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- Molecular dynamics (3)
- Electric pulsing (2)
- Electroporation (2)
- Lipid (2)
- Nanopore (2)
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- Acid Sensing ion channels (1)
- Actin polymerization (1)
- Alpha-1-antitrypsin (1)
- Angiogenesis (1)
- Anion-Quadrupole (1)
- Anion-pi (1)
- Anther (1)
- Apoptosis (1)
- Aquaporin (1)
- Axon guidance (1)
- BYDV (1)
- Barley Yellow Dwarf Virus (1)
- Binding affinity (1)
- Blebbing (1)
- Boric acid (1)
- Calcium (1)
- Cell cortex (1)
- Cell motility (1)
- Crosslinking (1)
- Density maps (1)
- Electropermeabilization (1)
- Endocrine Disruption (1)
- Estrogen Receptor (1)
- FRET (1)
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Articles 1 - 14 of 14
Full-Text Articles in Molecular Biology
Pore Selectivity And Gating Of Arabidopsis Nodulin 26 Intrinsic Proteins And Roles In Boric Acid Transport In Reproductive Growth, Tian Li
Doctoral Dissertations
Plant nodulin-26 intrinsic proteins (NIPs) are members of the aquaporin superfamily that serve as multifunctional channels of uncharged metabolites and water. They share the same canonical hourglass fold as the aquaporin family. The aromatic arginine (ar/R) selectivity filter controls transport selectivity based on size, hydrophobicity, and hydrogen bonding with substrates. In Arabidopsis thaliana, NIP II subclass proteins contain a conserved ar/R “pore signature” that is composed of Alanine at the helix 2 position (H2), Valine/Isoleucine at the helix 5 position (H5), and an Alanine (LE1) and an invariant Arginine (LE2) at the two loop E positions. In this study, …
Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne
Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne
Articles
A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.
The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells, …
Swarna Ramaswamy_Thesis, Swarna S. Ramaswamy
Swarna Ramaswamy_Thesis, Swarna S. Ramaswamy
Dissertations & Theses (Open Access)
STRUCTURAL INVESTIGATIONS OF LIGAND GATED ION CHANNELS
Swarna Ramaswamy, B.S
Advisor: Vasanthi Jayaraman, Ph.D.
Ion channels form an integral part of membrane proteins. In the nervous system including the central and the peripheral nervous system, ligand gated ion channels form a very important part of intercellular communications. They receive chemical signals and convert them to electrical signal, mainly by allowing ion passage across the cell membrane. Ion passage also translates into downstream signaling events. Faithful translation of these signals and transmittance is crucial for several physiological functions, implying that irregular ion channel function could lead to serious consequences.
This thesis …
Applications And Improvements In The Molecular Modeling Of Protein And Ligand Interactions, Jason Bret Harris
Applications And Improvements In The Molecular Modeling Of Protein And Ligand Interactions, Jason Bret Harris
Doctoral Dissertations
Understanding protein and ligand interactions is fundamental to treat disease and avoid toxicity in biological organisms. Molecular modeling is a helpful but imperfect tool used in computer-aided toxicology and drug discovery. In this work, molecular docking and structural informatics have been integrated with other modeling methods and physical experiments to better understand and improve predictions for protein and ligand interactions. Results presented as part of this research include:
1.) an application of single-protein docking for an intermediate state structure, specifically, modeling an intermediate state structure of alpha-1-antitrypsin and using the resulting model to virtually screen for chemical inhibitors that can …
Developing Crosslinking Constructs Of Protein Kinase R, Prisma E. Lopez
Developing Crosslinking Constructs Of Protein Kinase R, Prisma E. Lopez
Honors Scholar Theses
Protein Kinase R (PKR) is a key component of the innate immune antiviral response. PKR is activated upon binding to dsRNA. However, recent studies have shown that PKR can also bind to and become activated by duplex RNAs containing complex secondary structure. The mechanism of PKR binding and activation by these RNAs is currently not known. The approach taken here to determine the mechanism of PKR binding by these RNAs is through the development of PKR constructs that are capable of covalently binding to RNAs. Constructs were created by site-specific incorporation of an unnatural, photoactivatable amino acid within PKR. These …
