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Articles 1 - 30 of 100
Full-Text Articles in Biochemistry
Enhancement Of Reactive Oxygen Species Production And Chlamydial Infection By The Mitochondrial Nod-Like Family Member Nlrx1, Ali A. Abdul-Sater, Najwene Saïd-Sadier, Verissa M. Lam, Bhavni Singh, Matthew A. Pettengill, Fraser Soares, Ivan Tattoli, Simone Lipinski, Stephen E. Girardin, Philip Rosenstiel, David M. Ojcius
Enhancement Of Reactive Oxygen Species Production And Chlamydial Infection By The Mitochondrial Nod-Like Family Member Nlrx1, Ali A. Abdul-Sater, Najwene Saïd-Sadier, Verissa M. Lam, Bhavni Singh, Matthew A. Pettengill, Fraser Soares, Ivan Tattoli, Simone Lipinski, Stephen E. Girardin, Philip Rosenstiel, David M. Ojcius
All Dugoni School of Dentistry Faculty Articles
Chlamydia trachomatis infections cause severe and irreversible damage that can lead to infertility and blindness in both males and females. Following infection of epithelial cells, Chlamydia induces production of reactive oxygen species (ROS). Unconventionally, Chlamydiae use ROS to their advantage by activating caspase-1, which contributes to chlamydial growth. NLRX1, a member of the Nod-like receptor family that translocates to the mitochondria, can augment ROS production from the mitochondria following Shigella flexneri infections. However, in general, ROS can also be produced by membrane-bound NADPH oxidases. Given the importance of ROS-induced caspase-1 activation in growth of the chlamydial vacuole, we investigated the …
Dual Inhibition Of Sodium-Mediated Proton And Calcium Efflux Triggers Non-Apoptotic Cell Death In Malignant Gliomas, William Harley, Candace Floyd, Tamara Dunn, Xiao-Dong Zhang, Tsung-Yu Chen, Manu Hegde, Hasan Palandoken, Michael H. Nantz, Leonardo Leon, K.L. Carraway Iii, Bruce Lyeth, Fredric A. Gorin
Dual Inhibition Of Sodium-Mediated Proton And Calcium Efflux Triggers Non-Apoptotic Cell Death In Malignant Gliomas, William Harley, Candace Floyd, Tamara Dunn, Xiao-Dong Zhang, Tsung-Yu Chen, Manu Hegde, Hasan Palandoken, Michael H. Nantz, Leonardo Leon, K.L. Carraway Iii, Bruce Lyeth, Fredric A. Gorin
Chemistry and Biochemistry
Malignant glioma cells maintain an elevated intracellular pH (pHi) within hypoxic–ischemic tumormicroenvironments through persistent activation of sodium–proton transport (McLean et al., 2000). Amiloride has been reported to selectively kill human malignant glioma cell lines but not primary astrocytes (Hegde et al., 2004). While amiloride reduces pHi of malignant gliomas by inhibiting isoform 1 of sodium–proton exchange (NHE1), direct acidification was shown to be cytostatic rather than cytotoxic. At cytotoxic concentrations, amiloride has multiple drug targets including inhibition of NHE1 and sodium–calciumexchange. Amiloride's glioma cytotoxicity can be explained, at least in part, by dual inhibition of NHE1 and …
Measurements Of Gas‐Phase Inorganic And Organic Acids From Biomass Fires By Negative‐Ion Proton‐Transfer Chemical‐Ionization Mass Spectrometry, P. Veres, James M. Roberts, I. R. Burling, C. Warneke, Joost De Gouw, Robert J. Yokelson
Measurements Of Gas‐Phase Inorganic And Organic Acids From Biomass Fires By Negative‐Ion Proton‐Transfer Chemical‐Ionization Mass Spectrometry, P. Veres, James M. Roberts, I. R. Burling, C. Warneke, Joost De Gouw, Robert J. Yokelson
Chemistry and Biochemistry Faculty Publications
[1] Emissions from 34 laboratory biomass fires were investigated at the combustion facility of the U.S. Department of Agriculture Fire Sciences Laboratory in Missoula, Montana. Gas-phase organic and inorganic acids were quantified using negative-ion proton-transfer chemical-ionization mass spectrometry (NI-PT-CIMS), open-path Fourier transform infrared spectroscopy (OP-FTIR), and proton-transfer-reaction mass spectrometry (PTR-MS). NI-PT-CIMS is a novel technique that measures the mass-to-charge ratio (m/z) of ions generated from reactions of acetate (CH3C(O)O−) ions with inorganic and organic acids. The emission ratios for various important reactive acids with respect to CO were determined. Emission ratios for isocyanic acid (HNCO), 1,2 …
Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou
Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …
[Accepted Article Manuscript Version (Postprint)] Pex5 Mutants That Differentially Disrupt Pts1 And Pts2 Peroxisomal Matrix Protein Import In Arabidopsis, Bibi Khan, Bethany Zolman
[Accepted Article Manuscript Version (Postprint)] Pex5 Mutants That Differentially Disrupt Pts1 And Pts2 Peroxisomal Matrix Protein Import In Arabidopsis, Bibi Khan, Bethany Zolman
Biology Department Faculty Works
PEX5 and PEX7 are receptors required for the import of peroxisome-bound proteins containing one of two peroxisomal targeting signals (PTS1 or PTS2). To better understand the role of PEX5 in plant peroxisomal import, we characterized the Arabidopsis (Arabidopsis thaliana) pex5-10 mutant, which has a T-DNA insertion in exon 5 of the PEX5 gene. Sequencing results revealed that exon 5, along with the T-DNA, is removed in this mutant, resulting in a truncated pex5 protein. The pex5-10 mutant has germination defects and is completely dependent on exogenous Suc for early seedling establishment, based on poor utilization of seed-storage fatty acids. This …
The In Situ Function Of A Microbial Community Profiled By Ft-Ir: A Snapshot In Time, Ryan Roberts
The In Situ Function Of A Microbial Community Profiled By Ft-Ir: A Snapshot In Time, Ryan Roberts
Department of Biochemistry: Dissertations, Theses, and Student Research
Photographs of an ecosystem are an important tool in macro-community ecology. The photograph is a permanent record of species phenotype. In microbiology, biochemical activity provides the most descriptive information of an organism’s phenotype. A method for fingerprinting all biochemical activities occurring within a microbial community is analogous to a photograph. Infrared spectroscopy in the region between wavelengths 2500 to 20,000 nm (mid-IR) is a well established instrumental method for fingerprinting the total biochemical profile of axenic cultures. Spectra are complex and sensitive as demonstrated by the ability to discriminate between strains of bacteria, fungi, and algae. This thesis develops the …
An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic
An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translation, although the precise biological role remains largely unknown. To gain further insights into archaeal MSCs, possible protein-protein interactions with the atypical Methanothermobacter thermautotrophicus seryl-tRNA synthetase (MtSerRS) were investigated. Yeast two-hybrid analysis revealed arginyl-tRNA synthetase (MtArgRS) as an interacting partner of MtSerRS. Surface plasmon resonance confirmed stable complex formation, with a dissociation constant (KD) of 250 nm. Formation of the MtSerRS·MtArgRS complex …
Systematic Approach To Electrostatically Induced 2d Crystallization Of Nanoparticles At Liquid Interfaces, Sumit Kewalramani, Suntao Wang, Yuan Lin, Huong Giang Nguyen, Qian Wang, Masafumi Fukuto, Lin Yang
Systematic Approach To Electrostatically Induced 2d Crystallization Of Nanoparticles At Liquid Interfaces, Sumit Kewalramani, Suntao Wang, Yuan Lin, Huong Giang Nguyen, Qian Wang, Masafumi Fukuto, Lin Yang
Faculty Publications
We report an experimental demonstration of a strategy for inducing two-dimensional (2D)crystallization of charged nanoparticles on oppositely charged fluid interfaces. This strategy aims to maximize the interfacial adsorption of nanoparticles, and hence their lateral packing density, by utilizing a combination of weakly charged particles and a high surface charge density on the planar interface. In order to test this approach, we investigated the assembly of cowpea mosaic virus (CPMV) on positively charged lipid monolayers at the aqueous solution surface, by means of in situX-ray scattering measurements at the liquid–vapor interface. Theassembly was studied as a function of the solution …
Resonance Assignments And Secondary Structure Predictions Of The As(Iii) Metallochaperone Arsd In Solution, Jun Ye, Yanan He, Jack Skalicky, Barry P. Rosen, Timothy L. Stemmler
Resonance Assignments And Secondary Structure Predictions Of The As(Iii) Metallochaperone Arsd In Solution, Jun Ye, Yanan He, Jack Skalicky, Barry P. Rosen, Timothy L. Stemmler
