Structural Dynamics Of A Mitochondrial Trna Possessing Weak Thermodynamic Stability,
2014
Portland State University
Structural Dynamics Of A Mitochondrial Trna Possessing Weak Thermodynamic Stability, Hari Bhaskaran, Takaaki Taniguchi, Takeo Suzuki, Tsutomu Suzuki, John J. Perona
Chemistry Faculty Publications and Presentations
Folding dynamics are ubiquitously involved in controlling the multivariate functions of RNAs. While the high thermodynamic stabilities of some RNAs favor purely native states at equilibrium, it is unclear whether weakly stable RNAs exist in random, partially folded states or sample well-defined, globally folded conformations. Using a folding assay that precisely tracks the formation of native aminoacylable tRNA, we show that the folding of a weakly stable human mitochondrial (hmt) leucine tRNA is hierarchical with a distinct kinetic folding intermediate. The stabilities of the native and intermediate conformers are separated by only about 1.2 kcal/mol, and the species are readily …
Methylseleninic Acid Elevates Redd1 And Inhibits Prostate Cancer Cell Growth Despite Akt Activation And Mtor Dysregulation In Hypoxia,
2014
New York Medical College
Methylseleninic Acid Elevates Redd1 And Inhibits Prostate Cancer Cell Growth Despite Akt Activation And Mtor Dysregulation In Hypoxia, Indu Sinha, Joshua Allen, John T. Pinto, Raghu Sinha
NYMC Faculty Publications
Methylseleninic acid (MSeA) is a monomethylated selenium metabolite theoretically derived from subsequent β-lyase or transamination reactions of dietary Se-methylselenocysteine that has potent antitumor activity by inhibiting cell proliferation of several cancers. Our previous studies showed that MSeA promotes apoptosis in invasive prostate cancer cells in part by downregulating hypoxia-inducible factor HIF-1α. We have now extended these studies to evaluate the impact of MSeA on REDD1 (an mTOR inhibitor) in inducing cell death of invasive prostate cancer cells in hypoxia. In both PTEN+ and PTEN- prostate cancer cells we show that MSeA elevates REDD1 and phosphorylation of AKT along with p70S6K …
The Abcs Of The Ribosome,
2014
The Ohio State University
The Abcs Of The Ribosome, Kurt Fredrick, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
An ABC protein that binds the ribosomal exit site suggests a new mechanism for direct regulation of translation in response to changing ATP levels in the cell.
On Chip Preconcentration And Labeling Of Protein Biomarkers Using Monolithic Columns, Device Fabrication, Optimization, And Automation,
2014
Brigham Young University - Provo
On Chip Preconcentration And Labeling Of Protein Biomarkers Using Monolithic Columns, Device Fabrication, Optimization, And Automation, Rui Yang
Theses and Dissertations
Detection of disease specific biomarkers is of great importance in diagnosis and treatment of diseases. Modern bioanalytical techniques, such as liquid chromatography with mass spectrometry (LC-MS), have the ability to identify biomarkers, but their cost and scalability are two main drawbacks. Enzyme-linked immunosorbent assay (ELISA) is another potential tool, but it works best for proteins, rather than peptide biomarkers. Recently, microfluidics has emerged as a promising technique due to its small fluid volume consumption, rapidness, low fabrication cost, portability and versatility. Therefore, it shows prominent potential in the analysis of disease specific biomarkers. In this thesis, microfluidic systems that integrate …
Roles Of Igh Intronic Enhancer Eμ In Clonal Selection At The Pre-B To Immature B Cell Transition And In The Elimination Of Autoreactive B Cells,
2014
CUNY Graduate Center
Roles Of Igh Intronic Enhancer Eμ In Clonal Selection At The Pre-B To Immature B Cell Transition And In The Elimination Of Autoreactive B Cells, Cheng Peng
Dissertations, Theses, and Capstone Projects
The immunoglobulin heavy chain locus (Igh ) intronic enhancer, Eμ, enhances transcription of recombined Igh genes. We have previously shown that in mice with an Eμ-deficient Igh allele (V H δa ), Igμ is expressed at half of the wild-type levels in pre-B cells. We also described an Eμ-dependent "check-point", operating at the pre-B to immature B cell transition, for heavy chain allelic exclusion. We now show that deletion of Eμ results in a smaller immature B cell compartment, and the pre-BCR/BCR signaling is diminished in pre-B cells as a result of the reduced Igμ levels, making it …