Interactions Of Eukaryotic Translation Initiation Factors And 3' Untranslated Region Of Barley Yellow Dwarf Virus Mrna During Protein Synthesis: A Study Of Equilibrium Binding, Kinetics And Thermodynamics, Bidisha Banerjee
Dissertations, Theses, and Capstone Projects
Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley Yellow Dwarf Virus (BYDV) employs a cap-independent mechanism of translation initiation which is mediated by a structural element BTE (BYDV translation element) located in the 3’ UTR of its mRNA. eIF4F bound the BTE and a translational inactive mutant with high affinity; thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5-164% compared to WT were studied. Using fluorescence anisotropy …
Recruitment Of The Ribosomal 40s Subunit To The 3'Untranslated Region Of A Viral Mrna, Via The Eif4 Complex, Facilitates Cap-Independent Translation, Sohani Das Sharma
Recruitment Of The Ribosomal 40s Subunit To The 3'Untranslated Region Of A Viral Mrna, Via The Eif4 Complex, Facilitates Cap-Independent Translation, Sohani Das Sharma
Dissertations, Theses, and Capstone Projects
Translation of uncapped plant viral RNAs can be facilitated by either an internal ribosomal entry site (IRES) in the 5' untranslated region (UTR) or a cap-independent translation element (CITE) in the 3' UTR. Barley yellow dwarf virus (BYDV) mRNA, which lacks both cap and poly(A) tail, has a translation element (3'BTE) in its 3' UTR that is essential for efficient translation initiation at the 5'-proximal AUG. This mechanism requires binding of the eukaryotic initiation factor 4G (eIF4G) subunit of the heterodimer eIF4F to the 3'BTE and base pairing between the 3'BTE and the 5' UTR. Here we investigate how this …
Cellular Regulation Of Extension And Retraction Of Pseudopod-Like Blebs Produced By Nanosecond Pulsed Electric Field, Mikhail A. Rassokhin, Andrei G. Pakhomov
Cellular Regulation Of Extension And Retraction Of Pseudopod-Like Blebs Produced By Nanosecond Pulsed Electric Field, Mikhail A. Rassokhin, Andrei G. Pakhomov
Bioelectrics Publications
Recently we described a new phenomenon of anodotropic pseudopod-like blebbing in U937 cells exposed to nanosecond pulsed electric field (nsPEF). In Ca2+ -free buffer such exposure initiates formation of pseudopod-like blebs (PLBs), protrusive cylindrical cell extensions that are distinct from apoptotic and necrotic blebs. PLBs nucleate predominantly on anode-facing cell pole and extend toward anode during nsPEF exposure. Bleb extension depends on actin polymerization and availability of actin monomers. Inhibition of intracellular Ca2+ , cell contractility, and RhoA produced no effect on PLB initiation. Meanwhile, inhibition of WASP by wiskostatin causes dose-dependent suppression of PLB growth. Soon after …
The Nh2-Hypervariable Region Modulates The Binding Affinity Of Troponin T For Tropomyosin, Chinthaka Kaushalya Amarasinghe
The Nh2-Hypervariable Region Modulates The Binding Affinity Of Troponin T For Tropomyosin, Chinthaka Kaushalya Amarasinghe
Wayne State University Theses
The troponin complex plays a central role in the allosteric function of sarcomeric thin filaments by enacting conformational changes during the Ca2+-regulated contraction and relaxation of striated muscle. The troponin subunit T (TnT) has two binding sites for tropomyosin (Tm) and is responsible for anchoring the troponin complex to the thin filament. Although the C-terminal and middle regions of the TnT polypeptide chain are highly conserved among the three muscle type isoforms, the hypervariable N-terminal region has evolutionarily diverged significantly among isoforms. Previous studies have shown that the N-terminal variable region fine-tunes Ca2+ regulation of muscle contractility via modulation of …
Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He
Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He
Computer Science Faculty Publications
