Search results

Title: Multiplexing Fluorescence Anisotropy Using Frequency Encoding.
Creator: Schrell, Adrian M, Mukhitov, Nikita, Roper, Michael G
Abstract/Description: In this report, a method to multiplex fluorescence anisotropy measurements is described using frequency encoding. As a demonstration of the method, simultaneous competitive immunoassays for insulin and glucagon were performed by measuring the ratio of bound and free Cy5-insulin and FITC-glucagon in the presence of their respective antibodies. A vertically polarized 635 nm laser was pulsed at 73 Hz and used to excite Cy5-insulin, while a vertically polarized 488 nm laser pulsed at 137 Hz...
Show moreIn this report, a method to multiplex fluorescence anisotropy measurements is described using frequency encoding. As a demonstration of the method, simultaneous competitive immunoassays for insulin and glucagon were performed by measuring the ratio of bound and free Cy5-insulin and FITC-glucagon in the presence of their respective antibodies. A vertically polarized 635 nm laser was pulsed at 73 Hz and used to excite Cy5-insulin, while a vertically polarized 488 nm laser pulsed at 137 Hz excited FITC-glucagon. The total emission was split into parallel and perpendicular polarizations and collected onto separate photomultiplier tubes. The signals from each channel were demodulated using a fast Fourier transform, resolving the contributions from each fluorophore. Anisotropy calculations were carried out using the magnitude of the peaks in the frequency domain. The method produced the expected shape of the calibration curves with limits of detection of 0.6 and 5 nM for insulin and glucagon, respectively. This methodology could readily be expanded to other biological systems and further multiplexed to monitor increased numbers of analytes.
Show less
Date Issued: 2016-08-16
Identifier: FSU_pmch_27440478, 10.1021/acs.analchem.6b02131, PMC4991543, 27440478, 27440478
Format: Citation

Title: Proteomic Upregulation of Fatty Acid Synthase and Fatty Acid Binding Protein 5 and Identification of Cancer- and Race-Specific Pathway Associations in Human Prostate Cancer Tissues.
Creator: Myers, Jennifer S, von Lersner, Ariana K, Sang, Qing-Xiang Amy
Abstract/Description: Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence...
Show moreProtein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States. In this study, age-, stage-, and Gleason score-matched prostate tumor specimen from African American and Caucasian American men, along with non-malignant adjacent prostate tissue from these same patients, were compared. Protein expression changes and altered pathway associations were identified in prostate cancer generally and in African American prostate cancer specifically. In comparing tumor to non-malignant samples, 45 proteins were significantly cancer-associated and 3 proteins were significantly downregulated in tumor samples. Notably, fatty acid synthase (FASN) and epidermal fatty acid-binding protein (FABP5) were upregulated in human prostate cancer tissues, consistent with their known functions in prostate cancer progression. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3) was also upregulated in tumor samples. The Metastasis Associated Protein 3 (MTA3) pathway was significantly enriched in tumor samples compared to non-malignant samples. While the current experiment was unable to detect statistically significant differences in protein expression between African American and Caucasian American samples, differences in overrepresentation and pathway enrichment were found. Structural components (Cytoskeletal Proteins and Extracellular Matrix Protein protein classes, and Biological Adhesion Gene Ontology (GO) annotation) were overrepresented in African American but not Caucasian American tumors. Additionally, 5 pathways were enriched in African American prostate tumors: the Small Cell Lung Cancer, Platelet-Amyloid Precursor Protein, Agrin, Neuroactive Ligand-Receptor Interaction, and Intrinsic pathways. The protein components of these pathways were either basement membrane proteins or coagulation proteins.
Show less
Date Issued: 2016-07-05
Identifier: FSU_pmch_27471561, 10.7150/jca.15860, PMC4964129, 27471561, 27471561, jcav07p1452
Format: Citation

Title: Wavy membranes and the growth rate of a planar chemical garden: Enhanced diffusion and bioenergetics..
Creator: Ding, Yang, Batista, Bruno, Steinbock, Oliver, Cartwright, Julyan H E, Cardoso, Silvana S S
Abstract/Description: To model ion transport across protocell membranes in Hadean hydrothermal vents, we consider both theoretically and experimentally the planar growth of a precipitate membrane formed at the interface between two parallel fluid streams in a 2D microfluidic reactor. The growth rate of the precipitate is found to be proportional to the square root of time, which is characteristic of diffusive transport. However, the dependence of the growth rate on the concentrations of hydroxide and metal ions is...
Show moreTo model ion transport across protocell membranes in Hadean hydrothermal vents, we consider both theoretically and experimentally the planar growth of a precipitate membrane formed at the interface between two parallel fluid streams in a 2D microfluidic reactor. The growth rate of the precipitate is found to be proportional to the square root of time, which is characteristic of diffusive transport. However, the dependence of the growth rate on the concentrations of hydroxide and metal ions is approximately linear and quadratic, respectively. We show that such a difference in ionic transport dynamics arises from the enhanced transport of metal ions across a thin gel layer present at the surface of the precipitate. The fluctuations in transverse velocity in this wavy porous gel layer allow an enhanced transport of the cation, so that the effective diffusivity is about one order of magnitude higher than that expected from molecular diffusion alone. Our theoretical predictions are in excellent agreement with our laboratory measurements of the growth of a manganese hydroxide membrane in a microfluidic channel, and this enhanced transport is thought to have been needed to account for the bioenergetics of the first single-celled organisms.
Show less
Date Issued: 2016-08-16
Identifier: FSU_pmch_27486248, 10.1073/pnas.1607828113, PMC4995959, 27486248, 27486248, 1607828113
Format: Citation

Title: Synthesis of "neoprofen", a rigidified analogue of ibuprofen, exemplifying synthetic methodology for altering the 3-D topology of pharmaceutical substances.
Creator: Ramsubhag, Ron R, Massaro, Chelsea L, Dadich, Christina M, Janeczek, Andrew J, Hoang, Tung T, Mazzio, Elizabeth A, Eyunni, Suresh, Soliman, Karam F A, Dudley, Gregory B
Abstract/Description: 3,3-Dimethylcyclopentanes (neopentylenes) are ubiquitous in Nature but largely absent from synthetic pharmaceutical libraries. Neopentylenes define a hydrophobic and rigid 3-D topology with distinct molecular pharmacology, as exemplified here with two neopentylene-fused analogues of the synthetic anti-inflammatory drug, ibuprofen.
Date Issued: 2016-08-16
Identifier: FSU_pmch_27492587, 10.1039/c6ob01351a, PMC5008855, 27492587, 27492587
Format: Citation

Title: Generalized Ensemble Sampling of Enzyme Reaction Free Energy Pathways.
Creator: Wu, D, Fajer, M I, Cao, L, Cheng, X, Yang, W
Abstract/Description: Free energy path sampling plays an essential role in computational understanding of chemical reactions, particularly those occurring in enzymatic environments. Among a variety of molecular dynamics simulation approaches, the generalized ensemble sampling strategy is uniquely attractive for the fact that it not only can enhance the sampling of rare chemical events but also can naturally ensure consistent exploration of environmental degrees of freedom. In this review, we plan to provide a...
Show moreFree energy path sampling plays an essential role in computational understanding of chemical reactions, particularly those occurring in enzymatic environments. Among a variety of molecular dynamics simulation approaches, the generalized ensemble sampling strategy is uniquely attractive for the fact that it not only can enhance the sampling of rare chemical events but also can naturally ensure consistent exploration of environmental degrees of freedom. In this review, we plan to provide a tutorial-like tour on an emerging topic: generalized ensemble sampling of enzyme reaction free energy path. The discussion is largely focused on our own studies, particularly ones based on the metadynamics free energy sampling method and the on-the-path random walk path sampling method. We hope that this minipresentation will provide interested practitioners some meaningful guidance for future algorithm formulation and application study.
Show less
Date Issued: 2016-01-01
Identifier: FSU_pmch_27498634, 10.1016/bs.mie.2016.05.012, PMC4978182, 27498634, 27498634, S0076-6879(16)30047-7
Format: Citation

Title: Collective epithelial cell sheet adhesion and migration on polyelectrolyte multilayers with uniform and gradients of compliance.
Creator: Martinez, Jessica S, Schlenoff, Joseph B, Keller, Thomas C S
Abstract/Description: Polyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked,...
Show morePolyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked, UV-crosslinked to a uniform stiffness, or UV-crosslinked with an edge mask or through a neutral density optical gradient filter to form continuous compliance gradients were used to investigate how differences in PEMU stiffness affect the adhesion and migration of epithelial cell sheets from scales of the fish Poecilia sphenops (Black Molly) and Carassius auratus (Comet Goldfish). During the progressive collective cell migration, the edge cells (also known as 'leader' cells) in the sheets on softer uncrosslinked PEMUs and less crosslinked regions of the gradient formed more actin filaments and vinculin-containing adherens junctions and focal adhesions than formed in the sheet cells on stiffer PEMUs or glass. During sheet migration, the ratio of edge cell to internal cell (also known as 'follower' cells) motilities were greater on the softer PEMUs than on the stiffer PEMUs or glass, causing tension to develop across the sheet and periods of retraction, during which the edge cells lost adhesion to the substrate and regions of the sheet retracted toward the more adherent internal cell region. These retraction events were inhibited by the myosin II inhibitor Blebbistatin, which reduced the motility velocity ratios to those for sheets on the stiffer PEMUs. Blebbistatin also caused disassembly of actin filaments, reorganization of focal adhesions, increased cell spreading at the leading edge, as well as loss of edge cell-cell connections in epithelial cell sheets on all surfaces. Interestingly, cells throughout the interior region of the sheets on uncrosslinked PEMUs retained their actin and vinculin organization at adherens junctions after treatment with Blebbistatin. Like Blebbistatin, a Rho-kinase (ROCK) inhibitor, Y27632, promoted loss of cell-cell connections between edge cells, whereas a Rac1 inhibitor, NSC23766, primarily altered the lamellipodial protrusion in edge cells. Compliance gradient PAH-PEMUs promoted durotaxis of the cell sheets but not of individual keratocytes, demonstrating durotaxis, like plithotaxis, is an emergent property of cell sheet organization.
Show less
Date Issued: 2016-08-01
Identifier: FSU_pmch_27292313, 10.1016/j.yexcr.2016.06.002, PMC4967014, 27292313, 27292313, S0014-4827(16)30143-4
Format: Citation

