Cell and Developmental Biology Commons^™

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.

Secretion Of Interferon Gamma From Human Immune Cells Is Altered By Exposure To Tributyltin And Dibutyltin, Shanieek Lawrence, Jacqueline Reid, Margaret Whalen

Chemistry Faculty Research

Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion …

Purifying The Human Rna-Lariat Debranching Enzyme, Ammar Saigal

Honors Program Theses and Research Projects

This project is my first official research endeavor and it involved becoming acquainted with a large variety of biochemistry and molecular biology techniques. The goal is to elucidate the structure of a protein common to most if not all cells of organisms within the Domain Eukarya, which is one of the three taxonomic domains into which all life is categorized. This is the domain most relevant to human beings as it includes plants, fungi, and animals (from a strictly biologically-taxonomic perspective, the species Homo sapiens to which you and I belong is considered belonging to the Kingdom Animalia [Animal]).

Genetic Sex Conditions And Redefining Sex, Jayce O'Shields

Student Scholarship

Western culture has a tendency to value binaries and discreet categories that separate its social structure and provide a sense of order and organization. The value placed on binaries and categories may be advantageous in some aspects, but when it starts to infringe upon the legal and medical rights of individuals not easily placed in either binary category, it can become less advantageous.

A baby is usually classified as either male or female shortly after birth, and all future legal, social, and economic actions and rights of that individual are more or less decided according to this classification. A problem …

Transformation Of Stimulus Correlations By The Retina, Kristina D. Simmons, Jason Prentice, Gašper Tkačik, Jan Homann, Heather K. Yee, Stephanie E. Palmer, Philip C. Nelson, Vijay Balasubramanian

Publications and Research

Redundancies and correlations in the responses of sensory neurons may seem to waste neural resources, but they can also carry cues about structured stimuli and may help the brain to correct for response errors. To investigate the effect of stimulus structure on redundancy in retina, we measured simultaneous responses from populations of retinal ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure; these stimuli and recordings are publicly available online. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were modestly more correlated than in response to white noise checkerboards, but …

Smokeless Tobacco Use: A Risk Factor For Hyperhomocysteinemia In A Pakistani Population, Mohammad Perwaiz Iqbal, Mohsin Yakub

Department of Biological & Biomedical Sciences

Background

Smokeless tobacco (ST) use is highly prevalent in the South Asian populations. While there have been a number of reports on association of ST consumption with cancer, very few studies have been conducted to investigate its relationship with cardiovascular disease. Hyperhomocysteinemia is a well-recognized risk factor for cardiovascular disease; however, its association with ST use has never been investigated. The objective of this study was to evaluate the relationship of ST use with hyperhomocysteinemia in an urban Pakistani population.

Methodology/Principal Findings

In a cross-sectional study for assessment of risks of hyperhomocysteinemia, 872 healthy adults (355 males and 517 females …

Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva

Theses and Dissertations

The adrenal cortex is a crucial endocrine gland in the mammalian stress response. In chronic inflammatory stress, cortisol is elevated whereas adrenal androgens are decreased. Furthermore, ACTH levels have poor correlation with the plasma cortisol in these conditions, thus suggesting that other factors are driving the stress response during chronic inflammatory stress. Interleukin-6 (IL-6), a cytokine which is released during chronic inflammatory stress, is assumed to be one such factor. Thus the biochemical pathways by which IL-6 increases cortisol release from the zona fasciculata (ZF), and decreases adrenal androgen release from the zona reticularis (ZR) were investigated. Since IL-6 activates …

Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen

Theses and Dissertations

The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. …

The Development Of An In Vivo Microdialysis Collection Method Of Cytokines From Brain Tissue, Anthony W. Herbaugh

Graduate Theses and Dissertations

In this thesis, different methods to improve the microdialysis collection procedure for cytokines from brain tissue are presented. The first method was based on stopped flow and results indicating that no significant difference in relative recovery between stopped flow and continuous flow are shown. The second method is an antibody bead-based enhancement method. With the antibody bead-based method, a 3.5 fold increase in the collected concentrations of Chemokine (C-C motif) Ligand 2 (CCL2) were observed. However, there was no significant increase in the in vivo collection efficiency of Interleukin-6 (IL-6) using the antibody enhancement. Finally the development of an in-house …

Investigation Of The Role Of Tor And Nutrient Restriction On Lifespan Of Arabidopsis Thaliana, Debashree Banerjee

