Perspective, Invention, and Metatheater in Renaissance Literature

This dissertation challenges the misconception of post-Reformation England as iconophobic. On the contrary, it argues that early modern English poets and playwrights adapt Continental theories and techniques from painting, translating them into their own poetic and dramatic forms. It explores how allusions to contemporary perspectival images serve as governing metaphors and structural devices for the works in which they appear. Particularly in the genre of the Elizabethan epyllion and in works by Shakespeare, it suggests that texts are designed to be read “perspectively,” to borrow Shakespeare’s coinage, so that they are open to ambiguity and multiplicity, and capable of being interpreted in conflicting or complementary ways. In chapters on the Elizabethan epyllion, it examines how the rhetorical superfluity and linguistic play of Marlowe’s Hero and Leander and the satirical experience of “curious viewing” in Marston’s Metamorphosis of Pigmalion’s Image effect a shift in the period’s understanding of artistic invention. In chapters on Shakespeare, it reveals how the modern interest in Shakespearean metatheater — where the theater draws attention to itself as theater — is in fact grounded in the contemporary language of visual perspective. It shows how Shakespeare cues his original audiences to view his plays as perspectival double images, constituted not only by the embodied characters within the fictional worlds of his plays, but also as the physical, human actors of his professional playing company in early modern London. It contends that Shakespeare’s plays become increasingly visual and perspectival, changing meaning and resonance depending on venue, after his professional playing company, the King’s Men, acquire their second playhouse, the Blackfriars. This dissertation therefore traces evolutions in aesthetics and dramatic form occasioned by contemporary developments in the period’s larger visual culture, breaking new ground on the confluences between the visual, poetic, and dramatic arts

Variants and Polymorphisms of Three Repetitive DNA Families in the Human Genome

A novel 0.6 kb LINE family in human DNA, designated L2Hs, has been described (Musich and Dykes 1986). Studies employing clone N6.4, containing three 0.6 kb segments of this family, indicate that these sequences are interspersed and moderately repetitive. Two additional variant sequences of the L2Hs family, N6.1 and N6.3, have been identified. Restriction mapping of each cloned segment indicates similarities among N6.4, N6.3 and N6.1. When the cloned DNAs were cleaved with restriction enzymes and subjected to cross-hybridization, each cloned insert produced a pattern indicating that the sequences contained in N6.1 and N6.3 are represented in at least one of the three 0.6 kb segments within the clone N6.4. Hybridization of human genomic DNA digested with KpnI or KpnI+AccI reveals differences in nuclear organization for these segments. For any particular human DNA, the hybridization patterns for each of the three probes overlap. However, these differences indicate that the inserts in N6.1 and N6.3 and one of the N6.4 inserts each represents a subset of the L2Hs LINE family. Sequence analysis of N6.1 indicates that the probability of a functional translation product from N6.1 transcript is not high. The sequence contains stop and nonsense codons in all reading frames. However, the DNA has properties suggesting a structural, non-coding role. The N6.1 sequence contains 11 regions of alternating purine and pyrimidines which can affect the three dimensional structure and, therefore, the structural behavior of the molecule. In addition, putative binding regions for microtubule-associated proteins have been identified. A cloned variant of the XbaI family of repetitive DNAs, PuHu7, was identified. Studies of its genomic organization showed a tandem arrangement similar to other, previously described members of this family. The genomic organization of a previously undescribed repetitive DNA family is also reported. This family descriptor is the clone PuHu26. Hybridization of genomic DNA digested with HindIII showed that sequences homologous to PuHu26 are tandemly organized. Genomic DNA cleaved with EcoRI revealed that a subpopulation of the PuHu26 family contains EcoRI restriction sites spaced at multiples of approximately 172 bp

Suspected vs. Diagnosed Mental Illness, Race, and the NGRI Plea

This study investigated the effects of mental illness (suspected, diagnosed) and the defendant’s race (Black, White) on receiving the NGRI plea in a Second-Degree murder case. Participants were more likely to assign the NGRI plea to a Black defendant than a White defendant if the defendant had a diagnosed mental illness, but were more likely to assign a guilty plea to the Black defendant than the White when the diagnosis was only suspected

Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds.