Title: Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer.
Creator: Vallega, Karin A, Liu, NingNing, Myers, Jennifer S, Yu, Kaixian, Sang, Qing-Xiang Amy
Abstract/Description: African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels...
Show moreAfrican American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.
Show less
Date Issued: 2016-06-17
Identifier: FSU_pmch_27314854, 10.1371/journal.pone.0157741, PMC4912107, 27314854, 27314854, PONE-D-16-17121
Format: Citation

Title: Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS.
Creator: Dang, Xibei, Singh, Amar, Spetman, Brian D, Nolan, Krystal D, Isaacs, Jennifer S, Dennis, Jonathan H, Dalton, Stephen, Marshall, Alan G, Young, Nicolas L
Abstract/Description: Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free...
Show moreHistone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.
Show less
Date Issued: 2016-09-02
Identifier: FSU_pmch_27431976, 10.1021/acs.jproteome.6b00414, PMC6261780, 27431976, 27431976
Format: Citation

Title: A flexible iron(II) complex in which zero-field splitting is resistant to structural variation.
Creator: Zadrozny, Joseph M., Greer, Samuel M., Hill, Stephen, Freedman, Danna E.
Abstract/Description: The relationship between electronic structure and zero-field splitting dictates key design parameters for magnetic molecules. In particular, to enable the directed synthesis of new electronic spin based qubits, developing complexes where zero-field splitting energies are invariant to structural changes is a critical challenge. Toward those ends, we report three salts of a new compound, a four-coordinate iron(II) complex [ Fe(C3S5)(2)](2-) ([(18-crown-6) K](+) (1), Ph4P+ (2), Bu4N+ (3)) with a...
Show moreThe relationship between electronic structure and zero-field splitting dictates key design parameters for magnetic molecules. In particular, to enable the directed synthesis of new electronic spin based qubits, developing complexes where zero-field splitting energies are invariant to structural changes is a critical challenge. Toward those ends, we report three salts of a new compound, a four-coordinate iron(II) complex [ Fe(C3S5)(2)](2-) ([(18-crown-6) K](+) (1), Ph4P+ (2), Bu4N+ (3)) with a continuous structural variation in a single parameter, the dihedral angle (theta(d)) between the two C3S52- ligands, as a function of counterion (theta(d) = 89.98(4)degrees for 1 to 72.41(2)degrees for 3). Electron paramagnetic resonance data for 1-3 reveal zero-field splitting parameters that are unusually robust to the structural variation. Mossbauer spectroscopic measurements indicate that the structural variation in theta(d) primarily affects the highest-energy 3d-orbitals (d(xz) and d(yz)) of the iron(II) ion. These orbitals have the smallest impact on the zero-field splitting parameters, thus the distortion has a minor effect on D and E. These results represent the first part of a directed effort to understand how spin state energies may be fortified against structural distortions for future applications of qubits in non-crystalline environments.
Show less
Date Issued: 2016
Identifier: FSU_libsubv1_wos_000366826900047, 10.1039/c5sc02477c
Format: Citation

Title: Dual Detection System for Simultaneous Measurement of Intracellular Fluorescent Markers and Cellular Secretion.
Creator: Yi, Lian, Bandak, Basel, Wang, Xue, Bertram, Richard, Roper, Michael G
Abstract/Description: Glucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with...
Show moreGlucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with high-speed automated insulin immunoassays. As a demonstration of the system, intracellular [Ca] ([Ca]) was measured by imaging Fura-2 fluorescence simultaneously with insulin secretion from islets exposed to elevated glucose levels. Both [Ca] and insulin were oscillatory during application of 10 mM glucose with temporal and quantitative profiles similar to what has been observed elsewhere. In previous work, sinusoidal glucose levels have been used to test the entrainment of islets while monitoring either [Ca] or insulin levels; using this newly developed system, we show unambiguously that oscillations of both [Ca] and insulin release are entrained to oscillatory glucose levels and that the temporal correlation of these are maintained throughout the experiment. It is expected that the developed analytical system can be expanded to investigate a number of other intracellular messengers in islets or other stimulus-secretion pathways in different cells.
Show less
Date Issued: 2016-11-01
Identifier: FSU_pmch_27712062, 10.1021/acs.analchem.6b02404, PMC5089909, 27712062, 27712062
Format: Citation

Title: Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.
Creator: McKenna, Joseph P, Dhumpa, Raghuram, Mukhitov, Nikita, Roper, Michael G, Bertram, Richard
Abstract/Description: Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with...
Show morePancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.
Show less
Date Issued: 2016-10-27
Identifier: FSU_pmch_27788129, 10.1371/journal.pcbi.1005143, PMC5082885, 27788129, 27788129, PCOMPBIOL-D-16-00306
Format: Citation

Title: Evidence for a Proapoptotic Role of Matrix Metalloproteinase-26 in Human Prostate Cancer Cells and Tissues.
Creator: Khamis, Zahraa I., Iczkowski, Kenneth A., Man, Yan-Gao, Bou-Dargham, Mayassa J., Sang, Qing-Xiang Amy
Abstract/Description: Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate...
Show moreMatrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression.
Show less
Date Issued: 2016
Identifier: FSU_libsubv1_wos_000366281500011, 10.7150/jca.13067
Format: Citation

Title: Evolution of Physical and Electrochemical Properties of Polypyrrole during Extended Oxidation.
Creator: Schlenoff, Joseph B., Xu, Hong
Abstract/Description: The charge storage capacity and electrical conductivity of polypyrrole are followed through regimes of chemically reversible and irreversible electroactivity. Overoxidation of polypyrrole occurs at potentials in excess of 0.7 V vs. a saturated calomel electrode (SCE), as demonstrated by cyclic voltammetry of thin films. Material loss from polymer films as they are overoxidized is determined by in situ quartz microbalance experiments. The potential window for reversible electrochemistry in...
Show moreThe charge storage capacity and electrical conductivity of polypyrrole are followed through regimes of chemically reversible and irreversible electroactivity. Overoxidation of polypyrrole occurs at potentials in excess of 0.7 V vs. a saturated calomel electrode (SCE), as demonstrated by cyclic voltammetry of thin films. Material loss from polymer films as they are overoxidized is determined by in situ quartz microbalance experiments. The potential window for reversible electrochemistry in polypyrrole is compared to that for other conducting polymers. Reflectance FTIR of thick films reveals that hydroxyl groups, followed by carbonyls, result from overoxidation.
Show less
Date Issued: 1992
Identifier: FSU_migr_chm_faculty_publications-0004, 10.1149/1.2221238
Format: Citation

Title: Exploring Background Mutational Processes To Decipher Cancer Genetic Heterogeneity.
Creator: Goncearenco, Alexander, Rager, Stephanie L., Li, Minghui, Sang, Qing-Xiang, Rogozin, Igor B., Panchenko, Anna R.
Abstract/Description: Much remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and...
Show moreMuch remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and underlying somatic cancer mutagenesis, analyzes mutational profiles of cancer samples, identifies the combinations of underlying mutagenic processes including those related to infidelity of DNA replication and repair machinery, and various other endogenous and exogenous mutagenic factors. As a result, the combination of mutagenic processes can be identified in any query sample with subsequent comparison to mutational profiles derived from malignant and benign samples. In addition, mutagen or cancer-specific mutational background models are applied to calculate expected DNA and protein site mutability to decouple relative contributions of mutagenesis and selection in carcinogenesis, thus elucidating the site-specific driving events in cancer. MutaGene is freely available at https://www.ncbi.nlm.nih.gov/projects/mutagene/.
Show less
Date Issued: 2017-07-03
Identifier: FSU_libsubv1_wos_000404427000078, 10.1093/nar/gkx367
Format: Citation

Title: Local heterogeneities in cardiac systems suppress turbulence by generating multi-armed rotors.
Creator: Zhang, Zhihui, Steinbock, Oliver
Abstract/Description: Ventricular fibrillation is an extremely dangerous cardiac arrhythmia that is linked to rotating waves of electric activity and chaotically moving vortex lines. These filaments can pin to insulating, cylindrical heterogeneities which swiftly become the new rotation backbone of the local wave field. For thin cylinders, the stabilized rotation is sufficiently fast to repel the free segments of the turbulent filament tangle and annihilate them at the system boundaries. The resulting global wave...
Show moreVentricular fibrillation is an extremely dangerous cardiac arrhythmia that is linked to rotating waves of electric activity and chaotically moving vortex lines. These filaments can pin to insulating, cylindrical heterogeneities which swiftly become the new rotation backbone of the local wave field. For thin cylinders, the stabilized rotation is sufficiently fast to repel the free segments of the turbulent filament tangle and annihilate them at the system boundaries. The resulting global wave pattern is periodic and highly ordered. Our cardiac simulations show that also thicker cylinders can establish analogous forms of tachycardia. This process occurs through the spontaneous formation of pinned multi-armed vortices. The observed number of wave arms N depends on the cylinder radius and is associated to stability windows that for N = 2, 3 partially overlap. For N =. 1, 2, we find a small gap in which the turbulence is removed but the pinned rotor shows complex temporal dynamics. The relevance of our findings to human cardiology are discussed in the context of vortex pinning to more complex-shaped anatomical features and remodeled myocardium.
Show less
Date Issued: 2016-05-12
Identifier: FSU_libsubv1_wos_000377191300001, 10.1088/1367-2630/18/5/053018
Format: Citation

