Cell and Developmental Biology Commons^™

Two Phase Model To Study The Correlation Between Brain Tumor Growth Rate And The Formation Of Peritumoral Edema, Inmaculada Sorribes, Helen Byrne, Nicholas Moore, Harsh Jain

Biology and Medicine Through Mathematics Conference

No abstract provided.

Identification Of A Tola Protein Binding Site For Bacterial Toxins, Monica Ferrante

Honors Projects

Group A colicins are proteinaceous bacteriocins encoded by plasmids that exploit the cellular envelope protein TolA to translocate the cell wall barrier and cellular envelope of the bacterium Escherichia coli. These colicins offer protocols for studying certain protein-protein interactions involved in such membrane transport functions. Previous experimentations suggest the carboxyl-terminal domain of TolA protein contains specific amino acid binding regions required for the translocation of group A colicins into E. coli. The amino acid sequence of this domain varies between E. coli and other gram-negative bacterial species. It has been suggested that this diversity could be utilized to …

Transcriptional Profiling Reveals Extraordinary Diversity Among Skeletal Muscle Tissues, Erin E. Terry, Xiping Zhang, Christy Hoffmann, Laura D. Hughes, Scott A. Lewis, Jiajia Li, Matthew J. Wallace, Lance A. Riley, Collin M. Douglas, Miguel A. Gutierrez-Monreal, Nicholas F. Lahens, Ming C. Gong, Francisco H. Andrade, Karyn A. Esser, Michael E. Hughes

Physiology Faculty Publications

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect …

Disease-Linked Connexin26 S17f Promotes Volar Skin Abnormalities And Mild Wound Healing Defects In Mice (Vol. 8, E2845, 2017), Eric R. Press, Katanya C. Alaga, Kevin Barr, Qing Shao, Felicitas Bosen, Klaus Willecke, Dale W. Laird

Anatomy and Cell Biology Publications

No abstract provided.

Perinatal Pb2+ Exposure Alters The Expression Of Genes Related To The Neurodevelopmental Gaba-Shift In Postnatal Rats, Lorenz Simon Neuwirth, Greg R. Phillips, Abdeslem El Idrissi

Publications and Research

Background: Lead (Pb2+) is an environmental neurotoxicant that disrupts neurodevelopment, communication, and organization through competition with Ca2+ signaling. How perinatal Pb2+ exposure affects Ca2+-related gene regulation remains unclear. However, Ca2+ activates the L-Type voltage sensitive calcium channel β-3 subunit (Ca-β3), which autoregulates neuronal excitability and plays a role in the GABA-shift from excitatory-toinhibitory neurotransmission.

Method: A total of eight females (n = 4 Control and n = 4 Perinatal) and four males (n = 2 Control and n = 2 Perinatal) rats were used as breeders to serve as Dams and Sires. The Dam’s litters each ranged from N = …

Visualizing Mutation-Specific Differences In The Trafficking-Deficient Phenotype Of Kv11.1 Proteins Linked To Long Qt Syndrome Type 2, Allison R. Hall, Corey L. Anderson, Jennifer L. Smith, Tooraj Mirshahi, Samy-Claude Elayi, Craig T. January, Brian P. Delisle

Physiology Faculty Publications

KCNH2 encodes the Kv11.1 α-subunit that underlies the rapidly activating delayed-rectifier K⁺ current in the heart. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channel protein to the cell surface membrane. Several trafficking-deficient LQT2 mutations (e.g., G601S) generate Kv11.1 proteins that are sequestered in a microtubule-dependent quality control (QC) compartment in the transitional endoplasmic reticulum (ER). We tested the hypothesis that the QC mechanisms that regulate LQT2-linked Kv11.1 protein trafficking are mutation-specific. Confocal imaging analyses of HEK293 cells stably expressing the trafficking-deficient LQT2 mutation F805C showed that, …

Lanthanide-Doped Ceria Nanoparticles As Backside Coaters To Improve Silicon Solar Cell Efficiency, Ali Hajjiah, Effat Samir, Nader Shehata, Mohamed Salah

