Life Sciences Commons^™

Titus Thesis Figures.Docx, Titus Hou

Titus Hou

No abstract provided.

Titus Thesis.Docx, Titus Hou

Titus Hou

No abstract provided.

Effect Of Turmeric On The Promoter Activity Of The Cyp6a8 Gene Of Drosophila Melanogaster, Alexa Stroh

University of Tennessee Honors Thesis Projects

No abstract provided.

Solvation Thermodynamic Mapping In Computer Aided Drug Design, Steven Ramsey

All Dissertations, Theses, and Capstone Projects

The displacement of water from surfaces upon biomolecular recognition and association makes a significant contribution to the free energy changes of these processes. We therefore posit that accurate characterization of local structural and thermodynamic molecular water properties can improve computational model accuracy and predictivity of recognition and association processes. In this thesis, we discuss Solvation Thermodynamic Mapping (STM) methods that we have developed using inhomogeneous fluid solvation theory (IST) to better characterize active site water structural and thermodynamic properties on protein surfaces and the open source tools that we have developed, GIST-CPPTRAJ and SSTMap, which implement these methods which we ...

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

All Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits ...

Analyzing Neuronal Dendritic Trees With Convolutional Neural Networks, Olivier Trottier, Jonathon Howard

Yale Day of Data

In the biological sciences, image analysis software are used to detect, segment or classify a variety of features encountered in living matter. However, the algorithms that accomplish these tasks are often designed for a specific dataset, making them hardly portable to accomplish the same tasks on images of different biological structures. Recently, convolutional neural networks have been used to perform complex image analysis on a multitude of datasets. While applications of these networks abound in the technology industry and computer science, use cases are not as common in the academic sciences. Motivated by the generalizability of neural networks, we aim ...

A Three State Model Can Explain The Dynamics Of Class Iv Drosophila Dendritic Tips, Sabyasachi Sutradhar

Yale Day of Data

No abstract provided.

Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch

University of Massachusetts Medical School Faculty Publications

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we used cryoelectron microscopy to determine the capsid structure of the thermostable phage P74-26. We find the P74-26 capsid exhibits an overall architecture that is very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid ...

Debrowser: Interactive Differential Expression Analysis And Visualization Tool For Count Data, Alper Kucukural, Onur Yukselen, Deniz M. Ozata, Melissa J. Moore, Manuel Garber

Program in Bioinformatics and Integrative Biology Publications and Presentations

BACKGROUND: Sequencing data has become a standard measure of diverse cellular activities. For example, gene expression is accurately measured by RNA sequencing (RNA-Seq) libraries, protein-DNA interactions are captured by chromatin immunoprecipitation sequencing (ChIP-Seq), protein-RNA interactions by crosslinking immunoprecipitation sequencing (CLIP-Seq) or RNA immunoprecipitation (RIP-Seq) sequencing, DNA accessibility by assay for transposase-accessible chromatin (ATAC-Seq), DNase or MNase sequencing libraries. The processing of these sequencing techniques involves library-specific approaches. However, in all cases, once the sequencing libraries are processed, the result is a count table specifying the estimated number of reads originating from each genomic locus. Differential analysis to determine which loci ...

Extracellular Matrix In Development And Disease, Julia Thom Oxford, Jonathon C. Reeck, Makenna J. Hardy

Biomolecular Research Center Publications and Presentations

The evolution of multicellular metazoan organisms was marked by the inclusion of an extracellular matrix (ECM), a multicomponent, proteinaceous network between cells that contributes to the spatial arrangement of cells and the resulting tissue organization. The development of an ECM that provides support in larger organisms may have represented an advantage in the face of selection pressure for the evolution of the ECM.

Investigation Of Amyloid Β Oligomer Dissociation Mechanisms By Single Molecule Fluorescence Techniques, Hope Cook Abdalla

Theses and Dissertations--Chemistry

Alzheimer’s disease (AD) is currently considered the most prevalent neurodegenerative disease and places a large financial burden on society as healthcare resources are limited and the disease does not have a cure. Alzheimer’s disease is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles; however current literature suggests Aβ oligomers are the main aggregating species leading to AD symptoms. Therefore, the underlying cause of Alzheimer’s, accumulation of amyloid beta, is currently being studied in hopes of developing treatment options. Our research aims at determining the mechanism and kinetics of Aβ oligomer dissociation into non-toxic ...

