Jan Y.-H.,Rutgers University |
Heck D.E.,New York Medical College |
Casillas R.P.,MRIGlobal |
Laskin D.L.,Rutgers University |
Laskin J.D.,Rutgers University
Chemical Research in Toxicology | Year: 2015
The thioredoxin (Trx) system, which consists of Trx and thioredoxin reductase (TrxR), is a major cellular disulfide reduction system important in antioxidant defense. TrxR is a target of mechlorethamine (methylbis(2-chloroethyl)amine; HN2), a bifunctional alkylating agent that covalently binds to selenocysteine/cysteine residues in the redox centers of the enzyme, leading to inactivation and toxicity. Mammalian Trx contains two catalytic cysteines; herein, we determined if HN2 also targets Trx. HN2 caused a time- and concentration-dependent inhibition of purified Trx and Trx in A549 lung epithelial cells. Three Trx cross-linked protein complexes were identified in both cytosolic and nuclear fractions of HN2-treated cells. LC-MS/MS of these complexes identified both Trx and TrxR, indicating that HN2 cross-linked TrxR and Trx. This is supported by our findings of a significant decrease of Trx/TrxR complexes in cytosolic TrxR knockdown cells after HN2 treatment. Using purified recombinant enzymes, the formation of protein cross-links and enzyme inhibition were found to be redox status-dependent; reduced Trx was more sensitive to HN2 inactivation than the oxidized enzyme, and Trx/TrxR cross-links were only observed using reduced enzyme. These data suggest that HN2 directly targets catalytic cysteine residues in Trx resulting in enzyme inactivation and protein complex formation. LC-MS/MS confirmed that HN2 directly alkylated cysteine residues on Trx, including Cys32 and Cys35 in the redox center of the enzyme. Inhibition of the Trx system by HN2 can disrupt cellular thiol-disulfide balance, contributing to vesicant-induced lung toxicity. © 2015 American Chemical Society.
Jan Y.-H.,Rutgers University |
Heck D.E.,New York Medical College |
Malaviya R.,Rutgers University |
Casillas R.P.,MRIGlobal |
And 2 more authors.
Chemical Research in Toxicology | Year: 2014
Oxidative stress plays a key role in mechlorethamine (methylbis(2- chloroethyl)amine, HN2) toxicity. The thioredoxin system, consisting of thioredoxin reductase (TrxR), thioredoxin, and NADPH, is important in redox regulation and protection against oxidative stress. HN2 contains two electrophilic side chains that can react with nucleophilic sites in proteins, leading to changes in their structure and function. We report that HN2 inhibits the cytosolic (TrxR1) and mitochondrial (TrxR2) forms of TrxR in A549 lung epithelial cells. TrxR exists as homodimers under native conditions; monomers can be detected by denaturing and reducing SDS-PAGE followed by western blotting. HN2 treatment caused marked decreases in TrxR1 and TrxR2 monomers along with increases in dimers and oligomers under reducing conditions, indicating that HN2 cross-links TrxR. Cross-links were also observed in rat lung after HN2 treatment. Using purified TrxR1, NADPH reduced, but not oxidized, enzyme was inhibited and cross-linked by HN2. LC-MS/MS analysis of TrxR1 demonstrated that HN2 adducted cysteine- and selenocysteine-containing redox centers forming monoadducts, intramolecule and intermolecule cross-links, resulting in enzyme inhibition. HN2 cross-links two dimeric subunits through intermolecular binding to cysteine 59 in one subunit of the dimer and selenocysteine 498 in the other subunit, confirming the close proximity of the N- and C-terminal redox centers of adjacent subunits. Despite cross-linking and inhibition of TrxR activity by HN2, TrxR continued to mediate menadione redox cycling and generated reactive oxygen species. These data suggest that disruption of the thioredoxin system contributes to oxidative stress and tissue injury induced by HN2. © 2013 American Chemical Society.
Rockx B.,University of Texas Medical Branch |
Winegar R.,MRIGlobal |
Freiberg A.N.,University of Texas Medical Branch
Antiviral Research | Year: 2012
Nipah and Hendra virus are members of a newly identified genus of emerging paramyxoviruses, the henipaviruses. Both viruses have the ability to cause severe pulmonary infection and severe acute encephalitis. Following their discovery in the 1990s, outbreaks caused by these zoonotic paramyxoviruses have been associated with high public health and especially economic threat potential. Currently, only geographic groupings in Asia and Australia have been described for the henipaviruses. However, while few viral isolates are available and more detailed characterization is necessary, there has been recent evidence that divergent henipaviruses might be present on the African continent. This review endeavours to capture recent advances in the field of henipavirus research, with a focus on genome structure and replication mechanisms, reservoir hosts, genetic diversity, pathogenesis and animal models. © 2012 Elsevier B.V..
