Cell and Developmental Biology Commons^™

The Neurobiology Of Circadian Rhythms, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Daily rhythms in nature, such as the opening and closing of flowers or our patterns of sleep and wakefulness and their association with the perpetual alteration of night and day, were recognized in antiquity although their origins were not questioned until the eighteenth century. The French Astronomer Jean-Jacques d’Ortous de Mairan conducted an investigation into whether the leaves of the Mimosa plant opened in response to light.¹ While de Mairan’s experiments were the first to question the origin of such daily rhythms, Augustin Pyramus de Candolle is credited with the first suggestion that they arose through an internal timekeeping …

A Synthetic Porcine Reproductive And Respiratory Syndrome Virus Strain Confers Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. By using a set of 59 nonredundant, full-genome sequences of type 2 PRRSVs, a consensus genome (designated PRRSV-CON) was generated by aligning these 59 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the …

Identifying Protein Kinase Tbk1 As A Novel Inhibitor Of Intestinal Tumorigenesis, Amber L. Mathews

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer diagnosed in women and men， causing almost 600,000 annual deaths worldwide. There is a clear need to understand how CRC forms and progresses in order to improve the strategies of CRC prevention and therapy. A major factor that drives the development of CRC is genetic mutations that lead to activation of oncogenes and inactivation of tumor suppressor genes in intestinal epithelial cells (IECs). In addition, the initiation and progression of CRC involve environmental and immunological factors. In particular, chronic inflammatory conditions are known as an important risk factor for CRC. Intestinal …

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …

Mobilization Of Adipose Stromal Cells In Obesity And Cancer By Sparc And Its Proteolytic Isoforms, Chieh Tseng

Dissertations and Theses (Open Access)

Obesity increases cancer risk and progression as shown by epidemiologic studies. However, the underlying pathophysiology remained unclear. Adipose stromal cells (ASC) are adipose tissue-derived mesenchymal progenitors, abundant in white adipose tissue (WAT). In this study, we show that the ASC pool is expanded in obesity and is associated with promoted tumor growth. Next, by using a chimeric GFP-RFP bone marrow transplant model, we observed higher tumor infiltrating cells with ASC phenotype in obese mice compared to lean. Consistently, systemic circulating ASC frequency is six fold higher in tumor-bearing obese mice compared to lean. The tumor infiltrating cells with ASC phenotype …

The Tumor Suppressor Notch Inhibits Head And Neck Squamous Cell Carcinoma (Hnscc) Tumor Growth And Progression By Modulating Proto-Oncogenes Axl And Ctnnal1 (Α-Catulin), Shhyam Moorthy, Shhyam Moorthy

Dissertations and Theses (Open Access)

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy worldwide, with roughly 300,000 cancer related deaths occurring globally each year. The survival of patients with HNSCC has not changed significantly over the past decade, leading investigators to search for promising molecular targets. To identify new treatment targets and biomarkers that could better guide therapy, we previously characterized the genomic alterations from primary HNSCC patient samples. We were among the first to discover that NOTCH1 is one of the most frequently mutated genes in this cancer type. The spectrum of inactivating NOTCH1 mutations in HNSCC suggested …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao

Dissertations and Theses (Open Access)

Background: Calcification occurs often in the atherosclerotic lesions of patients with coronary heart disease and animals with hypercholesterolemia, such as apolipoprotein-E deficient (ApoE-/-) mice. However, the mechanism(s) underlying the development of calcification in atherosclerosis remains unclear. ApoE acts as a lipid transporter, but also has been recognized as a potential regulator of osteogenesis. Little information is available as to whether ApoE has any direct impact on osteogenesis and calcification in vascular smooth muscle cells (VSMC). Several signal transduction pathways play a role in regulation of calcification, including the Wnt/β-catenin system and potentially GTAP, an ubiquitin-conjugating enzyme responsible for protein …

Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations and Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

Third Ventricle Width As A Metric For Fast And Efficient Detection Of Atrophy In Traumatic Brain Injury, Christopher Scott Finuf

Theses and Dissertations

In an average year more than 1.7 million people will experience a traumatic brain injury (TBI) in the United States. It is known that atrophy occurs across a spectrum for TBI patients, ranging from mild to severe. Current conventional magnetic resonance imaging (MRI) methods are inconsistent in detecting this atrophy on the milder end of the spectrum. Also more contemporary imaging tools, although efficient, are too time consuming for clinical applicability. It is for these reasons that a quick and efficient measurement for detecting this atrophy is needed by clinicians. The measuring of third ventricle width had the potential to …

Response Of Bacterial Cells To Fluctuating Environment, Sudip Nepal

Graduate Theses and Dissertations

We have studied morphological and genomic variations occurring in a mesophilic bacterium Escherichia coli (E. coli) in a wide range of continuous and fluctuating hydrostatic pressures. For all the studies here the temperature is maintained at 37◦C, the optimal growth tem- perature of E. coli at atmospheric pressure. Cell division is inhibited at high hydrostatic pressures resulting in an increase of cell length. The increase of cell-length depends on the extent and duration of the stress applied on bacterial cells. We have studied the effect of high pressure stress in three different conditions – (i) Wild-type cells (almost no genetic …

