Cell and Developmental Biology Commons^™

Introducing An Indigenous Non-Toxigenic Aspergillus Flavus Strain Isolated From Iraqi Corn Grains As A Bio-Control Agent To Reduce Aflatoxin Contamination In Corn Grains, Ali Almatakeez

Graduate Theses and Dissertations

Mycotoxin contamination of cereal crops, such as maize and sorghum, is a global concern because of the potential health effects on humans and animals. Although substantial research has been conducting regarding mycotoxin prevention and mitigation, little information is available about the association of mycotoxin-producing fungi with corn and sorghum grain in Iraq. Identifying and refining indigenous atoxigenic strains to reduce mycotoxin contamination of maize and sorghum has the potential to enhance the nutritional value of these grains while reducing economic losses. However, to our knowledge, this tactic has not yet been adopted by agricultural authorities and farmers in Iraq. To …

Secretion Of Proteins And Antibody Fragments From Transiently Transfected Endothelial Progenitor Cells, Loree Heller, Reynald Thinard, Melanie Chevalier, Sezgi Arpag, Yu Jing, Ruth Greferath, Richard Heller, Claude Nicolau

Bioelectrics Publications

In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neuroinflammation can lead to blood-brain barrier (BBB) breakdown. After intravenous or intra-arterial injection into mice, endothelial progenitor cells (EPCs) home to the damaged BBB to promote neurovascular repair. Autologous EPCs transfected to express specific therapeutic proteins offer an innovative therapeutic option. Here, we demonstrate that EPC transfection by electroporation with plasmids encoding the reporter protein GFP or an anti-beta-amyloid antibody fragment (Fab) leads to secretion of each protein. We also demonstrate the secreted anti-beta-amyloid Fab protein functions in beta-amyloid aggregate solubilization.

Palbociclib Treatment Alters Nucleotide Biosynthesis And Glutamine Dependency In A549 Cells, Lindsey R. Conroy, Pawel Lorkiewicz, Liqing He, Xinmin Yin, Xiang Zhang, Shesh N. Rai, Brian F. Clem

Neuroscience Faculty Publications

Background

Aberrant activity of cell cycle proteins is one of the key somatic events in non-small cell lung cancer (NSCLC) pathogenesis. In most NSCLC cases, the retinoblastoma protein tumor suppressor (RB) becomes inactivated via constitutive phosphorylation by cyclin dependent kinase (CDK) 4/6, leading to uncontrolled cell proliferation. Palbociclib, a small molecule inhibitor of CDK4/6, has shown anti-tumor activity in vitro and in vivo, with recent studies demonstrating a functional role for palbociclib in reprogramming cellular metabolism. While palbociclib has shown efficacy in preclinical models of NSCLC, the metabolic consequences of CDK4/6 inhibition in this context are largely unknown.

Methods

In …

Bioavailability And Modes Of Action Of Novel Metal Based Phenanthroline Drugs, Tadhg O’Leary

Doctoral

Metal-basedcompounds have been utilised as chemotherapeutic agents for the last four decades due to their well-documented and clinically relevant anti-tumour properties.Acquired resistance is a challenge for the clinical use of these compounds and there is a continuing need to search for potential new therapeutic agents. Herein, the potential of two metal-basedcompounds containing chelated1,10-phenanthroline (1,10-Phen), one manganese-based (CMPD 73)andonecopper-based (CMPD 74), to act as novel therapeutic agents is explored.CMPD 73 displayed high micromolar (IC50>100μM) cytotoxic properties againstvarious cell systems but interestingly displayed increased cytotoxicity against ovarian (A2780), lung (A549) and cisplatin resistant mesothelioma cells(IC5040-50μM). CMPD 74 was equally cytotoxic against …

Inactivation Of Hippo And Cjun-N-Terminal Kinase (Jnk) Signaling Mitigate Fus Mediated Neurodegeneration In-Vivo, Ankita Sarkar, Abijeet Singh Mehta, Prajakta Deshpande, Madhuri Kango-Singh, Udai Bhan Pandey, Amit Singh

