Active-site protonation states in an Acyl-Enzyme intermediate of a Class A β-Lactamase with a Monobactam Substrate

The monobactam antibiotic aztreonam is used to treat cystic fibrosis patients with chronic pulmonary infections colonized by Pseudomonas aeruginosa strains expressing CTX-M extended-spectrum β-lactamases. The protonation states of active-site residues that are responsible for hydrolysis have been determined previously for the apo form of a CTX-M β-lactamase but not for a monobactam acyl-enzyme intermediate. Here we used neutron and high-resolution X-ray crystallography to probe the mechanism by which CTX-M extended-spectrum β-lactamases hydrolyze monobactam antibiotics. In these first reported structures of a class A β-lactamase in an acyl-enzyme complex with aztreonam, we directly observed most of the hydrogen atoms (as deuterium) within the active site. Although Lys 234 is fully protonated in the acyl intermediate, we found that Lys 73 is neutral. These findings are consistent with Lys 73 being able to serve as a general base during the acylation part of the catalytic mechanism, as previously proposed

Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

Autoantibodies are of growing interest in cancer research as potential biomarkers; yet the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population, and are more prevalent in women and older adults. Here we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women

Relational quality and media use in interpersonal relationships

Author final draft doi:10.1177/1461444807080339This study examined the relationship between relational quality and media use in interpersonal relationships. In addition, the impacts of other potentially important variables such as sex and relationship type of participants and their partners were explored. College student participants focused on interaction experiences with an acquaintance, friend, romantic partner, or family member. Questions addressed the sex of relational partners, how much of participants’ total communication with relational partners is conducted in each of three media (i.e., face-to-face, phone, and internet), and the quality of relationships. Results indicated that participant sex and partner sex did not affect reported media use, whereas relationship type had significant effects on the extent to which face-to-face and telephone communication were used. Specifically, among the college students studied, face-to-face communication was used least with family members and the telephone was used most with family members. Relationships with acquaintances had the lowest relational quality and romantic relationships, while closer, were less satisfying than either family or friendship relationships. Same-sex relationships were perceived as more satisfying than cross-sex relationships. Finally, media use did not predict relational closeness or satisfaction. Results are discussed in light of previous research on mediated interpersonal communication and conceptualizations of the role of communication technology in one’s social life are highlighted