The death-domain fold of the ASC PYRIN domain, presenting a basis for PYRIN/PYRIN recognition.

The PYRIN domain is a conserved sequence motif identified in more than 20 human proteins with putative functions in apoptotic and inflammatory signalling pathways. The three-dimensional structure of the PYRIN domain from human ASC was determined by NMR spectroscopy. The structure determination reveals close structural similarity to death domains, death effector domains, and caspase activation and recruitment domains, although the structural alignment with these other members of the death-domain superfamily differs from previously predicted amino acid sequence alignments. Two highly positively and negatively charged surfaces in the PYRIN domain of ASC result in a strong electrostatic dipole …

Endogenous Myoglobin in Breast Cancer Is Hypoxia-inducible by Alternative Transcription and Functions to Impair Mitochondrial Activity

Recently, immunohistochemical analysis of myoglobin (MB) in human breast cancer specimens has revealed a surprisingly widespread expression of MB in this nonmuscle context. The positive correlation with hypoxia-inducible factor 2α (HIF-2α) and carbonic anhydrase IX suggested that oxygen regulates myoglobin expression in breast carcinomas. Here, we report that MB mRNA and protein levels are robustly induced by prolonged hypoxia in breast cancer cell lines, in part via HIF-1/2-dependent transactivation. The hypoxia-induced MB mRNA originated from a novel alternative transcription start site 6 kb upstream of the ATG codon. MB regulation in normal and tumor tissue may thus be fundamentally diff…

Preconception sex selection demand and preferences in the United States

Objective Preconception sex selection for nonmedical reasons raises important moral, legal, and social issues. The main concern is based upon the assumption that a widely available service for sex selection will lead to a socially disruptive imbalance of the sexes. For a severe sex ratio distortion to occur, however, at least two conditions have to be met. First, there must be a significant preference for children of a particular sex, and second, there must be a considerable interest in employing sex selection technology. Our objective was to ascertain such demand and preferences among the United States general population. Design Cross-sectional web-based survey. Setting United States gener…

nmr structure of the pyrin domain of human asc