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Actin-Based Feedback Circuits In Cell Migration And Endocytosis, Xinxin Wang 2016 Washington University in St. Louis

Actin-Based Feedback Circuits In Cell Migration And Endocytosis, Xinxin Wang

Arts & Sciences Electronic Theses and Dissertations

In this thesis, we study the switch and pulse functions of actin during two important cellular processes, cell migration and endocytosis. Actin is an abundant protein that can polymerize to form a dendritic network. The actin network can exert force to push or bend the cell membrane. During cell migration, the actin network behaves like a switch, assembling mostly at one end or at the other end. The end with the majority of the actin network is the leading edge, following which the cell can persistently move in the same direction. The other end, with the minority of the actin ...


Ribosome*Rela Structures Reveal The Mechanism Of Stringent Response Activation, Anna B. Loveland, Eugene Bah, Rohini Madireddy, Ying Zhang, Axel F. Brilot, Nikolaus Grigorieff, Andrei A. Korostelev 2016 University of Massachusetts Medical School

Ribosome*Rela Structures Reveal The Mechanism Of Stringent Response Activation, Anna B. Loveland, Eugene Bah, Rohini Madireddy, Ying Zhang, Axel F. Brilot, Nikolaus Grigorieff, Andrei A. Korostelev

Open Access Articles

Stringent response is a conserved bacterial stress response underlying virulence and antibiotic resistance. RelA/SpoT-homolog proteins synthesize transcriptional modulators (p)ppGpp, allowing bacteria to adapt to stress. RelA is activated during amino-acid starvation, when cognate deacyl-tRNA binds to the ribosomal A (aminoacyl-tRNA) site. We report four cryo-EM structures of E. coli RelA bound to the 70S ribosome, in the absence and presence of deacyl-tRNA accommodating in the 30S A site. The boomerang-shaped RelA with a wingspan of more than 100 A wraps around the A/R (30S A-site/RelA-bound) tRNA. The CCA end of the A/R tRNA pins the ...


Assessment Of Post-Treatment Imaging Changes Following Radiotherapy Using Magnetic Susceptibility Techniques, Jean-Guy Belliveau 2016 The University of Western Ontario

Assessment Of Post-Treatment Imaging Changes Following Radiotherapy Using Magnetic Susceptibility Techniques, Jean-Guy Belliveau

Electronic Thesis and Dissertation Repository

Radiation therapy (RT) is a common treatment for brain neoplasms and is used alone or in combination with other therapies. The use of RT has been found to be successful in controlling tumors and extending the overall survival of patients; however, there are many unanswered questions regarding radiotherapy effects in the normal brain surrounding or infiltrated by tumor. Changes to the vascular and parenchyma have been documented, and more recently inflammatory mechanisms have been postulated to play a role in radiation injury. Traditional imaging techniques used within the clinic (CT and MRI) are often lacking in their ability to differentiate ...


Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta 2016 University of South Florida

Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta

Graduate Theses and Dissertations

Nipah belongs to the family of paramyxoviruses that cause numerous fatal diseases in humans and farm animals. There are no FDA approved drugs for Nipah or any of the paramyxoviruses. Designing antiviral therapies that are more resistant to viral mutations require understanding of molecular details underlying infection. This dissertation focuses on obtaining molecular insights into the very first step of infection by Nipah. Such details, in fact, remain unknown for all paramyxoviruses. Infection begins with the allosteric stimulation of Nipah virus host binding protein by host cell receptors. Understanding molecular details of this stimulation process have been challenging mainly because ...


Closing The Net On Retroviruses, Jeremy Luban 2016 University of Massachusetts Medical School

Closing The Net On Retroviruses, Jeremy Luban

Open Access Articles

Structural studies reveal how an antiviral factor forms a molecular net to restrict retroviruses including HIV-1.


