Distinct Spatiotemporal Regulation Of The Cytoprotective Heat Shock Response In Caenorhabditis Elegans,
2021
Florida Institute of Technology
Distinct Spatiotemporal Regulation Of The Cytoprotective Heat Shock Response In Caenorhabditis Elegans, Rosemary Nadine Plagens
Theses and Dissertations
Every organism studied to-date utilizes the heat shock response (HSR) to maintain protein-folding homeostasis (proteostasis) during temperature or other protein-folding stress. The HSR has been well characterized using acute heat stress (HS) in single-celled models, but less is known about how distinct cell types and tissues respond to HS. Furthermore, how metazoans respond to prolonged HS at the molecular level remains relatively unexplored. The model organism C. elegans, with its genetic tractability and distinct tissues and behaviors, has been used extensively in the field to characterize the acute HSR, but with considerable variability across labs regarding HS temperature and duration. …
Genetically Encoded Multivalent Liquid Glycan Array Displayed On M13 Bacteriophage,
2021
1Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada. Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk, Egypt
Genetically Encoded Multivalent Liquid Glycan Array Displayed On M13 Bacteriophage, Amira Khalil, Mirat Sojitra, Jasmine Maghera, Emily Rodrigues, Eric J. Carpenter, Shaurya Seth, Daniel Ferrer Vinals, Todd L. Lowary
Pharmacy
The central dogma of biology does not allow for the study of glycans using DNA sequencing. We report a liquid glycan array (LiGA) platform comprising a library of DNA ‘barcoded’ M13 virions that display 30–1,500 copies of glycans per phage. A LiGA is synthesized by acylation of the phage pVIII protein with a dibenzocyclooctyne, followed by ligation of azido-modified glycans. Pulldown of the LiGA with lectins followed by deep sequencing of the barcodes in the bound phage decodes the optimal structure and density of the recognized glycans. The LiGA is target agnostic and can measure the glycan-binding profile of lectins, …
Divergent Regulatory Roles Of Nurd Chromatin Remodeling Complex Subunits Gatad2 And Chd4 In Caenorhabditis Elegans,
2021
Florida Institute of Technology
Divergent Regulatory Roles Of Nurd Chromatin Remodeling Complex Subunits Gatad2 And Chd4 In Caenorhabditis Elegans, Nicole Lynn Golden
Theses and Dissertations
During stress, a protective cellular network known as the heat shock response (HSR) is induced to maintain protein-folding homeostasis, or proteostasis. While the HSR is essential for stress resistance, its misregulation is associated with neurodegenerative disease and cancer. Using the nematode model organism Caenorhabditis elegans, we have identified the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylase) as a novel regulator of the HSR. Here, we begin with a brief introduction of the HSR and chromatin remodeling complexes in C. elegans, prior to presenting our findings in a series of two chapters. In chapter one, we outline a set of …
Host-Parasite Interactions Within Food Webs,
2021
University of Arkansas, Fayetteville
Host-Parasite Interactions Within Food Webs, Adam Zvanut Hasik
Graduate Theses and Dissertations
Parasitism is one of the most common life history strategies employed in nature, yet the effects of parasites are often thought to be minimal, and the vast majority of studies fail to consider parasites and their effects on host organisms. This is likely a problem, as the magnitude of parasite-mediated effects on their hosts can be quite large. Additionally, the effects of parasites are known to extend beyond the host to affect other species interactions. I used a series of approaches to gain a more integral understanding of host-parasite interactions by studying (1) the effects of parasites on biotic interactions …
Transcriptomic And Functional Investigation Of Bacterial Biofilm Formation,
2021
University of South Florida
Transcriptomic And Functional Investigation Of Bacterial Biofilm Formation, Brooke R. Nemec
USF Tampa Graduate Theses and Dissertations
Staphylococcus aureus and Acinetobacter baumannii are two highly successful human pathogens, which have adopted very different, but effective survival strategies. The success of S. aureus is attributed to the tight regulation of an arsenal of virulence factors. Conversely, A. baumannii lacks what would be considered traditional virulence factors and, instead, has developed a high tolerance for environmental stress, which allows it to persist in unforgiving environments, including nosocomial settings and the human body. One common characteristic of these two organisms is their proclivity for biofilm formation. Herein, we discuss the diverse mechanisms governing biofilm formation for A. baumannii and S. …
Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer,
2021
University of South Florida
Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde
USF Tampa Graduate Theses and Dissertations
Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …
Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates Hif1Α During Chronic Hypoxia,
2021
University of South Florida
Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates Hif1Α During Chronic Hypoxia, Emily M. Mayo
USF Tampa Graduate Theses and Dissertations
Chronic pulmonary hypoxia commonly results in the sustained expression of HIF1 (hypoxia inducible factor 1), a heterodimeric transcription factor, that, if unrestrained, can result in dramatic vasculature remodeling, pulmonary arterial hypertension, and right-sided heart failure. Together, these pulmonary disorders cost approximately $100 billion annually to treat due to the limited therapeutic targets designed to inhibit HIF1 expression. In this study, we introduce a translational regulator of HIF1 expression, known as Cytosolic polyadenylation element binding proteins 2 (CPEB2). Our lab has previously demonstrated in cancer cells that alternatively spliced isoforms of CPEB2 regulate the translation of the HIF1 oxygen-dependent subunit, HIF1α, …
The Role Of Native Lens Α-Crystallin In Amyloid Suppression Using Β-Amyloid As A Model Amyloid Client,
2021
Portland State University
The Role Of Native Lens Α-Crystallin In Amyloid Suppression Using Β-Amyloid As A Model Amyloid Client, Leilani Lopes
University Honors Theses
Cataracts are a result of age-related protein aggregate formation in the eye lens, and the leading cause of blindness worldwide. α-crystallin, a small heat shock protein, acts a molecular chaperone that serves as the primary defense mechanism against protein aggregate formation in the lens. Recent evidence suggest amyloid formation in the lens may contribute to cataract formation, and that β-amyloid is present in lens epithelia of age-related cataracts. Previous studies have shown that αB-crystallin in other parts of the body, such as the brain, is protective against neurodegenerative diseases such as Alzheimer’s disease that are associated with plaque deposits containing …
Protein Motifs For Proton Transfers That Build The Transmembrane Proton Gradient,
2021
CUNY City College
Protein Motifs For Proton Transfers That Build The Transmembrane Proton Gradient, Divya Kaur, Umesh Khaniya, Yingying Zhang, M. R. Gunner
Publications and Research
Biological membranes are barriers to polar molecules, so membrane embedded proteins control the transfers between cellular compartments. Protein controlled transport moves substrates and activates cellular signaling cascades. In addition, the electrochemical gradient across mitochondrial, bacterial and chloroplast membranes, is a key source of stored cellular energy. This is generated by electron, proton and ion transfers through proteins. The gradient is used to fuel ATP synthesis and to drive active transport. Here the mechanisms by which protons move into the buried active sites of Photosystem II (PSII), bacterial RCs (bRCs) and through the proton pumps, Bacteriorhodopsin (bR), Complex I and Cytochrome …
Molecular Dynamics Simulations Provide Insight Into Stability Of Hyperthermophilic Endoglucanases,
2021
Stephen F Austin State University
Molecular Dynamics Simulations Provide Insight Into Stability Of Hyperthermophilic Endoglucanases, Logan E. Sheffield
Electronic Theses and Dissertations
Endoglucanases play a key role in the industrial production of bioethanol, but the most efficient method requires the utilization of high temperatures and is currently limited by the thermostability of endoglucanases. For this reason, it would be beneficial to discover more high-efficiency, thermostable enzymes to utilize in the hydrolytic process. In this study molecular dynamics simulations were performed on structurally similar endoglucanases with varying levels of thermostability to gain insight on what factors contribute to thermostability in endoglucanases. RMSD, RMSF, PCA, hydrogen bonding and salt bridges were analyzed. Finally, protein energy networks were constructed from nonbonded interaction potentials and analysis …
