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Effects Of Microgravity On Cancer Stem Cells Cultured In A Nasa Developed Bioreactor: Chemotherapeutic Implications., Sarah Elizabeth Daron Kelly

Theses, Dissertations and Capstones

The purpose of this study was to investigate the effects of simulated microgravity on cancer cell growth. Simulated microgravity is a condition in which cells are in constant free-fall and in which they are able to grow suspended without the shear and stress. Microgravity allows for important insights into the cellular mechanism and may be key in understanding why some cells thrive in this condition and others go into apoptosis. Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining cancer. SAOS-2 is a human bone cancer cell line which consists of a …

Deferasirox Decreases Age-Associated Iron Accumulation In The Aging F344bn Rat Heart, Ravi K. Arvapalli

Theses, Dissertations and Capstones

It is thought that aging in rats and humans is associated with increases in iron accumulation and these increases in iron may be associated with increased cellular apoptosis. Here we examine the relationship between cardiac iron levels and cardiomyocyte apoptosis in aged F344BN rats which were treated with an oral iron chelator (Deferasirox; 100mg/kg body. weight/day) for 6 months. Compared with 6- month controls, the levels of cardiac iron, cardiac apoptosis, FLC and DMT-1 were higher in 33-month hearts. Deferasirox treatment for six months decreased cardiac iron and this was associated with decreases in the number of apoptotic cardiac myocytes. …

Fusion, 2009, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Nerve, Muscle, Blood, Toil, Tears, And Sweat: England’S Pioneering Biophysicist, Soldier, And Statesman, Arshad Khan

Selected Works Temporary Series

No abstract provided.

Saving Lives And Changing Family Histories: Appropriate Counseling Of Pregnant Women And Men And Women Of Reproductive Age, Concerning The Risk Of Radiation Exposures During And Before Pregnancy, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Viewing Preschool Disruptive Behavior Disorders And Attention-Deficit/Hyperactivity Disorder Through A Developmental Lens: What We Know And What We Need To Know, Anil Chacko, Lauren Wakschlag, Carri Hill, Barbara Danis, Kimberly A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Although DSM-defined DBDs and ADHD manifest during early childhood in meaning¬ful ways, the emphasis of extending the DBD and ADHD nosology, which is based on studies of older youth, to younger children potentially limits the utility of these symptoms. Given that it is clear that DBDs and ADHD often emerge during early childhood and that early intervention is most efficacious, developing a more refined understanding of the clinical phenomenology of behavior disorders in early childhood is a critical next step. We contend that an approach that emphasizes the developmental specification of symptoms has the potential to address several long-standing issues …

Efficacy Of Deferasirox In Preventing Complications Of Iron Overload In The Iron Overloaded Gerbil, Rabaa M. Al-Rousan

Theses, Dissertations and Capstones

Iron overload is a significant, world-wide problem that results in several chronic diseases including cardiovascular, hepatic and pancreatic complications.The newly developed, orally effective, iron chelating agent deferasirox is thought to offer tremendous promise as an alternative to deferoxamine. However, the efficacy and safety profile of deferasirox is not yet clear. In the present study, the efficacy of deferasirox in removing iron from target tissues has been examined using the gerbil model of iron overload. Deferasirox administration resulted in a significant reduction of iron from cardiac and hepatic tissue. In addition deferasirox reduced iron induced increase in cardiac and hepatic oxidative …

Light-Induced Fos Expression In Intrinsically Photosensitive Retinal Ganglion Cells In Melanopsin Knockout (Opn4-/-) Mice, Gary E. Pickard, Scott B. Baver, Malcolm D. Ogilvie, Patricia J. Sollars

School of Veterinary and Biomedical Sciences: Faculty Publications

Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs) and exhibit robust synaptically driven ON-responses to light, yet they will continue to depolarize in response to light when all synaptic input from rod and cone photoreceptors is removed. The light-evoked increase in firing of classical ganglion cells is determined by synaptic input from ON-bipolar cells in the proximal sublamina of the inner plexiform layer. OFF-bipolar cells synapse with ganglion cell dendrites in the distal sublamina of the inner plexiform layer. Of the several types of ipRGC that have been described, M1 ipRGCs send dendrites exclusively into the …

