Master Role Research Articles

Nil’s and Iosif’s Rhetoric of Starchestvo

The ideal master-disciple relationship or starchestvo associated with Paisii Velichkovskii (1722-92) and his epigones rests on a complex monastic legacy stretching back to Christian Antiquity and includes early Russia’s two greatest native writing elders, Nil Sorskii (1433/4-1508) and Iosif Volotskii (1439/40-1515). Pedagogical networks, circulation of texts, structural continuities, and workings of the hierarchy’s nomenklatura system in the 16th century contributed to the solidification of Nil’s and Iosif’s literary and institutional legacy in which this rhetoric was embedded and expressed. Their genres and sub-genres combine testament, regulation, sermon, systematic exposition, polemic, hagiography, and epistle, all freely utilizing maxims, enthymemes (rhetorical syllogisms, sometimes as questions), emotional appeals, scare stories, and insults, as well as poetic imagery. Both recognize the disciples’ active role in master’s success, as they address a variety of audiences. Nil’s spiritual treatise discusses the need for the “reliable” teacher, while his epistles place each recipient in his proper relationship to authority. Iosif directly speaks in turn to the pastor and the senior elders and officials of their responsibilities; he shows the multiplicity of authority lines within the large cenobium; and he polemically defends formal structures and discipline. His hagiography depicts the ideal elder as advising hesychast-hermit, community disciplinarian, and politically indispensible supplicant to God. Crucial for our overall sense of starchestvo, Iosif’s applies the New Testament maxims concerning “binding” and “loosing” to the teacher as teacher, while Nil’s Tradition/Instruction, specifying that only those qualified to listen and speak guide others, bridges to the modern era.

Inventing Sempringham: Gilbert of Sempringham and the Origins of the Role of the Master (review)

Inventing Sempringham: Gilbert of Sempringham and the Origins of the Role of the Master (review)

Targeting rapid action of sex-steroid receptors in breast and prostate cancers

Human breast and prostate cancers are complex diseases caused by the progressive accumulation of gene mutations combined with epigenetic deregulation of critical genes and derangement of signaling pathways. Compelling evidence indicates that steroid hormones elicit non-genomic responses in cytoplasm of target cells. In this cellular location, steroid-coupled receptors recruit signaling effectors or scaffold proteins, thereafter activating multiple pathways leading to proliferation, survival, migration and invasiveness. Thus, the immediate challenge is the dissection of key upstream events regulating steroid response in target tissues to prevent progression and improve treatment of breast and prostate cancers. Progress in our understanding of the molecular mechanisms that play a master role in these cancers has strongly stimulated the search for specific inhibitors of key signaling molecules. This review aims to give an up-to-date report of the complex network regulating non-genomic action of steroid hormones in target cells. The final section highlights recent advances from our laboratory and future directions in alternative approaches for the treatment of breast and prostate cancers.

The Twain Shall Meet

This essay argues for an interdisciplinary, team-taught approach to the Introduction to Graduate Studies course in which faculty from literary and rhetoric/writing studies model the intersections of both fields through course texts, assignments, and theoretical frameworks. The authors also discuss the role of terminal master's programs in English and the need for graduate writing instruction.

Interaction of mammalian end binding proteins with CAP-Gly domains of CLIP-170 and p150glued

End binding proteins (EBs) track growing microtubule ends and play a master role in organizing dynamic protein networks. Mammalian cells express up to three different EBs (EB1, EB2, and EB3). Besides forming homodimers, EB1 and EB3 also assemble into heterodimers. One group of EB-binding partners encompasses proteins that harbor CAP-Gly domains. The binding properties of the different EBs towards CAP-Gly proteins have not been systematically investigated. This information is, however, important to compare and contrast functional differences. Here we analyzed the interactions between CLIP-170 and p150(glued) CAP-Gly domains with the three EB homodimers and the EB1-EB3 heterodimer. Using isothermal titration calorimetry we observed that some EBs bind to the individual CAP-Gly domains with similar affinities while others interact with their targets with pronounced differences. We further found that the two types of CAP-Gly domains use alternative mechanisms to target the C-terminal domains of EBs. We succeeded to solve the crystal structure of a complex composed of a heterodimer of EB1 and EB3 C-termini together with the CAP-Gly domain of p150(glued). Together, our results provide mechanistic insights into the interaction properties of EBs and offer a molecular framework for the systematic investigation of their functional differences in cells.

