3,349 results on '"Chang, Christopher"'
Search Results
202. Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice
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Xu, Guogang, Yang, Yongshi, Du, Yingzhen, Peng, Fujun, Hu, Peng, Wang, Runsheng, Yin, Ming, Li, Tianzhi, Tu, Lei, Sun, Jinlyu, Jiang, Taijiao, and Chang, Christopher
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- 2020
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203. The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS)
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Kucharik, Alison Haley and Chang, Christopher
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- 2020
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204. Spatial separation of triplet excitons drives endothermic singlet fission
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Korovina, Nadezhda V., Chang, Christopher H., and Johnson, Justin C.
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- 2020
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205. Searching for harmony in transition-metal signaling.
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Chang, Christopher J
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Animals ,Humans ,Neoplasms ,Transition Elements ,Metals ,Signal Transduction ,Oxidative Stress ,Biochemistry & Molecular Biology ,Medicinal and Biomolecular Chemistry ,Biochemistry and Cell Biology - Published
- 2015
206. Hybrid bioinorganic approach to solar-to-chemical conversion
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Nichols, Eva M, Gallagher, Joseph J, Liu, Chong, Su, Yude, Resasco, Joaquin, Yu, Yi, Sun, Yujie, Yang, Peidong, Chang, Michelle CY, and Chang, Christopher J
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Affordable and Clean Energy ,Carbon Dioxide ,Catalysis ,Electrolysis ,Hydrogen ,Light ,Materials Testing ,Methane ,Methanosarcina barkeri ,Photosynthesis ,Silicon ,Solar Energy ,Sunlight ,Temperature ,Water ,artificial photosynthesis ,solar fuels ,photocatalysis ,carbon dioxide fixation ,water splitting - Abstract
Natural photosynthesis harnesses solar energy to convert CO2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by living cells as a source of reducing equivalents for conversion of CO2 to the value-added chemical product methane. Using platinum or an earth-abundant substitute, α-NiS, as biocompatible hydrogen evolution reaction (HER) electrocatalysts and Methanosarcina barkeri as a biocatalyst for CO2 fixation, we demonstrate robust and efficient electrochemical CO2 to CH4 conversion at up to 86% overall Faradaic efficiency for ≥ 7 d. Introduction of indium phosphide photocathodes and titanium dioxide photoanodes affords a fully solar-driven system for methane generation from water and CO2, establishing that compatible inorganic and biological components can synergistically couple light-harvesting and catalytic functions for solar-to-chemical conversion.
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- 2015
207. Covalent organic frameworks comprising cobalt porphyrins for catalytic CO2 reduction in water
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Lin, Song, Diercks, Christian S, Zhang, Yue-Biao, Kornienko, Nikolay, Nichols, Eva M, Zhao, Yingbo, Paris, Aubrey R, Kim, Dohyung, Yang, Peidong, Yaghi, Omar M, and Chang, Christopher J
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Affordable and Clean Energy ,General Science & Technology - Abstract
Conversion of carbon dioxide (CO2) to carbon monoxide (CO) and other value-added carbon products is an important challenge for clean energy research. Here we report modular optimization of covalent organic frameworks (COFs), in which the building units are cobalt porphyrin catalysts linked by organic struts through imine bonds, to prepare a catalytic material for aqueous electrochemical reduction of CO2 to CO. The catalysts exhibit high Faradaic efficiency (90%) and turnover numbers (up to 290,000, with initial turnover frequency of 9400 hour(-1)) at pH 7 with an overpotential of -0.55 volts, equivalent to a 26-fold improvement in activity compared with the molecular cobalt complex, with no degradation over 24 hours. X-ray absorption data reveal the influence of the COF environment on the electronic structure of the catalytic cobalt centers.
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- 2015
208. An Aza-Cope Reactivity-Based Fluorescent Probe for Imaging Formaldehyde in Living Cells
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Brewer, Thomas F and Chang, Christopher J
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Cancer ,Aza Compounds ,Cell Survival ,Fluorescent Dyes ,Formaldehyde ,HEK293 Cells ,Humans ,MCF-7 Cells ,Molecular Structure ,Chemical Sciences ,General Chemistry - Abstract
Formaldehyde (FA) is a reactive carbonyl species (RCS) produced in living systems that has been implicated in epigenetics as well as in the pathologies of various cancers, diabetes, and heart, liver, and neurodegenerative diseases. Traditional methods for biological FA detection rely on sample destruction and/or extensive processing, resulting in a loss of spatiotemporal information. To help address this technological gap, we present the design, synthesis, and biological evaluation of a fluorescent probe for live-cell FA imaging that relies on a FA-induced aza-Cope rearrangement. Formaldehyde probe-1 (FAP-1) is capable of detecting physiologically relevant concentrations of FA in aqueous buffer and in live cells with high selectivity over potentially competing biological analytes. Moreover, FAP-1 can visualize endogenous FA produced by lysine-specific demethylase 1 in a breast cancer cell model, presaging the potential utility of this chemical approach to probe RCS biology.
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- 2015
209. Recognition- and Reactivity-Based Fluorescent Probes for Studying Transition Metal Signaling in Living Systems
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Aron, Allegra T, Ramos-Torres, Karla M, Cotruvo, Joseph A, and Chang, Christopher J
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Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Cell Line ,Tumor ,Chlamydomonas reinhardtii ,Fluorescent Dyes ,HEK293 Cells ,Humans ,Microscopy ,Fluorescence ,Neurotransmitter Agents ,Signal Transduction ,Synapses ,Transition Elements ,Chemical Sciences ,General Chemistry - Abstract
Metals are essential for life, playing critical roles in all aspects of the central dogma of biology (e.g., the transcription and translation of nucleic acids and synthesis of proteins). Redox-inactive alkali, alkaline earth, and transition metals such as sodium, potassium, calcium, and zinc are widely recognized as dynamic signals, whereas redox-active transition metals such as copper and iron are traditionally thought of as sequestered by protein ligands, including as static enzyme cofactors, in part because of their potential to trigger oxidative stress and damage via Fenton chemistry. Metals in biology can be broadly categorized into two pools: static and labile. In the former, proteins and other macromolecules tightly bind metals; in the latter, metals are bound relatively weakly to cellular ligands, including proteins and low molecular weight ligands. Fluorescent probes can be useful tools for studying the roles of transition metals in their labile forms. Probes for imaging transition metal dynamics in living systems must meet several stringent criteria. In addition to exhibiting desirable photophysical properties and biocompatibility, they must be selective and show a fluorescence turn-on response to the metal of interest. To meet this challenge, we have pursued two general strategies for metal detection, termed "recognition" and "reactivity". Our design of transition metal probes makes use of a recognition-based approach for copper and nickel and a reactivity-based approach for cobalt and iron. This Account summarizes progress in our laboratory on both the development and application of fluorescent probes to identify and study the signaling roles of transition metals in biology. In conjunction with complementary methods for direct metal detection and genetic and/or pharmacological manipulations, fluorescent probes for transition metals have helped reveal a number of principles underlying transition metal dynamics. In this Account, we give three recent examples from our laboratory and collaborations in which applications of chemical probes reveal that labile copper contributes to various physiologies. The first example shows that copper is an endogenous regulator of neuronal activity, the second illustrates cellular prioritization of mitochondrial copper homeostasis, and the third identifies the "cuprosome" as a new copper storage compartment in Chlamydomonas reinhardtii green algae. Indeed, recognition- and reactivity-based fluorescent probes have helped to uncover new biological roles for labile transition metals, and the further development of fluorescent probes, including ones with varied Kd values and new reaction triggers and recognition receptors, will continue to reveal exciting and new biological roles for labile transition metals.