Title: Linear and nonlinear dielectric theory for a slab: The connections between the phenomenological coefficients and the susceptibilities.
Creator: Fulton, Robert L.
Abstract/Description: The response of dielectric media to electromagnetic fields can be described by using either the response to a Maxwell field E or to an externally produced field E. The former response is measured by phenomenological (dielectric) coefficients and the latter by susceptibilities. With the purpose of clarifying some recent proposals, the connections between the linear (two-point) and first non-vanishing nonlinear (four-point) dielectric coefficients and the susceptibilities for media confined to...
Show moreThe response of dielectric media to electromagnetic fields can be described by using either the response to a Maxwell field E or to an externally produced field E. The former response is measured by phenomenological (dielectric) coefficients and the latter by susceptibilities. With the purpose of clarifying some recent proposals, the connections between the linear (two-point) and first non-vanishing nonlinear (four-point) dielectric coefficients and the susceptibilities for media confined to a slab are examined using a general procedure developed sometime ago. Unlike the relations found for correlations between a local polarization density and the integrated polarization densities (total polarizations), the point-point connections give rise to non-vanishing cross correlations between polarization densities which are parallel and perpendicular to the slab surfaces. The cross correlations in the two-point connections vanish when one polarization density is integrated to form the correlations between a local polarization density and the total polarization thereby losing angular information. The integrated parallel and perpendicular correlations remain different. When the four-point connections are similarly integrated most, but not all, cross correlations vanish. The angular correlations induced by the slab surfaces render the use of point-point correlations that are valid for isotropic media invalid for use in the integrated slab densities. In addition, the nonlinear fluctuations in the perpendicular components are drastically reduced relative to those in the parallel components or in isotropic media. Published by AIP Publishing.
Show less
Date Issued: 2016-08-28
Identifier: FSU_libsubv1_wos_000383875500008, 10.1063/1.4961225
Format: Citation

Title: Magnetic and Transport Properties of Electrochemically Oxidized Polyacetylene.
Creator: Reynolds, John, Schlenoff, Joseph B., Chien, James C. W.
Abstract/Description: The magnetic and transport properties of polyacetylene electrochemically oxidized in the presence of perchlorate ion have been determined. Room temperature dc conductivity is unaffected by doping between 10 -6
Show moreThe magnetic and transport properties of polyacetylene electrochemically oxidized in the presence of perchlorate ion have been determined. Room temperature dc conductivity is unaffected by doping between 10 -6 < y -< 10 -3~. A rapid conductivity increase occurs with increasing dopant level having a midpoint of transition at ca. y - 8 x 10-3 By comparison, the change in thermopower vs. y is sharper taking place within a tenfold increase in y with a midpoint at ca. y - 3 x 10 -3. The unparied spin concentrations remain constant as dopant concentration increases before the onset of a Dysonian lineshape at ca. y -= 10 -2. The results are interpreted as the melting of a glassy carrier state causing the sharp change of transport properties. A phase separation into metallic domains occurs at y = ca. 10 -~. Side reactions involving the electrolyte complicate the electrochemistry of po]yacetylene.
Show less
Date Issued: 1985
Identifier: FSU_migr_chm_faculty_publications-0008, 10.1149/1.2114027
Format: Citation

Title: Madness: A Multiresolution, Adaptive Numerical Environment For Scientific Simulation.
Creator: Harrison, Robert J., Beylkin, Gregory, Bischoff, Florian A., Calvin, Justus A., Fann, George I., Fosso-Tande, Jacob, Galindo, Diego, Hammond, Jeff R., Hartman-Baker, Rebecca,...
Show moreHarrison, Robert J., Beylkin, Gregory, Bischoff, Florian A., Calvin, Justus A., Fann, George I., Fosso-Tande, Jacob, Galindo, Diego, Hammond, Jeff R., Hartman-Baker, Rebecca, Hill, Judith C., Jia, Jun, Kottmann, Jakob S., Ou, M.-J. Yvonne, Pei, Junchen, Ratcliff, Laura E., Reuter, Matthew G., Richie-Halford, Adam C., Romero, Nichols A., Sekino, Hideo, Shelton, William A., Sundahl, Bryan E., Thornton, W. Scott, Valeev, Edward F., Vazquez-Mayagoitia, Alvaro, Vence, Nicholas, Yanai, Takeshi, Yokoi, Yukina
Show less
Abstract/Description: MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision that are based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code...
Show moreMADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision that are based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics.
Show less
Date Issued: 2016
Identifier: FSU_libsubv1_wos_000387347700008, 10.1137/15M1026171
Format: Citation

Title: Hysteresis and drift of spiral waves near heterogeneities: From chemical experiments to cardiac simulations.
Creator: Nakouzi, Elias, Totz, Jan Frederik, Zhang, Zhihui, Steinbock, Oliver, Engel, Harald
Abstract/Description: Dissipative patterns in excitable reaction-diffusion systems can be strongly affected by spatial heterogeneities. Using the photosensitive Belousov-Zhabotinsky reaction, we show a hysteresis effect in the transition between free and pinned spiral rotation. The latter state involves the rotation around a disk-shaped obstacle with an impermeable and inert boundary. The transition is controlled by changes in light intensity. For permeable heterogeneities of higher excitability, we observe spiral...
Show moreDissipative patterns in excitable reaction-diffusion systems can be strongly affected by spatial heterogeneities. Using the photosensitive Belousov-Zhabotinsky reaction, we show a hysteresis effect in the transition between free and pinned spiral rotation. The latter state involves the rotation around a disk-shaped obstacle with an impermeable and inert boundary. The transition is controlled by changes in light intensity. For permeable heterogeneities of higher excitability, we observe spiral drift along both linear and circular boundaries. Our results confirm recent theoretical predictions and, in the case of spiral drift, are further reproduced by numerical simulations with a modified Oregonator model. Additional simulations with a cardiac model show that orbital motion can also exist in anisotropic and three-dimensional systems.
Show less
Date Issued: 2016-02-04
Identifier: FSU_libsubv1_wos_000369439100004, 10.1103/PhysRevE.93.022203
Format: Citation

Title: Human Mesenchymal Stem Cells are Resistant to Paclitaxel by Adopting a Non-Proliferative Fibroblastic State.
Creator: Bosco, Dale, Kenworthy, Rachael, Zorio, Diego A. R., Sang, Qing-Xiang Amy
Abstract/Description: Human mesenchymal stem cell (hMSC) resistance to the apoptotic effects of chemotherapeutic drugs has been of major interest, as these cells can confer this resistance to tumor microenvironments. However, the effects of internalized chemotherapeutics upon hMSCs remain largely unexplored. In this study, cellular viability and proliferation assays, combined with different biochemical approaches, were used to investigate the effects of Paclitaxel exposure upon hMSCs. Our results indicate that...
Show moreHuman mesenchymal stem cell (hMSC) resistance to the apoptotic effects of chemotherapeutic drugs has been of major interest, as these cells can confer this resistance to tumor microenvironments. However, the effects of internalized chemotherapeutics upon hMSCs remain largely unexplored. In this study, cellular viability and proliferation assays, combined with different biochemical approaches, were used to investigate the effects of Paclitaxel exposure upon hMSCs. Our results indicate that hMSCs are highly resistant to the cytotoxic effects of Paclitaxel treatment, even though there was no detectable expression of the efflux pump P-glycoprotein, the usual means by which a cell resists Paclitaxel treatment. Moreover, Paclitaxel treatment induces hMSCs to adopt a non-proliferative fibroblastic state, as evidenced by changes to morphology, cellular markers, and a reduction in differentiation potential that is not directly coupled to the cytoskeletal effects of Paclitaxel. Taken together, our results show that Paclitaxel treatment does not induce apoptosis in hMSCs, but does induce quiescence and phenotypic changes.
Show less
Date Issued: 2015-06-01
Identifier: FSU_libsubv1_scholarship_submission_1475156513, 10.1371/journal.pone.0128511
Format: Citation

$Hermetic Sample Housing for X-ray Diffraction Studies$

Title: Hermetic Sample Housing for X-ray Diffraction Studies.
Creator: Schlenoff, Joseph B., Rink, W. Jack, Mathias, H.
Abstract/Description: A portable sample housing has been constructed for room-temperature powder geometry X-ray diffraction analysis of samples that are air or moisture sensitive. The housing can be easily handled in a glovebox, providing a means for direct loading and X-ray measurements on samples that should not be exposed to air or moisture after preparation. Its design allows adaptation to various makes of diffractometer that are limited to flat sample geometry. The design offers several improvements over...
Show moreA portable sample housing has been constructed for room-temperature powder geometry X-ray diffraction analysis of samples that are air or moisture sensitive. The housing can be easily handled in a glovebox, providing a means for direct loading and X-ray measurements on samples that should not be exposed to air or moisture after preparation. Its design allows adaptation to various makes of diffractometer that are limited to flat sample geometry. The design offers several improvements over existing technology, including the accommodation of large-area thin films and single crystals. Sample preparation and alignment in the X-ray beam have been found to be easy and efficient. The two-layer X-ray window of the device reduces the diffracted intensity by 40%, without any change in the relative intensities of the peaks in the spectrum.
Show less
Date Issued: 1993
Identifier: FSU_migr_chm_faculty_publications-0012, 10.1107/S0021889893013822
Format: Citation

