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Sample records for adsorption toxin tracking

  1. Investigation of diarrhetic shellfish toxins in Lingshan Bay, Yellow Sea, China, using solid-phase adsorption toxin tracking (SPATT).

    PubMed

    Li, Feng-Ling; Li, Zhao-Xin; Guo, Meng-Meng; Wu, Hai-Yan; Zhang, Ting-Ting; Song, Cai-Hu

    2016-08-01

    Early detection of toxin contamination in shellfish (i.e., prior to harvest) would be of considerable advantage to fish farmers, researchers and food safety administrators. In 2004, a solid-phase adsorption toxin tracking (SPATT) technique was developed to study algal toxins in New Zealand shellfish harvesting areas. In subsequent years, the basic idea have been further developed. Using a SPATT method, an investigation into diarrhetic shellfish toxins (DSTs) was conducted over a 10.5-month period in 2012 in shellfish farming areas in Lingshan Bay (Yellow Sea, China). This paper discusses the relationship among DSTs in toxic algae, seawater and contaminated shellfish. OA, DTX1 and PTX2 toxins were found in this shellfish farming area from summer to autumn. In shellfish the maximum concentrations of OA and DTX1 were 81 and 41 ng g(-1) respectively. PTX2 was very low. The maximum levels of OA and DTX1 in seawater were 165 and 56 ng g(-1) respectively, and were detected on June, separated by a 14-day period. Shellfish had accumulated the highest levels of OA and DTX1 recorded in this study. Comparison of the variations in DST levels in seawater showed there to be about 2 weeks for administrators to warn of the potential for toxin contamination in shellfish. Further research to explore the relationship between the variables of seawater temperature, sunlight and salinity, and DSTs in shellfish may help to establish a more suitable model for forecasting DST contamination in shellfish. PMID:27295385

  2. Development of solid phase adsorption toxin tracking (SPATT) for monitoring anatoxin-a and homoanatoxin-a in river water.

    PubMed

    Wood, Susanna A; Holland, Patrick T; MacKenzie, Lincoln

    2011-02-01

    Sampling and monitoring for cyanotoxins can be problematic as concentrations change with environmental and hydrological conditions. Current sampling practices (e.g. grab samples) provide data on cyanotoxins present only at one point in time and may miss areas or times of highest risk. Recent research has identified the widespread distribution of anatoxin-producing benthic cyanobacteria in rivers highlighting the need for development of effective sampling techniques. In this study we evaluated the potential of an in situ method known as solid phase adsorption toxin tracking (SPATT) for collecting and concentrating anatoxin-a (ATX) and homoanatoxin-a (HTX) in river water. Fifteen different adsorption substrates were screened for efficiency of ATX uptake, nine of which retained high proportions (>70%) of ATX. Four substrates were then selected for a 24-h trial in a SPATT bag format in the laboratory. The greatest decrease in ATX in the water was observed with powdered activated carbon (PAC) and Strata-X (a polymeric resin) SPATT bags. A 3-d field study in a river containing toxic benthic cyanobacterial mats was undertaken using PAC and Strata-X SPATT bags. ATX and HTX were detected in all SPATT bags. Surface grab samples were taken throughout the field study and ATX and HTX were only detected in one of the water samples, highlighting the limitations of this currently used method. Both Strata-X and PAC were found to be effective absorbent substrates. PAC has the advantage that it is cheap and readily available and appears to continue to sorb toxins over longer periods than Strata-X. SPATT has the potential to be integrated into current cyanobacterial monitoring programmes and would be a very useful and economical tool for early warning of ATX and HTX contamination in water. PMID:21074244

  3. Monitoring Domoic Acid production by Solid Phase Adsorption Toxin Tracking off the Santa Cruz Municipal Warf, Santa Cruz, California

    NASA Astrophysics Data System (ADS)

    Nolan, M.; Ziccarelli, L.; Kudela, R. M.

    2013-12-01

    Certain species of the diatom genus Pseudo-nitzschia are producers of the neurotoxin, domoic acid (DA). DA is known to cause amnesic shellfish poisoning also known as domoic acid poisoning, which can lead to permanent brain damage in humans and marine mammals. DA accumulates at higher trophic levels, generally due to consumption of toxic cells or through trophic transfer, and can potentially cause death of both humans and marine wildlife. The Santa Cruz Municipal Warf experiences periodic rises in DA concentrations, which can reach toxic levels in shellfish, fish, and other marine organisms. While these increases in toxicity often occur during Pseudo-nitzschia blooms, several periods of elevated DA have occurred when diatom abundance is restricted and/or dominated by non-toxic species, and there is increasing evidence that DA dissolved in seawater may be prevalent. One theory suggests that senescent or dead Pseudo-nitzschia cells sink to the benthos while retaining their toxin and are buried in sediment following the death of a bloom. Therefore, DA may accumulate in the benthos, where it is eventually released during storms or wave and tide conditions that disturb the sediment. We sampled DA in situ using Solid Phase Adsorption Toxin Tracking (SPATT) bags SPATT uses a synthetic resin to capture dissolved DA, allowing for the determination of integrated DA concentrations at known time intervals. The alternative method is mussel biotoxin monitoring, but it is less accurate due to uncertainties in the time of DA accumulation within the mussel, and the lack of uptake of dissolved DA by the mussel. We deployed and collected SPATT off the Santa Cruz Municipal Wharf at multiple depths beginning in February 2013. We expect to see increasing DA following the death of a harmful algal bloom. Under pre-bloom conditions, little to no DA has been detected in mussels or surface SPATT, but DA from SPATT is frequently observed at depth, suggesting that the sediment is exposed to

  4. Ricin detection: tracking active toxin.

    PubMed

    Bozza, William P; Tolleson, William H; Rosado, Leslie A Rivera; Zhang, Baolin

    2015-01-01

    Ricin is a plant toxin with high bioterrorism potential due to its natural abundance and potency in inducing cell death. Early detection of the active toxin is essential for developing appropriate countermeasures. Here we review concepts for designing ricin detection methods, including mechanism of action of the toxin, advantages and disadvantages of current detection assays, and perspectives on the future development of rapid and reliable methods for detecting ricin in environmental samples. PMID:25481398

  5. Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins.

    PubMed

    Fan, Lin; Sun, Geng; Qiu, Jiangbing; Ma, Qimin; Hess, Philipp; Li, Aifeng

    2014-12-19

    In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for 12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (<2 nm) and small mesopores (2 nmadsorption of toxins in seawater at high and low salinity but not in seawater at medium salinity, which demonstrated that the toxin molecules entered into micropores and mesopores (below 10nm in size) in seawaters of high and low salinity. More toxin or other matrix agglomerates were displayed on the surface of resin deployed in the seawater of medium salinity. Taking into consideration the pore-size distribution and surface images, it appears that intra-particle diffusion governs toxin adsorption in seawater at high salinity while film diffusion mainly controls the adsorption process in seawater at medium salinity. This is the first study to confirm that molecules of OA and DTX1 are able to enter into micropores (<2nm) and small mesopores (2-10nm) of HP20 resin in estuarine seawater with high salinity (∼27‰). PMID:25464996

  6. Equilibrium, kinetic and thermodynamic studies on the adsorption of the toxins of Bacillus thuringiensis subsp. kurstaki by clay minerals

    NASA Astrophysics Data System (ADS)

    Fu, Qingling; Deng, Yali; Li, Huishu; Liu, Jie; Hu, Hongqing; Chen, Shouwen; Sa, Tongmin

    2009-02-01

    The persistence of Bacillus thuringiensis ( Bt) toxins in soil is further enhanced through association with soil particles. Such persistence may improve the effectiveness of controlling target pests, but impose a hazard to non-target organisms in soil ecosystems. In this study, the equilibrium adsorption of the Bt toxin by four clay minerals (montmorillonite, kaolinite, goethite, and silicon dioxide) was investigated, and the kinetic and thermodynamic parameters were calculated. The results showed that Bt toxin could be adsorbed easily by minerals, and the adsorption was much easier at low temperature than at high temperature at the initial concentration varying from 0 to 1000 mg L -1. The adsorption fitted well to both Langmuir and Freundlich isotherm models, but the Freundlich equation was more suitable. The pseudo-second-order (PSO) was the best application model to describe the adsorption kinetic. The adsorption process appeared to be controlled by chemical process, and the intra-particle diffusion was not the only rate-controlling step. The negative standard free energy ( ΔGmθr) values of the adsorption indicated that the adsorption of the Bt toxin by the minerals was spontaneous, and the changes of the standard enthalpy ( ΔHmθr) showed that the adsorption of the Bt toxin by montmorillonite was endothermic while the adsorption by the other three minerals was exothermic.

  7. Adsorption characteristics of multiple microcystins and cylindrospermopsin on sediment: Implications for toxin monitoring and drinking water treatment.

    PubMed

    Maghsoudi, Ehsan; Prévost, Michèle; Vo Duy, Sung; Sauvé, Sébastien; Dorner, Sarah

    2015-09-01

    Adsorption of mixtures of cyanotoxins onto sediment as a dominant mechanism in the elimination of cyanotoxins from the aqueous phase has not been extensively investigated. The aim of this study was to investigate adsorption and desorption behavior of six microcystins including microcystin (MC)-LR, RR, YR, LY, LW and LF and cylindrospermopsin (CYN) on natural sediment. Freundlich and Langmuir isotherms could be fitted for MC-LR, RR, YR and CYN. Sorption kinetics showed immediate rapid adsorption for all cyanotoxins: CYN, MCLW and MCLF were adsorbed 72.6%, 56.7% and 55.3% respectively within 2 h. Results of desorption experiments demonstrated that less than 9% of cyanotoxins desorbed from sediment within 96 h. Adsorption of cyanotoxins onto three fractionated sediments particles, clay-silt (<75 μm), find sand (75-315 μm) and coarse sand (315-2000 μm) demonstrated that adsorption capacity of coarse sand fraction for all the tested cyanotoxins was less than 4% of the clay-silt fraction. Results of this study revealed that there is a potential for cyanotoxins to accumulate in the sediments of lakes, as well as in drinking water treatment plants. Monitoring programs must consider cyanotoxins in the particulate phase to avoid largely underestimating toxin concentrations following their release from blooms. PMID:26091872

  8. Detection and source tracking of Escherichia coli, harboring intimin and Shiga toxin genes, isolated from the Little Bighorn River, Montana.

    PubMed

    Hamner, Steve; Broadaway, Susan C; Berg, Ethan; Stettner, Sean; Pyle, Barry H; Big Man, Nita; Old Elk, Joseph; Eggers, Margaret J; Doyle, John; Kindness, Larry; Good Luck, Brandon; Ford, Timothy E; Camper, Anne C

    2014-08-01

    The Little Bighorn River flows through the Crow Indian Reservation in Montana. In 2008, Escherichia coli concentrations as high as 7179 MPN/100 ml were detected in the river at the Crow Agency Water Treatment Plant intake site. During 2008, 2009, and 2012, 10 different serotypes of E. coli, including O157:H7, harboring both intimin and Shiga toxin genes were isolated from a popular swim site of the Little Bighorn River in Crow Agency. As part of a microbial source tracking study, E. coli strains were isolated from river samples as well as from manure collected from a large cattle feeding operation in the upper Little Bighorn River watershed; 23% of 167 isolates of E. coli obtained from the manure tested positive for the intimin gene. Among these manure isolates, 19 were identified as O156:H8, matching the serotype of an isolate collected from a river sampling site close to the cattle feeding area. PMID:24044742

  9. Application of powdered activated carbon for the adsorption of cylindrospermopsin and microcystin toxins from drinking water supplies.

    PubMed

    Ho, Lionel; Lambling, Paul; Bustamante, Heriberto; Duker, Phil; Newcombe, Gayle

    2011-04-01

    Cylindrospermopsin (CYN) and microcystin are two potent toxins that can be produced by cyanobacteria in drinking water supplies. This study investigated the application of powdered activated carbon (PAC) for the removal of these toxins under conditions that could be experienced in a water treatment plant. Two different PACs were evaluated for their ability to remove CYN and four microcystin variants from various drinking water supplies. The removal of natural organic material by the PACs was also determined by measuring the levels of dissolved organic carbon and UV absorbance (at 254 nm). The PACs effectively removed CYN and the microcystins from each of the waters studied, with one of the PACs shown to be more effective, possibly due to its smaller particle diameter. No difference in removal of the toxins was observed using PAC contact times of 30, 45 and 60 min. Furthermore, the effect of water quality on the removal of the toxins was minimal. The microcystin variants were adsorbed in the order: MCRR > MCYR > MCLR > MCLA. CYN was found to be adsorbed similarly to MCRR. PMID:21459402

  10. FAST TRACK COMMUNICATION Tuning the spin state of iron phthalocyanine by ligand adsorption

    NASA Astrophysics Data System (ADS)

    Isvoranu, C.; Wang, B.; Schulte, K.; Ataman, E.; Knudsen, J.; Andersen, J. N.; Bocquet, M. L.; Schnadt, J.

    2010-12-01

    The future use of single-molecule magnets in applications will require the ability to control and manipulate the spin state and magnetization of the magnets by external means. There are different approaches to this control, one being the modification of the magnets by adsorption of small ligand molecules. In this paper we use iron phthalocyanine supported by an Au(111) surface as a model compound and demonstrate, using x-ray photoelectron spectroscopy and density functional theory, that the spin state of the molecule can be tuned to different values (S ~ 0, \\case {1}{2} , 1) by adsorption of ammonia, pyridine, carbon monoxide or nitric oxide on the iron ion. The interaction also leads to electronic decoupling of the iron phthalocyanine from the Au(111) support.

  11. Pertussis toxin

    SciTech Connect

    Sekura, R.D.; Moss, J.; Vaughan, M.

    1985-01-01

    This book contains 13 selections. Some of the titles are: Genetic and Functional Studies of Pertussis Toxin Substrates; Effect of Pertussis Toxin on the Hormonal Responsiveness of Different Tissues; Extracellular Adenylate Cyclase of Bordetella pertussis; and GTP-Regulatory Proteins are Introcellular Messagers: A Model for Hormone Action.

  12. Millipede toxin

    MedlinePlus

    ... toxin are: Hydrochloric acid Hydrogen cyanide Organic acids Phenol Cresols Benzoquinones Hydroquinones (in some millipedes) ... with plenty of soap and water. Do NOT use alcohol to wash the area. Wash eyes with ...

  13. Millipede toxin

    MedlinePlus

    ... release keeps away most predators. Some large millipede species can secrete these toxins as far as 80 ... reactions are mainly seen from contact with tropical species of millipedes. The outlook may be more serious ...

  14. Marine toxins.

    PubMed

    Whittle, K; Gallacher, S

    2000-01-01

    Seafood products are important both nutritionally and economically. Within Europe, some 12 billion Pounds of fishery products are consumed annually and an enormous variety of species are available. Although seafood is rarely implicated in food poisoning, compared to other food sources, it does provide some specific human health hazards unique to this particular resource. Generally, these are toxins from toxic microscopic algae which accumulate through the food-chain. The toxins can cause various neurological and gastrointestinal illnesses and, potentially, consumers are exposed from seafood produced within Europe, from imported products, or from seafood eaten while travelling abroad. The symptoms of illness which may be encountered, the source and mode of action of the toxins, and some emerging problems are described. European legislation aims to ensure the quality and safety of seafood products by prohibiting sale of some toxic species, setting toxin limits, requiring monitoring and controlling imports. PMID:10885118

  15. Tracking micro-optical resonances for identifying and sensing novel procaspase-3 protein marker released from cell cultures in response to toxins

    NASA Astrophysics Data System (ADS)

    Chen, Ying-Jen; Xiang, Wei; Klucken, Jochen; Vollmer, Frank

    2016-04-01

    The response of cells to toxins is commonly investigated by detecting intracellular markers for cell death, such as caspase proteins. This requires the introduction of labels by the permeabilization or complete lysis of cells. Here we introduce a non-invasive tool for monitoring a caspase protein in the extracellular medium. The tool is based on highly sensitive optical micro-devices, referred to as whispering-gallery mode biosensors (WGMBs). WGMBs are functionalized with antibodies for the specific and label-free detection of procaspase-3 released from human embryonic kidney HEK293 and neuroglioma H4 cells after introducing staurosporine and rotenone toxins, respectively. Additional tests show that the extracellular accumulation of procaspase-3 is concomitant with a decrease in cell viability. The hitherto unknown release of procaspase-3 from cells in response to toxins and its accumulation in the medium is further investigated by Western blot, showing that the extracellular detection of procaspase-3 is interrelated with cytotoxicity of alpha-synuclein protein (aSyn) overexpressed in H4 cells. These studies provide evidence for procaspase-3 as a novel extracellular biomarker for cell death, with applications in cytotoxicity tests. Such WGMBs could be applied to further identify as-yet unknown extracellular biomarkers using established antibodies against intracellular antigens.

  16. Tracking micro-optical resonances for identifying and sensing novel procaspase-3 protein marker released from cell cultures in response to toxins.

    PubMed

    Chen, Ying-Jen; Xiang, Wei; Klucken, Jochen; Vollmer, Frank

    2016-04-22

    The response of cells to toxins is commonly investigated by detecting intracellular markers for cell death, such as caspase proteins. This requires the introduction of labels by the permeabilization or complete lysis of cells. Here we introduce a non-invasive tool for monitoring a caspase protein in the extracellular medium. The tool is based on highly sensitive optical micro-devices, referred to as whispering-gallery mode biosensors (WGMBs). WGMBs are functionalized with antibodies for the specific and label-free detection of procaspase-3 released from human embryonic kidney HEK293 and neuroglioma H4 cells after introducing staurosporine and rotenone toxins, respectively. Additional tests show that the extracellular accumulation of procaspase-3 is concomitant with a decrease in cell viability. The hitherto unknown release of procaspase-3 from cells in response to toxins and its accumulation in the medium is further investigated by Western blot, showing that the extracellular detection of procaspase-3 is interrelated with cytotoxicity of alpha-synuclein protein (aSyn) overexpressed in H4 cells. These studies provide evidence for procaspase-3 as a novel extracellular biomarker for cell death, with applications in cytotoxicity tests. Such WGMBs could be applied to further identify as-yet unknown extracellular biomarkers using established antibodies against intracellular antigens. PMID:26963176

  17. Adsorption of mycotoxins in beverages onto functionalized mesoporous silicas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycotoxins, natural toxins produced by fungi, are a global concern as contaminates of agricultural commodities. Exposure to these toxins can be reduced by the use of binding materials. Templated mesoporous silicas are promising materials with favorable adsorptive properties for dyes, ions, and toxin...

  18. BOTULINUM TOXIN

    PubMed Central

    Nigam, P K; Nigam, Anjana

    2010-01-01

    Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C1, C2, D, E, F and G). All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. The weakness induced by injection with botulinum toxin A usually lasts about three months. Botulinum toxins now play a very significant role in the management of a wide variety of medical conditions, especially strabismus and focal dystonias, hemifacial spasm, and various spastic movement disorders, headaches, hypersalivation, hyperhidrosis, and some chronic conditions that respond only partially to medical treatment. The list of possible new indications is rapidly expanding. The cosmetological applications include correction of lines, creases and wrinkling all over the face, chin, neck, and chest to dermatological applications such as hyperhidrosis. Injections with botulinum toxin are generally well tolerated and side effects are few. A precise knowledge and understanding of the functional anatomy of the mimetic muscles is absolutely necessary to correctly use botulinum toxins in clinical practice. PMID:20418969

  19. Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

    NASA Astrophysics Data System (ADS)

    Wyrick, Jonathan; Einstein, T. L.; Bartels, Ludwig

    2015-03-01

    We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species' diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

  20. Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

    SciTech Connect

    Wyrick, Jonathan; Bartels, Ludwig; Einstein, T. L.

    2015-03-14

    We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species’ diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

  1. *CYANOBACTERIA AND THEIR TOXINS

    EPA Science Inventory

    Cyanobacteria, or blue-green algae, are naturally-occurring contaminants of surface waters worldwide. These photosynthesizing prokaryotes thrive in warm, shallow, nutrient-rich waters. Many produce potent toxins as secondary metabolites. Cyanobacteria toxins have been document...

  2. Botulinum toxin injection - larynx

    MedlinePlus

    Injection laryngoplasty; Botox-larynx: spasmodic dysphonia-BTX; Essential voice tremor (EVT)-btx; Glottic insufficiency; Percutaneous electromyography-guided botulinum toxin treatment; Percutaneous indirect laryngoscopy-guided botulinum toxin Treatment; ...

  3. Stool C. difficile toxin

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003590.htm Stool C. difficile toxin To use the sharing features on this page, please enable JavaScript. The stool C. difficile toxin test detects harmful substances produced by ...

  4. Botox (Botulinum Toxin)

    MedlinePlus

    ... people when there are many effective and safe cosmetic procedures that can temporarily reduce a very prominent ... form of botulinum toxin is Type A (Botox® Cosmetic, Allergan, Inc). Botulinum toxin, what we will now ...

  5. Detection of Protein Toxins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have focused on ricin, shiga-like toxin, botulinum neurotoxin (BoNT), and staphylococcal enterotoxin A (SEA), developing sensitive test methods for toxins and marker compounds in food matrices. Although animal models provide the best means for risk assessment, especially for crude toxins in compl...

  6. [Intoxication of botulinum toxin].

    PubMed

    Chudzicka, Aleksandra

    2015-09-01

    Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon. PMID:26449577

  7. Botulinum toxin injection - larynx

    MedlinePlus

    Injection laryngoplasty; Botox-larynx: spasmodic dysphonia-BTX; Essential voice tremor (EVT)-btx; Glottic insufficiency; Percutaneous electromyography-guided botulinum toxin treatment; Percutaneous indirect laryngoscopy- ...

  8. Future Avenues to Decrease Uremic Toxin Concentration.

    PubMed

    Vanholder, Raymond C; Eloot, Sunny; Glorieux, Griet L R L

    2016-04-01

    In this article, we review approaches for decreasing uremic solute concentrations in chronic kidney disease and in particular, in end-stage renal disease (ESRD). The rationale to do so is the straightforward relation between concentration and biological (toxic) effect for most toxins. The first section is devoted to extracorporeal strategies (kidney replacement therapy). In the context of high-flux hemodialysis and hemodiafiltration, we discuss increasing dialyzer blood and dialysate flows, frequent and/or extended dialysis, adsorption, bioartificial kidney, and changing physical conditions within the dialyzer (especially for protein-bound toxins). The next section focuses on the intestinal generation of uremic toxins, which in return is stimulated by uremic conditions. Therapeutic options are probiotics, prebiotics, synbiotics, and intestinal sorbents. Current data are conflicting, and these issues need further study before useful therapeutic concepts are developed. The following section is devoted to preservation of (residual) kidney function. Although many therapeutic options may overlap with therapies provided before ESRD, we focus on specific aspects of ESRD treatment, such as the risks of too-strict blood pressure and glycemic regulation and hemodynamic changes during dialysis. Finally, some recommendations are given on how research might be organized with regard to uremic toxins and their effects, removal, and impact on outcomes of uremic patients. PMID:26500179

  9. Defense against toxin weapons

    SciTech Connect

    Franz, D.R.

    1994-01-01

    The purpose of this manual is to provide basic information on biological toxins to military leaders and health-care providers at all levels to help them make informed decisions on protecting their troops from toxins. Much of the information contained herein will also be of interest to individuals charged with countering domestic and international terrorism. We typically fear what we do not understand.

  10. Preformed bacterial toxins.

    PubMed

    Crane, J K

    1999-09-01

    Food poisoning syndromes caused by four different bacteria are described. For all types, food kept at a permissive temperature allows growth of the vegetative forms of the bacteria and production of a toxin or toxins. The key features of these syndromes, as well as possible new trends of concern, are summarized in Table 1. PMID:10549427

  11. Toxins from Bacteria

    PubMed Central

    Henkel, James S.; Baldwin, Michael R.; Barbieri, Joseph T.

    2010-01-01

    Bacterial toxins damage the host at the site of bacterial infection or distanced from the site of infections. Bacterial toxins can be single proteins or organized as oligomeric protein complexes and are organized with distinct AB structure-function properties. The A domain encodes a catalytic activity; ADP-ribosylation of host proteins is the earliest post-translational modification determine to be performed by bacterial toxin, and now include glucosylation and proteolysis among other s. Bacterial toxins also catalyze the non-covalent modification of host protein function or can modify host cell properties through direct protein-protein interactions. The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers A domain across a lipid bilayer, either on the plasma membrane or the endosome. Bacterial toxins are often characterized based upon the section mechanism that delivers the toxin out of the bacterium, termed type I–VII. This review will overview the major families of bacterial toxins and will also describe the specific structure-function properties of the botulinum neurotoxins. PMID:20358680

  12. Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish

    PubMed Central

    Reguera, Beatriz; Riobó, Pilar; Rodríguez, Francisco; Díaz, Patricio A.; Pizarro, Gemita; Paz, Beatriz; Franco, José M.; Blanco, Juan

    2014-01-01

    Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L−1). They are the main threat, in terms of days of harvesting bans, to aquaculture in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins), and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated. PMID:24447996

  13. Transfer of Select Agents and Toxins: 2003-2013.

    PubMed

    Shelby, Bryan D; Cartagena, Debora; McClee, Vondguraus; Gangadharan, Denise; Weyant, Robbin

    2015-01-01

    The Federal Select Agent Program, which is composed of the Centers for Disease Control and Prevention Division of Select Agents and Toxins and the Animal and Plant Health Inspection Service Agricultural Select Agent Services, regulates entities that possess, use, or transfer biological select agents and toxins in the United States and must preapprove all transfers within or into the US. The requirement to preapprove transfers allows the Federal Select Agent Program to monitor and track shipments to receive alerts of theft, loss, or release during shipment, thereby protecting public health and safety. As part of the program, the Division of Select Agents and Toxins regulates biological select agents and toxins that have been identified by the US government as posing a severe threat to public health and safety. The division analyzed 4,402 transfers that occurred between March 2003 and December 2013 to identify frequently transferred biological select agents and toxins and the types of entities involved in transfers. During the study period, 1 package was lost during shipment and it was determined not to pose a threat to public health. The Federal Bureau of Investigation investigated the loss and concluded that the package was most likely damaged by the commercial carrier and discarded. Further, there were no reports of theft or release associated with biological select agents and toxins shipments. This report represents the first in-depth review of biological select agent and toxin transfers that were approved by the Division of Select Agents and Toxins. PMID:26186667

  14. Understanding malarial toxins.

    PubMed

    Starkl Renar, Katarina; Iskra, Jernej; Križaj, Igor

    2016-09-01

    Recognized since antiquity, malaria is one of the most infamous and widespread infectious diseases in humans and, although the death rate during the last century has been diminishing, it still accounts for more than a half million deaths annually. It is caused by the Plasmodium parasite and typical symptoms include fever, shivering, headache, diaphoresis and nausea, all resulting from an excessive inflammatory response induced by malarial toxins released into the victim's bloodstream. These toxins are hemozoin and glycosylphosphatidylinositols. The former is the final product of the parasite's detoxification of haeme, a by-product of haemoglobin catabolism, while the latter anchor proteins to the Plasmodium cell surface or occur as free molecules. Currently, only two groups of antimalarial toxin drugs exist on the market, quinolines and artemisinins. As we describe, they both target biosynthesis of hemozoin. Other substances, currently in various phases of clinical trials, are directed towards biosynthesis of glycosylphosphatidylinositol, formation of hemozoin, or attenuation of the inflammatory response of the patient. Among the innovative approaches to alleviating the effects of malarial toxins, is the development of antimalarial toxin vaccines. In this review the most important lessons learned from the use of treatments directed against the action of malarial toxins in antimalarial therapy are emphasized and the most relevant and promising directions for future research in obtaining novel antimalarial agents acting on malarial toxins are discussed. PMID:27353131

  15. Bacterial toxins: friends or foes?

    PubMed Central

    Schmitt, C. K.; Meysick, K. C.; O'Brien, A. D.

    1999-01-01

    Many emerging and reemerging bacterial pathogens synthesize toxins that serve as primary virulence factors. We highlight seven bacterial toxins produced by well-established or newly emergent pathogenic microbes. These toxins, which affect eukaryotic cells by a variety of means, include Staphylococcus aureus alpha-toxin, Shiga toxin, cytotoxic necrotizing factor type 1, Escherichia coli heat-stable toxin, botulinum and tetanus neurotoxins, and S. aureus toxic-shock syndrome toxin. For each, we discuss the information available on its synthesis and structure, mode of action, and contribution to virulence. We also review the role certain toxins have played in unraveling signal pathways in eukaryotic cells and summarize the beneficial uses of toxins and toxoids. Our intent is to illustrate the importance of the analysis of bacterial toxins to both basic and applied sciences. PMID:10221874

  16. Evaluation of Passive Samplers as a Monitoring Tool for Early Warning of Dinophysis Toxins in Shellfish

    PubMed Central

    Pizarro, Gemita; Moroño, Ángeles; Paz, Beatriz; Franco, José M.; Pazos, Yolanda; Reguera, Beatriz

    2013-01-01

    From June 2006 to January 2007 passive samplers (solid phase adsorbing toxin tracking, SPATT) were tested as a monitoring tool with weekly monitoring of phytoplankton and toxin content (liquid chromatography–mass spectrometry, LC-MS) in picked cells of Dinophysis and plankton concentrates. Successive blooms of Dinophysis acuminata, D. acuta and D. caudata in 2006 caused a long mussel harvesting closure (4.5 months) in the Galician Rías (NW Spain) and a record (up to 9246 ng·g resin-week−1) accumulation of toxins in SPATT discs. Best fit of a toxin accumulation model was between toxin accumulation in SPATT and the product of cell densities by a constant value, for each species of Dinophysis, of toxin content (average) in picked cells. Detection of Dinophysis populations provided earlier warning of oncoming diarrhetic shellfish poisoning (DSP) outbreaks than the SPATT, which at times overestimated the expected toxin levels in shellfish because: (i) SPATT accumulated toxins did not include biotransformation and depuration loss terms and (ii) accumulation of toxins not available to mussels continued for weeks after Dinophysis cells were undetectable and mussels were toxin-free. SPATT may be a valuable environmental monitoring and research tool for toxin dynamics, in particular in areas with no aquaculture, but does not provide a practical gain for early warning of DSP outbreaks. PMID:24152559

  17. Naturally Occurring Food Toxins

    PubMed Central

    Dolan, Laurie C.; Matulka, Ray A.; Burdock, George A.

    2010-01-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  18. [Toxins as a biological weapon].

    PubMed

    Płusa, Tadeusz

    2015-09-01

    The criteria for recognizing a chemical compound for the toxin are vague and gave it the possibility of inclusion in this group a number of biological agents. Toxins list is extensive, but the interest is focused on bacterial toxins, poisons derived from snake venoms, algae and plant proteins, and small molecules. Particular attention is focused on the so-called "sea" toxins, which include tetrodotoxin, brevetoxin and saxitoxin. This indicates the search for a new hitherto unknown potential bioterrorist threats. PMID:26449572

  19. Toxin plasmids of Clostridium perfringens.

    PubMed

    Li, Jihong; Adams, Vicki; Bannam, Trudi L; Miyamoto, Kazuaki; Garcia, Jorge P; Uzal, Francisco A; Rood, Julian I; McClane, Bruce A

    2013-06-01

    In both humans and animals, Clostridium perfringens is an important cause of histotoxic infections and diseases originating in the intestines, such as enteritis and enterotoxemia. The virulence of this Gram-positive, anaerobic bacterium is heavily dependent upon its prolific toxin-producing ability. Many of the ∼16 toxins produced by C. perfringens are encoded by large plasmids that range in size from ∼45 kb to ∼140 kb. These plasmid-encoded toxins are often closely associated with mobile elements. A C. perfringens strain can carry up to three different toxin plasmids, with a single plasmid carrying up to three distinct toxin genes. Molecular Koch's postulate analyses have established the importance of several plasmid-encoded toxins when C. perfringens disease strains cause enteritis or enterotoxemias. Many toxin plasmids are closely related, suggesting a common evolutionary origin. In particular, most toxin plasmids and some antibiotic resistance plasmids of C. perfringens share an ∼35-kb region containing a Tn916-related conjugation locus named tcp (transfer of clostridial plasmids). This tcp locus can mediate highly efficient conjugative transfer of these toxin or resistance plasmids. For example, conjugative transfer of a toxin plasmid from an infecting strain to C. perfringens normal intestinal flora strains may help to amplify and prolong an infection. Therefore, the presence of toxin genes on conjugative plasmids, particularly in association with insertion sequences that may mobilize these toxin genes, likely provides C. perfringens with considerable virulence plasticity and adaptability when it causes diseases originating in the gastrointestinal tract. PMID:23699255

  20. CYANOBACTERIA AND THEIR TOXINS.

    EPA Science Inventory

    Science Questions

    Harmful algal blooms (HAB) of cyanobacteria, also known as blue-green algae, have recently become more spatially and temporally prevalent in the US and worldwide. Cyanobacteria and their highly potent toxins are a significant hazard for human health and ...

  1. CYANOBACTERIA AND THEIR TOXINS

    EPA Science Inventory

    Science Questions

    Harmful algal blooms (HAB) of cyanobacteria, also known as blue-green algae, have recently become more spatially and temporally prevalent in the US and worldwide. Cyanobacteria and their highly potent toxins are a significant hazard for human health and ...

  2. Toxin-induced respiratory distress.

    PubMed

    McKay, Charles A

    2014-02-01

    This article describes the impact of various toxic substances on the airway and pulmonary system. Pulmonary anatomy and physiology provide the basis for understanding the response to toxin-induced injury. Simple asphyxiants displace oxygen from the inspired air. Respiratory irritants include water-soluble and water-insoluble compounds. Several inhaled agents produce direct airway injury, which may be mediated by caustic, thermal, and hydrocarbon exposures. Unique pulmonary toxins and toxicants are discussed, as well as inhaled toxin mixtures. Several inhaled toxins may also impair oxygen transport. The pulmonary system may also provide a mechanism for systemic toxin delivery on respiratory exposure. PMID:24275172

  3. [Protein toxins of Staphylococcus aureus].

    PubMed

    Shamsutdinov, A F; Tiurin, Iu A

    2014-01-01

    Main scientific-research studies regarding protein bacterial toxins of the most widespread bacteria that belong to Staphylococcus spp. genus and in particular the most pathogenic species for humans--Staphylococcus aureus, are analyzed. Structural and biological properties of protein toxins that have received the name of staphylococcus pyrogenic toxins (PTSAg) are presented. Data regarding genetic regulation of secretion and synthesis of these toxins and 3 main regulatory genetic systems (agr--accessory gene regulator, xpr--extracellular protein regulator, sar--staphylococcal accessory regulator) that coordinate synthesis of the most important protein toxins and enzymes for virulence of S. aureus, are presented. PMID:25051707

  4. Toxins and drug discovery.

    PubMed

    Harvey, Alan L

    2014-12-15

    Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. PMID:25448391

  5. Method for detecting biological toxins

    SciTech Connect

    Ligler, F.S.; Campbell, J.R.

    1992-01-01

    Biological toxins are indirectly detected by using polymerase chain reaction to amplify unique nucleic acid sequences coding for the toxins or enzymes unique to toxin synthesis. Buffer, primers coding for the unique nucleic acid sequences and an amplifying enzyme are added to a sample suspected of containing the toxin. The mixture is then cycled thermally to exponentially amplify any of these unique nucleic acid sequences present in the sample. The amplified sequences can be detected by various means, including fluorescence. Detection of the amplified sequences is indicative of the presence of toxin in the original sample. By using more than one set of labeled primers, the method can be used to simultaneously detect several toxins in a sample.

  6. Recombinant Toxins for Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Pastan, Ira; Fitzgerald, David

    1991-11-01

    Recombinant toxins target cell surface receptors and antigens on tumor cells. They kill by mechanisms different from conventional chemotherapy, so that cross resistance to conventional chemotherapeutic agents should not be a problem. Furthermore, they are not mutagens and should not induce secondary malignancies or accelerate progression of benign malignancies. They can be mass-produced cheaply in bacteria as homogeneous proteins. Either growth factor-toxin fusions or antibody-toxin fusions can be chosen, depending on the cellular target.

  7. Toxin Plasmids of Clostridium perfringens

    PubMed Central

    Li, Jihong; Adams, Vicki; Bannam, Trudi L.; Miyamoto, Kazuaki; Garcia, Jorge P.; Uzal, Francisco A.; Rood, Julian I.

    2013-01-01

    SUMMARY In both humans and animals, Clostridium perfringens is an important cause of histotoxic infections and diseases originating in the intestines, such as enteritis and enterotoxemia. The virulence of this Gram-positive, anaerobic bacterium is heavily dependent upon its prolific toxin-producing ability. Many of the ∼16 toxins produced by C. perfringens are encoded by large plasmids that range in size from ∼45 kb to ∼140 kb. These plasmid-encoded toxins are often closely associated with mobile elements. A C. perfringens strain can carry up to three different toxin plasmids, with a single plasmid carrying up to three distinct toxin genes. Molecular Koch's postulate analyses have established the importance of several plasmid-encoded toxins when C. perfringens disease strains cause enteritis or enterotoxemias. Many toxin plasmids are closely related, suggesting a common evolutionary origin. In particular, most toxin plasmids and some antibiotic resistance plasmids of C. perfringens share an ∼35-kb region containing a Tn916-related conjugation locus named tcp (transfer of clostridial plasmids). This tcp locus can mediate highly efficient conjugative transfer of these toxin or resistance plasmids. For example, conjugative transfer of a toxin plasmid from an infecting strain to C. perfringens normal intestinal flora strains may help to amplify and prolong an infection. Therefore, the presence of toxin genes on conjugative plasmids, particularly in association with insertion sequences that may mobilize these toxin genes, likely provides C. perfringens with considerable virulence plasticity and adaptability when it causes diseases originating in the gastrointestinal tract. PMID:23699255

  8. Lymphocyte receptors for pertussis toxin

    SciTech Connect

    Clark, C.G.; Armstrong, G.D. )

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  9. The assay of diphtheria toxin

    PubMed Central

    Gerwing, Julia; Long, D. A.; Mussett, Marjorie V.

    1957-01-01

    A precise assay of diphtheria toxin is described, based on the linear relationship between the diameter of the skin reaction to, and logarithm of the dose of, toxin. It eliminates the need for preliminary titrations, is economical, provides information about the slope of the log-dose response lines and, therefore, of the validity of the assay, and yields limits of error of potency from the internal evidence of the assay. A study has been made of the effects of avidity, combining power, toxicity and buffering on the assay of diphtheria toxins against the International Standards for both Diphtheria Antitoxin and Schick-Test Toxin. All the toxins assayed against the standard toxin, whatever their other properties might be, gave log-dose response lines of similar slope provided that they were diluted in buffered physiological saline. The assays were therefore valid. These experiments were repeated concurrently in non-immune and in actively immunized guinea-pigs, and comparable figures for potency obtained in both groups. The result was not significantly affected by the avidity or combining power of the toxin. However, non-avid toxins gave low values in Schick units when assayed, by the Römer & Sames technique, in terms of the International Standard for Diphtheria Antitoxin. The problem of the ultimate standard and the implications of these findings are discussed. PMID:13511133

  10. TOXINS FROM CYANOBACTERIA IN WATER

    EPA Science Inventory

    This project is part of a larger U. S. Environmental Protection Agency (EPA) effort, which includes the Office of Water, to investigate algal toxins in surface water supplies and drinking water. Toxins produced by cyanobacteria (blue-green algae) are among the most potent known ...

  11. Botulinum toxin: Bioweapon & magic drug

    PubMed Central

    Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

    2010-01-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin. PMID:21149997

  12. Temperature effects on kinetics of paralytic shellfish toxin elimination in Atlantic surfclams, Spisula solidissima

    NASA Astrophysics Data System (ADS)

    Monica Bricelj, V.; Cembella, Allan D.; Laby, David

    2014-05-01

    Surfclams, Spisula solidissima, pose a particular health risk for human consumption as they are characterized by accumulation of extremely high levels of toxins associated with paralytic shellfish poisoning (PSP), slow toxin elimination and an extremely high post-ingestive capacity for toxin bioconversion. Surfclam populations experience a wide range of temperatures along the NW Atlantic continental shelf, and are undergoing range contraction that has been attributed to global warming. In this study the influence of temperature (5, 12 and 21 °C) on detoxification kinetics of individual PSP toxins in two tissue compartments of juvenile surfclams (∼35 mm shell length) was determined under controlled laboratory conditions, over prolonged (2.4 months) depuration. Clams were toxified with a representative regional Gulf of Maine isolate of the dinoflagellate Alexandrium fundyense of known toxin profile, allowing tracking of changes in toxin composition and calculated toxicity in surfclam tissues. The visceral mass detoxified at all temperatures, although toxin loss rate increased with increasing temperature. In contrast, total toxin content and calculated toxicities in other tissues remained constant or even increased during depuration, suggesting a physiological or biochemical toxin-retention mechanism in this tissue pool and temperature-independent detoxification. In vivo toxin compositional changes in surfclam tissues found in this study provide evidence of specific toxin conversion pathways, involving both reductive and decarbamoylation pathways. We conclude that such toxin biotransformations, especially in non-visceral tissues, may introduce a discrepancy in describing kinetics of total toxicity (in saxitoxin equivalents [STXeq]) of S. solidissima over prolonged detoxification. Nevertheless, use of total toxicity values generated by routine regulatory monitoring based upon mouse bioassays or calculated from chemical analytical determination of molar toxin

  13. Binding of ATP by pertussis toxin and isolated toxin subunits

    SciTech Connect

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L. )

    1990-07-03

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.

  14. Food toxin detection with atomic force microscope

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Externally introduced toxins or internal spoilage correlated pathogens and their metabolites are all potential sources of food toxins. To prevent and protect unsafe food, many food toxin detection techniques have been developed to detect various toxins for quality control. Although several routine m...

  15. Detecting and discriminating among Shiga toxins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The virulence associated with Shiga toxin producing Escherichia coli (STEC) infections is from the Shiga toxins produced by the E. coli strain. Although Shiga toxins are associated with E. coli, the expression of the toxins is actually controlled by a temperate lambdoid phage that infects the host. ...

  16. Botulinum toxin for pain.

    PubMed

    Casale, Roberto; Tugnoli, Valeria

    2008-01-01

    Botulinum toxin (BTX) injection is being increasingly used 'off label' in the management of chronic pain. Data support the hypothesis of a direct analgesic effect of BTX, different to that exerted on muscle. Although the pain-reducing effect of BTX is mainly due to its ability to block acetylcholine release at the synapse, other effects on the nervous system are also thought to be involved. BTX affects cholinergic transmission in both the somatic and the autonomic nervous systems. Proposed mechanisms of action of BTX for pain relief of trigger points, muscular spasms, fibromyalgia and myofascial pain include direct action on muscle and indirect effects via action at the neuromuscular junction. Invitro and invivo data have shown that BTX has specific antinociceptive activity relating to its effects on inflammation, axonal transport, ganglion inhibition, and spinal and suprasegmental level inhibition. Our review of the mechanisms of action, efficacy, administration techniques and therapeutic dosage of BTX for the management of chronic pain in a variety of conditions shows that although muscular tone and movement disorders remain the most important therapeutic applications for BTX, research suggests that BTX can also provide benefits related to effects on cholinergic control of the vascular system, autonomic function, and cholinergic control of nociceptive and antinociceptive systems. Furthermore, it appears that BTX may influence the peripheral and central nervous systems. The therapeutic potential of BTX depends mainly on the ability to deliver the toxin to the target structures, cholinergic or otherwise. Evidence suggests that BTX can be administered at standard dosages in pain disorders, where the objective is alteration of muscle tone. For conditions requiring an analgesic effect, the optimal therapeutic dosage of BTX remains to be defined. PMID:18095750

  17. Shiga Toxin Producing Escherichia coli.

    PubMed

    Bryan, Allen; Youngster, Ilan; McAdam, Alexander J

    2015-06-01

    Shiga toxin-producing Escherichia coli (STEC) is among the common causes of foodborne gastroenteritis. STEC is defined by the production of specific toxins, but within this pathotype there is a diverse group of organisms. This diversity has important consequences for understanding the pathogenesis of the organism, as well as for selecting the optimum strategy for diagnostic testing in the clinical laboratory. This review includes discussions of the mechanisms of pathogenesis, the range of manifestations of infection, and the several different methods of laboratory detection of Shiga toxin-producing E coli. PMID:26004641

  18. Diphtheria toxin-based targeted toxin therapy for brain tumors.

    PubMed

    Li, Yan Michael; Vallera, Daniel A; Hall, Walter A

    2013-09-01

    Targeted toxins (TT) are molecules that bind cell surface antigens or receptors such as the transferrin or interleukin-13 receptor that are overexpressed in cancer. After internalization, the toxin component kills the cell. These recombinant proteins consist of an antibody or carrier ligand coupled to a modified plant or bacterial toxin such as diphtheria toxin (DT). These fusion proteins are very effective against brain cancer cells that are resistant to radiation therapy and chemotherapy. TT have shown an acceptable profile for toxicity and safety in animal studies and early clinical trials have demonstrated a therapeutic response. This review summarizes the characteristics of DT-based TT, the animal studies in malignant brain tumors and early clinical trial results. Obstacles to the successful treatment of brain tumors include poor penetration into tumor, the immune response to DT and cancer heterogeneity. PMID:23695514

  19. [Shiga toxin and tetanus toxin as a potential biologic weapon].

