A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a 2-nucleotide deletion in the open reading frame, which generates a non-stop mRNA. The allele frequency of this variant sequence is high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from the del/del donors exhibited an 84% reduction in the rate of penetration of a hyaluronic acid (HA) gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in HA gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. However, DEFB126 genotype and lectin binding were highly correlated with performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent cause of impaired reproductive function, provides an opportunity to better understand, clinically evaluate, and possibly treat human infertility.

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The viaB locus contains genes for the biosynthesis and export of the Vi capsular antigen of Salmonella enterica serotype Typhi. Wild-type serotype Typhi induces less CXC chemokine production in tissue culture models than does an isogenic viaB mutant. Here we investigated the in vivo relevance of these observations by determining whether the presence of the viaB region prevents inflammation in two animal models of gastroenteritis. Unlike S. enterica serotype Typhimurium, serotype Typhi or a serotype Typhi viaB mutant did not elicit marked inflammatory changes in the streptomycin-pretreated mouse model. In contrast, infection of bovine ligated ileal loops with a serotype Typhi viaB mutant resulted in more fluid accumulation and higher expression of the chemokine growth-related oncogene alpha (GRO␣) and interleukin-17 (IL-17) than did infection with the serotype Typhi wild type. There was a marked upregulation of IL-17 expression in both the bovine ligated ileal loop model and the streptomycin-pretreated mouse model, suggesting that this cytokine is an important component of the inflammatory response to infection with Salmonella serotypes. Introduction of the cloned viaB region into serotype Typhimurium resulted in a significant reduction of GRO␣ and IL-17 expression and in reduced fluid secretion. Our data support the idea that the viaB region plays a role in reducing intestinal inflammation in vivo.Salmonella enterica serotype Typhi causes a severe systemic infection in humans known as typhoid fever. In contrast, nontyphoidal Salmonella serotypes, such as S. enterica serotype Typhimurium, cause a localized infection in humans manifesting as gastroenteritis (41,64). The different clinical presentations of infections with serotype Typhi and serotype Typhimurium point to important differences during the interaction of these pathogens with their human host. One such difference is the host response elicited in the intestinal mucosa. Gastroenteritis is a typical diarrheal disease characterized by a massive neutrophil influx in the terminal ileum and colon and a predominance of neutrophils in the stool samples of patients (9,17,26). In contrast, typhoid fever is not a typical diarrheal disease, and the intestinal pathology is characterized by a predominantly mononuclear infiltrate (i.e., macrophages and dendritic cells) (17,23,29,30,46).The nature of these differences is poorly understood, partly because the strict adaptation of serotype Typhi to its human host severely limits our ability to study host-pathogen interactions in vivo. While higher primates (i.e., chimpanzees) are susceptible to infections, nonprimate vertebrates and even lower primates (i.e., rhesus macaques) are resistant to serotype Typhi (11). As a result, differences between infections with serotypes Typhi and Typhimurium have mostly been explored with tissue culture models. Although the in vivo relevance of results from tissue culture assays remains to be established in many cases, these studies have revealed marked differences during the interaction...

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Isolation of the avian embryo from its normal food material is an essential step in a fundamental study of embryonic nutrition. With present methods, however, it has not been possible to grow embryos in culture for much longer than one day. In 1932 Waddington described methods of growing explanted embryos on serum clots. Several years later Spratt (1947, 1952) devised simplified media for embryos cultured on agar with which he studied various aspects of morphogenesis and carbohydrate needs of the young embryo. New (1955) has recently reported another technique for growing explanted embryos which allows development to proceed to about 60 hours, 40 hours of which are in vitro. A number of workers have injected various nutrients, antimetabolites, drugs, poisons, and hormones, directly into the yolk sac or other areas of the egg (e.g. Landauer, 1954).