Publications

BACKGROUND

Many complementary solutions are available for the identifier mapping problem. This creates an opportunity for bioinformatics tool developers. Tools can be made to flexibly support multiple mapping services or mapping services could be combined to get broader coverage. This approach requires an interface layer between tools and mapping services.

RESULTS

Here we present BridgeDb, a software framework for gene, protein and metabolite identifier mapping. This framework provides a standardized interface layer through which bioinformatics tools can be connected to different identifier mapping services. This approach makes it easier for tool developers to support identifier mapping. Mapping services can be combined or merged to support multi-omics experiments or to integrate custom microarray annotations. BridgeDb provides its own ready-to-go mapping services, both in webservice and local database forms. However, the framework is intended for customization and adaptation to any identifier mapping service. BridgeDb has already been integrated into several bioinformatics applications.

CONCLUSION

By uncoupling bioinformatics tools from mapping services, BridgeDb improves capability and flexibility of those tools. All described software is open source and available at http://www.bridgedb.org.

Pax3 is a transcription factor expressed in somitic mesoderm, dorsal neural tube and pre-migratory neural crest during embryonic development. We have previously identified cis-acting enhancer elements within the proximal upstream genomic region of Pax3 that are sufficient to direct functional expression of Pax3 in neural crest. These elements direct expression of a reporter gene to pre-migratory neural crest in transgenic mice, and transgenic expression of a Pax3 cDNA using these elements is sufficient to rescue neural crest development in mice otherwise lacking endogenous Pax3. We show here that deletion of these enhancer sequences by homologous recombination is insufficient to abrogate neural crest expression of Pax3 and results in viable mice. We identify a distinct enhancer in the fourth intron that is also capable of mediating neural crest expression in transgenic mice and zebrafish. Our analysis suggests the existence of functionally redundant neural crest enhancer modules for Pax3.

The flooding of New Orleans in late August and September 2005 caused widespread sediment deposition in the flooded areas of the city. Post-flood sampling by US EPA revealed that 37% of sediment samples exceeded Louisiana corrective screening guidelines for arsenic of 12mg/kg, but there was debate over whether this contamination was pre-existing, as almost no pre-flood soil sampling for arsenic had been done in New Orleans. In this study, archived soil samples collected in 1998-1999 were location-matched with 70 residential sites in New Orleans where post-flood arsenic concentrations were elevated. Those same locations were sampled again during the recovery period 18 months later. During the recovery period, sampling for arsenic was also done for the first time at school sites and playgrounds within the flooded zone. Every sample of sediment taken 1-10 months after the flood exceeded the arsenic concentration found in the matched pre-flood soils. The average difference between the two sampling periods was 19.67mg/kg (95% CI 16.63-22.71) with a range of 3.60-74.61mg/kg. At virtually all of these sites (97%), arsenic concentrations decreased substantially by 18 months into the recovery period when the average concentration of matched samples was 3.26mg/kg (95% CI 1.86-4.66). However, 21 (30%) of the samples taken during the recovery period still had higher concentrations of arsenic than the matched sample taken prior to the flooding. In addition, 33% of samples from schoolyards and 13% of samples from playgrounds had elevated arsenic concentrations above the screening guidelines during the recovery period. These findings suggest that the flooding resulted in the deposition of arsenic-contaminated sediments. Diminution of the quantity of sediment at many locations has significantly reduced overall soil arsenic concentrations, but some locations remain of concern for potential long-term soil contamination.

The alpha(4)beta(1) integrin VLA-4 (very-late activation antigen-4) and the lineage-specific CD4 and CD8 receptors have been proposed as putative co-stimulatory receptors on T cells. To assess the relative contribution of signaling through the TCR, CD28 and these accessory molecules, we activated human T cells using soluble antibodies recognizing all four of these T-cell receptor classes (CD3, CD28, CD4/CD8, and VLA-4), and we assessed the degree of activation using higher-order flow cytometry detecting intracellular Erk1/2 phosphorylation and production of IL-2 and IFN-gamma. We found that: (1) co-stimulation via CD4/CD8, in addition to CD28, is required for optimal T-cell activation; (2) VLA-4 binding consistently potentiates CD4(+) and CD8(+) T-cell activation; (3) augmentation of T-cell activation through VLA-4 binding is most pronounced following engagement of CD4/CD8. These results confirm that multiple signals, including VLA-4 engagement, are necessary for maximal T-cell activation beyond that induced via the TCR and CD28.

PURPOSE

This qualitative study explored women's experiences with counseling about medication-induced birth defects, as well as how and when they would like to receive information on medication-induced birth defects from their health care providers (HCPs).

METHODS

We conducted four focus groups with 36 women of reproductive age (18-45 years old) in Pittsburgh, Pennsylvania. Twenty-one women were using medications to treat a chronic health condition, and two were pregnant. Content analysis was performed by three independent coders using a grounded theory approach. Discrepancies were resolved by consensus.

RESULTS

Women reported depending on their HCPs for information about the risks of teratogenic effects of medications on a pregnancy, but felt the information they had been provided was not always comprehensive. Women want HCPs to initiate discussions about potentially teratogenic medications at the time the medications are prescribed, regardless of whether the woman is sexually active or planning a pregnancy. Women want clear information about all potential outcomes for a fetus. Factors women reported as being critical to effective teratogenic risk counseling included privacy, sufficient time to discuss the topic, and a trusting relationship with their HCP.

CONCLUSIONS

Women of reproductive age think that providing information about the possible teratogenic effects of medications could be improved by routine discussions of teratogenic risks at the time medications are prescribed.

OBJECTIVE

To examine the relationship between lactation and subclinical cardiovascular disease in a population free of clinical cardiovascular disease.

METHODS

We conducted a cross-sectional analysis of 297 women who reported at least one live birth on enrollment in the Study of Women Across the Nation-Heart Study. Participants were mothers aged 45-58 years who were free of clinical cardiovascular disease. History of lactation was self-reported. Electron beam tomography was used to assess coronary and aortic calcification. B-mode ultrasonography was used to assess carotid adventitial diameter, intima-media thickness, and carotid plaque. Multivariable linear and logistic regression models were used to estimate whether lactation was independently associated with markers of subclinical cardiovascular disease.

RESULTS

In unadjusted models, compared with mothers who had breastfed all of their children for at least 3 months, mothers who had not breastfed were more likely to have coronary artery calcification (17% compared with 32%), aortic calcification (17% compared with 39%), carotid plaque (10% compared with 18%), and larger carotid adventitial diameters (mean+/-standard deviation 6.63+/-0.59 compared with 6.87+/-0.60 mm). After adjusting for measures of socioeconomic status and lifestyle and family history variables, mothers who had not breastfed remained more likely to have aortic calcification (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.47-10.00) and coronary artery calcification (OR 2.78, 95% CI 1.05-7.14) than mothers who had consistently breastfed. After further adjustment for body mass index and traditional risk factors for cardiovascular disease, mothers who had not breastfed remained more likely to have aortic calcification than mothers who had consistently breastfed (OR 5.26, 95% CI 1.47-20.00).

CONCLUSION

Mothers who do not breastfeed their infants seem to be at increased risk of vascular changes associated with future cardiovascular disease.

LEVEL OF EVIDENCE

II.