Biochemistry and Molecular Biology Faculty Publications
ArsD is a metallochaperone that delivers As(III) to the ArsA ATPase, the catalytic subunit of the ArsAB pump encoded by the arsRDABC operon of Escherichia coli plasmid R773. Conserved ArsD cysteine residues (Cys12, Cys13 and Cys18) construct the As(III) binding site of the protein, however a global structural understanding of this arsenic binding remains unclear. We have obtained NMR assignments for ArsD as a starting point for probing structural changes on the protein that occur in response to metalloid binding and upon formation of a complex with ArsA. The predicted solution structure of ArsD is in agreement with recently published …
Bilirubin: An Animal Pigment In The Zingiberales And Diverse Angiosperm Orders, Cary L. Pirone
Bilirubin: An Animal Pigment In The Zingiberales And Diverse Angiosperm Orders, Cary L. Pirone
FIU Electronic Theses and Dissertations
Strelitziaceae is a tropical monocot family comprising three genera and seven species: Ravenala Adans and Phenkospermum Endl., which are monotypic, and five species of Strelitzia Aiton. All species produce woody capsular fruits that contain vibrantly colored arillate seeds. Arils of the Strelitzia species are orange, those of Phenakospermum are red, and those of Ravenala are blue. Unlike most plant pigments, which degrade after cell death, aril pigments in the family persist for decades. Chemical properties of the compounds are unusual, and do not match those of known pigment classes (carotenoids, flavonoids, betalains, and the chlorophylls). I isolated the orange pigment …
Dnmt1 Stability Is Regulated By Proteins Coordinating Deubiquitination And Acetylation-Driven Ubiquitination, Zhanwen Du, Jing Song, Yong Wang, Yiqing Zhao, Kishore Guda, Shuming Yang, Hung Ying Kao, Yan Xu, Joseph Willis, Sanford D. Markowitz, David Sedwick, Robert M. Ewing, Zhenghe Wang
Dnmt1 Stability Is Regulated By Proteins Coordinating Deubiquitination And Acetylation-Driven Ubiquitination, Zhanwen Du, Jing Song, Yong Wang, Yiqing Zhao, Kishore Guda, Shuming Yang, Hung Ying Kao, Yan Xu, Joseph Willis, Sanford D. Markowitz, David Sedwick, Robert M. Ewing, Zhenghe Wang
Chemistry Faculty Publications
DNA methyltransferase 1 (DNMT1) is the primary enzyme that maintains DNA methylation. We describe a previously unknown mode of regulation of DNMT1 protein stability through the coordinated action of an array of DNMT1-associated proteins. DNMT1 was destabilized by acetylation by the acetyltransferase Tip60, which triggered ubiquitination by the E3 ligase UHRF1, thereby targeting DNMT1 for proteasomal degradation. In contrast, DNMT1 was stabilized by histone deacetylase 1 (HDAC1) and the deubiquitinase HAUSP (herpes virus–associated ubiquitin-specific protease). Analysis of the abundance of DNMT1 and Tip60, as well as the association between HAUSP and DNMT1, suggested that during the cell cycle the initiation …
Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean
Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean
Articles
Pandoraea species have emerged as opportunistic pathogens among cystic fibrosis (CF) and non-CF patients. Pandoraea pulmonicola is the predominant Pandoraea species among Irish CF patients. The objective of this study was to investigate the pathogenicity and potential mechanisms of virulence of Irish P. pulmonicola isolates and strains from other Pandoraea species. Three patients from whom the P. pulmonicola isolates were isolated have since died. The in vivo virulence of these and other Pandoraea strains was examined by determining the ability to kill Galleria mellonella larvae. The P. pulmonicola strains generally were the most virulent of the species tested, with three …
(1e,3e)-1,4-Bis(4-Methoxyphenyl)Buta1,3-Diene, Gopinathan Narayan, Nigam Rath, Suresh Das
(1e,3e)-1,4-Bis(4-Methoxyphenyl)Buta1,3-Diene, Gopinathan Narayan, Nigam Rath, Suresh Das
Chemistry & Biochemistry Faculty Works
The title compound, C18H18O2, which exhibits blue emission in the solid state, is an intermediate in the preparation of liquid crystals and polymers. The molecule is located on an inversion centre. In the crystal, molecules are arranged in a herringbone motif.