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- 2015
210. Bioinspired design of redox-active ligands for multielectron catalysis: effects of positioning pyrazine reservoirs on cobalt for electro- and photocatalytic generation of hydrogen from water
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Jurss, Jonah W, Khnayzer, Rony S, Panetier, Julien A, Roz, Karim A El, Nichols, Eva M, Head-Gordon, Martin, Long, Jeffrey R, Castellano, Felix N, and Chang, Christopher J
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Affordable and Clean Energy ,Chemical Sciences - Abstract
Mononuclear metalloenzymes in nature can function in cooperation with precisely positioned redox-active organic cofactors in order to carry out multielectron catalysis. Inspired by the finely tuned redox management of these bioinorganic systems, we present the design, synthesis, and experimental and theoretical characterization of a homologous series of cobalt complexes bearing redox-active pyrazines. These donor moieties are locked into key positions within a pentadentate ligand scaffold in order to evaluate the effects of positioning redox non-innocent ligands on hydrogen evolution catalysis. Both metal- and ligand-centered redox features are observed in organic as well as aqueous solutions over a range of pH values, and comparison with analogs bearing redox-inactive zinc(ii) allows for assignments of ligand-based redox events. Varying the geometric placement of redox non-innocent pyrazine donors on isostructural pentadentate ligand platforms results in marked effects on observed cobalt-catalyzed proton reduction activity. Electrocatalytic hydrogen evolution from weak acids in acetonitrile solution, under diffusion-limited conditions, reveals that the pyrazine donor of axial isomer 1-Co behaves as an unproductive electron sink, resulting in high overpotentials for proton reduction, whereas the equatorial pyrazine isomer complex 2-Co is significantly more active for hydrogen generation at lower voltages. Addition of a second equatorial pyrazine in complex 3-Co further minimizes overpotentials required for catalysis. The equatorial derivative 2-Co is also superior to its axial 1-Co congener for electrocatalytic and visible-light photocatalytic hydrogen generation in biologically relevant, neutral pH aqueous media. Density functional theory calculations (B3LYP-D2) indicate that the first reduction of catalyst isomers 1-Co, 2-Co, and 3-Co is largely metal-centered while the second reduction occurs at pyrazine. Taken together, the data establish that proper positioning of non-innocent pyrazine ligands on a single cobalt center is indeed critical for promoting efficient hydrogen catalysis in aqueous media, akin to optimally positioned redox-active cofactors in metalloenzymes. In a broader sense, these findings highlight the significance of electronic structure considerations in the design of effective electron-hole reservoirs for multielectron transformations.
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- 2015
211. Imaging agents
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Chang, Christopher J, Gunnlaugsson, Thorfinnur, and James, Tony D
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Boron Compounds ,Contrast Media ,Diagnostic Imaging ,Fluorescent Dyes ,Graphite ,Nanostructures ,Silicon Dioxide ,Chemical Sciences ,General Chemistry - Abstract
Guest editors Christopher J. Chang, Thorfinnur Gunnlaugsson and Tony D. James introduce the Imaging Agents issue of Chemical Society Reviews
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- 2015
212. Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems
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Lin, Vivian S, Chen, Wei, Xian, Ming, and Chang, Christopher J
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1.1 Normal biological development and functioning ,Underpinning research ,Fluorescent Dyes ,Humans ,Hydrogen Sulfide ,Molecular Imaging ,Chemical Sciences ,General Chemistry - Abstract
Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploits the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.
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- 2015
213. Metal–Polypyridyl Catalysts for Electro- and Photochemical Reduction of Water to Hydrogen
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Zee, David Z, Chantarojsiri, Teera, Long, Jeffrey R, and Chang, Christopher J
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Affordable and Clean Energy ,Chemical Sciences ,General Chemistry - Abstract
Climate change, rising global energy demand, and energy security concerns motivate research into alternative, sustainable energy sources. In principle, solar energy can meet the world's energy needs, but the intermittent nature of solar illumination means that it is temporally and spatially separated from its consumption. Developing systems that promote solar-to-fuel conversion, such as via reduction of protons to hydrogen, could bridge this production-consumption gap, but this effort requires invention of catalysts that are cheap, robust, and efficient and that use earth-abundant elements. In this context, catalysts that utilize water as both an earth-abundant, environmentally benign substrate and a solvent for proton reduction are highly desirable. This Account summarizes our studies of molecular metal-polypyridyl catalysts for electrochemical and photochemical reduction of protons to hydrogen. Inspired by concept transfer from biological and materials catalysts, these scaffolds are remarkably resistant to decomposition in water, with fast and selective electrocatalytic and photocatalytic conversions that are sustainable for several days. Their modular nature offers a broad range of opportunities for tuning reactivity by molecular design, including altering ancillary ligand electronics, denticity, and/or incorporating redox-active elements. Our first-generation complex, [(PY4)Co(CH3CN)2](2+), catalyzes the reduction of protons from a strong organic acid to hydrogen in 50% water. Subsequent investigations with the pentapyridyl ligand PY5Me2 furnished molybdenum and cobalt complexes capable of catalyzing the reduction of water in fully aqueous electrolyte with 100% Faradaic efficiency. Of particular note, the complex [(PY5Me2)MoO](2+) possesses extremely high activity and durability in neutral water, with turnover frequencies at least 8500 mol of H2 per mole of catalyst per hour and turnover numbers over 600 000 mol of H2 per mole of catalyst over 3 days at an overpotential of 1.0 V, without apparent loss in activity. Replacing the oxo moiety with a disulfide affords [(PY5Me2)MoS2](2+), which bears a molecular MoS2 triangle that structurally and functionally mimics bulk molybdenum disulfide, improving the catalytic activity for water reduction. In water buffered to pH 3, catalysis by [(PY5Me2)MoS2](2+) onsets at 400 mV of overpotential, whereas [(PY5Me2)MoO](2+) requires an additional 300 mV of driving force to operate at the same current density. Metalation of the PY5Me2 ligand with an appropriate Co(ii) source also furnishes electrocatalysts that are active in water. Importantly, the onset of catalysis by the [(PY5Me2)Co(H2O)](2+) series is anodically shifted by introducing electron-withdrawing functional groups on the ligand. With the [(bpy2PYMe)Co(CF3SO3)](1+) system, we showed that introducing a redox-active moiety can facilitate the electro- and photochemical reduction of protons from weak acids such as acetic acid or water. Using a high-throughput photochemical reactor, we examined the structure-reactivity relationship of a series of cobalt(ii) complexes. Taken together, these findings set the stage for the broader application of polypyridyl systems to catalysis under environmentally benign aqueous conditions.
