Cell and Developmental Biology Commons^™

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …

Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez

Electronic Theses, Projects, and Dissertations

Conventional medical treatments fail to address the underlying problems associated with the damage inflicted by a coronary event. Thus, the long-term prognosis of patients admitted for heart failure is disheartening, with reported survival rates of 25 percent. Recent advances in stem cell research highlight the potential benefits of autologous stem cell transplantation for stimulating repair in heart tissue. However, a majority of those suffering from cardiovascular diseases are older adults whose autologous cells no longer possess optimum functional capacity. Additional work is needed to identify the optimal cell types or conditions that will promote cardiovascular regeneration across all age groups. …

Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill

Electronic Theses, Projects, and Dissertations

Ovarian cancer is the fifth leading cause of cancer death in women between the ages of 35 and 74. With 22 thousand new cases and 15 thousand deaths annually ovarian cancer is among the most deadly cancers with a death to incidence ratio of 68%. With 70% of cases High Grade Serous Ovarian Carcinoma (HGSOC) is the most common type of ovarian cancer and causes 90% of ovarian cancer deaths. 80% of patients have reoccurrence within five years and only 15-30% of patients with recurrent metastatic ovarian cancer respond to current therapies, chemotherapy and surgery. One reason for the high …

Melanocortin 1 Receptor: Structure, Function, And Regulation, Erin M. Wolf Horrell, Mary C. Boulanger, John A. D'Orazio

Physiology Faculty Publications

The melanocortin 1 receptor (MC1R) is a melanocytic G_s protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV …

The Exceptionally High Reactivity Of Cys 621 Is Critical For Electrophilic Activation Of The Sensory Nerve Ion Channel Trpa1, Parmvir K. Bahia, Thomas A. Parks, Katherine R. Stanford, David A. Mitchell, Sameer Varma, Stanley M. Stevens Jr., Thomas E. Taylor-Clark

Molecular Biosciences Faculty Publications

Activation of the sensory nerve ion channel TRPA1 by electrophiles is the key mechanism that initiates nociceptive signaling, and leads to defensive reflexes and avoidance behaviors, during oxidative stress in mammals. TRPA1 is rapidly activated by subtoxic levels of electrophiles, but it is unclear how TRPA1 outcompetes cellular antioxidants that protect cytosolic proteins from electrophiles. Here, using physiologically relevant exposures, we demonstrate that electrophiles react with cysteine residues on mammalian TRPA1 at rates that exceed the reactivity of typical cysteines by 6,000-fold and that also exceed the reactivity of antioxidant enzymes. We show that TRPA1 possesses a complex reactive cysteine …

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Biology Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Chemistry Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.

Membrane Insertion For The Detection Of Lipopolysaccharides: Exploring The Dynamics Of Amphiphile-In-Lipid Assays, Loreen R. Stromberg, Nicolas W. Hengartner, Kirstie L. Swingle, Rodney A. Moxley, Steven W. Graves, Gabriel A. Montaño, Harshini Mukundan

School of Veterinary and Biomedical Sciences: Faculty Publications

Shiga toxin-producing Escherichia coli is an important cause of foodborne illness, with cases attributable to beef, fresh produce and other sources. Many serotypes of the pathogen cause disease, and differentiating one serotype from another requires specific identification of the O antigen located on the lipopolysaccharide (LPS) molecule. The amphiphilic structure of LPS poses a challenge when using classical detection methods, which do not take into account its lipoglycan biochemistry. Typically, detection of LPS requires heat or chemical treatment of samples and relies on bioactivity assays for the conserved lipid A portion of the molecule. Our goal was to develop assays …

Study Of Alternative Functions Of The Mitochondrial Protein Bak, Ma Su Su Aung

Student Theses and Dissertations

Research in the past 15 years has established roles for the pro-apoptotic proteins Bax and Bak in release of death signaling molecules from mitochondria. The process involves relocation of cytoplasmic Bax into the mitochondrial outer membrane to form a giant pore, MAC. Another MAC component, Bak, is constitutively present in the outer membrane regardless of apoptotic stimulation. In this study we investigated the role of Bak in mitochondrial function outside the context of apoptosis. We examined the effects of Bak elimination on emission of reactive oxygen species from mitochondria. Our results indicate a disturbance of free-radical production both in cultured …

Expression And Function Of Pannexins In The Inner Ear And Hearing, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Pannexin (Panx) is a gene family encoding gap junction proteins in vertebrates. So far, three isoforms (Panx1, 2 and 3) have been identified. All of three Panx isoforms express in the cochlea with distinct expression patterns. Panx1 expresses in the cochlea extensively, including the spiral limbus, the organ of Corti, and the cochlear lateral wall, whereas Panx2 and Panx3 restrict to the basal cells of the stria vascularis in the lateral wall and the cochlear bony structure, respectively. However, there is no pannexin expression in auditory sensory hair cells. Recent studies demonstrated that like connexin gap junction gene, Panx1 deficiency …

Modelling The Polarization, Migration And Neuromast Deposition In The Zebrafish Posterior Lateral Line System, Hildur Knutsdottir

Biology and Medicine Through Mathematics Conference

No abstract provided.