FoxM1: A Master Regulator of Tumor Metastasis

The FoxM1 transcription factor gene is overexpressed in cancer. Its expression is stimulated by oncogenic signaling pathways and reactive oxygen species. It is also a target of regulation by the tumor suppressor genes. The transcriptional activity of FoxM1 depends upon activation by cyclin and cyclin-dependent kinases as well as Plk1. FoxM1 stimulates expression of several genes involved in the cell cycle progression. Moreover, it supports proliferation of tumor cells by stimulating expression of the antioxidant genes and reducing oxidative stress. A new study provides evidence that FoxM1, in the absence of its inhibitor, the tumor suppressor Arf, drives metastasis of hepatocellular carcinoma (HCC). It induces an epithelial-mesenchymal-like transition phenotype in HCC cells, increases cell migration, and induces premetastatic niche at the distal organ of metastasis. FoxM1 directly activates genes involved in multiple steps of metastasis. In this review, we discuss the evidence for a master regulatory role of FoxM1 in tumor metastasis.

In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells

BackgroundLGD1069 (Targretin®) is a selective retinoid X receptor (RXR) ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes.MethodsHuman umbilical vein endothelial cells (HUVECs) were used for in vitro study. MTT assay and Sulforhodamine B assay were used for cell viability assay; the tube formation assay was used to investigate the effect of LGD1069 on angiogenesis in vitro. In vitro adhesion, migration and invasion of HUVEC cells were analyzed by Matrigel adhesion, migration and invasion assay. Gene expressions were measured by RT-PCR and Western blot analysis.ResultsOur data showed here that LGD1069 inhibited the activation of TGF-β/Smad pathway significantly. Furthermore, it was demonstrated that expression of Runx2 was suppressed pronouncedly during incubation with LGD1069. Runx2 is a DNA-binding transcription factor which plays a master role in tumor-induced angiogenesis and cancer cells metastasis by interaction with the TGF-β/Smad pathway of transcriptional modulators.ConclusionsOur results suggested that LGD1069 may impair angiogenic and metastatic potential induced by tumor cells through suppressing expression of Runx2 directly on human endothelial cells, which may point out new pathway through which LGD1069 display anti-angiogenic properties, and provide new molecular evidence to support LGD1069 as a potent anti-metastatic agent in cancer therapy.

Targeting rapid action of sex-steroid receptors in breast and prostate cancers

Human breast and prostate cancers are complex diseases caused by the progressive accumulation of gene mutations combined with epigenetic deregulation of critical genes and derangement of signaling pathways. Compelling evidence indicates that steroid hormones elicit non-genomic responses in cytoplasm of target cells. In this cellular location, steroid-coupled receptors recruit signaling effectors or scaffold proteins, thereafter activating multiple pathways leading to proliferation, survival, migration and invasiveness. Thus, the immediate challenge is the dissection of key upstream events regulating steroid response in target tissues to prevent progression and improve treatment of breast and prostate cancers. Progress in our understanding of the molecular mechanisms that play a master role in these cancers has strongly stimulated the search for specific inhibitors of key signaling molecules. This review aims to give an up-to-date report of the complex network regulating non-genomic action of steroid hormones in target cells. The final section highlights recent advances from our laboratory and future directions in alternative approaches for the treatment of breast and prostate cancers.

Peroxisome Proliferator-activated Receptor-γ Coactivator-1α Controls Transcription of the Sirt3 Gene, an Essential Component of the Thermogenic Brown Adipocyte Phenotype

Sirt3 (silent mating type information regulation 2, homolog 3), a member of the sirtuin family of protein deacetylases with multiple actions on metabolism and gene expression is expressed in association with brown adipocyte differentiation. Using Sirt3-null brown adipocytes, we determined that Sirt3 is required for an appropriate responsiveness of cells to noradrenergic, cAMP-mediated activation of the expression of brown adipose tissue thermogenic genes. The transcriptional coactivator Pgc-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) induced Sirt3 gene expression in white adipocytes and embryonic fibroblasts as part of its overall induction of a brown adipose tissue-specific pattern of gene expression. In cells lacking Sirt3, Pgc-1α failed to fully induce the expression of brown fat-specific thermogenic genes. Pgc-1α activates Sirt3 gene transcription through coactivation of the orphan nuclear receptor Err (estrogen-related receptor)-α, which bound the proximal Sirt3 gene promoter region. Errα knockdown assays indicated that Errα is required for full induction of Sirt3 gene expression in response to Pgc-1α. The present results indicate that Pgc-1α controls Sirt3 gene expression and this action is an essential component of the overall mechanisms by which Pgc-1α induces the full acquisition of a brown adipocyte differentiated phenotype.