Title: Kv1.3 Contains an Alternative C-Terminal ER Exit Motif and is Recruited into COPII Vesicles by Sec24a.
Creator: Stagg, Scott, Spear, John M., Koborssy, Dolly Al, Schwartz, Austin B, Johnson, Adam J, Audhya, Anjon, Fadool, Debra A
Abstract/Description: Background Potassium channels play a fundamental role in resetting the resting membrane potential of excitable cells. Determining the intracellular trafficking and localization mechanisms of potassium channels provides a platform to fully characterize their maturation and functionality. Previous investigations have discovered residues or motifs that exist in their primary structure, which directly promote anterograde trafficking of nascent potassium channels. Recently, a non-conical di-acidic...
Show moreBackground Potassium channels play a fundamental role in resetting the resting membrane potential of excitable cells. Determining the intracellular trafficking and localization mechanisms of potassium channels provides a platform to fully characterize their maturation and functionality. Previous investigations have discovered residues or motifs that exist in their primary structure, which directly promote anterograde trafficking of nascent potassium channels. Recently, a non-conical di-acidic motif (E483/484) has been discovered in the C-terminus of the mammalian homologue of the Shaker voltage-gated potassium channel subfamily member 3 (Kv1.3), and was shown to disrupt the anterograde trafficking of Kv1.3. Results We have further investigated the intracellular trafficking requirements of Kv1.3 both in vivo and in vitro. First, three alternative C-terminal acidic residues, E443, E445, E447 were probed for their involvement within the early secretory pathway of Kv1.3. Single point (E443A, E445A, and E447A) and double point (E443A-E445A, E445A-E447A) mutations exhibited no significant changes in their endoplasmic reticulum (ER) retention. The triple point mutant E443A-E445A-E447A displayed a modest ER retention while deletion of the C-terminus showed dramatic ER retention. Second, we demonstrate in vivo the requirement for the Sec24a isoform to confer anterograde trafficking using a siRNA knockdown assay. Third, we show in vitro the association of recombinantly expressed Kv1.3 and Sec24a proteins. Conclusion These results expand upon previous studies aimed at deciphering the Kv1.3 secretory trafficking mechanisms and further show in vitro evidence of the association between Kv1.3 and the COPII cargo adaptor subunit isoform Sec24a.
Show less
Date Issued: 2015-07-10
Identifier: FSU_libsubv1_scholarship_submission_1475170159, 10.1186/s12858-015-0045-6
Format: Citation

Title: Human Coronary Artery Smooth Muscle Cell Responses to Bioactive Polyelectrolyte Multilayer Interfaces.
Creator: Newcomer, Robert, Moussallem, Maroun, Keller, Thomas C. S., Schlenoff, Joseph B., Sang, Qing-Xiang
Abstract/Description: Under normal physiological conditions, mature human coronary artery smooth muscle cells (hCASMCs) exhibit a "contractile" phenotype marked by low rates of proliferation and protein synthesis, but these cells possess the remarkable ability to dedifferentiate into a "synthetic" phenotype when stimulated by conditions of pathologic stress. A variety of polyelectrolyte multilayer (PEMU) films are shown here to exhibit bioactive properties that induce distinct responses from cultured hCASMCs....
Show moreUnder normal physiological conditions, mature human coronary artery smooth muscle cells (hCASMCs) exhibit a "contractile" phenotype marked by low rates of proliferation and protein synthesis, but these cells possess the remarkable ability to dedifferentiate into a "synthetic" phenotype when stimulated by conditions of pathologic stress. A variety of polyelectrolyte multilayer (PEMU) films are shown here to exhibit bioactive properties that induce distinct responses from cultured hCASMCs. Surfaces terminated with Nafion or poly(styrenesulfonic acid) (PSS) induce changes in the expression and organization of intracellular proteins, while a hydrophilic, zwitterionic copolymer of acrylic acid and 3-[2-(acrylamido)-ethyl dimethylammonio] propane sulfonate (PAA-co-PAEDAPS) is resistant to cell attachment and suppresses the formation of key cytoskeletal components. Differential expression of heat shock protein 90 and actin is observed, in terms of both their magnitude and cellular localization, and distinct cytoplasmic patterns of vimentin are seen. The ionophore A23187 induces contraction in confluent hCASMC cultures on Nafion-terminated surfaces. These results demonstrate that PEMU coatings exert direct effects on the cytoskeletal organization of attaching hCASMCs, impeding growth in some cases, inducing changes consistent with phenotypic modulation in others, and suggesting potential utility for PEMU surfaces as a coating for coronary artery stents and other implantable medical devices.
Show less
Date Issued: 2011
Identifier: FSU_migr_chm_faculty_publications-0011, 10.4061/2011/854068
Format: Citation

Title: Biomimetic Mineral Self-organization From Silica-rich Spring Waters.
Creator: Manuel Garcia-Ruiz, Juan, Nakouzi, Elias, Kotopoulou, Electra, Tamborrino, Leonardo, Steinbock, Oliver
Abstract/Description: Purely inorganic reactions of silica, metal carbonates, and metal hydroxides can produce self-organized complex structures that mimic the texture of biominerals, the morphology of primitive organisms, and that catalyze prebiotic reactions. To date, these fascinating structures have only been synthesized using model solutions. We report that mineral self-assembly can be also obtained from natural alkaline silica-rich water deriving from serpentinization. Specifically, we demonstrate three main...
Show morePurely inorganic reactions of silica, metal carbonates, and metal hydroxides can produce self-organized complex structures that mimic the texture of biominerals, the morphology of primitive organisms, and that catalyze prebiotic reactions. To date, these fascinating structures have only been synthesized using model solutions. We report that mineral self-assembly can be also obtained from natural alkaline silica-rich water deriving from serpentinization. Specifically, we demonstrate three main types ofmineral self-assembly: (i) nanocrystalline biomorphs of barium carbonate and silica, (ii) mesocrystals and crystal aggregates of calcium carbonate with complex biomimetic textures, and (iii) osmosis-driven metal silicate hydrate membranes that form compartmentalized, hollow structures. Our results suggest that silica-induced mineral self-assembly could have been a common phenomenon in alkaline environments of early Earth and Earth-like planets.
Show less
Date Issued: 2017-03
Identifier: FSU_libsubv1_wos_000397044000036, 10.1126/sciadv.1602285
Format: Citation

Title: Bis[N-alkyl-NN-di(2-pyridylmethyl)amine]zinc(II) perchlorates display cis-facial stereochemistry in solid state and solution.
Creator: Zhu, Lei, Simmons, J., Yuan, Zhao, Daykin, Kirsten, Nguyen, Brian, Clark, Ronald, Shatruk, Michael
Abstract/Description: N-Alkyl-N,N-di(2-pyridylmethyl)amines are ligands commonly used by supramolecular chemists in molecular recognition and sensing applications. The metal coordination complexes of these ligands, in particular those with 2:1 (ligand:metal) molar ratio, have not been sufficiently characterised in solution. In this work, bis[N-alkyl-N,N-di(2-pyridylmethyl)amine]zinc(II) perchlorates are characterised in both solid and solution phases, using X-ray crystallography and NMR spectroscopy, respectively....
Show moreN-Alkyl-N,N-di(2-pyridylmethyl)amines are ligands commonly used by supramolecular chemists in molecular recognition and sensing applications. The metal coordination complexes of these ligands, in particular those with 2:1 (ligand:metal) molar ratio, have not been sufficiently characterised in solution. In this work, bis[N-alkyl-N,N-di(2-pyridylmethyl)amine]zinc(II) perchlorates are characterised in both solid and solution phases, using X-ray crystallography and NMR spectroscopy, respectively. Only the cis-facial stereoisomer is observed. Density functional theory calculations support the thermodynamic preference for this stereochemistry, as in one representative case the gas phase energy of the cis-facial configuration is lower than those of the trans-facial and meridional configurations by 4.0 and 4.5 kcal/mol, respectively.
Show less
Date Issued: 2013
Identifier: FSU_migr_chm_faculty_publications-0013, 10.1080/10610278.2013.844816
Format: Citation

Title: Comment on "Nonlinear dielectric response of polar liquids" [J. Chem. Phys. 142, 244502 (2015)].
Creator: Fulton, Robert L.
Date Issued: 2016-02-28
Identifier: FSU_libsubv1_wos_000371618800058, 10.1063/1.4942353
Format: Citation

Title: Overcoming The Crystallization And Designability Issues In The Ultrastable Zirconium Phosphonate Framework System.
Creator: Zheng, Tao, Yang, Zaixing, Gui, Daxiang, Liu, Zhiyong, Wang, Xiangxiang, Dai, Xing, Liu, Shengtang, Zhang, Linjuan, Gao, Yang, Chen, Lanhua, Sheng, Daopeng, Wang, Yanlong, Diwu,...
Show moreZheng, Tao, Yang, Zaixing, Gui, Daxiang, Liu, Zhiyong, Wang, Xiangxiang, Dai, Xing, Liu, Shengtang, Zhang, Linjuan, Gao, Yang, Chen, Lanhua, Sheng, Daopeng, Wang, Yanlong, Diwu, Juan, Wang, Jianqiang, Zhou, Ruhong, Chai, Zhifang, Albrecht-Schmitt, Thomas E., Wang, Shuao
Show less
Abstract/Description: Metal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. Herein, we overcome these challenges and obtain single...
Show moreMetal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. Herein, we overcome these challenges and obtain single crystals of three zirconium phosphonates that are suitable for structural analysis. These compounds are built by previously unknown isolated zirconium phosphonate clusters and exhibit combined high porosity and ultrastability even in fuming acids. SZ-2 possesses the largest void volume recorded in zirconium phosphonates and SZ-3 represents the most porous crystalline zirconium phosphonate and the only porous MOF material reported to survive in aqua regia. SZ-2 and SZ-3 can effectively remove uranyl ions from aqueous solutions over a wide pH range, and we have elucidated the removal mechanism.
Show less
Date Issued: 2017-05-30
Identifier: FSU_libsubv1_wos_000402303600001, 10.1038/ncomms15369
Format: Citation

