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Extracellular Matrix In Development And Disease, Julia Thom Oxford, Jonathon C. Reeck, Makenna J. Hardy 2019 Boise State University

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.


Limited Sequence Diversity Within A Population Supports Prebiotic Rna Reproduction, Ryo Mizuuchi, Niles Lehman 2019 Portland State University

Limited Sequence Diversity Within A Population Supports Prebiotic Rna Reproduction, Ryo Mizuuchi, Niles Lehman

Chemistry Faculty Publications and Presentations

The origins of life require the emergence of informational polymers capable of reproduction. In the RNA world on the primordial Earth, reproducible RNA molecules would have arisen from a mixture of compositionally biased, poorly available, short RNA sequences in prebiotic environments. However, it remains unclear what level of sequence diversity within a small subset of population is required to initiate RNA reproduction by prebiotic mechanisms. Here, using a simulation for template-directed recombination and ligation, we explore the effect of sequence diversity in a given population for the onset of RNA reproduction. We show that RNA reproduction is improbable in low ...


Protein Degradation Regulates Phospholipid Biosynthetic Gene Expression In Saccharomyces Cerevisiae, Bryan Salas-Santiago 2019 University of Massachusetts Amherst

Protein Degradation Regulates Phospholipid Biosynthetic Gene Expression In Saccharomyces Cerevisiae, Bryan Salas-Santiago

Doctoral Dissertations

Transcriptional regulation of most phospholipid biosynthetic genes in Saccharomyces cerevisiae is coordinated by inositol and choline. Inositol affects phosphatidic acid (PA) intracellular levels. Opi1p interacts physically with PA and is the main repressor of the phospholipid biosynthetic genes. It is localized in the endoplasmic reticulum (ER) bound to the ER membrane protein Scs2p. When PA levels drop, Opi1p is translocated into the nucleus repressing most phospholipid biosynthetic genes. The OPI1 locus was identified in a screen looking for overproduction and excretion of inositol (Opi-). Opi- mutants are generally associated with a defect in repression of the ...


Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados 2019 University of Massachusetts Amherst

Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados

Doctoral Dissertations

DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. These processes are coordinated to maintain genome integrity and ensure accurate duplication of genetic and epigenetic information. Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. In this study, we adapted ...


Of Course, Humans Are Not Unique!, Bernard Wallner 2019 University of Vienna

Of Course, Humans Are Not Unique!, Bernard Wallner

Animal Sentience

This commentary focuses on the question of the uniqueness of humans in comparison to other species and on the false assumption that single arguments support logical conclusions. Comparative analysis of genetic data in humans and nonhuman primates regarding the dopaminergic system of the subcortical mesolimbic reward system highlights homologous traits shared and modified by the process of evolution. Such an analytical approach is more relevant than claims of uniqueness.


Detection Of Beta-Lactamase Variants In Municipal Wastewater And Fresh Water, Sunil Pandey 2019 Eastern Illinois University

Detection Of Beta-Lactamase Variants In Municipal Wastewater And Fresh Water, Sunil Pandey

Masters Theses

The occurrence and spread of antibiotic-resistant genes (ARGs) are pressing public health problems worldwide. A key factor contributing to the spread of ARGs is lateral gene transfer. Wastewater treatment plants (WWTPs) are measured hot spots of microbial diversity and resistance because they receive polluted wastewater from diverse sources and contain a variety of different environments with dense bacterial loads. Due to the overuse of antibiotics the genetic capacities of microbes have profited. This helps every source of resistance gene and every means of horizontal gene transmission to develop the multiple mechanism of resistance to each antibiotic used clinically, agriculturally, or ...


Automatic 13C Chemical Shift Reference Correction Of Protein Nmr Spectral Data Using Data Mining And Bayesian Statistical Modeling, Xi Chen 2019 University of kencutky

Automatic 13C Chemical Shift Reference Correction Of Protein Nmr Spectral Data Using Data Mining And Bayesian Statistical Modeling, Xi Chen

Theses and Dissertations--Molecular and Cellular Biochemistry

Nuclear magnetic resonance (NMR) is a highly versatile analytical technique for studying molecular configuration, conformation, and dynamics, especially of biomacromolecules such as proteins. However, due to the intrinsic properties of NMR experiments, results from the NMR instruments require a refencing step before the down-the-line analysis. Poor chemical shift referencing, especially for 13C in protein Nuclear Magnetic Resonance (NMR) experiments, fundamentally limits and even prevents effective study of biomacromolecules via NMR. There is no available method that can rereference carbon chemical shifts from protein NMR without secondary experimental information such as structure or resonance assignment.

To solve this problem, we ...


