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From PAWP to ＂Pop＂： opening,up new pathways to fatherhood

Asian Journal of Andrology 2015年第3期17卷 443-444页

作者： melissa L vadnais George L Gerton Center for Research on Reproduction and Women's Health Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104-6160 USA

Infertility remains a significant problem for many couples. Approximately one in seven couples who attempt to conceive will fail to do so within 1 year. In about 65% of these cases, there is a male component of infertility.1 Despite normal semen parameters, the etiology of infertility remains uncertain in more than 50% of couples.2 Defects in sperm proteins and/ or structures may underlie certain cases of male infertility. Although many men would like to be called ＂Pop＂, ＂Dad＂, or ＂Papa＂, those who are classified with idiopathic male infertility have few options for becoming fathers. Recent studies by Aarabi et al.3 may open the door to new therapies.

关键词： CALCIUM OSCILLATIONS OOCYTE ACTIVATION BINDING-PROTEIN PLC-ZETA SPERM FERTILIZATION

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Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus antibodies

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Cellular & Molecular Immunology 2019年第1期16卷 53-64页

作者： Thaddeus C Deiss melissa vadnais Feng Wang Patricia L Chen Ali Torkamani Waithaka Mwangi Marie-Paule Lefranc Michael F Criscitiello Vaughn V Smider Comparative Immunogenetics Laboratory Department of Veterinary PathobiologyCollege of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843USA Department of Molecular Medicine The Scripps Research InstituteLa JollaCA 92037USA California Institute for Biomedical Research La JollaCA 92037USA Department of Integrative Structural and Computational Biology The Scripps Research InstituteLa JollaCA 92037USA Department of Diagnostic Medicine and Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKS 66506USA IMGT the International ImMunoGeneTics information systemLaboratoire d’ImmunoGénétique MoléculaireInstitut de Génétique HumaineCNRSUniversity of MontpellierMontpellier 34396France Department of Microbial Pathogenesis and Immunology College of MedicineTexas A&M UniversityBryanTX 77807USA Fabrus Inc.La JollaCA 92037USA

The antibody repertoire of Bos taurus is characterized by a subset of variable heavy(VH)chain regions with ultralong third complementarity determining regions(CDR3)which,compared to other species,can provide a potent response to challenging antigens like HIV *** unusual CDR3 can range to over seventy highly diverse amino acids in length and form uniqueβ-ribbon‘stalk’and disulfide bonded‘knob’structures,far from the typical antigen binding *** genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well *** we analyze sequences of Bos taurus antibody VH domains and find that the subset with ultralong CDR3 exclusively uses a single variable gene,IGHV1-7(VHBUL)rearranged to the longest diversity gene,*** eight nucleotide duplication at the 3′end of IGHV1-7 encodes a longer V-region producing an extended Fβ-strand that contributes to the stalk in a rearranged CDR3.A low amino acid variability was observed in CDR1 and CDR2,suggesting that antigen binding for this subset most likely only depends on the *** a novel,potentially AID mediated,deletional diversification mechanism of the *** VH ultralong CDR3 knob was discovered,in which interior codons of the IGHD8-2 region are removed while maintaining integral structural components of the knob and descending strand of the stalk in *** deletions serve to further diversify cysteine positions,and thus disulfide bonded ***,both germline and somatic genetic factors and processes appear to be involved in diversification of this structurally unusual cattle VH ultralong CDR3 repertoire.

关键词： bovine complementarity determining region 3 repertoire diversification deletions immunoglobulin heavy chain

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