Estrogen sulfotransferase (sult1e1) expression and function in mcf10a-series breast epithelial cells: role as a modifier of breast carcinogenesis and regulation by proliferation state

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. TaqMan Gene Expression assays were used to profile the mRNA expression of estrogen receptor (ERα and ERβ) and estrogen metabolism enzymes including cytosolic sulfotransferases (SULT1E1, SULT1A1, SULT2A1, and SULT2B1), steroid sulfatase (STS), aromatase (CYP19), 17β-hydroxysteroid dehydrogenases (17βHSD1 and 2), CYP1B1, and catechol-O-methyltransferase (COMT) in an MCF10A-derived lineage cell culture model for basal-like human breast cancer progression and in ERα-positive luminal MCF7 breast cancer cells. Low levels of ERα and ERβ mRNA were present in MCF10A-derived cell lines. SULT1E1 mRNA was more abundant in confluent relative to subconfluent MCF10A cells, a non-tumorigenic proliferative breast disease cell line. SULT1E1 was also expressed in preneoplastic MCF10AT1 and MCF10AT1K.cl2 cells, but was markedly repressed in neoplastic MCF10A-derived cell lines as well as in MCF7 cells. Steroid-metabolizing enzymes SULT1A1 and SULT2B1 were only expressed in MCF7 cells. STS and COMT were widely detected across cell lines. Pro-estrogenic 17βHSD1 mRNA was most abundant in neoplastic MCF10CA1a and MCF10DCIS.com cells, while 17βHSD2 mRNA was more prominent in parental MCF10A cells. CYP1B1 mRNA was most abundant in MCF7 cells. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) induced SULT1E1 and CYP19 mRNA but suppressed CYP1B1, STS, COMT, 17βHSD1, and 17βHSD2 mRNA in MCF10A lineage cell lines. In MCF7 cells, TSA treatment suppressed ERα, CYP1B1, STS, COMT, SULT1A1, and SULT2B1 but induced ERβ, CYP19 and SULT2A1 mRNA expression. The results indicate that relative to the MCF7 breast cancer cell line, key determinants of breast estrogen metabolism are differentially regulated in the MCF10A-derived lineage model for breast cancer progression. We recently reported that SULT1E1 expression is low in pre-confluent MCF10A breast epithelial cells but increases when the cells become confluent. Pulse-chase labeling experiments with bromouridine demonstrated that the confluence-mediated increase in SULT1E1 expression was due to increased mRNA synthesis. Because aryl hydrocarbon receptor (AhR) activation has been shown to suppress SULT1E1 expression and loss of cell-cell contact has been shown to activate AhR in other cell types, we tested whether the confluency-associated changes in SULT1E1 expression were mediated by the AhR. Relative to confluent MCF10A cells, pre-confluent cells had higher levels of CYP1A1 mRNA and greater activation of an AhR-responsive luciferase reporter, demonstrating that AhR was active in the pre-confluent cells. AhR and aryl hydrocarbon receptor nuclear translocator mRNA and protein levels were also higher in pre-confluent than in confluent cultures. Treatment of pre-confluent cells with the AhR antagonist, 3\u27-methoxy-4\u27-nitroflavone (MNF), or AhR knockdown significantly increased SULT1E1 expression. MCF10A cells stably transfected with a luciferase reporter containing ~7 kb of the SULT1E1 5\u27-flanking region showed both MNF- and confluence-inducible luciferase expression. Pre-confluent cells transiently transfected with the reporter showed both MNF treatment- and AhR knockdown-mediated luciferase induction, but mutation of a computationally predicted dioxin response element (DRE) at nt -3476 did not attenuate these effects. These results demonstrate that SULT1E1 expression in MCF10A cells is transcriptionally regulated by confluency through a suppressive action of the AhR, which is not mediated through a DRE at nt -3476. Tobacco smoke has been implicated as a risk factor for breast cancer. We evaluated the effect of tobacco smoke condensate (TSC) on expression of the estrogen-inactivating enzyme SULT1E1 in the MCF10A human breast epithelial cell line. Because TSC contains components that are known aryl hydrocarbon receptor (AhR) agonists, effects of TSC treatment were compared to those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and effects on SULT1E1 expression were compared to those on CYP1A1. Treatment for 24-72 h with 0.05-10 µg/ml TSC produced concentration-dependent increases in CYP1A1 mRNA content, decreases in SULT1E1 mRNA content, and increases in expression from a transfected AhR-responsive reporter plasmid. Treatment with 10 µg/ml TSC and 30 nM TCDD produced comparable increases in CYP1A1 mRNA levels (~300-fold) and decreases in SULT1E1 mRNA levels (~90%). Treatment with the AhR antagonist 3\u27-methoxy-4\u27-nitroflavone (PD168641, at 1 µM) completely inhibited TCDD-inducible CYP1A1 expression and partially reversed TCDD-mediated SULT1E1 suppression. PD168641 also inhibited TSC-mediated CYP1A1 induction and SULT1E1 suppression as indicated by rightward shifts of the TSC concentration-response curves. These findings support a role for the AhR in TSC-mediated regulation of CYP1A1 and SULT1E1 expression in human breast epithelial cells

Reaching Out and Beyond: Making Library Centered Connections

This poster is presented at the 2012 American Library Association Annual Conference in the Anaheim Convention Center. The hub on campus, academic libraries play a significant role in promoting diversity and academic success. Library resources and services have a great impact on university’s recruitment, retention and graduation. This poster session discusses some innovative practices in outreach, effective support in student learning, diverse models in services, and successful approaches in connecting with the campus community