Effects Of Bone Morphogenetic Protein-2 And Parathyroid Hormone-Related Peptide On Collagen Xi During Skeletal Development, Neda Shefa

Boise State University Theses and Dissertations

Long bones develop via endochondral ossification, a process in which cartilage precedes bone. During endochondral ossification prechondrogenic cells undergo proliferation and apoptose as cells of the periosteum differentiate into bone. The process of endochondral ossification is regulated by a group of endocrine as well as paracrine molecules that includes bone morphogenetic protein-2 (BMP-2) and parathyroid hormone-related peptide (PTHrP). Collagens are extracellular matrix molecules that are present in a spatiotemporal manner during endochondral ossification. Collagen XI alpha 1 (Col11a1) is a minor fibrillar collagen that is alternatively spliced during development and can result in up to eight different spliceforms. During endochondral …

Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola

Graduate Theses and Dissertations

Autophagy or cellular self-digestion, a lysosomal degradation pathway that is conserved from yeast to human, plays a key role in recycling cellular constituents, including damaged organelles. It also plays a pivotal role in the adaptation of cells to a plethora of distinct stressors including starvation. Autophagy has been extensively studied in mammals and yeast, but little is known in avian species. Thus, the major objective of the present study was to determine the effects of leptin on autophagy-related genes in chicken hypothalamus, muscle and liver. Leptin is an adipocytokine that is mostly produced by white adipose cells in mammals (as …

Transcriptomics Of Chicken Primordial Germ Cells, Nhung Thi Nguyen

Graduate Theses and Dissertations

Chicken primordial germ cells (PGCs) are derived from extraembryonic tissue of the embryo and first appear at stage X of development. They enter the bloodstream and migrate to the genital ridge, unite with somatic tissue to form a developing gonad, and then differentiate to sperm or ova (Fujimoto et al., 1976). Understanding molecular features of both male and female PGCs not only clarify the differentiation mechanism of such cells toward different germ lines, but will also help in selecting for highly productive types of commercial chicken. Most previous studies focused on the location of PGCs (Eyal-Giladi et al., 1981; Swift …

Compounds Released From Biomass Deconstruction: Understanding Their Effect On Cellulose Enzyme Hydrolysis And Their Biological Activity, Angele Djioleu

Graduate Theses and Dissertations

The effect of compounds produced during biomass pretreatment on cellulolytic enzyme was investigated. Liquid prehydrolyzates were prepared by pretreating switchgrass using 24 combinations of temperature, time, and sulfuric acid concentration based on a full factorial design. Temperature was varied from 140°C to 180°C; time ranged from 10 to 40 min; and the sulfuric acid concentrations were 0.5% or 1% (v/v). Identified products in the prehydrolyzates included xylose, glucose, hydroxymethylfurfural (HMF), furfural, acetic acid, formic acid, and phenolic compounds at concentration ranging from 0 to 21.4 g/L. Pretreatment conditions significantly affected the concentrations of compounds detected in prehydrolyzates. When assayed in …

Eicosapentaenoic Acid (Epa) From Porphyridium Cruentum: Increasing Growth And Productivity Of The Microalgae For Pharmaceutical Products, Maryam Asgharpour

Graduate Theses and Dissertations

One of the major nutritional requirements in our diet is an adequate intake of omega-3 specially eicosapentaenoic acid (EPA). In the present study, the effects of two temperatures (16°C & 20˚C) and light intensities (140 & 180µE/M2.S) and four nitrate levels (0.075, 0.3, 0.5 and 0.7g/L) on the cell growth and lipid productivity of Porphyridium cruentum, one of the most promising oil-rich species of microalgae, were investigated. A growth comparison was carried out using pure CO2 and 5% CO2/air. Additionally, the ratio of the fatty acids with omega-3 and omega-6 groups at various growth conditions were compared, since an appropriate …

Dancing Through Life: Molecular Dynamics Simulations And Network-Centric Modeling Of Allosteric Mechanisms In Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that …

Endothelin-B Receptor Activation In Astrocytes Regulates The Rate Of Oligodendrocyte Regeneration During Remyelination., Timothy R. Hammond, Brian Mcellin, Paul D Morton, Matthew Raymond, Jeff Dupree, Vittorio Gallo

Medicine Faculty Publications

Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, …

Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff

USF Tampa Graduate Theses and Dissertations

PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver. …

The Transient Receptor Potential Melastatin 2 (Trpm2) Channel Contributes To Beta-Amyloid Oligomer-Related Neurotoxicity And Memory Impairment, Valeriy G. Ostapchenko, Megan Chen, Monica S. Guzman, Yu-Feng Xie, Natalie Lavine, Jue Fan, Flavio H. Beraldo, Amanda C. Martyn, Jillian C. Belrose, Yasuo Mori, John F. Macdonald, Vania F. Prado, Marco A. M. Prado, Michael F. Jackson

Anatomy and Cell Biology Publications

In Alzheimer's disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of …