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We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases.

Activation of phagocytic NADPH oxidase requires association of its cytosolic subunits with the membrane-bound flavocytochrome. Extensive phosphorylation of the p47(phox) subunit of NADPH oxidase marks the initiation of this activation process. The p47(phox) subunit then translocates to the plasma membrane, bringing the p67(phox) subunit to cytochrome b558 to form the active NADPH oxidase complex. However, the detailed mechanism for targeting the p47(phox) subunit to the cell membrane during activation still remains unclear. Here, we show that the p47(phox) PX domain is responsible for translocating the p47(phox) subunit to the plasma membrane for subsequent activation of NADPH oxidase. We also demonstrate that translocation of the p47(phox) PX domain to the plasma membrane is not due to interactions with phospholipids but rather to association with the actin cytoskeleton. This association is mediated by direct interaction between the p47(phox) PX domain and moesin., (Copyright 2004 Wiley-Liss, Inc.)

SHP-1 is a cytosolic protein-tyrosine phosphatase that behaves as a negative regulator in eukaryotic cellular signaling pathways. To understand its regulatory mechanism, we have determined the crystal structure of the C-terminal truncated human SHP-1 in the inactive conformation at 2.8-A resolution and refined the structure to a crystallographic R-factor of 24.0%. The three-dimensional structure shows that the ligand-free SHP-1 has an auto-inhibited conformation. Its N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, which supports that the phosphatase activity of SHP-1 is primarily regulated by the N-SH2 domain. In addition, the C-SH2 domain of SHP-1 has a different orientation from and is more flexible than that of SHP-2, which enables us to propose an enzymatic activation mechanism in which the C-SH2 domains of SHPs could be involved in searching for phosphotyrosine activators.

Objective: To evaluate the treatment modalities and the prognostic factors of nasal cavity carcinoma., Methods: A retrospective study was done on 60 nasal cavity carcinoma patients treated from 1985 to 1992. Thirty-four patients received radiotherapy alone and 26 patients received surgery plus radiotherapy. Kaplan-Meier method was used to evaluate the survival, Log-rank test to assess the difference between these two groups and Cox proportional hazard model by multivariate analysis., Results: The overall 5- and 10-year survival rates were 55.9% and 36.9% respectively. The 5- and 10-year survival rates were 79.0% and 57.9% in patients with early lesions (stage I, II) and 44.1% and 26.0% in patients with advanced lesions (stage III, IV) (P = 0.005). There was no significant difference in the survival rate between radiotherapy alone and radiotherapy plus surgery (P = 0.33). Patients with squamous cell carcinoma had obviously poorer survival rate than patients with adenocarcinoma (P = 0.04). Patients with positive nodes had a lower survival rate compared with negative node patients (P = 0.09)., Conclusion: Histological type and clinical stage, but not method of treatment or neck node metastasis, are the important prognostic factors.