Biology Faculty Publications

Amyotrophic Lateral Sclerosis (ALS), a late-onset neurodegenerative disorder characterized by the loss of motor neurons in the central nervous system, has no known cure to-date. Disease causing mutations in human Fused in Sarcoma (FUS) leads to aggressive and juvenile onset of ALS. FUS is a well-conserved protein across different species, which plays a crucial role in regulating different aspects of RNA metabolism. Targeted misexpression of FUS in Drosophila model recapitulates several interesting phenotypes relevant to ALS including cytoplasmic mislocalization, defects at the neuromuscular junction and motor dysfunction. We screened for the genetic modifiers of human FUS-mediated neurodegenerative phenotype using molecularly …

Phenotypic Switching Of Bacterial Cells In Extreme Environments, Sudip Nepal

Graduate Theses and Dissertations

A large number of terrestrial microbial lives thrive in extremes of environmental conditions, including extremes of pressure, temperature, salinity, pH, and a combination of them. For example, all the marine biomass thrive at high hydrostatic pressure depending on depth. The temperature in the ocean can be very high near the hydrothermal vents and salinity and pH depends on the composition of salt in the surrounding areas. On the surface, hot springs, lakes and geysers provide high temperature conditions, while many places are permafrost regions with subzero temperatures. There is an emerging body of work on the viability, genomics, and metagenomics …

Evaluating The Effects Of Fasting Conditions In Combination With Temozolomide For The Treatment Of Glioblastoma Multiforme, Joseph Duffy

All NMU Master's Theses

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of adult brain cancer. The standard of care for GBM is maximal surgical resection followed by adjuvant treatment with the chemotherapeutic agent temozolomide (TMZ) and radiotherapy. O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein involved in TMZ resistance. Known as the Warburg effect, cancer cells will preferentially oxidize glucose to lactate in glycolysis. This less effective pathway of energy production means cancer cells must uptake significantly greater amounts of glucose to sustain physiological needs. One method that directly targets the bioavailability of glucose is fasting. Among other adaptations, fasting lowers …

Mechanistic And Translational Studies On Skeletal Malignancies, Jeremy Mcguire

USF Tampa Graduate Theses and Dissertations

New treatment strategies are desperately needed for treating skeletal malignancy. Skeletal malignancies can be either primary cancer that originated in the bone, such as osteosarcoma, or metastatic cancer that spread from another organ to the skeleton, as in the case of breast or prostate cancer. In this thesis, I will detail two projects that focus on the discovery of new treatment strategies for both primary skeletal malignancy and metastatic skeletal malignancy.

The first project focuses on the primary skeletal malignancy, osteosarcoma, a rare cancer that is commonly diagnosed in children and young adults and metastasizes to the lungs. The survival …

Biological And Proteomic Characterization Of Cornus Officinalis On Human 1.1b4 Pancreatic Β Cells: Exploring Use For T1d Interventional Application, Arielle E. Tawfik

USF Tampa Graduate Theses and Dissertations

Type 1 diabetes (T1D) is an autoimmune disease resulting in the loss of pancreatic β cells and subsequent loss of insulin production. Exogenous insulin coupled with continuous glucose monitoring is the only treatment for T1D. Therefore, novel interventional therapies are needed that can inhibit the autoimmune destruction and increase β cell proliferation and function. Based on initial in vitro studies, traditional Chinese medicine (TCM) extract, Cornus officinalis, may be able to serve in this function. CO has been used for 2 millennia for its glucose regulating potential and has shown efficacy in animal models but rarely studied in the context …

Mass Spectrometry Identification Of Membrane-Type 1 Matrix Metalloproteinase (Mt1-Mmp) Binding Partners Following Co-Immunoprecipitation In Mcf-7 Cells, Bradley Bork

