Molecular Biology Commons^™

Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors ...

Evaluation Of Motor Cortex Neuronal Morphology In Developmental Hyperserotonemia Rat Model, Colten Z. Dillinger

MSU Graduate Theses

Fetal serotonin levels are involved in the development of the serotonergic system in an autoregulatory manner as well as the organization and connectivity of non-serotonergic neurons. Insufficient serotonin levels during development result in improper neuronal maturation and decreased synaptogenesis. Conversely, excess developmental serotonin levels can alter the progression of serotonergic neurons, ultimately resulting in a chronic decrease of serotonin in the developed brain via a negative feedback mechanism. There is a known correlation between autistic patients and chronically decreased brain serotonin concentrations; this is potentially implicated in the impaired development of the autistic brain. Incomplete or delayed development of motor ...

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study ...

Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke

Shared Knowledge Conference

Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a high-speed ...

33 - Identification Of Proteins That Regulate Crispr Dna Uptake Of Pyrococcus Furiosus, Landon Clark

Georgia Undergraduate Research Conference (GURC)

The CRISPR-Cas (Clustered Regularly Interspace Short Palindromic Repeats-CRISPR associated) system is a prokaryotic, adaptive immune system used by bacterial and archaeal organism to fight infections by viruses and other harmful invasive DNAs. These prokaryotic CRISPR-Cas immune systems have been exploited as powerful genome editing tools that work many different organisms and cells including humans. The newly developed CRISPR-based technologies are transforming medicine and science and have been used in research applications for developing cures for certain cancers, HIV, hemophilia, etc. The function of the CRISPR-Cas systems follow three basis steps: (1) adaptation (invading DNA is integrated into the host genome ...

Mechanisms Mediating The Pro-Fibrotic Effects Of Estradiol, Haley Fulton

Georgia Undergraduate Research Conference (GURC)

Scleroderma is a connective tissue disease which promotes fibrosis of the skin and internal organs. Scleroderma patients have upregulated production of fibrotic extracellular matrix proteins and upregulated serum estradiol levels compared to control subjects. Estradiol effects eukaryotic transcription and gene expression when it enters the nucleus via one of its nuclear hormone receptors. Estrogen receptor one/ estrogen receptor alpha (ESR1) is present on the nuclear membrane and binds the ligand estrogen. These experiments were designed to study the various isoforms of ESR1 and determine if gene expression of ESR1 was greater in fibroblasts and human skin stimulated with estradiol than ...

Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao

Open Access Articles

Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology ...

Basic Cell And Molecular Biology 3e: What We Know And How We Found Ou, Gerald Bergtrom

Cell and Molecular Biology 3e: What We Know and How We Found Out - All Versions

No abstract provided.

T Cell Epitope Engineering: An Avian H7n9 Influenza Vaccine Strategy For Pandemic Preparedness And Response, Leonard Moise, Bethany M. Biron, Christine M. Boyle, Nese Kurt Yilmaz, Hyesun Jang, Celia A. Schiffer, Ted M. Ross, William D. Martin, Anne S. De Groot

Schiffer Lab Publications

The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4(+) T cell epitopes - without perturbing native antigen structure - by galvanizing HA-specific memory ...

Accurate Flexible Refinement Of Atomic Models Against Medium-Resolution Cryo-Em Maps Using Damped Dynamics, Julio A. Kovacs, Vitold E. Galkin, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Background: Dramatic progress has recently been made in cryo-electron microscopy technologies, which now make possible the reconstruction of a growing number of biomolecular structures to near-atomic resolution. However, the need persists for fitting and refinement approaches that address those cases that require modeling assistance.

Methods: In this paper, we describe algorithms to optimize the performance of such medium-resolution refinement methods. These algorithms aim to automatically optimize the parameters that define the density shape of the flexibly fitted model, as well as the time-dependent damper cutoff distance. Atomic distance constraints can be prescribed for cases where extra containment of parts of ...

The Impact Of Lncrna Dysregulation On Clinicopathology And Survival Of Breast Cancer: A Systematic Review And Meta-Analysis, Tian Tian, Meng Wang, Shuai Lin, Zhiming Dan, Kang Liu, Wenge Zhu, +Several Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Dysregulation of multiple long non-coding RNAs (lncRNAs) was reported to play major roles in breast cancer (BC). Here we aimed to collect most of the relevant literature to assess the prognostic value of lncRNAs in BC. To this end, we systematically searched PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang to identify published articles on the associations of lncRNAs with clinicopathology and/or survival of BC. Via this searching, we identified 70 articles involving 9,307 BC patients and regarding 48 lncRNAs. The expression of 41 lncRNAs was related to one or more clinicopathological parameters of ...

An Asymmetric Centromeric Nucleosome, Yuichi Ichikawa, Noriko Saitoh, Paul D. Kaufman

Open Access Articles

Nucleosomes contain two copies of each core histone, held together by a naturally symmetric, homodimeric histone H3-H3 interface. This symmetry has complicated efforts to determine the regulatory potential of this architecture. Through molecular design and in vivo selection, we recently generated obligately heterodimeric H3s, providing a powerful tool for discovery of the degree to which nucleosome symmetry regulates chromosomal functions in living cells (Ichikawa et al., 2017). We now have extended this tool to the centromeric H3 isoform (Cse4/CENP-A) in budding yeast. These studies indicate that a single Cse4 N- or C-terminal extension per pair of Cse4 molecules is ...