Solving The Low Dimensional Smoluchowski Equation With A Singular Value Basis Set, Gregory E. Scott, Martin Gruebele
Solving The Low Dimensional Smoluchowski Equation With A Singular Value Basis Set, Gregory E. Scott, Martin Gruebele
Chemistry and Biochemistry
Reaction kinetics on free energy surfaces with small activation barriers can be computed directly with the Smoluchowski equation. The procedure is computationally expensive even in a few dimensions. We present a propagation method that considerably reduces computational time for a particular class of problems: when the free energy surface suddenly switches by a small amount, and the probability distribution relaxes to a new equilibrium value. This case describes relaxation experiments. To achieve efficient solution, we expand the density matrix in a basis set obtained by singular value decomposition of equilibrium density matrices. Grid size during propagation is reduced from (100–1000) …
Biocompatibility Of Synthetic Poly(Ester Urethane)/Polyhedral Oligomeric Silsesquioxane Matrices With Embryonic Stem Cell Proliferation And Differentiation, Yan-Lin Guo, Wenshou Wang, Joshua U. Otaigbe
Biocompatibility Of Synthetic Poly(Ester Urethane)/Polyhedral Oligomeric Silsesquioxane Matrices With Embryonic Stem Cell Proliferation And Differentiation, Yan-Lin Guo, Wenshou Wang, Joshua U. Otaigbe
Faculty Publications
Incorporation of polyhedral oligomeric silsesquioxanes (POSS) into poly(ester urethanes) (PEU) as a building block results in a PEU/POSS hybrid polymer with increased mechanical strength and thermostability. An attractive feature of the new polymer is that it forms a porous matrix when cast in the form of a thin film, making it potentially useful in tissue engineering. In this study, we present detailed microscopic analysis of the PEU/POSS matrix and demonstrate its biocompatibility with cell culture. The PEU/POSS polymer forms a continuous porous matrix with open pores and interconnected grooves. From SEM image analysis, it is calculated that there are about …
Synthesis And Structural Characterization Of The Peptide Epitope Of The Ovarian Cancer Biomarker Ca125 (Muc16), Rebecca J. Whelan, Zach T. Berman, Lee J. Moore, Kathleen E. Knudson
Synthesis And Structural Characterization Of The Peptide Epitope Of The Ovarian Cancer Biomarker Ca125 (Muc16), Rebecca J. Whelan, Zach T. Berman, Lee J. Moore, Kathleen E. Knudson
Faculty & Staff Scholarship
A highly conserved region of 21 amino acids flanked by cysteine residues, contained within a larger repeated domain, has been proposed to be the antibody-binding site in the ovarian cancer biomarker CA125 (MUC16). In this study solid-phase peptide synthesis with Fmoc protection chemistry was used to assemble a 21-mer peptide corresponding to the most frequently occurring antibody binding sequence in CA125. Potentially significant sequence variants were also synthesized. Peptide secondary structure was investigated using Fourier transform infrared spectroscopy, revealing the consensus sequence peptide to be largely unstructured at physiological pH whether the cysteine residues were reduced or were oxidized to …