Major secondary structure elements such as α helices and β sheets can be computationally detected from cryoelectron microscopy (cryo-EM) density maps with medium resolutions of 5–10 A˚ . However, a critical piece of information for modeling atomic structures is missing, because there are no tools to detect β strands from cryo-EM maps at medium resolutions. We propose a method, StrandTwister, to detect the traces of β strands through the analysis of twist, an intrinsic nature of a β sheet. StrandTwister has been tested using 100 β sheets simulated at 10 A˚ resolution and 39 β sheets computationally detected from cryo-EM …
Molecular Mechanisms Of Neuropilin-Ligand Binding, Matthew W. Parker
Molecular Mechanisms Of Neuropilin-Ligand Binding, Matthew W. Parker
Theses and Dissertations--Molecular and Cellular Biochemistry
Neuropilin (Nrp) is an essential cell surface receptor with dual functionality in the cardiovascular and nervous systems. The first identified Nrp-ligand family was the Semaphorin-3 (Sema3) family of axon repulsion molecules. Subsequently, Nrp was found to serve as a receptor for the vascular endothelial growth factor (VEGF) family of pro-angiogenic cytokines. In addition to its physiological role, VEGF signaling via Nrp directly contributes to cancer stemness, growth, and metastasis. Thus, the Nrp/VEGF signaling axis is a promising anti-cancer therapeutic target. Interestingly, it has recently been shown that Sema3 and VEGF are functionally opposed to one another, with Sema3 possessing potent …
Calcium-Mediated Pore Expansion And Cell Death Following Nanoelectroporation, Olga N. Pakhomova, Betsy Gregory, Iurii Semenov, Andrei G. Pakhomov
Calcium-Mediated Pore Expansion And Cell Death Following Nanoelectroporation, Olga N. Pakhomova, Betsy Gregory, Iurii Semenov, Andrei G. Pakhomov
Bioelectrics Publications
Opening of long-lived pores in the cell membrane is the principal primary effect of intense, nanosecond pulsed electric field (nsPEF). Here we demonstrate that the evolution of pores, cell survival, the time and the mode of cell death (necrotic or apoptotic) are determined by the level of external Ca2+ after nsPEF. We also introduce a novel, minimally disruptive technique for nsEP exposure of adherent cells on indium tin oxide (ITO)-coated glass coverslips, which does not require cell detachment and enables fast exchanges of bath media. Increasing the Ca2+ level from the nominal 2–5 μM to 2 mM for …
Evaluations Of A Mechanistic Hypothesis For The Influence Of Extracellular Ions On Electroporation Due To High-Intensity, Nanosecond Pulsing, V. Sridhara, R. P. Joshi
Evaluations Of A Mechanistic Hypothesis For The Influence Of Extracellular Ions On Electroporation Due To High-Intensity, Nanosecond Pulsing, V. Sridhara, R. P. Joshi
Electrical & Computer Engineering Faculty Publications
The effect of ions present in the extracellular medium on electroporation by high-intensity, short-duration pulsing is studied through molecular dynamic simulations. Our simulation results indicate that mobile ions in the medium might play a role in creating stronger local electric fields across membranes that then reinforce and strengthen electroporation. Much faster pore formation is predicted in higher conductivity media. However, the impact of extracellular conductivity on cellular inflows, which depend on transport processes such as electrophoresis, could be different as discussed here. Our simulation results also show that interactions between cations (Na+ in this case) and the carbonyl oxygen of …
Numerical Study Of Lipid Translocation Driven By Nanoporation Due To Multiple High-Intensity, Ultrashort Electrical Pulses, Viswanadham Sridhara, Ravindra P. Joshi
Numerical Study Of Lipid Translocation Driven By Nanoporation Due To Multiple High-Intensity, Ultrashort Electrical Pulses, Viswanadham Sridhara, Ravindra P. Joshi
Electrical & Computer Engineering Faculty Publications
The dynamical translocation of lipids from one leaflet to another due to membrane permeabilization driven by nanosecond, high-intensity (>100 kV/cm) electrical pulses has been probed. Our simulations show that lipid molecules can translocate by diffusion through water-filled nanopores which form following high voltage application. Our focus is on multiple pulsing, and such simulations are relevant to gauge the time duration over which nanopores might remain open, and facilitate continued lipid translocations and membrane transport. Our results are indicative of a N1/2 scaling with pulse number for the pore radius. These results bode well for the use of pulse …