Effects Of 5-Hydroxytryptamine 2c Receptor Agonist Mk212 And 2a Receptor Antagonist Mdl100907 On Maternal Behavior In
Postpartum Female Rats,
2014
Southwest University, Chongqing, China
Effects Of 5-Hydroxytryptamine 2c Receptor Agonist Mk212 And 2a Receptor Antagonist Mdl100907 On Maternal Behavior In Postpartum Female Rats, Weihai Chen, Qi Zhang, Wenxin Su, Yu Yang, Jing Qiao, Nan Sui, Ming Li
Department of Psychology: Faculty Publications
Maternal behavior in rats is a highly motivated and well-organized social behavior. Given the known roles of serotonin (5-HT) in emotion, motivation, social behavior, and major depression – and its known interaction with dopamine – it is likely that serotonin also plays a crucial role in this behavior. So far, there are surprisingly few studies focusing on 5-HT in maternal behavior, except for maternal aggression. In the present study,we examined the effects of 5-HT2C receptor agonism and 5-HT2A receptor antagonism on maternal behavior in postpartum female rats.We hypothesized that activation of 5-HT2C receptors and blockade of 5-HT …
Identification And Characterization Of Protein Phopshatases Regulating The Sma/Mab Pathway In C. Elegans,
2014
CUNY Graduate Center
Identification And Characterization Of Protein Phopshatases Regulating The Sma/Mab Pathway In C. Elegans, Sheng Xiong
Dissertations, Theses, and Capstone Projects
TGF-beta signaling is a conserved signaling pathway among eukaryotes, which controls various normal cellular responses from cell proliferation to cell death. The mutations in its components are found in developmental disorders and cancer. Therefore, this signaling pathway is extensively investigated so that new therapeutic targets could be discovered and novel drugs could be developed. Previous studies suggested the involvement of phosphatases in regulation of TGF-beta signaling, but these studies were performed in cell culture rather than intact organisms. C. elegans is a tractable organism in which to study signaling in vivo. In C. elegans, growth is controled by a conserved …
Iron Regulates Mrna Translation Initiation Through Rna Iron Responsive Element (Ire),
2014
CUNY Graduate Center
Iron Regulates Mrna Translation Initiation Through Rna Iron Responsive Element (Ire), Jia Ma
Dissertations, Theses, and Capstone Projects
The non-coding IRE-RNA structure, a 30 nt stem loop structure, regulates synthesis of proteins in iron trafficking, cell cycling, and nervous system function. IRE-RNA binding with iron regulatory protein (IRP) proteins inhibits ribosome accessing mRNA. Increasing iron concentration decreases IRP binding with IRE-RNA. Previous models of IRE-mRNA translation regulation concentrate on Fe-S binding to IRP and IRP degradation after release from IRE-RNA. These models lack information on the details of decreasing IRE-RNA/IRP protein binding with iron concentration elevation. This research shows 1. Eukaryotic initiation factor 4F (eIF4F) binds to IRE-RNA with high affinity and works as a positive control element …
Lipid Dependence In Ras-Driven Tumors,
2014
CUNY Graduate Center
Lipid Dependence In Ras-Driven Tumors, Darin Salloum
Dissertations, Theses, and Capstone Projects
Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network. …
Conformational Features Of The Human U2-U6 Snrna Complex,
2014
CUNY Graduate Center
Conformational Features Of The Human U2-U6 Snrna Complex, Ravichandra Bachu
Dissertations, Theses, and Capstone Projects
The splicing of precursor messenger (pre-m) RNA, during which noncoding intervening sequences are excised and flanking coding regions ligated, is an integral reaction of gene expression. In eukaryotes, it is carried out by a dynamic RNA-protein complex called the spliceosome, in which five small nuclear (sn) RNA components are actively involved in recognition and chemical aspects of the process. A complex formed between U2 and U6 snRNAs is implicated in the chemistry of pre-mRNA splicing. The catalytic activity of the U2-U6 snRNA complex is dependent on the presence of Mg2+ ions, and the complex has been shown to have several …
Mechanism Of Phospho-Alpha-Tubulin-Driven Motility In Human Breast Epithelial Cells,
2014
CUNY Graduate Center
Mechanism Of Phospho-Alpha-Tubulin-Driven Motility In Human Breast Epithelial Cells, Shatarupa De