Algebraic Graph-Assisted Bidirectional Transformers For Molecular Property Prediction,
2021
Peking University, China
Algebraic Graph-Assisted Bidirectional Transformers For Molecular Property Prediction, Dong Chen, Kaifu Gao, Duc Duy Nguyen, Xin Chen, Yi Jiang, Guo-Wei Wei, Feng Pan
Mathematics Faculty Publications
The ability of molecular property prediction is of great significance to drug discovery, human health, and environmental protection. Despite considerable efforts, quantitative prediction of various molecular properties remains a challenge. Although some machine learning models, such as bidirectional encoder from transformer, can incorporate massive unlabeled molecular data into molecular representations via a self-supervised learning strategy, it neglects three-dimensional (3D) stereochemical information. Algebraic graph, specifically, element-specific multiscale weighted colored algebraic graph, embeds complementary 3D molecular information into graph invariants. We propose an algebraic graph-assisted bidirectional transformer (AGBT) framework by fusing representations generated by algebraic graph and bidirectional transformer, as well as …
Circrev1 Expression In Triple-Negative Breast Cancer,
2021
University of South Florida
Circrev1 Expression In Triple-Negative Breast Cancer, Meagan P. Horton
USF Tampa Graduate Theses and Dissertations
Triple-negative breast cancer (TNBC) comprises only 24% of breast cancer cases, yet is the second leading cause of cancer mortality in women due to its aggressive nature (1). This increase in mortality is due to the lack of receptors for three targetable growth factors (HER2, progesterone, and estrogen receptors). Our previous studies have indicated that these cancers are highly dysregulated in respect to alternative splicing. Hence, we undertook a study aimed at identifying circular RNAs (circRNAs) generated from back-splicing events which were dysregulated in TNBC. We have identified a novel circRNA transcript, circular REV1 (circREV1), which is upregulated in our …
Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease,
2021
University of Connecticut
Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed
Honors Scholar Theses
Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …
Temperature Regulation Of Plant Hormone Signaling During Stress And Development,
2021
Wilfrid Laurier University
Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina
Biology Faculty Publications
Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …
High Performance Mixed-Matrix Electrospun Membranes For Ammonium Removal From Wastewaters,
2021
University of Arkansas, Fayetteville
High Performance Mixed-Matrix Electrospun Membranes For Ammonium Removal From Wastewaters, Shu-Ting Chen, Sumith Ranil Wickramasinghe, Xianghong Qian
Chemical Engineering Faculty Publications and Presentations
Mixed-matrix electrospun membranes were developed to investigate ammonium removal from low ammonium concentration wastewaters for the first time. Particles derived from the inexpensive zeolite 13X were successfully incorporated into polyethersulfone (PES) matrices. The fabricated mixed-matrix electrospun membranes demonstrate high ammonium removal capacity reaching over 55 mg/gzeolite, more than 2.5 times higher than the previously fabricated mixed-matrix membranes via non-solvent induced phase inversion. Moreover, the membranes fabricated exhibit high permeability and ease of regeneration. Over 90% of total ammonium nitrogen (TAN) can be removed from low TAN wastewaters such as aquaculture wastewaters. In addition to zeolite 13X, other zeolite …
Diffusive Search And Trajectories On Tubular Networks A Propagator Approach,
2021
Department of Physics
Diffusive Search And Trajectories On Tubular Networks A Propagator Approach, Zubenelgenubi C. Scott, Aidan I. Brown, Saurabh S. Mogre, Laura M. Westrate
University Faculty Publications and Creative Works
Several organelles in eukaryotic cells, including mitochondria and the endoplasmic reticulum, form interconnected tubule networks extending throughout the cell. These tubular networks host many biochemical pathways that rely on proteins diffusively searching through the network to encounter binding partners or localized target regions. Predicting the behavior of such pathways requires a quantitative understanding of how confinement to a reticulated structure modulates reaction kinetics. In this work, we develop both exact analytical methods to compute mean first passage times and efficient kinetic Monte Carlo algorithms to simulate trajectories of particles diffusing in a tubular network. Our approach leverages exact propagator functions …
