Nasal carriage of Staphylococcus aureus has been identified as a risk factor for community-acquired and nosocomial infections. We screened 230 donors of diverse ethnic and socioeconomic backgrounds and identified 62 (27%) whose nasal secretions were colonized by S . aureus . In 18 donors in whom the various regions of the nasal luminal surface were separately sampled, the predominant region of S . aureus colonization was the moist squamous epithelium on the septum adjacent to the nasal ostium. Nasal fluid from carriers was defective in killing endogenous S . aureus and nasal carrier isolates of S . aureus but not a laboratory S . aureus strain. Transmission electron microscopy revealed that S . aureus isolates incubated in nasal fluid from carriers for 2 h at 37°C were less damaged than those incubated in noncarrier fluid and were coated with an electron-dense layer. Compared with that from healthy donors and patients with acute rhinitis, nasal fluid from carriers contained elevated concentrations of the neutrophil-derived defensins human neutrophil peptides 1 to 3 (47- and 4-fold increases, respectively), indicative of a neutrophil-mediated inflammatory host response to S . aureus colonization. The concentration of the inducible epithelial antimicrobial peptide human β-defensin 2 was also highly elevated compared to that in healthy donors, in whom the level was below the detection limit, or patients with acute rhinitis (sixfold increase). Thus, nasal carriage of S . aureus takes hold in nasal fluid that is permissive for colonization and induces a local inflammatory response that fails to clear the colonizing bacteria.

The brains of males and females differ, not only in regions specialized for reproduction, but also in other regions (controlling cognition, for example) where sex differences are not necessarily expected. Moreover, males and females are differentially susceptible to neurological and psychiatric disease. What are the origins of these sex differences? Two major sources of sexually dimorphic information could lead to sex differences in brain function. Male and female brain cells carry a different complement of sex chromosome genes and are influenced throughout life by a different mix of gonadal hormones. Until recently all sex differences in the brain have been attributed to the differential action of gonadal hormones. Recent findings, however, suggest that brain cells that differ in their genetic sex are not equivalent, and that difference may contribute to sex differences in brain function. Here we discuss evidence for sex chromosome effects on both neural and nonneural systems, which together provide support for the idea that XX and XY cells differentiate even before they are influenced by gonadal hormones, and even if they are exposed to similar levels of gonadal steroids. Fortunately, new model systems for studying sex chromosome effects have recently been developed, and they should help in testing further the role of sex chromosome genes.

The host defense roles of neutrophil elastase in a porcine skin wound chamber model were explored. Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid. The application to the wound of 0.10 and 0.25 mM N-methoxysuccinyl-alanine-alanine-proline-valine (AAPV) chloromethyl ketone, a specific neutrophil elastase inhibitor (NEI), blocked the proteolytic activation of protegrins and diminished the associated antimicrobial activity as detected by radial diffusion assay againstStaphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans or by bacterial gel overlay against S epidermidis and E coli. The application of the related cathepsin G inhibitor (CGI), benzyloxycarbonyl-glycine-leucine-phenylalanine (ZGLF) chloromethyl ketone, had no effect. In wound chambers that received 10⁶ colony-forming unit (CFU)/mL of S epidermidis, the presence of NEI significantly decreased the 24-hour clearance of bacteria from the wound compared to wounds treated with CGI or solvent only. Neither inhibitor, at 0.10 or 0.25 mM concentration, affected leukocyte accumulation or degranulation in the wound chambers. The in vitro microbicidal decrement due to NEI was restored by an amount of the specific protegrin (PG-1), which was equivalent to the measured difference of protegrin between control and inhibited chambers. Administration of 1 μg/mL exogenous PG-1 4 hours after chamber preparation was sufficient to normalize in vivo antimicrobial activity. Although pharmacologic NEIs are promising candidates as anti-inflammatory drugs, they may impair host defense in part by inhibiting the activation of cathelicidins by neutrophil elastase.

We compared global patterns of gene expression between two bird species, the chicken and zebra finch, with regard to sex bias of autosomal versus Z chromosome genes, dosage compensation, and evolution of sex bias. Both species appear to lack a Z chromosome–wide mechanism of dosage compensation, because both have a similar pattern of significantly higher expression of Z genes in males relative to females. Unlike the chicken Z chromosome, which has female-specific expression of the noncoding RNAMHM(male hypermethylated) and acetylation of histone 4 lysine 16 (H4K16) nearMHM, the zebra finch Z chromosome appears to lack theMHMsequence and acetylation of H4K16. The zebra finch also does not show the reduced male-to-female (M:F) ratio of gene expression nearMHMsimilar to that found in the chicken. Although the M:F ratios of Z chromosome gene expression are similar across tissues and ages within each species, they differ between the two species. Z genes showing the greatest species difference in M:F ratio were concentrated near theMHMregion of the chicken Z chromosome. This study shows that the zebra finch differs from the chicken because it lacks a specialized region of greater dosage compensation along the Z chromosome, and shows other differences in sex bias. These patterns suggest that different avian taxa may have evolved specific compensatory mechanisms.