Other Cell and Developmental Biology Commons^™

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Rapamycin Treatment Correlates Changes In Primary Cilia Expression With Cell Cycle Regulation In Epithelial Cells, Maha Jamal, Ane C.F. Nunes, Nosratola D. Vaziri, Ramani Ramchandran, Robert L. Bacallao, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are sensory organelles that regulate cell cycle and signaling pathways. In addition to its association with cancer, dysfunction of primary cilia is responsible for the pathogenesis of polycystic kidney disease (PKD) and other ciliopathies. Because the association between cilia formation or length and cell cycle or division is poorly understood, we here evaluated their correlation in this study. Using Spectral Karyotyping (SKY) technique, we showed that PKD and the cancer/tumorigenic epithelial cells PC3, DU145, and NL20-TA were associated with abnormal ploidy. We also showed that PKD and the cancer epithelia were highly proliferative. Importantly, the cancer epithelial cells …

Mitochondrial Deletions And Their Disease-Causing Effects, Austin Bell

Biological Sciences Undergraduate Honors Theses

The mitochondria perform a plethora of important functions within the cell, with one of the most paramount being ATP production. Deregulation of its function can have dire consequences on cellular functions. Mutations such as deletions within the mitochondrial DNA (mtDNA) can cause disease within the patients affected. These diseases often affect children, causing symptoms such as gradual loss of eyesight and hearing, diabetes, and other problems that lower the quality of life. The mitochondria are also very dynamic organelles that undergo rounds of fission and fusion to keep up with the metabolic needs of cells, necessitating a homeostatic balance between …

Glutamine Antagonist 6-Diazo-5-Oxo-L-Norleucine, A Hyaluronan Synthesis Inhibitor, Slows Triple Negative Breast Cancer Growth, Le Gia Cat Pham

Biological Sciences

Triple-negative breast cancers (TNBC) are the most aggressive subtype of breast cancer with few treatment options and poor outcomes. TNBCs are characterized by elevations in hexosamine biosynthetic pathway (HBP) enzyme expression, hyaluronan synthase 2 (HAS2) expression and hyaluronan (HA) production. Glutamine is an important substrate for HA production via the HBP. 6-diazo-5-oxo-L-norleucine (DON) is a well-known glutamine antagonist with validated antitumoral efficacy. This project examined the effects of DON on HA production and energy metabolism in TNBC cells. We examined the effect of DON treatment on Hs578T cells, which represent the mesenchymal stem-like subtype of TNBC. We specifically analyzed the …

Serpinb1 Effects On Human Pancreatic Ductal Cells, Praneeth Goli

College of Arts & Sciences Senior Theses

Rebuilding or expanding the body’s ability to regulate blood glucose levels by restoring or increasing the body’s ability to produce insulin, long-term, would be a major advancement in diabetes (type-1 and type-2) treatment and could serve as a potential cure [1]. Therefore, the holy grail of diabetes treatment and cure research is to regenerate or increase the insulin producing cells in diabetic individuals (type-1 and type-2) [1, 2]. SerpinB1 has been implicated as a biomolecular signal that stimulates an increase in insulin cell mass in murine and zebrafish models that exhibit physiologically normal compensatory islet hyperplasia. In humans, SerpinB1 is …

Understanding Intercellular Signaling During Lung Injury-Repair, Margo Patricia Cain

Dissertations and Theses (Open Access)

The mammalian lung is a complex system of specialized cell types with precise spatial organization designed to cooperate to perform gas exchange. These cell types together coordinate organ development, homeostasis, and repair after injury through signals either presented or secreted, known as ligands, to be received by receptors on the surface of another, or in some cases, the same cell. The alveolar region of the lung, the primary region of gas exchange, responds to various types of injuries with different lung repair mechanisms. In order to explore how the various cell types in the lung communicate to drive tissue repair …

The Bioethical Significance Of “The Origin Of Man’S Ethical Behavior” (October 1941, Unpublished) By Ernest Everett Just And Hedwig Anna Schnetzler Just, Theodore Walker Jr.

Journal of the South Carolina Academy of Science

Abstract –

E. E. Just (1883-1941) is an acknowledged “pioneer” in cell biology, and he is perhaps the pioneer in study of egg cell fertilization. Here we discover that Just also made pioneering contributions to general biology and evolutionary bioethics.

Within Just’s published contributions to observational cell biology, there are substantial fragments of his theory of ethical behavior, a theory with roots in cell biology. In addition to such previously available fragments, Just’s fully developed theory is now available. This recently discovered unpublished book-length manuscript argues for the biological origins of ethical behavior (evolving from cells to humans, within a …

How Cellular Metabolic State And The Chaperone Protein Hsp104 Interact To Affect The Spontaneous Formation Of The Yeast Prion [Ure3], Demyia Graham

Merge

No abstract provided.