An In Vitro Model Of Tumor Heterogeneity Resolves Genetic, Epigenetic, And Stochastic Sources Of Cell State Variability,
2021
Vanderbilt University
An In Vitro Model Of Tumor Heterogeneity Resolves Genetic, Epigenetic, And Stochastic Sources Of Cell State Variability, Corey A. Hayford, Darren R. Tyson, C. Jack Robbins Iii, Peter L. Frick, Vito Quaranta, Leonard Harris
Biomedical Engineering Faculty Publications and Presentations
Tumor heterogeneity is a primary cause of treatment failure and acquired resistance in cancer patients. Even in cancers driven by a single mutated oncogene, variability in response to targeted therapies is well known. The existence of additional genomic alterations among tumor cells can only partially explain this variability. As such, nongenetic factors are increasingly seen as critical contributors to tumor relapse and acquired resistance in cancer. Here, we show that both genetic and nongenetic factors contribute to targeted drug response variability in an experimental model of tumor heterogeneity. We observe significant variability to epidermal growth factor receptor (EGFR) inhibition among …
Molecular Mechanisims Underlying The Anti-Cancer Activity Of Gum Arabic From Acacia Sp. In Triple-Negative Breast Cancer Cells,
2021
United Arab Emirates University
Molecular Mechanisims Underlying The Anti-Cancer Activity Of Gum Arabic From Acacia Sp. In Triple-Negative Breast Cancer Cells, Sawsan Yaslam Hussein Alyafii
Theses
Metastatic breast cancer is the leading cause of cancer-related deaths among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive, accounting for 15-20% of all breast cancer cases. As TNBC cells lack the expression of hormone receptors estrogen receptors (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), TNBCs are unresponsive to hormonal therapy and often become highly resistant when exposed to standard chemotherapy, which has been identified as a major obstacle in TNBC treatment. Gum Arabic, a natural exudate produced from plants, is widely used traditionally for religious, cosmetics as well as medicinal purposes …
Modeling And Analysis Of Intracellular Signaling Networks And Cellular Decisions,
2021
New Jersey Institute of Technology
Modeling And Analysis Of Intracellular Signaling Networks And Cellular Decisions, Mustafa Ozen
Dissertations
Developing molecular network analysis methods is important due to their applications on complex biological systems such as target discovery, development of drugs, discovering drug effects, and finding treatments for many complex diseases, e.g., cancer, autoimmune, and mental disorders. An example of analysis techniques is the fault diagnosis analysis, in which the purpose is to quantify how much vulnerable the entire network is to dysfunction of one or multiple molecules. Such analysis can be done after proper network models are implemented, trained, and tested against the experimental data. In this dissertation, a Boolean modeling framework is implemented and methods to train …
Diversity And Substrate-Specificity Of Green Algae And Other Micro-Eukaryotes Colonizing Amphibian Clutches In Germany, Revealed By Dna Metabarcoding,
2021
Technische Universitat Braunschweig
Diversity And Substrate-Specificity Of Green Algae And Other Micro-Eukaryotes Colonizing Amphibian Clutches In Germany, Revealed By Dna Metabarcoding, Sten Anslan, Maria Sachs, Lois Rancilhac, Henner Brinkmann, Jörn Petersen, Sven Künzel, Anja Schwarz, Hartmut Arndt, Ryan R. Kerney, Miguel Vences
Biology Faculty Publications
Amphibian clutches are colonized by diverse but poorly studied communities of micro-organisms. One of the most noted ones is the unicellular green alga, Oophila amblystomatis, but the occurrence and role of other micro-organisms in the capsular chamber surrounding amphibian clutches have remained largely unstudied. Here, we undertook a multi-marker DNA metabarcoding study to characterize the community of algae and other micro-eukaryotes associated with agile frog (Rana dalmatina) clutches. Samplings were performed at three small ponds in Germany, from four substrates: water, sediment, tree leaves from the bottom of the pond, and R. dalmatina clutches. Sampling substrate strongly …
