acase@tulane.edu / Astrocytes are the most numerous nonneuronal cell-type within the brain. These glial cells support activities essential for neuronal function, regulating extracellular concentrations of ions and neurotransmitters, providing metabolic substrates, and maintaining the blood-brain barrier. In addition, astrocytes respond to central nervous system (CNS) disease by becoming reactive, a nonspecific but highly characteristic response that involves various molecular and morphological changes. Quantifiable changes in astrocyte activation and remodeling have been documented in chronic stress, neurodegenerative disease, mood disorders, and CNS infections. However, whether astrocytes remodel in the same way and whether all insults produce the same effect is largely unknown. Here, studies examine astrocyte morphology and immune activation in nonhuman primates across a wide range of CNS diseases including bacterial and viral infection, and self-injurious behaviors. Paraffin-embedded tissue was selected from the Tulane National Primate Research Center archives, and immunofluorescence with TLR2 and GFAP was used to examine immune activation of astrocytes in cortical tissue. In addition, reconstruction of astrocyte morphology using Neurolucida software revealed specific remodeling patterns for each CNS disease state. While immune activation through Toll-like receptor and GFAP expression generally increased in pathological states, specific astrocyte remodeling patterns were observed relative to pathology indicating that astrocyte response to CNS disease is dependent upon cortical location and pathological state. / 1 / Kim Lee

The "argument from species overlap" (abbreviated ASO) claims that some human and nonhuman animals possess similar sets of morally relevant characteristics, and are therefore similarly morally significant. The argument stands as a general challenge to moral theories, because many theories hold that all humans possess greater moral significance than all nonhuman animals. In this thesis I discuss responses to the ASO, primarily those of Peter Carruthers, Tom Regan, Evelyn Pluhar, and Peter Singer. Carruthers denies the conclusion of the ASO, while the other three do not. I argue that the ASO is a sound argument, and that Carruthers's attempts to counter it via his contractualist theory are unsuccessful. I next discuss the rights-based theories of Regan and Pluhar, which agree with the conclusion of the ASO but which, I believe, encounter significant theoretical difficulties. Finally, I address the ASO from a utilitarian perspective, first from Singer's utilitarian formulation and then from a "welfare-utilitarian" formulation. I answer a number of critical objections to welfare utilitarianism, and argue that the theory is most successful in facing the challenge of the ASO. / Master of Arts

No description available.

L-glutamate (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system. Monitoring extracellular Glu is critical to understanding Glu regulation to discriminate physiological and pathological roles. To overcome the limitations of previous in vivo extracellular Glu studies, we developed Glu selective microelectrode arrays with better spatial and temporal resolutions than commonly used techniques like microdialysis. We used these microelectrode arrays to characterize basal and potassium-evoked Glu neurotransmission in the normal rat brain. We then investigated disease-related Glu alterations in a rat model of Parkinson's disease and normal Glu regulation in young and aged rhesus monkeys. In the normal anesthetized rat striatum and frontal cortex, basal Glu was regulated by active release and uptake mechanisms, fully TTX-dependent, and measured at ~2 micromolar levels. Potassium-evoked Glu kinetics were fast, concentration-dependent, and rapidly reproducible at 15-20 seconds intervals. In the unilateral 6-hydroxydopamine-lesioned rat, there were significant bilateral increases in potassium-evoked Glu release in the striatum and frontal cortex compared to hemisphere-matched non-lesioned rats. Ipsilateral striatal effects may have been related to DA loss, while contralateral striatal effects and the bilateral frontal corticaleffects may have resulted from parkinsonian neurotransmitter changes or bilateral neuranatomical connectivity, especially in the cortex. There were also alterations in Glu kinetics in the nucleus accumbens in both non-lesioned and lesioned rats. With appropriate technological and methodological modifications, we successfully recorded normal Glu signaling in anesthetized nonhuman primates in the operating room. Fast potassium-evoked Glu signals were recorded in the motor cortex of all monkeys, and Glu ejections showed robust Glu uptake in the motor and frontal cortices of all monkeys. These findings are comparable to initial rat studies. Slow evoked Glu kinetics and high basal Glu levels with oscillatory behavior were recorded in the frontal cortex. The primary age-related differences between monkeys were the nearly ten-fold increases in the volumes of Glu ejected needed in the aged monkey to achieve amplitude-matched signals in the motor and frontal cortices and a decreased uptake rate in the motor cortex. Preliminary work with excised human tissue and future plans for patient-oriented research and clinical applications are discussed.

