Digital Commons Network^™

Centrosomal Profile Status Of Bladder Carcinoma In African-Americans And Caucasians: A Comparative Analysis, Rutugandha Deepak Paranjpe

Biology Theses

Urothelial carcinoma of bladder (UCB) in African-Americans (AA) presents as more advanced disease at diagnosis and has lower 5-year survival rate, compared to Caucasians. The clinical diagnosis of higher grade and stage can be attributed to a more aggressive disease course in AA. Given the clear association between CA and aggressiveness, we hypothesized that AA have a higher incidence and severity of CA in bladder tumors as compared to Caucasians. To test this hypothesis, we developed an innovative method to quantitate the degree of CA (both numeric and structural) within tumor samples and defined a measurable index called the Centrosome …

Melanocortin Administration To The Ventral Tegmental Area Alters Homeostatic And Hedonic Feeding, Haw-Han Yen

Biology Theses

Dopamine neurons of ventral tegmental area (VTA) are critical for control of homeostatic feeding, which relates to food intake necessary for maintaining normal physiological function. It also plays an important role in hedonic or ‘reward’ feeding. Alteration of mesolimbic dopamine pathways can change both baseline homeostatic and reward feeding. The melanocortin system of the hypothalamus also is important for control of feeding, and recently it has been shown that melanocortins can modulate the food intake by acting at dopamine pathways. Here, we tested whether injection of melanocortin receptor agonists into the VTA also affected reward feeding. Injection of melanocortin receptor …

Polycomb Recruitment At The Class Ii Transactivator, Nathaniel H. Boyd

Biology Theses

The Class II Transactivator (CIITA), is the master regulator of Major Histocompatibility Class II (MHC II) genes. Transcription of CIITA is characterized by a decrease in specific trimethylation of histone H3 lysine 27 (H3K27me3), catalyzed by the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2). While EZH2 is the known catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is present at the inactive CIITA promoter; the mechanisms of recruitment of PRC2 to mammalian promoters remains unknown. Here we identify two DNA-binding proteins, YY1 and Jarid2, which interact with and regulate PRC2 recruitment to CIITA promoters. Our study is …

Designingtargeted F4/80 Antibody Coated Tnf-Α Sirna Loaded Nanoparticles: A Novel Therapeutic Approach To Treat Inflammatory Bowel Disease, Poonam Rakhya

Biology Theses

ABSTRACT

Today, increasing evidences of systemic side effects with the treatments available for IBD limit their therapeutic outcomes. The challenge is to target anti-TNF-α agent to the inflamed tissue. Here, we have demonstrated that TNF-α siRNA can be efficiently loaded into F4-80 antibody (Ab) coated PLA-PEG-Mal nanoparticles (NPs) to target colonic macrophages (MPs). The NPs were characterized for particle size, cytotoxicity, binding characteristics, etc. These NPs are ~600 nm in diameter, non-cytotoxic, and are efficiently taken up by MPs inhibiting TNF-α secretion by the MPs in vitro. In vivo, the release of TNFa siRNA loaded inside F4/80 Ab coated NPs …

Effects Of Escapin Intermediate Products (Eip-K) On Biofilms Of Pseudomonas Aeruginosa, Marwa Nabil Abdelaziz Ahmed

Biology Theses

Escapin is an L-amino acid oxidase that produces antimicrobial metabolites collectively called “Escapin Intermediate Products” (EIP-K). EIP-K and H₂O₂ together were previously shown to be bactericidal towards diverse planktonic bacteria. The present work investigates the ability of EIP-K and H₂O₂ to antagonize bacterial biofilms, using Pseudomonas aeruginosa as a model. The project had three aims: 1) determine the most effective concentrations of EIP-K and H₂O₂ necessary to break down existing P. aeruginosa biofilms, using a crystal violet assay; 2) examine the ability of EIP-K + H₂O₂ to inhibit …

Oxidative Stress Suppresses The Heteromeric Kir4.1-Kir5.1 Channel Via S-Glutathionylation, Yang Wu

Biology Theses

Potassium transport channels regulate cellular excitability and membrane potentials. Dysfunction of potassium channels may happen under certain pathophysiological conditions via post-translational modification (PTM), inducing the S-glutathionylation, in oxidative stress. Here, we try to demonstrate the effect of ROS on Kir4.1 and Kir5.1 channel. It is found that the target subunit of ROS is Kir5.1 instead of Kir4.1 subunit. Kir4.1-Kir5.1 heteromeric channel is inhibited by different kinds of oxidants. The patch clamp study confirmed that these oxidants work on the intracellular side of the Kir5.1 subunit. Further experiments demonstrate that the inhibition of Kir4.1-Kir5.1 channels is through S-glutathionylation of the Kir5.1 …

