The [2Fe-2S]-containing transcription factor SoxR is conserved in diverse bacteria. SoxR is traditionally known as the regulator of a global oxidative stress response in Escherichia coli, but recent studies suggest that this function may be restricted to enteric bacteria. In the vast majority of nonenterics, SoxR is predicted to mediate a response to endogenously produced redox-active metabolites. We have examined the regulation and function of the SoxR regulon in the model antibiotic-producing filamentous bacterium Streptomyces coelicolor. Unlike the E. coli soxR deletion mutant, the S. coelicolor equivalent is not hypersensitive to oxidants, indicating that SoxR does not potentiate antioxidant defense in the latter. SoxR regulates five genes in S. coelicolor, including those encoding a putative ABC transporter, two oxidoreductases, a monooxygenase, and a possible NAD-dependent epimerase/dehydratase. Expression of these genes depends on the production of the benzochromanequinone antibiotic actinorhodin and requires intact [2Fe-2S] clusters in SoxR. These data indicate that actinorhodin, or a redox-active precursor, modulates SoxR activity in S. coelicolor to stimulate the production of a membrane transporter and proteins with homology to actinorhodin-tailoring enzymes. While the role of SoxR in S. coelicolor remains under investigation, these studies support the notion that SoxR has been adapted to perform distinct physiological functions to serve the needs of organisms that occupy different ecological niches and face different environmental challenges.

BackgroundIn a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated.ResultsWe found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF.ConclusionsGiα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.

What is already known on this topic? Filipino American adults have a higher risk of developing type 2 diabetes than White adults, other Asian adults, and residents of the Philippines despite their relatively low body weight.What is added by this report? Among Filipino American adults, the prevalence of overweight and obesity increased from the first to the 3rd generation, whereas rates of type 2 diabetes were only significantly higher in the 2nd generation than the 1st generation.What are the implications for public health practice? Overweight and obesity, diet quality, and other lifestyle factors may explain the higher type 2 diabetes rates among 2nd-generation Filipino American adults. Culturally appropriate interventions are needed to reduce lifestyle factors that result in high rates of type 2 diabetes among Filipino immigrants and their descendants.

This study investigated the relation of diet quality indexes (DQI) with breast cancer incidence among women from the Multiethnic Cohort (MEC). Participants completed a questionnaire with a validated food frequency questionnaire. Scores for Healthy Eating Index 2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean diet score (aMED), and Dietary Approaches to Stop Hypertension (DASH) were divided into quintiles (Q1-Q5). Cox regression was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for DQIs and breast cancer risk adjusted for known risk factors. The respective HRs for Q5 vs. Q1 were: 1.06 (95% CI, 0.98-1.14) for HEI-2015, 0.96 (95% CI, 0.90-1.04) for AHEI-2010, 1.01 (95% CI, 0.94-1.09) for aMED, and 0.95 (95% CI, 0.88-1.02) for DASH (p trend >0.05 for all). However, overweight and obesity were significantly associated with breast cancer incidence. Despite the null association for DQIs, diet quality may lower breast cancer risk through its positive influence on weight status.

IntroductionAlthough other studies have found evidence for perinatal health disparities among Pacific Islanders in other regions, no studies have evaluated racial/ethnic disparities in adverse perinatal health outcomes in the small US island territory of the Commonwealth of the Northern Mariana Islands (CNMI).MethodsWe used retrospective cohort data on 8,427 singleton births from 2007 to 2014 at the Commonwealth Healthcare Corporation (CHCC), the only hospital in the CNMI. We used multivariate logistic regression to estimate risk for preterm birth (<37 weeks) and macrosomia (>4,000 g) among the racial/ethnic groups in the CNMI.ResultsIndigenous CNMI mothers (Chamorros and Carolinians, hereinafter Chamorro/Carolinian) and other Pacific Islander mothers were significantly more likely to have a preterm birth than Chinese mothers (adjusted odds ratio [AOR] = 2.7; 95% confidence interval [CI], 2.0–3.6 for Chamorro/Carolinians and AOR = 2.9; 95% CI, 2.1–4.1 for other Pacific Islanders). Additionally, Chamorro/Carolinian mothers and other Pacific Islander mothers were also significantly more likely to deliver babies with macrosomia (AOR = 2.4; 95% CI, 1.7–3.5 and 2.3; 95% CI 1.4–3.6 respectively) than Filipino mothers.ConclusionAlthough underlying causes for these disparities are still unknown, these findings add to the limited knowledge on maternal and neonatal health among Pacific Islanders and provide support for further research and intervention development to aid in reducing racial/ethnic disparities of perinatal health in the CNMI.

Objectives Healthy eating patterns assessed by diet quality indexes (DQIs) have been related to lower risk of cancer incidence and mortality; however, the association between DQIs and breast cancer risk is still unclear. This study investigated the relation of DQIs with breast cancer incidence among diverse women from the Multiethnic Cohort (MEC). Methods At baseline (1993–1996), 101,291 female participants of five major racial/ethnic groups (African Americans, Native Hawaiians, Japanese Americans, Latinos and whites) aged 45–75 years completed a survey including a validated food frequency questionnaire. Scores for Healthy Eating Index 2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean diet score (aMED), and Dietary Approaches to Stop Hypertension (DASH) score were calculated and divided into quintiles (Q1-Q5). Cox regression was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DQIs and breast cancer risk, with adjustment for known risk factors including body mass index (BMI) among others. Results During a mean follow-up of 17.4 years, 7769 breast cancer cases were identified through linkage to tumor registries. The respective HRs for Q5 vs. Q1 were: 1.06 (95% CI, 0.98–1.14) for HEI-2015, 0.96 (95% CI, 0.90–1.04) for AHEI-2010, 1.01 (95% CI, 0.94–1.09) for aMED, and 0.95 (95% CI, 0.88–1.02) for DASH. No significant dose-response relations of DQIs with breast cancer risk were observed (all Ptrend ≥ 0.07). HRs analyzed by ethnic group also resulted in null findings with no significant dose-response relations and no significant Q5 vs. Q1 associations of DQIs with breast cancer risk (all Ptrend ≥ 0.14). For example, the respective HRs for the HEI-2015 by race/ethnicity were: 0.96 (95% CI, 0.81–1.14) for African Americans, 1.15 (95% CI, 0.90–1.46) for Native Hawaiians, 1.02 (95% CI, 0.89–1.17) for Japanese, 1.08 (95% CI, 0.88–1.33) for Latinas, and 1.08 (95% CI, 0.92–1.27) for whites. Conclusions Although adherence to DQIs was not associated with breast cancer risk overall or within racial/ethnic groups, nutrition remains important in breast cancer prevention as obesity, a strong modifiable risk factor, may be influenced by diet quality. Funding Sources This work was supported by grants from the National Cancer Institute.

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