Cell and Developmental Biology Commons^™

Mechanisms Of Nitrogenous Waste Excretion During The Complex Life Cycle Of The Sea Lamprey (Petromyzon Marinus), James M. Neal Mr.

Theses and Dissertations (Comprehensive)

Sea lampreys (Petromyzon marinus) are a phylogenetically ancient jawless fish, with a multi-staged life cycle characterized by a prolonged suspension-feeding larval stage, which is followed by metamorphosis into parasitic lampreys that feed on the protein-rich blood of fishes. The switch from a nutrient poor to protein-rich diet in the sea lamprey is associated with an increased capacity to deaminate excess amino acids and to excrete ammonia and urea following metamorphosis. The focus of this thesis was to determine if changes in nitrogenous waste transporter protein abundance facilitate ammonia and urea excretion during different stages of the sea lamprey …

Vegf And Angiopoietin-1 Exert Opposing Effects On Cell Junctions By Regulating The Rho Gef Syx, Siu P. Ngok, Rory Geyer, Miaoliang Liu, Antonis Kourtidis, Sudesh Agrawal, Chuanshen Wu, Himabindu Reddy Seerapu, Laura J. Lewis-Tuffin, Karen L. Moodie, Deborah Huveldt, Ruth Marx, Jay M. Baraban, Peter Storz, Arie Horowitz, Panos Z. Anastasiadis

Dartmouth Scholarship

Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was …

A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan

Dissertations and Theses (Open Access)

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates …

Tet1: A Unique Dna Demethylase For Maintenance Of Dna Methylation Pattern, Chunlei Jin

Dissertations and Theses (Open Access)

DNA methylation at the C5 position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification of the genome and has been implicated in numerous cellular processes in mammals, including embryonic development, transcription, X chromosome inactivation, genomic imprinting and chromatin structure. Like histone modifications, DNA methylation is also dynamic and reversible. However, in contrast to well defined DNA methyltransferases, the enzymes responsible for erasing DNA methylation still remain to be studied. The ten-eleven translocation family proteins (TET1/2/3) were recently identified as Fe(II)/2-oxoglutarate (2OG)-dependent 5mC dioxygenases, which consecutively convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine both in vitro and in mammalian …

Blt1 And Mid1 Provide Overlapping Membrane Anchors To Position The Division Plane In Fission Yeast, Merce Guzman-Vendrell, Suzanne Baldissard, Maria Almonacid, Adeline Mayeux, Anne Paoletti, James B. Moseley

Dartmouth Scholarship

Spatial control of cytokinesis is essential for proper cell division. The molecular mechanisms that anchor the dynamic assembly and constriction of the cytokinetic ring at the plasma membrane remain unclear. In the fission yeast Schizosaccharomyces pombe, the cytokinetic ring is assembled in the cell middle from cortical node precursors that are positioned by the anillin-like protein Mid1. During mitotic entry, cortical nodes mature and then compact into a contractile ring positioned in the cell middle. The molecular link between Mid1 and medial cortical nodes remains poorly defined. Here we show that Blt1, a previously enig- matic cortical node protein, promotes …

Scribble Acts In The Drosophila Fat-Hippo Pathway To Regulate Warts Activity, Shilpi Verghese, Indrayani Waghmare, Hailey Kwon, Katelin Hanes, Madhuri Kango-Singh

Biology Faculty Publications

Epithelial cells are the major cell-type for all organs in multicellular organisms. In order to achieve correct organ size, epithelial tissues need mechanisms that limit their proliferation, and protect tissues from damage caused by defective epithelial cells. Recently, the Hippo signaling pathway has emerged as a major mechanism that orchestrates epithelial development. Hippo signaling is required for cells to stop proliferation as in the absence of Hippo signaling tissues continue to proliferate and produce overgrown organs or tumors. Studies in Drosophila have led the way in providing a framework for how Hippo alters the pattern of gene transcription in target …