Dissertations, Theses, and Capstone Projects
Protein kinase C (PKC), an enzyme important in signaling pathways that give rise to various cell phenotypes, has been closely associated with metastatic phenotypes of breast cancer. Tissues from patients of varying degrees of tumorgenicity have shown an elevated expression of the PKCα isoform as well as other diacylglycerol (DAG)-sensitive isoforms. Moreover, independent studies with highly invasive breast cell lines, such as MDA-MB-231 cells, have also shown an elevated level of PKCα. Therefore, PKCα has long been a therapeutic target for breast cancer. Among its known substrates (recently identified by our laboratory), α6-tubulin will, upon phosphorylation by PKC, enhance migration …
Metabolic Checkpoints In Cancer Cell Cycle,
2014
CUNY Graduate Center
Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena
Dissertations, Theses, and Capstone Projects
Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from …
Mechanisms Of Deadenylation Regulation Under Different Cellular Conditions,
2014
CUNY Graduate Center
Mechanisms Of Deadenylation Regulation Under Different Cellular Conditions, Xiaokan Zhang
Dissertations, Theses, and Capstone Projects
Control of gene expression by regulating mRNA stability after DNA damage has the potential to contribute to the cells rapid response to stress. The main focus of this dissertation is to elucidate the role(s) of nuclear PARN deadenylase in controlling mRNA stability, hence gene expression, of factors in the p53 signaling pathway during the DNA damage response (DDR). Understanding the mechanisms of these regulatory pathways will provide new insights on how the control of gene expression upon DNA damage decides cellular fate, offering new opportunities for therapeutics. In Chapter II, I presented evidence that PARN along with the cleavage factor …
Paper-Based Standard Addition Assays,
2014
California Polytechnic State University – San Luis Obispo
Paper-Based Standard Addition Assays, Cory A. Chaplan, Haydn T. Mitchell, Andres W. Martinez
Chemistry and Biochemistry
Standard addition assays conducted on paper-based microfluidic devices are introduced as an alternative to external standards for calibrating quantitative tests. To demonstrate this technique, a colorimetric, paper-based, standard addition assay was optimized for the determination of glucose concentrations in the range of 0 to 5 mM. Comparable results were obtained from the assay via digital image colorimetry under three different lighting conditions.
Arabidopsis Accelerated Cell Death 11, Acd11, Is A Ceramide-1-Phosphate Transfer Protein And Intermediary Regulator Of Phytoceramide Levels,
2014
Memorial Sloan-Kettering Cancer Center
Arabidopsis Accelerated Cell Death 11, Acd11, Is A Ceramide-1-Phosphate Transfer Protein And Intermediary Regulator Of Phytoceramide Levels, Dhirendra K. Simanshu, Xiuhong Zhai, David Munch, Daniel Hofius, Jennifer E. Markham, Jacek Bielawski, Alicja Bielawska, Lucy Malinina, Julian G. Molotkovsky, John W. Mundy, Dinshaw J. Patel, Rhoderick E. Brown
Department of Biochemistry: Faculty Publications
The accelerated cell death 11 (acd11) mutant of Arabidopsis provides a genetic model for studying immune response activation and localized cellular suicide that halt pathogen spread during infection in plants. Here, we elucidate ACD11 structure and function and show that acd11 disruption dramatically alters the in vivo balance of sphingolipid mediators that regulate eukaryotic-programmed cell death. In acd11 mutants, normally low ceramide-1- phosphate (C1P) levels become elevated, but the relatively abundant cell death inducer phytoceramide rises acutely. ACD11 exhibits selective intermembrane transfer of C1P and phyto-C1P. Crystal structures establish C1P binding via a surface-localized, phosphate headgroup recognition center …
Polymeric Monolithic Stationary Phases For Capillary Reversed-Phase Liquid Chromatography Of Small Molecules,
2014
Brigham Young University - Provo
Polymeric Monolithic Stationary Phases For Capillary Reversed-Phase Liquid Chromatography Of Small Molecules, Kun Liu
Theses and Dissertations