    PubMed

    Toczyska, Izabela; Płusa, Tadeusz

    2015-09-01

    Toxins produced by the bacteria are of particular interest as potential cargo combat possible for use in a terrorist attack or war. Shiga toxin is usually produced by shiga toxigenic strains of Escherichia coli (STEC - shigatoxigenic Escherichia coli). To infection occurs mostly after eating contaminated beef. Clinical syndromes associated with Shiga toxin diarrhea, hemorrhagic colitis, hemolytic uremic syndrome (HUS - hemolytic uremic syndrome) or thrombotic thrombocytopenic purpura. Treatment is symptomatic. In HUS, in which mortality during an epidemic reaches 20%, extending the kidney injury dialysis may be necessary. Exposure to tetanus toxin produced by Clostridium tetani, resulting in the most generalized tetanus, characterized by increased muscle tension and painful contractions of individual muscle groups. In the treatment beyond symptomatic behavior (among others spasticity medications, anticonvulsants, muscle relaxants) is used tetanus antitoxin and antibiotics (metronidazole choice). A common complication is acute respiratory failure - then it is necessary to implement mechanical ventilation. PMID:26449578

  20. Epsilon toxin: a fascinating pore-forming toxin.

    PubMed

    Popoff, Michel R

    2011-12-01

    Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or type D. ETX belongs to the heptameric β-pore-forming toxins including aerolysin and Clostridium septicum alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells consisting in a β-barrel of 14 amphipatic β strands. By contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin and is responsible for enterotoxemia in animals, mainly sheep. ETX induces perivascular edema in various tissues and accumulates in particular in the kidneys and brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood-brain barrier and stimulate the release of glutamate, which accounts for the symptoms of nervous excitation observed in animal enterotoxemia. At the cellular level, ETX causes rapid swelling followed by cell death involving necrosis. The precise mode of action of ETX remains to be determined. ETX is a powerful toxin, however, it also represents a unique tool with which to vehicle drugs into the central nervous system or target glutamatergic neurons. PMID:21535407

  1. Removal of zearalenone toxin from synthetics gastric and body fluids using talc and diatomite: a batch kinetic study.

    PubMed

    Sprynskyy, Myroslav; Gadzała-Kopciuch, Renata; Nowak, Karolina; Buszewski, Bogusław

    2012-06-01

    Adsorption kinetics of zearalenone (ZEA) toxin from synthetic gastric fluid (SGF) and synthetic body fluid (SBF) by talc and diatomite was studied in the batch experiments. Chemical composition, morphology and structure of the used adsorbents were examined by scanning electron microscopy, FTIR spectroscopy and low-temperature nitrogen adsorption/desorption method. High performance liquid chromatography (HPLC) method was used for ZEA determining. The study results showed that ZEA is more effectively adsorbed on the talc (73% and 54% from SGF and SBF respectively). The efficiency on the diatomite was lower (53% and 42% from SGF and SBF respectively). The first order kinetics model was applied to describe the adsorption process. Rate of the ZEA adsorption from SGF is very rapid initially with about 95% of amount of the toxin adsorbed during first 5 min, while ZEA is adsorbed from SBF in two steps. The values of determined Gibbs free energy of adsorption (from -13 to -17 kJ/mol) indicated that adsorption of ZEA toxin by the both adsorbents are spontaneous and exothermic. PMID:22326340

  2. [Today's threat of ricin toxin].

    PubMed

    From, Sławomir; Płusa, Tadeusz

    2015-09-01

    Since the late 70s of the last century there were more than 700 incidents related to the use of the ricin toxin. For this reason, CDC (Center of Disease Control and Prevention) recognized toxin as a biological weapon category B. The lethal dose of ricin toxin after parenteral administration is 0.0001 mg/kg and after oral administration 0.2 mg. The first symptoms of poisoning occur within a few hours after application of toxin as a nausea, vomiting and abdominal pain. In the final stage there are observed: cardiac arrhythmia, collapse and symptoms suggestive of involvement of the central nervous system. Stage immediately preceding death is a state of coma. The ricin toxin is still the substance against which action has no optimal antidote. Developed a vaccine called RiVax is waiting for its registration. It should be pointed out that the availability of a ricin toxin makes it possible to use it for real bioterrorists. PMID:26449579

  3. Removal of cyanobacterial toxins by sediment passage

    NASA Astrophysics Data System (ADS)

    Gruetzmacher, G.; Boettcher, G.; Chorus, I.; Bartel, H.

    2003-04-01

    Cyanbacterial toxins ("Cyanotoxins") comprise a wide range of toxic substances produced by cyanobacteria ("blue-green algae"). Cyanobacteria occur in surface water word wide and can be found in high concentrations during so-called algal blooms when conditions are favourable (e.g. high nutrient levels, high temperatures). Some cyanobacteria produce hepato- or neurotoxins, of which the hepatotoxic microcystins are the most common in Germany. The WHO guideline value for drinking water was set at 1 μg/L. However, maximum concentrations in surface water can reach 25 mg/L, so that a secure method for toxin elimination has to be found when this water is used as source water for drinking water production. In order to assess if cyanotoxins can be removed by sediment passage the German Federal Environmental Agency (UBA) conducted laboratory- and field scale experiments as well as observations on bank filtration field sites. Laboratory experiments (batch- and column experiments for adsorption and degradation parameters) were conducted in order to vary a multitude of experimental conditions. These experiments were followed by field scale experiments on the UBA's experimental field in Berlin. This plant offers the unique possibility to conduct experiments on the behaviour of various agents - such as harmful substances - during infiltration and bank filtration under well-defined conditions on a field scale, and without releasing these substances to the environment. Finally the development of microcystin concentrations was observed between infiltrating surface water and a drinking water well along a transsecte of observation wells. The results obtained show that infiltration and bank filtration normally seem to be secure treatment methods for source water contaminated by microcystins. However, elimination was shown to be difficult under the following circumstances: - dying cyanobacterial population due to insufficient light and / or nutrients, low temperatures or application of

  4. [Toxins of Clostridium perfringens].

    PubMed

    Morris, W E; Fernández-Miyakawa, M E

    2009-01-01

    Clostridium perfringens is an anaerobic gram-positive spore-forming bacillus. It is one of the pathogens with larger distribution in the environment; it can be isolated from soil and water samples, which also belongs to the intestinal flora of animals and humans. However, on some occasions it can act as an opportunistic pathogen, causing diseases such as gas gangrene, enterotoxemia in sheep and goats and lamb dysentery, among others. In human beings, it is associated to diseases such as food poisoning, necrotic enterocolitis of the infant and necrotic enteritis or pigbel in Papua-New Guinea tribes. The renewed interest existing nowadays in the study of C. perfringens as a veterinarian and human pathogen, together with the advance of molecular biology, had enabled science to have deeper knowledge of the biology and pathology of these bacteria. In this review, we discuss and update the principal aspects of C. perfringens intestinal pathology, in terms of the toxins with major medical relevance at present. PMID:20085190

  5. Induction of apoptosis by Shiga toxins

    PubMed Central

    Tesh, Vernon L

    2010-01-01

    Shiga toxins comprise a family of structurally and functionally related protein toxins expressed by Shigella dysenteriae serotype 1 and multiple serotypes of Escherichia coli. While the capacity of Shiga toxins to inhibit protein synthesis by catalytic inactivation of eukaryotic ribosomes has been well described, it is also apparent that Shiga toxins trigger apoptosis in many cell types. This review presents evidence that Shiga toxins induce apoptosis of epithelial, endothelial, leukocytic, lymphoid and neuronal cells. Apoptotic signaling pathways activated by the toxins are reviewed with an emphasis on signaling mechanisms that are shared among different cell types. Data suggesting that Shiga toxins induce apoptosis through the endoplasmic reticulum stress response and clinical evidence demonstrating apoptosis in humans infected with Shiga toxin-producing bacteria are briefly discussed. The potential for use of Shiga toxins to induce apoptosis in cancer cells is briefly reviewed. PMID:20210553

  6. Antibody-based biological toxin detection

    SciTech Connect

    Menking, D.E.; Goode, M.T.

    1995-12-01

    Fiber optic evanescent fluorosensors are under investigation in our laboratory for the study of drug-receptor interactions for detection of threat agents and antibody-antigen interactions for detection of biological toxins. In a direct competition assay, antibodies against Cholera toxin, Staphylococcus Enterotoxin B or ricin were noncovalently immobilized on quartz fibers and probed with fluorescein isothiocyanate (FITC) - labeled toxins. In the indirect competition assay, Cholera toxin or Botulinum toxoid A was immobilized onto the fiber, followed by incubation in an antiserum or partially purified anti-toxin IgG. These were then probed with FITC-anti-IgG antibodies. Unlabeled toxins competed with labeled toxins or anti-toxin IgG in a dose dependent manner and the detection of the toxins was in the nanomolar range.

  7. Derailing Tracking.

    ERIC Educational Resources Information Center

    Black, Susan

    1993-01-01

    Reviews recent research on student achievement, self-concept, and curriculum and instruction showing the ineffectiveness of tracking and ability grouping. Certain court rulings show that tracking violates the equal protection clause of the Fourteenth Amendment. Innovative alternatives include cooperative learning, mastery learning, peer tutoring,…

  8. Beyond Tracking.

    ERIC Educational Resources Information Center

    Bates, Percy; And Others

    1992-01-01

    On the surface, educational tracking may seem like a useful tool for allowing students to work at their own pace, and to avoid discouraging competition, but abuses of the tracking idea have arisen through biased placement practices that have denied equal access to education for minority students. The articles in this issue explore a number of…

  9. Adsorption Refrigeration System

    SciTech Connect

    Wang, Kai; Vineyard, Edward Allan

    2011-01-01

    Adsorption refrigeration is an environmentally friendly cooling technology which could be driven by recovered waste heat or low-grade heat such as solar energy. In comparison with absorption system, an adsorption system has no problems such as corrosion at high temperature and salt crystallization. In comparison with vapor compression refrigeration system, it has the advantages of simple control, no moving parts and less noise. This paper introduces the basic theory of adsorption cycle as well as the advanced adsorption cycles such as heat and mass recovery cycle, thermal wave cycle and convection thermal wave cycle. The types, characteristics, advantages and drawbacks of different adsorbents used in adsorption refrigeration systems are also summarized. This article will increase the awareness of this emerging cooling technology among the HVAC engineers and help them select appropriate adsorption systems in energy-efficient building design.

  10. Rover tracks

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Tracks made by the Sojourner rover are visible in this image, taken by one of the cameras aboard Sojourner on Sol 3. The tracks represent the rover maneuvering towards the rock dubbed 'Barnacle Bill.' The rover, having exited the lander via the rear ramp, first traveled towards the right portion of the image, and then moved forward towards the left where Barnacle Bill sits. The fact that the rover was making defined tracks indicates that the soil is made up of particles on a micron scale.

    Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration.

  11. Sodium Channel Inhibiting Marine Toxins

    NASA Astrophysics Data System (ADS)

    Llewellyn, Lyndon E.

    Saxitoxin (STX), tetrodotoxin (TTX) and their many chemical relatives are part of our daily lives. From killing people who eat seafood containing these toxins, to being valuable research tools unveiling the invisible structures of their pharmacological receptor, their global impact is beyond measure. The pharmacological receptor for these toxins is the voltage-gated sodium channel which transports Na ions between the exterior to the interior of cells. The two structurally divergent families of STX and TTX analogues bind at the same location on these Na channels to stop the flow of ions. This can affect nerves, muscles and biological senses of most animals. It is through these and other toxins that we have developed much of our fundamental understanding of the Na channel and its part in generating action potentials in excitable cells.

  12. Uraemic toxins and new methods to control their accumulation: game changers for the concept of dialysis adequacy

    PubMed Central

    Glorieux, Griet; Tattersall, James

    2015-01-01

    The current concept of an adequate dialysis based only on the dialysis process itself is rather limited. We now have considerable knowledge of uraemic toxicity and improved tools for limiting uraemic toxin accumulation. It is time to make use of these. A broader concept of adequacy that focusses on uraemic toxicity is required. As discussed in the present review, adequacy could be achieved by many different methods in combination with, or instead of, dialysis. These include preservation of renal function, dietary intake, reducing uraemic toxin generation rate and intestinal absorption, isolated ultrafiltration and extracorporeal adsorption of key uraemic toxins. A better measure of the quality of dialysis treatment would quantify the uraemic state in the patient using levels of a panel of key uraemic toxins. Treatment would focus on controlling uraemic toxicity while reducing harm or inconvenience to the patient. Delivering more dialysis might not be the best way to achieve this. PMID:26251699

  13. Toxin yet not toxic: Botulinum toxin in dentistry.

    PubMed

    Archana, M S

    2016-04-01

    Paracelsus contrasted poisons from nonpoisons, stating that "All things are poisons, and there is nothing that is harmless; the dose alone decides that something is a poison". Living organisms, such as plants, animals, and microorganisms, constitute a huge source of pharmaceutically useful medicines and toxins. Depending on their source, toxins can be categorized as phytotoxins, mycotoxins, or zootoxins, which include venoms and bacterial toxins. Any toxin can be harmful or beneficial. Within the last 100 years, the perception of botulinum neurotoxin (BTX) has evolved from that of a poison to a versatile clinical agent with various uses. BTX plays a key role in the management of many orofacial and dental disorders. Its indications are rapidly expanding, with ongoing trials for further applications. However, despite its clinical use, what BTX specifically does in each condition is still not clear. The main aim of this review is to describe some of the unclear aspects of this potentially useful agent, with a focus on the current research in dentistry. PMID:27486290

  14. ARSENIC TREATMENT BY ADSORPTIVE TECHNOLOGY

    EPA Science Inventory

    Presentation will discuss the removal of arsenic from drinking water using the adsorptive media treatment process. Fundamental information is provided on the design and operation of adsorptive media technology including the selection of the adsorptive media. The information cites...

  15. A Simple Adsorption Experiment

    ERIC Educational Resources Information Center

    Guirado, Gonzalo; Ayllon, Jose A.

    2011-01-01

    The study of adsorption phenomenon is one of the most relevant and traditional physical chemistry experiments performed by chemistry undergraduate students in laboratory courses. In this article, we describe an easy, inexpensive, and straightforward way to experimentally determine adsorption isotherms using pieces of filter paper as the adsorbent…

  16. Selective toxin-lipid membrane interactions of natural, haemolytic Scyphozoan toxins analyzed by surface plasmon resonance.

    PubMed

    Helmholz, Heike

    2010-10-01

    A comparison of the molecular interaction of natural Scyphozoan lysins with their bioactivity in a haemolytic assay was performed by establishing an efficient, automatable and reproducible procedure for the measurement of protein-membrane interactions. The toxin-membrane interactions were analyzed utilising a chip-based technology with immobilized liposomes as artificial cell membranes. The technique was established with streptolysin O as a cholesterol-selective model toxin and its cholesterol-selectivity has been proven. The haemolytic potency of protein fractions derived from the venom of the jellyfish Aurelia aurita and Cyanea capillata was tested and EC50 values of 35.3mug/mL and 43.1mug/mL against sheep and 13.5mug/mL and 8.8mug/mL against rabbit erythrocytes were measured. Cell membrane binding as a first step in the haemolytic process was analyzed using the Biacore((R)) technology. Major cell membrane lipids (cholesterol, sphingomyelin and phosphatidylcholine) were immobilized as pure liposomes and in binary mixtures. A preference for cholesterol and sphingomyelin of both jellyfish species was demonstrated. The specificity of the method was proven with a non-haemolytic A. aurita protein fraction that did not express a lipid binding. Additionally, an inactivated C. capillata lysine with negligible haemolytic activity showed a remaining but reduced adsorption onto lipid layers. The binding level of the lytic venom fraction of these dominant boreal jellyfish species increased as a function of protein concentration. The binding strength was expressed in RU50 values ranging from 12.4mug/mL to 35.4mug/mL, which were in the same order of magnitude as the EC50 values in the haemolytic assay. PMID:20599534

  17. Risk assessment of shellfish toxins.

    PubMed

    Munday, Rex; Reeve, John

    2013-11-01

    Complex secondary metabolites, some of which are highly toxic to mammals, are produced by many marine organisms. Some of these organisms are important food sources for marine animals and, when ingested, the toxins that they produce may be absorbed and stored in the tissues of the predators, which then become toxic to animals higher up the food chain. This is a particular problem with shellfish, and many cases of poisoning are reported in shellfish consumers each year. At present, there is no practicable means of preventing uptake of the toxins by shellfish or of removing them after harvesting. Assessment of the risk posed by such toxins is therefore required in order to determine levels that are unlikely to cause adverse effects in humans and to permit the establishment of regulatory limits in shellfish for human consumption. In the present review, the basic principles of risk assessment are described, and the progress made toward robust risk assessment of seafood toxins is discussed. While good progress has been made, it is clear that further toxicological studies are required before this goal is fully achieved. PMID:24226039

  18. Risk Assessment of Shellfish Toxins

    PubMed Central

    Munday, Rex; Reeve, John

    2013-01-01

    Complex secondary metabolites, some of which are highly toxic to mammals, are produced by many marine organisms. Some of these organisms are important food sources for marine animals and, when ingested, the toxins that they produce may be absorbed and stored in the tissues of the predators, which then become toxic to animals higher up the food chain. This is a particular problem with shellfish, and many cases of poisoning are reported in shellfish consumers each year. At present, there is no practicable means of preventing uptake of the toxins by shellfish or of removing them after harvesting. Assessment of the risk posed by such toxins is therefore required in order to determine levels that are unlikely to cause adverse effects in humans and to permit the establishment of regulatory limits in shellfish for human consumption. In the present review, the basic principles of risk assessment are described, and the progress made toward robust risk assessment of seafood toxins is discussed. While good progress has been made, it is clear that further toxicological studies are required before this goal is fully achieved. PMID:24226039

  19. MCEARD - CYANOBACTERIA AND THEIR TOXINS

    EPA Science Inventory

    Harmful algal blooms (HAB) of cyanobacteria, also known as blue-green algae, have recently become more spatially and temporally prevalent in the US and worldwide. Waterborne cyanobacteria and their highly potent toxins are a significant hazard for human health and the ecosystem....

  20. Intravital imaging of Bacillus thuringiensis Cry1A toxin binding sites in the midgut of silkworm.

    PubMed

    Li, Na; Wang, Jing; Han, Heyou; Huang, Liang; Shao, Feng; Li, Xuepu

    2014-02-15

    Identification of the resistance mechanism of insects against Bacillus thuringiensis Cry1A toxin is becoming an increasingly challenging task. This fact highlights the need for establishing new methods to further explore the molecular interactions of Cry1A toxin with insects and the receptor-binding region of Cry1A toxins for their wider application as biopesticides and a gene source for gene-modified crops. In this contribution, a quantum dot-based near-infrared fluorescence imaging method has been applied for direct dynamic tracking of the specific binding of Cry1A toxins, CrylAa and CrylAc, to the midgut tissue of silkworm. The in vitro fluorescence imaging displayed the higher binding specificity of CrylAa-QD probes compared to CrylAc-QD to the brush border membrane vesicles of midgut from silkworm. The in vivo imaging demonstrated that more CrylAa-QDs binding to silkworm midgut could be effectively and distinctly monitored in living silkworms. Furthermore, frozen section analysis clearly indicated the broader receptor-binding region of Cry1Aa compared to that of Cry1Ac in the midgut part. These observations suggest that the insecticidal activity of Cry toxins may depend on the receptor-binding sites, and this scatheless and visual near-infrared fluorescence imaging could provide a new avenue to study the resistance mechanism to maintain the insecticidal activity of B. thuringiensis toxins. PMID:24252542

  1. Toxins as Weapons: A Historical Review.

    PubMed

    Pita, R; Romero, A

    2014-07-01

    This review article summarizes the use of toxins as weapons dating from the First World War until today, when there is a high concern of possible terrorist attacks with weapons of mass destruction. All through modern history, military programs and terrorist groups have favored toxins because of their high toxicity. However, difficulties of extraction or synthesis, as well as effective dissemination to cause a large number of casualties, have been the most important drawbacks. Special emphasis is focused on ricin and botulinum toxin, the most important toxins that have attracted the attention of military programs and terrorist groups. Other toxins like trichothecenes, saxitoxin, and Staphylococcal enterotoxin B (SEB) are also discussed. A short section about anthrax is also included: Although Bacillus anthracis is considered a biological weapon rather than a toxin weapon, it produces a toxin that is finally responsible for the anthrax disease. PMID:26227025

  2. Nemertean toxin genes revealed through transcriptome sequencing.

    PubMed

    Whelan, Nathan V; Kocot, Kevin M; Santos, Scott R; Halanych, Kenneth M

    2014-12-01

    Nemerteans are one of few animal groups that have evolved the ability to utilize toxins for both defense and subduing prey, but little is known about specific nemertean toxins. In particular, no study has identified specific toxin genes even though peptide toxins are known from some nemertean species. Information about toxin genes is needed to better understand evolution of toxins across animals and possibly provide novel targets for pharmaceutical and industrial applications. We sequenced and annotated transcriptomes of two free-living and one commensal nemertean and annotated an additional six publicly available nemertean transcriptomes to identify putative toxin genes. Approximately 63-74% of predicted open reading frames in each transcriptome were annotated with gene names, and all species had similar percentages of transcripts annotated with each higher-level GO term. Every nemertean analyzed possessed genes with high sequence similarities to known animal toxins including those from stonefish, cephalopods, and sea anemones. One toxin-like gene found in all nemerteans analyzed had high sequence similarity to Plancitoxin-1, a DNase II hepatotoxin that may function well at low pH, which suggests that the acidic body walls of some nemerteans could work to enhance the efficacy of protein toxins. The highest number of toxin-like genes found in any one species was seven and the lowest was three. The diversity of toxin-like nemertean genes found here is greater than previously documented, and these animals are likely an ideal system for exploring toxin evolution and industrial applications of toxins. PMID:25432940

  3. Nemertean Toxin Genes Revealed through Transcriptome Sequencing

    PubMed Central

    Whelan, Nathan V.; Kocot, Kevin M.; Santos, Scott R.; Halanych, Kenneth M.

    2014-01-01

    Nemerteans are one of few animal groups that have evolved the ability to utilize toxins for both defense and subduing prey, but little is known about specific nemertean toxins. In particular, no study has identified specific toxin genes even though peptide toxins are known from some nemertean species. Information about toxin genes is needed to better understand evolution of toxins across animals and possibly provide novel targets for pharmaceutical and industrial applications. We sequenced and annotated transcriptomes of two free-living and one commensal nemertean and annotated an additional six publicly available nemertean transcriptomes to identify putative toxin genes. Approximately 63–74% of predicted open reading frames in each transcriptome were annotated with gene names, and all species had similar percentages of transcripts annotated with each higher-level GO term. Every nemertean analyzed possessed genes with high sequence similarities to known animal toxins including those from stonefish, cephalopods, and sea anemones. One toxin-like gene found in all nemerteans analyzed had high sequence similarity to Plancitoxin-1, a DNase II hepatotoxin that may function well at low pH, which suggests that the acidic body walls of some nemerteans could work to enhance the efficacy of protein toxins. The highest number of toxin-like genes found in any one species was seven and the lowest was three. The diversity of toxin-like nemertean genes found here is greater than previously documented, and these animals are likely an ideal system for exploring toxin evolution and industrial applications of toxins. PMID:25432940

  4. Hybrid adsorptive membrane reactor

    DOEpatents

    Tsotsis, Theodore T.; Sahimi, Muhammad; Fayyaz-Najafi, Babak; Harale, Aadesh; Park, Byoung-Gi; Liu, Paul K. T.

    2011-03-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  5. Hybrid adsorptive membrane reactor

    NASA Technical Reports Server (NTRS)

    Tsotsis, Theodore T. (Inventor); Sahimi, Muhammad (Inventor); Fayyaz-Najafi, Babak (Inventor); Harale, Aadesh (Inventor); Park, Byoung-Gi (Inventor); Liu, Paul K. T. (Inventor)

    2011-01-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  6. Why do we study animal toxins?

    PubMed Central

    ZHANG, Yun

    2015-01-01

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  7. Why do we study animal toxins?

    PubMed

    Zhang, Yun

    2015-07-18

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  8. Botulinum Toxin in Pediatric Neurology

    PubMed Central

    Abdallah, Enas Abdallah Ali

    2015-01-01

    Botulinum neurotoxins are natural molecules produced by anaerobic spore-forming bacteria called Clostradium boltulinum. The toxin has a peculiar mechanism of action by preventing the release of acetylcholine from the presynaptic membrane. Consequently, it has been used in the treatment of various neurological conditions related to muscle hyperactivity and/or spasticity. Also, it has an impact on the autonomic nervous system by acting on smooth muscle, leading to its use in the management of pain syndromes. The use of botulinum toxin in children separate from adults has received very little attention in the literature. This review presents the current data on the use of botulinum neurotoxin to treat various neurological disorders in children. PMID:27335961

  9. The toxin and antidote puzzle

    PubMed Central

    2011-01-01

    Insects carry out essential ecological functions, such as pollination, but also cause extensive damage to agricultural crops and transmit human diseases such as malaria and dengue fever. Advances in insect transgenesis are making it increasingly feasible to engineer genes conferring desirable phenotypes, and gene drive systems are required to spread these genes into wild populations. Medea provides one solution, being able to spread into a population from very low initial frequencies through the action of a maternally-expressed toxin linked to a zygotically-expressed antidote. Several other toxin-antidote combinations are imaginable that distort the offspring ratio in favor of a desired transgene, or drive the population towards an all-male crash. We explore two such systems—Semele, which is capable of spreading a desired transgene into an isolated population in a confined manner; and Merea, which is capable of inducing a local population crash when located on the Z chromosome of a Lepidopteron pest. PMID:21876382

  10. Novel Class of Spider Toxin

    PubMed Central

    Vassilevski, Alexander A.; Fedorova, Irina M.; Maleeva, Ekaterina E.; Korolkova, Yuliya V.; Efimova, Svetlana S.; Samsonova, Olga V.; Schagina, Ludmila V.; Feofanov, Alexei V.; Magazanik, Lev G.; Grishin, Eugene V.

    2010-01-01

    Venom of the yellow sac spider Cheiracanthium punctorium (Miturgidae) was found unique in terms of molecular composition. Its principal toxic component CpTx 1 (15.1 kDa) was purified, and its full amino acid sequence (134 residues) was established by protein chemistry and mass spectrometry techniques. CpTx 1 represents a novel class of spider toxin with modular architecture. It consists of two different yet homologous domains (modules) each containing a putative inhibitor cystine knot motif, characteristic of the widespread single domain spider neurotoxins. Venom gland cDNA sequencing provided precursor protein (prepropeptide) structures of three CpTx 1 isoforms (a–c) that differ by single residue substitutions. The toxin possesses potent insecticidal (paralytic and lethal), cytotoxic, and membrane-damaging activities. In both fly and frog neuromuscular preparations, it causes stable and irreversible depolarization of muscle fibers leading to contracture. This effect appears to be receptor-independent and is inhibited by high concentrations of divalent cations. CpTx 1 lyses cell membranes, as visualized by confocal microscopy, and destabilizes artificial membranes in a manner reminiscent of other membrane-active peptides by causing numerous defects of variable conductance and leading to bilayer rupture. The newly discovered class of modular polypeptides enhances our knowledge of the toxin universe. PMID:20657014

  11. Phage display and Shiga toxin neutralizers.

    PubMed

    Bernedo-Navarro, Robert Alvin; Yano, Tomomasa

    2016-04-01

    The current work presents an overview of the use of phage display technology for the identification and characterization of potential neutralizing agents for Shiga toxins. The last major Shiga toxin-associated disease outbreak, which took place in Germany in 2011, showed the international community that Shiga toxins remain a serious threat to public health. This is also demonstrated by the lack of specific therapies against Shiga toxin-induced Hemolytic Uremic Syndrome (HUS). Since its inception, phage display technology has played a key role in the development of antigen-specific (poly)-peptides or antibody fragments with specific biological properties. Herein, we review the current literature regarding the application of phage display to identify novel neutralizing agents against Shiga toxins. We also briefly highlight reported discoveries of peptides and heavy chain antibodies (VHH fragments or nanobodies) that can neutralize the cellular damage caused by these potent toxins. PMID:26898657

  12. Bt Toxin Modification for Enhanced Efficacy

    PubMed Central

    Deist, Benjamin R.; Rausch, Michael A.; Fernandez-Luna, Maria Teresa; Adang, Michael J.; Bonning, Bryony C.

    2014-01-01

    Insect-specific toxins derived from Bacillus thuringiensis (Bt) provide a valuable resource for pest suppression. Here we review the different strategies that have been employed to enhance toxicity against specific target species including those that have evolved resistance to Bt, or to modify the host range of Bt crystal (Cry) and cytolytic (Cyt) toxins. These strategies include toxin truncation, modification of protease cleavage sites, domain swapping, site-directed mutagenesis, peptide addition, and phage display screens for mutated toxins with enhanced activity. Toxin optimization provides a useful approach to extend the utility of these proteins for suppression of pests that exhibit low susceptibility to native Bt toxins, and to overcome field resistance. PMID:25340556

  13. Doppler tracking

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher Jacob

    This study addresses the development of a methodology using the Doppler Effect for high-resolution, short-range tracking of small projectiles and vehicles. Minimal impact on the design of the moving object is achieved by incorporating only a transmitter in it and using ground stations for all other components. This is particularly useful for tracking objects such as sports balls that have configurations and materials that are not conducive to housing onboard instrumentation. The methodology developed here uses four or more receivers to monitor a constant frequency signal emitted by the object. Efficient and accurate schemes for filtering the raw signals, determining the instantaneous frequencies, time synching the frequencies from each receiver, smoothing the synced frequencies, determining the relative velocity and radius of the object and solving the nonlinear system of equations for object position in three dimensions as a function of time are developed and described here.

  14. [Use of botulinum toxin in strabismus].

    PubMed

    Wabbels, B

    2016-07-01

    Botulinum toxin can be a useful tool for treating acute sixth nerve palsy and excessive eye deviations due to unstable Graves' disease, when surgery is not yet possible. The diagnostic injection for estimation of possible postoperative double vision also makes sense. In convergence spasms, periocular botulinum toxin injections can be a therapeutic option. Botulinum toxin is not a first line option in infantile esotropia without binocularity or in adult horizontal strabismus. Side effects include ptosis and vertical deviations. PMID:27369733

  15. Adsorption of insecticidal Cry1Ab protein to humic substances. 1. Experimental approach and mechanistic aspects.

    PubMed

    Sander, Michael; Tomaszewski, Jeanne E; Madliger, Michael; Schwarzenbach, René P

    2012-09-18

    Adsorption is a key process affecting the fate of insecticidal Cry proteins (Bt toxins), produced by genetically modified Bt crops, in soils. However, the mechanisms of adsorption to soil organic matter (SOM) remain poorly understood. This work assesses the forces driving the adsorption of Cry1Ab to Leonardite humic acid (LHA), used as a model for SOM. We studied the effects of solution pH and ionic strength (I) on adsorption using a quartz crystal microbalance with dissipation monitoring and optical waveguide lightmode spectroscopy. Initial Cry1Ab adsorption rates were close to diffusion-limited and resulted in extensive adsorption, even at pH >6, at which LHA and Cry1Ab carry negative net charges. Adsorption increased with decreasing I at pH >6, indicating Cry1Ab-LHA patch-controlled electrostatic attraction via positively charged domains of Cry1Ab. Upon rinsing, only a fraction of Cry1Ab desorbed, suggesting a range of interaction energies of Cry1Ab with LHA. Different interaction energies likely resulted from nonuniformity in the LHA surface polarity, with higher Cry1Ab affinities to more apolar LHA regions due to the hydrophobic effect. Contributions from the hydrophobic effect were substantiated by comparison of the adsorption of Cry1Ab and the reference proteins albumin and lysozyme to LHA and to apolar and polar model surfaces. PMID:22862304

  16. Extended evaluation of polymeric and lipophilic sorbents for passive sampling of marine toxins.

    PubMed

    Zendong, Zita; Herrenknecht, Christine; Abadie, Eric; Brissard, Charline; Tixier, Céline; Mondeguer, Florence; Séchet, Véronique; Amzil, Zouher; Hess, Philipp

    2014-12-01

    Marine biotoxins are algal metabolites that can accumulate in fish or shellfish and render these foodstuffs unfit for human consumption. These toxins, released into seawater during algal occurrences, can be monitored through passive sampling. Acetone, methanol and isopropanol were evaluated for their efficiency in extracting toxins from algal biomass. Isopropanol was chosen for further experiments thanks to a slightly higher recovery and no artifact formation. Comparison of Oasis HLB, Strata-X, BondElut C18 and HP-20 sorbent materials in SPE-mode led to the choice of Oasis HLB, HP-20 and Strata-X. These three sorbents were separately exposed as passive samplers for 24 h to seawater spiked with algal extracts containing known amounts of okadaic acid (OA), azaspiracids (AZAs), pinnatoxin-G (PnTX-G), 13-desmethyl spirolide-C (SPX1) and palytoxins (PlTXs). Low density polyethylene (LDPE) and silicone rubber (PDMS) strips were tested in parallel on similar mixtures of spiked natural seawater for 24 h. These strips gave significantly lower recoveries than the polymeric sorbents. Irrespective of the toxin group, the adsorption rate of toxins on HP-20 was slower than on Oasis HLB and Strata-X. However, HP-20 and Strata-X gave somewhat higher recoveries after 24 h exposure. Irrespective of the sorbent tested, recoveries were generally highest for cyclic imines and OA group toxins, slightly lower for AZAs, and the lowest for palytoxins. Trials in re-circulated closed tanks with mussels exposed to Vulcanodinium rugosum or Prorocentrum lima allowed for further evaluation of passive samplers. In these experiments with different sorbent materials competing for toxins in the same container, Strata-X accumulated toxins faster than Oasis HLB, and HP-20, and to higher levels. The deployment of these three sorbents at Ingril French Mediterranean lagoon to detect PnTX-G in the water column showed accumulation of higher levels on HP-20 and Oasis HLB compared to Strata-X. This study

  17. Noninvasive Imaging Technologies Reveal Edema Toxin as a Key Virulence Factor in Anthrax

    PubMed Central

    Dumetz, Fabien; Jouvion, Grégory; Khun, Huot; Glomski, Ian Justin; Corre, Jean-Philippe; Rougeaux, Clémence; Tang, Wei-Jen; Mock, Michèle; Huerre, Michel; Goossens, Pierre Louis

    2011-01-01

    Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. PMID:21641378

  18. Toxin-induced hyperthermic syndromes.

    PubMed

    Rusyniak, Daniel E; Sprague, Jon E

    2005-11-01

    Toxin-induced hyperthermic syndromes are important to consider in the differential diagnosis of patients presenting with fever and muscle rigidity. If untreated, toxin-induced hyperthermia may result in fatal hyperthermia with multisystem organ failure. All of these syndromes have at their center the disruption of normal thermogenic mechanisms, resulting in the activation of the hypothalamus and sympathetic nervous systems.The result of this thermogenic dysregulation is excess heat generation combined with impaired heat dissipation. Although many similarities exist among the clinical presentations and pathophysiologies of toxin-induced hyperthermic syndromes, important differences exist among their triggers and treatments. Serotonin syndrome typically occurs within hours of the addition ofa new serotonergic agent or the abuse of stimulants such as MDMA or methamphetamine. Treatment involves discontinuing the offending agent and administering either a central serotonergic antagonist, such as cyproheptadine or chlorpromazine, a benzodiazepine, or a combination of the two. NMS typically occurs over hours to days in a patient taking a neuroleptic agent; its recommended treatment is generally the combination of a central dopamine agonist, bromocriptine or L-dopa, and dantrolene. In those patients in whom it is difficult to differentiate between serotonin and neuroleptic malignant syndromes, the physical examination may be helpful:clonus and hyperreflexia are more suggestive of serotonin syndrome,whereas lead-pipe rigidity is suggestive of NMS. In patients in whom serotonin syndrome and NMS cannot be differentiated, benzodiazepines represent the safest therapeutic option. MH presents rapidly with jaw rigidity, hyperthermia, and hypercarbia. Although it almost always occurs in the setting of surgical anesthesia, cases have occurred in susceptible individuals during exertion. The treatment of MH involves the use of dantrolene. Future improvements in understanding the

  19. Botulinum toxin: The Midas touch

    PubMed Central

    Shilpa, P. S.; Kaul, Rachna; Sultana, Nishat; Bhat, Suraksha

    2014-01-01

    Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of BT has been extensively studied. BT is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. The objective of this article is to review the nature, mechanism of action of BT, and its application in various head and neck diseases. PMID:24678189

  20. Botulinum toxin: The Midas touch.

    PubMed

    Shilpa, P S; Kaul, Rachna; Sultana, Nishat; Bhat, Suraksha

    2014-01-01

    Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of BT has been extensively studied. BT is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. The objective of this article is to review the nature, mechanism of action of BT, and its application in various head and neck diseases. PMID:24678189

  1. Tremorgenic toxin from Penicillium veruculosum.

    PubMed

    Cole, R J; Kirksey, J W; Moore, J H; Blankenship, B R; Diener, U L; Davis, N D

    1972-08-01

    A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD(50)) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD(50) values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name "verruculogen" is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described. PMID:4341967

  2. Tremorgenic Toxin from Penicillium verruculosum

    PubMed Central

    Cole, R. J.; Kirksey, J. W.; Moore, J. H.; Blankenship, B. R.; Diener, U. L.; Davis, N. D.

    1972-01-01

    A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD50) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD50 values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name „verruculogen” is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described. PMID:4341967

  3. Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of Vibrios

    PubMed Central

    Satchell, Karla J. F.

    2015-01-01

    Multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are a heterogeneous group of toxins found in a number of Vibrio species and other Gram-negative bacteria. The toxins are composed of conserved repeat regions and an autoprocessing protease domain that together function as a delivery platform for transfer of cytotoxic and cytopathic domains into target eukaryotic cell cytosol. Within the cells, the effectors can alter biological processes such as signaling or cytoskeletal structure, presumably to the benefit of the bacterium. Ten effector domains are found in the various Vibrio MARTX toxins, although any one toxin carries only two to five effector domains. The specific toxin variant expressed by a species can be modified by homologous recombination to acquire or lose effector domains, such that different strains within the same species can express distinct variants of the toxins. This review examines the conserved structural elements of the MARTX toxins and details the different toxin arrangements carried by Vibrio species and strains. The catalytic function of domains and how the toxins are linked to pathogenesis of human and animals is described. PMID:26185092

  4. Plant Insecticidal Toxins in Ecological Networks

    PubMed Central

    Ibanez, Sébastien; Gallet, Christiane; Després, Laurence

    2012-01-01

    Plant secondary metabolites play a key role in plant-insect interactions, whether constitutive or induced, C- or N-based. Anti-herbivore defences against insects can act as repellents, deterrents, growth inhibitors or cause direct mortality. In turn, insects have evolved a variety of strategies to act against plant toxins, e.g., avoidance, excretion, sequestration and degradation of the toxin, eventually leading to a co-evolutionary arms race between insects and plants and to co-diversification. Anti-herbivore defences also negatively impact mutualistic partners, possibly leading to an ecological cost of toxin production. However, in other cases toxins can also be used by plants involved in mutualistic interactions to exclude inadequate partners and to modify the cost/benefit ratio of mutualism to their advantage. When considering the whole community, toxins have an effect at many trophic levels. Aposematic insects sequester toxins to defend themselves against predators. Depending on the ecological context, toxins can either increase insects’ vulnerability to parasitoids and entomopathogens or protect them, eventually leading to self-medication. We conclude that studying the community-level impacts of plant toxins can provide new insights into the synthesis between community and evolutionary ecology. PMID:22606374

  5. Formation and Control of Cyanobacterial Toxins

    EPA Science Inventory

    This presentation will cover the formation of harmful algal blooms and the control of their toxins. Data will be presented from current ORD projects on the treatment of cyanobacterial toxins through drinking water treatment facilities. The results will demonstrate that current c...

  6. Target-Driven Evolution of Scorpion Toxins.

    PubMed

    Zhang, Shangfei; Gao, Bin; Zhu, Shunyi

    2015-01-01

    It is long known that peptide neurotoxins derived from a diversity of venomous animals evolve by positive selection following gene duplication, yet a force that drives their adaptive evolution remains a mystery. By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex. Despite the lack of positive selection signals in these two loops, they accumulated extensive sequence variations by relaxed purifying selection in prey and predators of scorpions. The evolutionary variability in the toxin-bound regions of sodium channels indicates that accelerated substitutions in the multigene family of scorpion toxins is a consequence of dealing with the target diversity. This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors. Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species. PMID:26444071

  7. Stool Test: C. Difficile Toxin (For Parents)

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Stool Test: C. Difficile Toxin KidsHealth > For Parents > Stool Test: C. Difficile Toxin Print A A A Text Size ... Questions en español Muestra de materia fecal: toxina C. difficile What It Is A stool (feces) sample ...

  8. [T-2 toxin: occurrence and detection].

    PubMed

    Dohnal, V; Jezková, A; Kuca, K; Jun, D

    2007-07-01

    The paper is focused on the occurrence and methods for the detection of T-2 toxin, one of the most toxic trichothecene Fusarium mycotoxin. Due to its physical-chemical properties and high toxicity, T-2 toxin is classified as a potential biological warfare agent. PMID:17969315

  9. The Ins and Outs of Anthrax Toxin

    PubMed Central

    Friebe, Sarah; van der Goot, F. Gisou; Bürgi, Jérôme

    2016-01-01

    Anthrax is a severe, although rather rare, infectious disease that is caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. The infectious form is the spore and the major virulence factors of the bacterium are its poly-γ-D-glutamic acid capsule and the tripartite anthrax toxin. The discovery of the anthrax toxin receptors in the early 2000s has allowed in-depth studies on the mechanisms of anthrax toxin cellular entry and translocation from the endocytic compartment to the cytoplasm. The toxin generally hijacks the endocytic pathway of CMG2 and TEM8, the two anthrax toxin receptors, in order to reach the endosomes. From there, the pore-forming subunit of the toxin inserts into endosomal membranes and enables translocation of the two catalytic subunits. Insertion of the pore-forming unit preferentially occurs in intraluminal vesicles rather than the limiting membrane of the endosome, leading to the translocation of the enzymatic subunits in the lumen of these vesicles. This has important consequences that will be discussed. Ultimately, the toxins reach the cytosol where they act on their respective targets. Target modification has severe consequences on cell behavior, in particular on cells of the immune system, allowing the spread of the bacterium, in severe cases leading to host death. Here we will review the literature on anthrax disease with a focus on the structure of the toxin, how it enters cells and its immunological effects. PMID:26978402

  10. The Ins and Outs of Anthrax Toxin.

    PubMed

    Friebe, Sarah; van der Goot, F Gisou; Bürgi, Jérôme

    2016-03-01

    Anthrax is a severe, although rather rare, infectious disease that is caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. The infectious form is the spore and the major virulence factors of the bacterium are its poly-γ-D-glutamic acid capsule and the tripartite anthrax toxin. The discovery of the anthrax toxin receptors in the early 2000s has allowed in-depth studies on the mechanisms of anthrax toxin cellular entry and translocation from the endocytic compartment to the cytoplasm. The toxin generally hijacks the endocytic pathway of CMG2 and TEM8, the two anthrax toxin receptors, in order to reach the endosomes. From there, the pore-forming subunit of the toxin inserts into endosomal membranes and enables translocation of the two catalytic subunits. Insertion of the pore-forming unit preferentially occurs in intraluminal vesicles rather than the limiting membrane of the endosome, leading to the translocation of the enzymatic subunits in the lumen of these vesicles. This has important consequences that will be discussed. Ultimately, the toxins reach the cytosol where they act on their respective targets. Target modification has severe consequences on cell behavior, in particular on cells of the immune system, allowing the spread of the bacterium, in severe cases leading to host death. Here we will review the literature on anthrax disease with a focus on the structure of the toxin, how it enters cells and its immunological effects. PMID:26978402

  11. New Adsorption Methods.

    ERIC Educational Resources Information Center

    Wankat, Phillip C.