Electronic Thesis and Dissertation Repository

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an integral multidomain membrane protease involved in extracellular matrix remodelling. No longer recognized solely as a destructive enzyme, MT1-MMP proteolytic and non-proteolytic activities are involved in a variety of cellular processes. I hypothesized that the diverse functions of MT1-MMP are dependent on domain-specific binding partner interactions that elicit a cellular response. Using a combination of co-immunoprecipitation and mass spectrometry, 248 unique proteins were isolated in MT1-MMP variant expressing MCF-7 cells. Newly identified binding partners suggest potential roles of MT1-MMP in the nucleus, endoplasmic reticulum, cytoplasm, and plasma membrane. Additionally, the cytoplasmic domain of MT1-MMP …

Regulators Of Ectopic Calcification In A Mouse Model Of Dish: A Multi-Omics Perspective, Matthew A. Veras

Electronic Thesis and Dissertation Repository

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory spondyloarthropathy and the second most common form of arthritis characterized by formation of ectopic mineral along the spine. Pathological findings in DISH include regional calcification of the anterior longitudinal ligament, paraspinal connective tissues, and annulus fibrosus (AF) of the intervertebral disc (IVD). Clinical symptoms of DISH include increased spine stiffness, decreased spinal range of motion, and in severe cases dysphagia and spinal cord/nerve root compression. The molecular pathways responsible for DISH have not been delineated and as such, there are no disease-modifying treatments. Clinical treatment for DISH is limited to surgical resection …

The Amino Terminal Domains Of Sheep Cx46 Or Cx50 Determine Their Gap Junction Channel Open Stability And Unitary Channel Conductance, Benny Yue

Electronic Thesis and Dissertation Repository

Connexins form intercellular communication channels known as gap junctions (GJs), which are found throughout the vertebrate species. GJs formed by different connexins harbor unique channel properties that have not been fully defined. High-resolution structures of native Cx46 and Cx50 GJs from sheep (sCx46 and sCx50) were recently resolved. Molecular dynamics studies identified the NT domains, especially the 9^th position, as key determinants in the differences of energetic barrier to K⁺ permeation in sCx46 and sCx50 GJs. We studied functional properties of GJs formed by sCx46, sCx50, NT domain swapped chimeras (sCx46-50NT and sCx50-46NT), and point variants at the …

Low-Cost Diagnostics: Using Paper As A Material And Pens As An Instrument, Annie Armitstead

Undergraduate Honors Theses

Lateral flow immunoassays (LFIs) are equipment-free tests that produce results quickly using small sample volumes. Colored lines appear as the test runs, indicating the presence of a biomarker. LFIs are ideal in a variety of settings. Development of these assays can be complicated for small team operations, and tests are not sufficiently adaptable for low resource settings. If robust point-of-care tests can be developed on site, they can expand the reach of global diagnostics, improving health around the world. We report a simple empowering LFI (seLFI) that only requires treated printer paper and a plastic backing card. This eliminates the …

Proteomic Identification Reveals The Role Of Ciliary Extracellular‐Like Vesicle In Cardiovascular Function, Ashraf M. Mohieldin, Rajasekharreddy Pala, Rinzhin T. Sherpa, Madhawi Alanazi, Ashwaq Alanazi, Kiumars Shamloo, Amir Ahsan, Wissam A. Aboualaiwi, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)‐like characteristics. The ciliary extracellular‐like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo …

B Cell Acute Lymphoblastic Leukemia Is Driven By Activating Janus Kinase Mutations Cooperating With Spi1 And Spib Deletions In A Murine Model, Michelle Lim

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is caused by genetic lesions in developing B cells that function as drivers for accumulation of additional mutations in an evolutionary selection process. We investigated secondary drivers of leukemogenesis and their mechanism(s) of arising in a mouse model of B-ALL driven by PU.1/Spi-B deletion (Mb1-CreDPB). Whole exome sequencing revealed recurrent mutations in Jak3 (encoding Janus Kinase 3) and Jak1. Mutations with high variant allele frequency (VAF) were dominated by C->T transition mutations that were compatible with AID, whereas the majority of mutations, with low VAF, were dominated by C->A transversions associated with …