Title: On the origin of high ionic conductivity in Na-doped SrSiO3.
Creator: Chien, Po-Hsiu, Jee, Youngseok, Huang, Chen, Dervisoglu, Riza, Hung, Ivan, Gan, Zhehong, Huang, Kevin, Hu, Yan-Yan
Abstract/Description: Understanding the local structure and ion dynamics is at the heart of ion conductor research. This paper reports on high-resolution solid-state Si-29, Na-23, and O-17 NMR investigation of the structure, chemical composition, and ion dynamics of a newly discovered fast ion conductor, Na-doped SrSiO3, which exhibited a much higher ionic conductivity than most of current oxide ion conductors. Quantitative analyses reveal that with a small dose (10 mol% Na doping, phase separation occurs, leading...
Show moreUnderstanding the local structure and ion dynamics is at the heart of ion conductor research. This paper reports on high-resolution solid-state Si-29, Na-23, and O-17 NMR investigation of the structure, chemical composition, and ion dynamics of a newly discovered fast ion conductor, Na-doped SrSiO3, which exhibited a much higher ionic conductivity than most of current oxide ion conductors. Quantitative analyses reveal that with a small dose (<10 mol%) of Na, the doped Na integrates into the SrSiO3 structure to form NaxSr1-xSiO3-0.5x, and with >10 mol% Na doping, phase separation occurs, leading to the formation of an amorphous phase beta-Na2Si2O5 and a crystalline Sr-rich phase. Variable-temperature Na-23 and O-17 magic-angle-spinning NMR up to 618 degrees C have shown significant changes in Na ion dynamics at high temperatures but little oxide ion motion, suggesting that Na ions are responsible for the observed high ionic conductivity. In addition, beta-Na2Si2O5 starts to crystallize at temperatures higher than 480 degrees C with prolonged heating, resulting in reduction in Na+ motion, and thus degradation of ionic conductivity. This study has contributed critical evidence to the understanding of ionic conduction in Na-doped SrSiO3 and demonstrated that multinuclear high-resolution and high-temperature solid-state NMR is a uniquely useful tool for investigating ion conductors at their operating conditions.
Show less
Date Issued: 2016
Identifier: FSU_libsubv1_wos_000377262200023, 10.1039/c5sc04270d
Format: Citation

Title: Pinning Of Scroll Waves To Flat And Highly Branched Unexcitable Heterogeneities.
Creator: Mahanta, Dhriti, Dutta, Sumana, Steinbock, Oliver
Abstract/Description: System heterogeneities such as organelles, cells, and anatomical features strongly affect nonlinear wave patterns in biological systems. These effects are more readily studied in otherwise homogeneous chemical reactions that allow the introduction of tailored structures. Following this approach, we investigate the dynamics of three-dimensional excitation vortices pinned to inert sheets with circular holes arranged on a hexagonal lattice. Experimentswith theBelousov-Zhabotinsky reaction and...
Show moreSystem heterogeneities such as organelles, cells, and anatomical features strongly affect nonlinear wave patterns in biological systems. These effects are more readily studied in otherwise homogeneous chemical reactions that allow the introduction of tailored structures. Following this approach, we investigate the dynamics of three-dimensional excitation vortices pinned to inert sheets with circular holes arranged on a hexagonal lattice. Experimentswith theBelousov-Zhabotinsky reaction and numerical simulations of an excitable reaction-diffusion model reveal vortex pinning that circumvents the rapid collapse of free vortex rings. The pinned scroll waves are affected by the topological mismatch between their looplike rotation backbone and the branched pinning structure. Depending on the initial condition, a multitude of stable vortex states exist, all ofwhich obey topological constraints, suggesting spinlike states for the involved obstacle holes.
Show less
Date Issued: 2017-03-07
Identifier: FSU_libsubv1_wos_000396039200010, 10.1103/PhysRevE.95.032204
Format: Citation

Title: Physical properties of the Ce2MAl7Ge4 heavy-fermion compounds (M = Co, Ir, Ni, Pd).
Creator: Ghimire, N. J., Cary, S. K., Eley, S., Wakeham, N. A., Rosa, P. F. S., Albrecht-Schmitt, T., Lee, Y., Janoschek, M., Brown, C. M., Civale, L., Thompson, J. D., Ronning, F.,...
Show moreGhimire, N. J., Cary, S. K., Eley, S., Wakeham, N. A., Rosa, P. F. S., Albrecht-Schmitt, T., Lee, Y., Janoschek, M., Brown, C. M., Civale, L., Thompson, J. D., Ronning, F., Bauer, E. D.
Show less
Abstract/Description: We report the synthesis, crystal structure, and characterization by means of single-crystal x-ray diffraction, neutron powder diffraction, and magnetic, thermal, and transport measurements of the new heavy-fermion compounds Ce2MAl7Ge4 (M = Co, Ir, Ni, Pd). These compounds crystallize in a noncentrosymmetric tetragonal space group P (4) over bar2(1)m, consisting of layers of square nets of Ce atoms separated by Ge-Al and M-Al-Ge blocks. Ce2CoAl7Ge4, Ce2IrAl7Ge4, and Ce2NiAl7Ge4 order...
Show moreWe report the synthesis, crystal structure, and characterization by means of single-crystal x-ray diffraction, neutron powder diffraction, and magnetic, thermal, and transport measurements of the new heavy-fermion compounds Ce2MAl7Ge4 (M = Co, Ir, Ni, Pd). These compounds crystallize in a noncentrosymmetric tetragonal space group P (4) over bar2(1)m, consisting of layers of square nets of Ce atoms separated by Ge-Al and M-Al-Ge blocks. Ce2CoAl7Ge4, Ce2IrAl7Ge4, and Ce2NiAl7Ge4 order magnetically below T-M = 1.8, 1.6, and 0.8 K, respectively. There is no evidence of magnetic ordering in Ce2PdAl7Ge4 down to 0.4 K. The small amount of entropy released in the magnetic state of Ce2MAl7Ge4 (M = Co, Ir, Ni) and the reduced specific heat jump at TM suggest a strong Kondo interaction in these materials. Ce2PdAl7Ge4 shows non-Fermi liquid behavior, possibly due to the presence of a nearby quantum critical point.
Show less
Date Issued: 2016-05-23
Identifier: FSU_libsubv1_wos_000376638200005, 10.1103/PhysRevB.93.205141
Format: Citation

Title: Personalized Chemotherapy Selection For Breast Cancer Using Gene Expression Profiles.
Creator: Yu, Kaixian, Sang, Qing-Xiang Amy, Lung, Pei-Yau, Tan, Winston, Lively, Ty, Sheffield, Cedric, Bou-Dargham, Mayassa J., Liu, Jun S., Zhang, Jinfeng
Abstract/Description: Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to...
Show moreChoosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens.
Show less
Date Issued: 2017-03-03
Identifier: FSU_libsubv1_wos_000395286700001, 10.1038/srep43294
Format: Citation

Title: Numerical Simulation of the Cyclic Voltammogram of Polyacetylene.
Creator: Diess, E., Haas, O., Schlenoff, Joseph B.
Abstract/Description: The measured cyclic voltammogram of a polyacety]ene-coated electrode bathed in an electrolyte solution was simulated numerically for various scan rates. The model used accounts for a modified Butler-Vo]mer-type heterogeneous kinetics at the electrode surface including a lateral interaction term which effects the observed hysteresis behavior. Within the polymer an electron flux obeying Ohm's law as well as electrolyte diffusion and migration is considered and Poisson's equation holds for...
Show moreThe measured cyclic voltammogram of a polyacety]ene-coated electrode bathed in an electrolyte solution was simulated numerically for various scan rates. The model used accounts for a modified Butler-Vo]mer-type heterogeneous kinetics at the electrode surface including a lateral interaction term which effects the observed hysteresis behavior. Within the polymer an electron flux obeying Ohm's law as well as electrolyte diffusion and migration is considered and Poisson's equation holds for electroneutrality. Donnan partition kinetics describes the flux and potential at the interface between the polymer and diffusion layer. Electrolyte diffusion is considered in the diffusion layer.
Show less
Date Issued: 1995
Identifier: FSU_migr_chm_faculty_publications-0003, 10.1149/1.2049971
Format: Citation

Title: Biochemical and biophysical investigations of the interaction between human glucokinase and pro-apoptotic BAD.
Creator: Rexford, Alix, Zorio, Diego A R, Miller, Brian G
Abstract/Description: The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method...
Show moreThe glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD. Consistent with published reports, recombinant BAD displays high affinity for Bcl-xL (KD = 7 nM), and phosphorylation of BAD at S118, within the BH3 domain, abolishes this interaction. Unexpectedly, we do not detect association of recombinant, full-length BAD with recombinant human pancreatic GCK over a range of protein concentrations using various biochemical methods including size-exclusion chromatography, chemical cross-linking, analytical ultracentrifugation, and isothermal titration calorimetry. Furthermore, fluorescence polarization assays and isothermal titration calorimetry detect no direct interaction between GCK and BAD BH3 peptides. Kinetic characterization of GCK in the presence of high concentrations of recombinant BAD show modest (<15%) increases in GCK activity, observable only at glucose concentrations well below the K0.5 value. GCK activity is unaffected by BAD BH3 peptides. These results raise questions as to the mechanism of action of stapled peptide analogs modeled after the BAD BH3 domain, which reportedly enhance the Vmax value of GCK and stimulate insulin release in BAD-deficient islets. Based on our results, we postulate that the BAD:GCK interaction, and any resultant regulatory effect(s) upon GCK activity, requires the participation of additional members of the mitochondrial complex.
Show less
Date Issued: 2017-02-09
Identifier: FSU_pmch_28182770, 10.1371/journal.pone.0171587, PMC5300155, 28182770, 28182770, PONE-D-16-49439
Format: Citation

