Structural Mechanism Of Laforin Function In Glycogen Dephosphorylation And Lafora Disease, 2015 University of Kentucky
Structural Mechanism Of Laforin Function In Glycogen Dephosphorylation And Lafora Disease, Madushi Raththagala, M. Kathryn Brewer, Matthew W. Parker, Amanda R. Sherwood, Brian K. Wong, Simon Hsu, Travis M. Bridges, Bradley C. Paasch, Lance M. Hellman, Satrio Husodo, David A. Meekins, Adam O. Taylor, Benjamin D. Turner, Kyle D. Auger, Vikas V. Dukhande, Srinivas Chakravarthy, Pascual Sanz, Virgil L. Woods Jr., Sheng Li, Craig Vander Kooi, Matthew S. Gentry
Molecular and Cellular Biochemistry Faculty Publication
Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated ...
An Efficient And Sensitive Method For Preparing Cdna Libraries From Scarce Biological Samples, 2015 University of Massachusetts Medical School Worcester
An Efficient And Sensitive Method For Preparing Cdna Libraries From Scarce Biological Samples, Catherine H. Sterling, Isana Veksler-Lublinsky, Victor R. Ambros
Program in Molecular Medicine Publications and Presentations
The preparation and high-throughput sequencing of cDNA libraries from samples of small RNA is a powerful tool to quantify known small RNAs (such as microRNAs) and to discover novel RNA species. Interest in identifying the small RNA repertoire present in tissues and in biofluids has grown substantially with the findings that small RNAs can serve as indicators of biological conditions and disease states. Here we describe a novel and straightforward method to clone cDNA libraries from small quantities of input RNA. This method permits the generation of cDNA libraries from sub-picogram quantities of RNA robustly, efficiently and reproducibly. We demonstrate ...
Targeted Cancer Therapy Systems: An In Silico Study Of Radiohalogenated Ligands In The Estrogen Receptor And The Synthesis Of A Molecular Toolkit For The Fabrication Of Customizable Nanoparticles, 2015 Northeastern University
Targeted Cancer Therapy Systems: An In Silico Study Of Radiohalogenated Ligands In The Estrogen Receptor And The Synthesis Of A Molecular Toolkit For The Fabrication Of Customizable Nanoparticles, Kelton Kerry Barnsley
Chemistry Master's Theses
Chemotherapy is often limited by off-target toxicity and the development of multi-drug resistance in response to treatment. Strategies which reduce off-target toxicity by passively or actively targeting cancer cells may improve the efficacy of chemotherapy. Herein, two projects relating to targeted therapy are described. In the first project, the binding modes of 1,1-bis(4-hydroxyphenyl)-2-phenylethylenes (THPEs), a class of synthetic estrogens previously developed by our group, in the human estrogen receptor alpha-ligand binding domain were studied using molecular modeling programs YASARA AutoDock and Schrodinger Glide. The results were internally consistent and supported the observation that a bromine or iodine ...
Development Of Methods For The Analysis Of Protein Post-Translational Modifications: Isoaspartic Acid And Protein Crosslinking, Min Liu
Analysis of protein posttranslational modifications (PTMs) plays pivotal roles for the understanding of their biological importance. Isoaspartic acid (isoAsp) as the smallest PTM is observed in vivo and in vitro. No mass difference and subtle difference in physiochemical property between isoAsp and Asp pose a great challenging for sensitive detection and ambiguous location of isoAsp site in complex samples. A novel assay of isoAsp by exploiting methylation specificity of protein isoaspartate methyltransferase (PIMT) at isoAsp and subsequent 18O-incorporation during methyl ester hydrolysis is presented for sensitive detection and unambiguous site location of several isoAsp residues in IgG1 (Anal Chem ...
Mcnamara 201412 Nih Scap Innocentive Challenge Solution - T-Bow Rainbow T-Cells And Tumor Cells Spatial Multiplexing Gene Expression Reporter System – Plus Supplement Plus Posters - 20141228s, 2014 M.D. Anderson Cancer Center
Mcnamara 201412 Nih Scap Innocentive Challenge Solution - T-Bow Rainbow T-Cells And Tumor Cells Spatial Multiplexing Gene Expression Reporter System – Plus Supplement Plus Posters - 20141228s, George Mcnamara
McNamara 201412 NIH SCAP InnoCentive Challenge Solution - T-Bow Rainbow T-cells and Tumor Cells Spatial Multiplexing Gene Expression Reporter System – plus supplement plus posters - 20141228S
The download is my/Cooper lab solution (submission) to the 2014 NIH Single Cell Analysis Program (SCAP) InnoCentive Challenge, "Follow That Cell". I submitted the Solution on 20141215Mon (with 20 minutes to spare). The Challenge web page is
Our Solution is to revolutionize live cell transcriptional reporter assays. Specifically, we propose to multiplex five promoter response elements to drive expression of different color fluorescent proteins that would bind to ...
