Thesis (Ph.D.)--Boston University. / The purpose of this dissertation is to set forth systematically and to analyze critically the theology of preaching of Aurelius Augustine, 345-430 A.D. Available source material was studied resulting in a subject index which disclosed the most promising lines of investigation. The dissertation deals with Augustine's theological orientation as it bears on his theology of preaching, the nature and purpose of preaching, the content of preaching, the method of preaching, and the actual preaching of Augustine. The guiding principle of Augustine's theology of preaching in his understanding of God as personal being. The God of the Christian revelation both is and cares for man. As the ultimate, God commands ment to preach through authorities He ordains in history: Scripture, church, and reason. As personal being in His ultimate reality, He compels men to preach. Men are moved to witness to His gracious love supremely demonstrated in Jesus Christ. The purpose of preaching is rooted in the nature of God. Theology of preaching proceeds from this revealed truth. It begins in metaphysics and issued in history. Theology of preaching is concerned throughout with God and man as personal beings, existing in an inviolable Creator/creature relationship in which God interacts with man without absorbing him. Preaching in instruction in the Christian faith. Christians preach because the God revealed in Jesus Christ commands and compels them to preach. The content of Christian preaching is the faith of the church, proceeding from belief in the Trinity, which faith is at once ultimate and existential truth. The method of preaching consists fundamentally in the personal preparation of the preacher as a Christian, the determination of the subject from Scripture, interpretation of Scripture according to sound principles, and communication to the hearers. Communication is from person to persons in the presence of God. Theology of preaching effects itself in the act of preaching for which it provides the origin and structure. Major issues of Augustine's theology of preaching are viewed in the perspective of some aspects of subsequent theological thought and homiletical method. Much later thought and practice is found to be illuminating, but revision is necessitated only in the area of Augustine's biblical exegesis. Augustine's theology of preaching is found to be biblically sound, classically Christian, and rationally coherent. [TRUNCATED]

Thesis advisor: Dominic F. Doyle / Thesis advisor: Brian Robinette / Thesis (STL) — Boston College, 2023. / Submitted to: Boston College. School of Theology and Ministry. / Discipline: Sacred Theology.

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Thesis advisor: Robert C. Bartlett / In my dissertation I seek to contribute to the revival of interest in Augustine’s political thought by attempting to uncover his doctrine of eternal law. While absent from his mature writings, including the City of God, this doctrine is central to the investigation of justice in Augustine’s early writings. After considering Augustine’s summary of this early investigation in the Confessions, the most surprising feature of which is Augustine’s insistence on the importance of specifically political questions to his mature understanding of justice, I take up the two treatments of eternal law. In the dialogue On Free Choice, the eternal law is contrasted with the temporal law and is understood in terms of the fundamental command to “order,” which means in the first place wisdom, but also “right and honorable” action. In the anti-Manichean polemic Contra Faustum, the eternal law is presented as the will of God that commands the preservation of the natural order, which means that actions are truly just insofar as they conduce to “mortal health.” I argue that these two discussions of eternal law indicate the limitations of any kind of “higher law” doctrine. On Free Choice demonstrates the difficulty of breaking free of the guidance of temporal law and its harmonization of the demands of eternal and temporal law depends on an understanding of moral virtue whose independence is rather assumed than proven. Contra Faustum shows that the natural ends of self-preservation, procreation, and civic peace are only the beginning points of moral reasoning, since the pursuit of those ends is governed by further moral criteria that cannot easily be understood in terms of nature. In the end, then, I argue that the doctrine of eternal law, while illuminating a great deal about the problems of politics and morality as Augustine encountered them, points to the crucial importance of the question of human virtue and of acquiring the prudence that provides for this virtue in light of the necessary limitations of political life. It is probably for this reason that Augustine does not return to the doctrine in his later writings and does not rely on it in his reconciliation of the two cities in the City of God. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Political Science.