Growth Mixture Modeling Of Academic Achievement In Children Of Varying Birth Weight Risk, Kimberly A. Espy, Julia Hua Fang, David Charak, Nori Minich, H. Gerry Taylor

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

The extremes of birth weight and preterm birth are known to result in a host of adverse outcomes, yet studies to date largely have used cross-sectional designs and variable-centered methods to understand long-term sequelae. Growth mixture modeling (GMM) that utilizes an integrated person- and variable-centered approach was applied to identify latent classes of achievement from a cohort of school-age children born at varying birth weights. GMM analyses revealed 2 latent achievement classes for calculation, problem-solving, and decoding abilities. The classes differed substantively and persistently in proficiency and in growth trajectories. Birth weight was a robust predictor of class membership for …

Power Of Models In Longitudinal Study: Findings From A Full- Crossed Simulation Design, Hua Fang, Gordon P. Brooks, Maria L. Rizzo, Kimberly A. Espy, Robert S. Barcikowski

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Because the power properties of traditional repeated measures and hierarchical multivariate linear models have not been clearly determined in the balanced design for longitudinal studies in the literature, the authors present a power comparison study of traditional repeated measures and hierarchical multivariate linear models under 3 variance-covariance structures. The results from a full-crossed simulation design suggest that traditional repeated measures have significantly higher power than do hierarchical multivariate linear models for main effects, but they have significantly lower power for interaction effects in most situations. Significant power differences are also exhibited when power is compared across different covariance structures.

Nerve, Muscle, Blood, Toil, Tears, And Sweat: England’S Pioneering Biophysicist, Soldier, And Statesman, Khan

Departmental Papers (Biology)

No abstract provided.

Reduced Genomic Potential For Secreted Plant Cell-Wall-Degrading Enzymes In The Ectomycorrhizal Fungus Amanita Bisporigera, Based On The Secretome Of Trichoderma Reesei, Subashini Nagendran, Heather E. Hallen-Adams, Janet M. Paper, Nighat Aslam, Jonathan D. Walton

Heather Hallen-Adams Publications

Based on the analysis of its genome sequence, the ectomycorrhizal (ECM) basidiomycetous fungus Laccaria bicolor was shown to be lacking many of the major classes of secreted enzymes that depolymerize plant cell wall polysaccharides. To test whether this is also a feature of other ECM fungi, we searched a survey genome database of Amanita bisporigera with the proteins found in the secretome of Trichoderma reesei (syn. Hypocrea jecorina), a biochemically well-characterized industrial fungus. Additional proteins were also used as queries to compensate for major groups of cell-wall-degrading enzymes lacking in the secretome of T. reesei and to substantiate conclusions …

Identification And Characterization Of Novel Sir3/Mecp2-Chromatin Interactions, Nicholas L. Adkins

Theses, Dissertations and Capstones

The eukaryotic genome is packaged into chromosomes that are made up of a highly organized and heavily regulated structure called chromatin. The proteins involved in the compaction of DNA into this condensed state are mostly understood at the level of the structure of the nucleosome. The higher order arrangement of chromatin and how it effects gene regulation is only partially understood and characterized. The compaction of nucleosomal arrays into 30-nm and higher structures are partially the responsibility of architectural, or structural, chromatin associated proteins. The following dissertation analyzes the individual chromatin contributions of two well studied architectural proteins, the yeast …

The Role Of Glutamate And Its Receptors In Mesocorticolimbic Dopaminergic Regions In Opioid Addiction, Yuan Guo, Hui-Ling Wang, Xiao-Hui Xiang, Yan Zhao

United States Public Health Resources

Accumulating evidence suggests that glutamate, as one of the most important excitatory neurotransmitters in the brain, plays a key role in drug addiction including opioid addiction. There is substantial evidence for glutamatergic projections into mesocorticolimbic dopaminergic neurons, which are associated with opioid psychological dependence and are also the key regions of enhancement effect. Glutamate may be involved in the process of opioid addiction not only by acting on its ionotropic and metabotropic glutamate receptors that activate several signal transduction pathways, but also by interacting with other neurotransmitters or neuropeptides such as opioids, dopamine, y-aminobutyric acid and substance P in the …

Regulation Of Alginate Production Of Pseudomonas Aeruginosa Pseudomonas Aeruginosa, Fredrick Heath Damron

