Antimicrobial and xenobiotic defence in the mammalian testis

Different mechanisms exist in the mammalian testis to protect the germ cells from autoimmune attack, invading microbes, and xenobiotic induced toxicity, which would otherwise be deleterious to the preservation of fertility. The general aim of this thesis was to study these testicular defence mechanisms, including the structural building blocks of the blood– testis barrier (BTB), antimicrobial peptides, proinflammatory cytokines and ATP-binding cassette (ABC) transporter proteins. Coxsackie and Adenovirus Receptor (CAR) is a cell adhesion molecule present in tight junctions of epithelial cells. We found that CAR was expressed in male germ cells in the human, the rat and the mouse testis, with a localization corresponding to the acrosomal structure of the elongated spermatids as well as in mature spermatozoa. CAR co-localized and co-immunoprecipitated with JAM-C in the mouse testis, suggesting that CAR may function in germ cell differentiation and polarization, similar to JAM-C. Interleukin-18 (IL-18) is a proinflammtory cytokine that contributes to host defence in epithelial barrier tissues. We found that IL-18, the IL-18 receptor and the interleukin-1β converting enzyme (ICE) was expressed in the rat testis throughout postnatal development. IL-18 protein and messenger ribonucleic acid (mRNA) were mainly localized in meiotic and post-meiotic germ cells. Only Pro-IL-18 was detected in interstitial fluid and in testicular cell extracts, suggesting that IL-18 normally is in its non-active form in the healthy testis, but may become activated during testicular infection. Recombinant IL-18 stimulated spermatogonial proliferation and thus may act as a growth factor during patho-physiological conditions in the testis. The nuclear protein High mobility group box chromosomal protein-1 (HMGB1) does also have extracellular immune-functions, including cytokine stimulation and direct antimicrobial activity. We found that HMGB1 was expressed in the nucleus and in the cytoplasm of Sertoli cells in the human and rat testis. HMGB1 protein was also present in interstitial fluid collected from non-treated rat testis, indicating extracellular release. HMGB1 purified from human and rat testis demonstrated strong and direct antibacterial activity and thus may act as an antimicrobial peptide in the seminiferous epithelium, contributing to the protection of the developing germ cells against invading pathogens. The ABC transporter family is responsible for active transport of substrates across membranes. They are located in barrier tissues such as the BTB and the blood– brain barrier (BBB) and protect against uptake of xenobiotics. We found that testes from immature (6-day-old) rats accumulated significantly higher levels of the ABC transporter substrate and anticancer drug doxorubicin, compared to the testes from 16- and 24-day old rats. This correlated with a significantly lower level of testicular expression of ABC transporters compared to 16- and 24-day-old rats. Thus, lack of a mature ABC transporter efflux system may render the immature testis more susceptible to xenobiotic-induced toxicity. The studies described here support the view that the mammalian testis has evolved several defence mechanisms to preserve fertility

When I Die, I Won\u27t Stay Dead: The Poetry of Bob Kaufman

This dissertation begins with the premise that critical attention to the work of Bob Kaufman is long overdue, and that Bob Kaufman is a significant American poet in the African American and Beat traditions. The purpose of this dissertation begins to rectify this need with a study of Bob Kaufman’s verse. My exploration of Kaufman necessitates some pointed attention to the cultural, social, and psychological influences that gave rise to his work, specifically his upbringing in the south, his travels, and the misrepresented times of his life in current biographical entries and some present scholarship. I will also address the notion of him as an oral poet within the context of the African American Oral tradition and the improvisational nature of Jazz music. I will also consider the surrealist impulse in Bob Kaufman’s work. Thus, this dissertation will treat Bob Kaufman’s use of the Surreal and the Jazz idiom as a social and political vehicle for his art. This practice locates him at the heart of modernism, and looks ahead to the postmodern in American Literature. In this regard, I will demonstrate how Bob Kaufman outdistances his Beat contemporaries and pre-figures the Black Arts and Cultural Movement of the 1960s not just in chronological order but in social and political content, and literary practice. My project seeks to understand Bob Kaufman’s overall aesthetic by close analysis of his major themes; linguistic prowess; his often overlooked southern surreal; the collision of music and poetry in his poems; his use of rhythm and typography as structural performance. To this end, I will examine the Solitudes collection with attention to his emphasis on poetic shape, structure and sound, and how to read the influence of Jazz in his printed work. I demonstrate why American literary scholarship should unearth the multi-layered mind field that is Bob Kaufman’s verse

Tau pathology in Alzheimer's disease and other dementias : translational approach from in vitro autoradiography to in vivo PET imaging