Lew.1wr1 Rats Have Increased Beta Cell Area And Decreased Pancreas Area During Their T1d Susceptibility Window, Evann Fowler

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Characterizing The Requirements For The Matricellular Protein, Dccn, In Nervous System Function, Elizabeth L. Catudio Garrett

Graduate Student Theses, Dissertations, & Professional Papers

The brain is organized as a complex network of specialized neurons that communicate via a combination of electrical and chemical signals. Our brains function to generate movement, control organ function, or direct complex behaviors; all of which requires the ability to regulate the flow of communication between circuits and networks. Work in this thesis addresses two areas of neuron communication: first, how does the release of more than one neurotransmitter from a single neuron impact behavior, and second, are matricellular proteins (MCPs) key contributors to synaptic transmission and neuron function? The conserved CCN family of MCPs have a …

Peroxiredoxin 6 And Inflammation In Alzheimer's Disease, Jared Ferrell-Penniman

Biological Sciences Theses and Dissertations

Alzheimer’s disease (AD) is known for its debilitating symptoms and poor prognosis. However, despite intense research into neurodegenerative diseases, there are few therapies targeted at the underlying mechanisms of the disease. Oxidative stress (OS) and inflammation are cellular phenomena thought to be key to the progression of the disease. Critically, peroxiredoxin 6 (Prx6), an antioxidant protein with multiple functions, has been identified from mammalian studies as a potential regulator of both OS and inflammation that may have a specific effect on AD. This project seeks to elucidate the role of Prx6 in AD as well as the underlying mechanisms. Drosophila …

Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago

Dissertations, Theses, and Capstone Projects

A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …

Embryonic Lethality Of Cranial Neural Crest Deletion Of Cdc73, Lilia Shen

Honors Scholar Theses

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and …

Sensory Primary Cilium Is A Responsive Camp Microdomain In Renal Epithelia, Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like cellular extensions that sense microenvironmental signals surrounding cells. The role of adenylyl cyclases in ciliary function has been of interest because the product of adenylyl cyclase activity, cAMP, is relevant to cilia-related diseases. In the present study, we show that vasopressin receptor type-2 (V2R) is localized to cilia in kidney epithelial cells. Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory function. Genetic knockdown of V2R, however, does not have any effect on ciliary length, although the effect of tolvaptan on ciliary length is dampened. Our study reveals that tolvaptan may have a cilia-specific …

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 …

Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield

Undergraduate Theses, Professional Papers, and Capstone Artifacts

The receptor tyrosine kinases (RTKs) are known to help regulate cell behaviors including differentiation, proliferation and migration during embryonic development of the neural crest. RTKs are believed to initiate signaling cascades in response to extracellular cues in part by controlling localization of Src-family kinases (SFKs). The scaffolding protein PAG1 binds SFKs and is believed to influence SFK activity and location within the cell by promoting interaction of SFKs with regulatory proteins and by drawing SFKs into different components of the endocytic pathway. By targeting the PAG1 gene in SH-SY5Y neuroblastoma cells with CRISPR/Cas9 plasmids, we created PAG1-mutant cell-lines in which …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Modified Cantilever Arrays Improve Sensitivity And Reproducibility Of Nanomechanical Sensing In Living Cells, Samadhan B. Patil, Rajai M. Al-Jehani, Hashem Etayash, Valerian Turbe, Keren Jiang, Joe Bailey, Walid Al-Akkad, Rania Soudy, Kamaljit Kaur, Rachel A. Mckendry, Thomas Thundat, Joseph W. Ndieyira

Pharmacy Faculty Articles and Research

Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating …

Cellular Mechanisms Of Slime Gland Refilling In Pacific Hagfish (Eptatretus Stoutii), Sarah Schorno, Todd E. Gillis, Douglas S. Fudge

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Hagfishes use their defensive slime to ward off gill-breathing predators. Slime gland refilling is a surprisingly slow process, and previous research has shown that the composition of the slime exudate changes significantly during refilling, which likely has consequences for the functionality of the slime. This study set out to expand our understanding of slime gland refilling by examining the cellular processes involved in refilling of the glands, as well as determining where in the gland the main slime cells – the gland thread cells and gland mucous cells – arise. Slime glands were electro-stimulated to exhaust their slime stores, left …

Characterization Of Theranostic Peptides For Glioblastoma Multiforme, Aaron Mellesmoen

All NMU Master's Theses

Glioblastoma multiforme (GBM) is a type of primary CNS tumor in which viable treatment options do not exist. Standard of care including tumor resection, chemotherapy, and radiation does little to extend the 5-year survival expectancy past 5.1%. Herein, two small-peptide molecules with inherent antitumor activity, blood-brain barrier permeability, and capability for tumor-specific drug deliverance and intraoperative visualization (termed theranostic) were of focus. Confocal microscopy was employed to characterize in vitro specificity of chlorotoxin, a 4 kDa scorpion venom peptide, and rBSG, the recombinant 25 kDa non-glycosylated extracellular domain of extracellular matrix metalloproteinase inducer (EMMPRIN; Basigin) isoform …