The mechanisms by which epithelial progenitor cells integrate local signals to balance proliferation with differentiation and regulate patterning during lung organogenesis are still poorly understood. The Hippo pathway and its transcription co-activator Yap have recently emerged as major regulators of progenitor cell expansion and differentiation in development and cancer. Here we investigated the role of Yap signaling in the cellular and molecular events associated with lung epithelial morphogenesis and differentiation. We provide evidence that when airway epithelial tubules are forming and branching, a nuclear to cytoplasmic shift of Yap marks the boundary between the progenitors of the distal lung and the airway compartment. At this transition zone, Yap specifies a transcriptional program that controls the expression of Sox2, restricting distal gene expression and initiating an airway progenitor cell program key to generate the airway epithelium and its branched tubular structures. In Yap deficient mice, epithelial progenitors are unable to properly respond to local Tgf beta-induced cues to control levels and distribution of Sox2, resulting in expansion of the distal epithelial compartment and inability to form airways. Moreover, we show that Yap levels and phosphorylation status play a major role in regulating differentiation of airway progenitors later in development and in adult life. Analysis of YAP-interacting partners in adult airway progenitors by Mass Spectroscopy suggests phosphorylated Yap interactions with ciliome proteins. Our study reveals a crucial role for Yap in specification and differentiation of airway progenitors likely to be also relevant in regeneration-repair of the adult airway epithelium.

Dysregulated Hippo pathway signaling promotes the onset of aggressive cancers through the induced nuclear activity of yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) (YAP/TAZ). Uncontrolled nuclear YAP/TAZ activity evokes tumor-initiating properties in a range of epithelial-derived cancers, including oral and breast cancers, but their downstream targets and mechanisms of action are unclear. Recent studies have suggested that the pro-tumorigenic roles for YAP/TAZ relate to their convergence with growth factor signaling pathways. Based on these previous studies, I hypothesized that YAP/TAZ driven transcription contributes to carcinoma progression, and that cooperation with transforming growth factor β (TGFβ)-induced signals promotes aggressive oncogenic traits. In this thesis I show that dysregulated YAP localization precedes oral squamous cell carcinoma (OSCC) development, and that nuclear YAP/TAZ activity drives cell proliferation, survival, and migration in vitro, and is required for tumor growth and metastasis in vivo. Global gene expression studies in OSCC cells revealed that YAP/TAZ-mediated gene expression correlates with expression changes that occur in human OSCCs identified by “The Cancer Genome Atlas” (TCGA), many of which encode cell cycle and survival regulators. By exploring the relationship with growth factor signaling, I found that YAP/TAZ induce pro-tumorigenic events by converging with TGFβ-induced signals, particularly in breast cancer cells where TGFβ is known to promote metastatic properties. My observations indicated that YAP/TAZ are necessary for maintaining and promoting TGFβ-induced tumorigenic phenotypes in breast cancer cells, and that these phenotypes result from the cooperative activity of YAP/TAZ, the TEA domain family of transcription factors (TEADs), and TGFβ-activated SMAD2/3 in the nucleus. Genome-wide expression analyses indicated that YAP/TAZ, TEADs, and TGFβ-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by these complexes, such as the novel targets neuronal growth regulator 1 (NEGR1) and urothelial cancer associated 1 (UCA1), are necessary to maintain tumorigenic activity in metastatic breast cancer cells. Nuclear YAP/TAZ also cooperate with TGFβ signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGFβ-mediated growth inhibition. This work thus defines novel roles for YAP/TAZ in cancer, offering molecular mechanisms that may be useful for identifying and targeting YAP/TAZ-driven cancers.