Differential Association Of Vitronectin And Fibronectin With Glass And Electrospun Fibers Of A Poly (D-Lysine) /Poly (Acrylic Acid), Syed Muhammad Sohaib Zafar Zafar 2016 University of South Florida

Differential Association Of Vitronectin And Fibronectin With Glass And Electrospun Fibers Of A Poly (D-Lysine) /Poly (Acrylic Acid), Syed Muhammad Sohaib Zafar Zafar

Graduate Theses and Dissertations

Proteins represent major constituent of the extracellular matrix which plays an important role in the formation, maintenance and remodeling of tissues, this project focuses on adsorption of two specific serum proteins fibronectin (FN) and vitronectin (VTN) responsible for mediating cell matrix interaction through integrin binding, tripeptide Arg-Gly-Asp (RGD) sequence found in these protein features are recognized by αβV3 integrin which ultimately helps in clot formation.


The Role Of Pyruvate Dehydrogenase And Acetyl-Coenzyme A Synthetase In Fatty Acid Synthesis In Developing Arabidopsis Seeds, Jinshan Ke, Robert H. Behal, Stephanie L. Back, Basil J. Nikolau, Eve S. Wurtele, David J. Oliver 2016 Iowa State University

The Role Of Pyruvate Dehydrogenase And Acetyl-Coenzyme A Synthetase In Fatty Acid Synthesis In Developing Arabidopsis Seeds, Jinshan Ke, Robert H. Behal, Stephanie L. Back, Basil J. Nikolau, Eve S. Wurtele, David J. Oliver

Basil Nikolau

Acetyl-coenzyme A (acetyl-CoA) formed within the plastid is the precursor for the biosynthesis of fatty acids and, through them, a range of important biomolecules. The source of acetyl-CoA in the plastid is not known, but two enzymes are thought to be involved: acetyl-CoA synthetase and plastidic pyruvate dehydrogenase. To determine the importance of these two enzymes in synthesizing acetyl-CoA during lipid accumulation in developing Arabidopsis seeds, we isolated cDNA clones for acetyl-CoA synthetase and for the ptE1α- and ptE1β-subunits of plastidic pyruvate dehydrogenase. To our knowledge, this is the first reported acetyl-CoA synthetase sequence from a plant source. The Arabidopsis ...


Inquiry Of Lipid Membranes Interacting With Functional Peptides And Polyphenol Drug Molecules, Chian Sing Ho 2016 University of South Florida

Inquiry Of Lipid Membranes Interacting With Functional Peptides And Polyphenol Drug Molecules, Chian Sing Ho

Graduate Theses and Dissertations

Cellular membranes are important targets for many membrane-active peptides and drug compounds. Here we are interested in deciphering how lipid membranes are perturbed by several membrane-active molecules, including the transmembrane domain of the influenza M2 protein (M2TM), aggregates formed by a synthetic polyglutamine peptide, and three polyphenol compounds (i.e., tamoxifen, genistein, and verapamil). We employ phase-separated ternary lipid model membranes in the form of giant unilamellar vesicles (GUVs) to simulate raft-like structures that have been proposed to govern many important processes in plasma membranes (e.g., intracellular singling and trafficking). Specifically, we use fluorescent microscopy to interrogate how those ...


Interaction Of Spliceosomal U2 Snrnp Protein P14 With Its Branch Site Rna Target, William Perea Vargas 2016 Graduate Center, City University of New York

Interaction Of Spliceosomal U2 Snrnp Protein P14 With Its Branch Site Rna Target, William Perea Vargas

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

Newly transcribed precursor messenger RNA (pre-mRNA) molecules contain coding sequences (exons) interspersed with non-coding intervening sequences (introns). These introns must be removed in order to generate a continuous coding sequence prior to translation of the message into protein. The mechanism through which these introns are removed is known as pre-mRNA splicing, a two-step reaction catalyzed be a large macromolecular machine, the spliceosome, located in the nucleus of eukaryotic cells. The spliceosome is a protein-directed ribozyme composed of small nuclear RNAs (snRNA) and hundreds of proteins that assemble in a very dynamic process. One of these snRNAs, the U2 snRNA, is ...