Title: A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis.
Creator: Bosco, Dale B, Roycik, Mark D, Jin, Yonghao, Schwartz, Martin A, Lively, Ty J, Zorio, Diego A R, Sang, Qing-Xiang Amy
Abstract/Description: Development of adipose tissue requires the differentiation of less specialized cells, such as human mesenchymal stem cells (hMSCs), into adipocytes. Since matrix metalloproteinases (MMPs) play critical roles in the cell differentiation process, we conducted investigations to determine if a novel mercaptosulfonamide-based MMP inhibitor (MMPI), YHJ-7-52, could affect hMSC adipogenic differentiation and lipid accumulation. Enzyme inhibition assays, adipogenic differentiation experiments, and...
Show moreDevelopment of adipose tissue requires the differentiation of less specialized cells, such as human mesenchymal stem cells (hMSCs), into adipocytes. Since matrix metalloproteinases (MMPs) play critical roles in the cell differentiation process, we conducted investigations to determine if a novel mercaptosulfonamide-based MMP inhibitor (MMPI), YHJ-7-52, could affect hMSC adipogenic differentiation and lipid accumulation. Enzyme inhibition assays, adipogenic differentiation experiments, and quantitative PCR methods were employed to characterize this inhibitor and determine its effect upon adipogenesis. YHJ-7-52 reduced lipid accumulation in differentiated cells by comparable amounts as a potent hydroxamate MMPI, GM6001. However, YHJ-7-82, a non-inhibitory structural analog of YHJ-7-52, in which the zinc-binding thiol group is replaced by a hydroxyl group, had no effect on adipogenesis. The two MMPIs (YHJ-7-52 and GM6001) were also as effective in reducing lipid accumulation in differentiated cells as T0070907, an antagonist of peroxisome-proliferator activated receptor gamma (PPAR-gamma), at a similar concentration. PPAR-gamma is a typical adipogenic marker and a key regulatory protein for the transition of preadiopocyte to adipocyte. Moreover, MMP inhibition was able to suppress lipid accumulation in cells co-treated with Troglitazone, a PPAR-gamma agonist. Our results indicate that MMP inhibitors may be used as molecular tools for adipogenesis and obesity treatment research.
Show less
Date Issued: 2017-02-24
Identifier: FSU_pmch_28234995, 10.1371/journal.pone.0172925, PMC5325569, 28234995, 28234995, PONE-D-16-48797
Format: Citation

Title: Biomimetic mineral self-organization from silica-rich spring waters.
Creator: García-Ruiz, Juan Manuel, Nakouzi, Elias, Kotopoulou, Electra, Tamborrino, Leonardo, Steinbock, Oliver
Abstract/Description: Purely inorganic reactions of silica, metal carbonates, and metal hydroxides can produce self-organized complex structures that mimic the texture of biominerals, the morphology of primitive organisms, and that catalyze prebiotic reactions. To date, these fascinating structures have only been synthesized using model solutions. We report that mineral self-assembly can be also obtained from natural alkaline silica-rich water deriving from serpentinization. Specifically, we demonstrate three main...
Show morePurely inorganic reactions of silica, metal carbonates, and metal hydroxides can produce self-organized complex structures that mimic the texture of biominerals, the morphology of primitive organisms, and that catalyze prebiotic reactions. To date, these fascinating structures have only been synthesized using model solutions. We report that mineral self-assembly can be also obtained from natural alkaline silica-rich water deriving from serpentinization. Specifically, we demonstrate three main types of mineral self-assembly: (i) nanocrystalline biomorphs of barium carbonate and silica, (ii) mesocrystals and crystal aggregates of calcium carbonate with complex biomimetic textures, and (iii) osmosis-driven metal silicate hydrate membranes that form compartmentalized, hollow structures. Our results suggest that silica-induced mineral self-assembly could have been a common phenomenon in alkaline environments of early Earth and Earth-like planets.
Show less
Date Issued: 2017-03-17
Identifier: FSU_pmch_28345049, 10.1126/sciadv.1602285, PMC5357132, 28345049, 28345049, 1602285
Format: Citation

Title: Cas6 processes tight and relaxed repeat RNA via multiple mechanisms: A hypothesis..
Creator: Sefcikova, Jana, Roth, Mitchell, Yu, Ge, Li, Hong
Abstract/Description: RNA molecules are flexible yet foldable. Proteins must cope with this structural duality when forming biologically active complexes with RNA. Recent studies of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-mediated RNA immunity illustrate some remarkable mechanisms with which proteins interact with RNA. Currently known structures of CRISPR-Cas6 endoribonucleases bound with RNA suggest a conserved protein recognition mechanism mediated by RNA stem-loops. However, a...
Show moreRNA molecules are flexible yet foldable. Proteins must cope with this structural duality when forming biologically active complexes with RNA. Recent studies of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-mediated RNA immunity illustrate some remarkable mechanisms with which proteins interact with RNA. Currently known structures of CRISPR-Cas6 endoribonucleases bound with RNA suggest a conserved protein recognition mechanism mediated by RNA stem-loops. However, a survey of CRISPR RNA reveals that many repeats either lack a productive stem-loop (Relaxed) or possess stable but inhibitory structures (Tight), which raises the question of how the enzyme processes structurally diverse RNA. In reviewing recent literature, we propose a bivalent trapping and an unwinding mechanism for CRISPR-Cas6 to interact with the Relaxed and the Tight repeat RNA, respectively. Both mechanisms aim to create an identical RNA conformation at the cleavage site for accurate processing.
Show less
Date Issued: 2017-06-01
Identifier: FSU_pmch_28493337, 10.1002/bies.201700019, PMC5699886, 28493337, 28493337
Format: Citation

Title: Beyond Structural Biology to Functional Biology: Solid-State NMR Experiments and Strategies for Understanding the M2 Proton Channel Conductance..
Creator: Qin, Huajun, Miao, Yimin, Cross, Timothy A, Fu, Riqiang
Abstract/Description: In terms of structural biology, solid-state NMR experiments and strategies have been well established for resonance assignments, leading to the determination of three-dimensional structures of insoluble membrane proteins in their native-like environment. It is also known that NMR has the unique capabilities to characterize structure-function relationships of membrane-bound biological systems beyond structural biology. Here, we report on solid-state NMR experiments and strategies for...
Show moreIn terms of structural biology, solid-state NMR experiments and strategies have been well established for resonance assignments, leading to the determination of three-dimensional structures of insoluble membrane proteins in their native-like environment. It is also known that NMR has the unique capabilities to characterize structure-function relationships of membrane-bound biological systems beyond structural biology. Here, we report on solid-state NMR experiments and strategies for extracting functional activities on a sub-millisecond time scale. Specifically, we use the His37-labeled full length M2 (M2FL) protein of the Influenza A virus embedded in synthetic lipid bilayers as an example to characterize the proton conduction mechanism and kinetics. The integral membrane M2 protein assembles as a tetrameric bundle to form a proton-conducting channel that is activated by low pH and is essential for the viral lifecycle. Our results present convincing evidence for the formation of imidazolium-imidazole hydrogen bonds in the His37 tetrad at low pH and that these hydrogen bonds have a low barrier that facilitates the proton conduction mechanism in the M2FL protein. Moreover, it has been possible to measure hydronium ion exchange between water and the protons in the His37 NH bonds based on chemical exchange spectroscopy with minimized spin diffusion. The results identify an exchange rate constant of ∼4000 s for pH 5.8 at -10 °C.
Show less
Date Issued: 2017-05-11
Identifier: FSU_pmch_28425709, 10.1021/acs.jpcb.7b02468, PMC5842430, 28425709, 28425709
Format: Citation

Title: Upregulation of minichromosome maintenance complex component 3 during epithelial-to-mesenchymal transition in human prostate cancer.
Creator: Stewart, Paul A, Khamis, Zahraa I, Zhau, Haiyen E, Duan, Peng, Li, Quanlin, Chung, Leland W K, Sang, Qing-Xiang Amy
Abstract/Description: Metastasis is often associated with epithelial-to-mesenchymal transition (EMT). To understand the molecular mechanisms of this process, we conducted proteomic analysis of androgen-repressed cancer of the prostate (ARCaP), an experimental model of metastatic human prostate cancer. The protein signatures of epithelial (ARCaPE) and mesenchymal (ARCaPM) cells were consistent with their phenotypes. Importantly, the expression of mini-chromosome maintenance 3 (MCM3) protein, a crucial subunit of...
Show moreMetastasis is often associated with epithelial-to-mesenchymal transition (EMT). To understand the molecular mechanisms of this process, we conducted proteomic analysis of androgen-repressed cancer of the prostate (ARCaP), an experimental model of metastatic human prostate cancer. The protein signatures of epithelial (ARCaPE) and mesenchymal (ARCaPM) cells were consistent with their phenotypes. Importantly, the expression of mini-chromosome maintenance 3 (MCM3) protein, a crucial subunit of DNA helicase, was significantly higher in ARCaPM cells than that of ARCaPE cells. This increased MCM3 protein expression level was verified using Western blot analysis of the ARCaP cell lineages. Furthermore, immunohistochemical analysis of MCM3 protein levels in human prostate tissue specimens showed elevated expression in bone metastasis and advanced human prostate cancer tissue samples. Subcutaneous injection experiments using ARCaPE and ARCaPM cells in a mouse model also revealed increased MCM3 protein levels in mesenchymal-derived tumors. This study identifies MCM3 as an upregulated molecule in mesenchymal phenotype of human prostate cancer cells and advanced human prostate cancer specimens, suggesting MCM3 may be a new potential drug target for prostate cancer treatment.
Show less
Date Issued: 2017-06-13
Identifier: FSU_pmch_28424404, 10.18632/oncotarget.16835, PMC5503607, 28424404, 28424404, 16835
Format: Citation

Title: The roles of surface chemistry, dissolution rate, and delivered dose in the cytotoxicity of copper nanoparticles.
Creator: Shi, Miao, de Mesy Bentley, Karen L, Palui, Goutam, Mattoussi, Hedi, Elder, Alison, Yang, Hong
Abstract/Description: The understanding of nanoparticle (NP) cytotoxicity is challenging because of incomplete information about physicochemical changes particles undergo once they come into contact with biological fluids. It is therefore essential to characterize changes in NP properties to better understand their biological fate and effects in mammalian cells. In this paper, we present a study on the effect of particle surface oxidation and dissolution rates of Cu NPs. Particle dissolution, cell-associated Cu...
Show moreThe understanding of nanoparticle (NP) cytotoxicity is challenging because of incomplete information about physicochemical changes particles undergo once they come into contact with biological fluids. It is therefore essential to characterize changes in NP properties to better understand their biological fate and effects in mammalian cells. In this paper, we present a study on the effect of particle surface oxidation and dissolution rates of Cu NPs. Particle dissolution, cell-associated Cu doses, and oxidative stress responses in A549 luciferase reporter cells were examined for Cu NPs modified with mercaptocarboxylic acids with different carbon chain lengths and a thiotic acid appended-PEG ligand (TA). We found that these Cu NPs released ionic species together with small particles upon oxidation and that surface chemistry influenced the morphology and dissolution rate. The dissolution rate was also shown to impact both the cellular Cu dosimetry and associated oxidative stress responses. The convergent results from dissolution and dosimetry measurements demonstrate that both intracellular and extracellular (i.e., NP uptake-independent) release of ionic species from Cu NPs greatly affect the cytotoxicity.
Show less
Date Issued: 2017-04-06
Identifier: FSU_pmch_28327771, 10.1039/c6nr09102d, PMC5482280, 28327771, 28327771
Format: Citation