    1984-01-01

    Discusses a simple method for following the movement of a solute in an adsorption or ion exchange system. This movement is used to study a variety of operational methods, including continuous flow and pulsed flow counter-current operations and simulated counter-current systems. Effect of changing thermodynamic variables is also considered. (JM)

  12. Brown spider dermonecrotic toxin directly induces nephrotoxicity

    SciTech Connect

    Chaim, Olga Meiri; Sade, Youssef Bacila; Bertoni da Silveira, Rafael; Toma, Leny; Kalapothakis, Evanguedes; Chavez-Olortegui, Carlos; Mangili, Oldemir Carlos; Gremski, Waldemiro; Dietrich, Carl Peter von; Nader, Helena B.; Sanches Veiga, Silvio . E-mail: veigass@ufpr.br

    2006-02-15

    Brown spider (Loxosceles genus) venom can induce dermonecrotic lesions at the bite site and systemic manifestations including fever, vomiting, convulsions, disseminated intravascular coagulation, hemolytic anemia and acute renal failure. The venom is composed of a mixture of proteins with several molecules biochemically and biologically well characterized. The mechanism by which the venom induces renal damage is unknown. By using mice exposed to Loxosceles intermedia recombinant dermonecrotic toxin (LiRecDT), we showed direct induction of renal injuries. Microscopic analysis of renal biopsies from dermonecrotic toxin-treated mice showed histological alterations including glomerular edema and tubular necrosis. Hyalinization of tubules with deposition of proteinaceous material in the tubule lumen, tubule epithelial cell vacuoles, tubular edema and epithelial cell lysis was also observed. Leukocytic infiltration was neither observed in the glomerulus nor the tubules. Renal vessels showed no sign of inflammatory response. Additionally, biochemical analyses showed such toxin-induced changes in renal function as urine alkalinization, hematuria and azotemia with elevation of blood urea nitrogen levels. Immunofluorescence with dermonecrotic toxin antibodies and confocal microscopy analysis showed deposition and direct binding of this toxin to renal intrinsic structures. By immunoblotting with a hyperimmune dermonecrotic toxin antiserum on renal lysates from toxin-treated mice, we detected a positive signal at the region of 33-35 kDa, which strengthens the idea that renal failure is directly induced by dermonecrotic toxin. Immunofluorescence reaction with dermonecrotic toxin antibodies revealed deposition and binding of this toxin directly in MDCK epithelial cells in culture. Similarly, dermonecrotic toxin treatment caused morphological alterations of MDCK cells including cytoplasmic vacuoles, blebs, evoked impaired spreading and detached cells from each other and from

  13. pH-dependent conformational changes of diphtheria toxin adsorbed to lipid monolayers by neutron and X-ray reflection

    NASA Astrophysics Data System (ADS)

    Kent, Michael; Yim, Hyun; Satija, Sushil; Kuzmenko, Ivan

    2006-03-01

    Several important bacterial toxins, such as diphtheria, tetanus, and botulinum, invade cells through a process of high affinity binding, internalization via endosome formation, and subsequent membrane penetration of the catalytic domain activated by a pH drop in the endosome. These toxins are composed of three domains: a binding domain, a translocation domain, and an enzyme. The translocation process is not well understood with regard to the detailed conformational changes that occur at each step, To address this, we performed neutron reflectivity measurements for diphtheria toxin bound to lipid monolayers as a function of pH. While the final membrane inserted conformation will not be reproduced with the present monolayer system, important insights can still be gained into several intermediate stages. In particular, we show that no adsorption occurs at pH = 7.6, but strong adsorption occurs over at a pH range from 6.5 to 6.0. Following binding, at least two stages of conformational change occur, as the thickness increases from pH 6.3 to 5.3 and then decreases from pH 5.3 to 4.5. In addition, the dimension of the adsorbed layer substantially exceeds that of the largest dimension in the crystal structure of monomeric diphtheria, suggesting that the toxin may be present as multimers.

  14. The toxin component of targeted anti-tumor toxins determines their efficacy increase by saponins.

    PubMed

    Weng, Alexander; Thakur, Mayank; Beceren-Braun, Figen; Bachran, Diana; Bachran, Christopher; Riese, Sebastian B; Jenett-Siems, Kristina; Gilabert-Oriol, Roger; Melzig, Matthias F; Fuchs, Hendrik

    2012-06-01

    Tumor-targeting protein toxins are composed of a toxic enzyme coupled to a specific cell binding domain that targets cancer-associated antigens. The anti-tumor treatment by targeted toxins is accompanied by dose-limiting side effects. The future prospects of targeted toxins for therapeutic use in humans will be determined by reduce side effects. Certain plant secondary metabolites (saponins) were shown to increase the efficacy of a particular epidermal growth factor receptor (EGFR)-targeted toxin, paralleled by a tremendous decrease of side effects. This study was conducted in order to investigate the effects of substituting different toxin moieties fused to an EGF ligand binding domain on the augmentative ability of saponins for each against therapeutic potential of the saponin-mediated efficacy increase for different anti-tumor toxins targeting the EGFR. We designed several EGFR-targeted toxins varying in the toxic moiety. Each targeted toxin was used in combination with a purified saponin (SA1641), isolated from the ornamental plant Gypsophila paniculata L. SA1641 was characterized and the SA1641-mediated efficacy increase was investigated on EGFR-transfected NIH-3T3 cells. We observed a high dependency of the SA1641-mediated efficacy increase on the nature of toxin used for the construction of the targeted toxin, indicating high specificity. Structural alignments revealed a high homology between saporin and dianthin-30, the two toxic moieties that benefit most from the combination with SA1641. We further demonstrate that SA1641 did not influence the plasma membrane permeability, indicating an intracellular interaction of SA1641 and the toxin components of targeted toxins. Surface plasmon resonance measurements point to a transient binding of SA1641 to the toxin components of targeted toxins. PMID:22309811

  15. Toxins

    MedlinePlus

    ... trace metals and others. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ... Ford MD. Acute poisoning. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  16. Clostridium perfringens Delta Toxin Is Sequence Related to Beta Toxin, NetB, and Staphylococcus Pore-Forming Toxins, but Shows Functional Differences

    PubMed Central

    Manich, Maria; Knapp, Oliver; Gibert, Maryse; Maier, Elke; Jolivet-Reynaud, Colette; Geny, Blandine; Benz, Roland; Popoff, Michel R.

    2008-01-01

    Clostridium perfringens produces numerous toxins, which are responsible for severe diseases in man and animals. Delta toxin is one of the three hemolysins released by a number of C. perfringens type C and possibly type B strains. Delta toxin was characterized to be cytotoxic for cells expressing the ganglioside GM2 in their membrane. Here we report the genetic characterization of Delta toxin and its pore forming activity in lipid bilayers. Delta toxin consists of 318 amino acids, its 28 N-terminal amino acids corresponding to a signal peptide. The secreted Delta toxin (290 amino acids; 32619 Da) is a basic protein (pI 9.1) which shows a significant homology with C. perfringens Beta toxin (43% identity), with C. perfringens NetB (40% identity) and, to a lesser extent, with Staphylococcus aureus alpha toxin and leukotoxins. Recombinant Delta toxin showed a preference for binding to GM2, in contrast to Beta toxin, which did not bind to gangliosides. It is hemolytic for sheep red blood cells and cytotoxic for HeLa cells. In artificial diphytanoyl phosphatidylcholine membranes, Delta and Beta toxin formed channels. Conductance of the channels formed by Delta toxin, with a value of about 100 pS to more than 1 nS in 1 M KCl and a membrane potential of 20 mV, was higher than those formed by Beta toxin and their distribution was broader. The results of zero-current membrane potential measurements and single channel experiments suggest that Delta toxin forms slightly anion-selective channels, whereas the Beta toxin channels showed a preference for cations under the same conditions. C. perfringens Delta toxin shows a significant sequence homolgy with C. perfringens Beta and NetB toxins, as well as with S. aureus alpha hemolysin and leukotoxins, but exhibits different channel properties in lipid bilayers. In contrast to Beta toxin, Delta toxin recognizes GM2 as receptor and forms anion-selective channels. PMID:19018299

  17. Roles of Anthrax Toxin Receptor 2 in Anthrax Toxin Membrane Insertion and Pore Formation

    PubMed Central

    Sun, Jianjun; Jacquez, Pedro

    2016-01-01

    Interaction between bacterial toxins and cellular surface receptors is an important component of the host-pathogen interaction. Anthrax toxin protective antigen (PA) binds to the cell surface receptor, enters the cell through receptor-mediated endocytosis, and forms a pore on the endosomal membrane that translocates toxin enzymes into the cytosol of the host cell. As the major receptor for anthrax toxin in vivo, anthrax toxin receptor 2 (ANTXR2) plays an essential role in anthrax toxin action by providing the toxin with a high-affinity binding anchor on the cell membrane and a path of entry into the host cell. ANTXR2 also acts as a molecular clamp by shifting the pH threshold of PA pore formation to a more acidic pH range, which prevents premature pore formation at neutral pH before the toxin reaches the designated intracellular location. Most recent studies have suggested that the disulfide bond in the immunoglobulin (Ig)-like domain of ANTXR2 plays an essential role in anthrax toxin action. Here we will review the roles of ANTXR2 in anthrax toxin action, with an emphasis on newly updated knowledge. PMID:26805886

  18. Roles of Anthrax Toxin Receptor 2 in Anthrax Toxin Membrane Insertion and Pore Formation.

    PubMed

    Sun, Jianjun; Jacquez, Pedro

    2016-02-01

    Interaction between bacterial toxins and cellular surface receptors is an important component of the host-pathogen interaction. Anthrax toxin protective antigen (PA) binds to the cell surface receptor, enters the cell through receptor-mediated endocytosis, and forms a pore on the endosomal membrane that translocates toxin enzymes into the cytosol of the host cell. As the major receptor for anthrax toxin in vivo, anthrax toxin receptor 2 (ANTXR2) plays an essential role in anthrax toxin action by providing the toxin with a high-affinity binding anchor on the cell membrane and a path of entry into the host cell. ANTXR2 also acts as a molecular clamp by shifting the pH threshold of PA pore formation to a more acidic pH range, which prevents premature pore formation at neutral pH before the toxin reaches the designated intracellular location. Most recent studies have suggested that the disulfide bond in the immunoglobulin (Ig)-like domain of ANTXR2 plays an essential role in anthrax toxin action. Here we will review the roles of ANTXR2 in anthrax toxin action, with an emphasis on newly updated knowledge. PMID:26805886

  19. Persistence of Bt Bacillus thuringiensis Cry1Aa toxin in various soils determined by physicochemical reactions

    NASA Astrophysics Data System (ADS)

    Helassa, N.; Noinville, S.; Déjardin, P.; Janot, J. M.; Quiquampoix, H.; Staunton, S.

    2009-04-01

    Insecticidal Cry proteins from the soil bacterium, Bacillus thuringiensis (Bt) are produced by a class of genetically modified (GM) crops, and released into soils through root exudates and upon decomposition of residues. In contrast to the protoxin produced by the Bacillus, the protein produced in GM crops does not require activation in insect midguts and thereby potentially looses some of its species specificity. Although gene transfer and resistance emergence phenomena are well documented, the fate of these toxins in soil has not yet been clearly elucidated. Cry proteins, in common with other proteins, are adsorbed on soils and soil components. Adsorption on soil, and the reversibility of this adsorption is an important aspect of the environmental behaviour of these toxins. The orientation of the molecule and conformational changes on surfaces may modify the toxicity and confer some protection against microbial degradation. Adsorption will have important consequences for both the risk of exposition of non target species and the acquisition of resistance by target species. We have adopted different approaches to investigate the fate of Cry1Aa in soils and model minerals. In each series of experiments we endeavoured to maintain the protein in a monomeric form (pH above 6.5 and a high ionic strength imposed with 150 mM NaCl). The adsorption and the desorbability of the Cry1Aa Bt insecticidal protein were measured on two different homoionic clays: montmorillonite and kaolinite. Adsorption isotherms obtained followed a low affinity interaction for both clays and could be fitted using the Langmuir equation. Binding of the toxin decreased as the pH increased from 6.5 (close to the isoelectric point) to 9. Maximum adsorption was about 40 times greater on montmorillonite (1.71 g g-1) than on kaolinite (0.04 g g-1) in line with the contrasting respective specific surface areas of the minerals. Finally, some of the adsorbed toxin was desorbed by water and more, about 36

  20. Fundamentals of high pressure adsorption

    SciTech Connect

    Zhou, Y.P.; Zhou, L.

    2009-12-15

    High-pressure adsorption attracts research interests following the world's attention to alternative fuels, and it exerts essential effect on the study of hydrogen/methane storage and the development of novel materials addressing to the storage. However, theoretical puzzles in high-pressure adsorption hindered the progress of application studies. Therefore, the present paper addresses the major theoretical problems that challenged researchers: i.e., how to model the isotherms with maximum observed in high-pressure adsorption; what is the adsorption mechanism at high pressures; how do we determine the quantity of absolute adsorption based on experimental data. Ideology and methods to tackle these problems are elucidated, which lead to new insights into the nature of high-pressure adsorption and progress in application studies, for example, in modeling multicomponent adsorption, hydrogen storage, natural gas storage, and coalbed methane enrichment, was achieved.

  1. Track Construction Manual.

    ERIC Educational Resources Information Center

    Banke, Ron; Di Gennaro, Guy; Ediger, Rick; Garner, Lanny; Hersom, Steve; Miller, Jack; Nemeth, Ron; Petrucelli, Jim; Sierks, Donna; Smith, Don; Swank, Kevin; West, Kevin

    This book establishes guidelines for the construction and maintenance of tracks by providing information for building new tracks or upgrading existing tracks. Subjects covered include running track planning and construction, physical layout, available surfaces, and maintenance. General track requirements and construction specifications are…

  2. On the Right Track.

    ERIC Educational Resources Information Center

    Bieber, Ed

    1983-01-01

    Suggests thinking of "tracks" as clues and using them as the focus of outdoor activities in the urban environment. Provides 24 examples of possible track activities, including: seeds on the ground (track of a nearby tree), litter (track of a litterbug), and peeling paint (track of weathering forces). (JN)

  3. Fungi and fungal toxins as weapons.

    PubMed

    Paterson, R Russell M

    2006-09-01

    Recent aggressive attacks on innocent citizens have resulted in governments increasing security. However, there is a good case for prevention rather than reaction. Bioweapons, mycotoxins, fungal biocontrol agents (FBCA), and even pharmaceuticals contain, or are, toxins and need to be considered in the context of the new paradigm. Is it desirable to discuss such issues? None of the fungi are (a) as toxic as botulinum toxin from Clostridium botulinum, and (b) as dangerous as nuclear weapons. One toxin may be defined as a pharmaceutical and vice versa simply by a small change in concentration or a moiety. Mycotoxins are defined as naturally occurring toxic compounds obtained from fungi. They are the biggest chronic health risk when incorporated into the diet. The current list of fungal toxins as biochemical weapons is small, although awareness is growing of the threats they may pose. T-2 toxin is perhaps the biggest concern. A clear distinction is required between the biological (fungus) and chemical (toxin) aspects of the issue. There is an obvious requirement to be able to trace these fungi and compounds in the environment and to know when concentrations are abnormal. Many FBCA, produce toxins. This paper indicates how to treat mycotoxicosis and decontaminate mycotoxins. There is considerable confusion and inconsistency surrounding this topic which requires assessment in an impartial and scientific manner. PMID:16908123

  4. Cyanobacterial toxins: risk management for health protection.

    PubMed

    Codd, Geoffrey A; Morrison, Louise F; Metcalf, James S

    2005-03-15

    This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats and biofilms of benthic species. Toxic cyanobacterial populations have been reported in freshwaters in over 45 countries, and in numerous brackish, coastal, and marine environments. The principal toxigenic genera are listed. Known sources of the families of cyanobacterial toxins (hepato-, neuro-, and cytotoxins, irritants, and gastrointestinal toxins) are briefly discussed. Key procedures in the risk management of cyanobacterial toxins and cells are reviewed, including derivations (where sufficient data are available) of tolerable daily intakes (TDIs) and guideline values (GVs) with reference to the toxins in drinking water, and guideline levels for toxigenic cyanobacteria in bathing waters. Uncertainties and some gaps in knowledge are also discussed, including the importance of exposure media (animal and plant foods), in addition to potable and recreational waters. Finally, we present an outline of steps to develop and implement risk management strategies for cyanobacterial cells and toxins in waterbodies, with recent applications and the integration of Hazard Assessment Critical Control Point (HACCP) principles. PMID:15737680

  5. Cyanobacterial toxins: risk management for health protection

    SciTech Connect

    Codd, Geoffrey A.; Morrison, Louise F.; Metcalf, James S

    2005-03-15

    This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats and biofilms of benthic species. Toxic cyanobacterial populations have been reported in freshwaters in over 45 countries, and in numerous brackish, coastal, and marine environments. The principal toxigenic genera are listed. Known sources of the families of cyanobacterial toxins (hepato-, neuro-, and cytotoxins, irritants, and gastrointestinal toxins) are briefly discussed. Key procedures in the risk management of cyanobacterial toxins and cells are reviewed, including derivations (where sufficient data are available) of tolerable daily intakes (TDIs) and guideline values (GVs) with reference to the toxins in drinking water, and guideline levels for toxigenic cyanobacteria in bathing waters. Uncertainties and some gaps in knowledge are also discussed, including the importance of exposure media (animal and plant foods), in addition to potable and recreational waters. Finally, we present an outline of steps to develop and implement risk management strategies for cyanobacterial cells and toxins in waterbodies, with recent applications and the integration of Hazard Assessment Critical Control Point (HACCP) principles.

  6. Extracorporeal adsorption of endotoxin.

    PubMed

    Staubach, K H; Rosenfeldt, J A; Veit, O; Bruch, H P

    1997-02-01

    In a porcine endotoxin shock model using a continuous intravenous endotoxin infusion of 250 ng/kg body weight per hour, the cardiorespiratory and hematologic parameters were studied while applying a new on-line polymyxin B immobilized adsorption system. This preliminary report shows that the new adsorbent can remove endotoxin selectively from the circulation and confers a good amount of protection from endotoxin-induced cardiopulmonary decompensation as well as hematologic alterations. Survival time could be extended from 216 min to 313 min. Whereas cardiac output and mean arterial pressure declined critically after 3 h in the controls, the treated group remained stable for another 3 h. These data show that endotoxin adsorption by polymyxin B coupled covalently to acrylic spheres as an adjunctive on-line measure in the septic syndrome seems feasible. PMID:10225785

  7. A coagulation-powdered activated carbon-ultrafiltration--multiple barrier approach for removing toxins from two Australian cyanobacterial blooms.

    PubMed

    Dixon, Mike B; Richard, Yann; Ho, Lionel; Chow, Christopher W K; O'Neill, Brian K; Newcombe, Gayle

    2011-02-28

    Cyanobacteria are a major problem for the world wide water industry as they can produce metabolites toxic to humans in addition to taste and odour compounds that make drinking water aesthetically displeasing. Removal of cyanobacterial toxins from drinking water is important to avoid serious illness in consumers. This objective can be confidently achieved through the application of the multiple barrier approach to drinking water quality and safety. In this study the use of a multiple barrier approach incorporating coagulation, powdered activated carbon (PAC) and ultrafiltration (UF) was investigated for the removal of intracellular and extracellular cyanobacterial toxins from two naturally occurring blooms in South Australia. Also investigated was the impact of these treatments on the UF flux. In this multibarrier approach, coagulation was used to remove the cells and thus the intracellular toxin while PAC was used for extracellular toxin adsorption and finally the UF was used for floc, PAC and cell removal. Cyanobacterial cells were completely removed using the UF membrane alone and when used in conjunction with coagulation. Extracellular toxins were removed to varying degrees by PAC addition. UF flux deteriorated dramatically during a trial with a very high cell concentration; however, the flux was improved by coagulation and PAC addition. PMID:21227576

  8. Regenerable adsorption system

    NASA Technical Reports Server (NTRS)

    Roychoudhury, Subir (Inventor); Perry, Jay (Inventor); Walsh, Dennis (Inventor)

    2006-01-01

    A method for regenerable adsorption includes providing a substrate that defines at least one layer of ultra short channel length mesh capable of conducting an electrical current therethrough, coating at least a portion of the substrate with a desired sorbent for trace contaminant control or CO.sub.2 sorption, resistively heating the substrate, and passing a flowstream through the substrate and in contact with the sorbent.

  9. Clostridium perfringens type A–E toxin plasmids

    PubMed Central

    Freedman, John C.; Theoret, James R.; Wisniewski, Jessica A.; Uzal, Francisco A.; Rood, Julian I.; McClane, Bruce A.

    2014-01-01

    Clostridium perfringens relies upon plasmid-encoded toxin genes to cause intestinal infections. These toxin genes are associated with insertion sequences that may facilitate their mobilization and transfer, giving rise to new toxin plasmids with common backbones. Most toxin plasmids carry a transfer of clostridial plasmids locus mediating conjugation, which likely explains the presence of similar toxin plasmids in otherwise unrelated C. perfringens strains. The association of many toxin genes with insertion sequences and conjugative plasmids provides virulence flexibility when causing intestinal infections. However, incompatibility issues apparently limit the number of toxin plasmids maintained by a single cell. PMID:25283728

  10. Cholera toxin-like toxin released by Salmonella species in the presence of mitomycin C.

    PubMed

    Molina, N C; Peterson, J W

    1980-10-01

    Several serotypes of Salmonella were shown to release increased amounts of a cholera toxin-like toxin during culture in vitro with mitomycin C (MTC). Filter-sterilized culture supernatants containing the toxin caused elongation of Chinese hamster ovary cells, which could be blocked by heating the supernatants at 100 degrees C for 15 min or by adding mixed gangliosides or monospecific cholera antitoxin. When MTC was not added to the Salmonella cultures, little or no toxin was detected in crude, unconcentrated culture supernatants. Optimal production of toxin was observed in the presence of 0.5 micrograms of MTC per ml in shake flask cultures of Casamino Acids-yeast extract medium, Syncase, or peptone saline at 37 degrees C. Meat infusion media (heart infusion and brain heart infusion) plus MTC resulted in poor toxin yield. Culture filtrates frequently could be diluted 1:8 and still result in elongation of Chinese hamster ovary cells. PMID:7002788

  11. Zwitteration: Coating Surfaces with Zwitterionic Functionality to Reduce Nonspecific Adsorption

    PubMed Central

    2015-01-01

    Coating surfaces with thin or thick films of zwitterionic material is an effective way to reduce or eliminate nonspecific adsorption to the solid/liquid interface. This review tracks the various approaches to zwitteration, such as monolayer assemblies and polymeric brush coatings, on micro- to macroscopic surfaces. A critical summary of the mechanisms responsible for antifouling shows how zwitterions are ideally suited to this task. PMID:24754399

  12. Radio tracking system

    NASA Technical Reports Server (NTRS)

    Breidenthal, J. C.; Komarek, T. A.

    1982-01-01

    The principles and techniques of deep space radio tracking are described along with the uses of tracking data in navigation and radio science. Emphasis is placed on the measurement functions of radio tracking.

  13. Effect of tribology processes on adsorption of albumin

    NASA Astrophysics Data System (ADS)

    Yan, Yu; Yang, Hongjuan; Wang, Linghe; Su, Yanjing; Qiao, Lijie

    2016-03-01

    As soon as artificial joint replacements are implanted into patients, the adsorption of proteins can occur. Joint implants operate in a protein-rich and relatively corrosive environment under tribological contact. The contacted area acted as an anodic part and the rest of the surface was more cathodic. Therefore, the adsorption of proteins is different in and outside the wear track. Adsorbed proteins would denature during rubbing and a tribofilm could form. The tribofilm can lubricate the surface and act as a barrier to corrosion damage. However, to observe the adsorption of proteins in situ has always been a challenge. Scanning Kelvin probe force microscope (SKPFM) was used to study the adsorption of albumin on the surface of CoCrMo alloy under simulated tribology movement. Fluorescence microscopy (FM) was employed to reveal the protein molecules in the wear scar. It was found that albumin molecules can decrease the surface potential and accelerate the corrosion process. In the wear track, albumin denatured and changed the surface potential as time progressed.

  14. Investigating the role of solanapyrone toxins in Ascochyta blight using toxin-deficient mutants of Asochyta rabiei

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ascochyta rabiei, the causal agent of Ascochyta blight of chickpea, produces solanapyrone toxins (solanapyrone A, B and C). However, very little is known about the genetics of toxin production and the role of the toxins in pathogenesis. Generating mutants deficient in the toxin biosynthesis would p...

  15. Toxic shock syndrome toxin-1, not α-toxin, mediated Bundaberg fatalities.

    PubMed

    Mueller, Elizabeth A; Merriman, Joseph A; Schlievert, Patrick M

    2015-12-01

    The 1928 Bundaberg disaster is one of the greatest vaccine tragedies in history. Of 21 children immunized with a diphtheria toxin-antitoxin preparation contaminated with Staphylococcus aureus, 18 developed life-threatening disease and 12 died within 48  h. Historically, the deaths have been attributed to α-toxin, a secreted cytotoxin produced by most S. aureus strains, yet the ability of the Bundaberg contaminant microbe to produce the toxin has never been verified. For the first time, the ability of the original strain to produce α-toxin and other virulence factors is investigated. The study investigates the genetic and regulatory loci mediating α-toxin expression by PCR and assesses production of the cytotoxin in vitro using an erythrocyte haemolysis assay. This analysis is extended to other secreted virulence factors produced by the strain, and their sufficiency to cause lethality in New Zealand white rabbits is determined. Although the strain possesses a wild-type allele for α-toxin, it must have a defective regulatory system, which is responsible for the strain's minimal α-toxin production. The strain encodes and produces staphylococcal superantigens, including toxic shock syndrome toxin-1 (TSST-1), which is sufficient to cause lethality in patients. The findings cast doubt on the belief that α-toxin is the major virulence factor responsible for the Bundaberg fatalities and point to the superantigen TSST-1 as the cause of the disaster. PMID:26432699

  16. Clostridium difficile and C. difficile Toxin Testing

    MedlinePlus

    ... C diff antigen; GDH Formal name: Clostridium difficile Culture; C. difficile Toxin, A and B; C. difficile Cytotoxin Assay; Glutamate Dehydrogenase Test Related tests: Stool Culture ; O&P At a Glance Test Sample The ...

  17. INVESTIGATOIN OF CYANOBACTERIA TOXINS IN WATER

    EPA Science Inventory

    Introduction:

    Approximately 80 alkaloid and cyclic peptide toxins produced by various freshwater and marine cyanobacteria (blue-green algae) have been identified and their structures determined. The U. S. Environmental Protection Agency has identified two neurotoxin alkalo...

  18. [Treatment of wrinkles with botulinum toxin].

    PubMed

    Lanzl, I; Merté, R-L

    2007-09-01

    The use of botulinum toxin A for the treatment of wrinkles is increasing. Botulinum toxin A inhibits exocytosis of acetylcholine from 3 to 12 months, depending on the target tissue. Low-dose botulinum toxin A is used to smooth hyperkinetic facial lines. This is especially successful in the upper facial parts, since the target muscles (procerus, corrugator supracilii, frontalis, orbicularis oculi) all directly overlie the osseous structures of the face. This is not the case for the lower facial parts, and more side effects are encountered when treating, for example, wrinkles around the mouth. Contraindications to the use of botulinum toxin A are diseases affecting neuromuscular signal transduction, allergic reactions to components of the solution, therapy with aminoglycosides or acetylsalicylic acid prior to treatment, infections in the planned treatment area, and pregnancy and lactation. Alternative and complementary treatments include erbium-YAG or CO2 laser, as well as augmentation and surgical plastic procedures. PMID:17823803

  19. Bacterial Toxins as Pathogen Weapons Against Phagocytes

    PubMed Central

    do Vale, Ana; Cabanes, Didier; Sousa, Sandra

    2016-01-01

    Bacterial toxins are virulence factors that manipulate host cell functions and take over the control of vital processes of living organisms to favor microbial infection. Some toxins directly target innate immune cells, thereby annihilating a major branch of the host immune response. In this review we will focus on bacterial toxins that act from the extracellular milieu and hinder the function of macrophages and neutrophils. In particular, we will concentrate on toxins from Gram-positive and Gram-negative bacteria that manipulate cell signaling or induce cell death by either imposing direct damage to the host cells cytoplasmic membrane or enzymatically modifying key eukaryotic targets. Outcomes regarding pathogen dissemination, host damage and disease progression will be discussed. PMID:26870008

  20. Nanoanalysis of the arthropod neuro-toxins

    PubMed Central

    Nakajima, Terumi

    2006-01-01

    Many kinds of venomous principles modulate physiological responses of mammalian signal transduction systems, on which they act selectively as enhancers, inhibitors or some other kind of effectors. These toxins become useful tools for physiological research. We have employed and characterized paralyzing toxins from the venom of spiders, insects and scorpions with a limited supply. We have developed rapid and sensitive mass spectrometric technology and applied for the identification of these toxins. Venom profiles are screened by MALDI-TOF fingerprinting analysis prior to purification of venomous components, then marked target toxins of small molecular mass (1000–5000) are characterized directly by means of mass spectrometric techniques such as Frit-FAB MS/MS, CID/PSD-TOF MS, Capil.-HPLC/Q-TOF MS/MS etc. PMID:25792792

  1. How Parkinsonian Toxins Dysregulate the Autophagy Machinery

    PubMed Central

    Dagda, Ruben K.; Das Banerjee, Tania; Janda, Elzbieta

    2013-01-01

    Since their discovery, Parkinsonian toxins (6-hydroxydopamine, MPP+, paraquat, and rotenone) have been widely employed as in vivo and in vitro chemical models of Parkinson’s disease (PD). Alterations in mitochondrial homeostasis, protein quality control pathways, and more recently, autophagy/mitophagy have been implicated in neurotoxin models of PD. Here, we highlight the molecular mechanisms by which different PD toxins dysregulate autophagy/mitophagy and how alterations of these pathways play beneficial or detrimental roles in dopamine neurons. The convergent and divergent effects of PD toxins on mitochondrial function and autophagy/mitophagy are also discussed in this review. Furthermore, we propose new diagnostic tools and discuss how pharmacological modulators of autophagy/mitophagy can be developed as disease-modifying treatments for PD. Finally, we discuss the critical need to identify endogenous and synthetic forms of PD toxins and develop efficient health preventive programs to mitigate the risk of developing PD. PMID:24217228

  2. [Botulinum toxin in disabling dermatological diseases].

    PubMed

    Messikh, R; Atallah, L; Aubin, F; Humbert, P

    2009-05-01

    Botulinum toxin could represent nowadays a new treatment modality especially for cutaneous conditions in course of which conventional treatments remain unsuccessful. Besides palmar and plantar hyperhidrosis, botulinum toxin has demonstrated efficacy in different conditions associated with hyperhidrosis, such as dyshidrosis, multiple eccrine hidrocystomas, hidradenitis suppurativa, Frey syndrome, but also in different conditions worsened by hyperhidrosis such as Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenital. Moreover, different cutaneous conditions associated with sensitive disorders and/or neurological involvements could benefit from botulinum toxin, for example anal fissures, leg ulcers, lichen simplex, notalgia paresthetica, vestibulitis. Endly, a case of cutis laxa was described where the patient was improved by cutaneous injections of botulinum toxin. PMID:19576479

  3. Hemolytic anemia caused by chemicals and toxins

    MedlinePlus

    Anemia - hemolytic - caused by chemicals or toxins ... Possible substances that can cause hemolytic anemia include: Anti-malaria drugs (quinine compounds) Arsenic Dapsone Intravenous water infusion (not half-normal saline or normal saline) Metals (chromium/chromates, ...

  4. Botulinum toxin. From poison to medicine.

    PubMed Central

    Davis, L E

    1993-01-01

    Although thousands of people in the world each year continue to be poisoned with botulinum toxin-food-borne, infantile, or wound botulism-the neurotoxin is now sufficiently understood to allow it to be used as a medicinal agent to paralyze specific muscles, giving temporary symptomatic relief from a variety of dystonic neurologic disorders. I review some of the epidemiologic, clinical, and pathophysiologic aspects of botulinum toxin and how the neurotoxin may act as a poison or a medicine. Images PMID:8470380

  5. Purification and characterization of Clostridium difficile toxin.

    PubMed Central

    Rolfe, R D; Finegold, S M

    1979-01-01

    Recent evidence indicates that toxigenic Clostridium difficile strains are a major cause of antimicrobial-associated ileocecitis in laboratory animals and pseudomembranous colitis in humans. C. difficile ATCC 9689 was cultivated in a synthetic medium to which 3% ultrafiltrated proteose peptone was added. Purification of the toxin from broth filtrate was accomplished through ultrafiltration (100,000 nominal-molecular-weight-limit membrane), precipitation with 75% (NH4)2SO4, and chromatographic separation using Bio-Gel A 5m followed by ion-exchange chromatography on a diethylaminoethyl-Sephadex A-25 column. The purified toxin displayed only one band on polyacrylamide gel electrophoresis, and approximately 170 pg was cytopathic for human amnion cells. The isolated toxin was neutralized by Clostridium sordelli antitoxin, heat labile (56 degrees C for 30 min), and inactivated at pH 4 and 9; it had an isoelectric point of 5.0, increased vascular permeability in rabbits, and caused ileocecitis in hamsters when injected intracecally. Treatment of the toxin with trypsin, chymotrypsin, pronase, amylase, or ethylmercurithiosalicylate caused inactivation, whereas lipase had no effect. By gel filtration, its molecular weight was estimated as 530,000. Upon reduction and denaturation, the toxin dissociated into 185,000- and 50,000-molecular-weight components, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive dissociation yielded only the 50,000-molecular-weight component. The toxin appears to be protoplasmic and is released into the surrounding environment upon autolysis of the cells. Attempts to correlate specific enzymatic activity with the toxin have been unsuccessful. These studies will help delineate the role of C. difficile toxin in antimicrobial-associated colitis and diarrhea. Images PMID:478634

  6. Toxicological Perspective on Climate Change: Aquatic Toxins.

    PubMed

    Botana, Luis M

    2016-04-18

    In recent years, our group and several others have been describing the presence of new, not previously reported, toxins of high toxicity in vectors that may reach the human food chain. These include tetrodotoxin in gastropods in the South of Europe, ciguatoxin in fish in the South of Spain, palytoxin in mussels in the Mediterranean Sea, pinnatoxin all over Europe, and okadaic acid in the south of the U.S. There seem to be new marine toxins appearing in areas that are heavy producers of seafood, and this is a cause of concern as most of these new toxins are not included in current legislation and monitoring programs. Along with the new toxins, new chemical analogues are being reported. The same phenomenom is being recorded in freshwater toxins, such as the wide appearance of cylindrospermopsin and the large worldwide increase of microcystin. The problem that this phenomenon, which may be linked to climate warming, poses for toxicologists is very important not only because there is a lack of chronic studies and an incomplete comprehension of the mechanism driving the production of these toxins but also because the lack of a legal framework for them allows many of these toxins to reach the market. In some cases, it is very difficult to control these toxins because there are not enough standards available, they are not always certified, and there is an insufficient understanding of the toxic equivalency factors of the different analogues in each group. All of these factors have been revealed and grouped through the massive increase in the use of LC-MS as a monitoring tool, legally demanded, creating more toxicological problems. PMID:26958981

  7. Dermatitis from purified sea algae toxin (debromoaplysiatoxin).

    PubMed

    Solomon, A E; Stoughton, R B

    1978-09-01

    Cutaneous inflammation was induced by debromoaplysiatoxin, a purified toxin extracted from Lyngbya majuscula Gomont. This alga causes a seaweed dermatitis that occurs in persons who have swum off the coast of Oahu in Hawaii. By topical application, the toxin was found to produce an irritant pustular folliculitis in humans and to cause a severe cutaneous inflammatory reaction in the rabbit and in hairless mice. PMID:686747

  8. Sea Anemone Toxins Affecting Potassium Channels

    NASA Astrophysics Data System (ADS)

    Diochot, Sylvie; Lazdunski, Michel

    The great diversity of K+ channels and their wide distribution in many tissues are associated with important functions in cardiac and neuronal excitability that are now better understood thanks to the discovery of animal toxins. During the past few decades, sea anemones have provided a variety of toxins acting on voltage-sensitive sodium and, more recently, potassium channels. Currently there are three major structural groups of sea anemone K+ channel (SAK) toxins that have been characterized. Radioligand binding and electrophysiological experiments revealed that each group contains peptides displaying selective activities for different subfamilies of K+ channels. Short (35-37 amino acids) peptides in the group I display pore blocking effects on Kv1 channels. Molecular interactions of SAK-I toxins, important for activity and binding on Kv1 channels, implicate a spot of three conserved amino acid residues (Ser, Lys, Tyr) surrounded by other less conserved residues. Long (58-59 amino acids) SAK-II peptides display both enzymatic and K+ channel inhibitory activities. Medium size (42-43 amino acid) SAK-III peptides are gating modifiers which interact either with cardiac HERG or Kv3 channels by altering their voltage-dependent properties. SAK-III toxins bind to the S3C region in the outer vestibule of Kv channels. Sea anemones have proven to be a rich source of pharmacological tools, and some of the SAK toxins are now useful drugs for the diagnosis and treatment of autoimmune diseases.

  9. Toxin-Antitoxin Systems of Staphylococcus aureus.

    PubMed

    Schuster, Christopher F; Bertram, Ralph

    2016-01-01

    Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery. PMID:27164142

  10. Toxin-Antitoxin Systems of Staphylococcus aureus

    PubMed Central

    Schuster, Christopher F.; Bertram, Ralph

    2016-01-01

    Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery. PMID:27164142

  11. Evaluation of antidiphtheria toxin nanobodies

    PubMed Central

    Shaker, Ghada H

    2010-01-01

    Nanobodies are the smallest fragments of naturally occurring single-domain antibodies that have evolved to be fully functional in the absence of a light chain. Conventional antibodies are glycoproteins comprising two heavy and two light chains. Surprisingly, all members of the Camelidae family possess a fraction of antibodies devoid of both light chains and the first constant domain. These types of antibodies are known as heavy-chain antibody (HcAb) nanobodies. There are three subclasses of IgG in dromedaries, namely IgG1, IgG2, and IgG3 of which IgG2 and IgG3 are of the HcAb type. These heavy chain antibodies constitute approximately 50% of the IgG in llama serum and as much as 75% of the IgG in camel serum. In the present work, the different IgG subclasses from an immunized camel (Camelus dromedarius) with divalent diphtheria-tetanus vaccine were purified using their different affinity for protein A and protein G and their absorbance measured at 280 nm. Purity control and characterization by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis of IgG subclasses was done under reducing conditions. Protein bands were visualized after staining with Coomassie Blue, showing two bands at 50 kDa and 30 kDa for IgG1, while IgG2 and IgG3 produced only one band at 46 kDa and 43 kDa, respectively. An enzyme-linked immunosorbent assay test using diphtheria toxin and purified IgG subclasses from the immunized camel were performed to evaluate their efficiency. Compared with conventional IgG1, heavy chain antibodies (nanobodies) were shown to be more efficient in binding to diphtheria toxin antigen. This study revealed the possibility of using IgG2 and IgG3 nanobodies as an effective antitoxin for the treatment of diphtheria in humans. PMID:24198468

  12. Inhibition of maize histone deacetylases by HC toxin, the host-selective toxin of Cochliobolus carbonum.

    PubMed Central

    Brosch, G; Ransom, R; Lechner, T; Walton, J D; Loidl, P

    1995-01-01

    HC toxin, the host-selective toxin of the maize pathogen Cochliobolus carbonum, inhibited maize histone deacetylase (HD) at 2 microM. Chlamydocin, a related cyclic tetrapeptide, also inhibited HD activity. The toxins did not affect histone acetyltransferases. After partial purification of histone deacetylases HD1-A, HD1-B, and HD2 from germinating maize embryos, we demonstrated that the different enzymes were similarly inhibited by the toxins. Inhibitory activities were reversibly eliminated by treating toxins with 2-mercaptoethanol, presumably by modifying the carbonyl group of the epoxide-containing amino acid Aeo (2-amino-9,10-epoxy-8-oxodecanoic acid). Kinetic studies revealed that inhibition of HD was of the uncompetitive type and reversible. HC toxin, in which the epoxide group had been hydrolyzed, completely lost its inhibitory activity; when the carbonyl group of Aeo had been reduced to the corresponding alcohol, the modified toxin was less active than native toxin. In vivo treatment of embryos with HC toxin caused the accumulation of highly acetylated histone H4 subspecies and elevated acetate incorporation into H4 in susceptible-genotype embryos but not in the resistant genotype. HDs from chicken and the myxomycete Physarum polycephalum were also inhibited, indicating that the host selectivity of HC toxin is not determined by its inhibitory effect on HD. Consistent with these results, we propose a model in which HC toxin promotes the establishment of pathogenic compatibility between C. carbonum and maize by interfering with reversible histone acetylation, which is implicated in the control of fundamental cellular processes, such as chromatin structure, cell cycle progression, and gene expression. PMID:8535144

  13. Random sequential adsorption of tetramers

    NASA Astrophysics Data System (ADS)

    Cieśla, Michał

    2013-07-01

    Adsorption of a tetramer built of four identical spheres was studied numerically using the random sequential adsorption (RSA) algorithm. Tetramers were adsorbed on a two-dimensional, flat and homogeneous surface. Two different models of the adsorbate were investigated: a rhomboid and a square one; monomer centres were put on vertices of rhomboids and squares, respectively. Numerical simulations allow us to establish the maximal random coverage ratio as well as the available surface function (ASF), which is crucial for determining kinetics of the adsorption process. These results were compared with data obtained experimentally for KfrA plasmid adsorption. Additionally, the density autocorrelation function was measured.

  14. Expression of functional diphtheria toxin receptors on highly toxin-sensitive mouse cells that specifically bind radioiodinated toxin.

    PubMed Central

    Naglich, J G; Rolf, J M; Eidels, L

    1992-01-01

    Diphtheria toxin (DT), a bacterial protein exotoxin, inactivates mammalian cell elongation factor 2 after toxin internalization by receptor-mediated endocytosis. To isolate the DT receptor, we cotransfected DT-resistant wild-type mouse L-M cells with a cDNA library constructed from RNA of highly toxin-sensitive monkey Vero cells and with a neomycin-resistance gene. Stably transfected G418-resistant L-M colonies were screened for DT sensitivity in a replica plate assay. After screening of 8000 colonies, one DT-sensitive (DTS) colony was isolated. The purified DTS mouse cells are highly toxin-sensitive; they are at least 1000-fold more sensitive than wild-type L-M cells and only approximately 10-fold less sensitive than Vero cells. Incubation of the DTS mouse cells with CRM 197, a nontoxic form of DT that competitively inhibits the binding of native DT to the toxin receptor, protected them from DT-mediated toxicity. More important, these DTS mouse cells express receptors on their cell surface that bind radioiodinated DT in a specific fashion, a property hitherto readily demonstrable only with highly toxin-sensitive cells of monkey origin. Furthermore, HA6DT, a DT fragment comprising the Mr 6000 carboxyl-terminal receptor-binding domain, inhibited the binding of radioiodinated toxin to these DTS mouse cells to the same extent as unlabeled DT. With these DTS mouse cells as a source of monkey cDNA, it should be possible to clone the gene encoding the DT receptor. PMID:1549577

  15. A biomimetic nanosponge that absorbs pore-forming toxins

    NASA Astrophysics Data System (ADS)

    Hu, Che-Ming J.; Fang, Ronnie H.; Copp, Jonathan; Luk, Brian T.; Zhang, Liangfang

    2013-05-01

    Detoxification treatments such as toxin-targeted anti-virulence therapy offer ways to cleanse the body of virulence factors that are caused by bacterial infections, venomous injuries and biological weaponry. Because existing detoxification platforms such as antisera, monoclonal antibodies, small-molecule inhibitors and molecularly imprinted polymers act by targeting the molecular structures of toxins, customized treatments are required for different diseases. Here, we show a biomimetic toxin nanosponge that functions as a toxin decoy in vivo. The nanosponge, which consists of a polymeric nanoparticle core surrounded by red blood cell membranes, absorbs membrane-damaging toxins and diverts them away from their cellular targets. In a mouse model, the nanosponges markedly reduce the toxicity of staphylococcal alpha-haemolysin (α-toxin) and thus improve the survival rate of toxin-challenged mice. This biologically inspired toxin nanosponge presents a detoxification treatment that can potentially treat a variety of injuries and diseases caused by pore-forming toxins.

  16. Mechanisms of Antigen Adsorption Onto an Aluminum-Hydroxide Adjuvant Evaluated by High-Throughput Screening.

    PubMed

    Jully, Vanessa; Mathot, Frédéric; Moniotte, Nicolas; Préat, Véronique; Lemoine, Dominique

    2016-06-01

    The adsorption mechanism of antigen on aluminum adjuvant can affect antigen elution at the injection site and hence the immune response. Our aim was to evaluate adsorption onto aluminum hydroxide (AH) by ligand exchange and electrostatic interactions of model proteins and antigens, bovine serum albumin (BSA), β-casein, ovalbumin (OVA), hepatitis B surface antigen, and tetanus toxin (TT). A high-throughput screening platform was developed to measure adsorption isotherms in the presence of electrolytes and ligand exchange by a fluorescence-spectroscopy method that detects the catalysis of 6,8-difluoro-4-methylumbelliferyl phosphate by free hydroxyl groups on AH. BSA adsorption depended on predominant electrostatic interactions. Ligand exchange contributes to the adsorption of β-casein, OVA, hepatitis B surface antigen, and TT onto AH. Based on relative surface phosphophilicity and adsorption isotherms in the presence of phosphate and fluoride, the capacities of the proteins to interact with AH by ligand exchange followed the trend: OVA < β-casein < BSA < TT. This could be explained by both the content of ligands available in the protein structure for ligand exchange and the antigen's molecular weight. The high-throughput screening platform can be used to better understand the contributions of ligand exchange and electrostatic attractions governing the interactions between an antigen adsorbed onto aluminum-containing adjuvant. PMID:27238481

  17. Solar tracking system

    DOEpatents

    Okandan, Murat; Nielson, Gregory N.

    2016-07-12

    Solar tracking systems, as well as methods of using such solar tracking systems, are disclosed. More particularly, embodiments of the solar tracking systems include lateral supports horizontally positioned between uprights to support photovoltaic modules. The lateral supports may be raised and lowered along the uprights or translated to cause the photovoltaic modules to track the moving sun.