Biology Faculty Publications

This paper introduces lanthanide-doped ceria nanoparticles as silicon solar cell back-side coaters, showing their influence on the solar cell efficiency. Ceria nanoparticles can be synthesized to have formed oxygen vacancies (O-vacancies), which are associated with converting cerium ions from the Ce⁴⁺ state ions to the Ce³⁺ ones. These O-vacancies follow the rule of improving silicon solar cell conductivity through a hopping mechanism. Besides, under near-ultra violet (near-UV) excitation, the reduced trivalent cerium Ce³⁺ ions are directly responsible for down converting the un-absorbed UV wavelengths to a resultant green photo-luminescence emission at ~520 nm, which is absorbed through …

Eukaryotic Translation Initiation Factor 4a Down-Regulation Mediates Interleukin-24-Induced Apoptosis Through Inhibition Of Translation, Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Atkas, Moire Sauane

Publications and Research

Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 50 -untranslated regions (50UTRs). These mRNAs encode proteins, which function in cell survival and proliferation. Consistently, overexpression of eIF4A conferred cancer cells with resistance to IL-24-induced cell death. It has been established …

Antioxidants And Cancer: Theories, Techniques, And Trials In Preventing Cancer, Gloria M. Calaf, Francisco Aguayo, Consolato M. Sergi, Angeles Juarranz, Debasish Roy

Publications and Research

No abstract provided.

High Salt Induces P-Glycoprotein Mediated Treatment Resistance In Breast Cancer Cells Through Store Operated Calcium Influx, Duaa Babaer, Suneetha Amara, Michael Ivy, Yan Zhao, Philip E. Lammers, Jens M. Titze, Venkataswarup Tiriveedhi

Biology Faculty Research

Recent evidence from our laboratory has demonstrated that high salt (Δ0.05 M NaCl) induced inflammatory response and cancer cell proliferation through salt inducible kinase-3 (SIK3) upregulation. As calcium influx is known to effect inflammatory response and drug resistance, we examined the impact of high salt on calcium influx in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 cells with high salt induced an enhanced intracellular calcium intensity, which was significantly decreased by store operated calcium entry (SOCE) inhibitor co-treatment. Further, high salt induced P-glycoprotein (P-gp) mediated paclitaxel drug resistance in breast cancer cells. Murine tumor studies demonstrated that injection of …

Examining The Roles Of Genetic And Environmental Factors In Drosophila Melanogaster Hematopoiesis And Innate Immune System, Minkyung Lee

Student Theses and Dissertations

Nearly 24 million people are affected by autoimmune diseases in the United States. Main causes of autoimmune diseases have been attributed to genetic predisposition and environmental exposure to chemicals such as hormones and pesticides. Due to the large population that are affected by autoimmune diseases, it is critical to understand the mechanisms behind them. In this study, we sought to explore both genetic and environmental factors that affect hematopoiesis, or the formation of specific blood cells, and immune system in Drosophila melanogaster. As Drosophila melanogaster have conserved pathways of hematopoiesis as humans, they were used as the model organism …

What We Do Not Know About Fungal Cell Adhesion Molecules, Peter N. Lipke

Publications and Research

There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from the six other fungal phyla are only sparsely described in the literature. In these other phyla, most of the research is at the cellular level, rather than at the molecular level, so there has been little characterization of the adhesion molecules themselves. A catalog of known adhesins shows some common features: high Ser/Thr content, tandem repeats, N- …

Preclinical Evaluation Of Novel Fatty Acid Synthase Inhibitors In Primary Colorectal Cancer Cells And A Patient-Derived Xenograft Model Of Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Anh-Thu Le, Timothy L. Scott, Robert M. Flight, Ji Tae Kim, Jennifer Harris, Jinpeng Liu, Chi Wang, Andrew J. Morris, Theru A. Sivakumaran, Teresa Fan, Hunter Moseley, Tianyan Gao, Eun Young Lee, Heidi L. Weiss, Timothy S. Heuer, George Kemble, B. Mark Evers

Toxicology and Cancer Biology Faculty Publications

Fatty Acid Synthase (FASN), a key enzyme of de novo lipogenesis, is upregulated in many cancers including colorectal cancer (CRC); increased FASN expression is associated with poor prognosis. Potent FASN inhibitors (TVBs) developed by 3-V Biosciences demonstrate anti-tumor activity in vitro and in vivo and a favorable tolerability profile in a Phase I clinical trial.