Gocats: A Tool For Categorizing Gene Ontology Into Subgraphs Of User-Defined Concepts, Eugene Waverly Hinderer Iii, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Gene Ontology is used extensively in scientific knowledgebases and repositories to organize a wealth of biological information. However, interpreting annotations derived from differential gene lists is often difficult without manually sorting into higher-order categories. To address these issues, we present GOcats, a novel tool that organizes the Gene Ontology (GO) into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. We tested GOcats performance using subcellular location categories to mine annotations from GO-utilizing knowledgebases and evaluated their accuracy against immunohistochemistry datasets in the Human Protein Atlas (HPA). In comparison to term categorizations …

Profiling The Circulating Mrna Transcriptome In Human Liver Disease, Aejaz Sayeed, Brielle E Dalvano, David E Kaplan, Usha Viswanathan, John Kulp, Alhaji H Janneh, Lu-Yu Hwang, Adam Ertel, Cataldo Doria, Timothy Block

Department of Cancer Biology Faculty Papers

The human circulation contains cell-free DNA and non-coding microRNA (miRNA). Less is known about the presence of messenger RNA (mRNA). This report profiles the human circulating mRNA transcriptome in people with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) to determine whether mRNA analytes can be used as biomarkers of liver disease. Using RNAseq and RT-qPCR, we investigate circulating mRNA in plasma from HCC and LC patients and demonstrate detection of transcripts representing more than 19,000 different protein coding genes. Remarkably, the circulating mRNA expression levels were similar from person to person over the 21 individuals whose samples were analyzed by …

Metabolic Network Analysis Of Filamentous Cyanobacteria, Daniel Alexis Norena-Caro

LSU Doctoral Dissertations

Cyanobacteria were the first organisms to use oxygenic photosynthesis, converting CO₂ into useful organic chemicals. However, the chemical industry has historically relied on fossil raw materials to produce organic precursors, which has contributed to global warming. Thus, cyanobacteria have emerged as sustainable stakeholders for biotechnological production. The filamentous cyanobacterium Anabaena sp. UTEX 2576 can metabolize multiple sources of Nitrogen and was studied as a platform for biotechnological production of high-value chemicals (i.e., pigments, antioxidants, vitamins and secondary metabolites). From a Chemical engineering perspective, the biomass generation in this organism was thoroughly studied by interpreting the cell as a microbial …

Molecular And Ultrastructure Study Of Tight Junction During Experimental Entamoeba Spp. Infection, Athraa A. Al-Hilfi Dr, Maha Khalil Al-Malak, Shereen Jawad Al-Ali, Muslim Abd-Ulrahman Al-Tomah

Karbala International Journal of Modern Science

Entamoeba spp. in particular E.histolytica is the main reason of human amoebiasis. The molecular mechanism of its pathogenicity is poorly understood, therefore the aim this study is to investigate these mechanism on both molecular and ultrastructure levels. Tight junction (TJ) genes Claudin-1 (Cldn1) and Occludin (Ocln) were investigated by real time PCR and the pathological changes by scanning electron microscopy (SEM) and transmission electron microscope (TEM), the result showed that the gene expression levels of TJ genes were significantly high in rats infected with E. histolytica E. dispar and E. moshkovskii after 28, 14, 7 days in compare with healthy …

Insights Into Desiccation Tolerance: Properties Of Late Embryogenesis Abundant Proteins From Embryos Of Artemia Franciscana, Blase Matthew Leblanc

LSU Doctoral Dissertations

LEA proteins are a family of intrinsically disordered proteins that are expressed in various life stages of anhydrobiotic organisms and have been strongly associated with survival during water stress. The brine shrimp Artemia franciscana is the only known anhydrobiotic animal that expresses LEA proteins from Groups 1, 3, and 6. Here, I report that AfrLEA6, a novel Group 6 LEA protein, is most highly expressed in embryos during diapause and decreases throughout pre-emergence development. Notably, there is an acute drop in expression upon termination of the diapause state and the titer of AfrLEA6 during diapause is 10-fold lower than values …