Publications

GspB is a serine-rich glycoprotein adhesin of Streptococcus gordonii that is exported to the bacterial surface by the accessory Sec system. This dedicated export pathway is comprised of seven components (SecA2, SecY2, and five accessory Sec proteins [Asp1 to Asp5]). The latter proteins have no known homologs beyond the Asps of other species. Asp1 to Asp3 are absolutely required for export of the substrate GspB, but their roles in this process are unknown. Using copurification analysis and far-Western blotting, we found that Asp2 and Asp3 could individually bind the serine-rich repeat (SRR) domains of GspB. Deletion of both SRR regions of GspB led to a decrease in its export, suggesting that binding of the Asps to the SRR regions is important for GspB transport by the accessory Sec system. The Asps also bound a heterologous substrate for the accessory Sec system containing a slow-folding MalE variant, but they did not bind wild-type MalE. The combined results indicate that the Asps may recognize the export substrate through preferential interactions with its unstructured or unfolded regions. Glycosylation of the SRR domains on GspB prevented Asp binding, suggesting that binding of the Asps to the preprotein occurs prior to its full glycosylation. Together, these findings suggest that Asp2 and Asp3 are likely to function in part as chaperones in the early phase of GspB transport.

OBJECTIVE

Understanding moderators of the relationship between physical activity (PA) and alcohol use is important for clarifying the mechanisms underlying these behaviors and informing health promotion interventions. This study examined age and gender as two candidate moderators of the PA-alcohol use link.

METHOD

As part of a correlational, cross-sectional population-based study of US 34,653 adults, participants were administered surveys assessing demographics, alcohol use, moderate and vigorous PA, and other characteristics. Composite indices of the frequency and quantity of alcohol use and PA were utilized in analyses.

RESULTS

Age moderated the association between past-year vigorous PA and alcohol use (ps ≤ .01). Vigorous PA was positively associated with alcohol use in individuals under 50 years of age (ps ≤ .05), but not in individuals over 50 years of age (ps ≥ 0.05). Gender moderated the association between past-year moderate PA and alcohol use (ps<.001). The relation was stronger in males (β=.72) than in females (β=.41). Each of the findings remained significant even when controlling for demographics, psychiatric variables, and other potential confounds.

CONCLUSION

Among the American population of adults, age appears to moderate the relationship between vigorous PA and alcohol use, whereas gender appears to moderate the relationship between moderate PA and alcohol use. These findings shed light on the underlying mechanisms that may account for increased alcohol use in exercisers and may have clinical implications for alcohol screening and interventions in adults who lead active lifestyles.

Activation of the G(s) G protein-coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive G(s) signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive G(s) activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive G(s) signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm(3) (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous G(s) activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients.

Treatment decisions associated with ductal carcinoma in situ (DCIS), including the decision to undergo breast reconstruction, may be more problematic for Latinas due to access and language issues. To help understand the factors that influence patients' receipt of reconstruction following mastectomy for DCIS, we conducted a population-based study of English- and Spanish-speaking Latina and non-Latina white women from 35 California counties. The objectives of this study were to identify the role of ethnicity and language in the receipt of reconstruction, the relationship between system-level factors and the receipt of reconstruction, and women's reasons for not undergoing reconstruction. Women aged 18 and older, who self-identified as Latina or non-Latino white and were diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions encompassing 35 counties. Approximately 24 months after diagnosis, they were surveyed about their DCIS treatment decisions. Survey data were merged with CCR records to obtain tumor and treatment data. The survey was successfully completed by 745 women, 239 of whom had a mastectomy and represent the sample included in this study. Whites had a higher completion rate than Latinas (67 and 55%, respectively). Analysis included descriptive statistics and logistic regression modeling. Mean age was 54 years. A greater proportion of whites had reconstruction (72%) compared to English-speaking Latinas (69%) and Spanish-speaking Latinas (40%). Multivariate analysis showed that women who were aged 65 and older, unemployed, and had a lower ratio of plastic surgeons in their county were less likely to have reconstructive surgery after mastectomy. The most frequent reasons mentioned not to receive reconstruction included lack of importance and desire to avoid additional surgery. Although ethnic/language differences in treatment selection were observed, multivariable analysis suggests that these differences could be explained by differential employment levels and geographic availability of plastic surgeons.

The relative contributions of circulating and locally produced IGF-I in growth remain controversial. The majority of circulating IGF-I is produced by the liver, and numerous mouse models have been developed to study the endocrine actions of IGF-I. A common drawback to these models is that the elimination of circulating IGF-I disrupts a negative feedback pathway, resulting in unregulated GH secretion. We generated a mouse with near total abrogation of circulating IGF-I by disrupting the GH signaling mediator, Janus kinase (JAK)2, in hepatocytes. We then crossed these mice, termed JAK2L, to GH-deficient little mice (Lit). Compound mutant (Lit-JAK2L) and control (Lit-Con) mice were treated with equal amounts of GH such that the only difference between the two groups was hepatic GH signaling. Both groups gained weight in response to GH but there was a reduction in the final weight of GH-treated Lit-JAK2L vs. Lit-Con mice. Similarly, lean mass increased in both groups, but there was a reduction in the final lean mass of Lit-JAK2L vs. Lit-Con mice. There was an equivalent increase in skeletal length in response to GH in Lit-Con and Lit-JAK2L mice. There was an increase in bone mineral density (BMD) in both groups, but Lit-JAK2L had lower BMD than Lit-Con mice. In addition, GH-mediated increases in spleen and kidney mass were absent in Lit-JAK2L mice. Taken together, hepatic GH-dependent production of IGF-I had a significant and nonredundant role in GH-mediated acquisition of lean mass, BMD, spleen mass, and kidney mass; however, skeletal length was dependent upon or compensated for by locally produced IGF-I.