Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, 2022 The Graduate Center, City University of New York
Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip
Dissertations, Theses, and Capstone Projects
Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at ...
A New Insight Into Fungal Cell Wall Architecture By Functional Genomics And Solid-State Nmr Along With Recent Advancements In Dynamic Nuclear Polarization For Analyzing Biomolecules, 2022 Louisiana State University
A New Insight Into Fungal Cell Wall Architecture By Functional Genomics And Solid-State Nmr Along With Recent Advancements In Dynamic Nuclear Polarization For Analyzing Biomolecules, Arnab Chakraborty
LSU Master's Theses
This dissertation summarizes the findings related to the way by which supramolecular architecture of fungal cell wall changes with genetic mutation, dispensing genes responsible for biosynthesis of cell wall polysaccharides. This is necessary because without perfect picture of how supramolecular assembly changes with genetic mutation it is hard to assess new anti-fungal targets. Alongside this we have highlighted how recent advancement into Dynamic Nuclear Polarization (DNP) methods improved characterization of biomolecules both in case of labeled and unlabeled samples.
First study utilized Solid-state NMR (SSNMR) which is a non-destructive technique hence enabled us for the first time to deduce how ...
Inferring Dynamics Of Biological Systems, 2022 George Mason University
Inferring Dynamics Of Biological Systems, Tracey G. Oellerich
Biology and Medicine Through Mathematics Conference
No abstract provided.
Supertertiary Structural Dynamics Modulate Function In Postsynaptic Density Protein 95, 2022 Clemson University
Supertertiary Structural Dynamics Modulate Function In Postsynaptic Density Protein 95, George L. Hamilton Iii
Proteins, RNA, and DNA serve as the primary sub-cellular machinery that give rise to the necessary functions of life. The long-standing paradigm has been that the structures of biomolecules, or the arrangement of the subunits that make up a biomolecule, determine biological function. However, biomolecules are not static objects. Instead, they often undergo structural rearrangements that are crucial to enabling and regulating their functions. In my thesis I present several studies of the interplay between the structures, dynamics, and functions of biomolecules that combine experimental fluorescence spectroscopy and computational methods to probe these systems at the single-molecule level. In particular ...
Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, 2022 University of Texas at Tyler
Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, Jason Distefano
Molecular building blocks are fundamental to biological synthesis and processes and have been utilized in advanced materials, drugs and drug delivery systems, and biotechnology. Proteins have been used as molecular building blocks for the construction of complex, well-ordered structures. Coiled-coil protein domains are essential subunits used for the oligomerization of protein complexes, gene expression, and structural elements of biological materials. The synthesis and assembly of proteins utilizing coiled-coil motifs are of great scientific interest due to their potential applications in disease treatment, biomechanical motors, nanoscale delivery systems, etc. However, assembling protein complexes with specific morphology is still challenging because the ...
Microbial Diversity And Community Structure In Sediments Associated With The Seagrass (Thallassia Testudinum) In Apalachicola Bay, Florida, Rahma Ahmed, Thomas Mcelroy, Troy Mutchler
Symposium of Student Scholars
Seagrass is an angiosperm which provides many ecosystem services in coastal areas, such as providing food, shelter and nurseries for many species, and decreasing the impact of waves on shorelines. A global assessment reported that 29% of known seagrass meadows are in a state of decline due to the effects of human activity. Seagrass is commonly found in shallow marine waters where they form meadows containing a microbiome that plays an important role in providing nutrients for seagrass growth, though little is known about the microorganisms within the seagrass meadow sediments. Our project collected sediments from seagrass meadows and adjacent ...
Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, 2022 College of Saint Benedict/Saint John's University
Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen
CSBSJU Distinguished Thesis
Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has ...
The Development Of Inhibitors For Sars-Cov-2 Orf8, 2022 College of Saint Benedict/Saint John's University
The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen
CSBSJU Distinguished Thesis
An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be ...
Conformational Dynamics And Allosteric Modulation Of The Sars-Cov-2 Spike, 2022 UMass Chan Medical School
Conformational Dynamics And Allosteric Modulation Of The Sars-Cov-2 Spike, Marco A. Diaz-Salinas, Qi Li, Ejemel Monir, Leonid Yurkovetskiy, Jeremy Luban, Kuang Shen, Yang Wang, James B. Munro
COVID-19 Publications by UMass Chan Authors
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Forster resonance energy transfer (smFRET) imaging, we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and in the presence of the D614G mutation. We find that D614G modulates the energetics of the RBD ...