Myocyte Enhancer Factor-2 Interacting Transcriptional Repressor (MITR) Is a Switch That Promotes Osteogenesis and Inhibits Adipogenesis of Mesenchymal Stem Cells by Inactivating Peroxisome Proliferator-activated Receptor γ-2

EZH2, a catalytic subunit of Polycomb-repressive complex 2 (PRC2), is a histone lysine methyltransferase that methylates lysine 27 of histone H3, resulting in gene silencing. It has been shown that EZH2 plays a pivotal role in fostering self-renewal and inhibiting the differentiation of embryonic stem cells. Mesenchymal stem cells (MSCs) can be induced to differentiate into adipogenic and osteogenic lineages, which are mutually exclusive. However, it is not clear whether the molecular events of EZH2-mediated epigenetic silencing may coordinate differentiation between osteoblasts and adipocytes. Disruption of the balance between adipogenesis and osteogenesis is associated with many diseases; thus, identifying a switch that determines the fate of MSC is critical. In this study, we used EZH2-ChIP-on-chip assay to identify differential EZH2 targets in the two differentiation stages on a genome-wide scale. After validating the targets, we found that myocyte enhancer factor-2 interacting transcriptional repressor (MITR)/HDAC9c was expressed in osteoblasts and greatly decreased in adipocytes. We demonstrated that MITR plays a crucial role in the acceleration of MSC osteogenesis and attenuation of MSC adipogenesis through interaction with peroxisome proliferator-activated receptor (PPAR) γ-2 in the nucleus of osteoblasts, which interrupts PPARγ-2 activity and prevents adipogenesis. Together, our results demonstrated that MITR plays a master switch role to balance osteogenic and adipogenic differentiation of MSCs through regulation of PPARγ-2 transcriptional activity.

Inhibiting aberrant Stat3 function with molecular therapeutics

Aberrantly activated signal transducer and activator of transcription 3 (Stat3) protein plays a master regulatory role in the progression and survival of human cancers through the upregulation of target protooncogenes. Numerous human cancers, including breast, ovarian, prostate, leukemia, lymphoma, multiple myeloma, and brain cancers have been shown to harbor constitutively active Stat3 protein resulting in the expression of protooncogenes. The transcriptionally active Stat3-Stat3 protein homodimer has been extensively targeted as a means to suppress the aberrant Stat3 function in human cancer. This review will outline the recent progress made toward identifying drug-like compounds capable of effectively inhibiting aberrant Stat3 signaling through the disruption of Stat3 protein-protein interactions.

Dilemma: The Art Teacher as a Liberal Educator

This paper discusses the dilemma facing the art teacher as a liberal educator. The author first reviews the evolution of liberal education from ancient times, through the Renaissance to modern times and discusses, through an extensive bibliography, ancient and modern theories which have impacted on the concept of “liberalism,” examining notions such as tolerance, individualism and autonomy which constitute the pillars of liberalism. The author discusses the contributions of philosophers and sociologists such as Thomas Hobbes, John Stuart Mill, Isaiah Berlin, and Will Kymlicka and then examines the two main approaches to liberalism: philosophical liberalism and political liberalism. The different emphases placed by these two approaches, on the individual and the group respectively, form the basis of the dilemma which faces the art teacher as a liberal educator. In order to understand the dilemma, the author draws a parallel between the two approaches and the role of the traditional art studio master and art educator. The goals of the studio master, who is devoted to the development of the individual, accord with philosophical liberalism, while those of the art educator, who is obliged to adhere to the demands of a school system, accord with political liberalism, which stresses equality for all. The ideal, says the author, resides in an amalgam of the two approaches and is symbolized in the term “artist-teacher” but she asks whether it is possible to truly merge the two approaches, at the same level, in the teaching process.

