Publications

Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP), a PKA-selective cAMP analog, alters the expression of approximately 4,500 of approximately 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPT-cAMP. Changes in mRNA and protein expression of several cell-cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2 h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.

Codon volatility is defined as the proportion of a codon's point-mutation neighbors that encode different amino acids. The cumulative volatility of a gene in relation to its associated genome was recently reported to be an indicator of selection pressure. We used this approach to measure selection on all available full-length HIV-1 subtype B genomes in the Los Alamos HIV Sequence Database, and compared these estimates against those obtained via established likelihood- and distance-based comparative methods. Volatility failed to correlate with the results of any of the comparative methods demonstrating that it is not a reliable indicator of selection pressure.

BACKGROUND

Little is known about the participation of minorities in health behavior research. This manuscript assesses factors associated with participation among women in four racial/ethnic groups.

METHODS

A total of 2800 Asian/Pacific Islander (API), Black, Latina, and non-Latina White women recruited through the San Francisco Mammography Registry was invited in 2002 and 2003 to participate in a telephone survey about breast cancer prevention.

RESULTS

Minorities participated at lower rates (49% for APIs, 60% for Latinas, and 64% for Blacks) than Whites (77%). Increased participation was associated with younger age for Latinas (OR = 1.90, 95% CI 1.05-3.44) and Whites (OR = 1.77, CI 1.08-2.91), and with a family history of breast cancer for APIs (OR = 2.09, CI 1.24-3.52). Decreased participation was associated with having less than a high school education for APIs (OR = 0.47, CI 0.26-0.86), Blacks (OR = 0.29, CI 0.11-0.78), and Latinas (OR = 0.51, CI 0.28-0.94).

CONCLUSIONS

Results suggest minorities' participation in health behavior research does not match Whites' and should be enhanced.

RATIONALE

Repeated, short-term exposures to ozone (O3) lead to attenuation of the acute lung function and airway inflammatory responses seen after a single exposure in healthy subjects, but it is unclear whether these acute responses also attenuate in subjects with asthma.

OBJECTIVE

To address this question by exposing 14 subjects with asthma to 0.2 ppm O3 for either 4 hours on a single day or 4 hours on 4 consecutive days (multiday [MD]). At least 3 weeks later, subjects underwent the alternate exposure.

METHODS

Spirometry was performed immediately pre- and postexposure and bronchoalveolar lavage (BAL) was obtained 18 hours after each exposure.

MAIN RESULTS

The decrease in FEV1 was greatest across Day 2 of the MD (MD2) exposure and then gradually declined on successive days of the MD exposure (mean +/- SD decrease in FEV1 of 25.4 +/- 18.0% across MD2 compared with 4.2 +/- 6.5% across MD4). Respiratory symptoms followed a similar pattern to that of FEV1. Although the concentration of neutrophils in BAL after the MD4 exposure was not significantly different from that after the single-day exposure (1.7 +/- 1.3 x 10(4) cells/ml vs. 1.2 +/- 0.8 x 10(4) cells/ml, p = 0.20), the concentration of alveolar macrophages did significantly increase in BAL after the MD exposure (19.9 +/- 9.7 x 10(4) cells/ml after MD4 vs. 12.1 +/- 6.4 x 10(4) cells/ml after the single day).

CONCLUSIONS

Alveolar macrophages are recruited to the airways of subjects with asthma with repeated short-term exposures to O3, suggesting a possible role for these cells in the chronic response to oxidant-induced injury.

Using high-throughput screening, Jo et al. in this issue of Chemistry & Biology [1] have identified SEW2871 as a structurally unique sphingosine 1-phosphate(1) (S1P(1)) receptor agonist. SEW2871 binds to and activates the S1P(1) receptor and initiates a survival signaling pathway similar to that of S1P.