The Developmental Regulation Of Gene And Cellular Networks In Locomotion, Manali Rupji

Biology Theses

A process such as locomotion requires a well-connected cellular network that is assembled by a gene network. Caenorhabditis elegans offers a tractable model system allowing integrative studies of gene and cellular networks. We have combined bioinformatics and cellular approaches to investigate such networks. The D motorneurons compose a cross – inhibitory network essential for sinuous locomotion. Its terminal selector gene, unc-30 establishes the anatomical and neurochemical fates in these neurons. Three genes: unc-5, flp-11 and unc-104 are expressed in the D mns as well as other motorneuron classes. Using transcriptional reporters, we found that UNC-30 influenced the expression of …

Mechanisms Of Localization Of Symbiont-Produced Natural Products In Host Colony, Fahmina Akhter

Biology Theses

The relationship between the bryozoan Bugula neritina and its symbiont "Candidatus Endobugula sertula" is a specific yet complex model for defensive symbiosis where the host larvae obtain chemical protection from predation by symbiont-produced bryostatin. The symbiotic bacteria are located in both larval and adult tissues of the host. However, the bryostatins levels are higher in larvae and in adult zooids with ovicells where the larvae are brooded, compared to adult zooids without ovicells. In this study, symbiont cell density and bryostatin biosynthetic gene expression were quantified in host tissues, using TaqMan probe based Q-PCR, to investigate the mechanisms for …

Modulation Of Local Reflexes During Centrally Commanded Movements, Uzma H. Tahir

Biology Theses

During centrally orchestrated movements, the nervous system must distinguish between appropriate and inappropriate reflexes. I studied local postural flexion reflexes of the crayfish that are evoked by unexpected touch. An isolated abdomen was used which permitted recording and stimulating of tailfan afferents, nerve cord interneurons, and postural motor neurons. Stimulation of the afferents evoked a postural flexion response of the medium tonic and large phasic motor neurons of the superficial flexor nerve; a flexion motor program was then excited by stimulating descending interneurons. Afferent stimulation evoked a smaller motor response during the motor program than before or after. These results …

In Silico Analysis Shows That Single Aminoacid Variations In Rhesus Macacque Fcγreceptor Affect Protein Stability And Binding Affinity To Igg1, Rashesh Sanghvi

Biology Theses

Rhesus macaques are a widely used animal model of human diseases and related immune responses. Fc receptors (FcRs) mediate the interaction between antibody molecules and innate killing mechanisms, consequently eliminating the pathogen. In rhesus macaques, FcRs are highly polymorphic. To evaluate the potential influence of FcgR polymorphisms on the interaction with antibody molecules, we performed in silico analysis using SIFT, Provean, nsSNPAnalyzer, I-Mutant, MuSTAB and iPTREE-STAB web servers. V20G in FcγRI, I137K in FcγRII and I233V in FcγRIII were further analyzed structurally using FOLD-X, AMMP and Chimera to calculate changes in folding and interaction energy and for structure visualization. Results …

Rational Design, Synthesis, And Evaluation Of Inhibitors For The Hiv-1 Tat Interacting Protein Tip60, Liza D. Ngo

Biology Theses

The histone acetyltransferase protein, Tip60, has many important functions in epigenetic regulation of gene expression and DNA repair. Our objective is to design, synthesize, and evaluate potent inhibitors for Tip60. Full-length Tip60 (fl-Tip60) and catalytic domain of Tip60 (cat-Tip60) were expressed in E. coli and purified with nickel affinity chromatography. Quantitative analysis of enzyme activities demonstrated that both enzyme forms had very high activity with the substrate H4. To create new Tip60 inhibitors, various histone H3 peptides conjugated with CoA were synthesized using the Fmoc solid-phase peptide synthesis and solution phase synthesis protocols. The results from the inhibition radioactive assay …

Neural Crosstalk Between Sympathetic Nervous System And Sensory Circuits To Brown Adipose Tissue, Yang Liu

Biology Theses

Brown adipose tissue (BAT) is a critical organ for non-shivering thermogenesis, which is under control of both sympathetic and sensory neural innervation. We utilized both a retrograde sympathetic nerve tract tracer pseudorabies virus and an anterograde sensory tract tracer the H129 strain of herpes simplex virus-1 to locate individual neurons across the neuroaxis that are part of the SNS outflow from brain to interscapular BAT and are part of the sensory input to the brain. We found specific neuronal phenotype of the double-infected neurons distributed from the hindbrain to the forebrain with highest densities in several discrete brain regions: the …