Targeting rapid action of sex steroid receptors in breast and prostate cancers

Human breast and prostate cancers are complex diseases caused by the progressive accumulation of gene mutations combined with epigenetic deregulation of critical genes and derangement of signaling pathways. Compelling evidence indicates that steroid hormones elicit non-genomic responses in cytoplasm of target cells. In this cellular location, steroid-coupled receptors recruit signaling effectors or scaffold proteins, thereafter activating multiple pathways leading to proliferation, survival, migration and invasiveness. Thus, the immediate challenge is the dissection of key upstream events regulating steroid response in target tissues to prevent progression and improve treatment of breast and prostate cancers. Progress in our understanding of the molecular mechanisms that play a master role in these cancers has strongly stimulated the search for specific inhibitors of key signaling molecules. This review aims to give an up-to-date report of the complex network regulating non-genomic action of steroid hormones in target cells. The final section highlights recent advances from our laboratory and future directions in alternative approaches for the treatment of breast and prostate cancers.

Hypoxia and Hypoxia-Inducible Factors: Master Regulators of Metastasis

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with poor prognosis. Hypoxia increases tumor glycolysis, angiogenesis, and other survival responses, as well as invasion and metastasis by activating relevant gene expressions through hypoxia-inducible factors (HIF). HIF-1α and HIF-2α undergo oxygen-dependent regulation, and their overexpression is frequently associated with metastasis and poor clinical outcomes. Recent studies show that each step of the metastasis process, from the initial epithelial-mesenchymal transition to the ultimate organotropic colonization, can potentially be regulated by hypoxia, suggesting a master regulator role of hypoxia and HIFs in metastasis. Furthermore, modulation of cancer stem cell self-renewal by HIFs may also contribute to the hypoxia-regulated metastasis program. The hypoxia-induced metastatic phenotype may be one of the reasons for the modest efficacy of antiangiogenic therapies and may well explain the recent provocative findings that antiangiogenic therapy increased metastasis in preclinical models. Multiple approaches to targeting hypoxia and HIFs, including HIF inhibitors, hypoxia-activated bioreductive prodrugs, and gene therapies may become effective treatments to prevent or reduce metastasis.

Multidisciplinary Teaching - Changing Collaboration during Building Design

Traditionally the design phase was carried out by one single person – the master builder. Industrialization and technical development led to a split of the role of the design master into two: the architect and the engineer. Today, demands on functionality such as energy and cost efficiency led to an increasing need of functioning collaboration in large teams during the design phase; as well as a need of new work methods within the process. This calls for employees who are experienced in collaborating in interdisciplinary teams. To fulfill this demand a multidisciplinary course in “Advanced building design” has been developed at the Technical University of Denmark. The goal of the course is to provide training in teamwork at the final stage of the engineering education. The course has been carried out twice. It was held by a multidisciplinary team of professors in periods 2008/09 and 2009/10. The team of professors and the student teams had similar working conditions. These teams were subject of a questionnaire investigation on collaboration and team work. The study has the following findings. Collaboration can be learned and improves in time. It is shown that the team leader is not necessarily to be found within on specific profession. The team-structure was generally flat and decisions were mostly made in consensus. It is worthwhile to offer a multidisciplinary course and give engineering students experience in collaboration methods.

Combining Master and Apprentice Roles: Potential for Learning in Distributed Manufacturing Networks

The purpose of this paper is to explore possible effects for learning when a manufacturing plant takes a double role, as being both master plant and apprentice plant, in a globally distributed industrialization process. Industrialization is here understood as the process of preparing new products for volume manufacturing. Two research questions are addressed. The first is what characterizes the dual roles. The second concerns how the dual roles affect knowledge integration and learning processes, and whether this arrangement facilitates learning between master and apprentice. Based on a study of a global telecom equipment company, the paper provides insights into some of the challenges and effects of dynamic switching of roles. By separating the network function from the strategic role of the plant, the study identifies four options for learning. The case adds to the literature on learning in manufacturing networks and to previous research on how distributed processes affect innovation capability.

A educação dos leigos no reino visigodo: reflexões sobre a Vita Sancti Aemiliani

Laymen education in the Visigothic kingdom: reflection on the Vita Sancti Aemiliani. The intention of this article is to study laymen education in the 7 th century Visigothic kingdom, starting from the assumption that, faced with the ecclesiastical reorganization under way, the educational process would identify with the work of Christianization. In that sense, it is understood that it would have manifested in several social spaces. To explain this question, we analyze a hagiography produced in the 7 th century by the bishop Braulio of Saragossa, Vita Sancti Aemiliani. In investigating this document, we observe its pedagogical character, as well as traces of the affirmation of an educational model that especially values the role of master.