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- 2015
214. Sensor targets
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Chang, Christopher J, Gunnlaugsson, Thorfinnur, and James, Tony D
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Biosensing Techniques ,Humans ,Chemical Sciences ,General Chemistry - Abstract
Guest editors Christopher J. Chang, Thorfinnur Gunnlaugsson and Tony D. James introduce the Sensor Targets issue of Chemical Society Reviews
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- 2015
215. Synthetic fluorescent probes for studying copper in biological systems.
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Cotruvo, Joseph A, Aron, Allegra T, Ramos-Torres, Karla M, and Chang, Christopher J
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Cell Line ,Animals ,Humans ,Mice ,Copper ,Fluorescent Dyes ,Biosensing Techniques ,General Chemistry ,Chemical Sciences - Abstract
The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues. Whereas copper and other transition metal ions are commonly thought of as static cofactors buried within protein active sites, emerging data points to the presence of additional loosely bound, labile pools that can participate in dynamic signalling pathways. Against this backdrop, we review advances in sensing labile copper pools and understanding their functions using synthetic fluorescent indicators. Following brief introductions to cellular copper homeostasis and considerations in sensor design, we survey available fluorescent copper probes and evaluate their properties in the context of their utility as effective biological screening tools. We emphasize the need for combined chemical and biological evaluation of these reagents, as well as the value of complementing probe data with other techniques for characterizing the different pools of metal ions in biological systems. This holistic approach will maximize the exciting opportunities for these and related chemical technologies in the study and discovery of novel biology of metals.
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- 2015
216. Water-Soluble Iron(IV)-Oxo Complexes Supported by Pentapyridine Ligands: Axial Ligand Effects on Hydrogen Atom and Oxygen Atom Transfer Reactivity.
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Chantarojsiri, Teera, Sun, Yujie, Long, Jeffrey R, and Chang, Christopher J
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Oxygen ,Hydrogen ,Water ,Ferric Compounds ,Benzyl Alcohol ,Pyridines ,Ligands ,Crystallography ,X-Ray ,Spectroscopy ,Mossbauer ,Molecular Structure ,Oxidation-Reduction ,Photochemistry ,Solubility ,Crystallography ,X-Ray ,Spectroscopy ,Mossbauer ,Inorganic & Nuclear Chemistry ,Inorganic Chemistry ,Chemical Engineering ,Other Chemical Sciences ,Physical Chemistry ,Physical Chemistry (incl. Structural) - Abstract
We report the photochemical generation and study of a family of water-soluble iron(IV)-oxo complexes supported by pentapyridine PY5Me2-X ligands (PY5Me2 = 2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine; X = CF3, H, Me, or NMe2), in which the oxidative reactivity of these ferryl species correlates with the electronic properties of the axial pyridine ligand. Synthesis of a systematic series of [Fe(II)(L)(PY5Me2-X)](2+) complexes, where L = CH3CN or H2O, and characterizations by several methods, including X-ray crystallography, cyclic voltammetry, and Mössbauer spectroscopy, show that increasing the electron-donating ability of the axial pyridine ligand tracks with less positive Fe(III)/Fe(II) reduction potentials and quadrupole splitting parameters. The Fe(II) precursors are readily oxidized to their Fe(IV)-oxo counterparts using either chemical outer-sphere oxidants such as CAN (ceric ammonium nitrate) or flash-quench photochemical oxidation with [Ru(bpy)3](2+) as a photosensitizer and K2S2O8 as a quencher. The Fe(IV)-oxo complexes are capable of oxidizing the C-H bonds of alkane (4-ethylbenzenesulfonate) and alcohol (benzyl alcohol) substrates via hydrogen atom transfer (HAT) and an olefin (4-styrenesulfonate) substrate by oxygen atom transfer (OAT). The [Fe(IV)(O)(PY5Me2-X)](2+) derivatives with electron-poor axial ligands show faster rates of HAT and OAT compared to their counterparts supported by electron-rich axial donors, but the magnitudes of these differences are relatively modest.
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- 2015
217. Voices of chemical biology.
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Bertozzi, Carolyn R, Stockwell, Brent R, Kubicek, Stefan, Dickinson, Bryan C, Chang, Christopher J, Schultz, Carsten, Silver, Pamela A, Gestwicki, Jason E, Chiosis, Gabriela, Chattopadhyay, Amitabha, Butcher, Rebecca A, Park, Seung Bum, Shoichet, Brian K, Flitsch, Sabine L, Zhang, Jin, Liu, David R, Ohnishi, Yasuo, Weerapana, Eranthie, Williams, Allison H, He, Chuan, Moroni, Anna, Thiel, Gerhard, Chang, Young-Tae, Waldmann, Herbert, Bogyo, Matthew, Oddershede, Lene B, Christopoulos, Arthur, Imperiali, Barbara, Ehrlich, Hermann, Chen, Xing, and Prescher, Jennifer A
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Interdisciplinary Communication ,Biology ,Chemistry ,Biochemistry & Molecular Biology ,Medicinal and Biomolecular Chemistry ,Biochemistry and Cell Biology - Published
- 2015
218. Nanowire-bacteria hybrids for unassisted solar carbon dioxide fixation to value-added chemicals.
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Liu, Chong, Gallagher, Joseph J, Sakimoto, Kelsey K, Nichols, Eva M, Chang, Christopher J, Chang, Michelle CY, and Yang, Peidong
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Bacteria ,Carbon Dioxide ,Hydrogen ,Silicon ,Water ,Solar Energy ,Sunlight ,Photosynthesis ,Nanowires ,artificial photosynthesis ,bacteria ,carbon dioxide fixation ,Nanoscience & Nanotechnology - Abstract
Direct solar-powered production of value-added chemicals from CO2 and H2O, a process that mimics natural photosynthesis, is of fundamental and practical interest. In natural photosynthesis, CO2 is first reduced to common biochemical building blocks using solar energy, which are subsequently used for the synthesis of the complex mixture of molecular products that form biomass. Here we report an artificial photosynthetic scheme that functions via a similar two-step process by developing a biocompatible light-capturing nanowire array that enables a direct interface with microbial systems. As a proof of principle, we demonstrate that a hybrid semiconductor nanowire-bacteria system can reduce CO2 at neutral pH to a wide array of chemical targets, such as fuels, polymers, and complex pharmaceutical precursors, using only solar energy input. The high-surface-area silicon nanowire array harvests light energy to provide reducing equivalents to the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production of acetic acid under aerobic conditions (21% O2) with low overpotential (η < 200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200 h). The resulting acetate (∼6 g/L) can be activated to acetyl coenzyme A (acetyl-CoA) by genetically engineered Escherichia coli and used as a building block for a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB) polymer, and three different isoprenoid natural products. As such, interfacing biocompatible solid-state nanodevices with living systems provides a starting point for developing a programmable system of chemical synthesis entirely powered by sunlight.
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- 2015
219. An oxidative fluctuation hypothesis of aging generated by imaging H2O2 levels in live Caenorhabditis elegans with altered lifespans
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Fu, Xinmiao, Tang, Yan, Dickinson, Bryan C, Chang, Christopher J, and Chang, Zengyi
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Biochemistry and Cell Biology ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Biological Sciences ,Aging ,Animals ,Caenorhabditis elegans ,Hydrogen Peroxide ,Longevity ,Oxidative Stress ,RNA Interference ,Reactive Oxygen Species ,Oxidative stress ,Oxidative fluctuation hypothesis of aging ,Hydrogen peroxide ,C aenorhabditis elegans ,Medical Biochemistry and Metabolomics ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
Reactive oxygen species (ROS) are important factors mediating aging according to the free radical theory of aging. Few studies have systematically measured ROS levels in relationship to aging, partly due to the lack of tools for detection of specific ROS in live animals. By using the H₂O₂-specific fluorescence probe Peroxy Orange 1, we assayed the H₂O₂ levels of live Caenorhabditis elegans with 41 aging-related genes being individually knocked down by RNAi. Knockdown of 14 genes extends the lifespan but increases H₂O₂ level or shortens the lifespan but decreases H₂O₂ level, contradicting the free radical theory of aging. Strikingly, a significant inverse correlation between lifespan and the normalized standard deviation of H₂O₂ levels was observed (p < 0.0001). Such inverse correlation was also observed in worms cultured under heat shock conditions. An oxidative fluctuation hypothesis of aging is thus proposed and suggests that the ability of animals to homeostatically maintain the ROS levels within a narrow range is more important for lifespan extension than just minimizing the ROS levels though the latter still being crucial.