Using both confocal immunofluorescence microscopy and biochemical approaches, we have examined the role of beta-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of angiotensin II type 1a receptors (AT1aR). In HEK-293 cells expressing hemagglutinin-tagged AT1aR, angiotensin stimulation triggered beta-arrestin-2 binding to the receptor and internalization of AT1aR-beta-arrestin complexes. Using red fluorescent protein-tagged ERK2 to track the subcellular distribution of ERK2, we found that angiotensin treatment caused the redistribution of activated ERK2 into endosomal vesicles that also contained AT1aR-beta-arrestin complexes. This targeting of ERK2 reflects the formation of multiprotein complexes containing AT1aR, beta-arrestin-2, and the component kinases of the ERK cascade, cRaf-1, MEK1, and ERK2. Myc-tagged cRaf-1, MEK1, and green fluorescent protein-tagged ERK2 coprecipitated with Flag-tagged beta-arrestin-2 from transfected COS-7 cells. Coprecipitation of cRaf-1 with beta-arrestin-2 was independent of MEK1 and ERK2, whereas the coprecipitation of MEK1 and ERK2 with beta-arrestin-2 was significantly enhanced in the presence of overexpressed cRaf-1, suggesting that binding of cRaf-1 to beta-arrestin facilitates the assembly of a cRaf-1, MEK1, ERK2 complex. The phosphorylation of ERK2 in beta-arrestin complexes was markedly enhanced by coexpression of cRaf-1, and this effect is blocked by expression of a catalytically inactive dominant inhibitory mutant of MEK1. Stimulation with angiotensin increased the binding of both cRaf-1 and ERK2 to beta-arrestin-2, and the association of beta-arrestin-2, cRaf-1, and ERK2 with AT1aR. These data suggest that beta-arrestins function both as scaffolds to enhance cRaf-1 and MEK-dependent activation of ERK2, and as targeting proteins that direct activated ERK to specific subcellular locations

Regulation of Synaptophysin Degradation by Mammalian Homologues of Seven in Absentia

Synaptophysin is an integral membrane protein of synaptic vesicles characterized by four transmembrane domains with both termini facing the cytoplasm. Although synaptophysin has been implicated in neurotransmitter release, and decreased synaptophysin levels have been associated with several neurodegenerative diseases, the molecular mechanism that regulates the degradation of synaptophysin remains unsolved. Using the cytoplasmic C terminus of synaptophysin as bait in a yeast two-hybrid screen, we identified two synaptophysin-binding proteins, Siah-1A and Siah-2, which are rat homologues of Drosophila Seven in Absentia. We demonstrated that Siah-1A and Siah-2 associate with synaptophysin both in vitro and in vivo and defined the binding domains of synaptophysin and Siah that mediate their association. Siah proteins exist in both cytosolic and membrane-associated pools and co-localize with synaptophysin on synaptic vesicles and early endosomes. In addition, Siah proteins interact specifically with the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 and facilitate the ubiquitination of synaptophysin. Furthermore, overexpression of Siah proteins promotes the degradation of synaptophysin via the ubiquitin-proteasome pathway. Our findings indicate that Siah proteins function as E3 ubiquitin-protein ligases to regulate the ubiquitination and degradation of synaptophysin

A latent trait look at pretest-posttest validation of criterion-referenced test items

Since Cox and Vargas (1966) introduced their pretest-posttest validity index for criterion-referenced test items, a great number of additions and modifications have followed. All are based on the idea of gain scoring; that is, they are computed from the differences between proportions of pretest and posttest item responses. Although the method is simple and generally considered as the prototype of criterion-referenced item analysis, it has many and serious disadvantages. Some of these go back to the fact that it leads to indices based on a dual test administration- and population-dependent item p values. Others have to do with the global information about the discriminating power that these indices provide, the implicit weighting they suppose, and the meaningless maximization of posttest scores they lead to. Analyzing the pretest-posttest method from a latent trait point of view, it is proposed to replace indices like Cox and Vargas’ Dpp by an evaluation of the item information function for the mastery score. An empirical study was conducted to compare the differences in item selection between both methods

GIT2 Acts as a Potential Keystone Protein in Functional Hypothalamic Networks Associated with Age-Related Phenotypic Changes in Rats