However, CRC characteristics associated with responsiveness to FASN inhibition are not fully understood. We evaluated the effect of TVB-3664 on tumor growth in nine CRC patient-derived xenografts (PDXs) and investigated molecular and metabolic changes associated with CRC responsiveness to FASN inhibition.

CRC cells and PDXs …

The Caspase Cascade During Hibernation In The Golden-Mantled Ground Squirrel, Spermophilus Lateralis, Michael David Treat

UNLV Theses, Dissertations, Professional Papers, and Capstones

In several human pathologies like heart attack, stroke, neurodegenerative diseases, and autoimmune disorders, widespread cell death, or apoptosis, is a major cause of organ dysfunction and death. Hibernating golden-mantled ground squirrels, Spermophilus lateralis, experience numerous conditions during the winter that are known to be pro-apoptotic in other mammal systems (e.g. extreme hypothermia, ischemia and reperfusion, acidosis, increased reactive oxygen species, bone and muscle disuse). However, studies suggest that hibernators may invoke a protective phenotype to limit widespread cell damage and loss during the hibernation season. Could regulating apoptosis provide protection against the harmful conditions experienced during the hibernation season? Could …

Assembly-Hub Function Of Er-Localized Snare Proteins In Biogenesis Of Tombusvirus Replication Compartment, Zsuzsanna Sasvari, Nikolay Kovalev, Paulina Alatriste Gonzalez, Kai Xu, Peter D. Nagy

Plant Pathology Faculty Publications

Positive-strand RNA viruses assemble numerous membrane-bound viral replicase complexes within large replication compartments to support their replication in infected cells. Yet the detailed mechanism of how given subcellular compartments are subverted by viruses is incompletely understood. Although, Tomato bushy stunt virus (TBSV) uses peroxisomal membranes for replication, in this paper, we show evidence that the ER-resident SNARE (soluble NSF attachment protein receptor) proteins play critical roles in the formation of active replicase complexes in yeast model host and in plants. Depletion of the syntaxin 18-like Ufe1 and Use1, which are components of the ER SNARE complex in the ERAS (ER …

Egfr Polymorphisms In Drosophila Melanogaster, Stacie Chue, Neha Mehta, Samantha Poon, Heather Trazino

Publications and Research

No abstract provided.

Fear Memory Recall Potentiates Opiate Reward Sensitivity Through Dissociable Dopamine D1 Versus D4 Receptor-Dependent Memory Mechanisms In The Prefrontal Cortex., Jing Jing Li, Hanna Szkudlarek, Justine Renard, Roger Hudson, Walter Rushlow, Steven R. Laviolette

Anatomy and Cell Biology Publications

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition …

Morphoregulatory Functions Of The Rna-Binding Motif Protein 3 In Cell Spreading, Polarity And Migration, J. Pilotte, W. Kiosses, S. W. Chan, H. P. Makarenkova, Esther E. Dupont-Versteegden, P. W. Vanderklish

Physical Therapy Faculty Publications

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 …

Till Death Do Us Part: The Marriage Of Autophagy And Apoptosis., Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Autophagy is a widely conserved catabolic process that is necessary for maintaining cellular homeostasis under normal physiological conditions and driving the cell to switch back to this status quo under times of starvation, hypoxia, and oxidative stress. The potential similarities and differences between basal autophagy and stimulus-induced autophagy are still largely unknown. Both act by clearing aberrant or unnecessary cytoplasmic material, such as misfolded proteins, supernumerary and defective organelles. The relationship between reactive oxygen species (ROS) and autophagy is complex. Cellular ROS is predominantly derived from mitochondria. Autophagy is triggered by this event, and by clearing the defective organelles effectively, …