Title: Exploring background mutational processes to decipher cancer genetic heterogeneity.
Creator: Goncearenco, Alexander, Rager, Stephanie L, Li, Minghui, Sang, Qing-Xiang, Rogozin, Igor B, Panchenko, Anna R
Abstract/Description: Much remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and...
Show moreMuch remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and underlying somatic cancer mutagenesis, analyzes mutational profiles of cancer samples, identifies the combinations of underlying mutagenic processes including those related to infidelity of DNA replication and repair machinery, and various other endogenous and exogenous mutagenic factors. As a result, the combination of mutagenic processes can be identified in any query sample with subsequent comparison to mutational profiles derived from malignant and benign samples. In addition, mutagen or cancer-specific mutational background models are applied to calculate expected DNA and protein site mutability to decouple relative contributions of mutagenesis and selection in carcinogenesis, thus elucidating the site-specific driving events in cancer. MutaGene is freely available at https://www.ncbi.nlm.nih.gov/projects/mutagene/.
Show less
Date Issued: 2017-07-03
Identifier: FSU_pmch_28472504, 10.1093/nar/gkx367, PMC5793731, 28472504, 28472504, 3796332
Format: Citation

Title: ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice..
Creator: Weerasekera, Lakshini, Rudnicka, Caroline, Sang, Qing-Xiang, Curran, Joanne E, Johnson, Matthew P, Moses, Eric K, Göring, Harald H H, Blangero, John, Hricova, Jana, Schlaich,...
Show moreWeerasekera, Lakshini, Rudnicka, Caroline, Sang, Qing-Xiang, Curran, Joanne E, Johnson, Matthew P, Moses, Eric K, Göring, Harald H H, Blangero, John, Hricova, Jana, Schlaich, Markus, Matthews, Vance B
Show less
Abstract/Description: Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood...
Show moreObesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood mononuclear cells from a well-characterised human cohort. Secondly, we examined the expression of ADAM19 in liver and gonadal white adipose tissue using an in vivo diet induced obesity mouse model. Finally, we investigated the effect of neutralising ADAM19 on diet induced weight gain, insulin resistance in vivo, and liver TNF- levels. Significantly, we show that, in humans, ADAM19 strongly correlates with parameters of the metabolic syndrome, particularly BMI, relative fat, HOMA-IR, and triglycerides. Furthermore, we identified that ADAM19 expression was markedly increased in the liver and gonadal white adipose tissue of obese and T2D mice. Excitingly, we demonstrate in our diet induced obesity mouse model that neutralising ADAM19 therapy results in weight loss, improves insulin sensitivity, and reduces liver TNF- levels. Our novel data suggest that ADAM19 is pro-obesogenic and enhances insulin resistance. Therefore, neutralisation of ADAM19 may be a potential therapeutic approach to treat obesity and T2D.
Show less
Date Issued: 2017-01-01
Identifier: FSU_pmch_28265178, 10.1155/2017/7281986, PMC5318628, 28265178, 28265178
Format: Citation

Title: The Impact of DNA Topology and Guide Length on Target Selection by a Cytosine-Specific Cas9.
Creator: Tsui, Tsz Kin Martin, Hand, Travis H, Duboy, Emily C, Li, Hong
Abstract/Description: Cas9 is an RNA-guided DNA cleavage enzyme being actively developed for genome editing and gene regulation. To be cleaved by Cas9, a double stranded DNA, or the protospacer, must be complementary to the guide region, typically 20-nucleotides in length, of the Cas9-bound guide RNA, and adjacent to a short Cas9-specific element called Protospacer Adjacent Motif (PAM). Understanding the correct juxtaposition of the protospacer- and PAM-interaction with Cas9 will enable development of versatile...
Show moreCas9 is an RNA-guided DNA cleavage enzyme being actively developed for genome editing and gene regulation. To be cleaved by Cas9, a double stranded DNA, or the protospacer, must be complementary to the guide region, typically 20-nucleotides in length, of the Cas9-bound guide RNA, and adjacent to a short Cas9-specific element called Protospacer Adjacent Motif (PAM). Understanding the correct juxtaposition of the protospacer- and PAM-interaction with Cas9 will enable development of versatile and safe Cas9-based technology. We report identification and biochemical characterization of Cas9 from Acidothermus cellulolyticus (AceCas9). AceCas9 depends on a 5'-NNNCC-3' PAM and is more efficient in cleaving negative supercoils than relaxed DNA. Kinetic as well as in vivo activity assays reveal that AceCas9 achieves optimal activity when combined with a guide RNA containing a 24-nucleotide complementarity region. The cytosine-specific, DNA topology-sensitive, and extended guide-dependent properties of AceCas9 may be explored for specific genome editing applications.
Show less
Date Issued: 2017-06-16
Identifier: FSU_pmch_28277645, 10.1021/acssynbio.7b00050, PMC5706465, 28277645, 28277645
Format: Citation

Title: Personalized chemotherapy selection for breast cancer using gene expression profiles.
Creator: Yu, Kaixian, Sang, Qing-Xiang Amy, Lung, Pei-Yau, Tan, Winston, Lively, Ty, Sheffield, Cedric, Bou-Dargham, Mayassa J, Liu, Jun S, Zhang, Jinfeng
Abstract/Description: Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to...
Show moreChoosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens.
Show less
Date Issued: 2017-03-03
Identifier: FSU_pmch_28256629, 10.1038/srep43294, PMC5335706, 28256629, 28256629, srep43294
Format: Citation

Title: The Solution Assembly of Biological Molecules Using Ion Mobility Methods: From Amino Acids to Amyloid β-Protein..
Creator: Bleiholder, Christian, Bowers, Michael T
Abstract/Description: Ion mobility spectrometry-mass spectrometry (IMS-MS) methods are increasingly used to study noncovalent assemblies of peptides and proteins. This review focuses on the noncovalent self-assembly of amino acids and peptides, systems at the heart of the amyloid process that play a central role in a number of devastating diseases. Three different systems are discussed in detail: the 42-residue peptide amyloid-β42 implicated in the etiology of Alzheimer's disease, several amyloid-forming peptides...
Show moreIon mobility spectrometry-mass spectrometry (IMS-MS) methods are increasingly used to study noncovalent assemblies of peptides and proteins. This review focuses on the noncovalent self-assembly of amino acids and peptides, systems at the heart of the amyloid process that play a central role in a number of devastating diseases. Three different systems are discussed in detail: the 42-residue peptide amyloid-β42 implicated in the etiology of Alzheimer's disease, several amyloid-forming peptides with 6-11 residues, and the assembly of individual amino acids. We also discuss from a more fundamental perspective the processes that determine how quickly proteins and their assemblies denature when the analyte ion has been stripped of its solvent in an IMS-MS measurement and how to soften the measurement so that biologically meaningful data can be recorded.
Show less
Date Issued: 2017-06-12
Identifier: FSU_pmch_28375705, 10.1146/annurev-anchem-071114-040304, PMC6287953, 28375705, 28375705
Format: Citation

Title: Antidiabetic Disruptors of the Glucokinase-Glucokinase Regulatory Protein Complex Reorganize a Coulombic Interface.
Creator: Martinez, Juliana A, Xiao, Qing, Zakarian, Armen, Miller, Brian G
Abstract/Description: The glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular...
Show moreThe glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular basis by which these natural and synthetic ligands modulate the GCK-GKRP interaction. We demonstrate that a small-molecule disruptor of the protein-protein interaction utilizes a two-step conformational selection mechanism to associate with a rare GKRP conformation constituting 3% of the total population. Conformational heterogeneity of GKRP is localized to the N-terminus and deleting this region eliminates the ability of sorbitol 6-phosphate to promote the GCK-GKRP interaction. Stabilizing ligands favor an extended N-terminus, which sterically positions two arginine residues for optimal Coulombic interaction with a pair of carboxylate side chains from GCK. Conversely, disruptors promote a more compact N-terminus in which an interfacial arginine residue is stabilized in an unproductive orientation through a cation-π interaction with tyrosine 75. Eliminating the ability to sample this binding impaired conformation enhances the intrinsic inhibitory activity of GKRP. Elucidating the molecular basis of ligand-mediated control over the GCK-GKRP interaction is expected to impact the development and future refinement of therapeutic agents for diabetes and cardiovascular disease, which result from improper GKRP regulation of GCK.
Show less
Date Issued: 2017-06-20
Identifier: FSU_pmch_28516783, 10.1021/acs.biochem.7b00377, PMC5831357, 28516783, 28516783
Format: Citation

Title: Overcoming the crystallization and designability issues in the ultrastable zirconium phosphonate framework system.
Creator: Zheng, Tao, Yang, Zaixing, Gui, Daxiang, Liu, Zhiyong, Wang, Xiangxiang, Dai, Xing, Liu, Shengtang, Zhang, Linjuan, Gao, Yang, Chen, Lanhua, Sheng, Daopeng, Wang, Yanlong, Diwu,...
Show moreZheng, Tao, Yang, Zaixing, Gui, Daxiang, Liu, Zhiyong, Wang, Xiangxiang, Dai, Xing, Liu, Shengtang, Zhang, Linjuan, Gao, Yang, Chen, Lanhua, Sheng, Daopeng, Wang, Yanlong, Diwu, Juan, Wang, Jianqiang, Zhou, Ruhong, Chai, Zhifang, Albrecht-Schmitt, Thomas E, Wang, Shuao
Show less
Abstract/Description: Metal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. Herein, we overcome these challenges and obtain single...
Show moreMetal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. Herein, we overcome these challenges and obtain single crystals of three zirconium phosphonates that are suitable for structural analysis. These compounds are built by previously unknown isolated zirconium phosphonate clusters and exhibit combined high porosity and ultrastability even in fuming acids. SZ-2 possesses the largest void volume recorded in zirconium phosphonates and SZ-3 represents the most porous crystalline zirconium phosphonate and the only porous MOF material reported to survive in aqua regia. SZ-2 and SZ-3 can effectively remove uranyl ions from aqueous solutions over a wide pH range, and we have elucidated the removal mechanism.
Show less
Date Issued: 2017-05-30
Identifier: FSU_pmch_28555656, 10.1038/ncomms15369, PMC5459948, 28555656, 28555656, ncomms15369
Format: Citation