Frontiers in Microbiology | Year: 2015
Concerns of infectious disease outbreaks have recently reached the forefront of global security issues and resulted in new engagements among foreign science advisors, host country scientists, and officials. There are lessons to be learned from the numerous organizations working in global regions of endemic disease who are building capacity to survey pathogens and prevent and contain epidemics. Working with foreign scientists, health professionals, and administrators can be challenging; building partnerships based on respect and mutual trust is key to achieve effective change. Engendering ownership, working towards mutual success, paying close attention to cultural norms and the local regulatory climate, close collaboration with other stakeholders, and imaginative problem solving all contribute to mission success. © 2015 Horn.
Cowherd Jr. C.,MRIGlobal
Proceedings of the Air and Waste Management Association's Annual Conference and Exhibition, AWMA | Year: 2012
Across the nation, open sources account for the majority of directly emitted PM10, and for emissions of gases, e.g., NH3, biogenic species, and other pollutants of regulatory concern. The use of vehicle-mounted continuous pollutant concentration monitors for mapping at "ground level" the locations and lateral structures of plumes crossing roadways downwind of emission release points was studied. One of the key ad vantages of this approach is the much lower cost of implementation in comparison with other monitoring strategies. This is an abstract of a paper presented at the 105th AWMA Annual Conference and Exhibition (San Antonio, TX 6/19-22/2012).
Court C.D.,MRIGlobal |
Court C.D.,Regional Research Institute
Ecological Economics | Year: 2012
Amid changing attitudes about the environment and emerging sustainability concerns in the late 1960s and 1970s, countries around the world began regulating multiple aspects of solid and hazardous wastes. Initial regulations and those occurring since all share the broader goal of curbing waste generation, especially that of hazardous wastes; but with few signs of progress. Using an input-output accounting framework that focuses on the domestic economy, data on the economy and hazardous waste generation are combined to provide a more complete picture of hazardous waste generation in the United States. The framework developed in this paper can be used to inform decisionmakers of the current state of the "hazardous waste economy" and can also be extended to account for other types of environmental factors. © 2012 Elsevier B.V.
Mriglobal | Date: 2013-12-17
Electric accumulators for vehicles; Electronic location and immobilization devices installed after purchase for use with vehicles; Mechanical and electronic measuring machines for identifying and analyzing structural damage to vehicles; Vehicle safety equipment, namely, electronic vibration, shock, motion, angle, temperature and voltage monitors; Vehicle tracking devices comprised of cellular radio modules, computer software and computer hardware, sensors, transmitters, receivers and global positioning satellite receivers, all for use in connection with vehicle tracking, vehicle monitoring and anti-theft vehicle alarms; None of the foregoing for use in connection with electronic on-board recorders for logging driver-related data, including driver hours of service, for routine management of commercial vehicle fleet operations. Land vehicle console parts, namely, wiring harnesses for control, monitoring and protection of industrial gasoline and diesel engines; Vehicle-mounted motor vehicle crash attenuators; None of the foregoing for use in connection with electronic on-board recorders for logging driver-related data, including driver hours of service, for routine management of commercial vehicle fleet operations.
Mriglobal | Date: 2014-08-26
A particle collector for collecting biological material using electrostatic precipitator (ESP) technology including a removable ESP collection tube having an electrode wire suspended therein, a high voltage power supply coupled to the electrode wire for generating an ionization field within the collection tube causing smaller particles entering the collection tube to precipitate onto the walls of the collection tube, electronics including a microcontroller for controlling the operation of the collector, and a housing assembly for housing the collection tube, the high voltage power supply and the electronics. Some embodiments include an interlock system for disabling high voltage to the electrode wire if certain system parameters are not met, a static discharge mechanism for dissipating excess electrostatic charge which may accumulate on the collection tube during operation, and an altitude adjustment mechanism for adjusting the amount of high voltage supplied to the electrode wire based upon the altitude at which the collector is being used. A portable hand-held embodiment of the particle collector is also disclosed.
Mriglobal | Date: 2013-08-21
A method of culturing fastidious bacteria where a conditioned cell culture medium is prepared in which eukaryotic cells have been cultured, but where the medium is substantially free of the cultured cells. Fastidious bacteria are cultured in the medium. The conditioned cell culture medium can contain secreted factors from the cells. These factors promote the growth of the fastidious bacteria. The fastidious bacterial culture is maintained for a time period sufficient for the fastidious bacteria to multiply. The fastidious bacteria are analyzed using PCR, DNA sequencing or microbiology characterization.
News Article | October 28, 2016
Lepton provides MRIGlobal with VSAT terminals and satellite service to support diagnostic laboratories in West Africa