, human 2IgB7-H3 (h2IgB7-H3) and mouse B7-H3 (mB7-H3) both increased T cell proliferation and IL-2, IFN-γ production, whereas human 4IgB7-H3 (h4IgB7-H3) reduced cytokine production and T cell proliferation compared to control. Furthermore, both h2IgB7-H3 and mB7-H3 upregulated the function of lipopolysacharide (LPS)-activated monocyte in vitro. Taken together, our data implied that during the evolution of vertebrates, B7-H3 exon duplication contributed to the generation of a new 4IgB7-H3 isoform in many mammalian species, which have carried out distinct functions in the immune responses

Uncultivated Brazilian green leaves are richer sources of carotenoids than are commercially produced leafy vegetables

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background. With the continuing problem of vitamin A deficiency, the recognition of the role of carotenoids in disease prevention, and international programs promoting biodiversity, determination of the carotenoid content of indigenous Brazilian foods is needed. Objective. To determine the principal carotenoids in native leaves and compare the levels with those in commercially produced leafy vegetables. Methods. The indigenous Brazilian leafy vegetables caruru, mentruz, taioba, serralha, and beldroega were analyzed with the use of a previously developed and validated high-performance liquid chromatography (HPLC) method. Parsley and coriander leaves, which were previously shown to be the richest in carotenoids among commercially produced leaves, were analyzed for comparison. Five sample lots of each vegetable collected at different times during the year were analyzed immediately after harvest. Results. Lutein concentrations were 119 +/- 21, 111 +/- 48, 104 +/- 44, 87 +/- 7, and 34 +/- 14 mu g/g, and beta-carotene contents were 114 +/- 22, 97 +/- 40, 66 +/- 18, 72 +/- 9, and 32 +/- 14 mu g/g for caruru, mentruz, taioba, serralha, and beldroega, respectively. Except for beldroega, these values were higher than those for commercial leaves. Parsley had 88 +/- 18 mu g/g of lutein and 65 +/- 13 mu g/g of beta-carotene. Coriander leaves contained 74 +/- 6 mu g/g of lutein and 55 +/- 5 mu g/g of beta-carotene. The violaxanthin and neoxanthin concentrations were also higher in the native leaves. Comparison with values for previously analyzed commercial leafy vegetables confirmed the higher carotenoid levels of the native leaves. Conclusions. The indigenous leaves investigated are richer sources of carotenoids than are commercially produced leafy vegetables.294320328Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2003/10151-4