Inhibition Of Hsv-1 Binding By Egcg-Stearate, Valerie Paschalis

Theses, Dissertations and Culminating Projects

Herpes simplex virus type 1 (HSV-1) is the causative agent of oral herpes, and is able to establish lifelong latent infection along with painful, recurring symptoms. Epigallocatechin-3- gallate (EGCG) is the most abundant polyphenol derived from green tea (Camellia sinensis), whose anti-inflammatory, antioxidant, anti-cancer, and antiviral properties have been widely studied. Although EGCG is not chemically stable and has poor hydrophobicity, lipophilic derivatives of EGCG have shown increased stability as well as increased antiviral efficacy against HSV. Previous studies have demonstrated that EGCG stearate (EGCG-S), a derivative of EGCG esterified at the 4’ position with stearic acid, is able to ...

Umsl Faculty Expertise, Chung Wong

Chung Wong

The Trim-Nhl Protein Nhl-2 Is A Co-Factor In The Nuclear And Somatic Rnai Pathways In C. Elegans, Gregory M. Davis, Shikui Tu, Jacqueline A. Wilce, Julie M. Claycomb, Zhiping Weng, Peter R. Boag

Program in Bioinformatics and Integrative Biology Publications and Presentations

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 ...

Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern

Open Access Articles

Presentation of antigenic peptides on MHC-II molecules is essential for tolerance to self and for initiation of immune responses against foreign antigens. DO (HLA-DO in humans, H2-O in mice) is a non-classical MHC-II protein that has been implicated in control of autoimmunity and regulation of neutralizing antibody responses to viruses. These effects likely are related to a role of DO in selecting MHC-II epitopes, but previous studies examining the effect of DO on presentation of selected CD4 T cell epitopes have been contradictory. To understand how DO modulates MHC-II antigen presentation, we characterized the full spectrum of peptides presented by ...

Membrane Protein Nanoparticles: The Shape Of Things To Come, Kailene S. Simon, Naomi L. Pollock, Sarah C. Lee

Open Access Articles

The use of styrene-maleic acid (SMA) for the purification of a wide range of membrane proteins (MPs) from both prokaryotic and eukaryotic sources has begun to make an impact in the field of MP biology. This method is growing in popularity as a means to purify and thoroughly investigate the structure and function of MPs and biological membranes. The amphiphilic SMA copolymer can effectively extract MPs directly from a native lipid bilayer to form discs approximately 10 nm in diameter. The resulting lipid particles, or styrene-maleic acid lipid particles (SMALPs), contain SMA, protein and membrane lipid. MPs purified in SMALPs ...

Resistance From Afar: Distal Mutation V36m Allosterically Modulates The Active Site To Accentuate Drug Resistance In Hcv Ns3/4a Protease, Aysegul Ozen, Kuan-Hung Lin, Keith P. Romano, Davide Tavella, Alicia Newton, Christos J. Petropoulos, Wei Huang, Cihan Aydin, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus rapidly evolves, conferring resistance to direct acting antivirals. While resistance via active site mutations in the viral NS3/4A protease has been well characterized, the mechanism for resistance of non-active site mutations is unclear. R155K and V36M often co-evolve and while R155K alters the electrostatic network at the binding site, V36M is more than 13 Angstrom away. In this study the mechanism by which V36M confers resistance, in the context of R155K, is elucidated with drug susceptibility assays, crystal structures, and molecular dynamics (MD) simulations for three protease inhibitors: telaprevir, boceprevir and danoprevir. The R155K and R155K ...