Physical Interaction Between Vivid And White Collar Complex Regulates Photoadaptation In Neurospora, Chen-Hui H. Chen, Bradley S. Demay, Amy S. Gladfelter, Jay Dunlap, Jennifer J. Loros
Physical Interaction Between Vivid And White Collar Complex Regulates Photoadaptation In Neurospora, Chen-Hui H. Chen, Bradley S. Demay, Amy S. Gladfelter, Jay Dunlap, Jennifer J. Loros
Dartmouth Scholarship
Photoadaptation, the ability to attenuate a light response on prolonged light exposure while remaining sensitive to escalating changes in light intensity, is essential for organisms to decipher time information appropriately, yet the underlying molecular mechanisms are poorly understood. In Neurospora crassa, VIVID (VVD), a small LOV domain containing blue-light photoreceptor protein, affects photoadaptation for most if not all light-responsive genes. We report that there is a physical interaction between VVD and the white collar complex (WCC), the primary blue-light photoreceptor and the transcription factor complex that initiates light-regulated transcriptional responses in Neurospora. Using two previously characterized VVD mutants, we show …
The Terebridae And Teretoxins: Combining Phylogeny And Anatomy For Concerted Discovery Of Bioactive Compounds, Nicolas Puillandre, Mandë Holford
The Terebridae And Teretoxins: Combining Phylogeny And Anatomy For Concerted Discovery Of Bioactive Compounds, Nicolas Puillandre, Mandë Holford
Publications and Research
The Conoidea superfamily, comprised of cone snails, terebrids, and turrids, is an exceptionally promising group for the discovery of natural peptide toxins. The potential of conoidean toxins has been realized with the distribution of the first Conus (cone snail) drug, Prialt (ziconotide), an analgesic used to alleviate chronic pain in HIV and cancer patients. Cone snail toxins (conotoxins) are highly variable, a consequence of a high mutation rate associated to duplication events and positive selection. As Conus and terebrids diverged in the early Paleocene, the toxins from terebrids (teretoxins) may demonstrate highly divergent and unique functionalities. Recent analyses of the …
Aromatic Acid Metabolites Of Escherichia Coli K-12 Can Induce The Marrab Operon, Lon Chubiz, Christopher Rao
Aromatic Acid Metabolites Of Escherichia Coli K-12 Can Induce The Marrab Operon, Lon Chubiz, Christopher Rao
Biology Department Faculty Works
MarR is a key regulator of the marRAB operon involved in antibiotic resistance and solvent stress tolerance in Escherichia coli. We show that two metabolic intermediates, 2,3-dihydroxybenzoate and anthranilate, involved in enterobactin and tryptophan biosynthesis, respectively, can activate marRAB transcription. We also found that a third intermediate involved in ubiquinone biosynthesis, 4-hydroxybenzoate, activates marRAB transcription in the absence of TolC. Of the three, however, only 2,3-dihydroxybenzoate directly binds MarR and affects its activity.