  18. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis

    PubMed Central

    Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko; Takehara, Masaya; Nagahama, Masahiro

    2016-01-01

    Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis. PMID:26807591

  19. Simultaneous removal of potent cyanotoxins from water using magnetophoretic nanoparticle of polypyrrole: adsorption kinetic and isotherm study.

    PubMed

    Hena, S; Rozi, R; Tabassum, S; Huda, A

    2016-08-01

    Cyanotoxins, microcystins and cylindrospermopsin, are potent toxins produced by cyanobacteria in potable water supplies. This study investigated the removal of cyanotoxins from aqueous media by magnetophoretic nanoparticle of polypyrrole adsorbent. The adsorption process was pH dependent with maximum adsorption occurring at pH 7 for microcystin-LA, LR, and YR and at pH 9 for microcystin-RR and cylindrospermopsin (CYN). Kinetic studies and adsorption isotherms reflected better fit for pseudo-second-order rate and Langmuir isotherm model, respectively. Thermodynamic calculations showed that the cyanotoxin adsorption process is endothermic and spontaneous in nature. The regenerated adsorbent can be successfully reused without appreciable loss of its original capacity. PMID:27072032

  20. Toxin from skin of frogs of the genus Atelopus: differentiation from Dendrobatid toxins.

    PubMed

    Fuhrman, F A; Fuhrman, G J; Mosher, H S

    1969-09-26

    A potent, dialyzable toxin (atelopidtoxin) occurs in the skin of frogs of the genus Atelopus. A concentrate of atelopidtoxin from Atelopus zeteki has an LD(50) in mice of 16 micrograms per kilogram. It differs from batrachotoxin, tetrodotoxin, and saxitoxin, the only known nonprotein substances of greater toxicity, as well as from all toxins previously isolated from amphibia. PMID:5807965

  1. Rethinking Critical Adsorption

    NASA Astrophysics Data System (ADS)

    Franck, Carl; Peach, Sarah; Polak, Robert D.

    1996-03-01

    Recent reflectivity experiments on near-critical mixtures of carbon disulfide and nitromethane contained in glass cells footnote Niraj S. Desai, Sarah Peach, and Carl Franck, Phys. Rev. E 52, 4129 (1995) have shown that preferential adsorption of one liquid component onto the wall can be controlled by chemical modification of the glass. The glass was treated with varying amounts of hexamethyldisilazane to decrease surface polarity and therefore enhance the adsorption of carbon disulfide in a surprisingly continuous way. The effect of the glass wall on the local liquid composition can be described by two different scaling hypotheses: using a short range field on the liquid closest to the wall, or pinning the amplitude of the order parameter at the surface. We have found that only the second approach is consistent with the experimental data, although this is difficult to reconcile with observed wetting critical phenomena. We also have reexamined the issue of substrate inhomogeneity and conclude that the substrates were indeed homogeneous on relevant length scales. Supported by the NSF under DMR-9320910 and the central facilities of the Materials Science Center at Cornell University.

  2. Adsorption behaviour of bulgur.

    PubMed

    Erbaş, Mustafa; Aykın, Elif; Arslan, Sultan; Durak, Atike N

    2016-03-15

    The aim of this research was to determine the adsorption behaviour of bulgur. Three different particle sizes (2adsorption, because of %E values lower than 10%. Bulgur must be stored below 70% relative humidity and with less than 10 g water per 100 g of dry mater. PMID:26575716

  3. Synthesis and Biology of Cyclic Imine Toxins, An Emerging Class of Potent, Globally Distributed Marine Toxins

    PubMed Central

    Stivala, Craig E.; Benoit, Evelyne; Araoz, Romulo; Servent, Denis; Novikov, Alexei

    2014-01-01

    From a small group of exotic compounds isolated only two decades ago, Cyclic Imine (CI) toxins have become a major class of marine toxins with global distribution. Their distinct chemical structure, biological mechanism of action, and intricate chemistry ensures that CI toxins will continue to be the subject of fascinating fundamental studies in the broad fields of chemistry, chemical biology, and toxicology. The worldwide occurrence of potent CI toxins in marine environments, their accumulation in shellfish, and chemical stability are important considerations in assessing risk factors for human health. This review article aims to provide an account of chemistry, biology, and toxicology of CI toxins from their discovery to the present day. PMID:25338021

  4. Synthesis and biology of cyclic imine toxins, an emerging class of potent, globally distributed marine toxins.

    PubMed

    Stivala, Craig E; Benoit, Evelyne; Aráoz, Rómulo; Servent, Denis; Novikov, Alexei; Molgó, Jordi; Zakarian, Armen

    2015-03-01

    From a small group of exotic compounds isolated only two decades ago, Cyclic Imine (CI) toxins have become a major class of marine toxins with global distribution. Their distinct chemical structure, biological mechanism of action, and intricate chemistry ensures that CI toxins will continue to be the subject of fascinating fundamental studies in the broad fields of chemistry, chemical biology, and toxicology. The worldwide occurrence of potent CI toxins in marine environments, their accumulation in shellfish, and chemical stability are important considerations in assessing risk factors for human health. This review article aims to provide an account of chemistry, biology, and toxicology of CI toxins from their discovery to the present day. PMID:25338021

  5. Direct Detection of the Biological Toxin in Acidic Environment by Electrochemical Impedimetric Immunosensor

    PubMed Central

    Chai, Changhoon; Lee, Jooyoung; Takhistov, Paul

    2010-01-01

    This study describes the direct detection of the biological toxin (Ricin) in acidic environment without pH adjustment by hydrophobically modified electrochemical impedance immunosensor (EII). The nano-porous aluminum substrate for EII was hydrophobically modified via self-assembled monolayer (SAM) of APTES. Biosensor for the detection of the Ricin was fabricated by the covalent cross-linking of antibody (Ab) with APTES-SAM. The immunoreactions between the immobilized Ab and the biological toxin in several diagnostic solutions were monitored by the electrochemical impedance spectroscopy (EIS) under the polarization of EII versus reference electrode. EII could detect the presence of the biological toxin in acidic foods in 20 mins without pH adjustment. The negatively charged ions including hydroxides would be adsorbed on the hydrophobic body of APTES-SAMs by the polarization during EIS analysis, and offset the effect of acids on the immunological activity of the immobilized Ab. It suggested that the adsorption of negatively charged ions helped to keep the immunological activities of the immobilized Ab on EII in acidic environment. Proposed mechanism of the localized pH adjustment that makes possible immunoreaction occurrence in low pH sample matrix is briefly discussed. PMID:22163535

  6. Animal Toxins: How is Complexity Represented in Databases?

    PubMed Central

    Jungo, Florence; Estreicher, Anne; Bairoch, Amos; Bougueleret, Lydie; Xenarios, Ioannis

    2010-01-01

    Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology. PMID:22069583

  7. Animal Toxins: How is Complexity Represented in Databases?

    PubMed

    Jungo, Florence; Estreicher, Anne; Bairoch, Amos; Bougueleret, Lydie; Xenarios, Ioannis

    2010-02-01

    Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology. PMID:22069583

  8. Global versus local adsorption selectivity

    NASA Astrophysics Data System (ADS)

    Pauzat, Françoise; Marloie, Gael; Markovits, Alexis; Ellinger, Yves

    2015-10-01

    The origin of the enantiomeric excess found in the amino acids present in the organic matter of carbonaceous meteorites is still unclear. Selective adsorption of one of the two enantiomers existing after a racemic formation could be part of the answer. Hereafter we report a comparative study of the adsorption of the R and S enantiomers of α-alanine and lactic acid on the hydroxylated { } chiral surface of α-quartz using numerical simulation techniques. Structurally different adsorption sites were found with opposite R versus S selectivity for the same molecule-surface couple, raising the problem of whether to consider adsorption as a local property or as a global response characteristic of the whole surface. To deal with the second term of this alternative, a statistical approach was designed, based on the occurrence of each adsorption site whose energy was calculated using first principle periodic density functional theory. It was found that R-alanine and S-lactic acid are the enantiomers preferentially adsorbed, even if the adsorption process on the quartz { } surface stays with a disappointingly poor enantio-selectivity. Nevertheless, it highlighted the important point that considering adsorption as a global property changes perspectives in the search for more efficient enantio-selective supports and more generally changes the way to apprehend adsorption processes in astro-chemistry/biology.

  9. Liquid-Phase Adsorption Fundamentals.

    ERIC Educational Resources Information Center

    Cooney, David O.

    1987-01-01

    Describes an experiment developed and used in the unit operations laboratory course at the University of Wyoming. Involves the liquid-phase adsorption of an organic compound from aqueous solution on activated carbon, and is relevant to adsorption processes in general. (TW)

  10. ADSORPTION MEDIA FOR ARSENIC REMOVAL

    EPA Science Inventory

    Presentation will discuss the use of adsorptive media for the removal of arsenic from drinking water. Presentation is a fundamental discussion on the use of adsorptive media for arsenic removal and includes information from several EPA field studies on removal of arsenic from dr...

  11. TrackEye tracking algorithm characterization

    NASA Astrophysics Data System (ADS)

    Valley, Michael T.; Shields, Robert W.; Reed, Jack M.

    2004-10-01

    TrackEye is a film digitization and target tracking system that offers the potential for quantitatively measuring the dynamic state variables (e.g., absolute and relative position, orientation, linear and angular velocity/acceleration, spin rate, trajectory, angle of attack, etc.) for moving objects using captured single or dual view image sequences. At the heart of the system is a set of tracking algorithms that automatically find and quantify the location of user selected image details such as natural test article features or passive fiducials that have been applied to cooperative test articles. This image position data is converted into real world coordinates and rates with user specified information such as the image scale and frame rate. Though tracking methods such as correlation algorithms are typically robust by nature, the accuracy and suitability of each TrackEye tracking algorithm is in general unknown even under good imaging conditions. The challenges of optimal algorithm selection and algorithm performance/measurement uncertainty are even more significant for long range tracking of high-speed targets where temporally varying atmospheric effects degrade the imagery. This paper will present the preliminary results from a controlled test sequence used to characterize the performance of the TrackEye tracking algorithm suite.

  12. TrackEye tracking algorithm characterization.

    SciTech Connect

    Reed, Jack W.; Shields, Rob W; Valley, Michael T.

    2004-08-01

    TrackEye is a film digitization and target tracking system that offers the potential for quantitatively measuring the dynamic state variables (e.g., absolute and relative position, orientation, linear and angular velocity/acceleration, spin rate, trajectory, angle of attack, etc.) for moving objects using captured single or dual view image sequences. At the heart of the system is a set of tracking algorithms that automatically find and quantify the location of user selected image details such as natural test article features or passive fiducials that have been applied to cooperative test articles. This image position data is converted into real world coordinates and rates with user specified information such as the image scale and frame rate. Though tracking methods such as correlation algorithms are typically robust by nature, the accuracy and suitability of each TrackEye tracking algorithm is in general unknown even under good imaging conditions. The challenges of optimal algorithm selection and algorithm performance/measurement uncertainty are even more significant for long range tracking of high-speed targets where temporally varying atmospheric effects degrade the imagery. This paper will present the preliminary results from a controlled test sequence used to characterize the performance of the TrackEye tracking algorithm suite.

  13. Tracking filter algorithm for automatic video tracking

    NASA Astrophysics Data System (ADS)

    McEver, Mark A.; Kimbrell, James E.

    2006-05-01

    In addition to servo control and power amplification, motion control systems for optical tracking pedestals feature capabilities such as electro-optical tracking using an integrated Automatic Video Tracker (AVT) card. An electro-optical system tracking loop is comprised of sensors mounted on a pointing pedestal, an AVT that detects a target in the sensor imagery, and a tracking filter algorithm that commands the pedestal to follow the target. The tracking filter algorithm receives the target boresight error from the AVT and calculates motion demands for the pedestal servo controller. This paper presents a tracking algorithm based on target state estimation using a Kalman filter. The servo demands are based on calculating the Kalman filter state estimate from absolute line-of-sight angles to the target. Simulations are used to compare its performance to tracking loops without tracking filters, and to other tracking filter algorithms, such as rate feedback loops closed around boresight error. Issues such as data latency and sensor alignment error are discussed.

  14. Crystal structure of Clostridium difficile toxin A.

    PubMed

    Chumbler, Nicole M; Rutherford, Stacey A; Zhang, Zhifen; Farrow, Melissa A; Lisher, John P; Farquhar, Erik; Giedroc, David P; Spiller, Benjamin W; Melnyk, Roman A; Lacy, D Borden

    2016-01-01

    Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Disease is mediated by the actions of two toxins, TcdA and TcdB, which cause the diarrhoea, as well as inflammation and necrosis within the colon(1,2). The toxins are large (308 and 270 kDa, respectively), homologous (47% amino acid identity) glucosyltransferases that target small GTPases within the host(3,4). The multidomain toxins enter cells by receptor-mediated endocytosis and, upon exposure to the low pH of the endosome, insert into and deliver two enzymatic domains across the membrane. Eukaryotic inositol-hexakisphosphate (InsP6) binds an autoprocessing domain to activate a proteolysis event that releases the N-terminal glucosyltransferase domain into the cytosol. Here, we report the crystal structure of a 1,832-amino-acid fragment of TcdA (TcdA1832), which reveals a requirement for zinc in the mechanism of toxin autoprocessing and an extended delivery domain that serves as a scaffold for the hydrophobic α-helices involved in pH-dependent pore formation. A surface loop of the delivery domain whose sequence is strictly conserved among all large clostridial toxins is shown to be functionally important, and is highlighted for future efforts in the development of vaccines and novel therapeutics. PMID:27571750

  15. Cyanobacterial Toxin Degrading Bacteria: Who Are They?

    PubMed Central

    Kormas, Konstantinos Ar.; Lymperopoulou, Despoina S.

    2013-01-01

    Cyanobacteria are ubiquitous in nature and are both beneficial and detrimental to humans. Benefits include being food supplements and producing bioactive compounds, like antimicrobial and anticancer substances, while their detrimental effects are evident by toxin production, causing major ecological problems at the ecosystem level. To date, there are several ways to degrade or transform these toxins by chemical methods, while the biodegradation of these compounds is understudied. In this paper, we present a meta-analysis of the currently available 16S rRNA and mlrA (microcystinase) genes diversity of isolates known to degrade cyanobacterial toxins. The available data revealed that these bacteria belong primarily to the Proteobacteria, with several strains from the sphingomonads, and one from each of the Methylobacillus and Paucibacter genera. Other strains belonged to the genera Arthrobacter, Bacillus, and Lactobacillus. By combining the ecological knowledge on the distribution, abundance, and ecophysiology of the bacteria that cooccur with toxic cyanobacterial blooms and newly developed molecular approaches, it is possible not only to discover more strains with cyanobacterial toxin degradation abilities, but also to reveal the genes associated with the degradation of these toxins. PMID:23841072

  16. Crystal structure of Clostridium difficile toxin A

    PubMed Central

    Chumbler, Nicole M.; Rutherford, Stacey A.; Zhang, Zhifen; Farrow, Melissa A.; Lisher, John P.; Farquhar, Erik; Giedroc, David P.; Spiller, Benjamin W.; Melnyk, Roman A.; Lacy, D. Borden

    2016-01-01

    Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Disease is mediated by the actions of two toxins, TcdA and TcdB, which cause the diarrhoea, as well as inflammation and necrosis within the colon1,2. The toxins are large (308 and 270 kDa, respectively), homologous (47% amino acid identity) glucosyltransferases that target small GTPases within the host3,4. The multidomain toxins enter cells by receptor-mediated endocytosis and, upon exposure to the low pH of the endosome, insert into and deliver two enzymatic domains across the membrane. Eukaryotic inositol-hexakisphosphate (InsP6) binds an autoprocessing domain to activate a proteolysis event that releases the N-terminal glucosyltransferase domain into the cytosol. Here, we report the crystal structure of a 1,832-amino-acid fragment of TcdA (TcdA1832), which reveals a requirement for zinc in the mechanism of toxin autoprocessing and an extended delivery domain that serves as a scaffold for the hydrophobic α-helices involved in pH-dependent pore formation. A surface loop of the delivery domain whose sequence is strictly conserved among all large clostridial toxins is shown to be functionally important, and is highlighted for future efforts in the development of vaccines and novel therapeutics. PMID:27512603

  17. Array biosensor for detection of toxins

    NASA Technical Reports Server (NTRS)

    Ligler, Frances S.; Taitt, Chris Rowe; Shriver-Lake, Lisa C.; Sapsford, Kim E.; Shubin, Yura; Golden, Joel P.

    2003-01-01

    The array biosensor is capable of detecting multiple targets rapidly and simultaneously on the surface of a single waveguide. Sandwich and competitive fluoroimmunoassays have been developed to detect high and low molecular weight toxins, respectively, in complex samples. Recognition molecules (usually antibodies) were first immobilized in specific locations on the waveguide and the resultant patterned array was used to interrogate up to 12 different samples for the presence of multiple different analytes. Upon binding of a fluorescent analyte or fluorescent immunocomplex, the pattern of fluorescent spots was detected using a CCD camera. Automated image analysis was used to determine a mean fluorescence value for each assay spot and to subtract the local background signal. The location of the spot and its mean fluorescence value were used to determine the toxin identity and concentration. Toxins were measured in clinical fluids, environmental samples and foods, with minimal sample preparation. Results are shown for rapid analyses of staphylococcal enterotoxin B, ricin, cholera toxin, botulinum toxoids, trinitrotoluene, and the mycotoxin fumonisin. Toxins were detected at levels as low as 0.5 ng mL(-1).

  18. Binding of NAD+ to pertussis toxin.

    PubMed

    Lobban, M D; Irons, L I; van Heyningen, S

    1991-06-24

    The equilibrium dissociation constant of NAD+ and pertussis toxin was determined by equilibrium dialysis and by the quenching of the protein's intrinsic fluorescence on titration with NAD+. A binding constant, Kd, of 24 +/- 2 microM at 30 degrees C was obtained from equilibrium dialysis, consistent with the previously determined value for the Michaelis constant, Km, of 30 +/- 5 microM for NAD+ (when the toxin is catalysing the ADP-ribosylation of water and of dithiothreitol). The intrinsic fluorescence of pertussis toxin was quenched by up to 60% on titration with NAD+, and after correction for dilution and inner filter effects, a Kd value of 27 microM at 30 degrees C was obtained, agreeing well with that found by equilibrium dialysis. The binding constants were measured at a number of temperatures using both techniques, and from this the enthalpy of binding of NAD+ to toxin was determined to be 30 kJ.mol-1, a typical value for a protein-ligand interaction. There is one binding site for NAD+ per toxin molecule. PMID:1648404

  19. A truncated diphtheria toxin based recombinant porcine CTLA-4 fusion toxin.

    PubMed

    Peraino, Jaclyn Stromp; Schenk, Marian; Zhang, Huiping; Li, Guoying; Hermanrud, Christina E; Neville, David M; Sachs, David H; Huang, Christene A; Duran-Struuck, Raimon; Wang, Zhirui

    2013-05-31

    Targeted cell therapies are possible through the generation of recombinant fusion proteins that combine a toxin, such as diphtheria toxin (DT), with an antibody or other molecule that confers specificity. Upon binding of the fusion protein to the cell of interest, the diphtheria toxin is internalized which results in protein synthesis inhibition and subsequent cell death. We have recently expressed and purified the recombinant soluble porcine CTLA-4 both with and without N-glycosylation in yeast Pichia pastoris for in vivo use in our preclinical swine model. The glycosylated and non-N-glycosylated versions of this recombinant protein each bind to a porcine CD80 expressing B-cell lymphoma line (LCL13271) with equal affinity (K(D)=13 nM). In this study we have linked each of the glycosylated and non-N-glycosylated soluble porcine CTLA-4 proteins to the truncated diphtheria toxin DT390 through genetic engineering yielding three versions of the porcine CTLA-4 fusion toxins: 1) monovalent glycosylated soluble porcine CTLA-4 fusion toxin; 2) monovalent non-N-glycosylated soluble porcine CTLA-4 fusion toxin and 3) bivalent non-N-glycosylated soluble porcine CTLA-4 fusion toxin. Protein synthesis inhibition analysis demonstrated that while all three fusion toxins are capable of inhibiting protein synthesis in vitro, the non-N-glycosylated porcine CTLA-4 isoforms function most efficiently. Binding analysis using flow cytometry of the porcine CTLA-4 fusion toxins to LCL13271 cells also demonstrated that the non-N-glycosylated porcine CTLA-4 isoforms bind to these cells with higher affinity compared to the glycosylated fusion toxin. The monovalent non-N-glycosylated porcine CTLA-4 fusion toxin was tested in vivo. NSG (NOD/SCID IL-2 receptor γ(-)/(-)) mice were injected with porcine CD80(+) LCL13271 tumor cells. All animals succumbed to tumors and those treated with the monovalent non-N-glycosylated porcine CTLA-4 fusion toxin survived longer based on a symptomatic scoring

  20. Cistrons encoding Escherichia coli heat-labile toxin.

    PubMed Central

    Dallas, W S; Gill, D M; Falkow, S

    1979-01-01

    The structure and products of the two cistrons encoding the Escherichia coli heat-labile toxin (LT) were studied. The LT deoxyribonucleic acid (DNA) region had been isolated as part of a DNA fragment from the plasmid P307, and this fragment was joined to the cloning vector pBR313. Deletion mutations of various lengths were introduced into the LT DNA region and into the adjacent DNA sequences. Analysis of the deletions indicated that the maximum size of the LT DNA region was 1.2 x 10(6) daltons. Two proteins of 11,500 daltons and 25,500 daltons had been shown to be encoded by the LT DNA region. The functions of these LT gene products were investigated. The 11,500-dalton protein had an adsorption activity for Y-1 adrenal cells, and this protein was shown to form aggregates of four or five monomers. The 25,500-dalton protein was shown to have an adenylate cyclase-activating activity. The two cistrons encoding for each of the LT proteins have been located on a genetic map of the LT DNA region. Both cistrons are probably transcribed from the same promoter. Images PMID:383697

  1. High temperature adsorption measurements

    SciTech Connect

    Bertani, R.; Parisi, L.; Perini, R.; Tarquini, B.

    1996-01-24

    Adsorption phenomena are a rich and rather new field of study in geothermal research, in particular at very high temperature. ENEL is interested in the exploitation of geothermal regions with superheated steam, and it is important to understand the behavior of water-rock interaction. We have analyzed in the 170-200 °C temperature range four samples of Monteverdi cuttings; the next experimental effort will be at 220 °C and over in 1996. The first results of the 1995 runs are collected in this paper. We can highlight four main items: 1. At relative pressures over 0.6 the capillarity forces are very important. 2. There is no significant temperature effect. 3. Adsorbed water can be present, and it is able to multiply by a factor of 15 the estimated reserve of super-heated steam only. 4. Pores smaller than 15 Å do not contribute to the adsorbed mass.

  2. High temperature adsorption measurements

    SciTech Connect

    Bertani, R.; Parisi, L.; Perini, R.; Tarquini, B.

    1996-12-31

    Adsorption phenomena are a rich and rather new field of study in geothermal research, in particular at very high temperature. ENEL is interested in the exploitation of geothermal regions with super-heated steam, and it is important to understand the behavior of water-rock interaction. We have analyzed in the 170-200{degrees}C temperature range four samples of Monteverdi cuttings; the next experimental effort will be at 220{degrees}C and over in 1996. The first results of the 1995 runs are collected in this paper. We can highlight four main items: (1) At relative pressures over 0.6 the capillarity forces are very important. (2) There is no significant temperature effect. (3) Adsorbed water can be present, and it is able to multiply by a factor of 15 the estimated reserve of super-heated steam only. (4) Pores smaller than 15 {Angstrom} do not contribute to the adsorbed mass.

  3. Chromium adsorption by lignin

    SciTech Connect

    Lalvani, S.B.; Huebner, A.; Wiltowski, T.S.

    2000-01-01

    Hexavalent chromium is a known carcinogen, and its maximum contamination level in drinking water is determined by the US Environmental Protection Agency (EPA). Chromium in the wastewaters from plating and metal finishing, tanning, and photographic industries poses environmental problems. A commercially available lignin was used for the removal of hexavalent as well as trivalent chromium from aqueous solution. It is known that hexavalent chromium is present as an anionic species in the solution. It was found that lignin can remove up to 63% hexavalent and 100% trivalent chromium from aqueous solutions. The removal of chromium ions was also investigated using a commercially available activated carbon. This absorbent facilitated very little hexavalent and almost complete trivalent chromium removal. Adsorption isotherms and kinetics data on the metal removal by lignin and activated carbon are presented and discussed.

  4. Toxin-induced resistance in Bacillus anthracis lethal toxin-treated macrophages

    PubMed Central

    Salles, Isabelle I.; Tucker, Amy E.; Voth, Daniel E.; Ballard, Jimmy D.

    2003-01-01

    In the current study, we show that macrophages adaptively resist anthrax lethal toxin (LT) through a toxin-activated process termed toxin-induced resistance (TIR). TIR was triggered by pretreatment of RAW 264.7 or J774A.1 macrophages with a low dose of LT for at least 6 h, which resulted in resistance to high doses of LT for 96 h. Activation of TIR required functional toxin, because LT subunits, mutants, and heat-inactivated toxin were unable to trigger resistance. TIR macrophages were not altered in toxin receptor levels or cell cycle profiles. Treatment of TIR macrophages with high doses of LT resulted in a sustained decline in full-length mitogen-activated protein kinase kinase 2, a known target of lethal factor, and a marked reduction in diphosphorylated extracellular response kinases 1,2 for 24 h. However, despite the sustained loss of full-length mitogen-activated protein kinase kinase 2, by 48 h, TIR macrophages regained diphosphorylated extracellular response kinases 1,2, suggesting an adaptation led to recovery of this signaling pathway. TIR macrophages were also able to maintain normal levels of ubiquitinylated proteins, whereas sensitive cells show a rapid reduction in ubiquitin-modified proteins before cell death, indicating a possible alteration in proteasome activity contributed to resistance. These results provide a paradigm for toxin-cell interactions and suggest macrophages are capable of adapting to and tolerating toxic doses of LT. PMID:14519843

  5. Construction, expression and characterization of chimaeric toxins containing the ribonucleolytic toxin restrictocin: intracellular mechanism of action.

    PubMed

    Rathore, D; Batra, J K

    1997-06-15

    Restrictocin is a ribonucleolytic toxin produced by the fungus Aspergillus restrictus. Two chimaeric toxins containing restrictocin directed at the human transferrin receptor have been constructed. Anti-TFR(scFv)-restrictocin is encoded by a gene produced by fusing the DNA encoding a single-chain antigen-combining region (scFv) of a monoclonal antibody, directed at the human transferrin receptor, at the 5' end of that encoding restrictocin. The other chimaeric toxin, restrictocin-anti-TFR(scFv), is encoded by a gene fusion containing the DNA encoding the single-chain antigen-combining region of antibody to human transferrin receptor at the 3' end of the DNA encoding restrictocin. These gene fusions were expressed in Escherichia coli, and fusion proteins purified from the inclusion bodies by simple chromatography techniques to near-homogeneity. The two chimaeric toxins were found to be equally active in inhibiting protein synthesis in a cell-free in vitro translation assay system. The chimaeric toxins were selectively toxic to the target cells in culture with potent cytotoxic activities. However, restrictocin-anti-TFR(scFv) was more active than anti-TFR(scFv)-restrictocin on all cell lines studied. By using protease and metabolic inhibitors, it can be shown that, to manifest their cytotoxic activity, the restrictocin-containing chimaeric toxins need to be proteolytically processed intracellularly and the free toxin or a fragment thereof thus generated is translocated to the target via a route involving the Golgi apparatus. PMID:9210405

  6. Antibodies against recombinant shiga toxin subunit B neutralize shiga toxin toxicity in HeLa cells.

    PubMed

    Gupta, Pallavi; Singh, Manglesh Kumar; Singh, Padma; Tiwari, Mugdha; Dhaked, Ram Kumar

    2010-06-01

    Shigella dysenteriae type 1 and Escherichia coli O157:H7 produce Shiga toxin 1 (Stx) and Shiga toxin1 (Stx1), respectively and these two toxins are almost identical. E. coli O157:H7 is the major cause of diarrhea-associated hemolytic uremic syndrome. Stx and Stx1 are AB5 type of toxin with a molecular weight of 70 kDa, comprising an enzymaticaly-active A subunit (32 kDa) and five receptor-binding B subunits (7.7 kDa). In this study DNA fragment (289 bp, Gene Bank Accn No. EF685161) coding for B chain of Stx was amplified from S. dysenteriae type1 and cloned. Shiga toxin-binding subunit was expressed and purified in native conditions by affinity and gel permeation chromatography with the yield of 5.1 mg/L in shake flask culture. For the purpose of immunization, the polypeptide was polymerized with glutaraldehyde. Hyper immune serum produced in mice reacted with the purified polypeptide and intact Shiga toxin. The anti-StxB antiserum effectively neutralized the cytotoxicity of Shiga toxin towards HeLa cells. PMID:20044923

  7. Use of botulinum toxin in Meige's disease.

    PubMed

    Maurri, S; Brogelli, S; Alfieri, G; Barontini, F

    1988-01-01

    Four patients with severe Meige's disease (blepharospasm-oromandibular dystonia) have been treated, after having given an informed consent, by local injections of purified botulinum toxin type "A". Previous systemic therapy with anticholinergics, dopamine antagonists and other drugs had been unsuccessful in all these subjects. Each patient was treated by saline solution injected with the same method as botulinum toxin, just once. The self-evaluation of patients and the clinical evaluation that some of us- unaware of the kind of therapy which had been performed- gave to the symptoms on the basis of videotapes, for each session of injection, showed that the injections of botulinum toxin are effective in the treatment of such disorder. The duration of the beneficial effect was slightly shorter in these patients than in patients with blepharospasm treated by the same method. PMID:3247565

  8. Methods for the detection of marine toxins

    SciTech Connect

    Wekell, M.M.; Manger, R.M.; Hadley, S.W.; Hungerford, J.M.

    1995-12-01

    Toxic materials have been dumped into the seas from waste streams and other pollutant sources such as runoff, etc. For protection of public health, it is essential that rapid, reliable and simple methods exist to detect marine toxins in seafoods. In addition, it is necessary to develop methods requiring a minimum of test material. Pure standards for many of the marine toxins are scarce. Reduced sample requirements extend the utility of detection methods in research and forensic applications as well. In the past, there was much reliance on the animal bioassay; however, this dependence hopefully will be reduced as newer instrumental techniques (chromatographic, mass spectrometric, electrophoretic), biochemical (immunochemical, receptor site assay), and cell bioassay methods are developed with a higher degree of precision and specificity. It is beneficial that a multiplicity of methods be available to detect marine toxins in seafoods. Each method has unique advantages and disadvantages.

  9. Toxin-Deficient Mutants from a Toxin-Sensitive Transformant of Cochliobolus Heterostrophus

    PubMed Central

    Yang, G.; Turgeon, B. G.; Yoder, O. C.

    1994-01-01

    Tox1 is the only genetic element identified which controls production of T-toxin, a linear polyketide involved in the virulence of Cochliobolus heterostrophus to its host plant, corn. Previous attempts to induce toxin-deficient (Tox(-)) mutants, using conventional mutagenesis and screening procedures, have been unsuccessful. As a strategy to enrich for Tox(-) mutants, we constructed a Tox1(+) strain that carried the corn T-urf13 gene (which confers T-toxin sensitivity) fused to a fungal mitochondrial signal sequence; the fusion was under control of the inducible Aspergillus nidulans pelA promoter which, in both A. nidulans and C. heterostrophus, is repressed by glucose and induced by polygalacturonic acid (PGA). We expected that a transformant carrying this construction would be sensitive to its own toxin when the T-urf13 gene was expressed. Indeed, the strain grew normally on medium containing glucose but was inhibited on medium containing PGA. Conidia of this strain were treated with ethylmethanesulfonate and plated on PGA medium. Among 362 survivors, 9 were defective in T-toxin production. Authenticity of each mutant was established by the presence of the transformation vector, proper mating type, and a restiction fragment length polymorphism tightly linked to the Tox1(+) locus. Progeny of each mutant crossed to a Tox1(+) tester segregated 1:1 (for wild type toxin production vs. no or reduced toxin production), indicating a single gene mutation in each case. Progeny of each mutant crossed to a Tox1(-) tester segregated 1 : 1 (for no toxin production vs. no or reduced toxin production) indicating that each mutation mapped at the Tox1 locus. Availability of Tox(-) mutants will permit mapping in the Tox1 region without interference from a known Tox1 linked translocation breakpoint. PMID:8088521

  10. To Track or Not to Track?

    ERIC Educational Resources Information Center

    Hesson, Heather

    2010-01-01

    Background: This paper was written for a graduate level action research course at Muskingum University, located in New Concord, OH. Purpose: The purpose of this research was to determine which method of instruction best serves ALL high school students. Is it more advantageous to track ("ability group") students or not to track students in high…

  11. Calculating track thrust with track functions

    NASA Astrophysics Data System (ADS)

    Chang, Hsi-Ming; Procura, Massimiliano; Thaler, Jesse; Waalewijn, Wouter J.

    2013-08-01

    In e+e- event shapes studies at LEP, two different measurements were sometimes performed: a “calorimetric” measurement using both charged and neutral particles and a “track-based” measurement using just charged particles. Whereas calorimetric measurements are infrared and collinear safe, and therefore calculable in perturbative QCD, track-based measurements necessarily depend on nonperturbative hadronization effects. On the other hand, track-based measurements typically have smaller experimental uncertainties. In this paper, we present the first calculation of the event shape “track thrust” and compare to measurements performed at ALEPH and DELPHI. This calculation is made possible through the recently developed formalism of track functions, which are nonperturbative objects describing how energetic partons fragment into charged hadrons. By incorporating track functions into soft-collinear effective theory, we calculate the distribution for track thrust with next-to-leading logarithmic resummation. Due to a partial cancellation between nonperturbative parameters, the distributions for calorimeter thrust and track thrust are remarkably similar, a feature also seen in LEP data.

  12. Preventing biosensor non-specific adsorption: Static to dynamic interfaces

    NASA Astrophysics Data System (ADS)

    Harwood, Lucy; Hopkins, Neal

    2012-02-01

    Biosensors are currently being developed for the detection of a wide range of analytes in a variety of scenarios. One such area is that of environmental monitoring for the presence of biological threats, from toxins through to viruses and bacteria. Environmental samples will contain a wide variety of contaminants, dependent on the location and prevalent environmental conditions. The sensing surfaces employed by biosensor instruments must be capable of resisting non-specific adsorption (NSA) of the contaminants whilst specifically capturing targets of interest. The ability to do so reduces the incidence of false positives and negatives increasing confidence in the system. We have assessed a range of biosensor surface chemistries of both two and three dimensional topography using a commercial BIAcore platform, for ability to prevent NSA of soluble materials of medical and military significance. This has highlighted that future solutions may benefit from dynamic interfaces as opposed to the conventional static interface often employed.

  13. ANALYSES OF WOUND EXUDATES FOR CLOSTRIDIAL TOXINS.

    PubMed

    NOYES, H E; PRITCHARD, W L; BRINKLEY, F B; MENDELSON, J A

    1964-03-01

    Noyes, Howard E. (Walter Reed Army Institute of Research, Washington, D.C.), William L. Pritchard, Floyd B. Brinkley, and Janice A. Mendelson. Analyses of wound exudates for clostridial toxins. J. Bacteriol. 87:623-629. 1964.-Earlier studies indicated that death of goats with traumatic wounds of the hindquarter could be related to the number of clostridia in the wounds, and that toxicity of wound exudates for mice and guinea pigs could be partially neutralized by commercial trivalent gas gangrene antitoxin. This report describes in vitro and in vivo analyses of wound exudates for known clostridial toxins. Wounds were produced by detonation of high-explosive pellets. Wound exudates were obtained by cold saline extraction of both necrotic tissues and gauze sponges used to cover the wounds. Exudates were sterilized by Seitz filtration in the cold. In vitro tests were used to measure alpha-, theta-, and mu-toxins of Clostridium perfringens and the epsilon-toxin of C. novyi. Mouse protection tests, employing commercial typing antisera, were used to analyze exudates for other clostridial toxins. Lethality of wound exudates for mice could be related to (i) the numbers of clostridia present in the wound, (ii) survival time of the goats, and (iii) positive lecithovitellin (LV) tests of the exudates. However, the LV tests could not be neutralized by antitoxin specific for C. perfringens alpha-toxin. Mice were not protected by typing antisera specific for types A, C, or D C. perfringens or C. septicum but were protected by antisera specific for type B C. perfringens and types A and B C. novyi. PMID:14127581

  14. Adsorption of polymeric brushes: Bridging

    NASA Astrophysics Data System (ADS)

    Johner, Albert; Joanny, Jean-François

    1992-04-01

    We study the adsorption of grafted polymer layers on a planar surface parallel to the grafting surface. The layer consists of two types of chains: nonadsorbed chains with a free end and adsorbed chains forming bridges between the two plates. In the limit of strong adsorption a dead zone exists in the vicinity of the adsorbing plate; its size increases with the adsorption strength. Two adsorption mechanisms are possible: adsorption of the last monomer only and adsorption of all the monomers. In both cases the adsorption regimes at equilibrium (when no external force acts on the plates) are discussed within the framework of the self-consistent mean-field theory. We also give scaling laws taking into account excluded volume correlations. Finally, we consider situations where a finite external force, either tangential or normal to the plates, is applied on the adsorbing plate. Pulling and tangential forces both reduce the fraction of bridges and eventually lead to rupture, whereas compressional forces favor bridging. For normal forces, force vs distance profiles between planes and crossed cylinders are given.

  15. Marine Toxins Targeting Ion Channels

    PubMed Central

    Arias, Hugo R.

    2006-01-01

    This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs), as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs), are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV), Ca2+ (CaV), and K+ (KV) channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR), and the ATP-activated (P2XnR) receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+), whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−). In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers) of ion channel functions to treat or to alleviate a specific ion channel-linked disease (e

  16. Bacterial Toxins and the Nervous System: Neurotoxins and Multipotential Toxins Interacting with Neuronal Cells

    PubMed Central

    Popoff, Michel R.; Poulain, Bernard

    2010-01-01

    Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types including neuronal cells. Various enterotoxins interact with the enteric nervous system, for example by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, in amplification of the diarrhea, or in intestinal inflammation process. Other toxins can pass the blood brain barrier and directly act on specific neurons. PMID:22069606

  17. Natural toxins for use in pest management.

    PubMed

    Duke, Stephen O; Cantrell, Charles L; Meepagala, Kumudini M; Wedge, David E; Tabanca, Nurhayat; Schrader, Kevin K

    2010-08-01

    Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly successful products based on natural compounds in the major pesticide classes. These include the herbicide glufosinate (synthetic phosphinothricin), the spinosad insecticides, and the strobilurin fungicides. These and other examples of currently marketed natural product-based pesticides, as well as natural toxins that show promise as pesticides from our own research are discussed. PMID:22069667

  18. Impact of CDT Toxin on Human Diseases

    PubMed Central

    Faïs, Tiphanie; Delmas, Julien; Serres, Arnaud; Bonnet, Richard; Dalmasso, Guillaume

    2016-01-01

    Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects. PMID:27429000

  19. Snake venom toxins: toxicity and medicinal applications.

    PubMed

    Chan, Yau Sang; Cheung, Randy Chi Fai; Xia, Lixin; Wong, Jack Ho; Ng, Tzi Bun; Chan, Wai Yee

    2016-07-01

    Snake venoms are complex mixtures of small molecules and peptides/proteins, and most of them display certain kinds of bioactivities. They include neurotoxic, cytotoxic, cardiotoxic, myotoxic, and many different enzymatic activities. Snake envenomation is a significant health issue as millions of snakebites are reported annually. A large number of people are injured and die due to snake venom poisoning. However, several fatal snake venom toxins have found potential uses as diagnostic tools, therapeutic agent, or drug leads. In this review, different non-enzymatically active snake venom toxins which have potential therapeutic properties such as antitumor, antimicrobial, anticoagulating, and analgesic activities will be discussed. PMID:27245678

  20. Impact of CDT Toxin on Human Diseases.

    PubMed

    Faïs, Tiphanie; Delmas, Julien; Serres, Arnaud; Bonnet, Richard; Dalmasso, Guillaume

    2016-01-01

    Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects. PMID:27429000

  1. Regulation of Toxin Production in Clostridium perfringens

    PubMed Central

    Ohtani, Kaori; Shimizu, Tohru

    2016-01-01

    The Gram-positive anaerobic bacterium Clostridium perfringens is widely distributed in nature, especially in soil and the gastrointestinal tracts of humans and animals. C. perfringens causes gas gangrene and food poisoning, and it produces extracellular enzymes and toxins that are thought to act synergistically and contribute to its pathogenesis. A complicated regulatory network of toxin genes has been reported that includes a two-component system for regulatory RNA and cell-cell communication. It is necessary to clarify the global regulatory system of these genes in order to understand and treat the virulence of C. perfringens. We summarize the existing knowledge about the regulatory mechanisms here. PMID:27399773

  2. Natural Toxins for Use in Pest Management

    PubMed Central

    Duke, Stephen O.; Cantrell, Charles L.; Meepagala, Kumudini M.; Wedge, David E.; Tabanca, Nurhayat; Schrader, Kevin K.

    2010-01-01

    Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly successful products based on natural compounds in the major pesticide classes. These include the herbicide glufosinate (synthetic phosphinothricin), the spinosad insecticides, and the strobilurin fungicides. These and other examples of currently marketed natural product-based pesticides, as well as natural toxins that show promise as pesticides from our own research are discussed. PMID:22069667

  3. Streptococcal toxins: role in pathogenesis and disease.

    PubMed

    Barnett, Timothy C; Cole, Jason N; Rivera-Hernandez, Tania; Henningham, Anna; Paton, James C; Nizet, Victor; Walker, Mark J

    2015-12-01

    Group A Streptococcus (Streptococcus pyogenes), group B Streptococcus (Streptococcus agalactiae) and Streptococcus pneumoniae (pneumococcus) are host-adapted bacterial pathogens among the leading infectious causes of human morbidity and mortality. These microbes and related members of the genus Streptococcus produce an array of toxins that act against human cells or tissues, resulting in impaired immune responses and subversion of host physiological processes to benefit the invading microorganism. This toxin repertoire includes haemolysins, proteases, superantigens and other agents that ultimately enhance colonization and survival within the host and promote dissemination of the pathogen. PMID:26433203

  4. Random sequential adsorption on fractals

    NASA Astrophysics Data System (ADS)

    Ciesla, Michal; Barbasz, Jakub

    2012-07-01

    Irreversible adsorption of spheres on flat collectors having dimension d < 2 is studied. Molecules are adsorbed on Sierpinski's triangle and carpet-like fractals (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled numerically using random sequential adsorption (RSA) algorithm. The paper concentrates on measurement of fundamental properties of coverages, i.e., maximal random coverage ratio and density autocorrelation function, as well as RSA kinetics. Obtained results allow to improve phenomenological relation between maximal random coverage ratio and collector dimension. Moreover, simulations show that, in general, most of known dimensional properties of adsorbed monolayers are valid for non-integer dimensions.

  5. Random sequential adsorption on fractals.

    PubMed

    Ciesla, Michal; Barbasz, Jakub

    2012-07-28

    Irreversible adsorption of spheres on flat collectors having dimension d < 2 is studied. Molecules are adsorbed on Sierpinski's triangle and carpet-like fractals (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled numerically using random sequential adsorption (RSA) algorithm. The paper concentrates on measurement of fundamental properties of coverages, i.e., maximal random coverage ratio and density autocorrelation function, as well as RSA kinetics. Obtained results allow to improve phenomenological relation between maximal random coverage ratio and collector dimension. Moreover, simulations show that, in general, most of known dimensional properties of adsorbed monolayers are valid for non-integer dimensions. PMID:22852643

  6. Alkali extraction of beta-d-glucans from Saccharomyces cerevisiae cell wall and study of their adsorptive properties toward zearalenone.

    PubMed

    Yiannikouris, Alexandros; François, Jean; Poughon, Laurent; Dussap, Claude-Gilles; Bertin, Gérard; Jeminet, Georges; Jouany, Jean-Pierre

    2004-06-01

    The isolated cell wall of Saccharomyces cerevisiae has some capacity to adsorb zearalenone (affinity near 30%) and reduce the bioavailability of toxins in the digestive tract. The adsorption process was quantified in vitro, and the data obtained when plotted with Hill's equation indicated a cooperative process. The model showed that the adsorption capacity was related to the yeast cell wall composition. This work focused on the role of various beta-d-glucan types in the efficacy of zearalenone adsorption by yeast cell wall and sought to elucidate some of the adsorption mechanisms. Zearalenone was mixed at 37 degrees C with a constant quantity of alkali-soluble or alkali-insoluble beta-d-glucans isolated from yeast cell walls, and the amount of adsorbed zearalenone was measured. Given that the alkali solubility of beta-d-glucans is a determining factor for their three-dimensional conformation and that the alkali-insoluble fraction had a greater affinity (up to 50%) than the alkali-soluble fraction ( approximately 16%), it was concluded that the three-dimensional structure strongly influences the adsorption process. The alkali insolubility of beta-d-glucans led to the formation of single and/or triple helices, which have been identified as the most favorable structures for zearalenone adsorption efficacy. The beta(1,3)-d-glucan and beta(1,6)-d-glucan compositions of the two alkali-extracted fractions and their involvement in the adsorption process are discussed. PMID:15161247

  7. Anthrax toxin-induced rupture of artificial lipid bilayer membranes.

    PubMed

    Nablo, Brian J; Panchal, Rekha G; Bavari, Sina; Nguyen, Tam L; Gussio, Rick; Ribot, Wil; Friedlander, Art; Chabot, Donald; Reiner, Joseph E; Robertson, Joseph W F; Balijepalli, Arvind; Halverson, Kelly M; Kasianowicz, John J

    2013-08-14

    We demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. When the solution pH is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. The results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm. PMID:23947891

  8. Anthrax toxin-induced rupture of artificial lipid bilayer membranes

    NASA Astrophysics Data System (ADS)

    Nablo, Brian J.; Panchal, Rekha G.; Bavari, Sina; Nguyen, Tam L.; Gussio, Rick; Ribot, Wil; Friedlander, Art; Chabot, Donald; Reiner, Joseph E.; Robertson, Joseph W. F.; Balijepalli, Arvind; Halverson, Kelly M.; Kasianowicz, John J.