Regulation Of Phialide Morphogenesis In Aspergillus Nidulans, 2014 University of Nebraska-Lincoln
Regulation Of Phialide Morphogenesis In Aspergillus Nidulans, Hu Yin
Dissertations and Theses in Biological Sciences
Filamentous fungi have two distinctive life cycles, vegetative growth and development for sexual or asexual spore formation. The asexual reproduction in development as conidiation in A. nidulans is the dominant form of producing spores effectively. A complex conidiophore structure is developed during asexual reproduction process. The conidiophore is formed from hyphal cell and consists of stalk, vesicle, metulae, phialide and conidial spores. Phialides are essential sporogenous cells in the conidiophore structure. The growth pattern is switched from acropetal to basipetal between phialide and spores, which makes phialide a unique cell type in A. nidulans and other phialide producing fungi. Study ...
Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker
Undergraduate Student Research Day Abstracts and Posters
The molecular chaperone protein Hsp70 is centrally involved in cellular homeostasis by assisting in the folding and degradation of protein substrates. Hsp70 is joined by co-chaperones, such as Hsp110, which contribute to specialized tasks of the Hsp70 complex. Imbalances of this heat shock protein system are believed to be involved with the deregulation of cancer pathways and other human diseases. Better understanding of how these heat shock proteins work at the molecular level, which has been investigated using molecular docking tools, will give more clues about biological function. Simulating the formation and function of Hsp70 based chaperone complexes could provide ...
Argument Map: Loewi's Argument That Neuro-Transmission Works With Chemical Signals Instead Of Eletrical (Short Version), 2014 Georgia Institute of Technology
Argument Map: Loewi's Argument That Neuro-Transmission Works With Chemical Signals Instead Of Eletrical (Short Version), Michael Hoffmann
Michael H.G. Hoffmann
This argument shows how the hypothesis that muscles are probably stimulated exclusively by chemical signals and not by electrical ones can be justified by Loewi's experimentum crucis.
Swarna Ramaswamy_Thesis, 2014 University of Texas Health Science Center at Houston
Swarna Ramaswamy_Thesis, Swarna S. Ramaswamy
UT GSBS Dissertations and 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 ...
Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., 2014 Dublin Institute of Technology
Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus A. Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh J. Byrne
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 ...
Redesign Of Trans-Splicing Molecules For The Correction Of Dystrophia Myotonica Type 1 Toxic Rna Transcripts, 2014 East Tennessee State University
Redesign Of Trans-Splicing Molecules For The Correction Of Dystrophia Myotonica Type 1 Toxic Rna Transcripts, Eleanor G. Harrison
Undergraduate Honors Theses
Dystrophia myotonica (DM1), one of the most common forms of muscular dystrophy, is caused by a repeated trinucleotide expansion in the DMPK gene. This mutation results in the accumulation of toxic cellular RNA transcripts. Spliceosome-mediated RNA trans-splicing (SMaRT) technology is a form of gene therapy that possesses the potential to correct these toxic RNA transcripts and thus cure the disease. Despite its promise, prior research applications of SMaRT technology to DM1 have been hampered by poor efficiency and have not been validated in a relevant model of the disease. In order to improve the efficiency of trans-splicing, this study examined ...
Microchip Thermal Gradient Gas Chromatography, 2014 Brigham Young University - Provo
Microchip Thermal Gradient Gas Chromatography, Anzi Wang
All Theses and Dissertations
Although the airbath oven is a reliable heating method for gas chromatography (GC), resistive heating is needed for higher analytical throughput and on-site chemical analysis because of size, heating rate and power requirements. In the last thirty years, a variety of resistive heating methods were developed and implemented for both benchtop and portable GC systems. Although fast heating rates and low power consumption have been achieved, losses in column efficiency and resolution, complex construction processes and difficulties experienced in recovering damaged columns have also become problematic for routine use of resistively heated columns. To solve these problems, a new resistively ...
Characterization And Role Of Msaabcr In Biofilm Development And Virulence In Staphylococcus Aureus, 2014 University of Southern Mississippi
Characterization And Role Of Msaabcr In Biofilm Development And Virulence In Staphylococcus Aureus, Gyan Sundar Sahukhal
Community-acquired, methicillin-resistant Staphylococcus aureus strains often cause localized infections in immune-compromised hosts, but some strains show enhanced virulence leading to severe infections even among healthy individuals with no predisposing risk factors. The genetic basis for this enhanced virulence has yet to be determined. S. aureus possesses a wide variety of virulence factors, the expression of which is carefully coordinated by a variety of regulators. Several virulence regulators have been well characterized, but others have yet to be thoroughly investigated. Previously, the msa gene as a regulator of several virulence genes, biofilm development, and antibiotic ...
Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, 2014 University of Tennessee - Knoxville
Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood
Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous ...
The Dissolution Of Cellulose In Ionic Liquids - A Molecular Dynamics Study, 2014 University of Tennessee - Knoxville
The Dissolution Of Cellulose In Ionic Liquids - A Molecular Dynamics Study, Barmak Mostofian
The use of ionic liquids for the dissolution of cellulose promises an alternative method for the thermochemical pretreatment of biomass that may be more efficient and environmentally acceptable than conventional techniques in aqueous solution. Understanding how ionic liquids act on cellulose is essential for improving pretreatment conditions and thus detailed knowledge of the interactions between solute and solvent molecules is necessary. Here, results from the first all-atom molecular dynamics simulation of an entire cellulose microfibril in 1-butyl-3-methylimidazolium chloride (BmimCl) are presented and the interactions and orientations of solvent ions with respect to glucose units on the hydrophobic and hydrophilic surfaces ...
Computer Simulations Of Enzymes, 2014 University of Tennessee - Knoxville
Computer Simulations Of Enzymes, Jianzhuang Yao
Enzymes are important catalysts in living systems, and understanding catalytic mechanisms of enzymes is an important task for modern biophysics and biochemistry. Computer simulations have emerged as very useful tools for understanding how enzymes work. In this dissertation, QM/MM MD simulations were applied to study the catalytic mechanisms of several enzymes, including sedolisin, S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases, and salicylic acid binding protein 2. For sedolisin, we focus on the acylation and deacylation reactions catalyzed by the enzymes. We proposed a general acid/base mechanism involving the Glu/Asp residues at the active site. MD and QM/MM free energy ...
Variability Of Vitamins B1, B2 And Minerals Content In Baobab (Adansonia Digitata) Leaves In East And West Africa, 2014 Département Technologie Alimentaire, IRSAT/CNRST, 03 BP 7047, Ouagadougou 03, Burkina Faso
Variability Of Vitamins B1, B2 And Minerals Content In Baobab (Adansonia Digitata) Leaves In East And West Africa, Hyacinthe Traore, Charles Parkouda, Adama Korbo, Diarra Compaoré/Sérémé, Mamoudou H. Dicko Prof., Jan J. Svejgaard, Bréhima Diawara
Pr. Mamoudou H. DICKO, PhD
The regional variability and age-age correlation on vitamin B1, vitamin B2 and minerals (Ca, Mg, P, K, Cu, Fe, Mn, Na, and Zn) concentration in baobab leaves were investigated. Baobab was cultivated from seeds from 11 african countries. Vitamins B1 and B2 content were assessed using microbiological VitaFast kits methods and minerals by atomic absorption and flame spectrometry methods. Overall, the results showed a higher content of vitamin B2 compared to vitamin B1 with the highest vitamin B2 content (1.04 +- 0.05 mg/100 g DM) from Senegal. The highest iron (Fe) content of 26.39 mg/100 g ...
The Oestrogen Receptor Alpha-Regulated Lncrna Neat1 Is A Critical Modulator Of Prostate Cancer, 2014 Weill Cornell Medical College
The Oestrogen Receptor Alpha-Regulated Lncrna Neat1 Is A Critical Modulator Of Prostate Cancer, Dimple Chakravarty, Andrea Sboner, Sujit S. Nair, Eugenia Giannopoulou, Ruohan Li, +16 Additional Authors
Biochemistry and Molecular Medicine Faculty Publications
The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical ...
An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, 2014 Washington University in St. Louis
An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher
Biology Faculty Publications
Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity ...
The Development Of A Valid And Reliable Biogeochemistry Concept Inventory, 2014 University of Nebraska-Lincoln
The Development Of A Valid And Reliable Biogeochemistry Concept Inventory, Chris Mead
DBER Speaker Series
Concept inventories are a commonly used tool to measure conceptual understanding. To date, concept inventories have been published for geology, chemistry, and biology, but no instrument has been designed to measure conceptual understanding at the intersection of those fields. To fill that gap, we constructed a 32‐item biogeochemistry concept inventory (BGC‐CI). Item response theory analysis, using the Rasch model, shows the BGC‐CI is a reliable and valid tool to measure the biogeochemistry knowledge of science majors. Because biogeochemistry is an interdisciplinary field, we were concerned about the unidimensionality of the instrument. However, our analysis showed the BGC ...