Dissertations, Masters Theses, Capstones, and Culminating Projects

The Target of Rapamycin (TOR) kinase is evolutionarily conserved and is a key regulator, controlling many cellular functions to promote survival and growth in all eukaryotes. Several model organisms have indicated a relationship between TOR signaling and life expectancy, such as yeast, fruit flies and mice. Abundant nutrient availability promotes rapid growth and development, whereas depletion of nutrients reduces the activity of the pathways that are involved in growth and nutrient processing. This reduction in activity increases life expectancy, which is supported by evolutionary theories. The confirmed presence of the TOR homolog (a major regulator of growth and cell proliferation) …

Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli Venkata Govri Chandra Sekhar, Anil Kumar, Amir Nasrolahi Shirazi, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized (1H NMR, 13C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemiacells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10mol) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines. Cancer is a leading cause of death worldwide. It is a group of diseases characterized by uncontrolled growth. Cancer …

Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed

Theses and Dissertations

GABA neurons in the ventral tegmental area of the midbrain are important components in the brain's reward circuit. Long term changes in this circuit occur through the process of synaptic plasticity. It has been shown that high frequency stimulation, as well as treatment with endocannabinoids, can cause GABA neurons in the ventral tegmental area to undergo long term depression, a form of synaptic plasticity that decreases excitability of cells. The present study elaborates on the mechanism whereby high frequency stimulation can result in long term depression of ventral tegmental area GABA neurons. Using the whole cell patch clamp technique in …

Development Of Novel Subunit Vaccine Against H5n1 Influenza, Lu Zhang

Graduate Theses and Dissertations

Influenza is a common infectious disease resulting from a frequently mutated RNA virus. Vaccination is currently the most effective method to prevent people from seasonal or pandemic influenza. The production of traditional egg-based influenza vaccine is time-consuming and provides limited effect against new strains. Therefore, it is necessary to develop a rapid method to produce influenza vaccines. We proposed a novel influenza vaccine based on the E.coli expression system. Hemagglutinin (HA) is the major target surface protein of influenza virus for vaccine development. In this study, we sub-cloned the HAs encoding gene into an E. coli expression vector; the signal …

A Novel Role Of Oncostatin M In Invasive Breast Cancer: Induction Of Cathepsin D And Lysosomal Trafficking, Jordan Barrie Koncinsky

Boise State University Theses and Dissertations

Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine shown to be important in inflammation, hematopoiesis, development and bone homeostasis. Despite its role as a growth suppressor for many cancers, including breast cancer, OSM is currently being studied for its ability to promote tumor invasion and metastasis. Cathepsin D (CTSD) is a lysosomal protease found to be overexpressed and hypersecreted in breast and other cancers. In this study, we found OSM to induce the expression of CTSD protein in human breast cancer cells via the STAT3 and JNK2 pathways. Next, we investigated mechanisms resulting in the increased secretion of CTSD …

Protective Effects Of Sphingomyelin Against Uv Photodamage In Human Keratinocytes, Kathleen De Guzman

Master's Theses

Ultraviolet (UV) radiation has been demonstrated in numerous studies to be a major risk factor for non-melanoma skin cancer development. Despite the emergence of current UV-preventative strategies, such as sunscreens and skin-protective clothing, the incidence of non-melanoma skin cancer has continued to rise. This has encouraged investigations on alternative methods for UV prevention. In particular, bovine milk sphingomyelin has been studied for its potential in protecting human skin against UV photodamage. While the previous studies have suggested that sphingomyelin exhibits UV-protective properties in a human skin equivalent model, the exact mechanisms behind sphingomyelin’s photoprotective effects are yet unknown.

This thesis …

Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff

Dissertations and Theses (Open Access)

Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been …

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

Dissertations and Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated …

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

Dissertations and Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of …

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy. Moreover, …

A New Species Of Euscorpius From Tinos Island, Greece (Scorpiones: Euscorpiidae), Victor Fet, Michael E. Soleglad, Aristeidis Parmakelis, Panayiota Kotsakiozi, Iasmi Stathi

Biological Sciences Faculty Research

The scorpion genus Euscorpius has been insufficiently studied on the Aegean Islands of Greece. We describe a new species from the Western Cyclades, E. kritscheri sp. n., from Tinos Island. The species-level status of this form is confirmed by a phylogenetic study based on multiple DNA markers. In addition, a population from nearby Andros Island is characterized as E. cf. kritscheri, which could be potentially a separate species.