Water-Based Lead Generation, 2022 The Graduate Center, City University of New York
Water-Based Lead Generation, Brian Olson
Dissertations, Theses, and Capstone Projects
Water-based Lead Generation. The opioid epidemic and the SARS-CoV-2 pandemic are current serious challenges whose devastating effects could be assuaged through the development of new drugs. Opioids that are functional painkillers, that are less likely to cause overdose, and small molecule drugs that could inhibit the life cycle of SARS-CoV-2 would be useful. The work herein investigated the use of water molecules for lead generation in drug development against opioid receptors and SARS-CoV-2 viral proteins. In opioid receptor binding sites, purported bridging waters were obtained from crystal waters or from molecular dynamics simulations, as Hydration Site Analysis was used to ...
An In Silico Approach To Investigate The Structural And Biochemical Basis Of The Rna Binding Functions Of Nucleolin, 2022 The Graduate Center, City University of New York
An In Silico Approach To Investigate The Structural And Biochemical Basis Of The Rna Binding Functions Of Nucleolin, Avdar San
Dissertations, Theses, and Capstone Projects
Nucleolin (NCL) is a stress responsive multifunctional nucleolar protein and accounts for 10% of the total nucleolar protein content. NCL belongs to the class of RNA binding proteins (RBPs) that regulate many important cellular processes through their interactions with different RNA molecules. The dysregulation of RBPs and the RNA metabolism pathways they intersect is a known driver of tumorigenesis. NCL regulates ribosome biogenesis, chromatin remodeling, microRNA processing, and gene expression on multiple levels. The RNA-protein interactions of NCL are primarily driven by its four RNA binding domains (RBDs). NCL is known to interact with a growing list of primary-miRNA (pri-miRNA ...
Extracellular Secretion Of A Cutinase With Polyester-Degrading Potential By E. Coli Using A Novel Signal Peptide From Amycolatopsis Mediterranei, 2022 Technological University Dublin
Extracellular Secretion Of A Cutinase With Polyester-Degrading Potential By E. Coli Using A Novel Signal Peptide From Amycolatopsis Mediterranei, Yeqi Tan, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan
Recent studies in this laboratory showed that an extracellular cutinase from A. mediterranei (AmCut) was able to degrade the plastics polycaprolactone and polybutylene succinate. Such plastics can be slow to degrade in soils due to a lack of efficient polyester degrading organisms. AmCut also showed potential for the biocatalytic synthesis of esters by reverse hydrolysis.
The gene for AmCut has an upstream leader sequence whose transcript is not present in the purified enzyme. In this study, we show using predictive modelling, that this sequence codes for an N-terminal signal peptide that directs transmembrane expression via the Sec secretion pathway.
Transcriptomes Of Electrophysiologically Recorded Dbx1-Derived Respiratory Neurons Of The Prebötzinger Complex In Neonatal Mice, Prajkta S. Kallurkar, Maria Cristina D. Picardo, Yae K. Sugimura, Margaret Saha, Gregory D. Conradi Smith, Christopher A. Del Negro
Arts & Sciences Articles
Breathing depends on interneurons in the preBötzinger complex (preBötC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBötC neurons. In a slice model of breathing with ~ 5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBötC neurons activate 100–300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300–500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3, Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling (Cracr2a, Sgk1 ...
Optimization And Standardization Of Dms Chemical Mapping Experiments For Probing Rna 3d Structure, 2022 University of Nebraska - Lincoln
Optimization And Standardization Of Dms Chemical Mapping Experiments For Probing Rna 3d Structure, Sarah Brady
Honors Theses, University of Nebraska-Lincoln
RNA plays a significant and crucial role in biological processes. The properties of RNA are ultimately responsible for each molecule’s unique function. The configuration and structural integrity of RNA is important for its functionality. Chemical mapping detailed in this thesis can be used to analyze the 3D structure of an RNA sequence. RNA is modified via methylation of adenine and cytosine bases using dimethyl sulfate, then reverse transcribed to DNA, then sequenced. The sites where the bases were methylated become mutations in the DNA sequence, allowing for identification of these locations when analyzing sequencing data. Conditions for modification can ...
Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck
Theses and Dissertations--Pharmacy
In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.
The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABAA receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABAA receptor interaction suggests ...