    2013-08-01

    We demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. When the solution pH is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. The results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm.

  9. EFFECTS OF MARINE ALGAL TOXINS ON THERMOREGULATION IN MICE.

    EPA Science Inventory

    Hypothermia is often seen in mice and rats exposed acutely to marine algal toxins, but the mechanism of action of these toxins on thermoregulation is not well understood. Our laboratory has assessed the thermoregulatory mechanisms of two marine algal toxins, maitotoxin and brevet...

  10. Pore-forming activity of clostridial binary toxins.

    PubMed

    Knapp, O; Benz, R; Popoff, M R

    2016-03-01

    Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as Bacillus binary toxins, including Bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. Clostridial binary toxins induce actin cytoskeleton disorganization through mono-ADP-ribosylation of globular actin and are responsible for enteric diseases. Clostridial and Bacillus binary toxins share structurally and functionally related binding components which recognize specific cell receptors, oligomerize, form pores in endocytic vesicle membrane, and mediate the transport of the enzymatic component into the cytosol. Binding components retain the global structure of pore-forming toxins (PFTs) from the cholesterol-dependent cytotoxin family such as perfringolysin. However, their pore-forming activity notably that of clostridial binding components is more related to that of heptameric PFT family including aerolysin and C. perfringens epsilon toxin. This review focuses upon pore-forming activity of clostridial binary toxins compared to other related PFTs. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. PMID:26278641

  11. Thermodynamic Considerations in Solid Adsorption of Bound Solutes for Patient Support in Liver Failure

    PubMed Central

    Patzer, John F.

    2008-01-01

    New detoxification modes of treatment for liver failure that use solid adsorbents to remove toxins bound to albumin in the patient bloodstream are entering clinical evaluations, frequently in head-to-head competition. While generally effective in reducing toxin concentration beyond that obtainable by conventional dialysis procedures, the solid adsorbent processes are largely the result of heuristic development. Understanding the principles and limitations inherent in competitive toxin binding, albumin versus solid adsorbent, will enhance the design process and, possibly, improve detoxification performance. An equilibrium thermodynamic analysis is presented for both the Molecular Adsorbent Recirculating System (MARS) and Fractionated Plasma Separation, Adsorption, and Dialysis System (Prometheus), two advanced systems with distinctly different operating modes but with similar equilibrium limitations. The Prometheus analysis also applies to two newer approaches: sorbent suspension reactor (SSR) and microspheres-based detoxification system (MDS). Primary results from the thermodynamic analysis are that: (1) the solute-albumin binding constant is of minor importance to equilibrium once it exceeds about 105 L mol−1; (2) the Prometheus approach requires larger solid adsorbent columns than calculated by adsorbent solute capacity alone; and (3) the albumin-containing recycle stream in the MARS approach is a major reservoir of removed toxin. A survey of published results indicates that MARS is operating under mass transfer control dictated by solute-albumin equilibrium in the recycle stream and Prometheus is approaching equilibrium limits under current clinical protocols. PMID:18638303

  12. Centrifugal Adsorption Cartridge System

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Tsao, Yow-Min D.; Lee, Wenshan

    2004-01-01

    The centrifugal adsorption cartridge system (CACS) is an apparatus that recovers one or more bioproduct(s) from a dilute aqueous solution or suspension flowing from a bioreactor. The CACS can be used both on Earth in unit gravity and in space in low gravity. The CACS can be connected downstream from the bioreactor; alternatively, it can be connected into a flow loop that includes the bioreactor so that the liquid can be recycled. A centrifugal adsorption cartridge in the CACS (see figure) includes two concentric cylinders with a spiral ramp between them. The volume between the inner and outer cylinders, and between the turns of the spiral ramp is packed with an adsorbent material. The inner cylinder is a sieve tube covered with a gas-permeable, hydrophobic membrane. During operation, the liquid effluent from the bioreactor is introduced at one end of the spiral ramp, which then constrains the liquid to flow along the spiral path through the adsorbent material. The spiral ramp also makes the flow more nearly uniform than it would otherwise be, and it minimizes any channeling other than that of the spiral flow itself. The adsorbent material is formulated to selectively capture the bioproduct(s) of interest. The bioproduct(s) can then be stored in bound form in the cartridge or else eluted from the cartridge. The centrifugal effect of the spiral flow is utilized to remove gas bubbles from the liquid. The centrifugal effect forces the bubbles radially inward, toward and through the membrane of the inner cylinder. The gas-permeable, hydrophobic membrane allows the bubbles to enter the inner cylinder while keeping the liquid out. The bubbles that thus enter the cylinder are vented to the atmosphere. The spacing between the ramps determines rate of flow along the spiral, and thereby affects the air-bubble-removal efficiency. The spacing between the ramps also determines the length of the fluid path through the cartridge adsorbent, and thus affects the bioproduct

  13. Photographing Track Meets.

    ERIC Educational Resources Information Center

    Palmer, Erik

    2001-01-01

    Argues that the sport of track and field, because of the sport itself and its relatively easy access to photographers, is an obvious target for cameras. Discusses rules of the track that photographers must follow; picking a location; and equipment. Discusses shooting four specific track and field events and offers behind the scenes photos. (SR)

  14. Solar tracking apparatus

    DOEpatents

    Hammons, Burrell E.

    1980-01-01

    The invention relates to a solar tracking device which tracks the position of the sun using paired, partially-shaded photocells. Auxiliary photocells are used for initial acquisition of the sun and for the suppression of false tracking when the sun is obscured by clouds.

  15. Solar tracking apparatus

    DOEpatents

    Hammons, B.E.

    The invention relates to a solar tracking device which tracks the position of the sun using paired, partially-shaded photocells. Auxilliary photocells are used for initial acquisition of the sun and for the suppression of false tracking when the sun is obscured by clouds.

  16. Track and Field Facilities.

    ERIC Educational Resources Information Center

    Wood, Tony

    2001-01-01

    Discusses planning and design tips that help ensure track and field facilities are successful and well-suited to both school and community use. Examines approaches to determining the best track surface and ways to maximize track and field flexibility with limited space. (GR)

  17. Bromide Adsorption by Reference Minerals and Soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bromide, Br-, adsorption behavior was investigated on amorphous Al and Fe oxide, montmorillonite, kaolinite, and temperate and tropical soils. Bromide adsorption decreased with increasing solution pH with minimal adsorption occurring above pH 7. Bromide adsorption was higher for amorphous oxides t...

  18. A Cell-Based Fluorescent Assay to Detect the Activity of Shiga Toxin and Other Toxins That Inhibit Protein Synthesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Escherichia coli O157:H7, a major cause of food-borne illness, produces Shiga toxins that block protein synthesis by inactivating the ribosome. In this chapter we describe a simple cell-based fluorescent assay to detect Shiga toxins and inhibitors of toxin activity. The assay can also be used to d...

  19. Molecular adsorption on graphene

    NASA Astrophysics Data System (ADS)

    Kong, Lingmei; Enders, Axel; Rahman, Talat S.; Dowben, Peter A.

    2014-11-01

    Current studies addressing the engineering of charge carrier concentration and the electronic band gap in epitaxial graphene using molecular adsorbates are reviewed. The focus here is on interactions between the graphene surface and the adsorbed molecules, including small gas molecules (H2O, H2, O2, CO, NO2, NO, and NH3), aromatic, and non-aromatic molecules (F4-TCNQ, PTCDA, TPA, Na-NH2, An-CH3, An-Br, Poly (ethylene imine) (PEI), and diazonium salts), and various biomolecules such as peptides, DNA fragments, and other derivatives. This is followed by a discussion on graphene-based gas sensor concepts. In reviewing the studies of the effects of molecular adsorption on graphene, it is evident that the strong manipulation of graphene’s electronic structure, including p- and n-doping, is not only possible with molecular adsorbates, but that this approach appears to be superior compared to these exploiting edge effects, local defects, or strain. However, graphene-based gas sensors, albeit feasible because huge adsorbate-induced variations in the relative conductivity are possible, generally suffer from the lack of chemical selectivity.

  20. Molecular adsorption on graphene.

    PubMed

    Kong, Lingmei; Enders, Axel; Rahman, Talat S; Dowben, Peter A

    2014-11-01

    Current studies addressing the engineering of charge carrier concentration and the electronic band gap in epitaxial graphene using molecular adsorbates are reviewed. The focus here is on interactions between the graphene surface and the adsorbed molecules, including small gas molecules (H(2)O, H(2), O(2), CO, NO(2), NO, and NH(3)), aromatic, and non-aromatic molecules (F4-TCNQ, PTCDA, TPA, Na-NH(2), An-CH(3), An-Br, Poly (ethylene imine) (PEI), and diazonium salts), and various biomolecules such as peptides, DNA fragments, and other derivatives. This is followed by a discussion on graphene-based gas sensor concepts. In reviewing the studies of the effects of molecular adsorption on graphene, it is evident that the strong manipulation of graphene's electronic structure, including p- and n-doping, is not only possible with molecular adsorbates, but that this approach appears to be superior compared to these exploiting edge effects, local defects, or strain. However, graphene-based gas sensors, albeit feasible because huge adsorbate-induced variations in the relative conductivity are possible, generally suffer from the lack of chemical selectivity. PMID:25287516

  1. Botulinum toxin (botox) chemodenervation for facial rejuvenation.

    PubMed

    Carruthers, J; Carruthers, A

    2001-05-01

    A positive attitude toward life at any age is now seen to be consistent with inclusion in all societal activities. A mere increase in years is no longer enough reason for "ageism." Botulinum Toxin (Botox) aesthetic treatments, because of their outstanding effectiveness and safety, can continue to play a positive role in the rebuttal of "ageism." PMID:11457686

  2. Toxins and antimicrobial peptides: interactions with membranes

    NASA Astrophysics Data System (ADS)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  3. Natural toxins for use in pest management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly ...

  4. (-)-Botryodiplodin, A Unique Ribose Analog Toxin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many toxins owe their mechanisms of action to being structural analogs of essential metabolites, messengers or structural components. Examples range from tubo-curare to penicillin. Ribose plays a unique role in the metabolism of living organisms, whether prokaryotes or eukaryotes. It and its deri...

  5. Cyanobacterial toxins: biosynthetic routes and evolutionary roots.

    PubMed

    Dittmann, Elke; Fewer, David P; Neilan, Brett A

    2013-01-01

    Cyanobacteria produce an unparalleled variety of toxins that can cause severe health problems or even death in humans, and wild or domestic animals. In the last decade, biosynthetic pathways have been assigned to the majority of the known toxin families. This review summarizes current knowledge about the enzymatic basis for the production of the hepatotoxins microcystin and nodularin, the cytotoxin cylindrospermopsin, the neurotoxins anatoxin and saxitoxin, and the dermatotoxin lyngbyatoxin. Elucidation of the biosynthetic pathways of the toxins has paved the way for the development of molecular techniques for the detection and quantification of the producing cyanobacteria in different environments. Phylogenetic analyses of related clusters from a large number of strains has also allowed for the reconstruction of the evolutionary scenarios that have led to the emergence, diversification, and loss of such gene clusters in different strains and genera of cyanobacteria. Advances in the understanding of toxin biosynthesis and evolution have provided new methods for drinking-water quality control and may inspire the development of techniques for the management of bloom formation in the future. PMID:23051004

  6. Botulinum Toxin in Neurogenic Detrusor Overactivity

    PubMed Central

    Ferreira, Rúiter Silva; Rassi, Mauricio Carneiro

    2012-01-01

    Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks) and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life. PMID:23094220

  7. Molecular basis for tetanus toxin coreceptor interactions.

    PubMed

    Chen, Chen; Baldwin, Michael R; Barbieri, Joseph T

    2008-07-01

    Tetanus toxin (TeNT) elicits spastic paralysis through the cleavage of vesicle-associated membrane protein-2 (VAMP-2) in neurons at the interneuronal junction of the central nervous system. While TeNT retrograde traffics from peripheral nerve endings to the interneuronal junction, there is limited understanding of the neuronal receptors utilized by tetanus toxin for the initial entry into nerve cells. Earlier studies implicated a coreceptor for tetanus toxin entry into neurons: a ganglioside binding pocket and a sialic acid binding pocket and that GT1b bound to each pocket. In this study, a solid phase assay characterized the ganglioside binding specificity and functional properties of both carbohydrate binding pockets of TeNT. The ganglioside binding pocket recognized the ganglioside sugar backbone, Gal-GalNAc, independent of sialic acid-(5) and sialic acid-(7) and GM1a was an optimal substrate for this pocket, while the sialic acid binding pocket recognized sialic acid-(5) and sialic acid-(7) with "b"series of gangliosides preferred relative to "a" series gangliosides. The high-affinity binding of gangliosides to TeNT HCR required functional ganglioside and sialic acid binding pockets, supporting synergistic binding to coreceptors. This analysis provides a model for how tetanus toxin utilizes coreceptors for high-affinity binding to neurons. PMID:18543947

  8. Pasteurella multocida Toxin Manipulates T Cell Differentiation

    PubMed Central

    Hildebrand, Dagmar; Heeg, Klaus; Kubatzky, Katharina F.

    2015-01-01

    Pasteurella multocida causes various diseases in a broad range of wild and domestic animals. Toxigenic strains of the serotypes A and D produce an AB protein toxin named Pasteurella multocida toxin (PMT). PMT constitutively activates the heterotrimeric G protein subunits Gαq, Gα13, and Gαi through deamidation of a glutamine residue, which results in cytoskeletal rearrangements as well as increased proliferation and survival of the host cell. In human monocytes, PMT alters the lipopolysaccharide (LPS)-induced activation toward a phenotype that suppresses T cell activation. Here we describe that the toxin also modulates CD4-positive T helper (Th) cells directly. PMT amplifies the expansion of Th cells through enhanced cell cycle progression and suppression of apoptosis and manipulates the differentiation of Th subclasses through activation of Signal Transducers and Activators of Transcription (STAT) family members and induction of subtype-specific master transcription factors. A large population of toxin-treated T cells is double-positive for Foxp3 and RORγt, the transcription factors expressed by Treg and Th17 cells, respectively. This suggests that these cells could have the potential to turn into Th17 cells or suppressive Treg cells. However, in terms of function, the PMT-differentiated cells behave as inflammatory Th17 cells that produce IL-17 and trigger T cell proliferation. PMID:26635744

  9. Short-Cycle Adsorption Refrigerator

    NASA Technical Reports Server (NTRS)

    Chan, C. K.

    1988-01-01

    Modular adsorption/Joule-Thomson-effect refrigerator offers fast regeneration; adsorption/desorption cycle time expected to be 1 minute. Pressurized hydrogen generated by bank of compressor modules during heating phase passes through system of check valves and expands in Joule-Thomson junction as it enters refrigeration chamber. Hydrogen absorbs heat from load before it is sucked out by another bank of compressor modules in cooling phase.

  10. Finite resolution multitarget tracking

    NASA Astrophysics Data System (ADS)

    Mušicki, Darko; Morelande, Mark R.

    2005-09-01

    Target tracking algorithms have to operate in an environment of uncertain measurement origin, due to the presence of randomly detected target measurements as well as clutter measurements from unwanted random scatterers. A majority of Bayesian multi-target tracking algorithms suffer from computational complexity which is exponential in the number of tracks and the number of shared measurements. The Linear Multi-target (LM) tracking procedure is a Bayesian multi-target tracking approximation with complexity which is linear in the number of tracks and the number of shared measurements. It also has a much simpler structure than the "optimal" Bayesian multi-target tracking, with apparently negligible decrease in performance. A vast majority of target tracking algorithms have been developed with the assumption of infinite sensor resolution, where a measurement can have only one source. This assumption is not valid for real sensors, such as radars. This paper presents a multi-target tracking algorithm which removes this restriction. The procedure utilizes a simple structure of LM tracking procedure to obtain a LM Finite Resolution (LMfr) tracking procedure which is much simpler than the previously published efforts. Instead of calculating the probability of measurement merging for each combination of potentially merging targets, we evaluate only one merging hypotheses for each measurement and each track. A simulation study is presented which compares LMfr-IPDA with LM-IPDA and IPDA target tracking in a cluttered environment utilizing a finite resolution sensor with five crossing targets. The study concentrates on the false track discrimination performance and the track retention capabilities.

  11. Alpha-Toxin and Gamma-Toxin Jointly Promote Staphylococcus aureus Virulence in Murine Septic Arthritis

    PubMed Central

    Nilsson, Ing-Marie; Hartford, Orla; Foster, Timothy; Tarkowski, Andrzej

    1999-01-01

    Septic arthritis is a common and feared complication of staphylococcal infections. Staphylococcus aureus produces a number of potential virulence factors including certain adhesins and enterotoxins. In this study we have assessed the roles of cytolytic toxins in the development of septic arthritis by inoculating mice with S. aureus wild-type strain 8325-4 or isogenic mutants differing in the expression of alpha-, beta-, and gamma-toxin production patterns. Mice inoculated with either an alpha- or beta-toxin mutant showed degrees of inflammation, joint damage, and weight decrease similar to wild-type-inoculated mice. In contrast, mice inoculated with either double (alpha- and gamma-toxin-deficient)- or triple (alpha-, beta-, and gamma-toxin-deficient)-mutant S. aureus strains showed lower frequency and severity of arthritis, measured both clinically and histologically, than mice inoculated with the wild-type strain. We conclude that simultaneous production of alpha- and gamma-toxin is a virulence factor in S. aureus arthritis. PMID:10024541

  12. Neutralizing Monoclonal Antibodies against Disparate Epitopes on Ricin Toxin's Enzymatic Subunit Interfere with Intracellular Toxin Transport.

    PubMed

    Yermakova, Anastasiya; Klokk, Tove Irene; O'Hara, Joanne M; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J

    2016-01-01

    Ricin is a member of the A-B family of bacterial and plant toxins that exploit retrograde trafficking to the Golgi apparatus and endoplasmic reticulum (ER) as a means to deliver their cytotoxic enzymatic subunits into the cytoplasm of mammalian cells. In this study we demonstrate that R70 and SyH7, two well-characterized monoclonal antibodies (mAbs) directed against distinct epitopes on the surface of ricin's enzymatic subunit (RTA), interfere with toxin transport from the plasma membrane to the trans Golgi network. Toxin-mAb complexes formed on the cell surface delayed ricin's egress from EEA-1(+) and Rab7(+) vesicles and enhanced toxin accumulation in LAMP-1(+) vesicles, suggesting the complexes were destined for degradation in lysosomes. Three other RTA-specific neutralizing mAbs against different epitopes were similar to R70 and SyH7 in terms of their effects on ricin retrograde transport. We conclude that interference with toxin retrograde transport may be a hallmark of toxin-neutralizing antibodies directed against disparate epitopes on RTA. PMID:26949061

  13. Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

    SciTech Connect

    Won, JaeSeon; Nam, PilWon; Lee, YongChan; Choe, MuHyeon

    2009-04-24

    Recombinant antibody-toxins are constructed via the fusion of a 'carcinoma-specific' antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G{sub 4}S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]{sub 2}) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

  14. Alpha-toxin of Staphylococcus aureus.

    PubMed Central

    Bhakdi, S; Tranum-Jensen, J

    1991-01-01

    Alpha-toxin, the major cytotoxic agent elaborated by Staphylococcus aureus, was the first bacterial exotoxin to be identified as a pore former. The protein is secreted as a single-chain, water-soluble molecule of Mr 33,000. At low concentrations (less than 100 nM), the toxin binds to as yet unidentified, high-affinity acceptor sites that have been detected on a variety of cells including rabbit erythrocytes, human platelets, monocytes and endothelial cells. At high concentrations, the toxin additionally binds via nonspecific absorption to lipid bilayers; it can thus damage both cells lacking significant numbers of the acceptor and protein-free artificial lipid bilayers. Membrane damage occurs in both cases after membrane-bound toxin molecules collide via lateral diffusion to form ring-structured hexamers. The latter insert spontaneously into the lipid bilayer to form discrete transmembrane pores of effective diameter 1 to 2 nm. A hypothetical model is advanced in which the pore is lined by amphiphilic beta-sheets, one surface of which interacts with lipids whereas the other repels apolar membrane constitutents to force open an aqueous passage. The detrimental effects of alpha-toxin are due not only to the death of susceptible targets, but also to the presence of secondary cellular reactions that can be triggered via Ca2+ influx through the pores. Well-studied phenomena include the stimulation of arachidonic acid metabolism, triggering of granule exocytosis, and contractile dysfunction. Such processes cause profound long-range disturbances such as development of pulmonary edema and promotion of blood coagulation.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1779933

  15. [Treatment of spasticity with botulinum toxin].

    PubMed

    Mémin, B; Pollak, P; Hommel, M; Perret, J

    1992-01-01

    Spasticity following upper motor neuron lesion can be alleviated by few treatments such as physiotherapy, drugs and neurosurgery. However, they all have side effects, limitations or lack of selectivity. We tentatively used the paralyzing effects of botulinum toxin. Since the late 1970's the use of this toxin has increased and it has been extended to numerous muscles and diseases of various causes. In this pilot and open study we use botulinum toxin in spasticity. Eight patients (7 stroke, 1 head injury) with longstanding severe spasticity (minimum: 12 months, maximum: 15 years) were included. Spasticity greatly interfered with their activity in daily life and was resistant to oral antispastic medications. Six patients suffered from pain and 4 had cutaneous lesions especially maceration of the palm of the hand. A-botulinum toxin was injected with a 30-gauged needle. The sites chosen for injection were the following muscles: biceps brachii, brachioradialis, flexor digitorum, flexor carpi, tibialis anterior, flexor digitorum longus. Altogether 41 injections were performed. There were no side effects. Spasticity was improved in all patients. Five patients reported significant pain relief on a visual analogical scale. Most of them reported a benefit in their limb tone and referred to subjective improvement in the activity of daily life and nursing. The beneficial effects of one injection lasted more than 5 months. Seven patients received a second course of treatment. A double-blind study of botulinum toxin in spasticity is to be undertaken to assess its effectiveness and safety when prescribed in the required dose to treat this condition. PMID:1604136

  16. Protein Adsorption in Three Dimensions

    PubMed Central

    Vogler, Erwin A.

    2011-01-01

    Recent experimental and theoretical work clarifying the physical chemistry of blood-protein adsorption from aqueous-buffer solution to various kinds of surfaces is reviewed and interpreted within the context of biomaterial applications, especially toward development of cardiovascular biomaterials. The importance of this subject in biomaterials surface science is emphasized by reducing the “protein-adsorption problem” to three core questions that require quantitative answer. An overview of the protein-adsorption literature identifies some of the sources of inconsistency among many investigators participating in more than five decades of focused research. A tutorial on the fundamental biophysical chemistry of protein adsorption sets the stage for a detailed discussion of the kinetics and thermodynamics of protein adsorption, including adsorption competition between two proteins for the same adsorbent immersed in a binary-protein mixture. Both kinetics and steady-state adsorption can be rationalized using a single interpretive paradigm asserting that protein molecules partition from solution into a three-dimensional (3D) interphase separating bulk solution from the physical-adsorbent surface. Adsorbed protein collects in one-or-more adsorbed layers, depending on protein size, solution concentration, and adsorbent surface energy (water wettability). The adsorption process begins with the hydration of an adsorbent surface brought into contact with an aqueous-protein solution. Surface hydration reactions instantaneously form a thin, pseudo-2D interface between the adsorbent and protein solution. Protein molecules rapidly diffuse into this newly-formed interface, creating a truly 3D interphase that inflates with arriving proteins and fills to capacity within milliseconds at mg/mL bulk-solution concentrations CB. This inflated interphase subsequently undergoes time-dependent (minutes-to-hours) decrease in volume VI by expulsion of either-or-both interphase water and

  17. Object tracking with stereo vision

    NASA Technical Reports Server (NTRS)

    Huber, Eric

    1994-01-01

    A real-time active stereo vision system incorporating gaze control and task directed vision is described. Emphasis is placed on object tracking and object size and shape determination. Techniques include motion-centroid tracking, depth tracking, and contour tracking.

  18. Vehicle track loading simulation

    NASA Astrophysics Data System (ADS)

    Chalupa, Milan; Severa, Libor; Vlach, Radek

    2011-12-01

    The paper describes possible design of the vehicle track computational model and basic testing procedure of the track dynamic loading simulation. The proposed approach leads to an improvement of track vehicle course stability. The computational model is built for MSC. ADAMS, AVT computational simulating system. Model, which is intended for MSC computational system, is built from two basic parts. The first one is represented by geometrical part, while the second one by contact computational part of the model. The aim of the simulating calculation consist in determination of change influence of specific vehicle track constructive parameters on changes of examined qualities of the vehicle track link and changes of track vehicle course stability. The work quantifies the influence of changes of track preloading values on the demanded torque changes of driving sprocket. Further research possibilities and potential are also presented.

  19. Preliminary spectroscopic characterization of six toxins from Latin American scorpions.

    PubMed

    Possani, L; Steinmetz, W E; Dent, M A; Alagón, A C; Wüthrich, K

    1981-07-28

    This paper reports on spectroscopic studies of six toxins from the Latin American scorpions Centruroides noxius Hoffmann, Centruroides elegans Thorell and Tityus serrulatus Lutz and Mello. The isolation and purification of five of these toxins was described previously. The preparation of toxin II.9.2.2 from the venom of C. noxius is first described here. Circular dichroism and nuclear magnetic resonance spectra indicate similarities and differences between these scorpion toxins and previously characterized snake toxins. While there is evidence that the toxins from scorpions and snakes both contain extended beta-sheet secondary structures, the spectral properties of the scorpion toxins are overall of a different type from those of snake toxins. Among the six scorpion toxins those from T. serrulatus have spectral properties markedly different from those of the Centruroides species. Furthermore, thermal denaturation and amide proton exchange measurements showed that the globular structures of the Tityus toxins were markedly less stable and less rigid than those of the Centruroides toxins. PMID:7284435

  20. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  1. Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice.

    PubMed

    Losada-Eaton, D M; Fernandez-Miyakawa, M E

    2010-12-01

    Epsilon toxin produced by Clostridium perfringens type B and D is a potent toxin that is responsible for a highly fatal enterotoxemia in sheep and goats. In vitro, epsilon toxin produces contraction of the rat ileum as the result of an indirect action, presumably mediated through the autonomic nervous system. To examine the impact of epsilon toxin in the intestinal transit, gastric emptying (GE) and gastrointestinal transit (GIT) were evaluated after intravenous and oral administration of epsilon toxin in mice. Orally administered epsilon toxin produced a delay on the GIT. Inhibition of the small intestinal transit was observed as early as 1 h after the toxin was administered orally but the effects were not observed after 1 week. Epsilon toxin also produced an inhibition in GE and a delay on the GIT when relatively high toxin concentrations were given intravenously. These results indicate that epsilon toxin administered orally or intravenously to mice transitorily inhibits the GIT. The delay in the GIT induced by epsilon toxin could be relevant in the pathogenesis of C. perfringens type B and D enterotoxemia. PMID:20434186

  2. Mode of action of mosquitocidal Bacillus thuringiensis toxins.

    PubMed

    Soberón, Mario; Fernández, Luisa E; Pérez, Claudia; Gill, Sarjeet S; Bravo, Alejandra

    2007-04-01

    Cry toxins from Bacillus thuringiensis (Bt) are used for insect control. Their primary action is to lyse midgut epithelial cells. In lepidopteran insects, Cry1A monomeric toxins interact with a first receptor and this interaction triggers toxin oligomerization. The oligomeric structure interacts then with a second GPI-anchored receptor that induces insertion into membrane microdomains and larvae death. In the case of mosquitocidal Bt strains, two different toxins participate, Cry and Cyt. These toxins have a synergistic effect and Cyt1Aa overcomes Cry toxin-resistance. We will summarize recent findings on the identification of Cry receptors in mosquitoes and the mechanism of synergism: Cyt1Aa synergizes or suppresses resistance to Cry toxins by functioning as a Cry membrane-bound receptor. PMID:17145072

  3. Investigation of adsorptive fractionation of humic acid on graphene oxide using fluorescence EEM-PARAFAC.

    PubMed

    Lee, Bo-Mi; Seo, Young-Soo; Hur, Jin

    2015-04-15

    In this study, the adsorptive fractionation of a humic acid (HA, Elliott soil humic acid) on graphene oxide (GO) was examined at pH 4 and 6 using absorption spectroscopy and fluorescence excitation-emission matrix (EEM)-parallel factor analysis (PARAFAC). The extent of the adsorption was greater at pH 4.0 than at pH 6.0. Aromatic molecules within the HA were preferentially adsorbed onto the GO surface, and the preferential adsorption was more pronounced at pH 6, which is above the zero point of charge of GO. A relative ratio of two PARAFAC humic-like components (ex/em maxima at 270/510 nm and at (250, 265)/440 nm) presented an increasing trend with larger sizes of ultrafiltered humic acid fractions, suggesting the potential for using fluorescence EEM-PARAFAC for tracking the changes in molecular sizes of aromatic HA molecules. The individual adsorption behaviors of the two humic-like components revealed that larger sized aromatic components within HA had a higher adsorption affinity and more nonlinear isotherms compared to smaller sized fractions. Our results demonstrated that adsorptive fractionation of HA occurred on the GO surface with respect to their aromaticity and the sizes, but the degree was highly dependent on solution pH as well as the amount of adsorbed HS (or available surface sites). The observed adsorption behaviors were reasonably explained by a combination of different mechanisms previously suggested. PMID:25682051

  4. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.

    PubMed

    Patil, Shilpadevi; Willett, Olga; Thompkins, Terin; Hermann, Robert; Ramanathan, Sathish; Cornett, Elyse M; Fox, Charles J; Kaye, Alan David

    2016-03-01

    Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients. PMID:26879873

  5. Tracking dynamic team activity

    SciTech Connect

    Tambe, M.

    1996-12-31

    AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesis underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.

  6. Staphylococcus aureus toxins--their functions and genetics.

    PubMed

    Grumann, Dorothee; Nübel, Ulrich; Bröker, Barbara M

    2014-01-01

    The outcome of encounters between Staphylococcus (S.) aureus and its human host ranges from life-threatening infection through allergic reactions to symptom-free colonization. The pan-genome of this bacterial species encodes numerous toxins, known or strongly suspected to cause specific diseases or symptoms. Three toxin families are in the focus of this review, namely (i) pore-forming toxins, (ii) exfoliative toxins and (iii) superantigens. The majority of toxin-encoding genes are located on mobile genetic elements (MGEs), resulting in a pronounced heterogeneity in the endowment with toxin genes of individual S. aureus strains. Recent population genomic analysis have provided a framework for an improved understanding of the temporal and spatial scales of the motility of MGEs and their associated toxin genes. The distribution of toxin genes among clonal lineages within the species S. aureus is not random, and phylogenetic (sub-)lineages within clonal complexes feature characteristic toxin signatures. When studying pathogenesis, this lineage association, which is caused by the clonal nature of S. aureus makes it difficult to discriminate effects of specific toxins from contributions of the genetic background and/or other associated genetic factors. PMID:23541411

  7. ATDB: a uni-database platform for animal toxins

    PubMed Central

    He, Quan-Yuan; He, Quan-Ze; Deng, Xing-Can; Yao, Lei; Meng, Er; Liu, Zhong-Hua; Liang, Song-Ping

    2008-01-01

    Venomous animals possess an arsenal of toxins for predation and defense. These toxins have great diversity in function and structure as well as evolution and therefore are of value in both basic and applied research. Recently, toxinomics researches using cDNA library sequencing and proteomics profiling have revealed a large number of new toxins. Although several previous groups have attempted to manage these data, most of them are restricted to certain taxonomic groups and/or lack effective systems for data query and access. In addition, the description of the function and the classification of toxins is rather inconsistent resulting in a barrier against exchanging and comparing the data. Here, we report the ATDB database and website which contains more than 3235 animal toxins from UniProtKB/Swiss-Prot and TrEMBL and related toxin databases as well as published literature. A new ontology (Toxin Ontology) was constructed to standardize the toxin annotations, which includes 745 distinct terms within four term spaces. Furthermore, more than 8423 TO terms have been manually assigned to 2132 toxins by trained biologists. Queries to the database can be conducted via a user-friendly web interface at http://protchem.hunnu.edu.cn/toxin. PMID:17933766

  8. Sea Anemone (Cnidaria, Anthozoa, Actiniaria) Toxins: An Overview

    PubMed Central

    Frazão, Bárbara; Vasconcelos, Vitor; Antunes, Agostinho

    2012-01-01

    The Cnidaria phylum includes organisms that are among the most venomous animals. The Anthozoa class includes sea anemones, hard corals, soft corals and sea pens. The composition of cnidarian venoms is not known in detail, but they appear to contain a variety of compounds. Currently around 250 of those compounds have been identified (peptides, proteins, enzymes and proteinase inhibitors) and non-proteinaceous substances (purines, quaternary ammonium compounds, biogenic amines and betaines), but very few genes encoding toxins were described and only a few related protein three-dimensional structures are available. Toxins are used for prey acquisition, but also to deter potential predators (with neurotoxicity and cardiotoxicity effects) and even to fight territorial disputes. Cnidaria toxins have been identified on the nematocysts located on the tentacles, acrorhagi and acontia, and in the mucous coat that covers the animal body. Sea anemone toxins comprise mainly proteins and peptides that are cytolytic or neurotoxic with its potency varying with the structure and site of action and are efficient in targeting different animals, such as insects, crustaceans and vertebrates. Sea anemones toxins include voltage-gated Na+ and K+ channels toxins, acid-sensing ion channel toxins, Cytolysins, toxins with Kunitz-type protease inhibitors activity and toxins with Phospholipase A2 activity. In this review we assessed the phylogentic relationships of sea anemone toxins, characterized such toxins, the genes encoding them and the toxins three-dimensional structures, further providing a state-of-the-art description of the procedures involved in the isolation and purification of bioactive toxins. PMID:23015776

  9. Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: an overview.

    PubMed

    Frazão, Bárbara; Vasconcelos, Vitor; Antunes, Agostinho

    2012-08-01

    The Cnidaria phylum includes organisms that are among the most venomous animals. The Anthozoa class includes sea anemones, hard corals, soft corals and sea pens. The composition of cnidarian venoms is not known in detail, but they appear to contain a variety of compounds. Currently around 250 of those compounds have been identified (peptides, proteins, enzymes and proteinase inhibitors) and non-proteinaceous substances (purines, quaternary ammonium compounds, biogenic amines and betaines), but very few genes encoding toxins were described and only a few related protein three-dimensional structures are available. Toxins are used for prey acquisition, but also to deter potential predators (with neurotoxicity and cardiotoxicity effects) and even to fight territorial disputes. Cnidaria toxins have been identified on the nematocysts located on the tentacles, acrorhagi and acontia, and in the mucous coat that covers the animal body. Sea anemone toxins comprise mainly proteins and peptides that are cytolytic or neurotoxic with its potency varying with the structure and site of action and are efficient in targeting different animals, such as insects, crustaceans and vertebrates. Sea anemones toxins include voltage-gated Na⁺ and K⁺ channels toxins, acid-sensing ion channel toxins, Cytolysins, toxins with Kunitz-type protease inhibitors activity and toxins with Phospholipase A2 activity. In this review we assessed the phylogentic relationships of sea anemone toxins, characterized such toxins, the genes encoding them and the toxins three-dimensional structures, further providing a state-of-the-art description of the procedures involved in the isolation and purification of bioactive toxins. PMID:23015776

  10. Shiga toxins: from structure and mechanism to applications.

    PubMed

    Chan, Yau Sang; Ng, Tzi Bun

    2016-02-01

    Shiga toxins are a group of type 2 ribosome-inactivating proteins (RIPs) produced in several types of bacteria. The toxins possess an AB5 structure, which comprises a catalytic A chain with N-glycosidase activity, and five identical B chains and recognize and bind to the target cells with specific carbohydrate moieties. In humans, the major molecular target which recognizes the Shiga toxins is the Gb3 receptor, which is mainly expressed on the cell surface of endothelial cells of the intestine, kidney, and the brain. This causes these organs to be susceptible to the toxicity of Shiga toxins. When a person is infected by Shiga toxin-producing bacteria, the toxin is produced in the gut, translocated to the circulatory system, and carried to the target cells. Toxicity of the toxin causes inflammatory responses and severe cell damages in the intestine, kidneys, and brain, bringing about the hemolytic uremic syndrome (HUS), which can be fatal. The Shiga toxin requires a couple of steps to exert its toxicity to the target cells. After binding with the target cell surface receptor, the toxin requires a complicated process to be transported into the cytosol of the cell before it can approach the ribosomes. The mechanisms for the interactions of the toxin with the cells are described in this review. The consequences of the toxin on the cells are also discussed. It gives an overview of the steps for the toxin to be produced and transported, expression of catalytic activity, and the effects of the toxin on the target cells, as well as effects on the human body. PMID:26685676

  11. Tracking toxic chemicals

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    A new report tracking industrial pollution in North America indicates some good news, in terms of downward trends in the release and transfer of these substances.The July report, which tracks 165 chemicals released in the United States and Canada, shows that the total amount of 3.2 million tonnes of chemical releases and transfers from industrial facilities tracked by the North American Commission for Environmental Cooperation (CEC) decreased by 2% overall from 1995 to 1998.

  12. Toxins for Transgenic Resistance to Hemipteran Pests

    PubMed Central

    Chougule, Nanasaheb P.; Bonning, Bryony C.

    2012-01-01

    The sap sucking insects (Hemiptera), which include aphids, whiteflies, plant bugs and stink bugs, have emerged as major agricultural pests. The Hemiptera cause direct damage by feeding on crops, and in some cases indirect damage by transmission of plant viruses. Current management relies almost exclusively on application of classical chemical insecticides. While the development of transgenic crops expressing toxins derived from the bacterium Bacillus thuringiensis (Bt) has provided effective plant protection against some insect pests, Bt toxins exhibit little toxicity against sap sucking insects. Indeed, the pest status of some Hemiptera on Bt-transgenic plants has increased in the absence of pesticide application. The increased pest status of numerous hemipteran species, combined with increased prevalence of resistance to chemical insecticides, provides impetus for the development of biologically based, alternative management strategies. Here, we provide an overview of approaches toward transgenic resistance to hemipteran pests. PMID:22822455

  13. Transcriptional Stimulation of Anthrax Toxin Receptors by Anthrax Edema Toxin and Bacillus anthracis Sterne Spore

    PubMed Central

    Xu, Qingfu; Hesek, Eric D.; Zeng, Mingtao

    2007-01-01

    We used quantitative real-time RT-PCR to not only investigate the mRNA levels of anthrax toxin receptor 1 (ANTXR1) and 2 (ANTXR2) in the murine J774A.1 macrophage cells and different tissues of mice, but also evaluate the effect of anthrax edema toxin and Bacillus anthracis Sterne spores on the expression of mRNA of these receptors. The mRNA transcripts of both receptors was detected in J774A.1 cells and mouse tissues such as the lung, heart, kidney, spleen, stomach, jejunum, brain, skeleton muscle, and skin. The ANTXR2 mRNA level was significantly higher than that of ANTXR1 in J774A.1 cells and all tissues examined. The mRNA expression of both receptors in the lung was the highest among the tissues evaluated. Interestingly, the mRNA expression of both receptors in J774A.1 cells was up-regulated by edema toxin. In addition, ANTXR mRNA expression in the lung was down-regulated after subcutaneous inoculation of B. anthracis Sterne spores as well as after intranasal administration of anthrax toxin-based vaccine BioThrax™. These results suggest that anthrax edema toxin and B. anthracis Sterne spore are involved in the ANTXR mRNA regulation in host cells. PMID:17459655

  14. Clostridium perfringens epsilon toxin: the third most potent bacterial toxin known.

    PubMed

    Alves, Guilherme Guerra; Machado de Ávila, Ricardo Andrez; Chávez-Olórtegui, Carlos Delfin; Lobato, Francisco Carlos Faria

    2014-12-01

    Epsilon toxin (ETX) is produced by Clostridium perfringens type B and D strains and causes enterotoxemia, a highly lethal disease with major impacts on the farming of domestic ruminants, particularly sheep. ETX belongs to the aerolysin-like pore-forming toxin family. Although ETX has striking similarities to other toxins in this family, ETX is often more potent, with an LD50 of 100 ng/kg in mice. Due to this high potency, ETX is considered as a potential bioterrorism agent and has been classified as a category B biological agent by the Centers for Disease Control and Prevention (CDC) of the United States. The protoxin is converted to an active toxin through proteolytic cleavage performed by specific proteases. ETX is absorbed and acts locally in the intestines then subsequently binds to and causes lesions in other organs, including the kidneys, lungs and brain. The importance of this toxin for veterinary medicine and its possible use as a biological weapon have drawn the attention of researchers and have led to a large number of studies investigating ETX. The aim of the present work is to review the existing knowledge on ETX from C. perfringens type B and D. PMID:25234332

  15. Tracking in anatomic pathology.

    PubMed

    Pantanowitz, Liron; Mackinnon, Alexander C; Sinard, John H

    2013-12-01

    Bar code-based tracking solutions, long present in clinical pathology laboratories, have recently made an appearance in anatomic pathology (AP) laboratories. Tracking of AP "assets" (specimens, blocks, slides) can enhance laboratory efficiency, promote patient safety, and improve patient care. Routing of excess clinical material into research laboratories and biorepositories are other avenues that can benefit from tracking of AP assets. Implementing tracking is not as simple as installing software and turning it on. Not all tracking solutions are alike. Careful analysis of laboratory workflow is needed before implementing tracking to assure that this solution will meet the needs of the laboratory. Such analysis will likely uncover practices that may need to be modified before a tracking system can be deployed. Costs that go beyond simply that of purchasing software will be incurred and need to be considered in the budgeting process. Finally, people, not technology, are the key to assuring quality. Tracking will require significant changes in workflow and an overall change in the culture of the laboratory. Preparation, training, buy-in, and accountability of the people involved are crucial to the success of this process. This article reviews the benefits, available technology, underlying principles, and implementation of tracking solutions for the AP and research laboratory. PMID:23634908

  16. Host receptors for bacteriophage adsorption.

    PubMed

    Bertozzi Silva, Juliano; Storms, Zachary; Sauvageau, Dominic

    2016-02-01

    The adsorption of bacteriophages (phages) onto host cells is, in all but a few rare cases, a sine qua non condition for the onset of the infection process. Understanding the mechanisms involved and the factors affecting it is, thus, crucial for the investigation of host-phage interactions. This review provides a survey of the phage host receptors involved in recognition and adsorption and their interactions during attachment. Comprehension of the whole infection process, starting with the adsorption step, can enable and accelerate our understanding of phage ecology and the development of phage-based technologies. To assist in this effort, we have established an open-access resource--the Phage Receptor Database (PhReD)--to serve as a repository for information on known and newly identified phage receptors. PMID:26755501

  17. Use of botulinum toxin in musculoskeletal pain

    PubMed Central

    Singh, Jasvinder A

    2013-01-01

    Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs) of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A) for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ) pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed. PMID:24715952

  18. Insecticidal toxins from black widow spider venom

    PubMed Central

    Rohou, A.; Nield, J.; Ushkaryov, Y.A.

    2007-01-01

    The biological effects of Latrodectus spider venom are similar in animals from different phyla, but these symptoms are caused by distinct phylum-specific neurotoxins (collectively called latrotoxins) with molecular masses ranging from 110 to 140 kDa. To date, the venom has been found to contain five insecticidal toxins, termed α, β, γ, δ and ε-latroinsectotoxins (LITs). There is also a vertebrate-specific neurotoxin, α-latrotoxin (α-LTX), and one toxin affecting crustaceans, α-latrocrustatoxin (α-LCT). These toxins stimulate massive release of neurotransmitters from nerve terminals and act (1) by binding to specific receptors, some of which mediate an exocytotic signal, and (2) by inserting themselves into the membrane and forming ion-permeable pores. Specific receptors for LITs have yet to be identified, but all three classes of vertebrate receptors known to bind α-LTX are also present in insects. All LTXs whose structures have been elucidated (α-LIT, δ-LIT, α-LTX and α-LCT) are highly homologous and have a similar domain architecture, which consists of a unique N-terminal sequence and a large domain composed of 13–22 ankyrin repeats. Three-dimensional (3D) structure analysis, so far done for α-LTX only, has revealed its dimeric nature and an ability to form symmetrical tetramers, a feature probably common to all LTXs. Only tetramers have been observed to insert into membranes and form pores. A preliminary 3D reconstruction of a δ-LIT monomer demonstrates the spatial similarity of this toxin to the monomer of α-LTX. PMID:17210168

  19. Shiga toxin-producing Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In United States, it is estimated that non-O157 Shiga toxin-producing Escherichia coli (STEC) cause more illnesses than STEC O157:H7, and the majority of cases of non-O157 STEC infections is due to serogroups O26, O45, O103, O111, O121, and O145, referred to as the top six non-O157 STEC. The diseas...

