Cell Biology Commons^™

Biomechanical And Biophysical Properties Of Breast Cancer Cells Under Varying Glycemic Regimens, Diganta Dutta, Xavier-Lewis Palmer, Jose Ortega-Rodas, Vasundhara Balraj, Indrani Ghosh Dastider, Surabhi Chandra

Electrical & Computer Engineering Faculty Publications

Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, …

Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw

School of Medicine Faculty Publications

Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression …

Regulation Of The Heat Shock Response And Hsf-1 Nuclear Stress Bodies In C. Elegans, Andrew Deonarine

USF Tampa Graduate Theses and Dissertations

The Heat Shock Response (HSR) is a highly conserved stress responsive molecular pathway that functions to promote appropriate protein folding in the cell. The HSR accomplishes this primarily through the use of molecular chaperones that serve to bind to misfolded or unfolded proteins to assist in stabilizing and folding proteins back to their native functional state. The master regulator of this pathway is a transcription factor known as Heat Shock Factor 1 (HSF1). HSF1 regulates molecular chaperone expression in the cell’s basal state, but can also be stress induced by diverse biotic and abiotic signals including thermal shock, oxidative stress, …

Acute Systemic Inflammatory Response Alters Transcription Profile Of Genes Related To Immune Response And Ca 2+ Homeostasis In Hippocampus; Relevance To Neurodegenerative Disorders, Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder

School of Medicine Faculty Publications

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 …

Fine-Tuning Of Alanyl-Trna Synthetase Quality Control Alleviates Global Dysregulation Of The Proteome, Paul Kelly, Arundhati Kavoor, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

One integral step in the transition from a nucleic acid encoded-genome to functional proteins is the aminoacylation of tRNA molecules. To perform this activity, aminoacyl-tRNA synthetases (aaRSs) activate free amino acids in the cell forming an aminoacyl-adenylate before transferring the amino acid on to its cognate tRNA. These newly formed aminoacyl-tRNA (aa-tRNA) can then be used by the ribosome during mRNA decoding. In Escherichia coli, there are twenty aaRSs encoded in the genome, each of which corresponds to one of the twenty proteinogenic amino acids used in translation. Given the shared chemicophysical properties of many amino acids, aaRSs have …

Role Of Ceramide-1 Phosphate In Regulation Of Sphingolipid And Eicosanoid Metabolism In Lung Epithelial Cells, Brittany A. Dudley

USF Tampa Graduate Theses and Dissertations

Ceramide 1-Phosphate (C1P) is a sphingolipid metabolite which plays a large role in inflammation, cell survival and proliferation¹. C1P is known to have both pro- and anti-apoptotic roles in lung cancer cells, governed by ceramide kinase (CERK), upstream of precursor ceramide (Cer)². Previous work reveals C1P serves as the liaison between sphingolipid and eicosanoid synthesis, by decreasing the dissociation rate of group IVA cytosolic PLA₂ (cPLA_2α) from the Golgi membrane, C1P directly activates this phospholipase for downstream eicosanoid synthesis and subsequent inflammatory response³. CERK has been discovered to modulate eicosanoid synthesis, …

Overcoming Barriers For Sirna Therapeutics: From Bench To Bedside, Muhammad Imran Sajid, Muhammad Moazzam, Shun Kato, Kayley Yeseom Cho, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described …

Herb-Layer Dynamics In An Old-Growth Forest: Vegetation–Environment Relationships And Response To Invasion-Related Perturbations, Taylor M. Buskey, Margaret E. Maloney, Julia I. Chapman, Ryan W. Mcewan

Biology Faculty Publications

Temperate forests of eastern North America are subject to multiple invasions from non-native species that have the potential to drive long-term dynamics in biodiversity. Garlic mustard (Alliaria petiolata (M. Bieb.) Cavara and Grande) is an invasive plant in many deciduous forests, and management efforts often focus on removing this species to initiate native species restoration. Agrilus planipennis Fairmaire (emerald ash borer; Coleoptera: Buprestidae) is a non-native insect pest that has caused substantial loss of ash trees (Fraxinus spp. L.) in North America. Our goal was to understand how the herbaceous layer in an old-growth forest responded to the removal of …

Mechanistic Insights Into Strigolactone Biosynthesis, Signaling And Regulation During Plant Growth And Development, Kaiser Iqbal Wani, Andleeb Zehra, Sadaf Choudhary, M Naeem, M. Masroor A. Khan, Christian Danve Castroverde, Tariq Aftab