Assessment Of Submerged Vegetation As Indicators Of Irgarol Contamination, Melissa V. Fernandez
Assessment Of Submerged Vegetation As Indicators Of Irgarol Contamination, Melissa V. Fernandez
FIU Electronic Theses and Dissertations
Irgarol 1051 is a common antifoulant toxic to certain marine organisms. Submerged aquatic vegetation (SAV) are exposed to this herbicide when it leaches into the marine environment from painted structures, making SAVs ideal candidates to function as sentinel indicator of contamination. In the initial stage of this study, Coconut Grove and Key Largo Harbor were assessed for environmental exposure to Irgarol. Water, sediment and SAVs were collected, the latter two subject to automated solid phase extraction, and all samples analyzed by GC/MS-SIM for Irgarol and its metabolite, M1. Of the vegetation analyzed, Halodule and Syringodium had the highest capacity to …
Selection For Non-Amyloidogenic Mutants Of Islet Amyloid Polypeptide (Iapp) Identifies An Extended Region For Amyloidogenicity, Ayano Fox, Thibaut Snollaerts, Camille Errecart Casanova, Anastasia Calciano, Luiza A. Nogaj, David A. Moffet
Selection For Non-Amyloidogenic Mutants Of Islet Amyloid Polypeptide (Iapp) Identifies An Extended Region For Amyloidogenicity, Ayano Fox, Thibaut Snollaerts, Camille Errecart Casanova, Anastasia Calciano, Luiza A. Nogaj, David A. Moffet
Chemistry and Biochemistry Faculty Works
The aggregation of the 37-residue polypeptide IAPP, as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of pancreatic β-islet cells in type II diabetes. While IAPP has been known to be the primary component of type II diabetes amyloid, the molecular interactions responsible for this aggregation have not been identified. To identify the aggregation-prone region(s), we constructed a library of randomly generated point mutants of IAPP. This mutant IAPP library was expressed in E. coli as genetic fusions to the reporter protein enhanced green fluorescent protein (EGFP). Because IAPP aggregates rapidly, both …
Negative Dielectrophoretic Capture Of Bacterial Spores In Food Matrices, Mehti Koklu, Seungkyung Park, Suresh D. Pillai, Ali Beskok
Negative Dielectrophoretic Capture Of Bacterial Spores In Food Matrices, Mehti Koklu, Seungkyung Park, Suresh D. Pillai, Ali Beskok
Mechanical & Aerospace Engineering Faculty Publications
A microfluidic device with planar square electrodes is developed for capturing particles from high conductivity media using negative dielectrophoresis (n-DEP). Specifically, Bacillus subtilis and Clostridium sporogenes spores, and polystyrene particles are tested in NaCl solution (0.05 and 0.225 S/m), apple juice (0.225 S/m), and milk (0.525 S/m). Depending on the conductivity of the medium, the Joule heating produces electrothermal flow (ETF), which continuously circulates and transports the particles to the DEP capture sites. Combination of the ETF and n-DEP results in different particle capture efficiencies as a function of the conductivity. Utilizing 20 μm height DEP chambers, “almost complete” and …
Kinetic Characterization Of Salmonella Flik-Flhb Interactions Demonstrates Complexity Of The Type Iii Secretion Substrate-Specificity Switch, Daniel P. Morris, Eric D. Roush, J. Will Thompson, M. Arthur Moseley, James W. Murphy, Jonathan L. Mcmurry
Kinetic Characterization Of Salmonella Flik-Flhb Interactions Demonstrates Complexity Of The Type Iii Secretion Substrate-Specificity Switch, Daniel P. Morris, Eric D. Roush, J. Will Thompson, M. Arthur Moseley, James W. Murphy, Jonathan L. Mcmurry
Faculty and Research Publications
The bacterial flagellum is a complex macromolecular machine consisting of more than 20000 proteins, most of which must be exported from the cell via a dedicated Type III secretion apparatus. At a defined point in flagellar morphogenesis, hook completion is sensed and the apparatus switches substrate specificity type from rod and hook proteins to filament ones. How the switch works is a subject of intense interest. FIiK and F1hBs play central roles. In the present study, two optical biosensing methods were used to characterize FIiK-F1hB interactions using wild-type and two variant FlhBs from mutants with severe flagellar structural defects. Binding …
Frataxin And Mitochondrial Fes Cluster Biogenesis, Timothy L. Stemmler, Emmanuel Lesuisse, Debumar Pain, Andrew Dancis
Frataxin And Mitochondrial Fes Cluster Biogenesis, Timothy L. Stemmler, Emmanuel Lesuisse, Debumar Pain, Andrew Dancis
Biochemistry and Molecular Biology Faculty Publications
Friedreich’s ataxia is an inherited neurodegenerative disease caused by frataxin deficiency. Frataxin is a conserved mitochondrial protein that plays a role in Fe-S cluster assembly in mitochondria. Fe-S clusters are modular cofactors that perform essential functions throughout the cell. They are synthesized by a multi-step and multi-subunit mitochondrial machinery that includes a scaffold protein Isu for assembling a protein bound Fe-S cluster intermediate. Frataxin interacts with Isu, iron, and with the cysteine desulfurase Nfs1 that supplies sulfur, thus placing it at the center of mitochondrial Fe-S cluster biosynthesis.