Antler development and coupled osteoporosis in the skeleton of red deer Cervus elaphus: expression dynamics for regulatory and effector genes

Antlers of deer display the fastest and most robust bone development in the animal kingdom. Deposition of the minerals in the cartilage preceding ossification is a specific feature of the developing antler. We have cloned 28 genes which are upregulated in the cartilaginous section (called mineralized cartilage) of the developing ("velvet") antler of red deer stags, compared to their levels in the fetal cartilage. Fifteen of these genes were further characterized by their expression pattern along the tissue zones (i.e., antler mesenchyme, precartilage, cartilage, bone), and by in situ hybridization of the gene activities at the cellular level. Expression dynamics of genes col1A1, col1A2, col3A1, ibsp, mgp, sparc, runx2, and osteocalcin were monitored and compared in the ossified part of the velvet antler and in the skeleton (in ribs and vertebrae). Expression levels of these genes in the ossified part of the velvet antler exceeded the skeletal levels 10-30-fold or more. Gene expression and comparative sequence analyses of cDNAs and the cognate 5' cis-regulatory regions in deer, cattle, and human suggested that the genes runx2 and osx have a master regulatory role. GC-MS metabolite analyses of glucose, phosphate, ethanolamine-phosphate, and hydroxyproline utilizations confirmed the high activity of mineralization genes in governing the flow of the minerals from the skeleton to the antler bone. Gene expression patterns and quantitative metabolite data for the robust bone development in the antler are discussed in an integrated manner. We also discuss the potential implication of our findings on the deer genes in human osteoporosis research.

Genetic manipulation of individual somatic mammary cells in vivo reveals a master role of STAT5a in inducing alveolar fate commitment and lactogenesis even in the absence of ovarian hormones

Assessing the molecular control of development and cell fate in individual cells in the intact mammary epithelium has not been possible to date. By exploiting an intraductal retrovirus (RCAS)-mediated gene delivery method to introduce a marker gene, we found that ductal epithelial cells are turned over with a half time of approximately 1 month in adult virgin mice. However, following RCAS-mediated introduction of a constitutively activated STAT5a ( caSTAT5a), caSTAT5a-activated ductal epithelial cells expand and replace other cells in the epithelium, eventually forming a mammary gland resembling that in a late pregnant mouse, suggesting that STAT5a activation alone is sufficient to mediate pregnancy-induced mammary cell expansion, alveolar cell fate commitment, and lactogenesis. Furthermore, such caSTAT5a-induced alveolar differentiation does not require ovarian functions, although caSTAT5a-induced cell proliferation is partly reduced in ovariectomized mice. In conclusion, in this first report of studying the developmental role of a gene in a few cells in a normally developed virgin mammary ductal tree, STAT5a activation causes alveolar fate commitment and lactogenesis, and with the help of ovarian hormones, drives alveolar expansion.

Obestatin inhibits dopamine release in rat hypothalamus

We have investigated the effects of the gastric peptide obestatin injected into the arcuate nucleus of the rat hypothalamus on the hypothalamic mRNA expression of peptides which play master roles as feeding behavior modulators. We have also evaluated the effects of obestatin on dopamine, norepinephrine and serotonin release from rat hypothalamic synaptosomes in vitro. After 4 daily intrahypothalamic injections of obestatin (1 nmol/kg), we recorded a significant reduction of daily caloric intake and body weight gain. Gene expressions of either anorexigenic (cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, proopiomelanocortin) or orexigenic (agouti-related peptide, neuropeptide Y, orexin-A) peptide mRNAs in the hypothalamus, as evaluated by real-time quantitative PCR, were not different in respect to vehicle treated rats. Moreover, ghrelin/obestatin prepropeptide gene expression in the hypothalamus was not affected by obestatin treatment. In hypothalamic synaptosomes perfused with obestatin (1–100 nM), we found a dose-dependent inhibition of depolarization-induced dopamine release, while norepinephrine and serotonin releases were not modified by obestatin treatment. When ghrelin (1 nM) and obestatin (1 nM) were co-perfused, we observed that ghrelin reversed obestatin-induced inhibition of dopamine release, and obestatin was able to block ghrelin-induced inhibition of serotonin release. We can conclude that obestatin plays an anorectic role in the hypothalamus which could be partially mediated by the acute inhibition of dopamine release, with the possible involvement of antagonism of the hypothalamic serotonin inhibitory effects of ghrelin.