Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells

Background In 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. Results We 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. Conclusions Giα 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.Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; ChinaFil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados UnidosFil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Feng, Gen-Sheng. University of California at San Diego; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados UnidosFil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados Unido

Disparities in Adverse Perinatal Outcomes Among Pacific Islanders in the Commonwealth of the Northern Mariana Islands.

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

Disparities in Adverse Perinatal Outcomes Among Pacific Islanders in the Commonwealth of the Northern Mariana Islands.

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

Expression of the Streptomyces coelicolor SoxR Regulon Is Intimately Linked with Actinorhodin Production▿ †

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

Management information systems plan for Dutch Boy Philippines, Inc. (DB-MIS)

The Management Information Systems Plan for Dutch Boy Philippines is a three-year plan directed to achieve maximum use of information resources as well as the different business applications of the company. This will cover the departments namely: Technical, Production, Quality Assurance, Materials Management, Engineering, Production Planning and Control, Personnel, Purchasing, Administration, Marketing, Credit and Collection. Accounting, Sales, Customer Services, Technical Services, Project Management, Internal Audit, Management Information Systems, and Finished Goods Warehouse. The MIS plan supports both the middle and the top management as it streamlines their operations and eliminates the redundancy to further aid in their decision-making. In addition, this will evaluate the overall performance of their operations and finally, generate a recommendation for the company\u27s improvement