Analysis Of Gompertzian Growth In Aggregating Multicellular Tumor Nodules, Gwendolyn A. Deger 2016 University of Massachusetts Boston

Analysis Of Gompertzian Growth In Aggregating Multicellular Tumor Nodules, Gwendolyn A. Deger

Graduate Masters Theses

Past studies have shown that tumor growth generally follows an exponential growth function or, with a limiting growth constraint, the sigmoid Gompertzian function, where a terminal tumor size is reached at late times. The classical Gompertzian description of tumor growth applies in the case of two-dimensional (2D) in vitro cell studies due to the effect of physical limitations on possible growth area. This project asked whether Gompertzian form applies to the in vitro growth of multifocal 3D tumor nodules, whose size is determined by aggregation events as well as cell proliferation. Previous reports have indicated that these three-dimensional (3D) spheroids ...


Protein Adsorption Using A Lattice Toy Model, Ari J. Weiland 2016 Macalester College

Protein Adsorption Using A Lattice Toy Model, Ari J. Weiland

Macalester Journal of Physics and Astronomy

Protein adsorption is an important subfield of Biophysics particularly relevant in medical science. Using a computational simulation with a basic but configurable two-dimensional square lattice model of approximate amino acid interactions, I investigated the entropic effects of protein adsorption on a weakly attractive surface. These simulations allow for a precise calculation of the partition functions of these complex systems, from which I can then analyze other thermodynamic properties.


Force Generation And Contraction Of Random Actomyosin Bundles., Dietmar B. Oelz 2016 Courant Institute (NYU)

Force Generation And Contraction Of Random Actomyosin Bundles., Dietmar B. Oelz

Biology and Medicine Through Mathematics Conference

No abstract provided.


Geometric Control Of Yap-Dependent Mechanotransduction: A Proposed Model, Ngozi A. Eze, Heather A. Cirka, Kristen L. Billiar 2016 Worcester Polytechnic Institute

Geometric Control Of Yap-Dependent Mechanotransduction: A Proposed Model, Ngozi A. Eze, Heather A. Cirka, Kristen L. Billiar

UMass Center for Clinical and Translational Science Research Retreat

The Billiar lab is interested in the interplay between mechanical tension and programmed cell death (namely, apoptosis) in cells growing on micro-contact printed aggregates. The Billiar lab uses a bioinspired hydrogel to develop an in vitro model for mechanosensitive signaling in mammalian cells. The micro-contact printed cell aggregates experience a loss of tensional homeostasis at the center of the aggregates, which results in selective cell death at the center, but not periphery of the aggregates, followed by calcification, similar to excised diseased aortic valves. However, the subcellular mechanisms responsible for transducing the mechanical cues from the loss of tensional homeostasis ...


Id4 Acts As A Tumor Suppressor Via P53: Mechanistic Insight, Derrick J. Morton Jr. 2016 Clark Atlanta University

Id4 Acts As A Tumor Suppressor Via P53: Mechanistic Insight, Derrick J. Morton Jr.

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Overexpression of tumor-derived mutant p53 is a common event in tumorigenesis, suggesting an advantageous selective pressure in cancer initiation and progression. Given that p53 is found to be mutated in 50% of all human cancers, restoration of mutant p53 to its wild type biological function has been a widely sought after avenue for cancer therapy. Most research efforts have largely focused on restoration of mutant p53 by artificial means given that p53 has some degree of conformational flexibility allowing for introduction of short peptides and artificial compounds. Recently, theoretical modeling and studies focused on restoration of mutant p53 by physiological ...


Rna Interference Knock-Down Suggests That Pirl6 Functions In The Male Gametophyte Of Arabidopsis Thaliana, Savannah R. McNichol 2016 Whitman College

Rna Interference Knock-Down Suggests That Pirl6 Functions In The Male Gametophyte Of Arabidopsis Thaliana, Savannah R. Mcnichol

Honors Theses

Signal transduction pathways are critical to the success of multicellular organisms because they direct normal cellular processes and healthy responses to stimuli. Conversely, signaling pathway malfunctions can have large consequences for the survival of an organism and its progeny. Leucine-rich repeat proteins (LRRs) are a superfamily of proteins found in all eukaryotes that are capable of forming specific protein-protein interactions, and thus are well-suited to function in these signal transduction pathways. The Ras-group LRRs are one class of LRRs that interact with Ras or Ras-like small G-proteins. In the plant model system Arabidopsis thaliana, the Plant Intracellular Ras-group Leucine-rich-repeat (PIRL ...