  20. Ratcheting up protein translocation with anthrax toxin

    PubMed Central

    Feld, Geoffrey K; Brown, Michael J; Krantz, Bryan A

    2012-01-01

    Energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. They are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton-gradient-driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order-to-disorder mechanism (akin to a heat-engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton-gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation. PMID:22374876

  1. Shiga toxin binds to activated platelets.

    PubMed

    Ghosh, S A; Polanowska-Grabowska, R K; Fujii, J; Obrig, T; Gear, A R L

    2004-03-01

    Hemolytic uremic syndrome (HUS) is associated with acute renal failure in children and can be caused by Shiga toxin (Stx)-producing Escherichia coli. Thrombocytopenia and formation of renal thrombi are characteristic of HUS, suggesting that platelet activation is involved in its pathogenesis. However, whether Shiga toxin directly activates platelets is controversial. The present study evaluates if potential platelet sensitization during isolation by different procedures influences platelet interaction with Shiga toxin. Platelets isolated from sodium citrate anticoagulated blood were exposed during washing to EDTA and higher g forces than platelets prepared from acid-citrate-dextrose (ACD) plasma. Platelet binding of Stx was significantly higher in EDTA-washed preparations relative to ACD-derived platelets. Binding of Stx was also increased with ACD-derived platelets when activated with thrombin (1 U mL-1) and exposure of the Gb3 Stx receptor was detected only on platelets subjected to EDTA, higher g forces or thrombin. EDTA-exposed platelets lost their normal discoid shape and were larger. P-selectin (CD62P) exposure was significantly increased in EDTA-washed preparations relative to ACD-derived platelets, suggesting platelet activation. Taken together, these results suggest that direct binding of Stx occurs only on 'activated' platelets rather than on resting platelets. The ability of Stx to interact with previously activated platelets may be an important element in understanding the pathogenesis of HUS. PMID:15009469

  2. Cholera toxin interactions with lipid bilayers.

    PubMed

    Tosteson, M T; Tosteson, D C; Rubnitz, J

    1980-01-01

    The purpose of the experiments described in this paper was to assess the binding of cholera toxin to bilayers containing its receptor, the monosialoganglioside, GMl. The assay was based on the fact that GMl confers on the bilayer a negative surface charge. The magnitude of this surface charge was estimated by measuring the electrical conductance (G) of the bilayers exposed to nonactin-K+ under conditions where G is directly proportional to the potassium concentration in the aqueous solutions immediatey adjacent to the membrane surface. When bilayers were formed from mixtures of GMl and glycerolmonooleate (GMO), it was found that the molar ratio of the lipids in the bilayer was the same as that in the membrane forming solution. It was further found that cholera toxin or the binding subunit of the toxin (choleragenoid) bind to GMO bilayers containing GMl (but not to GMO bilayers containing phosphatidyl serine or disialoganglioside GDla). The value of the apparent dissociation constant for the binding of choleragen to its receptor was found to be 10(-11) M, comparable to values found in intact cells. PMID:6933823

  3. NVC-422 Inactivates Staphylococcus aureus Toxins

    PubMed Central

    Jekle, Andreas; Yoon, Jungjoo; Zuck, Meghan; Najafi, Ramin; Wang, Lu; Shiau, Timothy; Francavilla, Charles; Rani, Suriani Abdul; Eitzinger, Christian; Nagl, Markus; Anderson, Mark

    2013-01-01

    Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the host or gaining entry into host cells. They can cause pathogenesis by inhibiting or stimulating certain host functions. For example, in systemic Staphylococcus aureus infections, virulence factors such as toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB) cause sepsis or toxic shock by uncontrolled stimulation of T lymphocytes and by triggering a cytokine storm. In vitro, these superantigens stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and the release of many cytokines. NVC-422 (N,N-dichloro-2,2-dimethyltaurine) is a broad-spectrum, fast-acting topical anti-infective agent against microbial pathogens, including antibiotic-resistant microbes. Using mass spectrometry, we demonstrate here that NVC-422 oxidizes methionine residues of TSST-1, SEA, SEB, and exfoliative toxin A (ETA). Exposure of virulence factors to 0.1% NVC-422 for 1 h prevented TSST-1-, SEA-, SEB-, and ETA-induced cell proliferation and cytokine release. Moreover, NVC-422 also delayed and reduced the protein A- and clumping factor-associated agglutination of S. aureus cultures. These results show that, in addition to its well-described direct microbicidal activity, NVC-422 can inactivate S. aureus virulence factors through rapid oxidation of methionines. PMID:23208720

  4. Bioengineered kidney tubules efficiently excrete uremic toxins

    PubMed Central

    Jansen, J.; Fedecostante, M.; Wilmer, M. J.; Peters, J. G.; Kreuser, U. M.; van den Broek, P. H.; Mensink, R. A.; Boltje, T. J.; Stamatialis, D.; Wetzels, J. F.; van den Heuvel, L. P.; Hoenderop, J. G.; Masereeuw, R.

    2016-01-01

    The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs. PMID:27242131

  5. Emerging food pathogens and bacterial toxins.

    PubMed

    Bielecki, Jacek

    2003-01-01

    Many different foodborne diseases have been described. For example, Shigella bacteria, hepatitis A virus and Norwalk virus were shown as a unwashed hands microorganisms, but pathogen Campylobacter and Escherichia coli were named as raw and undercooked meat and poultry or raw milk and untreated water born bacteria. However, two of them: Listeria monocytogenes and Yersinia enterocolitica are known as growing at refrigerator temperatures. Essential virulence determinants of Listeria monocytogenes pathogenicity are well known as a bacterial toxins. Basic molecular mechanisms of pathogenicity depending from these toxins were presented. It was shown that other bacterial toxins may act as very danger food poisoning substances. This is why elimination of pathogenic microorganisms from foods is an obvious solution in some food processes, however this approach is not practical or even desirable in many processes. Thus, risk assessment and microbial monitoring will continue to play important roles in ensuring food safety. Some technological advances have the capability of delivering detection systems that can not only monitor pathogenic microorganisms, but also entire microbial populations in the food matrix. PMID:15058810

  6. Perfringolysin O: The Underrated Clostridium perfringens Toxin?

    PubMed Central

    Verherstraeten, Stefanie; Goossens, Evy; Valgaeren, Bonnie; Pardon, Bart; Timbermont, Leen; Haesebrouck, Freddy; Ducatelle, Richard; Deprez, Piet; Wade, Kristin R.; Tweten, Rodney; Van Immerseel, Filip

    2015-01-01

    The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O (PFO, classically referred to as θ toxin), a pore-forming cholesterol-dependent cytolysin (CDC). PFO is secreted as a water-soluble monomer that recognizes and binds membranes via cholesterol. Membrane-bound monomers undergo structural changes that culminate in the formation of an oligomerized prepore complex on the membrane surface. The prepore then undergoes conversion into the bilayer-spanning pore measuring approximately 250–300 Å in diameter. PFO is expressed in nearly all identified C. perfringens strains and harbors interesting traits that suggest a potential undefined role for PFO in disease development. Research has demonstrated a role for PFO in gas gangrene progression and bovine necrohemorrhagic enteritis, but there is limited data available to determine if PFO also functions in additional disease presentations caused by C. perfringens. This review summarizes the known structural and functional characteristics of PFO, while highlighting recent insights into the potential contributions of PFO to disease pathogenesis. PMID:26008232

  7. Adsorption on a stepped substrate

    NASA Astrophysics Data System (ADS)

    Merikoski, J.; Timonen, J.; Kaski, K.

    1994-09-01

    The effect of substrate steps on the adsorption of particles is considered. The problem is formulated as a lattice-gas model with nearest neighbor interactions and it is studied by a numerical transfer-matrix method. In particular, the influence of the substrate-induced row potential on adsorbed monolayers is discussed. It is found that strong row-transition-like features appear in the presence of a row potential and it is suggested that these may be seen in adsorption on vicinal faces.

  8. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin

    PubMed Central

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

    2016-01-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

  9. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    PubMed

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

    2016-01-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

  10. Clonal Spread of a Clostridium difficile Strain with a Complete Set of Toxin A, Toxin B, and Binary Toxin Genes among Polish Patients with Clostridium difficile-Associated Diarrhea

    PubMed Central

    Pituch, Hanna; Kreft, Deborah; Obuch-Woszczatyński, Piotr; Wultańska, Dorota; Meisel-Mikołajczyk, Felicja; Łuczak, Mirosław; van Belkum, Alex

    2005-01-01

    Clinically relevant Clostridium difficile strains usually produce toxins A and B. Some C. difficile strains can produce an additional binary toxin. We report clonality among five strains carrying all toxin genes from Polish patients with C. difficile-associated diarrhea. In another strain, possible recombination between binary toxin genes is documented. PMID:15635019

  11. Overview of Scorpion Species from China and Their Toxins

    PubMed Central

    Cao, Zhijian; Di, Zhiyong; Wu, Yingliang; Li, Wenxin

    2014-01-01

    Scorpions are one of the most ancient groups of terrestrial animals. They have maintained a steady morphology over more than 400 million years of evolution. Their venom arsenals for capturing prey and defending against predators may play a critical role in their ancient and conservative appearance. In the current review, we present the scorpion fauna of China: 53 species covering five families and 12 genera. We also systematically list toxins or genes from Chinese scorpion species, involving eight species covering four families. Furthermore, we review the diverse functions of typical toxins from Chinese scorpion species, involving Na+ channel modulators, K+ channel blockers, antimicrobial peptides and protease inhibitors. Using scorpion species and their toxins from China as an example, we build the bridge between scorpion species and their toxins, which helps us to understand the molecular and functional diversity of scorpion venom arsenal, the dynamic and functional evolution of scorpion toxins, and the potential relationships of scorpion species and their toxins. PMID:24577583

  12. The impact of toxins on the developing brain.

    PubMed

    Lanphear, Bruce P

    2015-03-18

    The impact of toxins on the developing brain is usually subtle for an individual child, but the damage can be substantial at the population level. Numerous challenges must be addressed to definitively test the impact of toxins on brain development in children: We must quantify exposure using a biologic marker or pollutant; account for an ever-expanding set of potential confounders; identify critical windows of vulnerability; and repeatedly examine the association of biologic markers of toxins with intellectual abilities, behaviors, and brain function in distinct cohorts. Despite these challenges, numerous toxins have been implicated in the development of intellectual deficits and mental disorders in children. Yet, too little has been done to protect children from these ubiquitous but insidious toxins. The objective of this review is to provide an overview on the population impact of toxins on the developing brain and describe implications for public health. PMID:25581143

  13. Recent insights into Clostridium perfringens beta-toxin.

    PubMed

    Nagahama, Masahiro; Ochi, Sadayuki; Oda, Masataka; Miyamoto, Kazuaki; Takehara, Masaya; Kobayashi, Keiko

    2015-02-01

    Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT) that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin. PMID:25654787

  14. Recent Insights into Clostridium perfringens Beta-Toxin

    PubMed Central

    Nagahama, Masahiro; Ochi, Sadayuki; Oda, Masataka; Miyamoto, Kazuaki; Takehara, Masaya; Kobayashi, Keiko

    2015-01-01

    Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT) that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin. PMID:25654787

  15. Candidalysin is a fungal peptide toxin critical for mucosal infection.

    PubMed

    Moyes, David L; Wilson, Duncan; Richardson, Jonathan P; Mogavero, Selene; Tang, Shirley X; Wernecke, Julia; Höfs, Sarah; Gratacap, Remi L; Robbins, Jon; Runglall, Manohursingh; Murciano, Celia; Blagojevic, Mariana; Thavaraj, Selvam; Förster, Toni M; Hebecker, Betty; Kasper, Lydia; Vizcay, Gema; Iancu, Simona I; Kichik, Nessim; Häder, Antje; Kurzai, Oliver; Luo, Ting; Krüger, Thomas; Kniemeyer, Olaf; Cota, Ernesto; Bader, Oliver; Wheeler, Robert T; Gutsmann, Thomas; Hube, Bernhard; Naglik, Julian R

    2016-04-01

    Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name 'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans. PMID:27027296

  16. Shiga Toxin: Expression, Distribution, and Its Role in the Environment

    PubMed Central

    Mauro, Steven A.; Koudelka, Gerald B.

    2011-01-01

    In this review, we highlight recent work that has increased our understanding of the production and distribution of Shiga toxin in the environment. Specifically, we review studies that offer an expanded view of environmental reservoirs for Shiga toxin producing microbes in terrestrial and aquatic ecosystems. We then relate the abundance of Shiga toxin in the environment to work that demonstrates that the genetic mechanisms underlying the production of Shiga toxin genes are modified and embellished beyond the classical microbial gene regulatory paradigms in a manner that apparently “fine tunes” the trigger to modulate the amount of toxin produced. Last, we highlight several recent studies examining microbe/protist interactions that postulate an answer to the outstanding question of why microbes might harbor and express Shiga toxin genes in the environment. PMID:22069728

  17. CONTAMINANT ADSORPTION AND OXIDATION VIA FENTON REACTION

    EPA Science Inventory

    A ground water treatment process is proposed involving two cgemical processes: adsorption and oxidation. Adsorption of an organic compound onto granulated activated carbon (GAC) containing iron conveniently results in immobilizing and concentrating contaminants from the ground w...

  18. Adsorption of Organics from Domestic Water Supplies.

    ERIC Educational Resources Information Center

    McGuire, Michael J.; Suffet, Irwin H.

    1978-01-01

    This article discusses the current state of the art of organics removal by adsorption. Various theoretical explanations of the adsorption process are given, along with practical results from laboratory, pilot-scale, and full-scale applications. (CS)

  19. Fusarial toxins: secondary metabolites of Fusarium fungi.

    PubMed

    Nesic, Ksenija; Ivanovic, Snezana; Nesic, Vladimir

    2014-01-01

    Exposure to mycotoxins occurs worldwide, even though there are geographic and climatic differences in the amounts produced and occurrence of these substances.Mycotoxins are secondary chemical metabolites of different fungi. They are natural contaminants of cereals, so their presence is often inevitable. Among many genera that produce mycotoxins, Fusarium fungi are the most widespread in cereal-growing areas of the planet. Fusarium fungi produce a diversity of mycotoxin types, whose distributions are also diverse. What is produced and where it is produced is influenced primarily by environmental conditions, and crop production and storage methods. The amount of toxin produced depends on physical (viz., moisture, relative humidity, temperature, and mechanical damage), chemical (viz., carbon dioxide,oxygen, composition of substrate, insecticides and fungicides), and biological factors (viz., plant variety, stress, insects, spore load, etc.). Moisture and temperature have a major influence on mold growth rate and mycotoxin production.Among the most toxic and prevalent fusaria) toxins are the following: zearalenone,fumonisins, moniliformin and trichothecenes (T-2/HT-2 toxin, deoxynivalenol,diacetoxyscirpenol, nivalenol). Zearalenone (ZEA; ZON, F-2 toxin) isaphy to estrogenic compound, primarily a field contaminant, which exhibits estrogenic activity and has been implicated in numerous mycotoxicoses of farm animals,especially pigs. Recently, evidence suggests that ZEA has potential to stimulate the growth of human breast cancer cells. Fumonisins are also cancer-promoting metabolites,of which Fumonisin 8 I (FBI) is the most important. Moniliformin (MON) isalso highly toxic to both animals and humans. Trichothecenes are classified as gastrointestinal toxins, dermatotoxins, immunotoxins, hematotoxins, and gene toxins.T-2 and HT-2 toxin, and diacetoxyscirpenol (DAS, anguidine) are the most toxic mycotoxins among the trichothecene group. Deoxynivalenol (DON, vomitoxin) and

  20. Military Importance of Natural Toxins and Their Analogs.

    PubMed

    Pitschmann, Vladimír; Hon, Zdeněk

    2016-01-01

    Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks. PMID:27136512

  1. Can Tracking Improve Learning?

    ERIC Educational Resources Information Center

    Duflo, Esther; Dupas, Pascaline; Kremer, Michael

    2009-01-01

    Tracking students into different classrooms according to their prior academic performance is controversial among both scholars and policymakers. If teachers find it easier to teach a homogeneous group of students, tracking could enhance school effectiveness and raise test scores of both low- and high-ability students. If students benefit from…

  2. On the Wrong Track.

    ERIC Educational Resources Information Center

    Black, Susan

    1992-01-01

    By any measure--student achievement, social development, or democratic values--ability grouping and tracking practices are indefensible and unsupported by research. Tracking allows schools to practice in-school segregation and perpetuate unequal opportunities and unequal socialization within classrooms. Jonathan Kozol's investigation shows how…

  3. Large scale tracking algorithms.

    SciTech Connect

    Hansen, Ross L.; Love, Joshua Alan; Melgaard, David Kennett; Karelitz, David B.; Pitts, Todd Alan; Zollweg, Joshua David; Anderson, Dylan Z.; Nandy, Prabal; Whitlow, Gary L.; Bender, Daniel A.; Byrne, Raymond Harry

    2015-01-01

    Low signal-to-noise data processing algorithms for improved detection, tracking, discrimination and situational threat assessment are a key research challenge. As sensor technologies progress, the number of pixels will increase signi cantly. This will result in increased resolution, which could improve object discrimination, but unfortunately, will also result in a significant increase in the number of potential targets to track. Many tracking techniques, like multi-hypothesis trackers, suffer from a combinatorial explosion as the number of potential targets increase. As the resolution increases, the phenomenology applied towards detection algorithms also changes. For low resolution sensors, "blob" tracking is the norm. For higher resolution data, additional information may be employed in the detection and classfication steps. The most challenging scenarios are those where the targets cannot be fully resolved, yet must be tracked and distinguished for neighboring closely spaced objects. Tracking vehicles in an urban environment is an example of such a challenging scenario. This report evaluates several potential tracking algorithms for large-scale tracking in an urban environment.

  4. Explaining cloud chamber tracks

    SciTech Connect

    Broyles, A.A.

    1992-06-16

    The operation of many detection devices is usually explained in terms of the ionization tracks produced by particles despite the fact that the corresponding incident wave functions extended over the entire sensitive regions of the detectors. The mechanisms by which the wave function appears to collapse to a track is analyzed here.

  5. TMDL TRACKING SYSTEM

    EPA Science Inventory

    Resource Purpose:The TMDL Tracking System database contains information on the waters listed under section 303(d) of the Clean Water Act and to track those listed waters through TMDL development. The purpose of the database is to allow EPA, the States/Territories/Tribes, ...

  6. Incentives from Curriculum Tracking

    ERIC Educational Resources Information Center

    Koerselman, Kristian

    2013-01-01

    Curriculum tracking creates incentives in the years before its start, and we should therefore expect test scores to be higher during those years. I find robust evidence for incentive effects of tracking in the UK based on the UK comprehensive school reform. Results from the Swedish comprehensive school reform are inconclusive. Internationally, I…

  7. Track record in meteorites

    NASA Astrophysics Data System (ADS)

    Durrani, S. A.

    1981-02-01

    The use of nuclear-track analysis in meteoritic crystals with reference to several areas of research is reviewed. The applications discussed include: fission-track retention ages and cooling rates of meteoritic parent bodies, cosmic-ray studies, determination of pre-atmospheric sizes of meteorites, and search for superheavy elements.

  8. 2 Tracks for Faculty

    ERIC Educational Resources Information Center

    Wilson, Robin

    2012-01-01

    The academic work force has been transformed over the past several decades, less by design than out of expediency. In 1969, professors who were either tenured or tenure-track made up 78 percent of the faculty. Those working part time made up only 18.5 percent. By 2009, those proportions had almost flipped, with tenured and tenure-track making up…

  9. UWB Tracking Software Development

    NASA Technical Reports Server (NTRS)

    Gross, Julia; Arndt, Dickey; Ngo, Phong; Phan, Chau; Dusl, John; Ni, Jianjun; Rafford, Melinda

    2006-01-01

    An Ultra-Wideband (UWB) two-cluster Angle of Arrival (AOA) tracking prototype system is currently being developed and tested at NASA Johnson Space Center for space exploration applications. This talk discusses the software development efforts for this UWB two-cluster AOA tracking system. The role the software plays in this system is to take waveform data from two UWB radio receivers as an input, feed this input into an AOA tracking algorithm, and generate the target position as an output. The architecture of the software (Input/Output Interface and Algorithm Core) will be introduced in this talk. The development of this software has three phases. In Phase I, the software is mostly Matlab driven and calls C++ socket functions to provide the communication links to the radios. This is beneficial in the early stage when it is necessary to frequently test changes in the algorithm. Phase II of the development is to have the software mostly C++ driven and call a Matlab function for the AOA tracking algorithm. This is beneficial in order to send the tracking results to other systems and also to improve the tracking update rate of the system. The third phase is part of future work and is to have the software completely C++ driven with a graphics user interface. This software design enables the fine resolution tracking of the UWB two-cluster AOA tracking system.

  10. Stable and fluid ethylphosphocholine membranes in a poly(dimethylsiloxane) microsensor for toxin detection in flooded waters.

    PubMed

    Phillips, K Scott; Dong, Yi; Carter, David; Cheng, Quan

    2005-05-01

    Highly stable and fluid supported bilayer membranes were fabricated by fusion of positively charged ethylphosphocholine (DOPC+) vesicles into poly(dimethylsiloxane) (PDMS) microchannels for immunosensing of cholera toxin (CT) in flooded waters. Compared to phosphatidylcholine (PC) layers in the microchannels, DOPC+ membranes show exceptionally strong resistance to air-dry damage, as demonstrated by fluorescence recovery after photobleaching (FRAP) measurements and protein adsorption studies. In FRAP experiments, the mobile fraction of PC membranes was found to decrease by 10% upon drying/rehydration and the lateral diffusion coefficient decreased from 2.2 to 1.6 microm(2)/s, whereas the mobile fraction and diffusion coefficient for DOPC+ membranes remain virtually unchanged during this process. Characterization by confocal microscopy reveals that only 1% of the DOPC+ membrane in the microchannels was removed by the drying/rehydration process, as compared to 11% for PC. Protein adsorption trends indicate that the charge of DOPC+ membranes allows for tuning of solution conditions to enable the desired protein-membrane interaction to predominate at the interface. A flow-based immunoassay for bacterial toxin was developed with 5% GM1/DOPC+ membranes in PDMS channels, and a detection limit of 250 amol for CT was obtained from the calibration curves. The assay was successfully applied to detection of CT spiked in water samples from the Santa Ana River, with nearly identical response and sensitivity. PMID:15859616

  11. TRACKED VEHICLE Rev 75

    SciTech Connect

    Raby, Eric Y.

    2007-05-08

    Revision 75 of the Tracked Vehicle software is a soft real-time simulation of a differentially steered, tracked mobile robot, which, because of the track flippers, resembles the iRobot PackBot (http://www.irobot.com/). Open source libraries are used for the physics engine (http://www.ode.org/), the display and user interface (http://www.mathies.com/cpw/), and the program command line and configuration file parameters (http://www.boost.org/). The simulation can be controlled by a USB joystick or the keyboard. The configuration file contains demonstration model parameters of no particular vehicle. This simulation can be used as a starting point for those doing tracked vehicle simulations. This simulation software is essentially a research tool which can be modified and adapted for certain types of tracked vehicle research. An open source license allows an individual researchers to tailor the code to their specific research needs.

  12. TRACKED VEHICLE Rev 75

    2007-05-08

    Revision 75 of the Tracked Vehicle software is a soft real-time simulation of a differentially steered, tracked mobile robot, which, because of the track flippers, resembles the iRobot PackBot (http://www.irobot.com/). Open source libraries are used for the physics engine (http://www.ode.org/), the display and user interface (http://www.mathies.com/cpw/), and the program command line and configuration file parameters (http://www.boost.org/). The simulation can be controlled by a USB joystick or the keyboard. The configuration file contains demonstration model parametersmore » of no particular vehicle. This simulation can be used as a starting point for those doing tracked vehicle simulations. This simulation software is essentially a research tool which can be modified and adapted for certain types of tracked vehicle research. An open source license allows an individual researchers to tailor the code to their specific research needs.« less

  13. Adsorption and excess fission xenon

    NASA Technical Reports Server (NTRS)

    Podosek, F. A.; Bernatowicz, T. J.; Kramer, F. E.

    1982-01-01

    The adsorption of Xe and Kr on lunar soil 10084 was measured by a method that employs only very low fractions of monolayer coverage. Results are presented as parameters for calculation of the Henry constant for adsorption as a function of temperature. The adsorption potentials are about 3 kcal/mole for Kr and 5 kcal/mole for Xe; heating the sample in vacuum increased the Xe potential to nearly 7 kcal/mole. Henry constants at the characteristic lunar temperature are about 0.3 cu cm STP/g-atm. These data were applied to consider whether adsorption is important in producing the excess fission Xe effect characteristic of highland breccias. Sorption equilibrium with a transient lunar atmosphere vented fission Xe produces concentrations seven orders of magnitude lower than observed concentrations. Higher concentrations result because of the resistance of the regolith to upward diffusion of Xe. A diffusion coefficient of 0.26 sq cm/sec is estimated for this process.

  14. NO Adsorption on Pd(111)

    NASA Astrophysics Data System (ADS)

    Garda, Graciela R.; Ferullo, Ricardo M.; Castellani, Norberto J.

    The reactive behavior of NO on Pd(111) has been studied using a semiempirical theoretical method. The adsorption sites and the related electronic structure have been considered. In particular, the dissociation process has been studied and compared with CO. Different dissociation mechanisms have been proposed and the formation of NCO species has been considered. The results follow the trends reported in the experimental literature.

  15. ADSORPTIVE MEDIA TECHNOLOGIES: MEDIA SELECTION

    EPA Science Inventory

    The presentation provides information on six items to be considered when selecting an adsorptive media for removing arsenic from drinking water; performance, EBCT, pre-treatment, regeneration, residuals, and cost. Each item is discussed in general and data and photographs from th...

  16. Protein Adsorption in Microengraving Immunoassays

    PubMed Central

    Song, Qing

    2015-01-01

    Microengraving is a novel immunoassay forcharacterizing multiple protein secretions from single cells. During the immunoassay, characteristic diffusion and kinetic time scales τD and τK determine the time for molecular diffusion of proteins secreted from the activated single lymphocytes and subsequent binding onto the glass slide surface respectively. Our results demonstrate that molecular diffusion plays important roles in the early stage of protein adsorption dynamics which shifts to a kinetic controlled mechanism in the later stage. Similar dynamic pathways are observed for protein adsorption with significantly fast rates and rapid shifts in transport mechanisms when C0* is increased a hundred times from 0.313 to 31.3. Theoretical adsorption isotherms follow the trend of experimentally obtained data. Adsorption isotherms indicate that amount of proteins secreted from individual cells and subsequently captured on a clean glass slide surface increases monotonically with time. Our study directly validates that protein secretion rates can be quantified by the microengraving immunoassay. This will enable us to apply microengraving immunoassays to quantify secretion rates from 104–105 single cells in parallel, screen antigen-specific cells with the highest secretion rate for clonal expansion and quantitatively reveal cellular heterogeneity within a small cell sample. PMID:26501282

  17. ADSORPTION OF SURFACTANT ON CLAYS

    EPA Science Inventory

    Surfactants used to enhance remediation of soils by soil washing are often lost in the process. Neither the amount nor the cause of this loss is known. It is assumed that clays present in the soil are responsible for the loss of the surfactant. In this papere, adsorption prope...

  18. ARSENIC REMOVAL USING ADSORPTION TECHNOLOGIES

    EPA Science Inventory

    The recently promulgated Arsenic Rule will require that many new drinking water systems treat their water to remove arsenic. Many groundwaters that have arsenic in their source water will likely consider adsorption technology as a reasonable approach to remove arsenic. Adsorptio...

  19. ADSORPTION TECHNOLOGIES FOR ARSENIC REMOVAL

    EPA Science Inventory

    The recently promulgated Arsenic Rule will require that many new drinking water systems treat their water to remove arsenic. Many groundwaters that have arsenic in their source water will likely consider adsorption technology as a reasonable approach to remove arsenic. Adsorptio...

  20. Role of receptors in Bacillus thuringiensis crystal toxin activity.

    PubMed

    Pigott, Craig R; Ellar, David J

    2007-06-01

    Bacillus thuringiensis produces crystalline protein inclusions with insecticidal or nematocidal properties. These crystal (Cry) proteins determine a particular strain's toxicity profile. Transgenic crops expressing one or more recombinant Cry toxins have become agriculturally important. Individual Cry toxins are usually toxic to only a few species within an order, and receptors on midgut epithelial cells have been shown to be critical determinants of Cry specificity. The best characterized of these receptors have been identified for lepidopterans, and two major receptor classes have emerged: the aminopeptidase N (APN) receptors and the cadherin-like receptors. Currently, 38 different APNs have been reported for 12 different lepidopterans. Each APN belongs to one of five groups that have unique structural features and Cry-binding properties. While 17 different APNs have been reported to bind to Cry toxins, only 2 have been shown to mediate toxin susceptibly in vivo. In contrast, several cadherin-like proteins bind to Cry toxins and confer toxin susceptibility in vitro, and disruption of the cadherin gene has been associated with toxin resistance. Nonetheless, only a small subset of the lepidopteran-specific Cry toxins has been shown to interact with cadherin-like proteins. This review analyzes the interactions between Cry toxins and their receptors, focusing on the identification and validation of receptors, the molecular basis for receptor recognition, the role of the receptor in resistant insects, and proposed models to explain the sequence of events at the cell surface by which receptor binding leads to cell death. PMID:17554045

  1. Tumor Targeting and Drug Delivery by Anthrax Toxin

    PubMed Central

    Bachran, Christopher; Leppla, Stephen H.

    2016-01-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery. PMID:27376328

  2. Nanoparticle-detained toxins for safe and effective vaccination

    NASA Astrophysics Data System (ADS)

    Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Zhang, Liangfang

    2013-12-01

    Toxoid vaccines--vaccines based on inactivated bacterial toxins--are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here, we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal α-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. Compared with vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin-mediated adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate that this study will open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.

  3. Tumor Targeting and Drug Delivery by Anthrax Toxin.

    PubMed

    Bachran, Christopher; Leppla, Stephen H

    2016-01-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery. PMID:27376328

  4. Extrapolating target tracks

    NASA Astrophysics Data System (ADS)

    Van Zandt, James R.

    2012-05-01

    Steady-state performance of a tracking filter is traditionally evaluated immediately after a track update. However, there is commonly a further delay (e.g., processing and communications latency) before the tracks can actually be used. We analyze the accuracy of extrapolated target tracks for four tracking filters: Kalman filter with the Singer maneuver model and worst-case correlation time, with piecewise constant white acceleration, and with continuous white acceleration, and the reduced state filter proposed by Mookerjee and Reifler.1, 2 Performance evaluation of a tracking filter is significantly simplified by appropriate normalization. For the Kalman filter with the Singer maneuver model, the steady-state RMS error immediately after an update depends on only two dimensionless parameters.3 By assuming a worst case value of target acceleration correlation time, we reduce this to a single parameter without significantly changing the filter performance (within a few percent for air tracking).4 With this simplification, we find for all four filters that the RMS errors for the extrapolated state are functions of only two dimensionless parameters. We provide simple analytic approximations in each case.

  5. A common origin for the bacterial toxin-antitoxin systems parD and ccd, suggested by analyses of toxin/target and toxin/antitoxin interactions.

    PubMed

    Smith, Andrew B; López-Villarejo, Juan; Diago-Navarro, Elizabeth; Mitchenall, Lesley A; Barendregt, Arjan; Heck, Albert J; Lemonnier, Marc; Maxwell, Anthony; Díaz-Orejas, Ramón

    2012-01-01

    Bacterial toxin-antitoxin (TA) systems encode two proteins, a potent inhibitor of cell proliferation (toxin) and its specific antidote (antitoxin). Structural data has revealed striking similarities between the two model TA toxins CcdB, a DNA gyrase inhibitor encoded by the ccd system of plasmid F, and Kid, a site-specific endoribonuclease encoded by the parD system of plasmid R1. While a common structural fold seemed at odds with the two clearly different modes of action of these toxins, the possibility of functional crosstalk between the parD and ccd systems, which would further point to their common evolutionary origin, has not been documented. Here, we show that the cleavage of RNA and the inhibition of protein synthesis by the Kid toxin, two activities that are specifically counteracted by its cognate Kis antitoxin, are altered, but not inhibited, by the CcdA antitoxin. In addition, Kis was able to inhibit the stimulation of DNA gyrase-mediated cleavage of DNA by CcdB, albeit less efficiently than CcdA. We further show that physical interactions between the toxins and antitoxins of the different systems do occur and define the stoichiometry of the complexes formed. We found that CcdB did not degrade RNA nor did Kid have any reproducible effect on the tested DNA gyrase activities, suggesting that these toxins evolved to reach different, rather than common, cellular targets. PMID:23029540

  6. Surveillance snapshot of Clostridium difficile infection in hospitals across Queensland detects binary toxin producing ribotype UK 244.

    PubMed

    Huber, Charlotte A; Hall, Lisa; Foster, Nikki F; Gray, Mareeka; Allen, Michelle; Richardson, Leisha J; Robson, Jennifer; Vohra, Renu; Schlebusch, Sanmarie; George, Narelle; Nimmo, Graeme R; Riley, Thomas V; Paterson, David L

    2014-12-01

    In North America and Europe, the binary toxin positive Clostridium difficile strains of the ribotypes 027 and 078 have been associated with death, toxic megacolon and other adverse outcomes. Following an increase in C. difficile infections (CDIs) in Queensland, a prevalence study involving 175 hospitals was undertaken in early 2012, identifying 168 cases of CDI over a 2 month period. Patient demographics and clinical characteristics were recorded, and C. difficile isolates were ribotyped and tested for the presence of binary toxin genes. Most patients (106/168, 63.1%) were aged over 60 years. Overall, 98 (58.3%) developed symptoms after hospitalisation; 89 cases (53.0%) developed symptoms more than 48 hours after admission. Furthermore, 27 of the 62 (67.7%) patients who developed symptoms in the community ad been hospitalised within the last 3 months. Thirteen of the 168 (7.7%) cases identified had severe disease, resulting in admission to the Intensive Care Unit or death within 30 days of the onset of symptoms. The 3 most common ribotypes isolated were UK 002 (22.9%), UK 014 (13.3%) and the binary toxin-positive ribotype UK 244 (8.4%). The only other binary toxin positive ribotype isolated was UK 078 (n = 1). Of concern was the detection of the binary toxin positive ribotype UK 244, which has recently been described in other parts of Australia and New Zealand. No isolates were of the international epidemic clone of ribotype UK 027, although ribotype UK 244 is genetically related to this clone. Further studies are required to track the epidemiology of ribotype UK 244 in Australia and New Zealand. PMID:25631588

  7. Purification and characterization of Shiga toxin 2f, an immunologically unrelated subtype of Shiga toxin 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Shiga-like toxin 2 (Stx2) is one of the most important virulence factors in enterohaemorrhagic Escherichia coli (E. coli) strains such as O157H7. Subtypes of Stx2 are diverse with respect to their sequence, toxicity, and distribution. The most diverse Stx2 subtype, Stx2f, is difficult to...

  8. Characterization of shiga toxin subtypes and virulence genes in Porcine shiga toxin-producing Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Similar to ruminants, swine have been shown to be a reservoir for Shiga toxin-producing Escherichia coli (STEC), and pork products have been linked with outbreaks associated with STEC O157 and O111:H-. STEC strains, isolated in a previous study from fecal samples of late-finisher pigs, belonged to a...

  9. Binding of Diphtheria Toxin to Phospholipids in Liposomes

    NASA Astrophysics Data System (ADS)

    Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

    1980-04-01

    Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

  10. Dye adsorption behavior of Luffa cylindrica fibers.

    PubMed

    Demir, H; Top, A; Balköse, D; Ulkü, S

    2008-05-01

    Using natural Luffa cylindrica fibers as adsorbent removal of methylene blue dye from aqueous solutions at different temperatures and dye concentrations was investigated in this study. Thermodynamics and kinetics of adsorption were also investigated. The adsorption isotherms could be well defined with Langmuir model instead of Freundlich model. The thermodynamic parameters of methylene blue (MB) adsorption indicated that the adsorption is exothermic and spontaneous. The average MB adsorption capacity was found out as 49 mg/g and average BET surface area of fibers was calculated as 123 m(2)/g. PMID:17919814

  11. Gas adsorption on microporous carbon thin films

    SciTech Connect

    O'Shea, S.; Pailthorpe, B.A.; Collins, R.E.; Furlong, D.N. )

    1992-05-01

    A gas adsorption study was performed on amorphous hydrogenated carbon thin films which are deposited by reactive magnetron sputtering using acetylene gas. It is found that the films are highly microporous. Annealing significantly increases the adsorption capacity of the films and decreases the effects of low-pressure hysteresis in the adsorption isotherms. The general gas adsorption behavior closely resembles that of powdered activated carbons. The Dubinin-Radushkevich equation can be used to model the submonolayer adsorption isotherm for a variety of gases. 38 refs., 9 figs., 3 tabs.

  12. Overview of Botulinum Toxins for Aesthetic Uses.

    PubMed

    Gart, Michael S; Gutowski, Karol A

    2016-07-01

    Botulinum toxin type A (BTA) can be used for facial aesthetics. The 3 currently available BTA types include onabotulinumtoxinA (Botox; Botox Cosmetic, Allergan, Irvine, CA), abobotulinumtoxinA (Dysport; Ipsen, Ltd, Berkshire, UK), and incobotulinumtoxinA (Xeomin; Merz Pharmaceuticals, Frankfurt, Germany). The mechanism of action and clinical uses for treatment of dynamic lines of the forehead, brow, glabella, lateral orbit, nose, and lips are presented, as well as treatment of masseter hypertrophy, platysmal bands, and improvements of the perioral region. Specific BTA injection sites and suggested doses are presented. PMID:27363760

  13. Adsorption Behavior of Nonplanar Phthalocyanines: Competition of Different Adsorption Conformations

    PubMed Central

    2016-01-01

    Using density functional theory augmented with state-of-the-art van der Waals corrections, we studied the geometric and electronic properties of nonplanar chlorogallium-phthalocyanine GaClPc molecules adsorbed on Cu(111). Comparing these results with published experimental data for adsorption heights, we found indications for breaking of the metal–halogen bond when the molecule is heated during or after the deposition process. Interestingly, the work-function change induced by this dissociated geometry is the same as that computed for an intact adsorbate layer in the “Cl-down” configuration, with both agreeing well with the experimental photoemission data. This is unexpected, as the chemical natures of the adsorbates and the adsorption distances are markedly different in the two cases. The observation is explained as a consequence of Fermi-level pinning due to fractional charge transfer at the interface. Our results show that rationalizing the adsorption configurations on the basis of electronic interface properties alone can be ambiguous and that additional insight from dispersion-corrected DFT simulations is desirable. PMID:27066160

  14. Human Monoclonal Antibodies against Clostridium difficile Toxins A and B Inhibit Inflammatory and Histologic Responses to the Toxins in Human Colon and Peripheral Blood Monocytes

    PubMed Central

    Koon, Hon Wai; Shih, David Q.; Hing, Tressia C.; Yoo, Jun Hwan; Ho, Samantha; Chen, Xinhua; Kelly, Ciarán P.; Targan, Stephan R.

    2013-01-01

    Clostridium difficile infection (CDI) is a common and debilitating nosocomial infection with high morbidity and mortality. C. difficile mediates diarrhea and colitis by releasing two toxins, toxin A and toxin B. Since both toxins stimulate proinflammatory signaling pathways in human colonocytes and both are involved in the pathophysiology of CDI, neutralization of toxin A and B activities may represent an important therapeutic approach against CDI. Recent studies indicated that human monoclonal antibodies (MAbs) against toxins A and B reduce their cytotoxic and secretory activities and prevent CDI in hamsters. Moreover, anti-toxin A and anti-toxin B MAbs together with antibiotics also effectively reduced recurrent CDI in humans. However, whether these MAbs neutralize toxin A- and toxin B-associated immune responses in human colonic mucosa or human peripheral blood monocyte cells (PBMCs) has never been examined. We used fresh human colonic biopsy specimens and peripheral blood monocytes to evaluate the effects of these antibodies against toxin A- and B-associated cytokine release, proinflammatory signaling, and histologic damage. Incubation of anti-toxin A (MK3415) or anti-toxin B (MK6072) MAbs with human PBMCs significantly inhibited toxin A- and toxin B-mediated tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) expression. MK3415 and MK6072 also diminished toxin A- and toxin B-mediated NF-κB p65 phosphorylation in human monocytes, respectively, and significantly reduced toxin A- and B-induced TNF-α and IL-1β expression as well as histologic damage in human colonic explants. Our results underline the effectiveness of MK3415 and MK6072 in blocking C. difficile toxin A- and toxin B-mediated inflammatory responses and histologic damage. PMID:23629713

  15. Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B

    PubMed Central

    Genth, Harald; Schelle, Ilona; Just, Ingo

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the “Large clostridial glycosylating toxins.” These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB—together with Toxin A (TcdA)—is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn2+ > Co2+ > Mg2+ >> Ca2+, Cu2+, Zn2+. TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn2+ and 180 µM for Mg2+. TcsL and TcdB further require co-stimulation by monovalent K+ (not by Na+). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K+ and Mg2+ (rather than Mn2+) in mammalian target cells. PMID:27089365

  16. Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B.

    PubMed

    Genth, Harald; Schelle, Ilona; Just, Ingo

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the "Large clostridial glycosylating toxins." These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB-together with Toxin A (TcdA)-is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn(2+) > Co(2+) > Mg(2+) > Ca(2+), Cu(2+), Zn(2+). TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn(2+) and 180 µM for Mg(2+). TcsL and TcdB further require co-stimulation by monovalent K⁺ (not by Na⁺). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K⁺ and Mg(2+) (rather than Mn(2+)) in mammalian target cells. PMID:27089365

  17. Diarrhetic Shellfish Toxins and Other Lipophilic Toxins of Human Health Concern in Washington State

    PubMed Central

    Trainer, Vera L.; Moore, Leslie; Bill, Brian D.; Adams, Nicolaus G.; Harrington, Neil; Borchert, Jerry; da Silva, Denis A. M.; Eberhart, Bich-Thuy L.