Theses, Dissertations and Capstones

Pseudomonas aeruginosa (P.a.) is a major threat to the health and well being of a person living with cystic fibrosis (CF). P.a. is capable of conversion to mucoidy or alginate overproducing phenotype. Mucoidy facilitates the chronic infection of P.a. infection in the CF lung. Mutations in the anti-sigma factor mucA, result in activation of the sigma factor AlgU which promotes expression of alginate through the alginate biosynthetic operon. However, P.a. can produce alginate independent of mucA mutation via a mechanism known as regulated proteolysis. Proteases AlgW and MucP can degrade MucA to liberate and activate AlgU. In this dissertation, two …

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …

Are Morphological Specializations Of The Hyolingual System In Chameleons And Salamanders Tuned To Demands On Performance?, Anthony Herrel, Stephen M. Deban, Vicky Schaerlaeken, Jean-Pierre Timmermans, D. Adriaens

Integrative Biology Faculty and Staff Publications

Extremely specialized and long tongues used for prey capture have evolved independently in plethodontid salamanders and chameleons. In both systems, the demands on tongue projection are probably similar: to maximize projection velocity and distance. Consequently, many of the design features of the projection system in these two groups have converged to an astonishing degree. Both involve the use of power amplification systems based on helically wound muscle fibers that load internal connective tissue sheets as illustrated in previous studies. Demands imposed on tongue retraction, however, are different to some degree. Although in both groups there is a clear demand for …

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …

Identification And Characterization Of A New Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator (Rta)- Responsive Element Involved In Rta-Mediated Transactivation, Hui-Ju Wen, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is well established as a key transcriptional activator that regulates the KSHV life cycle from latency to lytic replication. It is expressed immediately after infection and activates a number of viral genes leading to virus replication. The RTA-responsive element (RRE) in the RTA target gene promoters is critical for RTA to mediate this transactivation. A number of non-conserved RREs have been identified in various RTA-responsive promoters, and AT-rich sequences have been proposed to serve as RTA targets, but no consensus RRE sequence has been identified so far. Two nonconserved RREs (RRE1 …

Use Of Average Mutual Information For Studying Changes In Hiv Populations, Khalid Sayood, Federico Hoffman, Charles Wood

Nebraska Center for Virology: Faculty Publications

Average mutual information (AMI) has been used in a number of applications in bioinformatics. In this paper we present its use to study genetic changes in populations; in particular populations of HIV viruses. Disease progression of HIV-1 infection in infants can be rapid resulting in death within the the first year, or slow, allowing the infant to survive beyond the first year. We study the development of rapid and slow progressing HIV population using AMI charts based on average mutual information among amino acids in the env gene from a population of 1142 clones derived from seven infants with slow …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Expression Of Semaphorin 3f And Its Receptors In Epithelial Ovarian Cancer, Fallopian Tubes, And Secondary Müllerian Tissues, Christina D. Drenberg, Sandra Livingston, Ren Chen, Patricia A. Kruk, Santo V. Nicosia

Pathology and Cell Biology Faculty Publications

While semaphorins and their receptors appear to play a role in tumor carcinogenesis, little is known about the role of semaphorin 3F (S3F) in epithelial ovarian cancer (EOC) development. Therefore, we sought to determine the clinical relationship between S3F and its receptors, neuropilin-2 (NP-2) and neuropilin-1 (NP-1) with EOC progression. We analyzed the immunohistological expression of S3F, NP-2, and NP-1 in clinical specimens of normal ovaries (N), benign cystadenomas (Cy), well-differentiated adenocarcinomas (WD), poorly-differentiated adenocarcinomas (PD), inclusion cysts (IC), paraovarian cysts (PC), and fallopian tubes (FT). Tissue sections were evaluated for staining intensity and percentage of immunoreactive epithelia. We found …

Impact Of The Short-Term Consumption Of A Moderately High Fat Diet On Nitric Oxide Production And Bioavailibility, Kan Huang

Theses, Dissertations and Capstones

Nitric oxide (NO) plays an essential role in the regulation of numerous biological processes. Its bioavailability is assured by a well regulated balance between NO generation and NO removal. Disruptions in this balance contribute to the pathogenesis of various diseases, including hypertension, Alzheimer’s disease, diabetes mellitus and arthritis. Many factors contribute to the maintenance of NO bioavailability by controlling nitric oxide synthase (NOS) expression, NOS activity, the availability of substrates and cofactors involved in the generation of NO by NOS, levels of reactive oxygen species (ROS), and the formation and mobilization of NO reservoirs. Dietary factors have a significant impact …