Pituitary adenylate cyclase activating polypeptide (PACAP) is associated with Alzheimer's disease (AD), but its age-related effects are unknown. We chose the rhesus macaque due to its closeness to human anatomy and physiology. We examined four variables: aging, cognitive performance, amyloid plaques and PACAP. Delayed nonmatching-to-sample recognition memory scores declined with age and correlated with PACAP levels in the striatum, parietal and temporal lobes. Because amyloid plaques were the only AD pathology in the old rhesus macaque, we further studied human amyloid precursor protein (hAPP) transgenic mice. Aging was associated with decreased performance in the Morris Water Maze (MWM). In wild type (WT) C57BL/ 6 mice, the performance was decreased at age 24-26 month whereas in hAPP transgenic mice, it was decreased as early as 9-12 month. Neuritic plaques in adult hAPP mice clustered in hippocampus and adjacent cortical regions, but did not propagate further into the frontal cortex. Cerebral PACAP protein levels were reduced in hAPP mice compared to age-matched WT mice, but the genetic predisposition dominated cognitive decline. Taken together, these data suggest an association among PACAP levels, aging, cognitive function and amyloid load in nonhuman primates, with both similarities and differences from human AD brains. Our results suggest caution in choosing animal models and in extrapolating data to human AD studies.

archives@tulane.edu / Immune signatures are patterns of gene and protein expression in immune cells that characterize states of activation and response. As such, signatures indicative of viral control during natural infection may guide vaccine development efforts to achieve similar patterns of protection. Here, we used nonhuman primate (NHP) models of Zika virus (ZIKV) and simian immunodeficiency virus (SIV, as a model for HIV) to explore outcomes of infection in these important human pathogens. We employed a multifaceted approach including high dimensional flow cytometry and RNA sequencing to understand cellular responses to ZIKV generally and during pregnancy, as well as to identify the impacts of infection in astrocytes, a neuroglial target of ZIKV thought to be important in the development of neurologic disease. We found that CD8 T cells may restrict ZIKV persistence in tissues but ultimately have a minimal role in protection to either primary or secondary challenge. However, we showed that immune manipulation, either naturally through pregnancy or artificially through depletion experiments, can skew metabolic and innate immune pathways in unexpected ways. While cellular immunity appeared to minimally impact ZIKV infection, such responses in SIV are important in controlling viral replication, which we inversely showed by tracking patterns of viral mutation to evade CD8 responses. We also identified transcriptional signatures in ZIKV infection that may underlie the development of neurologic diseases and found that different virus lineages have unique impacts on gene expression. Together, these experiments showcase the utility of profiling approaches in understanding the immune complexity that accompanies viral infection. / 1 / Blake Schouest

Twenty-one 8-14 kg adult male stumptailed macaques, Macaca arctoides, were fed a standard laboratory diet and divided into 3 groups. The high-dose group and low-dose group were exposed to cigarette smoke at the human equivalent of 3 packs and 1 pack per day, respectively, 7 days per week, for 3-5 years. Eight animals served as cage and sham controls. Peak blood carboxyhemoglobin (COHb) levels measured immediately after smoking showed levels of 0.5 ± 0.1%, 3.6 ± 1.0%, and 5.7 ± 2.8% for. sham controls, low, and high dose smokers, respectively. Hemoglobin and hematocrit values were 2-7% higher (N.S. to P < 0.05) for smoking groups, presumably as a consequence of chronically elevated COHb levels. No significant differences were seen in total plasma cholesterol and lipoprotein cholesterol concentration measured at four intervals over a period of one year. We conclude from these data that, while fed a low fat diet, chronic cigarette smoke inhalation fails to alter plasma lipoprotein levels in this animal model.