Explicitly Separating Growth And Motility In A Glioblastoma Tumor Model, Tracy Stepien, Erica Rutter, Meng Fan, Yang Kuang

Biology and Medicine Through Mathematics Conference

No abstract provided.

Force Generation And Contraction Of Random Actomyosin Bundles., Dietmar B. Oelz

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling Tracheal Occlusion In The Embryonic Lung, Uduak George

Biology and Medicine Through Mathematics Conference

No abstract provided.

Flow-Dependent Myosin Recruitment During Drosophila Cellularization Requires Zygotic Dunk Activity, Bing He, Adam Martin, Eric Wieschaus

Dartmouth Scholarship

Actomyosin contractility underlies force generation in morphogenesis ranging from cytokinesis to epithelial extension or invagination. In Drosophila, the cleavage of the syncytial blastoderm is initiated by an actomyosin network at the base of membrane furrows that invaginate from the surface of the embryo. It remains unclear how this network forms and how it affects tissue mechanics. Here, we show that during Drosophila cleavage, myosin recruitment to the cleavage furrows proceeds in temporally distinct phases of tension-driven cortical flow and direct recruitment, regulated by different zygotic genes. We identify the gene dunk, which we show is transiently transcribed when cellularization starts …

Dibutyltin-Induced Alterations Of Interleukin 1beta Secretion From Human Immune Cells, Shyretha Brown, Shahin Tehrani, Margaret M. Whalen

Chemistry Faculty Research

Dibutyltin (DBT) is used to stabilize polyvinyl chloride plastics (including pipes that distribute drinking water) and as a de-worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha and interferon gamma from lymphocytes. Interleukin (IL)-1β is a proinflammatory cytokine that regulates cellular growth, tissue restoration and immune response regulation. IL-1β plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h and 6 days) modify the secretion of IL-1β from increasingly reconstituted preparations of human immune cells (highly enriched human …

Interaction Of Tau With The Rna-Binding Protein Tia1 Regulates Tau Pathophysiology And Toxicity, Tara Vanderweyde, Daniel J. Apicco, Katherine Youmans-Kidder, Peter E. A. Ash, Casey Cook, Edroaldo Lummertz Da Rocha, Karen Jansen-West, Alissa A. Frame, Allison Citro, John D. Leszyk, Pavel Ivanov, Jose F. Abisambra, Martin Steffen, Hu Li, Leonard Petrucelli, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown …

A Revisited Phylogeography Of Nautilus Pompilius, Lauren E. Vandepas, Frederick D. Dooley, Gregory J. Barord, Billie J. Swalla, Peter D. Ward

Publications and Research

The cephalopod genus Nautilus is considered a “living fossil” with a contested number of extant and extinct species, and a benthic lifestyle that limits movement of animals between isolated seamounts and landmasses in the Indo-Pacific. Nautiluses are fished for their shells, most heavily in the Philippines, and these fisheries have little monitoring or regulation. Here, we evaluate the hypothesis that multiple species of Nautilus (e.g., N. belauensis, N. repertus and N. stenomphalus) are in fact one species with a diverse phenotypic and geologic range. Using mitochondrial markers, we show that nautiluses from the Philippines, eastern Australia (Great Barrier Reef), Vanuatu, …

Mechanics Of Early Retina And Lens Development In The Embryo, Alina Oltean

McKelvey School of Engineering Graduate Student Theses & Dissertations

Mechanical forces play an essential role in morphogenesis, the shaping of embryonic structures. This research focuses mainly on eye development, a problem that has been studied for decades using a variety of approaches. However, the mechanics of the early stages of eye formation remain incompletely understood.

The embryonic eyes begin as bilateral protrusions called optic vesicles (OVs) that grow outward from the anterior end of the brain tube. The optic vesicles contact and adhere to the overlying surface ectoderm (SE) via extracellular matrix (ECM). Then, both layers thicken in the region of contact to form the retinal and lens placodes, …

Embryonic And Post-Embryonic Hoxa13 Expression In The Four-Toed Salamander, Hemidactylium Scutatum., Breanna R. Lee

Senior Honors Projects, 2010-2019

The process of somitogenesis occurs during embryological development and results in the definition of persisting axial segments. The four toed salamander, Hemidactylium scutatum, exhibits post-embryonic segmentation while most other vertebrates stop segmentation at the end of embryological development. HoxA13, a transcription factor expressed along the developing anteroposterior axis, plays a role in specifying caudal segmental identity, cell ingression into the pre-somitic mesoderm (PSM), and PSM truncation. HoxA13’s responsibilities in influencing embryological development make it an interesting candidate for involvement in post-embryonic segment addition mechanisms. This study explores the role of HoxA13 in tail segmentation in H. scutatum embryonic, larval, …