Cartilage On The Move: Cartilage Lineage Tracing During Tadpole Metamorphosis, Ryan R. Kerney, Alison L. Brittain, Brian K. Hall, Daniel R. Buchholz

Biology Faculty Publications

The reorganization of cranial cartilages during tadpole metamorphosis is a set of complex processes. The fates of larval cartilage-forming cells (chondrocytes) and sources of adult chondrocytes are largely unknown. Individual larval cranial cartilages may either degenerate or remodel, while many adult cartilages appear to form de novo during metamorphosis. Determining the extent to which adult chondrocytes/cartilages are derived from larval chondrocytes during metamorphosis requires new techniques in chondrocyte lineage tracing. We have developed two transgenic systems to label cartilage cells throughout the body with fluorescent proteins. One system strongly labels early tadpole cartilages only. The other system inducibly labels forming …

Characterization Of The Stem Cell Niche In Drosophila Testes, Vittorio Mena Jr.

Seton Hall University Dissertations and Theses (ETDs)

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Rapid Range Expansion In The Great Plains Narrow-Mouthed Toad (Gastrophryne Olivacea) And A Revised Taxonomy For North American Microhylids, Jeffrey W. Streicher, Christian L. Cox, Jonathan A. Campbell, Eric N. Smith, Rafael O. De Sá

Biology Faculty Publications

We investigated genetic variation within the Great Plains narrow-mouthed toad, Gastrophryne olivacea, across its geographic range in the United States and Mexico. An analysis of mitochondrial DNA (mtDNA) from 105 frogs revealed remarkably low levels of genetic diversity in individuals inhabiting the central United States and northern Mexico. We found that this widespread matrilineal lineage is divergent (ca. 2% in mtDNA) from haplotypes that originate from the western United States and western coast of Mexico. Using a dataset that included all five species of Gastrophryne and both species of the closely related genus Hypopachus, we investigated the phylogenetic …

Developing Monitoring Methods For Leptasterias Spp. As Sentinel Species In Detecting Local Environmental Changes, Zachary Sturbaum, Kathryn Nuessly, Riley J. Smith, C. Sarah Cohen

STAR Program Research Presentations

Leptasterias spp., a six-rayed sea star, is found in rocky intertidal habitats ranging from Alaska to central California. Leptasterias spp. can be monitored on a broad scale throughout their range by a variety of means using timed counts and random plot censusing in order to detect both large-scale and local-level changes in the environment due to climate change, land-based human activity, or other environmental events. Leptasterias brood their young externally until the embryos grow into fully developed juveniles. These juveniles disperse by crawling away, limiting their dispersal potential. This localized dispersal provides an opportunity to use Leptasterias spp …

Platelets And Anti-Angiogenic Resistance In Ovarian Carcinoma, Justin N. Bottsford-Miller

Dissertations and Theses (Open Access)

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified.

Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of …

Plant Lectin Can Target Receptors Containing Sialic Acid, Exemplified By Podoplanin, To Inhibit Transformed Cell Growth And Migration, Jhon Ochoa-Alvarez, Harini Krishnan, Yongquan Shen, Nimish Acharya, Min Han, Dean Mcnulty, Hitoki Hasegawa

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors …

Mecp2 Binds To Nucleosome Free (Linker Dna) Regions And To H3k9/H3k27 Methylated Nucleosomes In The Brain, Anita A. Thambirajah, Marlee K. Ng, Lindsay J. Frehlick, Andra Li, Jason J. Serpa, Evgeniy V. Petrotchenko, Begonia Silva-Moreno, Kristal K. Missiaen, Christoph H. Borchers, J. Adam Hall, Ryan Mackie, Frank Lutz, Brent E. Gowen, Michael Hendzel, Philippe T. Georgel, Juan Ausió