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- 2015
220. Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas.
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Hong-Hermesdorf, Anne, Miethke, Marcus, Gallaher, Sean D, Kropat, Janette, Dodani, Sheel C, Chan, Jefferson, Barupala, Dulmini, Domaille, Dylan W, Shirasaki, Dyna I, Loo, Joseph A, Weber, Peter K, Pett-Ridge, Jennifer, Stemmler, Timothy L, Chang, Christopher J, and Merchant, Sabeeha S
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Biochemistry & Molecular Biology ,Medicinal and Biomolecular Chemistry ,Biochemistry and Cell Biology - Published
- 2015
221. Erratum: Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas
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Hong-Hermesdorf, Anne, Miethke, Marcus, Gallaher, Sean D, Kropat, Janette, Dodani, Sheel C, Chan, Jefferson, Barupala, Dulmini, Domaille, Dylan W, Shirasaki, Dyna I, Loo, Joseph A, Weber, Peter K, Pett-Ridge, Jennifer, Stemmler, Timothy L, Chang, Christopher J, and Merchant, Sabeeha S
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Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Biochemistry and Cell Biology ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Published
- 2015
222. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells
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Duregotti, Elisa, Negro, Samuele, Scorzeto, Michele, Zornetta, Irene, Dickinson, Bryan C, Chang, Christopher J, Montecucco, Cesare, and Rigoni, Michela
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Neurodegenerative ,Neurosciences ,Regenerative Medicine ,Underpinning research ,1.1 Normal biological development and functioning ,Neurological ,Animals ,Axons ,Coculture Techniques ,Cytochromes c ,DNA ,Mitochondrial ,Mitochondria ,Neurotoxins ,Phagocytosis ,Schwann Cells ,Snakes ,Spiders ,Synapses ,motor axon degeneration ,presynaptic neurotoxins ,mitochondrial alarmins ,Schwann cells - Abstract
An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases.
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- 2015
223. Application of compressed sensing to genome wide association studies and genomic selection
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Vattikuti, Shashaank, Lee, James J., Chang, Christopher C., Hsu, Stephen D. H., and Chow, Carson C.
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Quantitative Biology - Genomics ,Statistics - Applications - Abstract
We show that the signal-processing paradigm known as compressed sensing (CS) is applicable to genome-wide association studies (GWAS) and genomic selection (GS). The aim of GWAS is to isolate trait-associated loci, whereas GS attempts to predict the phenotypic values of new individuals on the basis of training data. CS addresses a problem common to both endeavors, namely that the number of genotyped markers often greatly exceeds the sample size. We show using CS methods and theory that all loci of nonzero effect can be identified (selected) using an efficient algorithm, provided that they are sufficiently few in number (sparse) relative to sample size. For heritability h2 = 1, there is a sharp phase transition to complete selection as the sample size is increased. For heritability values less than one, complete selection can still occur although the transition is smoothed. The transition boundary is only weakly dependent on the total number of genotyped markers. The crossing of a transition boundary provides an objective means to determine when true effects are being recovered; we discuss practical methods for detecting the boundary. For h2 = 0.5, we find that a sample size that is thirty times the number of nonzero loci is sufficient for good recovery., Comment: 30 pages, 11 figures. Version to appear in journal GigaScience
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- 2013
224. The Myth of Mycotoxins and Mold Injury
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Chang, Christopher and Gershwin, M. Eric
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- 2019
- Full Text
- View/download PDF
225. Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas
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Hong-Hermesdorf, Anne, Miethke, Marcus, Gallaher, Sean D, Kropat, Janette, Dodani, Sheel C, Chan, Jefferson, Barupala, Dulmini, Domaille, Dylan W, Shirasaki, Dyna I, Loo, Joseph A, Weber, Peter K, Pett-Ridge, Jennifer, Stemmler, Timothy L, Chang, Christopher J, and Merchant, Sabeeha S
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Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Cations ,Divalent ,Chlamydomonas reinhardtii ,Copper ,Gene Expression Profiling ,Homeostasis ,Hydrogen-Ion Concentration ,Isotope Labeling ,Isotopes ,Lysosomes ,Molecular Imaging ,Plastocyanin ,Polyphosphates ,Transcription Factors ,Transcriptome ,Zinc ,Biochemistry and Cell Biology ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
We identified a Cu-accumulating structure with a dynamic role in intracellular Cu homeostasis. During Zn limitation, Chlamydomonas reinhardtii hyperaccumulates Cu, a process dependent on the nutritional Cu sensor CRR1, but it is functionally Cu deficient. Visualization of intracellular Cu revealed major Cu accumulation sites coincident with electron-dense structures that stained positive for low pH and polyphosphate, suggesting that they are lysosome-related organelles. Nano-secondary ion MS showed colocalization of Ca and Cu, and X-ray absorption spectroscopy was consistent with Cu(+) accumulation in an ordered structure. Zn resupply restored Cu homeostasis concomitant with reduced abundance of these structures. Cu isotope labeling demonstrated that sequestered Cu(+) became bioavailable for the synthesis of plastocyanin, and transcriptome profiling indicated that mobilized Cu became visible to CRR1. Cu trafficking to intracellular accumulation sites may be a strategy for preventing protein mismetallation during Zn deficiency and enabling efficient cuproprotein metallation or remetallation upon Zn resupply.
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- 2014
226. Copper is an endogenous modulator of neural circuit spontaneous activity.
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Dodani, Sheel C, Firl, Alana, Chan, Jefferson, Nam, Christine I, Aron, Allegra T, Onak, Carl S, Ramos-Torres, Karla M, Paek, Jaeho, Webster, Corey M, Feller, Marla B, and Chang, Christopher J
- Subjects
Hippocampus ,Neurons ,Retina ,Animals ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Mice ,Knockout ,Mice ,Rats ,Rats ,Sprague-Dawley ,Copper ,Molybdenum ,Stilbenes ,Cation Transport Proteins ,Chelating Agents ,Fluorescent Dyes ,Microscopy ,Fluorescence ,Calcium Signaling ,Structure-Activity Relationship ,Action Potentials ,Dose-Response Relationship ,Drug ,Female ,Male ,copper signaling ,fluorescent sensor ,molecular imaging ,neural activity ,Copper Transporter 1 ,Inbred C57BL ,Transgenic ,Knockout ,Sprague-Dawley ,Microscopy ,Fluorescence ,Dose-Response Relationship ,Drug ,Neurosciences ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Neurological - Abstract
For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.