Effect Of Arsenic Exposure On Early Eye Development In Zebrafish (Danio Rerio), Remy S. Babich

Electronic Theses and Dissertations

Arsenic is a metalloid that contaminates drinking water supplies worldwide. Due to concerns for human health, the World Health Organization (WHO) and the U.S. Environmental Protection Agency (EPA) have established a safe level in drinking water of ≤ 10 ppb. Arsenic has been shown to have carcinogenic effects in humans at high and low doses. Chronic exposure may result in dermal conditions such as hyperkeratosis and hyperpigmentation. Recently, arsenic exposure has also been linked to lower IQ values in children. The effect of arsenic on neurogenesis, specifically eye development, has not been widely explored. This study aimed to examine the ...

Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger

Arts & Sciences Electronic Theses and Dissertations

Behavior in higher eukaryotes is a complex process which integrates signals in the environment, the genetic makeup of the organism, and connectivity in the nervous system to produce extremely diverse adaptations to the phenomenon of existence. Unraveling the subcellular components that contribute to behavioral output is important for both understanding how behavior occurs in an unperturbed state, as well as understanding how behavior changes when the underlying systems that generate it are altered. Of the numerous molecular species that make up a cell, the regulation of messenger RNAs (mRNAs), the coding template of all proteins, is of key importance to ...

Gq Noncanonical Roles In Translational Regulation, Brett Demarco

Electronic Theses and Dissertations

This study investigates protein nucleic acid interactions, focusing on G-quadruplex (GQ) forming DNA/RNA in human disease. GQ structures are formed in DNA/RNA, when four guanine residues form planar tetrads stabilized by Hoogsteen base pairing, that stack forming a GQ structure stabilized by potassium ions. These GQ structures are targeted by the arginine glycine-glycine (RGG) RNA-binding domain. Fragile X mental retardation protein (FMRP), a translation regulator protein implicated in the fragile X syndrome, has an RGG domain and has been previously shown to interact with neuronal GQ forming messenger RNA (mRNA). We have investigated three neuronal FMRP mRNA targets ...

A Population Of Gut Epithelial Enterochromaffin Cells Is Mechanosensitive And Requires Piezo2 To Convert Force Into Serotonin Release, Constanza Alcaino, Kaitlyn R. Knutson, Anthony J. Treichel, Gulcan Yildiz, Peter R. Strege, David R. Linden, Joyce H. Li, Andrew B. Leiter, Joseph H. Szurszewski, Gianrico Farrugia, Arthur Beyder

Open Access Articles

Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell ...

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R. Schwartz, Megan E. Honeywell, Gary Ren, Alyssa D. Schwartz, Shelly R. Peyton, Michael J. Lee

Program in Systems Biology Publications and Presentations

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested ...

Microbial Ecology Of South Florida Surface Waters: Examining The Potential For Anthropogenic Influences, Chase P. Donnelly

HCNSO Student Theses and Dissertations

South Florida contains one of the largest subtropical wetlands in the world, and yet not much is known about the microbes that live in these surface waters. These microbes play an important role in chemical cycling and maintaining good water quality for both human and ecosystem health. The hydrology of Florida’s surface waters is tightly regulated with the use of canal and levee systems run by the US Army Corps of Engineers and The South Florida Water Management District. These canals run through the Everglades, agriculture, and urban environments to control water levels in Lake Okeechobee, the Water Conservation ...

Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho

Electronic Thesis and Dissertation Repository

IL-1β is a potent inflammatory cytokine promptly expressed in activated myeloid cells. PU.1 is a lineage-determining transcription factor that regulates myeloid-specific genes by activating distal enhancers. This study addresses the functional importance of a potential enhancer of IL-1β, and how PU.1 regulates its activity state. A putative enhancer RNA (eRNA) was transcribed from the enhancer, and eRNA knock-down with antisense oligonucleotides inhibited IL-1β production. Furthermore, enhancer-promoter interactions in stimulated macrophages were detected via chromatin conformation capture (3C) analysis. The role of PU.1 was examined in PU.1-overexpressed B16-BL6 cells, which responded to LPS and expressed IL-1β mRNA ...

Improving Biomanufacturing Production With Novel Elp-Based Transcriptional Regulators, Juya Jeon, Logan R. Readnour, Kevin V. Solomon

The Summer Undergraduate Research Fellowship (SURF) Symposium

Microbes can be used to produce valuable drugs, chemicals, and biofuels, but their potential has not been fully realized due to low production yields. To improve biomanufacturing processes and yield, we are developing novel, transcriptional regulators using biosynthesis technology in order to improve cellular health and overall production. Our regulator contains elastin-like polypeptides (ELPs), which make ideal sensors since they exhibit a sharp, inverse phase transition to indicators of cell health such as intracellular pH and ionic strength, and external stimuli such as temperature. We hypothesize that ELP can be fused to transcription factors to control expression of target genes ...