Biological Sciences Faculty Research

Methyl-CpG-binding protein 2 (MeCP2) is a chromatin-binding protein that mediates transcriptional regulation, and is highly abundant in brain. The nature of its binding to reconstituted templates has been well characterized in vitro. However, its interactions with native chromatin are less understood. Here we show that MeCP2 displays a distinct distribution within fractionated chromatin from various tissues and cell types. Artificially induced global changes in DNA methylation by 3-aminobenzamide or 5-aza-2′-deoxycytidine, do not significantly affect the distribution or amount of MeCP2 in HeLa S3 or 3T3 cells. Most MeCP2 in brain is chromatin-bound and localized within highly nuclease-accessible regions. We …

The Role Of Actin Binding Proteins In Cell Motility, Elizabeth Ojukwu

Honors Scholar Theses

Actin binding proteins (ABPs) play key roles in the dynamic organization of the actin cytoskeleton during cell movement. The general localization of ABPs during dynamic cellular processes has been characterized. However, their specific functions and mechanisms of regulating the cytoskeleton during motile cellular processes remain unclear. Two approaches have been utilized to ask how these proteins contribute to cytoskeletal function during motility. Using homologous recombination, mutant cell lines lacking α-actinin, fimbrin or both proteins have been created. By analyzing mutants that lack these proteins, we hope to disrupt processes that require a functional cytoskeleton such as phagocytosis, random motility, development, …

Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter

Mahurin Honors College Capstone Experience/Thesis Projects

Oxaliplatin is a third generation anticancer drug that has proven to be successful in fighting ovarian and testicular cancer. We are interested in determining how oxaliplatin and oxaliplatin derivatives interact with proteins, as well as how that interaction is affected by the size and shape of these platinum compounds. We have synthesized oxaliplatin as it is used in cancer treatment, as well as similar platinum compounds with the same diaminocyclohexane ligand as oxaliplatin but with additional bulk added to the nitrogen atoms. We are reacting oxaliplatin with key amino acids, including methionine, and will be comparing the kinetics of this …

Effect Of Combining Bcl-2 Inhibition And Radiation On Apoptotic Cell Death In Human Breast Cancer Cell Lines As Determined By Clonogenic Assay And Western Blots, Amari Sasha Howard

Renée Crown University Honors Thesis Projects - All

Cancer is a group of diseases characterized by abnormal control of cell growth and cell survival. Current treatment for cancer employs a combination of modalities including surgery, radiation, chemotherapeutic drugs, and immunotherapy. Our lab focuses on personalized medicine and treatments that can specifically target molecular features of a tumor as presented by the particular patient being treated. Cancers often exhibit an over-expression or under-expression of certain proteins that play a large role in regulating the process of apoptosis, which is programmed cell death. This study focuses on proposing drug treatment for cancer that is personalized in that it targets a …

Role Of Progesterone Receptors In Neonatal Ovary Development, Marta N. Dzyadyk

Renée Crown University Honors Thesis Projects - All

In female mammals, proper oocyte development is a vital prerequisite for future gamete viability and fertility. This development of oocytes, known as oogenesis, begins with the migration of primordial germ cells to the genital ridge of the early embryo, where multiple rounds of mitotic division occur without complete cytokinesis. The result is temporary cyst morphology. Cyst breakdown is a crucial process in the next developmental stage, resulting in formation of the single oocytes which will grow in follicles surrounded by granulosa cells and eventually develop into eggs. These aspects of embryogenesis are conserved across multiple species, including Drosophila, mice, and …

Analyzing The Roles Of Scl And Gata3 In Zebrafish Spinal Cord Interneuron Specification And Function, Kadiah Oyah Kamara

Renée Crown University Honors Thesis Projects - All

My project focuses on the V2 cells of the zebrafish spinal cord. The V2 cells are an unusual class of spinal cells because they all originate from molecularly indistinguishable p2 progenitor cells in the spinal cord. However, as these cells become post-mitotic and differentiate, they start to express different transcription factor genes that allow them to initially develop into two sets of molecularly distinct cells. As differentiation continues, at least one more class of molecularly distinct cells develops. Just as in other vertebrates, in zebrafish the V2 cells differentiate into at least two functionally distinct classes of cells, specifically, the …