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- 2014
227. A well-defined terminal vanadium(III) oxo complex.
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King, Amanda E, Nippe, Michael, Atanasov, Mihail, Chantarojsiri, Teera, Wray, Curtis A, Bill, Eckhard, Neese, Frank, Long, Jeffrey R, and Chang, Christopher J
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Oxygen ,Vanadium ,Organometallic Compounds ,Molecular Structure ,Quantum Theory ,Models ,Molecular ,Models ,Molecular ,Inorganic & Nuclear Chemistry ,Inorganic Chemistry ,Chemical Engineering ,Other Chemical Sciences ,Physical Chemistry ,Physical Chemistry (incl. Structural) - Abstract
The ubiquity of vanadium oxo complexes in the V+ and IV+ oxidation states has contributed to a comprehensive understanding of their electronic structure and reactivity. However, despite being predicted to be stable by ligand-field theory, the isolation and characterization of a well-defined terminal mononuclear vanadium(III) oxo complex has remained elusive. We present the synthesis and characterization of a unique terminal mononuclear vanadium(III) oxo species supported by the pentadentate polypyridyl ligand 2,6-bis[1,1-bis(2-pyridyl)ethyl]pyridine (PY5Me2). Exposure of [V(II)(NCCH3)(PY5Me2)](2+) (1) to either dioxygen or selected O-atom-transfer reagents yields [V(IV)(O)(PY5Me2)](2+) (2). The metal-centered one-electron reduction of this vanadium(IV) oxo complex furnishes a stable, diamagnetic [V(III)(O)(PY5Me2)](+) (3) species. The vanadium(III) oxo species is unreactive toward H- and O-atom transfer but readily reacts with protons to form a putative vanadium hydroxo complex. Computational results predict that further one-electron reduction of the vanadium(III) oxo species will result in ligand-based reduction, even though pyridine is generally considered to be a poor π-accepting ligand. These results have implications for future efforts toward low-valent vanadyl chemistry, particularly with regard to the isolation and study of formal vanadium(II) oxo species.
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- 2014
228. Contributors
- Author
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Agmon-Levin, Nancy, primary, Alarcón, Graciela S., additional, Amengual, Olga, additional, Ardoin, Stacy P., additional, Arora, Swati, additional, Atisha-Fregoso, Yemil, additional, Atkinson, John P., additional, Atsumi, Tatsuya, additional, Ayoub, Isabelle, additional, Barilla-LaBarca, Maria-Louise, additional, Bermas, Bonnie L., additional, Bernatsky, Sasha, additional, Bertsias, George, additional, Bichile, Tanmayee, additional, Blanco, Patrick, additional, Bohgaki, Miyuki, additional, Bonsmann, Gisela, additional, Borghi, Maria Orietta, additional, Boumpas, Dimitrios T., additional, Bourn, Rebecka, additional, Buyon, Jill P., additional, Caricchio, Roberto, additional, Chan, Edward K.L., additional, Chang, Christopher, additional, Charrier, Manon, additional, Chighizola, Cecilia Beatrice, additional, Clarke, Ann E., additional, Crispín, José C., additional, Cuneo, Bettina, additional, Dörner, Thomas, additional, Damato, Erika M., additional, Denniston, Alastair K.O., additional, Devlin, Amy, additional, Diamond, Betty, additional, Ernandez, T., additional, Falasinnu, Titilola, additional, Fernandez-Ruiz, Ruth, additional, Fitzpatrick, Brianna, additional, Forbess, Lindsy, additional, Frangou, Eleni A., additional, Fritzler, Marvin J., additional, Fu, Shu Man, additional, Furie, Richard, additional, Gaskin, Felicia, additional, Gladman, Dafna, additional, Gordon, Caroline, additional, Grammer, Amrie C., additional, Greidinger, Eric L., additional, Greiling, Teri M., additional, Han, Shuhong, additional, Hansen, James E., additional, Hasni, Sarfaraz A., additional, Hassan, Fadi, additional, Hedrich, Christian M., additional, Hiromura, Keiju, additional, Horowitz, Diane, additional, Huang, Xin, additional, Hunt, David, additional, Izmirly, Peter M., additional, James, Judith A., additional, Jarjour, Wael N., additional, Jefferies, Caroline A., additional, Jefferies, Caroline, additional, Jiang, Xiaoyue, additional, Kaplan, Mariana J., additional, Katsuyama, Takayuki, additional, Khamashta, Munther, additional, Kingsmore, Kathryn M., additional, Koike, Takao, additional, Kono, Dwight H., additional, Kriegel, Martin A., additional, Kuhn, Annegret, additional, Kyttaris, Vasileios C, additional, La Cava, Antonio, additional, Ladouceur, Alexandra, additional, Lahita, Robert G., additional, Landmann, Aysche, additional, Lazaro, Estibaliz, additional, Lennard Richard, Mara L., additional, Lino, Andreia C., additional, Lipsky, Peter E., additional, Liszewski, M. Kathryn, additional, Lo, Mindy S., additional, Lu, Qianjin, additional, Mahieu, Mary, additional, Malkiel, Susan, additional, Manzi, Susan, additional, Marder, Galina, additional, Mayadas, T.N., additional, Meroni, Pier Luigi, additional, Merrill, Joan T., additional, Mohan, Chandra, additional, Mok, Chi Chiu, additional, Moulton, Vaishali R., additional, Murray, Philip I., additional, Naffaa, Mohammad E., additional, Nangaku, Masaomi, additional, Niewold, Timothy, additional, Okubo, K., additional, Olsen, Nancy J., additional, Pal, Trina, additional, Paz, Ziv, additional, Perl, Andras, additional, Pons-Estel, Guillermo J., additional, Qu, Bo, additional, Rahman, Anisur, additional, Raman, Ziaur S.M., additional, Ramsey-Goldman, Rosalind, additional, Reeves, Westley H., additional, Richez, Christophe, additional, Rosetti, Florencia, additional, Rovin, Brad H., additional, Rubin, Robert L., additional, Saeli, Stephanie, additional, Saggu, G., additional, Sammaritano, Lisa R., additional, Satoh, Minoru, additional, Sawalha, Amr H., additional, Saxena, Amit, additional, Sciascia, Savino, additional, Shaharir, Syahrul Sazliyana, additional, Sharabi, Amir, additional, Shen, Nan, additional, Shmerling, Robert H., additional, Simard, Julia F., additional, Sisirak, Vanja, additional, Slight-Webb, Samantha, additional, Stillman, Isaac Ely, additional, Sung, Sun-Sang J., additional, Thakkar, Payal, additional, Theofilopoulos, Argyrios N., additional, Thomas, Jr, Donald E., additional, Tissera, Hiromi, additional, Touma, Zahi, additional, Tsao, Betty P., additional, Ugarte-Gil, Manuel F., additional, Urowitz, Murray B., additional, Vieira, Silvio Manfredo, additional, Wainwright, Benjamin, additional, Wallace, Daniel J., additional, Wang, Hongyang, additional, Wu, Haijing, additional, Yahia, Soad Haj, additional, Yu, C. Yung, additional, Zhao, Zhenhuan, additional, and Zhuang, Haoyang, additional
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- 2021
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229. The mechanism of skin damage
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Huang, Xin, primary, Wu, Haijing, additional, Chang, Christopher, additional, and Lu, Qianjin, additional
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- 2021
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230. Coding for Parallel Links to Maximize Expected Decodable-Message Value
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Chang, Christopher S. and Klimesh, Matthew A.