Investigation Of Flow Disturbances And Multi-Directional Wall Shear Stress In The Stenosed Carotid Artery Bifurcation Using Particle Image Velocimetry, Amanda L. Dicarlo

Electronic Thesis and Dissertation Repository

Hemodynamics and shear forces are associated with pathological changes in the vascular wall and its function, resulting in the focal development of atherosclerosis. Flow complexities that develop in the presence of established plaques create environments favourable to thrombosis formation and potentially plaque rupture leading to stroke. The carotid artery bifurcation is a common site of atherosclerosis development. Recently, the multi-directional nature of shear stress acting on the endothelial layer has been highlighted as a risk factor for atherogenesis, emphasizing the need for accurate measurements of shear stress magnitude as well direction. In the absence of comprehensive patient specific datasets numerical ...

Orbit: A New Paradigm For Genetic Engineering Of Mycobacterial Chromosomes, Kenan C. Murphy, Samantha J. Nelson, Subhalaxmi Nambi, Kadamba Papavinasasundaram, Christina E. Baer, Christopher M. Sassetti

Open Access Articles

Two efficient recombination systems were combined to produce a versatile method for chromosomal engineering that obviates the need to prepare double-stranded DNA (dsDNA) recombination substrates. A synthetic "targeting oligonucleotide" is incorporated into the chromosome via homologous recombination mediated by the phage Che9c RecT annealase. This oligonucleotide contains a site-specific recombination site for the directional Bxb1 integrase (Int), which allows the simultaneous integration of a "payload plasmid" that contains a cognate recombination site and a selectable marker. The targeting oligonucleotide and payload plasmid are cotransformed into a RecT- and Int-expressing strain, and drug-resistant homologous recombinants are selected in a single step ...

The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Dwight Forshee

ELAIA

The microbiome is a dynamic community that can positively and negatively influence host health. Lactobacillus reuteri is a probiotic that has received much attention for its ability to inhibit pathogens such as Salmonella typhimurium, Escherichia coli, and Clostridium difficile. It does so by its unique ability to metabolize glycerol into the antimicrobial compound 3-HPA, which is commonly referred to as reuterin. The ability to secrete reuterin is dependent not only on glycerol availability but also the concentration of glucose. In fact, there appears to be a “goldilocks” ratio between glucose and glycerol as either too much or too little glucose ...

The Caenorhabditis Elegans Oxidative Stress Response Requires The Nhr-49 Transcription Factor, Queenie Hu, Dayana R. D'Amora, Lesley T. Macneil, Albertha J. M. Walhout, Terrance J. Kubiseski

Open Access Articles

The overproduction of reactive oxygen species (ROS) in cells can lead to the development of diseases associated with aging. We have previously shown that C. elegans BRAP-2 (Brca1 associated binding protein 2) regulates phase II detoxification genes such as gst-4, by increasing SKN-1 activity. Previously, a transcription factor (TF) RNAi screen was conducted to identify potential activators that are required to induce gst-4 expression in brap-2(ok1492) mutants. The lipid metabolism regulator NHR-49/HNF4 was among 18 TFs identified. Here, we show that knockdown of nhr-49 suppresses the activation of gst-4 caused by brap-2 inactivation and that gain-of-function alleles of ...

Solvent Stable Microbial Lipases: Current Understanding And Biotechnological Applications, Barry Ryan, Priyanka Priyanka, Yeqi Tan, Gemma K Kinsella, Gary T. Henehan

Articles

Objective: This review examines on our current understanding of microbial lipase solvent tolerance, with a specific focus on the molecular strategies employed to improve lipase stability in a non-aqueous environment.

Results: It provides an overview of known solvent tolerant lipases and of approaches to improving solvent stability such as; enhancing stabilising interactions, modification of residue flexibility and surface charge alteration. It shows that judicious selection of lipase source supplemented by appropriate enzyme stabilisation, can lead to a wide application spectrum for lipases.

Conclusion: Organic solvent stable lipases are, and will continue to be, versatile and adaptable biocatalytic workhorses commonly employed ...