The Expression Pattern Of The Xenopus Laevis Rod-Derived Cone Viability Factor1 (Rdcvf1), Vera Osafo

Renée Crown University Honors Thesis Projects - All

In the United States alone, more than one million people are blind. One of the leading causes of blindness is the retinal disease, Retinitis Pigmentosa (RP). RP is a heterogeneous group of inherited disorders characterized by the initial loss of rod photoreceptors. Approximately 100,000 people in the United States and 1.5 million people worldwide are affected by RP. Unfortunately, there is no cure. In humans with RP, it is known that the loss of rod photoreceptors leads to degeneration of cones. Rods photoreceptors are responsible for vision under low light conditions and cone photoreceptors are required for color vision and …

Endotoxin-Induced Inflammation & Morphine-Induced Conditioned Place Preference In The Hiv-1 Transgenic Rat, Natasha F. Homji-Mishra

Seton Hall University Dissertations and Theses (ETDs)

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Fluorescence-Based Reporter For Gauging Cyclic Di-Gmp Levels In Pseudomonas Aeruginosa, Morten T. Rybtke, Bradley R. Borlee, Keiji Murakami, Yasuhiko Irie, Morten Hentzer, Thomas E. Nielsen, Michael Givskov, Matthew R. Parsek, Tim Tolker-Nielsen

Biology Faculty Publications

The increased tolerance toward the host immune system and antibiotics displayed by biofilm-forming Pseudomonas aeruginosa and other bacteria in chronic infections such as cystic fibrosis bronchopneumonia is of major concern. Targeting of biofilm formation is believed to be a key aspect in the development of novel antipathogenic drugs that can augment the effect of classic antibiotics by decreasing antimicrobial tolerance. The second messenger cyclic di-GMP is a positive regulator of biofilm formation, and cyclic di-GMP signaling is now regarded as a potential target for the development of antipathogenic compounds. Here we describe the development of fluorescent monitors that can gauge …

Microrna Regulation Of Prostate Cancer Stem/Progenitor Cells And Prostate Cancer Development, Can Liu

Dissertations and Theses (Open Access)

Most human tumors contain a population of cells with stem cell properties, called cancer stem cells (CSCs), which are believed to be responsible for tumor establishment, metastasis, and resistance to clinical therapy. It’s crucial to understand the regulatory mechanisms unique to CSCs, so that we may design CSC-specific therapeutics. Recent discoveries of microRNA (miRNA) have provided a new avenue in understanding the regulatory mechanisms of cancer. However, how miRNAs may regulate CSCs is still poorly understood. Here, we present miRNA expression profiling in six populations of prostate cancer (PCa) stem/progenitor cells that possess distinct tumorigenic properties. Six miRNAs were identified …

Development And Evaluation Of A Mouse Neocortical Cells Neurodevelopment Assay To Assess The Effects Of Pyrethroids, Stephanie I. Savino

Pell Scholars and Senior Theses

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the global insecticide market with household, agricultural and public health applications. With increasing use of pyrethroids over recent years, human exposure to these chemicals is likely. The acute toxicity of pyrethroids to mammalian adults has been documented as moderately toxic by the U.S. Environmental Protection Agency. However, little evidence is available regarding the potential toxicological effects of pyrethroids on mammalian neurodevelopment. In this study, a neurodevelopment assay was developed for future investigation of potential pyrethroid effects on the neuronal development of Mus musculus neocortical cells.

Chronic Stress Promotes Tumor Growth Through Increased Bdnf Production And Neo-Innervation, Julie K. Allen

Dissertations and Theses (Open Access)

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor growth.