Preclinical Outcomes Of Intratumoral Modulation Therapy For Glioblastoma, Andrea R. Di Sebastiano, Andrew Deweyert, Simon Benoit, Erin Iredale, Hu Xu, Cleusa De Oliveira, Eugene Wong, Susanne Schmid, Matthew O. Hebb

Anatomy and Cell Biology Publications

Glioblastoma (GBM) is the leading cause of high fatality cancer arising within the adult brain. Electrotherapeutic approaches offer new promise for GBM treatment by exploiting innate vulnerabilities of cancer cells to low intensity electric fields. This report describes the preclinical outcomes of a novel electrotherapeutic strategy called Intratumoral Modulation Therapy (IMT) that uses an implanted stimulation system to deliver sustained, titratable, low intensity electric fields directly across GBM-affected brain regions. This pilot technology was applied to in vitro and animal models demonstrating significant and marked reduction in tumor cell viability and a cumulative impact of concurrent IMT and chemotherapy in …

Transcending The Cell Fate Stereotype: Cell Penetrating Peptide Technology Helps Induce Pluripotency In Multiple Cell Types, Kelsey Clearman

Master of Science in Integrative Biology Theses

Induced pluripotent stem cells (iPSCs) are one of the most promising new technologies in the field of regenerative medicine. iPSCs can be generated directly from a patient’s own fibroblast cells then converted into any cell type, thus overcoming challenges associated with embryonic stem cells and graft-vs-host disease that result from current methods. Generation of iPSCs from fibroblasts is traditionally accomplished by ectopic expression of four key transcription factors (TFs): Oct4, Sox2, Klf4, and c-Myc also known as OSKM. These TFs have been shown to be involved in maintaining pluripotency and inhibiting embryonic stem (ES) cell differentiation. Reprogramming fibroblasts into iPSCs …

Same-Sex Marriage And The Baby Carriage: A Post-Obergefell Analysis Of Art Funding For Same-Sex Couples In The United States, Charmaine Mech

Georgia Journal of International & Comparative Law

No abstract provided.

Biosemiotics As An Argument For The Recontextualization Of Biological Discoveries: A Critical Analysis Of The Biosemiotic Model Of Marcello Barbieri., Augustus Morrissey Snyder

Senior Honors Projects, 2010-2019

The primary purpose of this project was to investigate and explain the philosophical approach of biosemiotics to understanding living systems in contrast to the current scientific paradigm. Secondary goals were to evaluate the potential merits and relevance of this approach to biology and to introduce such a topic for discussion to biologists in a formal academic setting. My method consisted of critical textual analysis supplemented by analogy and biological examples where appropriate. In general, contemporary biosemiotics argues for a teleologic recontextualization of biological discoveries in practice and education. This is accomplished in a sophisticated fashion through the application and modification …

Mammalian Cell-Derived Vesicles For The Isolation Of Organelle Specific Transmembrane Proteins To Conduct Single Molecule Studies, Faruk H. Moonschi, Ashley M. Fox-Loe, Xu Fu, Christopher I. Richards

Chemistry Faculty Publications

Cell-derived vesicles facilitate the isolation of transmembrane proteins in their physiological membrane maintaining their structural and functional integrity. These vesicles can be generated from different cellular organelles producing, housing, or transporting the proteins. Combined with single molecule imaging, isolated organelle specific vesicles can be employed to study the trafficking and assembly of the embedded proteins. Here we present a method for organelle specific single molecule imaging via isolation of ER and plasma membrane vesicles from HEK293T cells by employing OptiPrep gradients and nitrogen cavitation. The isolation was validated through Western blotting, and the isolated vesicles were used to perform single …

Determinants Of Multi-Scale Patterning In Growth Plate Cartilage, Alek Erickson

Theses & Dissertations

ABSTRACT

Functional architectures of complex adaptive systems emerge by dynamic control over properties of individual components. During skeletal development, growth plate cartilage matches bone geometries to body plan requisites by spatiotemporally regulating chondrocyte actions. Bone growth potential is managed by the proximodistal patterning of chondrocyte populations into differentiation zones, while growth vectors are specified by the unique columnar arrangement of clonal groups. Chondrocyte organization at both tissue and cell levels is influenced by a cartilage-wide communication network that relies on zone-specific release and interpretation of paracrine signals. Despite genetic characterization of signaling interactions necessary for cartilage maturation, the regulatory mechanisms …