Tauopathies, including Alzheimer's disease (AD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), are complex neurodegenerative disorders characterized by the pathological accumulation of tau proteins in the brain. These often overlapping disorders, with intricate pathologies and growing prevalence, lack definitive treatments, highlighting the necessity for advanced research. Positron emission tomography (PET) imaging aids in the diagnosis and monitoring of diseases, by providing in vivo insights into pathological features. This thesis focused on deciphering the binding properties and brain regional distribution of PET tracers for accurate disease differentiation. Spanning four studies, we aimed to bridge in vitro and in vivo PET data to investigate tau pathology and its association with dementia-related markers such as reactive astrogliosis, peripheral inflammation, and dopaminergic dysfunction. The 2nd generation tau PET tracers, 3H-MK6240 and 3H-PI2620, demonstrated high affinity and specificity in AD post-mortem brain tissues, especially in early-onset AD, compared to controls. 3H-PI2620, 3H-MK6240, and 3HRO948 displayed similar binding patterns in AD tissue, with multiple binding sites and equivalent high affinities (Papers I and II). 3H-PI2620 showed specificity in CBD and PSP tissues, in contrast to 3H-MK6240. However, differentiating CBD from PSP brains with 3H-PI2620 remained challenging in multiple brain regions, potentially due to complex tracer-target interactions (Papers II and III). Reactive astrogliosis PET tracers 3H-Deprenyl and 3H-BU99008 bound primarily to stable distinct high-affinity binding sites in AD, CBD and PSP, but also to transient binding sites, differing by brain region and condition. This pattern implied that these tracers may interact with similar or diverse subtypes or populations of astrocytes, expressing varying ratios of transient sites, which may vary depending on the brain location and the disease (Paper III). Using 3H-FEPE2I, we delineated a reduction in dopamine transporter (DAT) levels within the putamen across CBD, PSP and Parkinson's Disease (PD) brains. Concomitantly, elevated 3H-Raclopride binding reflected higher dopamine D2 receptor (D2R) levels in PSP and PD. Nonetheless, our observations underscored the heterogeneity inherent to these neurodegenerative pathologies, emphasizing the criticality of individual variability in neuropathological manifestations (Paper III). Lastly, we investigated late middle-aged cognitively unimpaired Hispanic individuals, in dichotomous groups of in vivo amyloid-β (Aβ) PET (18F-Florbetaben) and plasma neurofilament light (NfL) biomarkers. Our findings suggest that elevated plasma inflammation and tau burden as measured by 18FMK6240, can be detected at early preclinical stages of AD, offering potential for early diagnosis (Paper IV). This thesis underscored the importance of PET imaging in advancing our understanding of tauopathies. The innovative use of multiple PET tracers provided crucial insights into their potential use in clinics to distinguish pathological features of AD, CBD and PSP. The findings emphasized the need for more studies applying a multifaceted approach to studying and managing these complex neurodegenerative disorders, combining advanced imaging techniques with a broad spectrum of biological markers

Effects of selected surfactants on nutrient uptake and soil microbial community

Title from PDF of title page (University of Missouri--Columbia, viewed on June 6, 2012).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Thesis advisors: Dr. Robert J. Kremer, Dr. Frieda Eivazi, Dr. Kelly Neldon, and Dr. Peter P. MotavalliIncludes bibliographical references.M.S. University of Missouri--Columbia 2011."December 2011"Surfactants with solvent and wetting abilities are used in the formulation of herbicides to enhance spraying capabilities. These chemicals eventually enter into the soil and may disrupt different chemical, physical and biological processes. The aim of this study was to examine the effects on nutrient uptake in corn and soil microbial community due to application of surfactants at different rates, herbicides, and surfactant-herbicide combinations in silt loam and silty clay loam soils. Surfactants used were Activator 90, Agri-Dex and Thrust. Herbicides used were glyphosate, atrazine, and bentazon. Corn was planted in fertilized soils and moisture levels maintained. After seven weeks, plant foliage were ground and stored for elemental analyses with Inductively Coupled Plasma Emission Spectrophotometer (ICP). Soil samples were analyzed with Polymerase Chain Reaction (PCR-DGGE) and Phospholipid Fatty Acids analyses (PLFA) to assess microbial diversity. The treatments did not greatly affect nutrient uptake by corn. Visual differences between both soils and among treatments were observed with DNA band expression, although few significant differences due to treatments were found. PLFA biomarkers were variably affected by soils and different treatments relative to control. In general treatments did not significantly affect plant nutrient uptake or microbial community, perhaps as a result of the onetime application of small quantities of chemicals. Differences between both soils reflected the overall contribution of soil texture, chemical and physical characteristics. Formulation additives should be considered when evaluating effects of pesticide applications on plant quality and soil biology

Magnetic Line Source Diffraction by a PEMC Step in Lossy Medium

In this chapter, we investigate a magnetic line source diffraction problem concerned with a step. To study the diffraction problem in lossy medium, we follow the Wiener-Hopf technique and steepest decent method to solve it for impedance step. By equating the impedances of the step to zero, the solution reduces for magnetic line source diffraction by PEC step. Then we transform the obtained solution for PEMC step by using duality transformation. Perfect electromagnetic conductor (PEMC) theory is novel idea developed by Lindell and Sihvola. This media is interlinked with two conductors namely perfect electric conductor (PEC) and perfect magnetic conductor (PMC). Both PEC and PMC are the limiting cases of perfect electromagnetic conductor (PEMC). We study the magnetic line source diffraction by PEMC step placed in different soils (i) gravel sand (ii) sand and (iii) clay. By using the permittivity, permeability and conductivity of these lossy mediums we predict the loss effect on the diffracted field. Such kind of study is very useful in antenna and wave propagation for subsurface targets and to investigate antenna radiation patterns