Stability Of Norwalk Virus Capsid Protein Interfaces Evaluated By In Silico Nanoindentation, Prakhar Bansal 2016 University of Connecticut

Stability Of Norwalk Virus Capsid Protein Interfaces Evaluated By In Silico Nanoindentation, Prakhar Bansal

University Scholar Projects

Studying the mechanical properties of viral capsids can give several insights into not only the lifecycle of the virus, but also into potential drug targets to thwart the progression of viral infection. Nanoindentation using an atomic force microscope is a useful technique for determining structural properties of small molecules and particles, and is commonly used to study viral capsids. This technique utilizes the probe of the microscope to push down on the capsid and record the forces along the indentation path. We ran this experiment in silico where we simulated the nanoindentation of Norwalk virus capsids using molecular dynamics. Running ...


Computational Investigations Into The Molecular Underpinnings Of Eyesight Signaling Pathways, Shaan Kamal 2016 University of Connecticut

Computational Investigations Into The Molecular Underpinnings Of Eyesight Signaling Pathways, Shaan Kamal

University Scholar Projects

Phosphodiesterase 6 (PDE6) is a critical enzyme in the eyesight-signaling pathway. When activated, PDE6 hydrolyzes cGMP to GMP, which deactivates cGMP- gated ion channels, causing hyperpolarization of the cell and activating the sensory neurons responsible for vision. Within the PDE family, PDE6 is the only enzyme known to have an inhibitory subunit (PDE6-γ), which allows for the regulation of cGMP levels. When PDE6-γ is bound to PDE6, the enzyme is turned “off” and cannot catalyze cGMP. The α subunit of the G-protein transducin removes PDE6-γ and activates PDE6. PDE6 has proven problematic to isolate, making it difficult to study experimentally ...


Complex Non-Equilibrium Structural Dynamics In Globular Proteins, Xiaohu Hu 2016 University of Tennessee - Knoxville

Complex Non-Equilibrium Structural Dynamics In Globular Proteins, Xiaohu Hu

Doctoral Dissertations

Internal structural motions in proteins are essential to their functions. In this present dissertation, we present the results from an extensive set of molecular dynamics simulations of three very different globular proteins and demonstrate that the structural fluctuations observed are highly complex, manifesting in non-ergodic and self-similar subdiffusive dynamics with non-exponential relaxation behavior. The characteristic time of the motion observed at a given timescale is dependent on the length of the observation time, indicating an aging effect. By comparing the simulation results to the existing single-molecule fluorescence spectroscopic data on other globular proteins, we found the characteristic relaxation time for ...


Influence Of Cholesterol On Single Arginine-Containing Transmembrane Helical Peptides, Jordana K. Thibado 2016 University of Arkansas, Fayetteville

Influence Of Cholesterol On Single Arginine-Containing Transmembrane Helical Peptides, Jordana K. Thibado

Chemistry & Biochemistry Undergraduate Honors Theses

An essential component of animal cells, cholesterol exerts significant influence on the physical properties of the cell membrane and in turn, its constituents. One such category of constituents, the membrane proteins, are responsible for diverse and essential biological functions and often contain polar amino acids. Although sparse within the hydrophobic interior of lipid-bilayer membranes, polar amino acid residues are highly conserved and may play pivotal roles in determining specific structural and functional properties of key proteins. To gain greater understanding of the lipid membrane environment, and more broadly, cellular function, a model peptide framework termed “GWALP23” (acetyl-GGALWLALALAL12AL14 ...


Thermal Analysis Of Borosilicate Glass For Its Biological Applications, Gregory Humble 2016 Southern Polytechnic State University

Thermal Analysis Of Borosilicate Glass For Its Biological Applications, Gregory Humble

Symposium of Student Scholars

Borosilicate glass doped with varying wt% of cerium oxide is investigated for biological applications. Thermal studies of each formulation were conducted using an SDT Q600 differential scanning calorimeter. 30mg samples of 350 - 425 μm particle size of each type of glass were heated to 1200°C in order to obtain the glass transition, crystallization, and melting temperatures. Samples were then heated to 900°C at several heating rates, ranging from 2°C/min to 100°C/min, then compared against each other as well as against an undoped borosilicate glass.


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