The Role Of Hippo Pathway In Mitosis And Cancer, Xingcheng Chen

Theses & Dissertations

The Hippo signaling pathway has been recently elucidated as a tumor suppressor pathway controlling cell proliferation and apoptosis. The core of this pathway is a kinase cascade which contains MST1/2 (Mammalian sterile 20-like kinase 1/2), LATS1/2 (large tumor suppressor 1/2) and downstream effector named Yes-associated protein (YAP). MST1/2 transduce their kinase activity mainly through directly phosphorylating LATS1/2. Once phosphorylated and activated, LATS1/2 subsequently phosphorylate and inhibit YAP from translocating to nucleus. Current studies involving the Hippo pathway focus on determining its oncogenic role in various organs/tissues. While those studies provide important insight into the tumor suppressor properties of this pathway, …

Functional Signature Ontology-Based Identification And Validation Of Novel Therapeutic Targets And Natural Products For The Treatment Of Cancer, Beth Neilsen

Theses & Dissertations

Multiple studies have revealed that Ras-driven tumors acquire vulnerabilities by adapting cellular mechanisms that promote uncontrolled proliferation and suppress apoptosis. Kinase Suppressor of Ras 1 (KSR1) modulates ERK activation downstream of oncogenic Ras, and knockdown of KSR1 selectively kills malignant, Ras-driven cancer cells, but does not kill immortalized, non-transformed human colon epithelial cells (HCECs). KSR1^-/- mice are fertile and phenotypically normal, but resistant to Ras-driven tumor formation suggesting KSR1 represents a vulnerability in cancer cells.

To identify additional vulnerabilities in cancer, a screening approach termed Functional Signature Ontology (FUSION) was used to screen 14,355 genes and 1,200 natural product …

The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest

Theses & Dissertations

MUC1 is overexpressed in over 90% of pancreatic cancer cases, and its interaction with beta-catenin promotes progression of the disease. Various in vitro and in vivo methods show that beta-catenin and MUC1 interact by way of the cytoplasmic tail of MUC1 (MUC1.CT). This interaction occurs in the membrane of pancreatic cancer cells but is found to a smaller extent in the nucleus as well. Biophysical methods suggest that MUC1 interacts with beta-catenin through a sequence of amino acids in the tail of MUC1 that sit very near the transmembrane domain of MUC1. In pancreatic ductal adenocarcinoma cells, it appears that …

Connexin32: Sorting, Endocytosis And Assembly, Anuttoma Ray

Theses & Dissertations

Gap junctions (GJ)s are conglomeration of several cell-cell channels at cell-to-cell contact sites involved in the direct intercellular exchange of small growth regulatory molecules. Defects in assembly of GJ-forming proteins, called connexins (Cxs), are observed in many cancers, yet the molecular basis of this defect remains unknown. Connexin32 (Cx32) is expressed by the polarized cells in epithelia. The carboxyl-terminal tail (CT) of Cx32, although not required to initiate GJ formation, orchestrates several aspects of GJ dynamics, function and growth. Our studies have discovered that the CT of Cx32 harbors a tyrosine-based [YXXØ]-type and two dileucine-based [DE]XXXL[LI]-type motifs, which govern the …

Overcoming Tcf4-Driven Bcr Signaling In Diffuse Large B-Cell Lymphoma, Keenan Hartert

Theses & Dissertations

Diffuse Large B-cell Lymphoma (DLBCL) is the most common subtype of lymphoma. Despite a cure rate of 40% with standard R-CHOP therapy, patients that refract or relapse are subject to a dismal prognosis. Cases of DLBCL can be classified by their molecular expression phenotype, with the GCB-like subtype aligning with the profile of a germinal center B-cell and the ABC-like subtype aligning to that of an activated B-cell. Aggressive disease is often characterized by high levels of B-cell Receptor (BCR) signaling. This pathway engages downstream kinases responsible for stimulating proliferation and survival that play a key role under the normal …