Biology Faculty Publications

Strigolactones (SLs) constitute a group of carotenoid-derived phytohormones with butenolide moieties. These hormones are involved in various functions, including regulation of secondary growth, shoot branching and hypocotyl elongation, and stimulation of seed germination. SLs also control hyphal branching of arbuscular mycorrhizal (AM) fungi, and mediate responses to both abiotic and biotic cues. Most of these functions stem from the interplay of SLs with other hormones, enabling plants to appropriately respond to changing environmental conditions. This dynamic interplay provides opportunities for phytohormones to modulate and augment one another. In this article, we review our current mechanistic understanding of SL biosynthesis, receptors …

Cryo‑Electron Microscopy Structure Of The 70s Ribosome From Enterococcus Faecalis, Eileen L. Murphy, Kavindra V. Singh, Bryant Avila, Torsten Kleffmann, Steven T. Gregory, Barbara E. Murray, Kurt L. Krause, Reza Khayat, Gerwald Jogl

Publications and Research

Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. Here, we report the cryo-EM structure of the E. faecalis 70S ribosome to a global resolution of 2.8 Å. Structural differences are clustered in peripheral and solvent exposed regions when compared with Escherichia coli, whereas functional centres, including antibiotic binding sites, are similar to other bacterial ribosomes. Comparison of intersubunit conformations among five classes obtained after three-dimensional classification identifies several rotated states. Large ribosomal subunit protein bL31, which forms intersubunit bridges to …

Minimal Structural Elements Required For Midline Repulsive Signaling And Regulation Of Drosophila Robo1, Haley E. Brown, Timonthy A. Evans

Biological Sciences Faculty Publications and Presentations

The Roundabout (Robo) family of axon guidance receptors has a conserved ectodomain arrangement of five immunoglobulin-like (Ig) domains plus three fibronectin type III (Fn) repeats. Based on the strong evolutionary conservation of this domain structure among Robo receptors, as well as in vitro structural and domain-domain interaction studies of Robo family members, this ectodomain arrangement is predicted to be important for Robo receptor signaling in response to Slit ligands. Here, we define the minimal ectodomain structure required for Slit binding and midline repulsive signaling in vivo by Drosophila Robo1. We find that the majority of the Robo1 ectodomain is dispensable …

Sonoporation-Mediated Loading Of Trehalose In Cells For Cryopreservation., Charles W. Shaffer Iv, David F. Grimm, Michael A. Menze, Jonathan A. Kopechek

Undergraduate Research Events

Trehalose, a non-reducing disaccharide, is present in many microorganisms and metazoans. In these organisms, trehalose acts as a stress protectant and helps preserve lipid membranes of cells during states of desiccation and freezing. Trehalose is required on both sides of the cell membrane to achieve a significant cryoprotective effect. Specific loading methods for trehalose are required since this sugar is impermeant to mammalian cells. Trehalose loading in mammalian cells has been achieved by fluid-phase endocytosis and genetic modification for the expression of trehalose transporters, however cryoprotective outcomes are unable to compete with established methods of cryopreservation for mammalian cells. Sonoporation …

Tdp-43 Mediated Blood-Brain Barrier Permeability And Leukocyte Infiltration Promote Neurodegeneration In A Low-Grade Systemic Inflammation Mouse Model, Frank Zamudio, Anjanet R. Loon, Shayna Smeltzer, Khawla Benyamine, Nanda K. Navalpur Shanmugam, Nicholas J. F. Stewart, Daniel C. Lee, Kevin Nash, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases.

METHODS: To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected …

Expression And Localization Of The 14-3-3 (Ywha) Protein Family Within Mammals, Neha Kumrah, Santanu De

Mako: NSU Undergraduate Student Journal

The 14-3-3 (YWHA) are a family of homologous, acidic, and highly conserved proteins expressed abundantly and ubiquitously in a wide array of organisms ranging from plants to animals, including humans, which regulate important cellular events. Within mammals, seven isoforms of 14-3-3 exist: β, γ, ε, ζ, η, τ, and σ (stratifin), each of which is encoded by a unique gene. Studies have shown similar expression patterns among mammalian species. The 14-3-3 proteins are commonly expressed and have proven to play critical roles in proper cellular localization, function, and homeostatic regulation. Numerous researchers have investigated the expression and localization patterns of …