Title: Diffusion of Sites versus Polymers in Polyelectrolyte Complexes and Multilayers.
Creator: Fares, Hadi, Schlenoff, Joseph
Abstract/Description: It has long been assumed that the spontaneous formation of materials such as complexes and multilayers from charged polymers depends on (inter)diffusion of these polyelectrolytes. Here, we separately examine the mass transport of polymer molecules and extrinsic sites—charged polyelectrolyte repeat units balanced by counterions—within thin films of polyelectrolyte complex, PEC, using sensitive isotopic labeling techniques. The apparent diffusion coefficients of these sites within PEC films of...
Show moreIt has long been assumed that the spontaneous formation of materials such as complexes and multilayers from charged polymers depends on (inter)diffusion of these polyelectrolytes. Here, we separately examine the mass transport of polymer molecules and extrinsic sites—charged polyelectrolyte repeat units balanced by counterions—within thin films of polyelectrolyte complex, PEC, using sensitive isotopic labeling techniques. The apparent diffusion coefficients of these sites within PEC films of poly(diallyldimethylammonium), PDADMA, and poly(styrenesulfonate), PSS, are at least 2 orders of magnitude faster than the diffusion of polyelectrolytes themselves. This is because site diffusion requires only local rearrangements of polyelectrolyte repeat units, placing far fewer kinetic limitations on the assembly of polyelectrolyte complexes in all of their forms. Site diffusion strongly depends on the salt concentration (ionic strength) of the environment, and diffusion of PDADMA sites is faster than that of PSS sites, accounting for the asymmetric nature of multilayer growth. Site diffusion is responsible for multilayer growth in the linear and into the exponential regimes, which explains how PDADMA can mysteriously “pass through” layers of PSS. Using quantitative relationships between site diffusion coefficient and salt concentration, conditions were identified that allowed the diffusion length to always exceed the film thickness, leading to full exponential growth over 3 orders of magnitude thickness. Both site and polymer diffusion were independent of molecular weight, suggesting that ion pairing density is a limiting factor. Polyelectrolyte complexes are examples of a broader class of dynamic bulk polymeric materials that (self-) assemble via the transport of cross-links or defects rather than actual molecules.
Show less
Date Issued: 2017-10-05
Identifier: FSU_libsubv1_scholarship_submission_1543269470_f050f9b2, 10.1021/jacs.7b07905
Format: Citation

Title: Driving Forces for Oppositely Charged Polyioon Association in Aqueous Solution: Enthalpic, Entropic but Not Electrostatic.
Creator: Fu, Jingcheng, Schlenoff, Joseph
Abstract/Description: Driving forces for association between oppositely charged biological or synthetic polymers in aqueous solution have long been identified as electrostatic in origin. This attraction is broken down into an entropic component, due to loss of counterions, and an enthalpic component, stemming from Coulombic attraction between opposite charges. While the balance between entropic and enthalpic contributions shifts according to the conditions, the presence of exotherms or endotherms on mixing, though...
Show moreDriving forces for association between oppositely charged biological or synthetic polymers in aqueous solution have long been identified as electrostatic in origin. This attraction is broken down into an entropic component, due to loss of counterions, and an enthalpic component, stemming from Coulombic attraction between opposite charges. While the balance between entropic and enthalpic contributions shifts according to the conditions, the presence of exotherms or endotherms on mixing, though small, are viewed as signatures of Coulombic interactions which support theories of polyelectrolyte association rooted in continuum electrostatics. Here, a head-to-head comparison is made between mechanisms based on electrostatics and those based on specific ion pairing, or ion exchange. Using a Hofmeister series of counterions for a common polycation, poly(diallyldimethylammonium), enthalpy changes on association with poly(styrenesulfonate) are shown to derive from changes in water perturbation, revealed by Raman scattering studies of water O–H vibrations. The free energy for complexation is almost completely entropic over all salt concentrations.
Show less
Date Issued: 2016-01-15
Identifier: FSU_libsubv1_scholarship_submission_1543268476_8c636203, 10.1021/jacs.5b11878
Format: Citation

Title: Saloplastics: Processing Compact Polyelectrolyte Complexes.
Creator: Schlenoff, Joseph, Schaaf, Pierre
Abstract/Description: Polyelectrolyte complexes (PECs) are prepared by mixing solutions of oppositely charged polyelectrolytes. These diffuse, amorphous precipitates may be compacted into dense materials, CoPECs, by ultracentrifugation (ucPECs) or extrusion (exPECs). The presence of salt water is essential in plasticizing PECs to allow them to be reformed and fused. When hydrated, CoPECs are versatile, rugged, biocompatible, elastic materials with applications including bioinspired materials, supports for enzymes...
Show morePolyelectrolyte complexes (PECs) are prepared by mixing solutions of oppositely charged polyelectrolytes. These diffuse, amorphous precipitates may be compacted into dense materials, CoPECs, by ultracentrifugation (ucPECs) or extrusion (exPECs). The presence of salt water is essential in plasticizing PECs to allow them to be reformed and fused. When hydrated, CoPECs are versatile, rugged, biocompatible, elastic materials with applications including bioinspired materials, supports for enzymes and (nano)composites. In this review, various methods for making CoPECs are described, as well as fundamental responses of CoPEC mechanical properties to salt concentration. Possible applications as synthetic cartilage, enzymatically active biocomposites, self‐healing materials, and magnetic nanocomposites are presented.
Show less
Date Issued: 2015-03-13
Identifier: FSU_libsubv1_scholarship_submission_1543268228_25a15aaa, 10.1002/adma.201500176
Format: Citation

Title: Janus Nanofilms.
Creator: Ghoussoub, Yara, Schlenoff, Joseph
Abstract/Description: To make a two-dimensional Janus object, the perfluorinated anionic polyelectrolyte Nafion was adsorbed to the surface of ultrathin films of polyelectrolyte complex. Nafion changed the wetting characteristics of the polyelectrolyte multilayer (PEMU) of poly(diallyldimethylammonium) and poly(styrenesulfonate) from hydrophilic to hydrophobic. PEMUs assembled on aluminum substrates and terminated with Nafion could be released by exposure to alkali solution, producing free-floating films in the...
Show moreTo make a two-dimensional Janus object, the perfluorinated anionic polyelectrolyte Nafion was adsorbed to the surface of ultrathin films of polyelectrolyte complex. Nafion changed the wetting characteristics of the polyelectrolyte multilayer (PEMU) of poly(diallyldimethylammonium) and poly(styrenesulfonate) from hydrophilic to hydrophobic. PEMUs assembled on aluminum substrates and terminated with Nafion could be released by exposure to alkali solution, producing free-floating films in the 100 nm thickness regime. Water contact angle measurements showed a strong difference in hydrophilicity between the two sides of this Janus film, which was further characterized using atomic force microscopy and X-ray photoelectron spectroscopy (XPS). XPS revealed different fluorine contents on both sides of the PEMU, which could be translated to a Nafion gradient through the film. Fourier transform infrared spectroscopy showed the Nafion-containing films were much more resistant to decomposition by high salt concentration.
Show less
Date Issued: 2016-04-07
Identifier: FSU_libsubv1_scholarship_submission_1543269187_3ddc9070, 10.1021/acs.langmuir.6b00672
Format: Citation

National High Magnetic Field Laboratory (25)	+ -
Institute of Molecular Biophysics (20)	+ -
Department of Physics (5)	+ -
Department of Chemical and Biomedical Engineering (4)	+ -
Department of Biological Science (3)	+ -

Department of Material Science and Engineering (3)	+ -
Program in Neuroscience (3)	+ -
Department of Earth, Ocean and Atmospheric Science (2)	+ -
Department of Mathematics (2)	+ -
Department of Scientific Computing (2)	+ -
Department of Statistics (2)	+ -

Humans (23)	+ -
Animals (12)	+ -
Chemistry (12)	+ -
Male (6)	+ -
Protein Binding (5)	+ -

Chemistry, Inorganic (4)	+ -
Chemistry, Organic (4)	+ -
Gene Expression Regulation, Neoplastic (4)	+ -
Mice (4)	+ -
Models, Molecular (4)	+ -
Molecular Structure (4)	+ -
Thermodynamics (4)	+ -
Amino Acid Sequence (3)	+ -
Archaeal Proteins/metabolism (3)	+ -
Bacterial Proteins/metabolism (3)	+ -
Cell Line (3)	+ -
Cell Line, Tumor (3)	+ -
Cyclotrons (3)	+ -
Female (3)	+ -
Glucokinase/metabolism (3)	+ -
Mass Spectrometry/methods (3)	+ -
Molecular Dynamics Simulation (3)	+ -
Neoplasm Staging (3)	+ -
Nucleic Acid Conformation (3)	+ -
Peptides/chemistry (3)	+ -
Prostatic Neoplasms/pathology (3)	+ -
Viral Matrix Proteins/chemistry (3)	+ -
ADAM Proteins/genetics (2)	+ -
ADAM Proteins/metabolism (2)	+ -
Adaptor Proteins, Signal Transducing/metabolism (2)	+ -

text (143)	+ -
journal article (106)	+ -
book part (1)	+ -

Search In

Pages

Pages

Sort Results By:

Narrow results by:

Collection

Topical Subject

Genre

Type of Resource

Language

Creator

Found In

Owner