BMP signaling in the development of the mouse esophagus and forestomach.

The stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain- or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26(CAG-loxpstoploxp-caBmprIa)) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1a(flox/flox) embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach.

Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer.

CD133 is one of the most common stem cell markers, and functional single nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk and patient survival. We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic regression analysis for associations of these SNPs with GC risk and Cox hazards regression analysis for survival. We found that compared with the miRNA binding site rs2240688 AA genotype, AC + CC genotypes were associated with significantly increased GC risk (adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR = 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all patients, the risk rs3130 TT variant genotype was significantly associated with overall survival (OS) (adjusted P(trend) = 0.016 and 0.007 under additive and recessive models, respectively). These findings suggest that these two CD133 miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible predictors for survival in GC patients but require further validation by larger studies.

Ptolemaic Mummy Stuffings, 2: A Comic Fragment and Grammatical Text in the Yale Collection (P. CtYBR inv. 5019, 5043)

This is the second installment of a three-part project to publish a group of ten Ptolemaic papyri purchased by Yale’s Beinecke Library in 1998 (acquisition “1998b”), which came to the Beinecke as three hard wads that were apparently the stuffing from the stomach cavity of a mummified animal. This article publishes: (1) P.CtYBR inv. 5019, a fragment of line ends in iambic tetrameter catalectic meter from an unknown comedy; the format suggests that this is a further example of certain type of Ptolemaic writing exercise. (2) P.CtYBR inv. 5043, a fragmentary grammatical text of uncertain import.