Background: Extensive research has characterized the embryonic development of a four-chambered heart in mammals. After birth, mammalian cardiomyocytes undergo a transition characterized by a final cell cycle with nuclear division (karyokinesis) in the absence of cytoplasmic division (cytokinesis), generating mature binucleated cardiomyocytes. Downregulation of pro-proliferative signaling and epigenetic changes permanently ‘lock’ cardiomyocytes out of the cell cycle, and nearly all subsequent growth is accomplished via cellular hypertrophy. Before this transition, cardiomyocytes exhibit robust proliferative potential, but afterward are unable to divide. Rationale & Hypothesis: Recent evidence suggests that non-coding RNAs influence early neonatal cardiac development and hypertrophy. We hypothesize that transient expression of regulatory miRNAs may impact the neonatal heart’s transition from proliferation to hypertrophy. Results: Cardiac mRNA and miRNA were systematically analyzed using microarrays to identify targets that were transiently and significantly changing after birth. Through our analysis we identified three primary ontogenies significantly changing: metabolism, extracellular matrix remodeling, and cell cycle regulation. Global analysis of micro-RNA expression patterns during perinatal heart development identified miR-205 as a novel candidate for modulating cardiomyocyte maturation. We observed miR-205 expression undergoing a 20-fold increase from 1-day postpartum (1D) to 5D, returning to prenatal levels by 10D. It is expressed in cardiomyocytes of the epicardium, the primary location of fetal cardiomyocyte proliferation. MiR-205 targets two important cell cycle regulators: Pten phosphatase of the PI3K/AKT pathway, and Yap1 in the Hippo pathway. Both pathways have proven to be essential for proper heart development. Previous research showed that germline deletion of miR-205 results in death at 5D. To define its role in the heart, we generated an αMHC-Cre postnatal miR-205 cardiac-specific deletion mouse model. Systematic characterization of miR-205-/- hearts confirmed miR-205’s interaction with Pten and Yap1 by western blot and immunohistochemistry. Postnatal miR-205-/- hearts exhibit Hippo pathway dysregulation, increased cardiomyocyte number, more actively cycling cardiomyocytes beyond 7D, and no difference in binucleation. We also generated a DOX-inducible cardiac-specific miR-205 over-expression mouse model. Perinatal miR-205OE hearts expedited the transitional period, with more cardiomyocytes present at 5D and no difference at 14D. These hearts show increased Hippo signaling immediately after birth, suggesting compensatory mechanisms to ensure sufficient cardiomyocyte number. Conclusions: Our data strongly supports miR-205 as a regulator of cardiomyocyte maturation in the neonatal heart, by promoting the neonatal cardiomyocyte transition from hyperplastic to hypertrophic growth. In turn, miR-205’s antiproliferative properties originate in part from suppressing the expression of Pten and Yap1.

In his three major polemical campaigns, that is, against the Manichees, Donatists and Pelagians, Augustine used imagery derived from medicine and was, in tum influenced by the language he used. While much of the language of sickness and disease remained conventional, some usages came to bear significant theological weight, notably infirmitas and contagio. The former became a designation for the culpable weakness affecting each member of the human race since the Fall. The latter became a technical term for the transmission of original sin associated with concupiscentia. Sickness imagery assumes the analogy of the soul and body, advancing his project to integrate the two parts of the human person. It also enabled him to discuss humanity's fallen nature without slipping into Manichaean determinism or Pelagian autonomy. Finally, sickness imagery enabled Augustine to suspend the tension between the inherited guilt and free-will in readily accessible metaphor. Images of health and healing also helped Augustine sustain tensions in his thought. But even more significantly, the image of Christ the Physician proved critical throughout his polemical career. Against the Manichees it is the Divine Physician who lays out the stages of sacred history according to a great therapeutic strategy for the human race. Against the Donatists it is the wisdom of the Physician who prescribes painful means of cure which is urged against Donatist complaints of persecution. Finally, against the Pelagians, Christus Medicus becomes a technical soteriological term. This family of metaphors, drawn from the Scriptures, classical literature, pagan religion and common experience appear time and time again. While they may have become commonplace in the writings of other Christian authors, in Augustine's polemical theology they came to shape and inform key aspects of his thought.

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This study provides a new reading of Geoffrey Chaucer’s Prioress’s Tale and considers its purpose within the context of the Canterbury Tales. I argue that the Tale, as an exemplum, demonstrates the dangers of tale-telling, and exposes the moral discrepancies of the Canterbury tale-telling competition and the pilgrims’ use of stories as verbal assaults against one another. I argue that the Tale condemns the unchristian-like “actions” of the Christians within its frame as they respond to the clergeon’s murder; the Tale’s ending presents a cathartic response from this congregation, which indicates their understanding of the clergeon’s martyrdom. It also provokes a similar response from the Canterbury pilgrims, which serves to silence them, and to create a paradox that disrupts possible responses to the Tale. Further, Chaucer’s Retraction at the end of the Tales is intended to silence the poet’s critics through the creation of a similar paradox.