    2013-01-01

    The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs) in Washington State for the protection of human health. Following these cases of diarrhetic shellfish poisoning, monitoring for DSTs in Washington State became formalized in 2012, guided by routine monitoring of Dinophysis species by the SoundToxins program in Puget Sound and the Olympic Region Harmful Algal Bloom (ORHAB) partnership on the outer Washington State coast. Here we show that the DSTs at concentrations above the guidance level of 16 μg okadaic acid (OA) + dinophysistoxins (DTXs)/100 g shellfish tissue were widespread in sentinel mussels throughout Puget Sound in summer 2012 and included harvest closures of California mussel, varnish clam, manila clam and Pacific oyster. Concentrations of toxins in Pacific oyster and manila clam were often at least half those measured in blue mussels at the same site. The primary toxin isomer in shellfish and plankton samples was dinophysistoxin-1 (DTX-1) with D. acuminata as the primary Dinophysis species. Other lipophilic toxins in shellfish were pectenotoxin-2 (PTX-2) and yessotoxin (YTX) with azaspiracid-2 (AZA-2) also measured in phytoplankton samples. Okadaic acid, azaspiracid-1 (AZA-1) and azaspiracid-3 (AZA-3) were all below the levels of detection by liquid chromatography tandem mass spectrometry (LC-MS/MS). A shellfish closure at Ruby Beach, Washington, was the first ever noted on the Washington State Pacific coast due to DSTs. The greater than average Fraser River flow during the summers of 2011 and 2012 may have provided an environment conducive to dinoflagellates and played a role in the prevalence of toxigenic Dinophysis in Puget Sound. PMID:23760013

  18. Diarrhetic shellfish toxins and other lipophilic toxins of human health concern in Washington State.

    PubMed

    Trainer, Vera L; Moore, Leslie; Bill, Brian D; Adams, Nicolaus G; Harrington, Neil; Borchert, Jerry; da Silva, Denis A M; Eberhart, Bich-Thuy L

    2013-06-01

    The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs) in Washington State for the protection of human health. Following these cases of diarrhetic shellfish poisoning, monitoring for DSTs in Washington State became formalized in 2012, guided by routine monitoring of Dinophysis species by the SoundToxins program in Puget Sound and the Olympic Region Harmful Algal Bloom (ORHAB) partnership on the outer Washington State coast. Here we show that the DSTs at concentrations above the guidance level of 16 μg okadaic acid (OA) + dinophysistoxins (DTXs)/100 g shellfish tissue were widespread in sentinel mussels throughout Puget Sound in summer 2012 and included harvest closures of California mussel, varnish clam, manila clam and Pacific oyster. Concentrations of toxins in Pacific oyster and manila clam were often at least half those measured in blue mussels at the same site. The primary toxin isomer in shellfish and plankton samples was dinophysistoxin-1 (DTX-1) with D. acuminata as the primary Dinophysis species. Other lipophilic toxins in shellfish were pectenotoxin-2 (PTX-2) and yessotoxin (YTX) with azaspiracid-2 (AZA-2) also measured in phytoplankton samples. Okadaic acid, azaspiracid-1 (AZA-1) and azaspiracid-3 (AZA-3) were all below the levels of detection by liquid chromatography tandem mass spectrometry (LC-MS/MS). A shellfish closure at Ruby Beach, Washington, was the first ever noted on the Washington State Pacific coast due to DSTs. The greater than average Fraser River flow during the summers of 2011 and 2012 may have provided an environment conducive to dinoflagellates and played a role in the prevalence of toxigenic Dinophysis in Puget Sound. PMID:23760013

  19. Adsorption of lipase on polypropylene powder.

    PubMed

    Gitlesen, T; Bauer, M; Adlercreutz, P

    1997-04-01

    Adsorption of different lipases by EP-100 polypropylene powder from crude and pure lipase preparations was studied. Langmuir isotherms described the adsorption equilibria well both for protein and lipase activity adsorption. Adsorption isotherms for five different proteins all gave a similar saturation level of 220 mg protein per g carrier. Twelve commercial lipase preparations were tested for selectivity in the adsorption of lipase. For all preparations the selectivity factor was larger than one. In a crude lipase preparation from Pseudomonas fluorescence, the specific activity in solution decreased by two orders of magnitude after adsorption. The adsorption was not significantly influenced by pH changes in the adsorption buffer, indicating that hydrophobic and not electrostatic interactions are the dominating adsorption forces. Adsorption of a crude lipase from Candida rugosa (Sigma) was fast and equilibrium was reached in 30 and 100 min for protein and lipase activity adsorption respectively. Desorption in aqueous solution was negligible. Investigations with seven different lipases showed no correlation between the specific lipolytic activity of dissolved enzyme in aqueous solution and the specific activity of adsorbed enzyme in an esterification reaction in organic solvent. PMID:9106498

  20. Adsorption of organic chemicals in soils.

    PubMed Central

    Calvet, R

    1989-01-01

    This paper presents a review on adsorption of organic chemicals on soils sediments and their constituents. The first part of this review deals with adsorption from gas and liquid phases and gives a discussion on the physical meaning of the shape of adsorption isotherms. Results show that no general rules can be proposed to describe univocally the relation between the shape of isotherms and the nature of adsorbate-adsorbent system. Kinetics of adsorption is discussed through the description of various models. Theoretical developments exist both for the thermodynamics and the kinetics of adsorption, but there is a strong need for experimental results. Possible adsorption mechanisms are ion exchange, interaction with metallic cations, hydrogen bonds, charge transfers, and London-van der Waals dispersion forces/hydrophobic effect. However, direct proofs of a given mechanism are rare. Several factors influence adsorption behavior. Electronic structure of adsorbed molecules, properties of adsorbents, and characteristics of the liquid phase are discussed in relation to adsorption. Such properties as water solubility, organic carbon content of adsorbing materials, and the composition of the liquid phase are particularly important. Evaluation of adsorption can be obtained through either laboratory measurements or use of several correlations. Adsorption measurements must be interpreted, taking into account treatment of adsorbent materials, experimental conditions, and secondary phenomena such as degradations. Correlations between adsorption coefficients and water-octanol partition coefficient or water solubility are numerous. They may be useful tools for prediction purposes. Relations with transport, bioavailability, and degradation are described. PMID:2695323

  1. Phosphate adsorption on lanthanum loaded biochar.

    PubMed

    Wang, Zhanghong; Shen, Dekui; Shen, Fei; Li, Tianyu

    2016-05-01

    To attain a low-cost and high-efficient phosphate adsorbent, lanthanum (La) loaded biochar (La-BC) prepared by a chemical precipitation method was developed. La-BC and its pristine biochar (CK-BC) were comparatively characterized using zeta potential, BET surface area, scanning electron microscopy/energy dispersive spectrometer (SEM-EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). The adsorption ability and the mechanisms during adsorption process for the La-BC samples were also investigated. La loaded on the surface of biochar can be termed as La-composites (such as LaOOH, LaONO3 and La(OH)3), leading to the decrease of negative charge and surface area of biochar. La-BC exhibited the high adsorption capacity to phosphate compared to CK-BC. Adsorption isotherm and adsorption kinetic studies showed that the Langmuir isotherm and second order model could well describe the adsorption process of La-BC, indicating that the adsorption was dominated by a homogeneous and chemical process. The calculated maximum adsorption capacity was as high as 46.37 mg g(-1) (computed in P). Thermodynamic analysis revealed that the adsorption was spontaneous and endothermic. SEM, XRD, XPS and FT-IR analysis suggested that the multi-adsorption mechanisms including precipitation, ligand exchange and complexation interactions can be evidenced during the phosphate adsorption process by La-composites in La-BC. PMID:26871732

  2. Isolation of diphtheria toxin-sensitive mouse cells from a toxin-resistant population transfected with monkey DNA.

    PubMed Central

    Naglich, J G; Eidels, L

    1990-01-01

    Diphtheria toxin (DTX)-sensitive mouse cells were isolated from a toxin-resistant thymidine kinase (TK)-negative L-M(TK-) mouse cell population that was transfected with DNA from highly toxin-sensitive monkey Vero cells. Sensitivity to DTX was screened by using a replica plate assay. The purified toxin-sensitive mouse cells were characterized with respect to their ability to bind, internalize, and translocate DTX into the cytosol. In contrast to the L-M(TK-) cells, these DTX-sensitive mouse cells were able to bind and internalize radioiodinated toxin into intracellular vesicles at 37 degrees C. Specific binding of radioiodinated toxin to their cell surface (at 4 degrees C) could not be demonstrated. However, the following evidence for functional receptors capable of binding DTX was obtained: (i) when the toxin-sensitive mouse cells were first allowed to bind DTX at 4 degrees C, followed by washing the cells and shifting the temperature to 37 degrees C (allowing cell surface-bound toxin to enter the cells), the cells were killed; (ii) when cells with surface-bound DTX were exposed briefly to an acidic medium (allowing the toxin to penetrate the plasma membrane directly), protein synthesis was inhibited; and (iii) when cells were incubated with DTX in the presence of the CRM 197, a nontoxic form of DTX with binding properties similar to native DTX, the cytotoxic effect of DTX was markedly decreased. The results demonstrate that the toxin-sensitive mouse cells are killed by a mechanism similar to that observed in naturally occurring toxin-sensitive cell lines. The data further suggest that the transfected mouse cells express functional receptors for DTX. Images PMID:2402506

  3. Maximum power tracking

    SciTech Connect

    O'Sullivan, G.

    1983-03-01

    By definition, a maximum power tracking device causes the photovoltaic array to operate on the locus of maximum power points within a specified accuracy. There are limitations to the application of maximum power tracking. A prerequisite is that the load be capable of absorbing all of the power availble at all times. Battery chargers, electrical heaters, water pumps, and most significantly, returning power to the utility grid, are prime examples of applications that are adaptable to maximum power tracking. Maximum power tracking is available to either dc or ac loads. An inverter equipped with a means of changing input voltage by controlling its input impedance can deliver maximum power to ac loads. The inverter can be fixed or variable frequency and fixed or variable voltage, but must be compatible with the ac load. The discussion includes applications, techniques, and cost factors.

  4. Enhanced optical tracking

    NASA Astrophysics Data System (ADS)

    McSheery, Tracy

    2008-04-01

    Enhanced tracking is accomplished by increasing the resolution, frame rate and processing capabilities in tracking dynamic regions of interest for vision applications. In many proven algorithms, the ability to distinguish an object and track it is dependent on the system performance in more than one attribute. We have conducted studies on proven techniques such as Active Appearance Models, Principle Component Analysis and Eigen tracking. All perform better as the camera resolution increases, and camera frame rate increases. Additional opportunities have been observed by combining these techniques, taking advantage of Multicore CPUs, and GPU graphic card processing. Results from an 8 Megapixel commercial sensor combined with a Field Programmable Gate array are presented, and algorithm performance compared with down scaled images of the same scenes, and simulated typical 30 hertz frame rates verses the 120 hertz to 300 hertz typical of this smart camera.

  5. Energy Tracking Software Platform

    SciTech Connect

    Ryan Davis; Nathan Bird; Rebecca Birx; Hal Knowles

    2011-04-04

    Acceleration has created an interactive energy tracking and visualization platform that supports decreasing electric, water, and gas usage. Homeowners have access to tools that allow them to gauge their use and track progress toward a smaller energy footprint. Real estate agents have access to consumption data, allowing for sharing a comparison with potential home buyers. Home builders have the opportunity to compare their neighborhood's energy efficiency with competitors. Home energy raters have a tool for gauging the progress of their clients after efficiency changes. And, social groups are able to help encourage members to reduce their energy bills and help their environment. EnergyIT.com is the business umbrella for all energy tracking solutions and is designed to provide information about our energy tracking software and promote sales. CompareAndConserve.com (Gainesville-Green.com) helps homeowners conserve energy through education and competition. ToolsForTenants.com helps renters factor energy usage into their housing decisions.

  6. 9 CFR 121.3 - VS select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... genetically modified. (d) VS select agents or toxins that meet any of the following criteria are excluded from... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent...

  7. 9 CFR 121.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic...

  8. 9 CFR 121.3 - VS select agents and toxins.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and toxins listed in paragraph (b) of this section that have been genetically modified. (d) VS select... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... synthetic nucleic acids, and recombinant and/or synthetic organisms: (1) Nucleic acids that can...

  9. 9 CFR 121.3 - VS select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... genetically modified. (d) VS select agents or toxins that meet any of the following criteria are excluded from... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent...

  10. 9 CFR 121.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic...

  11. 9 CFR 121.3 - VS select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and toxins listed in paragraph (b) of this section that have been genetically modified. (d) VS select... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... synthetic nucleic acids, and recombinant and/or synthetic organisms: (1) Nucleic acids that can...

  12. Structural interactions of a voltage sensor toxin with lipid membranes.

    PubMed

    Mihailescu, Mihaela; Krepkiy, Dmitriy; Milescu, Mirela; Gawrisch, Klaus; Swartz, Kenton J; White, Stephen

    2014-12-16

    Protein toxins from tarantula venom alter the activity of diverse ion channel proteins, including voltage, stretch, and ligand-activated cation channels. Although tarantula toxins have been shown to partition into membranes, and the membrane is thought to play an important role in their activity, the structural interactions between these toxins and lipid membranes are poorly understood. Here, we use solid-state NMR and neutron diffraction to investigate the interactions between a voltage sensor toxin (VSTx1) and lipid membranes, with the goal of localizing the toxin in the membrane and determining its influence on membrane structure. Our results demonstrate that VSTx1 localizes to the headgroup region of lipid membranes and produces a thinning of the bilayer. The toxin orients such that many basic residues are in the aqueous phase, all three Trp residues adopt interfacial positions, and several hydrophobic residues are within the membrane interior. One remarkable feature of this preferred orientation is that the surface of the toxin that mediates binding to voltage sensors is ideally positioned within the lipid bilayer to favor complex formation between the toxin and the voltage sensor. PMID:25453087

  13. Materials used in toxin detection, from A to Z

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whether it is during extraction, isolation, or detection the analysis of toxins invariably entails the interactions with materials that can bind to or otherwise interact with the toxin or the matrix in which it is lodged. As a result an enormous variety of materials have been developed to facilitate...

  14. IDENTIFICATION OF MICROCYSTIN TOXINS FROM A STRAIN OF MICROCYSTIS AERUGINOSA

    EPA Science Inventory

    Microcystin toxins are cyclic heptapeptides produced by several genera and species of cyanobacteria that are responsible for the "green scum" frequently observed on eutrophic surface waters. These toxins, which are a million times more toxic than cyanide ion, have caused deaths o...

  15. Parallel Evolution of Bacillus thuringiensis Toxin Resistance in Lepidoptera

    PubMed Central

    Baxter, Simon W.; Badenes-Pérez, Francisco R.; Morrison, Anna; Vogel, Heiko; Crickmore, Neil; Kain, Wendy; Wang, Ping; Heckel, David G.; Jiggins, Chris D.

    2011-01-01

    Despite the prominent and worldwide use of Bacillus thuringiensis (Bt) insecticidal toxins in agriculture, knowledge of the mechanism by which they kill pests remains incomplete. Here we report genetic mapping of a membrane transporter (ABCC2) to a locus controlling Bt Cry1Ac toxin resistance in two lepidopterans, implying that this protein plays a critical role in Bt function. PMID:21840855

  16. EFFECT OF MARINE TOXINS ON THERMOREGULATION IN MICE.

    EPA Science Inventory

    Marine algal toxins are extremely toxic and can represent a major health problem to humans and animals. Temperature regulation is one of many processes to be affected by exposure to these toxins. Mice and rats become markedly hypothermic when subjected to acute exposure to the ma...

  17. Structural interactions of a voltage sensor toxin with lipid membranes

    PubMed Central

    Mihailescu, Mihaela; Krepkiy, Dmitriy; Milescu, Mirela; Gawrisch, Klaus; Swartz, Kenton J.; White, Stephen

    2014-01-01

    Protein toxins from tarantula venom alter the activity of diverse ion channel proteins, including voltage, stretch, and ligand-activated cation channels. Although tarantula toxins have been shown to partition into membranes, and the membrane is thought to play an important role in their activity, the structural interactions between these toxins and lipid membranes are poorly understood. Here, we use solid-state NMR and neutron diffraction to investigate the interactions between a voltage sensor toxin (VSTx1) and lipid membranes, with the goal of localizing the toxin in the membrane and determining its influence on membrane structure. Our results demonstrate that VSTx1 localizes to the headgroup region of lipid membranes and produces a thinning of the bilayer. The toxin orients such that many basic residues are in the aqueous phase, all three Trp residues adopt interfacial positions, and several hydrophobic residues are within the membrane interior. One remarkable feature of this preferred orientation is that the surface of the toxin that mediates binding to voltage sensors is ideally positioned within the lipid bilayer to favor complex formation between the toxin and the voltage sensor. PMID:25453087

  18. An alternative treatment approach in tetanus: Botulinum toxin.

    PubMed

    Demir, Nazlim Aktug; Sumer, Sua; Ural, Onur; Ozturk, Serefnur; Celik, Jale Bengi

    2015-01-01

    Tetanus is a preventable infectious disease caused by tetanus toxin (tetanospasmin) produced by Clostridium tetani. Tetanus is still an important health problem in low- and middle-income countries (LMICs). Botulinum toxin administration is a treatment approach that has been used in recent years to reduce rigidity and spasms in tetanus patients. This case report focuses on its efficacy. PMID:25234426

  19. 9 CFR 121.3 - VS select agents and toxins.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false VS select agents and toxins. 121.3 Section 121.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... toxins listed in this section have the potential to pose a severe threat to animal health or to...

  20. The effects of diphtheria toxin on the Cecropia silkworm.

    PubMed

    PAPPENHEIMER, A M; WILLIAMS, C M

    1952-05-01

    1. The metamorphosis of the Cecropia silkworm is accompanied by large and systematic changes in the insect's sensitivity to diphtheria toxin. 2. Injection of less than 1 gamma of toxin into mature caterpillars, prepupae, or developing adults causes cessation of development followed by delayed death 1 to 5 weeks later. 3. Dormant pupae, on the contrary, are resistant to 70 gamma of toxin and may survive even this enormous dose for over 4 weeks. One-hundredth of this dose, however, prevents pupae from initiating adult development. 4. Tetanus toxin, to which the insect is insensitive, failed to duplicate any of these effects. 5. Maximal sensitivity to diphtheria toxin is characteristic of those stages in the life history which depend on the presence and function of the cytochrome system. Resistance to the toxin, as in the case of the diapausing pupa, is correlated with the existence and utilization of metabolic pathways other than the usual cytochrome system. 6. This correlation persists within the individual insect. Thus, within the diapausing pupa, the toxin fails to affect the heart in which a normal cytochrome system is absent, but, within the same insect, causes a degeneration of the intersegmental muscles in which an intact cytochrome system is present. 7. These several lines of evidence are interpreted in support of the conclusion that diphtheria toxin acts by blocking the synthesis of one or more components in the cytochrome system. PMID:14955616

  1. Effects of marine algal toxins on thermoregulation in mice.

    PubMed

    Gordon, Christopher J; Ramsdell, John S

    2005-01-01

    Hypothermia is often seen in mice and rats exposed acutely to marine algal toxins, but the mechanism of action of these toxins on thermoregulation is not well understood. Our laboratory has assessed the thermoregulatory mechanisms of two marine algal toxins, maitotoxin and brevetoxin in the mouse. Radiotelemetry was used to measure core temperature in the unrestrained mouse while it was housed in a temperature gradient allowing the exhibition of thermoregulatory behavior. Both maitotoxin (338 ng/kg) and brevetoxin (180 microg/kg) were shown to elicit profound hypothermic responses accompanied by a preference for cooler ambient temperatures in the gradient. This behavioral response would suggest that the toxins alter the central neural control of body temperature, resulting in a regulated reduction in body temperature. Following recovery from the acute hypothermic effects of brevetoxin, mice developed an elevation in their daytime core temperature that persisted for several days after exposure. This fever-like response may represent a delayed toxicological effect of the marine algal toxins that is manifested through the thermoregulatory system. Overall, algal toxins have acute and delayed effects on temperature regulation in the mouse. A better understanding of the mechanisms of action of the toxins on thermoregulation should lead to improved methods for treating victims of ciguatera and other toxin exposures. PMID:16111859

  2. Oxidative Stress in Shiga Toxin Production by Enterohemorrhagic Escherichia coli

    PubMed Central

    Licznerska, Katarzyna; Nejman-Faleńczyk, Bożena; Bloch, Sylwia; Dydecka, Aleksandra; Topka, Gracja; Gąsior, Tomasz; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2016-01-01

    Virulence of enterohemorrhagic Escherichia coli (EHEC) strains depends on production of Shiga toxins. These toxins are encoded in genomes of lambdoid bacteriophages (Shiga toxin-converting phages), present in EHEC cells as prophages. The genes coding for Shiga toxins are silent in lysogenic bacteria, and prophage induction is necessary for their efficient expression and toxin production. Under laboratory conditions, treatment with UV light or antibiotics interfering with DNA replication are commonly used to induce lambdoid prophages. Since such conditions are unlikely to occur in human intestine, various research groups searched for other factors or agents that might induce Shiga toxin-converting prophages. Among other conditions, it was reported that treatment with H2O2 caused induction of these prophages, though with efficiency significantly lower relative to UV-irradiation or mitomycin C treatment. A molecular mechanism of this phenomenon has been proposed. It appears that the oxidative stress represents natural conditions provoking induction of Shiga toxin-converting prophages as a consequence of H2O2 excretion by either neutrophils in infected humans or protist predators outside human body. Finally, the recently proposed biological role of Shiga toxin production is described in this paper, and the “bacterial altruism” and “Trojan Horse” hypotheses, which are connected to the oxidative stress, are discussed. PMID:26798420

  3. Oxidative Stress in Shiga Toxin Production by Enterohemorrhagic Escherichia coli.

    PubMed

    Licznerska, Katarzyna; Nejman-Faleńczyk, Bożena; Bloch, Sylwia; Dydecka, Aleksandra; Topka, Gracja; Gąsior, Tomasz; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2016-01-01

    Virulence of enterohemorrhagic Escherichia coli (EHEC) strains depends on production of Shiga toxins. These toxins are encoded in genomes of lambdoid bacteriophages (Shiga toxin-converting phages), present in EHEC cells as prophages. The genes coding for Shiga toxins are silent in lysogenic bacteria, and prophage induction is necessary for their efficient expression and toxin production. Under laboratory conditions, treatment with UV light or antibiotics interfering with DNA replication are commonly used to induce lambdoid prophages. Since such conditions are unlikely to occur in human intestine, various research groups searched for other factors or agents that might induce Shiga toxin-converting prophages. Among other conditions, it was reported that treatment with H2O2 caused induction of these prophages, though with efficiency significantly lower relative to UV-irradiation or mitomycin C treatment. A molecular mechanism of this phenomenon has been proposed. It appears that the oxidative stress represents natural conditions provoking induction of Shiga toxin-converting prophages as a consequence of H2O2 excretion by either neutrophils in infected humans or protist predators outside human body. Finally, the recently proposed biological role of Shiga toxin production is described in this paper, and the "bacterial altruism" and "Trojan Horse" hypotheses, which are connected to the oxidative stress, are discussed. PMID:26798420

  4. Short Toxin-like Proteins Abound in Cnidaria Genomes

    PubMed Central

    Tirosh, Yitshak; Linial, Itai; Askenazi, Manor; Linial, Michal

    2012-01-01

    Cnidaria is a rich phylum that includes thousands of marine species. In this study, we focused on Anthozoa and Hydrozoa that are represented by the Nematostella vectensis (Sea anemone) and Hydra magnipapillata genomes. We present a method for ranking the toxin-like candidates from complete proteomes of Cnidaria. Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. Fundamental features that were emphasized in training ClanTox include cysteines and their spacing along the sequences. Among the 83,000 proteins derived from Cnidaria representatives, we found 170 candidates that fulfill the properties of toxin-like-proteins, the vast majority of which were previously unrecognized as toxins. An additional 394 short proteins exhibit characteristics of toxin-like proteins at a moderate degree of confidence. Remarkably, only 11% of the predicted toxin-like proteins were previously classified as toxins. Based on our prediction methodology and manual annotation, we inferred functions for over 400 of these proteins. Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of the proteins belong to small families of paralogs. We conclude that the evolutionary expansion of toxin-like proteins in Cnidaria contributes to their fitness in the complex environment of the aquatic ecosystem. PMID:23202321

  5. Regulation of toxin gene expression in Clostridium perfringens.

    PubMed

    Ohtani, Kaori; Shimizu, Tohru

    2015-05-01

    The Gram-positive, anaerobic, spore-forming, rod-shaped Clostridium perfringens is widely distributed in nature, especially in soil and the gastrointestinal tract of humans and animals. C. perfringens causes clostridial myonecrosis (or gas gangrene), enteritis and enterotoxemia in humans and livestock by producing numerous extracellular toxins and enzymes. The toxin gene expression is regulated by a two-component regulatory system and regulatory RNA VirR/VirS-VR-RNA cascade. The VirR/VirS system was originally found in a type A strain, but a recent report showed that it is also important for the toxin gene regulation in other types of strains. Two types of cell-cell signaling, i.e., agr-system and AI-2 signaling, are also important for the regulation of toxin genes. Several regulatory systems independent from the VirR/VirS system, including virX, the orphan histidine kinase ReeS and orphan response regulator RevR, are also involved in the regulation of toxin genes. In addition, the expression of toxin genes is upregulated after contact with Caco-2 cells. C. perfringens has a complex regulatory network for toxin gene expression and thus the coordination of toxin gene expression is important for the process of infection. PMID:25303832

  6. T-2 toxin Analysis in Poultry and Cattle Feedstuff

    PubMed Central

    Gholampour Azizi, Issa; Azarmi, Masumeh; Danesh Pouya, Naser; Rouhi, Samaneh

    2014-01-01

    Background: T-2 toxin is a mycotoxin that is produced by the Fusarium fungi. Consumption of food and feed contaminated with T-2 toxin causes diseases in humans and animals. Objectives: In this study T-2 toxin was analyzed in poultry and cattle feedstuff in cities of Mazandaran province (Babol, Sari, Chalus), Northern Iran. Materials and Methods: In this study, 90 samples were analyzed for T-2 toxin contamination by the ELISA method. Results: Out of 60 concentrate and bagasse samples collected from various cities of Mazandaran province, 11.7% and 3.3% were contaminated with T-2 toxin at concentrations > 25 and 50 µg/kg, respectively. For mixed poultry diets, while 10% of the 30 analyzed samples were contaminated with > 25 µg/kg, none of the tested samples contained T-2 toxin at levels > 50 µg/kg. Conclusions: The results obtained from this study show that poultry and cattle feedstuff can be contaminated with different amounts of T-2 toxin in different conditions and locations. Feedstuff that are contaminated by this toxin cause different diseases in animals; thus, potential transfer of mycotoxins to edible by-products from animals fed mycotoxin-contaminated feeds drives the need to routinely monitor mycotoxins in animal feeds and their components. This is the basis on which effective management of mycotoxins and their effects can be implemented. PMID:24872939

  7. [Toxins of Clostridium perfringens as a natural and bioterroristic threats].

    PubMed

    Omernik, Andrzej; Płusa, Tadeusz

    2015-09-01

    Clostridium perfringens is absolutely anaerobic rod-shaped, sporeforming bacterium. The morbidity is connected with producing toxins. Depending on the type of toxin produced Clostridium perfringens can be divided into five serotypes:A-E. Under natural conditions, this bacterium is responsible for local outbreaks of food poisoning associated with eating contaminated food which which was improperly heat treated. Some countries with lower economic level are endemic foci of necrotizing enteritis caused by Clostridium perfringens. The bacterium is also a major cause of gas gangrene. It is a disease, associated with wound infection, with potentially fatal prognosis in the case of treatment's delays. In the absence of early radical surgery, antibiotic therapy and (if available) hyperbaric treatment leads to the spread of toxins in the body causing shock, coma and death. Due to the force of produced toxins is a pathogen that poses a substrate for the production of biological weapons. It could potentially be used to induce outbreaks of food poisoning and by missiles contamination by spore lead to increased morbidity of gas gangrene in injured soldiers. C. perfringens types B and D produce epsilon toxin considered to be the third most powerful bacterial toxin. Because of the ability to disperse the toxin as an aerosol and a lack of methods of treatment and prevention of poisoning possible factors it is a potential tool for bioterrorism It is advisable to continue research into vaccines and treatments for poisoning toxins of C. perfringens. PMID:26449576

  8. Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin

    PubMed Central

    Oda, Masataka; Terao, Yutaka; Sakurai, Jun; Nagahama, Masahiro

    2015-01-01

    Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1–250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251–370 aa, C-domain), which is the membrane-binding site. Immunization of mice with the C-domain of alpha-toxin prevents the gas gangrene caused by C. perfringens, whereas immunization with the N-domain has no effect. The central loop domain (55–93 aa), especially H….SW84Y85….G, plays an important role in the interaction with ganglioside GM1a. The toxin binds to lipid rafts in the presence of a GM1a/TrkA complex, and metabolites from phosphatidylcholine to diacylglycerol through the enzymatic activity of alpha-toxin itself. These membrane dynamics leads to the activation of endogenous PLCγ-1 via TrkA. In addition, treatment with alpha-toxin leads to the formation of diacylglycerol at membrane rafts in ganglioside-deficient DonQ cells; this in turn triggers endocytosis and cell death. This article summarizes the current the membrane-binding mechanism of alpha-toxin in detail. PMID:26633512

  9. Purification of Clostridium botulinum type G progenitor toxin.

    PubMed

    Nukina, M; Mochida, Y; Sakaguchi, S; Sakaguchi, G

    1988-04-01

    Clostridium botulinum type G cultured for 6 days at 30 degrees C in proteose peptone-yeast extract-glucose medium produced toxin of 1.3 x 10(4) LD50/ml. The toxin was precipitated at pH 4.0, extracted with 0.2 M phosphate buffer, pH 6.0, and activated with trypsin. Sonic treatment and trypsinization of the residual precipitate released additional toxin, the toxicity of which corresponded to that detected in whole culture. Activated toxin obtained from the first extract and that from the residual precipitate were combined and purified by salting out, acid precipitation, gel filtration on Sephadex G-200, chromatography on SP-Sephadex, and a second gel filtration on Sephadex G-200. The yield of purified toxin from 10 liters of culture was 22.9 mg an 1.1 X 10(8) mouse ip LD50 with a specific toxicity of 3.0 X 10(7) mouse ip LD50/mg nitrogen. The molecular weight of the toxin was about 500,000, corresponding to that of L toxin of the other types. No M nor LL toxin was detected. PMID:3293334

  10. EFFECTS OF SHIGA TOXIN ON ISOLATED PORCINE GRANULOCYTES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Shiga toxin (Stx) binding to polymorphonuclear leukocytes (PMN) is hypothesized to play a role in the pathogenesis of Shiga toxin-producing Escherichia coli (STEC) disease in humans. Pigs are an excellent model for studying the role of PMN in STEC disease because, like humans, they are ...

  11. Synthetic peptides with antigenic specificity for bacterial toxins.

    PubMed

    Sela, M; Arnon, R; Jacob, C O

    1986-01-01

    The attachment of a diphtheria toxin-specific synthetic antigenic determinant and a synthetic adjuvant to a synthetic polymeric carrier led to production of a totally synthetic macromolecule which provoked protective antibodies against diphtheria when administered in aqueous solution. When peptides related to the B subunit of cholera toxin were synthesized and attached to tetanus toxoid, antibodies produced against the conjugate reacted in some but not all cases with intact cholera toxin and (especially with peptide CTP 3, residues 50-64) neutralized toxin reactivity, as tested by permeability in rabbit skin, fluid accumulation in ligated small intestinal loops and adenylate cyclase activation. Polymerization of the peptide without any external carrier, or conjugation with the dipalmityl lysine group, had as good an effect in enhancing the immune response as its attachment to tetanus toxoid. Prior exposure to the carrier suppressed the immune response to the epitope attached to it, whereas prior exposure to the synthetic peptide had a good priming effect when the intact toxin was given; when two different peptides were attached to the same carrier, both were expressed. Antisera against peptide CTP 3 were highly cross-reactive with the heat-labile toxin of Escherichia coli and neutralized it to the same extent as cholera toxin, which is not surprising in view of the great homology between the two proteins. A synthetic oligonucleotide coding for CTP 3 has been used to express the peptide in a form suitable for immunization. It led to a priming effect against the intact cholera toxin. PMID:2426052

  12. Clostridial Binary Toxins: Iota and C2 Family Portraits

    PubMed Central

    Stiles, Bradley G.; Wigelsworth, Darran J.; Popoff, Michel R.; Barth, Holger

    2011-01-01

    There are many pathogenic Clostridium species with diverse virulence factors that include protein toxins. Some of these bacteria, such as C. botulinum, C. difficile, C. perfringens, and C. spiroforme, cause enteric problems in animals as well as humans. These often fatal diseases can partly be attributed to binary protein toxins that follow a classic AB paradigm. Within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-ADP-ribosylation of globular actin by the A component. However, much less is known about B component binding to cell-surface receptors. These toxins share sequence homology amongst themselves and with those produced by another Gram-positive, spore-forming bacterium also commonly associated with soil and disease: Bacillus anthracis. This review focuses upon the iota and C2 families of clostridial binary toxins and includes: (1) basics of the bacterial source; (2) toxin biochemistry; (3) sophisticated cellular uptake machinery; and (4) host–cell responses following toxin-mediated disruption of the cytoskeleton. In summary, these protein toxins aid diverse enteric species within the genus Clostridium. PMID:22919577

  13. Detection of shiga toxins by lateral flow assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shiga toxin-producing Escherichia coli (STEC) produce Shiga toxins (Stxs) that can cause human disease and death. The contamination of food products with STEC represents a food safety problem that necessitates rapid and effective detection strategies to mitigate risk. In this manuscript we report ...

  14. Adsorption processing - Optimization through understanding

    SciTech Connect

    Not Available

    1986-01-01

    Adsorption processes used in the natural gas industry for dehydration, sweetening and liquids recovery are batch systems, very similar to laboratory chromatographs. For continuous processing a plant must contain multiple adsorbers, so that while one column adsorbs, another or others can be desorbed and prepared for their next turn at adsorption. Variations in the cycle, the number of adsorbers and the way multiple towers may be sequenced; in series, in parallel, etc. are so numerous that an entire presentation could be devoted to the reasons and results of the various arrangements. For a consideration of the process fundamentals and the way they can be manipulated, this discussion concentrates on a simple two tower system typical of what is frequently used to dehydrate gas ahead of a cryogenic plant; a turboexpander unit or a peak shaving LNG facility.

  15. Adsorption kinetics of diatomic molecules.

    PubMed

    Burde, Jared T; Calbi, M Mercedes

    2014-05-01

    The adsorption dynamics of diatomic molecules on solid surfaces is examined by using a Kinetic Monte Carlo algorithm. Equilibration times at increasing loadings are obtained, and explained based on the elementary processes that lead to the formation of the adsorbed film. The ability of the molecules to change their orientation accelerates the overall uptake and leads to competitive kinetic behaviour between the different orientations. The dependence of the equilibration time on coverage follows the same decreasing trend obtained experimentally for ethane adsorption on closed-end carbon nanotube bundles. The exploration of molecule-molecule interaction effects on this trend provides relevant insights to understand the kinetic behaviour of other species, from simpler molecules to larger polyatomic molecules, adsorbing on surfaces with different binding strength. PMID:24654004

  16. Advanced Doppler tracking experiments

    NASA Technical Reports Server (NTRS)

    Armstrong, J. W.

    1989-01-01

    The Doppler tracking method is currently the only technique available for broadband gravitational wave searches in the approx. 10(exp -4) to 10(exp -1) Hz low frequency band. A brief review is given of the Doppler method, a discussion of the main noise sources, and a review of experience with current spacecraft and the prospects for sensitivity improvements in an advanced Doppler tracking experiment.

  17. Studies on Vapor Adsorption Systems

    NASA Technical Reports Server (NTRS)

    Shamsundar, N.; Ramotowski, M.

    1998-01-01

    The project consisted of performing experiments on single and dual bed vapor adsorption systems, thermodynamic cycle optimization, and thermal modeling. The work was described in a technical paper that appeared in conference proceedings and a Master's thesis, which were previously submitted to NASA. The present report describes some additional thermal modeling work done subsequently, and includes listings of computer codes developed during the project. Recommendations for future work are provided.

  18. Optimum conditions for adsorptive storage.

    PubMed

    Bhatia, Suresh K; Myers, Alan L

    2006-02-14

    The storage of gases in porous adsorbents, such as activated carbon and carbon nanotubes, is examined here thermodynamically from a systems viewpoint, considering the entire adsorption-desorption cycle. The results provide concrete objective criteria to guide the search for the "Holy Grail" adsorbent, for which the adsorptive delivery is maximized. It is shown that, for ambient temperature storage of hydrogen and delivery between 30 and 1.5 bar pressure, for the optimum adsorbent the adsorption enthalpy change is 15.1 kJ/mol. For carbons, for which the average enthalpy change is typically 5.8 kJ/mol, an optimum operating temperature of about 115 K is predicted. For methane, an optimum enthalpy change of 18.8 kJ/mol is found, with the optimum temperature for carbons being 254 K. It is also demonstrated that for maximum delivery of the gas the optimum adsorbent must be homogeneous, and that introduction of heterogeneity, such as by ball milling, irradiation, and other means, can only provide small increases in physisorption-related delivery for hydrogen. For methane, heterogeneity is always detrimental, at any value of average adsorption enthalpy change. These results are confirmed with the help of experimental data from the literature, as well as extensive Monte Carlo simulations conducted here using slit pore models of activated carbons as well as atomistic models of carbon nanotubes. The simulations also demonstrate that carbon nanotubes offer little or no advantage over activated carbons in terms of enhanced delivery, when used as storage media for either hydrogen or methane. PMID:16460092

  19. MATERIAL TRACKING USING LANMAS

    SciTech Connect

    Armstrong, F.

    2010-06-07

    LANMAS is a transaction-based nuclear material accountability software product developed to replace outdated and legacy accountability systems throughout the DOE. The core underlying purpose of LANMAS is to track nuclear materials inventory and report transactions (movement, mixing, splitting, decay, etc.) to the Nuclear Materials Management and Safeguards System (NMMSS). While LANMAS performs those functions well, there are many additional functions provided by the software product. As a material is received onto a site or created at a site, its entire lifecycle can be tracked in LANMAS complete to its termination of safeguards. There are separate functions to track material movements between and within material balance areas (MBAs). The level of detail for movements within a MBA is configurable by each site and can be as high as a site designation or as detailed as building/room/rack/row/position. Functionality exists to track the processing of materials, either as individual items or by modeling a bulk process as an individual item to track inputs and outputs from the process. In cases where sites have specialized needs, the system is designed to be flexible so that site specific functionality can be integrated into the product. This paper will demonstrate how the software can be used to input material into an account and track it to its termination of safeguards.

  20. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds. PMID:22885596

  1. Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

    SciTech Connect

    Cronin, M.J.; Evans, W.S.; Rogol, A.D.; Weiss, A.A.; Thorner, M.O.; Orth, D.N.; Nicholson, W.E.; Yasumoto, T.; Hewlett, E.L.

    1986-08-01

    Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release.

  2. Toxin activity assays, devices, methods and systems therefor

    DOEpatents

    Koh, Chung-Yan; Schaff, Ulrich Y.; Sommer, Gregory Jon

    2016-04-05

    Embodiments of the present invention are directed toward devices, system and method for conducting toxin activity assay using sedimentation. The toxin activity assay may include generating complexes which bind to a plurality of beads in a fluid sample. The complexes may include a target toxin and a labeling agent, or may be generated due to presence of active target toxin and/or labeling agent designed to be incorporated into complexes responsive to the presence of target active toxin. The plurality of beads including the complexes may be transported through a density media, wherein the density media has a lower density than a density of the beads and higher than a density of the fluid sample, and wherein the transporting occurs, at least in part, by sedimentation. Signal may be detected from the labeling agents of the complexes.

  3. Use of lactose against the deadly biological toxin ricin.

    PubMed

    Nagatsuka, Takehiro; Uzawa, Hirotaka; Ohsawa, Isaac; Seto, Yasuo; Nishida, Yoshihiro

    2010-04-01

    Developing a technology for detecting and decontaminating biological toxins is needed. Ricin from Ricinus communis is a highly poisonous toxin; it was formerly used for an assassination in London and in postal attacks in the United States. Ricin is readily available from castor beans and could be used as a biological agent. We propose using glycotechnology against the illegal use of ricin. Lactose (a natural ligand of this toxin) was incorporated into polyacrylamide-based glycopolymers at variable sugar densities (18-100%) and evaluated with surface plasmon resonance (SPR) spectroscopy and the real agent, ricin. Glycopolymers (18-65% lactose densities) effectively interfered with the toxin-lactoside adhesion event (>99% efficiency within 20 min). This supported the notion of using the mammary sugar lactose against a deadly biological toxin. PMID:20369893

  4. Discovery of a widely distributed toxin biosynthetic gene cluster

    PubMed Central

    Lee, Shaun W.; Mitchell, Douglas A.; Markley, Andrew L.; Hensler, Mary E.; Gonzalez, David; Wohlrab, Aaron; Dorrestein, Pieter C.; Nizet, Victor; Dixon, Jack E.

    2008-01-01

    Bacteriocins represent a large family of ribosomally produced peptide antibiotics. Here we describe the discovery of a widely conserved biosynthetic gene cluster for the synthesis of thiazole and oxazole heterocycles on ribosomally produced peptides. These clusters encode a toxin precursor and all necessary proteins for toxin maturation and export. Using the toxin precursor peptide and heterocycle-forming synthetase proteins from the human pathogen Streptococcus pyogenes, we demonstrate the in vitro reconstitution of streptolysin S activity. We provide evidence that the synthetase enzymes, as predicted from our bioinformatics analysis, introduce heterocycles onto precursor peptides, thereby providing molecular insight into the chemical structure of streptolysin S. Furthermore, our studies reveal that the synthetase exhibits relaxed substrate specificity and modifies toxin precursors from both related and distant species. Given our findings, it is likely that the discovery of similar peptidic toxins will rapidly expand to existing and emerging genomes. PMID:18375757

  5. Engineered nanoparticles mimicking cell membranes for toxin neutralization.

    PubMed

    Fang, Ronnie H; Luk, Brian T; Hu, Che-Ming J; Zhang, Liangfang

    2015-08-01

    Protein toxins secreted from pathogenic bacteria and venomous animals rely on multiple mechanisms to overcome the cell membrane barrier to inflict their virulence effect. A promising therapeutic concept toward developing a broadly applicable anti-toxin platform is to administer cell membrane mimics as decoys to sequester these virulence factors. As such, lipid membrane-based nanoparticulates are an ideal candidate given their structural similarity to cellular membranes. This article reviews the virulence mechanisms employed by toxins at the cell membrane interface and highlights the application of cell-membrane mimicking nanoparticles as toxin decoys for systemic detoxification. In addition, the implication of particle/toxin nanocomplexes in the development of toxoid vaccines is discussed. PMID:25868452

  6. A Novel Mode of Translocation for Cytolethal Distending Toxin

    PubMed Central

    Guerra, Lina; Nemec, Kathleen N.; Massey, Shane; Tatulian, Suren A.; Thelestam, Monica; Frisan, Teresa; Teter, Ken

    2008-01-01

    Summary Thermal instability in the toxin catalytic subunit may be a common property of toxins that exit the endoplasmic reticulum (ER) by exploiting the mechanism of ER-associated degradation (ERAD). The Haemophilus ducreyi cytolethal distending toxin (HdCDT) does not utilize ERAD to exit the ER, so we predicted the structural properties of its catalytic subunit (HdCdtB) would differ from other ER-translocating toxins. Here, we document the heat-stable properties of HdCdtB which distinguish it from other ER-translocating toxins. Cell-based assays further suggested that HdCdtB does not unfold before exiting the ER and that it may move directly from the ER lumen to the nucleoplasm. These observations suggest a novel mode of ER exit for HdCdtB. PMID:19118582

  7. Linking bacterial type I toxins with their actions.

    PubMed

    Brielle, Régine; Pinel-Marie, Marie-Laure; Felden, Brice

    2016-04-01

    Bacterial type I toxin-antitoxin systems consist of stable toxin-encoding mRNAs whose expression is counteracted by unstable RNA antitoxins. Accumulating evidence suggests that these players belong to broad regulatory networks influencing overall bacterial physiology. The majority of known transmembrane type I toxic peptides have conserved structural characteristics. However, recent studies demonstrated that their mechanisms of toxicity are diverse and complex. To better assess the current state of the art, type I toxins can be grouped into two classes according to their location and mechanisms of action: membrane-associated toxins acting by pore formation and/or by nucleoid condensation; and cytosolic toxins inducing nucleic acid cleavage. This classification will evolve as a result of future investigations. PMID:26874964

  8. Treatment of Gastrointestinal Sphincters Spasms with Botulinum Toxin A

    PubMed Central

    Brisinda, Giuseppe; Sivestrini, Nicola; Bianco, Giuseppe; Maria, Giorgio

    2015-01-01

    Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications. The range of clinical applications has grown to encompass several neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the gastrointestinal tract. Although toxin blocks cholinergic nerve endings in the autonomic nervous system, it has also been shown that it does not block non-adrenergic non-cholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions easier, in the outpatient setting, at a lower cost and without permanent complications. This review presents current data on the use of botulinum toxin A in the treatment of pathological conditions of the gastrointestinal tract. PMID:26035487

  9. Essential Staphylococcus aureus toxin export system

    PubMed Central

    Chatterjee, Som S.; Joo, Hwang-Soo; Duong, Anthony C.; Dieringer, Thomas D.; Tan, Vee Y.; Song, Yan; Fischer, Elizabeth R.; Cheung, Gordon Y. C.; Li, Min; Otto, Michael

    2012-01-01

    Widespread antibiotic resistance among important bacterial pathogens such as Staphylococcus aureus1 calls for alternative routes of drug development. Interfering with critical virulence determinants is considered a promising novel approach to control bacterial infection2. Phenol-soluble modulins (PSMs) are peptide toxins with multiple key roles in pathogenesis3–5 and a major impact on the ability of highly virulent S. aureus to cause disease3,6. However, targeting PSMs for therapeutic intervention is hampered by their multitude and diversity. Here, we report that an ABC transporter with previously unknown function is responsible for the export of all PSM classes, thus representing a single target to interfere simultaneously with the production of all PSMs. The transporter had a strong effect on virulence phenotypes, such as neutrophil lysis, and the development of S. aureus infection, similar in extent to the sum of all PSMs. Furthermore, it proved essential for bacterial growth. Moreover, it protected the producer from the antimicrobial activity of secreted PSMs and contributed to defense against PSM-mediated bacterial interference. Our study reveals a non-canonical, dedicated secretion mechanism for an important toxin class and identifies this mechanism as a comprehensive potential target for the development of drugs efficiently inhibiting growth and virulence of pathogenic staphylococci. PMID:23396209

  10. The Biochemical Toxin Arsenal from Ant Venoms

    PubMed Central

    Touchard, Axel; Aili, Samira R.; Fox, Eduardo Gonçalves Paterson; Escoubas, Pierre; Orivel, Jérôme; Nicholson, Graham M.; Dejean, Alain

    2016-01-01

    Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents. PMID:26805882

  11. The Biochemical Toxin Arsenal from Ant Venoms.

    PubMed

    Touchard, Axel; Aili, Samira R; Fox, Eduardo Gonçalves Paterson; Escoubas, Pierre; Orivel, Jérôme; Nicholson, Graham M; Dejean, Alain

    2016-01-01

    Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents. PMID:26805882

  12. Spectroscopic study of food and food toxins

    NASA Astrophysics Data System (ADS)

    King, Gavin; Walsh, James E.; Martin, Suzanne

    2003-03-01

    Fungal infection of food causes billions of dollars of lost revenue per annum as well as health problems, to animals and humans, if consumed in sufficient quantities. Modern food sorting techniques rely on colour or other physical characteristics to filter diseased or otherwise unsuitable foodstuffs from healthy foodstuffs. Their speeds are such that up to 40,000 objects per second can be moved at 4 metres per second, through 1 m wide chutes that offer a wide view for colour and shape sorting. Grain type foods such as coffee or peanuts are often vulnerable to toxic infection from invading fungi. If this happens, then their texture, taste and colour can change. Up to now, only visible wavelengths and colour identification have been used to bulk-sort food, but there has been little research in the ultra violet regions of the spectrum to help identify fungus or toxin infection. This research specifically concentrated on the ultra violet (UV) spectral characteristics of food in an attempt to identify possible spectral changes that occur when healthy food items like peanuts become infected with toxin-producing fungi. Ultimately, the goal is to design, build and construct an optical detection system that can use these 'spectral fingerprints' to more quickly and efficiently detect toxically infected food items.