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Computer Science - Information Theory ,68P30 - Abstract
Future communication scenarios for NASA spacecraft may involve multiple communication links and relay nodes, so that there is essentially a network in which there may be multiple paths from a sender to a destination. The availability of individual links may be uncertain. In this paper, scenarios are considered in which the goal is to maximize a payoff that assigns weight based on the worth of data and the probability of successful transmission. Ideally, the choice of what information to send over the various links will provide protection of high value data when many links are unavailable, yet result in communication of significant additional data when most links are available. Here the focus is on the simple network of multiple parallel links, where the links have known capacities and outage probabilities. Given a set of simple inter-link codes, linear programming can be used to find the optimal timesharing strategy among these codes. Some observations are made about the problem of determining all potentially useful codes, and techniques to assist in such determination are presented., Comment: 7 pages, submitted to ISIT2009
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- 2009
231. Mitochondrial DNA damage: Molecular marker of vulnerable nigral neurons in Parkinson's disease
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Sanders, Laurie H, McCoy, Jennifer, Hu, Xiaoping, Mastroberardino, Pier G, Dickinson, Bryan C, Chang, Christopher J, Chu, Charleen T, Van Houten, Bennett, and Greenamyre, JT
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Biological Sciences ,Biomedical and Clinical Sciences ,Neurosciences ,Aging ,Neurodegenerative ,Brain Disorders ,Parkinson's Disease ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Aged ,Aged ,80 and over ,Animals ,Biomarkers ,Cells ,Cultured ,Cerebral Cortex ,DNA Damage ,DNA ,Mitochondrial ,Dopaminergic Neurons ,Electron Transport Complex I ,Humans ,Hydrogen Peroxide ,Male ,Middle Aged ,Parkinson Disease ,Parkinsonian Disorders ,Rats ,Inbred Lew ,Rotenone ,Substantia Nigra ,Parkinson's disease ,Mitochondrial DNA damage ,Abasic sites ,Clinical Sciences ,Neurology & Neurosurgery ,Biochemistry and cell biology - Abstract
DNA damage can cause (and result from) oxidative stress and mitochondrial impairment, both of which are implicated in the pathogenesis of Parkinson's disease (PD). We therefore examined the role of mitochondrial DNA (mtDNA) damage in human postmortem brain tissue and in in vivo and in vitro models of PD, using a newly adapted histochemical assay for abasic sites and a quantitative polymerase chain reaction (QPCR)-based assay. We identified the molecular identity of mtDNA damage to be apurinic/apyrimidinic (abasic) sites in substantia nigra dopamine neurons, but not in cortical neurons from postmortem PD specimens. To model the systemic mitochondrial impairment of PD, rats were exposed to the pesticide rotenone. After rotenone treatment that does not cause neurodegeneration, abasic sites were visualized in nigral neurons, but not in cortex. Using a QPCR-based assay, a single rotenone dose induced mtDNA damage in midbrain neurons, but not in cortical neurons; similar results were obtained in vitro in cultured neurons. Importantly, these results indicate that mtDNA damage is detectable prior to any signs of degeneration - and is produced selectively in midbrain neurons under conditions of mitochondrial impairment. The selective vulnerability of midbrain neurons to mtDNA damage was not due to differential effects of rotenone on complex I since rotenone suppressed respiration equally in midbrain and cortical neurons. However, in response to complex I inhibition, midbrain neurons produced more mitochondrial H2O2 than cortical neurons. We report selective mtDNA damage as a molecular marker of vulnerable nigral neurons in PD and suggest that this may result from intrinsic differences in how these neurons respond to complex I defects. Further, the persistence of abasic sites suggests an ineffective base excision repair response in PD.
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- 2014
232. Molecular medicine and neurodegenerative diseases.
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Chang, Christopher J, Cravatt, Benjamin F, Johnson, Douglas S, and Lim, Mi Hee
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Humans ,Neurodegenerative Diseases ,Cell Death ,Amyloid beta-Peptides ,Molecular Medicine ,General Chemistry ,Chemical Sciences - Published
- 2014
233. Dephosphorylation of Tyrosine 393 in Argonaute 2 by Protein Tyrosine Phosphatase 1B Regulates Gene Silencing in Oncogenic RAS-Induced Senescence
- Author
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Yang, Ming, Haase, Astrid D, Huang, Fang-Ke, Coulis, Gérald, Rivera, Keith D, Dickinson, Bryan C, Chang, Christopher J, Pappin, Darryl J, Neubert, Thomas A, Hannon, Gregory J, Boivin, Benoit, and Tonks, Nicholas K
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Biotechnology ,Cancer ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Argonaute Proteins ,Cell Line ,Cellular Senescence ,Gene Silencing ,Humans ,MicroRNAs ,Phosphorylation ,Protein Tyrosine Phosphatase ,Non-Receptor Type 1 ,Reactive Oxygen Species ,Tyrosine ,ras Proteins ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Oncogenic RAS (H-RAS(V12)) induces premature senescence in primary cells by triggering production of reactive oxygen species (ROS), but the molecular role of ROS in senescence remains elusive. We investigated whether inhibition of protein tyrosine phosphatases by ROS contributed to H-RAS(V12)-induced senescence. We identified protein tyrosine phosphatase 1B (PTP1B) as a major target of H-RAS(V12)-induced ROS. Inactivation of PTP1B was necessary and sufficient to induce premature senescence in H-RAS(V12)-expressing IMR90 fibroblasts. We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B. Phosphorylation of AGO2 at Tyr 393 inhibited loading with microRNAs (miRNAs) and thus miRNA-mediated gene silencing, which counteracted the function of H-RAS(V12)-induced oncogenic miRNAs. Overall, our data illustrate that premature senescence in H-RAS(V12)-transformed primary cells is a consequence of oxidative inactivation of PTP1B and inhibition of miRNA-mediated gene silencing.
- Published
- 2014
234. Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress.
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Kashyap, Des Raj, Rompca, Annemarie, Gaballa, Ahmed, Helmann, John D, Chan, Jefferson, Chang, Christopher J, Hozo, Iztok, Gupta, Dipika, and Dziarski, Roman
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Humans ,Bacillus subtilis ,Escherichia coli ,Metals ,Reactive Oxygen Species ,Sulfhydryl Compounds ,Carrier Proteins ,Gene Expression Regulation ,Bacterial ,Oxidative Stress ,Virology ,Microbiology ,Immunology ,Medical Microbiology - Abstract
Mammalian Peptidoglycan Recognition Proteins (PGRPs) are a family of evolutionary conserved bactericidal innate immunity proteins, but the mechanism through which they kill bacteria is unclear. We previously proposed that PGRPs are bactericidal due to induction of reactive oxygen species (ROS), a mechanism of killing that was also postulated, and later refuted, for several bactericidal antibiotics. Here, using whole genome expression arrays, qRT-PCR, and biochemical tests we show that in both Escherichia coli and Bacillus subtilis PGRPs induce a transcriptomic signature characteristic of oxidative stress, as well as correlated biochemical changes. However, induction of ROS was required, but not sufficient for PGRP killing. PGRPs also induced depletion of intracellular thiols and increased cytosolic concentrations of zinc and copper, as evidenced by transcriptome changes and supported by direct measurements. Depletion of thiols and elevated concentrations of metals were also required, but by themselves not sufficient, for bacterial killing. Chemical treatment studies demonstrated that efficient bacterial killing can be recapitulated only by the simultaneous addition of agents leading to production of ROS, depletion of thiols, and elevation of intracellular metal concentrations. These results identify a novel mechanism of bacterial killing by innate immunity proteins, which depends on synergistic effect of oxidative, thiol, and metal stress and differs from bacterial killing by antibiotics. These results offer potential targets for developing new antibacterial agents that would kill antibiotic-resistant bacteria.