Highly cross-linked monoliths prepared from single cross-linking monomers were found to increase surface area and stability. Therefore, seven cross-linking monomers, i.e., 1,3-butanediol dimethacrylate (1,3-BDDMA), 1,4-butanediol dimethacrylate (1,4-BDDMA), neopentyl glycol dimethacrylate (NPGDMA), 1,5-pentanediol dimethacrylate (1,5-PDDMA), 1,6-hexanediol dimethacrylate (1,6-HDDMA), 1,10-decanediol dimethacrylate (1,10-DDDMA), and 1,12-dodecanediol dimethacrylate (1,12-DoDDMA), were used to synthesize highly cross-linked monolithic columns in 75-µm i.d. capillaries by one-step UV-initiated polymerization using dodecanol and methanol as porogens for reversed-phase liquid chromatography (RPLC) of small molecules. Selection of porogen type and concentration was investigated in detail. Isocratic elution of alkylbenzenes at a flow rate of 300 nL/min was conducted for all of …
Validation Of Predicted Mrna Splicing Mutations Using High-Throughput Transcriptome Data,
2014
University of Western Ontario
Validation Of Predicted Mrna Splicing Mutations Using High-Throughput Transcriptome Data, Coby Viner, Stephanie Dorman, Ben Shirley, Peter Rogan
Biochemistry Publications
Interpretation of variants present in complete genomes or exomes reveals numerous sequence changes, only a fraction of which are likely to be pathogenic. Mutations have been traditionally inferred from allele frequencies and inheritance patterns in such data. Variants predicted to alter mRNA splicing can be validated by manual inspection of transcriptome sequencing data, however this approach is intractable for large datasets. These abnormal mRNA splicing patterns are characterized by reads demonstrating either exon skipping, cryptic splice site use, and high levels of intron inclusion, or combinations of these properties. We present, Veridical, an in silico method for the automatic validation …
Bsa–Boronic Acid Conjugate As Lectin Mimetics,
2014
Cleveland State University
Bsa–Boronic Acid Conjugate As Lectin Mimetics, Satya Nandana Narla, Poornima Pinnamaneni, Huan Nie, Yu Li, Xue-Long Sun
Chemistry Faculty Publications
We report bovine serum albumin (BSA)–boronic acid (BA) conjugates as lectin mimetics and their glyco-capturing capacity. The BSA–BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized by Alizarin Red S (ARS) assay and SDS–PAGE gel. The BSA–BA conjugates were immobilized onto maleimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by ARS displacement assay. Further, surface plasmon resonance (SPR) analysis of the glyco-capturing activity of the BSA–BA conjugates was conducted by immobilizing BSA–BA onto SPR gold chip. Overall, we demonstrated a BSA–BA-based …
Redox-Dependent Stability, Protonation, And Reactivity Of Cysteine-Bound Heme Proteins,
2014
Dartmouth College
Redox-Dependent Stability, Protonation, And Reactivity Of Cysteine-Bound Heme Proteins, Fangfang Zhong, George P. Lisi, Daniel P. Collins, John H. Dawson, Ekaterina V. Pletneva
Dartmouth Scholarship
Cysteine-bound hemes are key components of many enzymes and biological sensors. Protonation (deprotonation) of the Cys ligand often accompanies redox transformations of these centers. To characterize these phenomena, we have engineered a series of Thr78Cys/Lys79Gly/Met80X mutants of yeast cytochrome c (cyt c) in which Cys78 becomes one of the axial ligands to the heme. At neutral pH, the protonation state of the coordinated Cys differs for the ferric and ferrous heme species, with Cys binding as a thiolate and a thiol, respectively. Analysis of redox-dependent stability and alkaline transitions of these model proteins, as well as comparisons to Cys …
Collisional Dynamic Elements Of The Pyrazine - N2o System:Middle And Low J States,
2014
Brigham Young University - Provo
Collisional Dynamic Elements Of The Pyrazine - N2o System:Middle And Low J States, La Moyne Tyler Mix
Theses and Dissertations
Unimolecular reactions based on the Lindemann - Hinchelwood mechanism are important to understanding combustion and atmospheric processes. The main feature of this mechanism is the energy transfer probability distribution function, P(E',E). We have chosen to study P(E',E) through gas phase collisional dynamics probed with IR transient absorption spectroscopy. Post-collision absorption line widths for the pyrazine-N2O system are used to calculate lab frame translational temperatures. The translational temperatures reveal that collisions with large rotational energy transfer also transfer large amounts of translational energy. For J states >47 the relationship is linear indicating a constant impact parameter. Line widths for J=47 through …