Mechanism Of Translation Inhibition By Type Ii Gnat Toxin Atat2, Stepan V Ovchinnikov, Dmitry Bikmetov, Alexei Livenskyi, Marina Serebryakova, Brendan Wilcox, Kyle Mangano, Dmitrii I Shiriaev, Ilya A Osterman, Petr V Sergiev, Sergei Borukhov, Nora Vazquez-Laslop, Alexander S Mankin, Konstantin Severinov, Svetlana Dubiley

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Type II toxin-antitoxins systems are widespread in prokaryotic genomes. Typically, they comprise two proteins, a toxin, and an antitoxin, encoded by adjacent genes and forming a complex in which the enzymatic activity of the toxin is inhibited. Under stress conditions, the antitoxin is degraded liberating the active toxin. Though thousands of various toxin-antitoxins pairs have been predicted bioinformatically, only a handful has been thoroughly characterized. Here, we describe the AtaT2 toxin from a toxin-antitoxin system from Escherichia coli O157:H7. We show that AtaT2 is the first GNAT (Gcn5-related N-acetyltransferase) toxin that specifically targets charged glycyl tRNA. In vivo, the AtaT2 …

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]₄ and c[WR]₅ consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …

Does The Presence Of Multiple Β-Lactamases In Gram-Negative Bacilli Impact The Results Of Antimicrobial Susceptibility Tests And Extended-Spectrum Β-Lactamase And Carbapenemase Confirmation Methods?, Fred C. Tenover, Caitlin M. Dela Cruz, Scott Dewell, Victoria M. Le, Isabella A. Tickler

Biology Faculty Publications

Objectives: Many multidrug-resistant Gram-negative bacilli (MDR-GNB) harbour multiple β-lactamases. The aim of this study was to assess the impact of multiple β-lactamase carriage on the accuracy of susceptibility tests and extended-spectrum β-lactamase (ESBL) and carbapenemase confirmation methods.

Methods: A total of 50 MDR-GNB, of which 29 carried multiple β-lactamases, underwent broth microdilution (BMD) and disk diffusion (DD) testing as well as confirmation tests for ESBLs and carbapenemases. Whole-genome sequencing (WGS) was used for β-lactamase gene identification.

Results: Categorical agreement of BMD and DD testing results ranged from 86.5 to 97.7% for 10 β-lactam agents. BMD and DD algorithms for ESBL …

Identifying New Markers And Mechanisms Of Mitochondrial Defect During Aging, Catherine Chang

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Mitochondrial dysfunction is a hallmark of aging and has been closely tied to age-related pathologies, such as cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Though the consequences of mitochondrial defects are well documented, little is known about the molecular events that occur with age that transform healthy mitochondria into dysfunctional ones. Past studies have attempted to uncover the underlying proteomic changes in age, however, most of these results do not take into account population heterogeneity often associated with aging, thus highlighting the need for single-cell analysis. Technological barriers have impeded in-depth proteomic studies of aging mitochondria on a single …

The Influence Of Riparian Invasion By The Terrestrial Shrub Lonicera Maackii On Aquatic Macroinvertebrates In Temperate Forest Headwater Streams, Michelle N. Little, Kevin W. Custer, Eric B. Borth, Julia I. Chapman, Mitchell J. Kukla, Corey Kuminecz, Margaret E. Maloney, Michaela J. Woods, Ryan Mcewan

Biology Faculty Publications

The ecology of headwater streams is tightly linked to the riparian zone through organic matter subsidies which are highly susceptible to alteration due to biological invasion. Lonicera maackii is a non-native shrub that is a highly successful invader of headwater stream riparian zones in the American Midwest. We assessed effects on benthic macroinvertebrates across a gradient of invasion intensity from references sites with minimal invasion to a site that had a very heavy invasion. Benthic macroinvertebrates were sampled throughout the year and compositional differences were assessed using Non-metric Multidimensional Scaling ordination, and by comparing the prevalence of sensitive (Ephemeroptera, Plectoptera, …

Regulation Of A Messenger: Raising Oskar, It Takes A Village, Livia V. Bayer

Dissertations, Theses, and Capstone Projects

D. melanogaster oogenesis serves as an excellent system to study the life of an mRNA. Tremendous work has been done to understand the numerous complex mechanisms of mRNA regulation, still there is still so much that is yet to be discovered. In this thesis, I present studies I carried out to address several aspects of oskar mRNA post-transcriptional regulation. Leading me to extend our current understanding of the carefully controlled regulation of oskar mRNA life cycle via a myriad of proteins. I found that a specific NPC component, Nup154 is necessary not only for its export from the nucleus, but …