- Published
- 2014
235. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis.
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Polishchuk, Elena V, Concilli, Mafalda, Iacobacci, Simona, Chesi, Giancarlo, Pastore, Nunzia, Piccolo, Pasquale, Paladino, Simona, Baldantoni, Daniela, van IJzendoorn, Sven CD, Chan, Jefferson, Chang, Christopher J, Amoresano, Angela, Pane, Francesca, Pucci, Piero, Tarallo, Antonietta, Parenti, Giancarlo, Brunetti-Pierri, Nicola, Settembre, Carmine, Ballabio, Andrea, and Polishchuk, Roman S
- Subjects
Cells ,Cultured ,Hela Cells ,Lysosomes ,Golgi Apparatus ,Hepatocytes ,Bile ,Animals ,Mice ,Knockout ,Humans ,Mice ,Copper ,Cation Transport Proteins ,Microtubule-Associated Proteins ,RNA ,Small Interfering ,Fluorescent Antibody Technique ,Exocytosis ,Protein Transport ,Homeostasis ,Mutation ,Male ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Adenosine Triphosphatases ,Hep G2 Cells ,Dynactin Complex ,Copper-transporting ATPases ,HeLa Cells ,Developmental Biology ,Biological Sciences ,Medical and Health Sciences - Abstract
Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease.
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- 2014
236. Hydrogen sulfide inhibits activation of the renin-angiotensin system in diabetic heart
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Yong, Qian-Chen, Chang, Christopher J, Lefer, David J, Baker, Kenneth M, and Kumar, Rajesh
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Cardiovascular ,Hypertension ,Heart Disease ,Diabetes ,5.1 Pharmaceuticals ,2.1 Biological and endogenous factors ,Metabolic and Endocrine ,Biochemistry & Molecular Biology ,Chemical Sciences ,Biological Sciences ,Medical and Health Sciences - Published
- 2014
237. P54 Hydrogen sulfide inhibits activation of the renin-angiotensin system in diabetic heart
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Yong, Qian-Chen, Chang, Christopher J, Lefer, David J, Baker, Kenneth M, and Kumar, Rajesh
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Hypertension ,Diabetes ,Cardiovascular ,Heart Disease ,Development of treatments and therapeutic interventions ,Aetiology ,2.1 Biological and endogenous factors ,5.1 Pharmaceuticals ,Metabolic and endocrine ,Chemical Sciences ,Biological Sciences ,Medical and Health Sciences ,Biochemistry & Molecular Biology - Published
- 2014
238. Making light of stress
- Author
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Chan, Jefferson and Chang, Christopher J
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Medical Biotechnology ,Biological Sciences ,Biomedical and Clinical Sciences ,Animals ,Chemical and Drug Induced Liver Injury ,Female ,Fluorescence Resonance Energy Transfer ,Liver ,Optical Imaging ,Oxidative Stress - Published
- 2014
239. Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin.
- Author
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Huang, Carlos P, Fofana, Mariama, Chan, Jefferson, Chang, Christopher J, and Howell, Stephen B
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Cell Line ,Cell Line ,Tumor ,Animals ,Humans ,Mice ,Neoplasms ,Boron Compounds ,Cisplatin ,Sulfides ,Copper ,Cation Transport Proteins ,Antineoplastic Agents ,Gene Expression Regulation ,Neoplastic ,Up-Regulation ,Drug Resistance ,Neoplasm ,Gene Knockdown Techniques ,SLC31 Proteins ,Tumor ,Gene Expression Regulation ,Neoplastic ,Drug Resistance ,Neoplasm ,Cancer ,2.1 Biological and endogenous factors ,Analytical Chemistry ,Chemical Sciences - Abstract
Mammalian cells express two copper (Cu) influx transporters, CTR1 and CTR2. CTR1 serves as an influx transporter for both Cu and cisplatin (cDDP). In mouse embryo fibroblasts, reduction of CTR1 expression renders cells resistant to cDDP whereas reduction of CTR2 makes them hypersensitive both in vitro and in vivo. To investigate the role of CTR2 on intracellular Cu and cDDP sensitivity its expression was molecularly altered in the human epithelial 2008 cancer cell model. Intracellular exchangeable Cu(+) was measured with the fluorescent probe Coppersensor-3 (CS3). The ability of CS3 to report on changes in intracellular Cu(+) was validated by showing that Cu chelators reduced its signal, and that changes in signal accompanied alterations in expression of the major Cu influx transporter CTR1 and the two Cu efflux transporters, ATP7A and ATP7B. Constitutive knock down of CTR2 mRNA by ∼50% reduced steady-state exchangeable Cu by 22-23% and increased the sensitivity of 2008 cells by a factor of 2.6-2.9 in two separate clones. Over-expression of CTR2 increased exchangeable Cu(+) by 150% and rendered the 2008 cells 2.5-fold resistant to cDDP. The results provide evidence that CS3 can quantitatively assess changes in exchangeable Cu(+), and that CTR2 regulates both the level of exchangeable Cu(+) and sensitivity to cDDP in a model of human epithelial cancer. This study introduces CS3 and related sensors as novel tools for probing and assaying Cu-dependent sensitivity to anticancer therapeutics.
- Published
- 2014
240. Preface for the Forum on Imaging and Sensing: Probing and Utilizing the Elements of Life for Studying and Improving Health and Society
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Chang, Christopher J and Raymond, Kenneth N
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Good Health and Well Being ,Biosensing Techniques ,Health ,Humans ,Molecular Imaging ,Inorganic Chemistry ,Physical Chemistry (incl. Structural) ,Other Chemical Sciences ,Inorganic & Nuclear Chemistry - Published
- 2014
241. Methanogens, Methane and Gastrointestinal Motility
- Author
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Triantafyllou, Konstantinos, Chang, Christopher, and Pimentel, Mark
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Clinical Research ,Oral and gastrointestinal ,Affordable and Clean Energy ,Constipation ,Gastroparesis ,Irritable bowel syndrome ,Methane ,Methanococcus ,Medical Biochemistry and Metabolomics ,Clinical sciences - Abstract
Anaerobic fermentation of the undigested polysaccharide fraction of carbohydrates produces hydrogen in the intestine which is the substrate for methane production by intestinal methanogens. Hydrogen and methane are excreted in the flatus and in breath giving the opportunity to indirectly measure their production using breath testing. Although methane is detected in 30%-50% of the healthy adult population worldwide, its production has been epidemiologically and clinically associated with constipation related diseases, like constipation predominant irritable bowel syndrome and chronic constipation. While a causative relation is not proven yet, there is strong evidence from animal studies that methane delays intestinal transit, possibly acting as a neuromuscular transmitter. This evidence is further supported by the universal finding that methane production (measured by breath test) is associated with delayed transit time in clinical studies. There is also preliminary evidence that antibiotic reduction of methanogens (as evidenced by reduced methane production) predicts the clinical response in terms of symptomatic improvement in patients with constipation predominant irritable bowel syndrome. However, we have not identified yet the mechanism of action of methane on intestinal motility, and since methane production does not account for all constipation associated cases, there is need for high quality clinical trials to examine methane as a biomarker for the diagnosis or as a biomarker that predicts antibiotic treatment response in patients with constipation related disorders.