The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process

Involvement of Phospholipase D2 in Lysophosphatidate-induced Transactivation of Platelet-derived Growth Factor Receptor-β in Human Bronchial Epithelial Cells

Lysophosphatidate (LPA) mediates multiple cellular responses via heterotrimeric G protein coupled LPA-1, LPA-2, and LPA-3 receptors. Many G protein-coupled receptors stimulate ERK following tyrosine phosphorylation of growth factor receptors; however, the mechanism(s) of transactivation of receptor tyrosine kinases are not well defined. Here, we provide evidence for the involvement of phospholipase D (PLD) in LPA-mediated transactivation of platelet-derived growth factor receptor-beta (PDGF-R beta). In primary cultures of human bronchial epithelial cells (HBEpCs), LPA stimulated tyrosine phosphorylation of PDGF-R beta and threonine/tyrosine phosphorylation of ERK1/2. The LPA-mediated activation of ERK and tyrosine phosphorylation of PDGF-R beta was attenuated by tyrphostin AG 1296, an inhibitor of PDGF-R kinase, suggesting transactivation of PDGF-R by LPA. Furthermore, LPA-, but not PDGF beta-chain homodimer-induced tyrosine phosphorylation of PDGF-R beta was partially blocked by pertussis toxin, indicating coupling of LPA-R(s) to Gi. Exposure of HBEpCs to LPA activated PLD. Butan-1-ol, which acts as an acceptor of phosphatidate generated by the PLD pathway, blocked LPA-mediated transactivation of PDGF-R beta. This effect was not seen with butan-3-ol, suggesting PLD involvement. The role of PLD1 and PLD2 in the PDGF-R beta transactivation by LPA was investigated by infection of cells with adenoviral constructs of wild type and catalytically inactive mutants of PLD. LPA activated both PLD1 and PLD2 in HBEpCs; however, infection of cells with cDNA for wild type PLD2, but not PLD1, increased the tyrosine phosphorylation of PDGF-R beta in response to LPA. Also, the LPA-mediated tyrosine phosphorylation of PDGF-R beta was attenuated by the catalytically inactive mutant mPLD2-K758R. Infection of HBEpCs with adenoviral constructs of wild type hPLD1, mPLD2, and the inactive mutants of hPLD1 and mPLD2 resulted in association of PLD2 wild type and inactive mutant proteins with the PDGF-R beta compared with PLD1. These results show for the first time that transactivation of PDGF-R beta by LPA in HBEpCs is regulated by PLD2

Perspective, Invention, and Metatheater in Renaissance Literature

This dissertation challenges the misconception of post-Reformation England as iconophobic. On the contrary, it argues that early modern English poets and playwrights adapt Continental theories and techniques from painting, translating them into their own poetic and dramatic forms. It explores how allusions to contemporary perspectival images serve as governing metaphors and structural devices for the works in which they appear. Particularly in the genre of the Elizabethan epyllion and in works by Shakespeare, it suggests that texts are designed to be read “perspectively,” to borrow Shakespeare’s coinage, so that they are open to ambiguity and multiplicity, and capable of being interpreted in conflicting or complementary ways. In chapters on the Elizabethan epyllion, it examines how the rhetorical superfluity and linguistic play of Marlowe’s Hero and Leander and the satirical experience of “curious viewing” in Marston’s Metamorphosis of Pigmalion’s Image effect a shift in the period’s understanding of artistic invention. In chapters on Shakespeare, it reveals how the modern interest in Shakespearean metatheater — where the theater draws attention to itself as theater — is in fact grounded in the contemporary language of visual perspective. It shows how Shakespeare cues his original audiences to view his plays as perspectival double images, constituted not only by the embodied characters within the fictional worlds of his plays, but also as the physical, human actors of his professional playing company in early modern London. It contends that Shakespeare’s plays become increasingly visual and perspectival, changing meaning and resonance depending on venue, after his professional playing company, the King’s Men, acquire their second playhouse, the Blackfriars. This dissertation therefore traces evolutions in aesthetics and dramatic form occasioned by contemporary developments in the period’s larger visual culture, breaking new ground on the confluences between the visual, poetic, and dramatic arts