Form factors of decuplet baryons in a covariant quark-diquark approach

The electromagnetic and gravitational form factors of decuplet baryons are systematically studied with a covariant quark-diquark approach. The model parameters are firstly discussed and determined through comparison with the lattice calculation results integrally. Then, the electromagnetic properties of the systems including electromagnetic radii, magnetic moments, and electric-quadrupole moments are calculated. The obtained results are in agreement with experimental measurements and the results of other models. Finally, the gravitational form factors and the mechanical properties of the decuplet baryons, such as mass radii, energy densities, and spin distributions, are also calculated and discussed.Comment: 19 pages, 27 figure

Form factors of Ω−\Omega^- in a covariant quark-diquark approach

The electromagnetic and gravitational form factors of $\Omega^-$, a spin-3/2 hyperon composed of three $s$ quarks, are calculated by using a covariant quark-diquark approach. The model parameters are determined by fitting to the form factors of the lattice QCD calculations. Our obtained electromagnetic radii, magnetic moment, and electric-quadrupole moment are in agreement with the experimental measurements and some other model calculations. Furthermore, the mass and spin distributions of $\Omega^-$ from the gravitational form factors are also displayed. It is found that the mass radius is smaller than its electromagnetic ones. Finally, the interpretations of the energy density and momentum current distribution are also discussed

FROM HIGH THROUGHPUT INHIBITOR DISCOVERY TO HIGHLY EFFICIENT CELLULAR DELIVERY OF THERAPEUTIC PROTEIN AND DRUG

Ph.DDOCTOR OF PHILOSOPH

Robust approach for variable selection with high dimensional Logitudinal data analysis

This paper proposes a new robust smooth-threshold estimating equation to select important variables and automatically estimate parameters for high dimensional longitudinal data. A novel working correlation matrix is proposed to capture correlations within the same subject. The proposed procedure works well when the number of covariates p increases as the number of subjects n increases. The proposed estimates are competitive with the estimates obtained with the true correlation structure, especially when the data are contaminated. Moreover, the proposed method is robust against outliers in the response variables and/or covariates. Furthermore, the oracle properties for robust smooth-threshold estimating equations under "large n, diverging p" are established under some regularity conditions. Extensive simulation studies and a yeast cell cycle data are used to evaluate the performance of the proposed method, and results show that our proposed method is competitive with existing robust variable selection procedures.Comment: 32 pages, 7 tables, 5 figure

Distributed Leadership in University Quality Management: An Exploration in a Sino-Foreign Cooperative University in China

Along with the rapid development of Transnational Higher Education (TNE) in China, the quality of TNE has become one of the most concerning problems in academia. Most current studies only emphasise how to meet the minimum quality standards required by the home and host quality assurance accreditation bodies rather than continuously improving educational quality. This leaves a significant research gap to fill. This thesis views quality management (QM) as having two folds meaning quality assurance (QA) and quality enhancement (QE). It needs both institutional and individual efforts from formal and informal leaders through their active participation in QM through leadership activities. This thesis aims to explore this issue in China's TNE by integrating Distributed Leadership (DL) and Professional Agency (PA) to address the knowledge gap in the literature. This study employs a single case study and selects a Sino-British University as the research site. Seven formal leaders and seven faculty were interviewed. Three types of data were collected: their lived experiences in their actions, collaborations, and change activities related to QA and QE; their individual characteristics and factors about their competence and readiness; and socio-cultural factors of the university, such as policies, power relations, and culture and values. This study explores their interplays and how they shape leadership activities at individual and organisational levels. Thematic analysis is applied to analyse the collected data in order to generate themes. The results confirm the proposed theoretical framework, which illustrates a prospective QM model in TNE through the lens of DL and PA. Both QA and QE exist at the University, but the leadership agency shows QE is central, which is exercised through formal and informal leaders’ PA in developing leadership capacity, forming a shared understanding of goals in enhancing the quality of education, fostering a change culture, and building trust. Nevertheless, the PA between the two groups of participants shows divergent characteristics regarding their identity, agentic actions and competence and readiness. Formal leaders' PA focuses on building a favourable climate for educational quality at the university by setting up working procedures, policies, and mechanisms to facilitate the improvement of work practices, professional learning, collaborations, and bottom-up changes. In contrast, the faculty's PA focused on leading pedagogical changes related to learning, teaching, and research. DL demonstrates multiple formats of DL in the processes of QM. The findings highlight a bi-directional flow of influence between formal leaders and informal leaders, which is mediated by trust. Based on the results, a model is developed to illustrate the leadership distribution manifested in managing the quality at the university. Four practical recommendations are made for the university to promote DL. It needs to: focus on organisational culture and value building, support formal leaders and faculty's identity and orientations, motivate faculty's competence and engagement, and provide a supportive structure. This study has enriched the existing knowledge about educational quality in the TNE context. It bridges a knowledge gap by examining how to engage staff members, particularly faculty, by fulfilling their personal and social development needs through DL and PA. Practically, this research is insightful for the existing and potential transnational projects worldwide by offering a reference on improving the quality of their education to sustain long-term organisational development

Brain pericyte biology: from physiopathological mechanisms to potential therapeutic applications in ischemic stroke

Pericytes play an indispensable role in various organs and biological processes, such as promoting angiogenesis, regulating microvascular blood flow, and participating in immune responses. Therefore, in this review, we will first introduce the discovery and development of pericytes, identification methods and functional characteristics, then focus on brain pericytes, on the one hand, to summarize the functions of brain pericytes under physiological conditions, mainly discussing from the aspects of stem cell characteristics, contractile characteristics and paracrine characteristics; on the other hand, to summarize the role of brain pericytes under pathological conditions, mainly taking ischemic stroke as an example. Finally, we will discuss and analyze the application and development of pericytes as therapeutic targets, providing the research basis and direction for future microvascular diseases, especially ischemic stroke treatment