Novel Polymer Coupling Chemistry Based Upon Latent Cysteine-Like Residues And Thiazolidine Chemistry, Jospeh S. Carlson, Megan R. Hill, Taiga Young, Philip Costanzo
Novel Polymer Coupling Chemistry Based Upon Latent Cysteine-Like Residues And Thiazolidine Chemistry, Jospeh S. Carlson, Megan R. Hill, Taiga Young, Philip Costanzo
Chemistry and Biochemistry
Chain end functional polymers were prepared via reversible addition–fragmentation transfer (RAFT) polymerization techniques that were further chain extended with acrylonitrile. Under reducing conditions, latent cysteine-like residues were exposed at the chain ends. A variety of reduction conditions were explored and base polymers were then tethered together via thiazolidine chemistry.
Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani
Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani
Department of Biological & Biomedical Sciences
Background: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). Results: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase …
Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano
Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano
NYMC Faculty Publications
The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH. We found that only one of the catalases, HPI, produces oxidants in response to UVB light, indicating a potential role for the nucleotide in ROS production. This prompts us to speculate that NADPH may act as a cofactor regulating ROS generation by mammalian catalases. Structural analysis of the NADPH domains …
The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou
The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou
Natural Sciences and Mathematics | Faculty Scholarship
A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …
Study Of The Efficacy, Biodistribution, And Safety Profile Of Therapeutic Gutless Adenovirus Vectors As A Prelude To A Phase I Clinical Trial For Glioblastoma, Akm Ghulam Muhammad, Mariana Puntel, Marianela Candolfi, A Salem, Kader Yagiz, C Farrokhi, Kurt Kroeger, Weidong Xiong, James Curtin, Chunyan Liu, K Lawrence, Niyati Bondale, Jonathan Lerner, G Baker, David Foulad, Robert Pechnick, Donna Palmer, Philip Ng, Pedro Lowenstein, Maria Castro
Study Of The Efficacy, Biodistribution, And Safety Profile Of Therapeutic Gutless Adenovirus Vectors As A Prelude To A Phase I Clinical Trial For Glioblastoma, Akm Ghulam Muhammad, Mariana Puntel, Marianela Candolfi, A Salem, Kader Yagiz, C Farrokhi, Kurt Kroeger, Weidong Xiong, James Curtin, Chunyan Liu, K Lawrence, Niyati Bondale, Jonathan Lerner, G Baker, David Foulad, Robert Pechnick, Donna Palmer, Philip Ng, Pedro Lowenstein, Maria Castro
Articles
Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in humans. Systemic immunity against gene therapy vectors has been shown to hamper therapeutic efficacy; however, helper-dependent high-capacity adenovirus (HC-Ad) vectors elicit sustained transgene expression, even in the presence of systemic anti-adenoviral immunity. We engineered HC-Ads encoding the conditional cytotoxic herpes simplex type 1 thymidine kinase (TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Flt3L). Flt3L expression is under the control of the regulatable Tet-ON system. In anticipation of a phase I clinical trial for GBM, we assessed the therapeutic efficacy, biodistribution, and clinical and …
Aryl Boronic Acid Inhibition Of Synthetic Melanin Polymerization, Jason M. Belitsky
Aryl Boronic Acid Inhibition Of Synthetic Melanin Polymerization, Jason M. Belitsky
Faculty & Staff Scholarship
Inhibitors of melanin formation are sought after for a range of applications. Boronophenylalanine is known to inhibit melanogenesis via boronic acid-catechol interactions. A spectroscopic assay was developed to study the polymerization of L-dopa to synthetic melanin in the presence of para-substituted aryl boronic acids. The best inhibition was observed for aryl boronic acids with electron-withdrawing substituents. The IC50 values exhibit a correlation with the Hammett sigma(p) parameter (rho = 0.97, r(2) = 0.92).