Habitat Variation Among Aquatic Gastropod Assemblages Of Indiana, U.S.A., Mark Pyron, Jayson Beugly, Matthew Spielman, Jennifer Pritchett, Stephen J. Jacquemin

Biological Sciences Faculty Publications

We collected aquatic gastropods at 137 sites in lakes and streams of Indiana and tested for patterns of assemblages with environmental variables. The survey resulted in 32 species with a mean of 2.8 species at each site, and a mean abundance at each site of 144 individuals. Nonmetric multidimensional scaling (NMS) multivariate analyses resulted in watershed drainage area, water conductivity, substrate category frequency, and dissolved oxygen as significant correlates of gastropod assemblage structure. Gastropod assemblages of lakes were not significantly different than assemblages of streams in the ordination. Prosobranch taxa occurred in higher abundances than pulmonate taxa at sites with …

Differential Effects Of Th1, Monocyte/Macrophage And Th2 Cytokine Mixtures On Early Gene Expression For Molecules Associated With Metabolism, Signaling And Regulation In Central Nervous System Mixed Glial Cell Cultures, Robert P. Lisak, Joyce A. Benjamins, Beverly Bealmear, Liljana Nedelkoska, Diane Studzinski, Ernest Retland, Bin Yao, Susan Land

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS) in multiple sclerosis (MS).

Methods

We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M).

Results

In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, …

Primate Phylogenomics: Developing Numerous Nuclear Non-Coding, Non-Repetitive Markers For Ecological And Phylogenetic Applications And Analysis Of Evolutionary Rate Variation, Zuogang Peng, Navin Elango, Derek E. Wildman, Soojin V. Yi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Genetic analyses are often limited by the availability of appropriate molecular markers. Markers from neutrally evolving genomic regions may be particularly useful for inferring evolutionary histories because they escape the constraints of natural selection. For the majority of taxa however, obtaining such markers is challenging. Advances in genomics have the potential to alleviate the shortage of neutral markers. Here we present a method to develop numerous markers from putatively neutral regions of primate genomes.

Results

We began with the available whole genome sequences of human, chimpanzee and macaque. Using computational methods, we identified a total of 280 potential …

Incorporation Of Membrane-Bound, Mammalian-Derived Immunomodulatory Proteins Into Influenza Whole Virus Vaccines Boosts Immunogenicity And Protection Against Lethal Challenge, Andrew S. Herbert, Lynn Heffron, Roy Sundick, Paul C. Roberts

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.

Results

We have evaluated the immunogenicity of inactivated cytokine-bearing influenza …

Bacterial Selenoproteins: A Role In Pathogenesis And Targets For Antimicrobial Development, Sarah Rosario

Electronic Theses and Dissertations

Selenoproteins are unique proteins in which selenocysteine is inserted into the polypeptide chain by highly specialized translational machinery. They exist within all three kingdoms of life. The functions of these proteins in biology are still being defined. In particular, the importance of selenoproteins in pathogenic microorganisms has received little attention. We first established that a nosocomial pathogen, Clostridium difficile, utilizes a selenoenzyme dependent pathway for energy metabolism. Following this initial characterization, we demonstrate that this pathway is linked to production of toxins by this organism. Finally, we show that interruption of selenium metabolism is a viable pathway for development of …

The Effect Of Dust-Mites On Nitric Oxide Production, Süleyman Yazar, Eser Kiliç, Meti̇n Atambay, Aysun Bay Karabulut, Özlem Makbule Aycan, Gülden Sönmez Tamer, Ni̇lgün Daldal

Turkish Journal of Medical Sciences

Aim: We aimed to investigate the effect of house dust mite on the level of nitric oxide in patients who had dust mite in their houses and suffering from rhinitis and/or asthma and/or eczema-like allergic symptoms and were positive for skin tests (Prick). Materials and Methods: The effect of dust-mites on nitric oxide concentration was investigated using Griess method in patients who had allergic symptoms and were positive for skin tests. Results: The plasma nitric oxide level was found to be statistically higher in patients who had dust mite in their houses and suffering from allergic symptoms and were positive …