Peptidylarginine Deiminases 2 And 4 Modulate Innate And Adaptive Immune Responses In Tlr-7-Dependent Lupus., Yudong Liu, Yaíma L Lightfoot, Nickie Seto, Santanu Mondal, Padmavathy Nandha Premnath, Paul R. Thompson

University of Massachusetts Medical School Publications

The peptidylarginine deiminases PAD2 and PAD4 are implicated in the pathogenesis of several autoimmune diseases. PAD4 may be pathogenic in systemic lupus erythematosus (SLE) through its role in neutrophil extracellular trap (NET) formation that promotes autoantigen externalization, immune dysregulation, and organ damage. The role of this enzyme in mouse models of autoimmunity remains unclear, as pan-PAD chemical inhibitors improve clinical phenotype, whereas PAD4-KO models have given conflicting results. The role of PAD2 in SLE has not been investigated. The differential roles of PAD2 and PAD4 in TLR-7-dependent lupus autoimmunity were examined. Padi4-/- displayed decreased autoantibodies, type I IFN responses, immune ...

Carbohydrate Extraction From The Chorella Vulgaris Microalgae Strain, William Hammann, Wayne Seames, Andrew Ross

Essential Studies UNDergraduate Showcase

The cultivation and exploitation of microalgae biomass as a source of renewable fuels and other chemicals has been an active area of research due to microalgae’s high productivity and the relatively high concentrations of valuable intracellular components, like lipids (fatty acid-based oils), proteins, and polysaccharides. Commercialization of this technology will help mitigate global climate change by reducing fossil-derived products by producing analog renewable fuels and chemicals. Traditionally, the main focus of microalgae-based fuels/chemicals research and development has been on the lipids that many strains generate, but current research shows that solely recovering the oils may not be cost ...

General Decapping Activators Target Different Subsets Of Inefficiently Translated Mrnas, Feng He, Alper Celik, Chan Wu, Allan Jacobson

Open Access Articles

The Dcp1-Dcp2 decapping enzyme and the decapping activators Pat1, Dhh1, and Lsm1 regulate mRNA decapping, but their mechanistic integration is unknown. We analyzed the gene expression consequences of deleting PAT1, LSM1, or DHH1, or the DCP2 C-terminal domain, and found that: i) the Dcp2 C-terminal domain is an effector of both negative and positive regulation; ii) rather than being global activators of decapping, Pat1, Lsm1, and Dhh1 directly target specific subsets of yeast mRNAs and loss of the functions of each of these factors has substantial indirect consequences for genome-wide mRNA expression; and iii) transcripts targeted by Pat1, Lsm1, and ...

Chemical Analysis Of Aerosol Particle Surfaces, Hillary Woolf

Fall Student Research Symposium 2018

Aerosol particles are thought to impact climate properties. The ability to probe aerosols to understand their chemical properties has been difficult due to a lack of appropriate analytical techniques. Here we present interface-specific SHS techniques to allow for in situ analysis of aerosol particles. Transportation of aerosols from their collection site to the laboratory disturbs their chemical and physical properties thus making it difficult to take accurate measurements of aerosol particles. We show that using a CCD detector is a more effective option for producing more sensitive results and can greatly reduce sampling time and could possibly detect measurements from ...

Potent Cas9 Inhibition In Bacterial And Human Cells By Acriic4 And Acriic5 Anti-Crispr Proteins, Jooyoung Lee, Aamir Mir, Alireza Edraki, Bianca Garcia, Nadia Amrani, Hannah E. Lou, Ildar Gainetdinov, April Pawluk, Raed Ibraheim, Xin D. Gao, Pengpeng Liu, Alan R. Davidson, Karen L. Maxwell, Erik J. Sontheimer

Open Access Articles

In their natural settings, CRISPR-Cas systems play crucial roles in bacterial and archaeal adaptive immunity to protect against phages and other mobile genetic elements, and they are also widely used as genome engineering technologies. Previously we discovered bacteriophage-encoded Cas9-specific anti-CRISPR (Acr) proteins that serve as countermeasures against host bacterial immunity by inactivating their CRISPR-Cas systems (A. Pawluk, N. Amrani, Y. Zhang, B. Garcia, et al., Cell 167:1829-1838.e9, 2016, https://doi.org/10.1016/j.cell.2016.11.017). We hypothesized that the evolutionary advantages conferred by anti-CRISPRs would drive the widespread occurrence of these proteins in nature (K ...

Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery ...

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 ...

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

UT GSBS Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3 ...