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 2018 University of Massachusetts Medical School

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 2018 University of Massachusetts Medical School

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 2018 University of Massachusetts Medical School

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 ...


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 2018 University of Massachusetts Medical School

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 2018 Olivet Nazarene University

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 ...


General Decapping Activators Target Different Subsets Of Inefficiently Translated Mrnas, Feng He, Alper Celik, Chan Wu, Allan Jacobson 2018 University of Massachusetts Medical School

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 ...


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 2018 University of Massachusetts Medical School

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 ...


Ph-Induced Folding Of The Caspase-Cleaved Par-4 Tumor Suppressor: Evidence Of Structure Outside Of The Coiled Coil Domain, Andrea M. Clark, Komala Ponniah, Meghan S. Warden, Emily M. Raitt, Andrea C. Yawn, Stephen M. Pascal 2018 Old Dominion University

Ph-Induced Folding Of The Caspase-Cleaved Par-4 Tumor Suppressor: Evidence Of Structure Outside Of The Coiled Coil Domain, Andrea M. Clark, Komala Ponniah, Meghan S. Warden, Emily M. Raitt, Andrea C. Yawn, Stephen M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) is a 38 kDa largely intrinsically disordered tumor suppressor protein that functions in cancer cell apoptosis. Par-4 down-regulation is often observed in cancer while up-regulation is characteristic of neurodegenerative conditions such as Alzheimer’s disease. Cleavage of Par-4 by caspase-3 activates tumor suppression via formation of an approximately 25 kDa fragment (cl-Par-4) that enters the nucleus and inhibits Bcl-2 and NF-ƙB, which function in pro-survival pathways. Here, we have investigated the structure of cl-Par-4 using biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and intrinsic tyrosine fluorescence. The results demonstrate pH-dependent folding of ...


River Bank Inducement Influence On A Shallow Groundwater Microbial Community And Its Effects On Aquifer Reactivity, Natalie June Gayner 2018 University of Wisconsin-Milwaukee

River Bank Inducement Influence On A Shallow Groundwater Microbial Community And Its Effects On Aquifer Reactivity, Natalie June Gayner

Theses and Dissertations

Placing groundwater wells next to riverbanks to draw in surface water, known as riverbank inducement (RBI), is common and proposed as a promising and sustainable practice for municipal and public water production across the globe. However, these systems require further investigation to determine risks associated with river infiltration especially with rivers containing wastewater treatment plant (WWTP) effluent. Since microbes drive biogeochemical transformations in groundwater and largely affect water quality, it is important to understand how the microbial communities in drinking water wells are affected by river infiltration. This study investigated if, and to what extent, the microbial community in a ...


Evaluation Of Motor Cortex Neuronal Morphology In Developmental Hyperserotonemia Rat Model, Colten Z. Dillinger 2018 Missouri State University

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 ...


Functional Consequence Of Psat1 Association On Pkm2'S Inherent Enzymatic Activity., Alexis Avidan Vega 2018 University of Louisville

Functional Consequence Of Psat1 Association On Pkm2'S Inherent Enzymatic Activity., Alexis Avidan Vega

Electronic Theses and Dissertations

Pyruvate kinase M2 (PKM2) is predominantly found in tumors, where it allows the cancer cell to adapt to metabolic conditions through allosteric regulation of its activity. We recently discovered that phosphoserine aminotransferase 1 (PSAT1) associates with and activates PKM2. Here, I sought to affirm PSAT1's ability to increase PKM2 activity through kinetic and association studies of wild-type or mutant PKM2 enzymes. I demonstrate that His-tagged WT and mutant PKM2 enzymes are active, exhibit different kinetics, yet cannot be activated by PSAT1. Comparison studies using untagged WT PKM2 suggest that inclusion of the His-tag disrupts PSAT1 association. In support, pull-down ...


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 2018 East Tennessee State Universtiy

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 ...


A Simple Metabolic Switch May Activate Apomixis In Arabidopsis Thaliana, David Alan Sherwood 2018 Utah State University

A Simple Metabolic Switch May Activate Apomixis In Arabidopsis Thaliana, David Alan Sherwood

All Graduate Theses and Dissertations

Apomixis, asexual or clonal seed production in plants, can decrease the cost of producing hybrid seed and enable currently open pollinated crops to be converted to more vigorous and higher yielding hybrids that can reproduce themselves through their own seed. Sexual reproduction may be triggered by a programmed stress signaling event that occurs in both the meiocyte, just prior to meiosis, and later in the egg just prior to embryo sac maturation. The prevention of stress signaling and the activation of a pro-growth signal prior to meiosis triggered apomeiosis, the first half of apomixis. The same approach was used prior ...


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