In the past forty years, there has been an unprecedented explosion of theological writings regarding the place of the nonhuman creation in ethics. The purpose of this dissertation is to propose a taxonomy of four paradigms of eco-theological thought that will categorize these writings and facilitate the identification, situation, and constructive development of the paradigm of cosmocentric transfiguration. This taxonomy takes shape within the tensions of three theological foundations: cosmology, anthropology, and eschatology. These tensions establish two categorical distinctions between, on the one hand, conservation and transfiguration, and, on the other, anthropocentrism and cosmocentrism. The variations within these poles yield the four paradigms. &lt;br&gt;The first paradigm is anthropocentric conservation, represented by Thomas Aquinas. It maintains that humanity bears an essentially unique dignity and eschatological telos that renders the nonhuman creation resources for human use in via toward that telos. The second is cosmocentric conservation, represented by Thomas Berry. It maintains that humanity is part of a cosmic community of intrinsic worth that demands protection and preservation, not human manipulation or eschatological redemption. The third is anthropocentric transfiguration, represented by Orthodox theologians such as Dumitru Staniloae. It maintains that humans are priests of creation charged with the task of recognizing the cosmos as the eternal sacrament of divine love and using it to facilitate communion among themselves and with God. The fourth is cosmocentric transfiguration, represented by both Jürgen Moltmann and Andrew Linzey. It maintains that humans are called to become proleptic witnesses to an eschatological hope for peace that includes the intrinsically valuable members of the cosmic community. &lt;br&gt;Cosmocentric transfiguration, while under-represented and underdeveloped, provides a unique opportunity to affirm both scientific claims about the nature of the cosmos and the theological hope for redemption. In addition, it offers a powerful vision to address the current ecological crisis with regard to humanity's relationship to both individual nonhuman life forms and the cosmos at large. This vision calls for humans to protest the mechanisms of death, suffering, and predation by living at peace, to whatever extent context permits, with all individual creatures while at the same time preserving the very system they protest by protecting the integrity of species, eco-systems, and the environment at large. These findings warrant further research regarding the viability of cosmocentric transfiguration, in particular its exegetical warrant in scripture, its foundations in traditional voices of Christian thought, its interdisciplinary potential for integration of the sciences, and its internal coherency. / McAnulty College and Graduate School of Liberal Arts; / Theology / PhD; / Dissertation;

Following a call from Linton (2010) to think more relationally about water this thesis seeks to explore the infolding and unfolding relations that take-form between bodies around particular characteristics of freshwater. There is a tradition of exploration regarding the sustainability, quality, monitoring and management of water when we encounter research on human associations with fluvial hydrology, and whilst this work is important, this project looks to enrol more nascent and contemporary geographical themes to broaden our understanding of encounters with freshwater landscapes, and take a more relational approach to fluvial geographies. These works then shall address a gap in the geographical literature and describe the personal, pre-personal and affective worlds that emerge when bodies become down by the river. Whilst this is not specifically a walking project, walking the course of the River Severn serves as a trajectory along which processual ideas of bodies on the move shall be mobilised. A series of creatively written segues will link together a sequence of theoretical and conceptually driven site ontologies (Marston et al 2005; Woodward et al 2010) and relations associated with the Severn and freshwater more broadly. The flow and form of the thesis will reflect the multivariant characteristics of water and its varying speeds and slownesses. The chapters will step into puddles, mooch about in a ships graveyard, rethink the source of a river, paddle a coracle and set the scene for how an ontological, relational approach to fluvial landscapes can contribute to geographical thinking. The works will focus on human-nonhuman relations, vibrant materialities and elemental mobilities, in so doing enable further understanding of how we can apprehend sites as moments of coherence in a turbulent world, and contribute to broadening our scope of knowledge of the more-than-human.

Cette recherche vise à fonder les droits des animaux non humains (ou humains) d’une manière hobbesienne. Cette manière est celle du droit naturel (ou jusnaturalisme). Nous montrons tout d'abord pourquoi le droit naturel est un cadre normatif spécifique qui doit être distingué de tout autre système normatif, en particulier de la morale ou de l’éthique. Dans un contexte hobbesien, les droits des animaux non humains ne sont pas des droits moraux mais des droits naturels. Nous montrons ensuite comment on peut écarter grâce au droit naturel toute morale défavorable aux animaux non humains. En fondant les droits naturels des animaux non humains, cette recherche poursuit des travaux déjà engagés sur la voie hobbesienne. Mais nous relions plus particulièrement la question des droits naturels des animaux non humains à la question de savoir quel type de protection juridique doit leur être accordé en vertu d’arguments de type hobbesien. Nous montrons finalement pourquoi l’égalité animale est une nécessité juridique dans le contexte d’une défense jusnaturaliste des animaux non humains, ce qui se traduit en droit positif par leur personnification juridique anthropomorphique. / This research aims to ground nonhuman (or human) animal rights in a Hobbesian way. This is that of natural law (i.e., jusnaturalism). First, we show why natural law is a specific normative framework that should be distinguished from any other normative system, especially morals or ethics. In a Hobbesian framework, nonhuman animal rights are not moral rights but natural rights. We show then how any morals detrimental to nonhuman animals can be eliminated through natural law. By grounding nonhuman animals’ natural rights, this research pushes forward works already engaged in this Hobbesian manner. But we relate more particularly the nonhuman animals’ natural rights issue to the question of what kind of legal protection they should be granted on the basis of Hobbesian-like arguments. Finally, we show why animal equality is a legal necessity in the context of a jusnaturalist defense of nonhuman animals, which legally results in their anthropomorphic legal personification.