DCC is a candidate tumor-suppressor gene encoding a protein with sequence similarity to cell adhesion molecules such as N-CAM. A set of overlapping YAC clones that contains the entire DCC coding ...region was isolated. Studies of this YAC contig showed that the DCC gene spans approximately 1.4 Mb. For elucidation of exon-intron structure, lambda phage clones containing all known coding sequences were isolated from a genomic library. These clones were used to demonstrate the existence of 29 DCC exons, and the sequences of the exon-intron boundaries were determined for each. Twenty-three polymorphic markers from chromosome 18 were then studied in a panel of primary colorectal tumors that had lost some, but not all, of chromosome 18. In most of these tumors, the region that was lost included DCC. Finally, Southern blot and PCR-based approaches were used to search for subtle mutations in several DCC exons. One tumor that had a point mutation in exon 28 was found, resulting in a proline to histidine substitution. A second tumor with a point mutation in intron 13 was also found. The regional map and genomic structure of DCC should provide the means to more extensively study DCC gene alterations and protein function in normal and neoplastic cells.
The nature and extent of negative and multiple HLA antigen disease associations are investigated theoretically under two models. The first model assumes that an HLA antigen is involved directly in ...predisposing individuals to disease. The second model assumes that the association of a particular HLA antigen(s) with a disease is the result of linkage disequilibrium between the allele determining the antigen and alleles at a nearby locus which confers susceptibility to disease. We determined whether observed decreases in antigen frequencies among a patient group are simply the inevitable result of the fact that if one or more alleles at a locus is increased in frequency, then others must be decreased. Under the antigen predisposing model exact predictions concerning allele and antigen class frequencies at the predisposing locus, and the non-predisposing loci, are given. The predictions are examined using HLA-DR data for multiple sclerosis.
Princeton guide to ecology Levin, Simon A; Carpenter, Stephen R
2009, 2009., 20090727, 2009-07-27
eBook, Book
The Princeton Guide to Ecology is a concise, authoritative one-volume reference to the field's major subjects and key concepts. Edited by eminent ecologist Simon Levin, with contributions from an ...international team of leading ecologists, the book contains more than ninety clear, accurate, and up-to-date articles on the most important topics within seven major areas: autecology, population ecology, communities and ecosystems, landscapes and the biosphere, conservation biology, ecosystem services, and biosphere management. Complete with more than 200 illustrations (including sixteen pages in color), a glossary of key terms, a chronology of milestones in the field, suggestions for further reading on each topic, and an index, this is an essential volume for undergraduate and graduate students, research ecologists, scientists in related fields, policymakers, and anyone else with a serious interest in ecology.
Endothelial activation and monocyte adhesion to endothelium are key events in inflammation. Sphingosine-1-phosphate (S1P) is a sphingolipid that binds to G protein-coupled receptors on endothelial ...cells (ECs). We examined the role of S1P in modulating endothelial activation and monocyte-EC interactions in vivo.
We injected C57BL/6J mice intravenously with tumor necrosis factor (TNF)-alpha in the presence and absence of the S1P1 receptor agonist SEW2871 and examined monocyte adhesion. Aortas from TNF-alpha-injected mice had a 4-fold increase in the number of monocytes bound, whereas aortas from TNF-alpha plus SEW2871-treated mice had few monocytes bound (P<0.0001). Using siRNA, we found that inhibiting the S1P1 receptor in vascular ECs blocked the ability of S1P to prevent monocyte-EC interactions in response to TNF-alpha. We examined signaling pathways downstream of S1P1 and found that 100 nM S1P increased phosphorylation of Akt and decreased activation of c-jun.
Thus, we provide the first evidence that S1P signaling through the endothelial S1P1 receptor protects the vasculature against TNF-alpha-mediated monocyte-EC interactions in vivo.
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