- Published
- 2014
242. Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens.
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Basu, Subhasree, Rajakaruna, Suren, Dickinson, Bryan C, Chang, Christopher J, and Menko, A Sue
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Eye Disease and Disorders of Vision ,1.1 Normal biological development and functioning ,Underpinning research ,Animals ,Cell Respiration ,Chick Embryo ,Epithelial Cells ,Epithelium ,Fluorescent Dyes ,Hydrogen Peroxide ,Lens ,Crystalline ,Mitochondria ,Onium Compounds ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
PurposeHydrogen peroxide (H2O2) is an endogenously produced reactive oxygen species (ROS) present in a variety of mammalian systems. This particular ROS can play dichotomous roles, being beneficial in some cases and deleterious in others, which reflects the level and location of H2O2 production. While much is known about the redox regulation of ROS by antioxidant and repair systems in the lens, little is known about the endogenous production of H2O2 in embryonic lens tissue or the physiologic relevance of endogenous H2O2 to lens development. This gap in knowledge exists primarily from a lack of reagents that can specifically detect endogenous H2O2 in the intact lens. Here, using a recently developed chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6-AM), which selectively detects H2O2 over related ROS, we examined the endogenous H2O2 signals in the embryonic lens.MethodsEmbryonic day 10 chick whole lenses in ex vivo organ culture and lens epithelial cells in primary culture were loaded with the H2O2 probe PF6-AM. To determine the relationship between localization of mitochondria with active membrane potential and the region of H2O2 production in the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks generation of intracellular ROS production, was used to confirm that the signal from PF6-AM was due to endogenous ROS production. All imaging was performed by live confocal microscopy.ResultsPF6-AM detected endogenous H2O2 in lens epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells grown in primary culture. No endogenous H2O2 signal could be detected in differentiating lens fiber cells with this probe. Treatment with DPI markedly attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the lens epithelium, suggesting that basal generation of ROS occurs in this region. The lens epithelial cells producing an endogenous H2O2 signal were also rich in actively respiring mitochondria.ConclusionsPF6-AM can be used as an effective reagent to detect the presence and localization of endogenous H2O2 in live lens cells.
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- 2014
243. Improvement of human keratinocyte migration by a redox active bioelectric dressing.
- Author
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Banerjee, Jaideep, Das Ghatak, Piya, Roy, Sashwati, Khanna, Savita, Sequin, Emily K, Bellman, Karen, Dickinson, Bryan C, Suri, Prerna, Subramaniam, Vish V, Chang, Christopher J, and Sen, Chandan K
- Subjects
Keratinocytes ,Humans ,Microscopy ,Electron ,Scanning ,Enzyme-Linked Immunosorbent Assay ,Flow Cytometry ,Spectrometry ,X-Ray Emission ,Electric Stimulation ,Bandages ,Wound Healing ,Cell Movement ,Oxidation-Reduction ,Re-Epithelialization ,General Science & Technology - Abstract
Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization.
- Published
- 2014
244. Outcomes of Pleural Space Infections in Patients With Indwelling Pleural Catheters for Active Malignancies.
- Author
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Chang, Christopher H., Ost, David E., Jimenez, Carlos A., Saltijeral, Sahara N., Eapen, Georgie A., Casal, Roberto F., Sabath, Bruce F., Lin, Julie, Cerrillos, Eben, Tinoco, Tamara Nevarez, and Grosu, Horiana B.
- Published
- 2024
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245. Oxidative cyclization reagents reveal tryptophan cation–π interactions.
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Xie, Xiao, Moon, Patrick J., Crossley, Steven W. M., Bischoff, Amanda J., He, Dan, Li, Gen, Dao, Nam, Gonzalez-Valero, Angel, Reeves, Audrey G., McKenna, Jeffrey M., Elledge, Susanna K., Wells, James A., Toste, F. Dean, and Chang, Christopher J.
- Abstract
Methods for selective covalent modification of amino acids on proteins can enable a diverse array of applications, spanning probes and modulators of protein function to proteomics1–3. Owing to their high nucleophilicity, cysteine and lysine residues are the most common points of attachment for protein bioconjugation chemistry through acid–base reactivity3,4. Here we report a redox-based strategy for bioconjugation of tryptophan, the rarest amino acid, using oxaziridine reagents that mimic oxidative cyclization reactions in indole-based alkaloid biosynthetic pathways to achieve highly efficient and specific tryptophan labelling. We establish the broad use of this method, termed tryptophan chemical ligation by cyclization (Trp-CLiC), for selectively appending payloads to tryptophan residues on peptides and proteins with reaction rates that rival traditional click reactions and enabling global profiling of hyper-reactive tryptophan sites across whole proteomes. Notably, these reagents reveal a systematic map of tryptophan residues that participate in cation–π interactions, including functional sites that can regulate protein-mediated phase-separation processes.Global profiling of hyper-reactive tryptophan sites across whole proteomes using tryptophan chemical ligation by cyclization (Trp-CLiC) reveals a systematic map of tryptophan residues that participate in cation–π interactions, including functional sites that can regulate protein-mediated phase-separation processes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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246. Ciliary localization of a light-activated neuronal GPCR shapes behavior
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Winans, Amy M., primary, Friedmann, Drew, additional, Stanley, Cherise, additional, Xiao, Tong, additional, Liu, Tsung-li, additional, Chang, Christopher J., additional, and Isacoff, Ehud Y., additional
- Published
- 2023
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247. S681 Trends of Functional Dyspepsia Hospitalizations and Prevalence of Psychiatric and Non-Psychiatric Co-Morbidities: A Decade-Long Nationwide Analysis
- Author
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Pamarthy, Rahul, primary, Boppana, Vaishnavi, additional, Ali, Hassam, additional, and Chang, Christopher, additional
- Published
- 2023
- Full Text
- View/download PDF
248. S3740 A Rare Case of Metastatic Renal Cell Carcinoma in the Stomach
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Ghosh, Niloy, primary, Alam, Syed, additional, and Chang, Christopher, additional
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- 2023
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249. In vivo bioluminescence imaging of labile iron in xenograft models and liver using FeAL-1, an iron-activatable form of D-luciferin
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Gonciarz, Ryan L., primary, Jiang, Honglin, additional, Tram, Linh, additional, Hugelshofer, Cedric L., additional, Ekpenyong, Oscar, additional, Knemeyer, Ian, additional, Aron, Allegra T., additional, Chang, Christopher J., additional, Flygare, John A., additional, Collisson, Eric A., additional, and Renslo, Adam R., additional
- Published
- 2023
- Full Text
- View/download PDF
250. Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells
- Author
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Tsuchida, Connor A., primary, Brandes, Nadav, additional, Bueno, Raymund, additional, Trinidad, Marena, additional, Mazumder, Thomas, additional, Yu, Bingfei, additional, Hwang, Byungjin, additional, Chang, Christopher, additional, Liu, Jamin, additional, Sun, Yang, additional, Hopkins, Caitlin R., additional, Parker, Kevin R., additional, Qi, Yanyan, additional, Hofman, Laura, additional, Satpathy, Ansuman T., additional, Stadtmauer, Edward A., additional, Cate, Jamie H.D., additional, Eyquem, Justin, additional, Fraietta, Joseph A., additional, June, Carl H., additional, Chang, Howard Y., additional, Ye, Chun Jimmie, additional, and Doudna, Jennifer A., additional
- Published
- 2023
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