Challenges Of Constructing Entrainment Map For Arbitrary Circadian Models, 2022 Colby College
Challenges Of Constructing Entrainment Map For Arbitrary Circadian Models, Yuxuan (Nelson) Wu
The entrainment map, developed by Dr.Diekman and Dr.Bose, is claimed to be a 1-dimensional map that produces a better prediction for phase-locking than methods than the phase response curve for circadian models. In his paper, he constructs the entrainment map for the two-dimensional circadian model, the Novak-Tyson model, and the other two higher-dimensional circadian models. For this thesis, we concentrate on exploring if it is viable to construct the entrainment map for other circadian models that are not included in his paper: the Becker-Weimann model and the Relogio model. In addition, we discuss the challenges of constructing the ...
Mimicking The Namib Desert Beetle With Hydrophilic And Hydrophobic Surfaces, 2022 The University of Akron
Mimicking The Namib Desert Beetle With Hydrophilic And Hydrophobic Surfaces, Tyler Bracewell
Williams Honors College, Honors Research Projects
The Namib Desert beetle, Stenocara gracilipes, condenses fog that rolls in off the west coast of Namibia to provide itself with the water it needs for the day. By lifting its abdomen into the air to collect the water vapor, it condenses on hydrophilic bumps that are about 500μm in diameter and are spaced apart about 500-1500μm. Once the water reaches a critical size, the droplet rolls off the hydrophilic bump and onto the flat hydrophobic surface of the elytra. Since the beetle is angled with its abdomen in the air, the water rolls down to its mouth. A design ...
The Hiv-1 Capsid Core Is An Opportunistic Nuclear Import Receptor [Preprint], 2021 University of Virginia
The Hiv-1 Capsid Core Is An Opportunistic Nuclear Import Receptor [Preprint], Guangai Xue, Hyun Jae Yu, University Of Massachusetts Medical School, Anna T. Gres, Mehmet Hakan Guney, Stefan G. Sarafianos, Jeremy Luban, Vineet N. Kewalramani
UMass Chan Medical School Faculty Publications
The movement of viruses and other large macromolecular cargo through nuclear pore complexes (NPCs) is poorly understood. The human immunodeficiency virus type 1 (HIV-1) provides an attractive model to interrogate this process due to the genetic and cell biological assays to score virus nuclear entry in living cells. Although initial studies of HIV-1 infection of nondividing cells focused on karyophilic virion proteins, subsequent work revealed the viral capsid (CA), the chief structural component of the pre-integration complex (PIC), to be a critical determinant in nuclear transport1. In support of this model, HIV-1 interactions with NPCs can be altered through ...
Analytical Considerations And Methods For Comprehensive Analysis Of Bacterial Phospholipidomics Using Hilic-Ms/Ms, 2021 University of Tennessee, Knoxville
Analytical Considerations And Methods For Comprehensive Analysis Of Bacterial Phospholipidomics Using Hilic-Ms/Ms, David Thomas Reeves
Omics technologies have rapidly evolved over the last half century through vast improvements in efficient extraction methodologies, advances in instrumentation for data collection, and a wide assortment of informatics tools to help deconvolute sample data sets. However, there are still untapped pools of molecules that warrant further analytical attention. As the frontline defense of the cell against exterior influences, the phospholipid membrane is key in structure, defense, and signaling, but current omics studies are only just now catching up to the potential hidden within cellular lipid profiles. Examination of shifts in phospholipid speciation and character could provide researchers with a ...
Expression And Purification Of Cytochrome 2u1 And Canine 1a2 And Metabolism Of Caffeine By Cytochrome 1a2, 2021 Missouri State University
Expression And Purification Of Cytochrome 2u1 And Canine 1a2 And Metabolism Of Caffeine By Cytochrome 1a2, Brenda M. Wekesa
MSU Graduate Theses
Cytochrome P450 enzymes are a large family of membrane heme proteins involved in eliminating drugs and the synthesis or elimination of steroids, eicosanoids, and vitamins. CYP2U1 is one of the poorly characterized P450 enzymes classified as orphan cytochrome P450 with unknown exact biological function. It is expressed in the brain and thymus as a catalyst in the hydroxylation of arachidonic acid. Unlike other cytochrome P450s, CYP2U1 is a bit unusual with forty extra amino acids. If a mutation occurs, it can lead to an early onset inherited disorder of the central nervous system called Hereditary Spastic Paraplegias (HSP). Most of ...