Results: First, I examined whether sympathetic nerves are present in human ovarian cancer samples as well as orthotopic ovarian cancer models. Immunohistochemical (IHC) staining for neurofilament revealed that catecholaminergic neurons are present within tumor tissue. In order to determine …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Identification Of Amino Acids Essential For Estrone-3-Sulfate Transport Within Transmembrane Domain 2 Of Organic Anion Transporting Polypeptide 1b1, Nan Li, Weifang Hong, Hong Huang, Hanping Lu, Guangyun Lin, Mei Hong

School of Information Faculty Publications

As an important structure in membrane proteins, transmembrane domains have been found to be crucial for properly targeting the protein to cell membrane as well as carrying out transport functions in transporters. Computer analysis of OATP sequences revealed transmembrane domain 2 (TM2) is among those transmembrane domains that have high amino acid identities within different family members. In the present study, we identify four amino acids (Asp70, Phe73, Glu74, and Gly76) that are essential for the transport function of OATP1B1, an OATP member that is specifically expressed in the human liver. A substitution of these four amino acids with alanine …

A Fap46 Mutant Provides New Insights Into The Function And Assembly Of The C1d Complex Of The Ciliary Central Apparatus, Jason M. Brown, Christen G. Dipetrillo, Elizabeth F. Smith, George B. Witman

Dartmouth Scholarship

Virtually all motile eukaryotic cilia and flagella have a '9+2' axoneme in which nine doublet microtubules surround two singlet microtubules. Associated with the central pair of microtubules are protein complexes that form at least seven biochemically and structurally distinct central pair projections. Analysis of mutants lacking specific projections has indicated that each may play a unique role in the control of flagellar motility. One of these is the C1d projection previously shown to contain the proteins FAP54, FAP46, FAP74 and FAP221/Pcdp1, which exhibits Ca(2+)-sensitive calmodulin binding. Here we report the isolation and characterization of a Chlamydomonas reinhardtii null mutant for …

Treatment Of Aortic Heart Valve Conduit With Glutamine And Heat Shock As A Means To Deter The Constituent Cellular Population From Becoming Apoptotic, Alyce Marie Linthurst Jones

Theses and Dissertations in Biomedical Sciences

Cryopreserved allograft heart valves represent the best solution for a patient with a failing heart valve. However, the constituent cells become apoptotic and within months of transplant the heart valve becomes acellular and the recipient's cells do not repopulate the allograft (3, 51). A strategy to prevent this situation would be to minimize or prevent apoptosis from occurring by strategically altering steps during heart valve processing. Recently it has been demonstrated that: 1) Heat shock protein 70 is a negative modulator of the apoptotic cascade; 2) Cells in culture exposed to hypothermic conditions produce heat shock protein 70 upon rewarming; …

Neurodegeneration - A Means To An End, Amit Singh

Biology Faculty Publications

Cell death, a global phenomenon found throughout the animal kingdom, is a mechanism to maintain tissue homeostasis and for adaptation to changes in the environment [1,2]. Millions of cells die in our body daily- they succumb to stress and commit suicide by a mechanism referred to as cell death or apoptosis [2-4]. Under normal conditions cells are continuously replaced by new cells from the stemor progenitor- cells. For example, an optimum balance in shedding of dead cells from the skin and their replenishment by new ones maintain our health and hygiene. In this context, apoptosis is a mechanism to eliminate …

Computer Simulation And Mathematical Models Of The Noncentrosomal Plant Cortical Microtubule Cytoskeleton, Ezgi Can Eren, Natarajan Gautam, Ram Dixit

Biology Faculty Research

There is rising interest in modeling the noncentrosomal cortical microtubule cytoskeleton of plant cells, particularly its organization into ordered arrays and the mechanisms that facilitate this organization. In this review, we discuss quantitative models of this highly complex and dynamic structure both at a cellular and molecular level. We report differences in methodologies and assumptions of different models as well as their controversial results. Our review provides insights for future studies to resolve these controversies, in addition to underlining the common results between various models. We also highlight the need to compare the results from simulation and mathematical models with …