  13. Gene Therapy and Targeted Toxins for Glioma

    PubMed Central

    Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

    2011-01-01

    The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

  14. Gene Therapy and Targeted Toxins for Glioma

    PubMed Central

    King, Gwendalyn D.; Curtin, James F.; Candolfi, Marianela; Kroeger, Kurt; Lowenstein, Pedro R.; Castro, Maria G.

    2006-01-01

    The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted, this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:16457645

  15. Normal and Pathologic Concentrations of Uremic Toxins

    PubMed Central

    Duranton, Flore; Cohen, Gerald; De Smet, Rita; Rodriguez, Mariano; Jankowski, Joachim; Vanholder, Raymond

    2012-01-01

    An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD. PMID:22626821

  16. Toxin-antitoxins and bacterial virulence.

    PubMed

    Lobato-Márquez, Damián; Díaz-Orejas, Ramón; García-Del Portillo, Francisco

    2016-09-01

    Bacterial virulence relies on a delicate balance of signals interchanged between the invading microbe and the host. This communication has been extensively perceived as a battle involving harmful molecules produced by the pathogen and host defenses. In this review, we focus on a largely unexplored element of this dialogue, as are toxin-antitoxin (TA) systems of the pathogen. TA systems are reported to respond to stresses that are also found in the host and, as a consequence, could modulate the physiology of the intruder microbe. This view is consistent with recent studies that demonstrate a contribution of distinct TA systems to virulence since their absence alters the course of the infection. TA loci are stress response modules that, therefore, could readjust pathogen metabolism to favor the generation of slow-growing or quiescent cells 'before' host defenses irreversibly block essential pathogen activities. Some toxins of these TA modules have been proposed as potential weapons used by the pathogen to act on host targets. We discuss all these aspects based on studies that support some TA modules as important regulators in the pathogen-host interface. PMID:27476076

  17. Cardiovascular-Active Venom Toxins: An Overview.

    PubMed

    Rebello Horta, Carolina Campolina; Chatzaki, Maria; Rezende, Bruno Almeida; Magalhães, Bárbara de Freitas; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Ribeiro Oliveira-Mendes, Bárbara Bruna; do Carmo, Anderson Oliveira; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

    2016-01-01

    Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses. PMID:26812904

  18. Comparative genomics of Shiga toxin encoding bacteriophages

    PubMed Central

    2012-01-01

    Background Stx bacteriophages are responsible for driving the dissemination of Stx toxin genes (stx) across their bacterial host range. Lysogens carrying Stx phages can cause severe, life-threatening disease and Stx toxin is an integral virulence factor. The Stx-bacteriophage vB_EcoP-24B, commonly referred to as Ф24B, is capable of multiply infecting a single bacterial host cell at a high frequency, with secondary infection increasing the rate at which subsequent bacteriophage infections can occur. This is biologically unusual, therefore determining the genomic content and context of Ф24B compared to other lambdoid Stx phages is important to understanding the factors controlling this phenomenon and determining whether they occur in other Stx phages. Results The genome of the Stx2 encoding phage, Ф24B was sequenced and annotated. The genomic organisation and general features are similar to other sequenced Stx bacteriophages induced from Enterohaemorrhagic Escherichia coli (EHEC), however Ф24B possesses significant regions of heterogeneity, with implications for phage biology and behaviour. The Ф24B genome was compared to other sequenced Stx phages and the archetypal lambdoid phage, lambda, using the Circos genome comparison tool and a PCR-based multi-loci comparison system. Conclusions The data support the hypothesis that Stx phages are mosaic, and recombination events between the host, phages and their remnants within the same infected bacterial cell will continue to drive the evolution of Stx phage variants and the subsequent dissemination of shigatoxigenic potential. PMID:22799768

  19. Adsorptive properties of flyash carbon

    SciTech Connect

    Graham, U.M.; Rathbone, R.F.; Robl, T.L.

    1996-10-01

    Flyash carbon constitutes the char particles that are left in flyash after the incomplete combustion of coal in the furnace, rendering flyash above spec for ASTM C618 applications for cement. A beneficiation process allows the selective separation of unburned carbon from flyash to be used for upgrading into a higher value product. Flyash carton is composed of several microscopically distinguishable types; inertinite is relatively unreactive in the thermal processing of coal and occurs essentially unaltered in the flyash while {open_quotes}coke{close_quotes} is produced from the melting, devolatilization, swelling and resolidification of the reactive macerals vitrinite and liptinite. The porosity, surface area, and surface chemistry of flyash carbons are characterized using mercury porosimetry, BET analysis, and vapor- and liquid-phase adsorption of various organic compounds. Results suggest that different carbon forms in flyash affect the degree of adsorption of phenols as will as other hydrocarbon pollutants onto the flyash carbon. A comparison of adsorptability of the flyash carbon compared to commercially available active carbons are discussed.

  20. Towards an understanding of the role of Clostridium perfringens toxins in human and animal disease

    PubMed Central

    Uzal, Francisco A; Freedman, John C; Shrestha, Archana; Theoret, James R; Garcia, Jorge; Awad, Milena M; Adams, Vicki; Moore, Robert J; Rood, Julian I; McClane, Bruce A

    2014-01-01

    Clostridium perfringens uses its arsenal of >16 toxins to cause histotoxic and intestinal infections in humans and animals. It has been unclear why this bacterium produces so many different toxins, especially since many target the plasma membrane of host cells. However, it is now established that C. perfringens uses chromosomally encoded alpha toxin (a phospholipase C) and perfringolysin O (a pore-forming toxin) during histotoxic infections. In contrast, this bacterium causes intestinal disease by employing toxins encoded by mobile genetic elements, including C. perfringens enterotoxin, necrotic enteritis toxin B-like, epsilon toxin and beta toxin. Like perfringolysin O, the toxins with established roles in intestinal disease form membrane pores. However, the intestinal disease-associated toxins vary in their target specificity, when they are produced (sporulation vs vegetative growth), and in their sensitivity to intestinal proteases. Producing many toxins with diverse characteristics likely imparts virulence flexibility to C. perfringens so it can cause an array of diseases. PMID:24762309

  1. Scorpion toxins from Centruroides noxius and Tityus serrulatus. Primary structures and sequence comparison by metric analysis.

    PubMed Central

    Possani, L D; Martin, B M; Svendsen, I; Rode, G S; Erickson, B W

    1985-01-01

    The complete primary structures of toxin II-14 from the Mexican scorpion Centruroides noxius Hoffmann and toxin gamma from the Brazilian scorpion Tityus serrulatus Lutz and Mello have been determined. Cleavage of toxin gamma after Met-6 with CNBr produced the 55-residue peptide 7-61, which maintained the four disulphide bonds but was not toxic to mice at a dose 3 times the lethal dose of native toxin gamma. Pairwise comparison by metric analysis of segment 1-50 of toxin gamma and the corresponding segments from two other South American scorpion toxins, five North American scorpion toxins, nine North African scorpion toxins and one Central Asian scorpion toxin showed that the three Brazilian toxins are intermediate between the North American and North African toxins. This result is consistent with the hypothesis that the South American and African continents were joined by a land connection in the distant past. Images Fig. 1. PMID:4052021

  2. Characterization of toxin plasmids in Clostridium perfringens type C isolates.

    PubMed

    Gurjar, Abhijit; Li, Jihong; McClane, Bruce A

    2010-11-01

    Clostridium perfringens type C isolates cause enteritis necroticans in humans or necrotizing enteritis and enterotoxemia in domestic animals. Type C isolates always produce alpha toxin and beta toxin but often produce additional toxins, e.g., beta2 toxin or enterotoxin. Since plasmid carriage of toxin-encoding genes has not been systematically investigated for type C isolates, the current study used Southern blot hybridization of pulsed-field gels to test whether several toxin genes are plasmid borne among a collection of type C isolates. Those analyses revealed that the surveyed type C isolates carry their beta toxin-encoding gene (cpb) on plasmids ranging in size from ∼65 to ∼110 kb. When present in these type C isolates, the beta2 toxin gene localized to plasmids distinct from the cpb plasmid. However, some enterotoxin-positive type C isolates appeared to carry their enterotoxin-encoding cpe gene on a cpb plasmid. The tpeL gene encoding the large clostridial cytotoxin was localized to the cpb plasmids of some cpe-negative type C isolates. The cpb plasmids in most surveyed isolates were found to carry both IS1151 sequences and the tcp genes, which can mediate conjugative C. perfringens plasmid transfer. A dcm gene, which is often present near C. perfringens plasmid-borne toxin genes, was identified upstream of the cpb gene in many type C isolates. Overlapping PCR analyses suggested that the toxin-encoding plasmids of the surveyed type C isolates differ from the cpe plasmids of type A isolates. These findings provide new insight into plasmids of proven or potential importance for type C virulence. PMID:20823204

  3. Mass spectrometric detection of protein-based toxins.

    PubMed

    Tevell Åberg, Annica; Björnstad, Kristian; Hedeland, Mikael

    2013-09-01

    This review focuses on mass spectrometric detection of protein-based toxins, which are among the most toxic substances known. Special emphasis is given to the bacterial toxins botulinum neurotoxin from Clostridium botulinum and anthrax toxins from Bacillus anthracis as well as the plant toxin ricin produced by Ricinus communis. A common feature, apart from their extreme toxicity, is that they are composed of 2 polypeptide chains, one of which is responsible for cell uptake and another that has enzymatic function with the ability to destroy basic cellular functions. These toxins pose a threat, both regarding natural spread and from a terrorism perspective. In order for public health and emergency response officials to take appropriate action in case of an outbreak, whether natural or intentional, there is a need for fast and reliable detection methods. Traditionally, large molecules like proteins have been detected using immunological techniques. Although sensitive, these methods suffer from some drawbacks, such as the risk of false-positives due to cross-reactions and detection of inactive toxin. This article describes recently developed instrumental methods based on mass spectrometry for the reliable detection of botulinum neurotoxins, anthrax toxins, and ricin. Unequivocal identification of a protein toxin can be carried out by mass spectrometry-based amino acid sequencing. Furthermore, in combination with antibody affinity preconcentration and biochemical tests with mass spectrometric detection demonstrating the toxin's enzymatic activity, very powerful analytical methods have been described. In conclusion, the advent of sensitive, easily operated mass spectrometers provides new possibilities for the detection of protein-based toxins. PMID:23971809

  4. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    PubMed

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. PMID:26780946

  5. Retrocyclins neutralize bacterial toxins by potentiating their unfolding.

    PubMed

    Kudryashova, Elena; Seveau, Stephanie; Lu, Wuyuan; Kudryashov, Dmitri S

    2015-04-15

    Defensins are a class of immune peptides with a broad range of activities against bacterial, fungal and viral pathogens. Besides exerting direct anti-microbial activity via dis-organization of bacterial membranes, defensins are also able to neutralize various unrelated bacterial toxins. Recently, we have demonstrated that in the case of human α- and β-defensins, this later ability is achieved through exploiting toxins' marginal thermodynamic stability, i.e. defensins act as molecular anti-chaperones unfolding toxin molecules and exposing their hydrophobic regions and thus promoting toxin precipitation and inactivation [Kudryashova et al. (2014) Immunity 41, 709-721]. Retrocyclins (RCs) are humanized synthetic θ-defensin peptides that possess unique cyclic structure, differentiating them from α- and β-defensins. Importantly, RCs are more potent against some bacterial and viral pathogens and more stable than their linear counterparts. However, the mechanism of bacterial toxin inactivation by RCs is not known. In the present study, we demonstrate that RCs facilitate unfolding of bacterial toxins. Using differential scanning fluorimetry (DSF), limited proteolysis and collisional quenching of internal tryptophan fluorescence, we show that hydrophobic regions of toxins normally buried in the molecule interior become more exposed to solvents and accessible to proteolytic cleavage in the presence of RCs. The RC-induced unfolding of toxins led to their precipitation and abrogated activity. Toxin inactivation by RCs was strongly diminished under reducing conditions, but preserved at physiological salt and serum concentrations. Therefore, despite significant structural diversity, α-, β- and θ-defensins employ similar mechanisms of toxin inactivation, which may be shared by anti-microbial peptides from other families. PMID:25670244

  6. Antibodies against recombinant catalytic domain of lethal toxin of Clostridium sordellii neutralize lethal toxin toxicity in HeLa cells.

    PubMed

    Arya, Preetika; Ponmariappan, S; Singh, Lokendra; Prasad, G B K S

    2013-02-01

    Lethal toxin of Clostridium sordellii (MLD 150 ng/kg) is one of the most potent Clostridial toxins and is responsible for most of the diseases including sudden death syndrome in cattle, sheep and toxic shock syndrome, necrotizing faciitis, neonatal omphalitis and gangrene in humans. Lethal toxin (TcsL) is a single chain protein of about 270 kDa. In the present study, 1.6 kb DNA fragment encoding for the catalytic domain of TcsL was PCR amplified, cloned in pQE30 UA vector and expressed in E. coli SG 13009. The expression of recombinant lethal toxin protein (rTcsL) was optimized and it was purified under native conditions using a single step Ni-NTA affinity chromatography. The purified recombinant protein was used for the production of polyclonal antibodies in mice and rabbit. The raised antibodies reacted specifically with the purified rTcsL and intact native lethal toxin on Western blot. The biological activity of the recombinant protein was tested in HeLa cells where it showed the cytotoxicity. Further, the polyclonal antibodies were used for in-vitro neutralization of purified rTcsL, acid precipitated C. sordellii and C. difficile native toxins in HeLa cells. Mice and rabbit anti-rTcsL sera effectively neutralized the cytotoxicity of rTcsL and C. sordellii native toxin but it did not neutralize the cytotoxicity of C. difficile toxin in HeLa cells. PMID:22894159

  7. Staphylococcus aureus toxic shock syndrome toxin 1 and Streptococcus pyogenes erythrogenic toxin A modulate inflammatory mediator release from human neutrophils.

    PubMed Central

    Hensler, T; Köller, M; Geoffroy, C; Alouf, J E; König, W

    1993-01-01

    We studied the influence of staphylococcal toxic shock syndrome toxin 1 and streptococcal erythrogenic (pyrogenic) toxin A (ETA) on intact and digitonin-permeabilized human polymorphonuclear granulocytes (PMNs). As was shown by reversed-phase high-performance liquid chromatography analysis, toxic shock syndrome toxin 1 or ETA alone, in the absence of any additional stimulus, did not induce the generation of the chemoattractant leukotriene B4 (LTB4) from PMNs in a wide range of concentrations. In addition, pretreatment of intact PMNs with either toxin potentiated formyl-methionyl-leucyl-phenylalanine (fMLP)- and washed Staphylococcus aureus cell-induced generation of LTB4 in a time- and dose-dependent manner. This increase included LTB4 as well as its inactive omega-oxidated compounds. Further studies revealed evidence that toxin exposure was accompanied by enhanced cellular receptor expression for fMLP as well as for LTB4. The intrinsic GTPase activity of membrane fractions was modulated by both toxins. Short-term incubation with ETA increased the GTPase activity of PMNs up to 141%. Inhibitory effects were obtained when GTP-binding protein functions were stimulated with sodium fluoride (NaF). In addition, specific binding of Gpp(NH)p to GTP-binding protein was inhibited by both toxins during the first 10 min of incubation and was restored at later times of incubation. Our data therefore suggest that both toxins significantly affect the signal transduction pathways of human PMNs, which results in immunomodulatory functions. PMID:8381770

  8. Staphylococcus aureus toxic shock syndrome toxin 1 and Streptococcus pyogenes erythrogenic toxin A modulate inflammatory mediator release from human neutrophils.

    PubMed

    Hensler, T; Köller, M; Geoffroy, C; Alouf, J E; König, W

    1993-03-01

    We studied the influence of staphylococcal toxic shock syndrome toxin 1 and streptococcal erythrogenic (pyrogenic) toxin A (ETA) on intact and digitonin-permeabilized human polymorphonuclear granulocytes (PMNs). As was shown by reversed-phase high-performance liquid chromatography analysis, toxic shock syndrome toxin 1 or ETA alone, in the absence of any additional stimulus, did not induce the generation of the chemoattractant leukotriene B4 (LTB4) from PMNs in a wide range of concentrations. In addition, pretreatment of intact PMNs with either toxin potentiated formyl-methionyl-leucyl-phenylalanine (fMLP)- and washed Staphylococcus aureus cell-induced generation of LTB4 in a time- and dose-dependent manner. This increase included LTB4 as well as its inactive omega-oxidated compounds. Further studies revealed evidence that toxin exposure was accompanied by enhanced cellular receptor expression for fMLP as well as for LTB4. The intrinsic GTPase activity of membrane fractions was modulated by both toxins. Short-term incubation with ETA increased the GTPase activity of PMNs up to 141%. Inhibitory effects were obtained when GTP-binding protein functions were stimulated with sodium fluoride (NaF). In addition, specific binding of Gpp(NH)p to GTP-binding protein was inhibited by both toxins during the first 10 min of incubation and was restored at later times of incubation. Our data therefore suggest that both toxins significantly affect the signal transduction pathways of human PMNs, which results in immunomodulatory functions. PMID:8381770

  9. Development and characterization of monoclonal antibodies against Shiga toxin 2 and their application for toxin detection in milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human infection of Shiga toxin producing Escherichia coli (STEC) is one of the most prevalent foodborne diseases. Shiga toxin 2 (Stx2) is the major contributor to hemolytic-uremic syndrome (HUS) and other systemic complications caused by STEC. Although outbreaks of HUS due to the consumption of dair...

  10. Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

    PubMed Central

    Androga, Grace O.; Hart, Julie; Foster, Niki F.; Charles, Adrian; Forbes, David

    2015-01-01

    Large clostridial toxin-negative, binary toxin-positive (A− B− CDT+) strains of Clostridium difficile are almost never associated with clinically significant C. difficile infection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A− B− CDT+ ribotype 033 (RT033) strain of C. difficile from a young patient with ulcerative colitis and severe diarrhea. PMID:26354812

  11. OCULUS Sea Track Fusion Service

    NASA Astrophysics Data System (ADS)

    Panagiotou, Stylianos C.; Rizogiannis, Constantinos; Katsoulis, Stavros; Lampropoulos, Vassilis; Kanellopoulos, Sotirios; Thomopoulos, Stelios C. A.

    2015-06-01

    Oculus Sea is a complete solution regarding maritime surveillance and communications at Local as well as Central Command and Control level. It includes a robust and independent track fusion service whose main functions include: 1) Interaction with the User to suggest the fusion of two or more tracks, confirm Track ID and Vessel Metadata creation for the fused track, and suggest de-association of two tracks 2) Fusion of same vessel tracks arriving simultaneously from multiple radar sensors featuring track Association, track Fusion of associated tracks to produce a more accurate track, and Multiple tracking filters and fusion algorithms 3) Unique Track ID Generator for each fused track 4) Track Dissemination Service. Oculus Sea Track Fusion Service adopts a system architecture where each sensor is associated with a Kalman estimator/tracker that obtains an estimate of the state vector and its respective error covariance matrix. Finally, at the fusion center, association and track state estimation fusion are carried out. The expected benefits of this system include multi-sensor information fusion, enhanced spatial resolution, and improved target detection.

  12. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    PubMed

    Wong, Emily S W; Hardy, Margaret C; Wood, David; Bailey, Timothy; King, Glenn F

    2013-01-01

    Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the Spider

  13. Development of a diphtheria toxin-based recombinant porcine IL-2 fusion toxin for depleting porcine CD25+ cells.

    PubMed

    Peraino, Jaclyn Stromp; Schenk, Marian; Li, Guoying; Zhang, Huiping; Farkash, Evan A; Sachs, David H; Huang, Christene A; Duran-Struuck, Raimon; Wang, Zhirui

    2013-12-15

    Regulatory T cells (Tregs) have been widely recognized as crucial players in controlling immune responses. Because their major role is to ensure that the immune system is not over reactive, Tregs have been the focus of multiple research studies including those investigating transplantation tolerance, autoimmunity and cancer treatment. On their surface Tregs constitutively express CD25, a high affinity receptor for the cytokine interleukin-2 (IL-2). The reagents constructed in this study were generated by genetically linking porcine IL-2 to the truncated diphtheria toxin (DT390). This reagent functions by first binding to the cell surface via the porcine IL-2/porcine CD25 interaction then the DT390 domain facilitates internalization followed by inhibition of protein synthesis resulting in cell death. Four versions of the porcine IL-2 fusion toxin were designed in an interest to find the most effective isoform: 1) monovalent glycosylated porcine IL-2 fusion toxin (Gly); 2) monovalent non-N-glycosylated porcine IL-2 fusion toxin (NonGly); 3) bivalent glycosylated porcine IL-2 fusion toxin (Bi-Gly); 4) bivalent non-N-glycosylated porcine IL-2 fusion toxin (Bi-NonGly). Using a porcine CD25(+) B cell lymphoma cell line (LCL13271) in vitro analysis of the fusion toxins' ability to inhibit protein synthesis demonstrated that the Bi-NonGly fusion toxin is the most efficient reagent. These in vitro results are consistent with binding affinity as the Bi-NonGly fusion toxin binds strongest to CD25 on the same LCL13271 cells. The Bi-Gly fusion toxin significantly prolonged the survival (p=0.028) of tumor-bearing NOD/SCID IL-2 receptor γ(-/-) (NSG) mice injected with LCL13271 cells compared with untreated controls. This recombinant protein has great potential to function as a useful tool for in vivo depletion of porcine CD25(+) cells for studying immune regulation. PMID:24055128

  14. Cluster analysis of toxins profile pattern as a tool for tracing shellfish contaminated with PSP-toxins.

    PubMed

    Wong, Chun-Kwan; Hung, Patricia; Ng, Henry C C; Lee, Siu-Yuen; Kam, Kai-Man

    2011-11-01

    Paralytic shellfish poisoning (PSP) is one of the most lethal biotoxin-induced diseases worldwide, which may pose serious public health threat and potential devastating economic damage on fisheries industry in the affected region(s). To prevent the importation of PSP contaminated shellfish to a community, detailed documentation on the supply chain and routine surveillance systems are, in principle, crucial measures to protect people from this intoxication. However, difficulties have always been encountered on the traceability of the source/origin of contaminated shellfish. In the present study, we reported the potential application of PSP-toxins profiles with similarity analysis that can be used to identify epidemiological linkage between shellfish samples collected from markets and patients during a PSP outbreak. PSP-toxins were identified and quantified by ion-pair chromatographic separation followed by post-column oxidation to fluorescent imino purine derivatives. Samples from a PSP incident and other surveillance samples collected in our past 7-year record were also compared for their similarity in PSP-toxins profiles patterns. Molar distributions (nmol%) of 10 PSP-toxins were analyzed by Unweighted Pair Group Method with Arithmetric averages (UPGMA). Three prominent clusters emerged with similarity levels reaching over 80% for each, suggesting that each group of samples probably originated from a same source/batch. The PSP-toxins profiles and toxicities determined from surveillance samples could provide premonitory clues on the occurrences of PSP incident and outbreak with corresponding toxin profiles in the later time. Due to species-specific characteristics of PSP-toxins composition and profile in shellfish under varieties of environmental and physiological conditions, PSP-toxins profile can be a specific and useful biochemical indicator for tracing PSP contaminated shellfish provided that spatio-temporal occurrence patterns of toxins profiles are available

  15. SVM-Based Prediction of Propeptide Cleavage Sites in Spider Toxins Identifies Toxin Innovation in an Australian Tarantula

    PubMed Central

    Wong, Emily S. W.; Hardy, Margaret C.; Wood, David; Bailey, Timothy; King, Glenn F.

    2013-01-01

    Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the Spider

  16. Foodborne toxins of marine origin: ciguatera.

    PubMed

    Juranovic, L R; Park, D L

    1991-01-01

    Ciguatera poisoning has long been recognized as a serious problem in the tropical and subtropical regions of the world. Due to international and interstate commerce and tourist travel the phenomenon is spreading to other parts of the globe. Various species of fish (surgeonfish, snapper, grouper, barracuda, jack, amberjack among others) have been implicated in this type of poisoning. These fish accumulate toxins in their flesh and viscera through the consumption of smaller fish that have been previously contaminated by feeding on toxic dinoflagellates. The most probable source of ciguatera is thought to be the benthic microorganism, Gambierdiscus toxicus, which produces both CTX and MTX, but other species of dinoflagellates such as Prorocentrum lima may also contribute with secondary toxins associated with the disease. Potentially ciguatoxic dinoflagellates have been isolated, cultured under laboratory conditions and dinoflagellate growth requirements as well as some factors affecting toxin production have been determined. Also, data from their ecological environment have been accumulated in an attempt to reveal a relationship with the epidemiology of ciguatera outbreaks. Several bioassays have been employed to determine the ciguatoxicity of fish. Cats have been used due to their sensitivity, but regurgitation has made dosage information difficult to obtain. Mongooses have also been used but they often carry parasitic and other type of diseases which complicate the bioassay. Mice have been used more commonly; they offer a more reliable model, can be easily housed, readily are dosed in several ways, and manifest diverse symptoms similar to human intoxications; but the amount of toxic extract needed, time consumed, complicated extraction techniques, and instrumentation involved limit the use of this assay commercially. Other bioassays have been explored including the brine shrimp, chicken, mosquito, crayfish nerve cord, guinea pig ileum, guinea pig atrium, and other

  17. Magnetic Low-Friction Track

    NASA Astrophysics Data System (ADS)

    Paetkau, Mark; Bahniwal, Manpreet; Gamblen, James

    2008-05-01

    The standard low-friction tracks used to test Newton's laws are the air track and the low-friction cart track. Both are commercially available and provide low-friction environments to test various physics concepts. At a recent science fair, one of the authors (JG) presented a magnetically levitated cart and track. A literature search found no previous testing of magnetically levitated carts. This paper compares a magnetically levitated cart against the two standard low-friction tracks.

  18. Adsorption of goethite onto quartz and kaolinite

    USGS Publications Warehouse

    Goldberg, M.C.; Weiner, Eugene R.; Boymel, P.M.

    1984-01-01

    The adsorption of colloidal goethite onto quartz and kaolinite substrates has been studied as a function of pH and NaCl concentration. Goethite adsorption was measured quantitatively by Fourier-transform infrared spectroscopy. The results indicate that adsorption onto both substrates is due primarily to coulombic forces; however, the pH dependence of adsorption is very different for the two substrates. This is explained by the fact that the surface charge on quartz is entirely pH-dependent, while kaolinite has surface faces which carry a permanent negative charge. Adsorption of goethite on to kaolinite increases markedly with increasing NaCl concentration, while adsorption onto quartz is relatively independent of NaCl concentration. This can be explained by the influence of NaCl concentration upon the development of surface charge on the substrates. A method is described for separating surface-bound goethite from free goethite.

  19. Adsorption of octylamine on titanium dioxide

    NASA Astrophysics Data System (ADS)

    Siwińska, Daria; Kołodziejczak-Radzimska, Agnieszka; Krysztafkiewicz, Andrzej; Jesionowski, Teofil

    2009-05-01

    Processes of adsorption and desorption of a model active substance (octylamine) on the surface of unmodified titanium dioxide (E 171) have been performed. The effects of concentration of octylamine and time of the process on the character of adsorption have been studied and the efficiency of the adsorption/desorption has been determined. The samples obtained have been studied by X-ray diffraction. The nitrogen adsorption/desorption isotherms, particle size distribution and absorption capacities of water, dibutyl phthalate and paraffin oil have been determined. The efficiency of octylamine adsorption on the surface of the titanium dioxide has been found positively correlated with the concentration of octylamine in the initial solution. The desorption of octylamine has decreased with increasing concentration of this compound adsorbed. For octylamine in low concentrations the physical adsorption has been found to dominate, which is desirable when using TiO 2 in the production of pharmaceuticals.

  20. Structural Insights into Bacillus thuringiensis Cry, Cyt and Parasporin Toxins

    PubMed Central

    Xu, Chengchen; Wang, Bi-Cheng; Yu, Ziniu; Sun, Ming

    2014-01-01

    Since the first X-ray structure of Cry3Aa was revealed in 1991, numerous structures of B. thuringiensis toxins have been determined and published. In recent years, functional studies on the mode of action and resistance mechanism have been proposed, which notably promoted the developments of biological insecticides and insect-resistant transgenic crops. With the exploration of known pore-forming toxins (PFTs) structures, similarities between PFTs and B. thuringiensis toxins have provided great insights into receptor binding interactions and conformational changes from water-soluble to membrane pore-forming state of B. thuringiensis toxins. This review mainly focuses on the latest discoveries of the toxin working mechanism, with the emphasis on structural related progress. Based on the structural features, B. thuringiensis Cry, Cyt and parasporin toxins could be divided into three categories: three-domain type α-PFTs, Cyt toxin type β-PFTs and aerolysin type β-PFTs. Structures from each group are elucidated and discussed in relation to the latest data, respectively. PMID:25229189

  1. Cholera Toxin and Cell Growth: Role of Membrane Gangliosides

    PubMed Central

    Hollenberg, Morley D.; Fishman, Peter H.; Bennett, Vann; Cuatrecasas, Pedro

    1974-01-01

    The binding of cholera toxin to three transformed mouse cell lines derived from the same parent strain, and the effects of the toxin on DNA synthesis and adenylate cyclase activity, vary in parallel with the ganglioside composition of the cells. TAL/N cells of early passage, which contain large quantities of gangliosides GM3, GM2, GM1, and GDla, as well as the glycosyltransferases necessary for the synthesis of these gangliosides, bind the most cholera toxin and are the most sensitive to its action. TAL/N cells of later passage, which lack chemically detectable GM1 and GDla and which have no UDP-Gal:GM2 galactosyltransferase activity, are intermediate in binding and response to the toxin. SVS AL/N cells, which lack GM2 in addition to GM1 and GDla and which have little detectable UDP-GalNAc:GM3N-acetylgalactosaminyltransferase activity, bind the least amount of toxin. The SVS AL/N cells are the least responsive to inhibition of DNA synthesis and stimulation of adenylate cyclase activity by cholera toxin. Gangliosides (especially GM1), which appear to be the natural membrane receptors for cholera toxin, may normally have important roles in the regulation of cell growth and cAMP-mediated responses. PMID:4530298

  2. Identification and Characterization of Clostridium sordellii Toxin Gene Regulator

    PubMed Central

    Sirigi Reddy, Apoorva Reddy; Girinathan, Brintha Parasumanna; Zapotocny, Ryan

    2013-01-01

    Toxigenic Clostridium sordellii causes uncommon but highly lethal infections in humans and animals. Recently, an increased incidence of C. sordellii infections has been reported in women undergoing obstetric interventions. Pathogenic strains of C. sordellii produce numerous virulence factors, including sordellilysin, phospholipase, neuraminidase, and two large clostridial glucosylating toxins, TcsL and TcsH. Recent studies have demonstrated that TcsL toxin is an essential virulence factor for the pathogenicity of C. sordellii. In this study, we identified and characterized TcsR as the toxin gene (tcsL) regulator in C. sordellii. High-throughput sequencing of two C. sordellii strains revealed that tcsR lies within a genomic region that encodes TcsL, TcsH, and TcsE, a putative holin. By using ClosTron technology, we inactivated the tcsR gene in strain ATCC 9714. Toxin production and tcsL transcription were decreased in the tcsR mutant strain. However, the complemented tcsR mutant produced large amounts of toxins, similar to the parental strain. Expression of the Clostridium difficile toxin gene regulator tcdR also restored toxin production to the C. sordellii tcsR mutant, showing that these sigma factors are functionally interchangeable. PMID:23873908

  3. Microcystis aeruginosa toxin: cell culture toxicity, hemolysis, and mutagenicity assays.

    PubMed Central

    Grabow, W O; Du Randt, W C; Prozesky, O W; Scott, W E

    1982-01-01

    Crude toxin was prepared by lyophilization and extraction of toxic Microcystis aeruginosa from four natural sources and a unicellular laboratory culture. The responses of cultures of liver (Mahlavu and PCL/PRF/5), lung (MRC-5), cervix (HeLa), ovary (CHO-K1), and kidney (BGM, MA-104, and Vero) cell lines to these preparations did not differ significantly from one another, indicating that toxicity was not specific for liver cells. The results of a trypan blue staining test showed that the toxin disrupted cell membrane permeability within a few minutes. Human, mouse, rat, sheep, and Muscovy duck erythrocytes were also lysed within a few minutes. Hemolysis was temperature dependent, and the reaction seemed to follow first-order kinetics. Escherichia coli, Streptococcus faecalis, and Tetrahymena pyriformis were not significantly affected by the toxin. The toxin yielded negative results in Ames/Salmonella mutagenicity assays. Microtiter cell culture, trypan blue, and hemolysis assays for Microcystis toxin are described. The effect of the toxin on mammalian cell cultures was characterized by extensive disintegration of cells and was distinguishable from the effects of E. coli enterotoxin, toxic chemicals, and pesticides. A possible reason for the acute lethal effect of Microcystis toxin, based on cytolytic activity, is discussed. Images PMID:6808921

  4. Toxin Diversity Revealed by a Transcriptomic Study of Ornithoctonus huwena

    PubMed Central

    He, Quanze; Liu, Jinyan; Luo, Ji; Zhu, Li; Lu, Shanshan; Huang, Pengfei; Chen, Xinyi; Zeng, Xiongzhi; Liang, Songping

    2014-01-01

    Spider venom comprises a mixture of compounds with diverse biological activities, which are used to capture prey and defend against predators. The peptide components bind a broad range of cellular targets with high affinity and selectivity, and appear to have remarkable structural diversity. Although spider venoms have been intensively investigated over the past few decades, venomic strategies to date have generally focused on high-abundance peptides. In addition, the lack of complete spider genomes or representative cDNA libraries has presented significant limitations for researchers interested in molecular diversity and understanding the genetic mechanisms of toxin evolution. In the present study, second-generation sequencing technologies, combined with proteomic analysis, were applied to determine the diverse peptide toxins in venom of the Chinese bird spider Ornithoctonus huwena. In total, 626 toxin precursor sequences were retrieved from transcriptomic data. All toxin precursors clustered into 16 gene superfamilies, which included six novel superfamilies and six novel cysteine patterns. A surprisingly high number of hypermutations and fragment insertions/deletions were detected, which accounted for the majority of toxin gene sequences with low-level expression. These mutations contribute to the formation of diverse cysteine patterns and highly variable isoforms. Furthermore, intraspecific venom variability, in combination with variable transcripts and peptide processing, contributes to the hypervariability of toxins in venoms, and associated rapid and adaptive evolution of toxins for prey capture and defense. PMID:24949878

  5. Structural Basis of Clostridium perfringens Toxin Complex Formation

    SciTech Connect

    Adams,J.; Gregg, K.; Bayer, E.; Boraston, A.; Smith, S.

    2008-01-01

    The virulent properties of the common human and livestock pathogen Clostridium perfringens are attributable to a formidable battery of toxins. Among these are a number of large and highly modular carbohydrate-active enzymes, including the {mu}-toxin and sialidases, whose catalytic properties are consistent with degradation of the mucosal layer of the human gut, glycosaminoglycans, and other cellular glycans found throughout the body. The conservation of noncatalytic ancillary modules among these enzymes suggests they make significant contributions to the overall functionality of the toxins. Here, we describe the structural basis of an ultra-tight interaction (Ka = 1.44 x 1011 M-1) between the X82 and dockerin modules, which are found throughout numerous C. perfringens carbohydrate-active enzymes. Extensive hydrogen-bonding and van der Waals contacts between the X82 and dockerin modules give rise to the observed high affinity. The {mu}-toxin dockerin module in this complex is positioned {approx}180 relative to the orientation of the dockerin modules on the cohesin module surface within cellulolytic complexes. These observations represent a unique property of these clostridial toxins whereby they can associate into large, noncovalent multitoxin complexes that allow potentiation of the activities of the individual toxins by combining complementary toxin specificities.

  6. Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells.

    PubMed

    Singh, Y; Leppla, S H; Bhatnagar, R; Friedlander, A M

    1989-07-01

    Anthrax lethal toxin consists of two separate proteins, protective antigen and lethal factor (LF). Certain macrophages and a mouse macrophage-like cell line, J774A.1, are lysed by low concentrations of lethal toxin. In contrast, another macrophage cell line, IC-21, and all other cell types tested were resistant to this toxin. To discover the basis for this difference, each step in the intoxication process was examined. No differences between sensitive and resistant cells were found in receptor binding or proteolytic activation of protective antigen, steps that are required prior to LF binding. To determine whether resistance results from a defect in translocation to the cytosol, we introduced LF into J774A.1 and IC-21 cells and a nonmacrophage cell line (L6 myoblast) by osmotic lysis of pinocytic vesicles. Only J774A.1 cells were lysed; no effect was observed in IC-21 and L6 cells. These results suggest that resistant cells either lack the intracellular target of LF or fail to process LF to an active form. The relatively low potency of LF introduced into J774A.1 cells by osmotic lysis suggests that protective antigen may also be required at a stage subsequent to endocytosis. PMID:2500434

  7. Metabolism of the Fusarium Mycotoxins T-2 Toxin and HT-2 Toxin in Wheat.

    PubMed

    Nathanail, Alexis V; Varga, Elisabeth; Meng-Reiterer, Jacqueline; Bueschl, Christoph; Michlmayr, Herbert; Malachova, Alexandra; Fruhmann, Philipp; Jestoi, Marika; Peltonen, Kimmo; Adam, Gerhard; Lemmens, Marc; Schuhmacher, Rainer; Berthiller, Franz

    2015-09-01

    To investigate the metabolic fate of HT-2 toxin (HT2) and T-2 toxin (T2) in wheat (Triticum aestivum L.), an untargeted metabolomics study utilizing stable isotopic labeling and liquid chromatography-high resolution mass spectrometry was performed. In total, 11 HT2 and 12 T2 derived in planta biotransformation products were annotated putatively. In addition to previously reported mono- and diglucosylated forms of HT2, evidence for the formation of HT2-malonyl-glucoside and feruloyl-T2, as well as acetylation and deacetylation products in wheat was obtained for the first time. To monitor the kinetics of metabolite formation, a time course experiment was conducted involving the Fusarium head blight susceptible variety Remus and the resistant cultivar CM-82036. Biotransformation reactions were observed already at the earliest tested time point (6 h after treatment), and formed metabolites showed different kinetic profiles. After ripening, less than 15% of the toxins added to the plants were determined to be unmetabolized. PMID:26278508

  8. Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications.

    PubMed

    Yeo, Chew Chieng; Abu Bakar, Fauziah; Chan, Wai Ting; Espinosa, Manuel; Harikrishna, Jennifer Ann

    2016-02-01

    Toxin-antitoxin (TA) systems are found in nearly all prokaryotic genomes and usually consist of a pair of co-transcribed genes, one of which encodes a stable toxin and the other, its cognate labile antitoxin. Certain environmental and physiological cues trigger the degradation of the antitoxin, causing activation of the toxin, leading either to the death or stasis of the host cell. TA systems have a variety of functions in the bacterial cell, including acting as mediators of programmed cell death, the induction of a dormant state known as persistence and the stable maintenance of plasmids and other mobile genetic elements. Some bacterial TA systems are functional when expressed in eukaryotic cells and this has led to several innovative applications, which are the subject of this review. Here, we look at how bacterial TA systems have been utilized for the genetic manipulation of yeasts and other eukaryotes, for the containment of genetically modified organisms, and for the engineering of high expression eukaryotic cell lines. We also examine how TA systems have been adopted as an important tool in developmental biology research for the ablation of specific cells and the potential for utility of TA systems in antiviral and anticancer gene therapies. PMID:26907343

  9. Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications

    PubMed Central

    Yeo, Chew Chieng; Abu Bakar, Fauziah; Chan, Wai Ting; Espinosa, Manuel; Harikrishna, Jennifer Ann

    2016-01-01

    Toxin-antitoxin (TA) systems are found in nearly all prokaryotic genomes and usually consist of a pair of co-transcribed genes, one of which encodes a stable toxin and the other, its cognate labile antitoxin. Certain environmental and physiological cues trigger the degradation of the antitoxin, causing activation of the toxin, leading either to the death or stasis of the host cell. TA systems have a variety of functions in the bacterial cell, including acting as mediators of programmed cell death, the induction of a dormant state known as persistence and the stable maintenance of plasmids and other mobile genetic elements. Some bacterial TA systems are functional when expressed in eukaryotic cells and this has led to several innovative applications, which are the subject of this review. Here, we look at how bacterial TA systems have been utilized for the genetic manipulation of yeasts and other eukaryotes, for the containment of genetically modified organisms, and for the engineering of high expression eukaryotic cell lines. We also examine how TA systems have been adopted as an important tool in developmental biology research for the ablation of specific cells and the potential for utility of TA systems in antiviral and anticancer gene therapies. PMID:26907343

  10. Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery.

    PubMed

    Cataudella, Ilaria; Trusina, Ala; Sneppen, Kim; Gerdes, Kenn; Mitarai, Namiko

    2012-08-01

    Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called 'conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli. We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated. PMID:22495927

  11. Human intoxication with paralytic shellfish toxins: clinical parameters and toxin analysis in plasma and urine.

    PubMed

    García, Carlos; Lagos, Marcelo; Truan, Dominique; Lattes, Karinna; Véjar, Omar; Chamorro, Beatriz; Iglesias, Verónica; Andrinolo, Darío; Lagos, Néstor

    2005-01-01

    This study reports the data recorded from four patients intoxicated with shellfish during the summer 2002, after consuming ribbed mussels (Aulacomya ater) with paralytic shellfish toxin contents of 8,066 +/- 61.37 microg/100 gr of tissue. Data associated with clinical variables and paralytic shellfish toxins analysis in plasma and urine of the intoxicated patients are shown. For this purpose, the evolution of respiratory frequency, arterial blood pressure and heart rate of the poisoned patients were followed and recorded. The clinical treatment to reach a clinically stable condition and return to normal physiological parameters was a combination of hydration with saline solution supplemented with Dobutamine (vasoactive drug), Furosemide (diuretic) and Ranitidine (inhibitor of acid secretion). The physiological condition of patients began to improve after four hours of clinical treatment, and a stable condition was reached between 12 to 24 hours. The HPLC-FLD analysis showed only the GTX3/GTX2 epimers in the blood and urine samples. Also, these epimers were the only paralytic shellfish toxins found in the shellfish extract sample. PMID:16238098

  12. Yeast killer plasmid mutations affecting toxin secretion and activity and toxin immunity function

    SciTech Connect

    Bussey, H.; Sacks, W.; Galley, D.; Saville, D.

    1982-04-01

    M double-stranded RNA (MdsRNA) plasmid mutants were obtained by mutagenesis and screening of a diploid killer culture partially heat cured of the plasmid, so that a high proportion of the cells could be expected to have only one M plasmid. Mutants with neutral (K/sup -/), immune (R/sup +/) or suicide (killer (K/sup +/), sensitive (R/sup -/)) phenotypes were examined. All mutants became K/sup -/ R/sup -/ sensitives on heat curing of the MdsRNA plasmid, and showed cytoplasmic inheritance by random spore analysis. In some cases, M plasmid mutations were indicated by altered mobility of the MdsRNA by agarose gel electrophoresis or by altered size of in vitro translation products from denatured dsRNA. Neutral mutants were of two types: nonsecretors of the toxin protein or secretors of an inactive toxin. Of three neutral nonsecretors examined, one (NLP-1), probably a nonsense mutation, made a smaller protoxin precursor in vitro and in vivo, and two made full-size protoxin molecules. The in vivo protoxin of 43,000 molecular weight was unstable in the wild type and kinetically showed a precursor product relationship to the processed, secreted 11,000-molecular-weight toxin. In one nonsecretor (N1), the protoxin appeared more stable in a pulse-chase experiment, and could be altered in a recognition site required for protein processing.

  13. Phylogenetic analysis of Shiga toxin 1 and Shiga toxin 2 genes associated with disease outbreaks

    PubMed Central

    Lee, James E; Reed, Junelina; Shields, Malcolm S; Spiegel, Kathleen M; Farrell, Larry D; Sheridan, Peter P

    2007-01-01

    Background Shiga toxins 1 and 2 (Stx1 and Stx2) are bacteriophage-encoded proteins that have been associated with hemorrhagic colitis, hemolytic uremic syndrome and other severe disease conditions. Stx1 and Stx2 are genetically and immunologically distinct but share the same compound toxin structure, method of entry and enzymatic function. Results Phylogenetic analysis was performed using Stx1 and Stx2 amino acid and nucleotide sequences from 41 strains of Escherichia coli, along with known stx sequences available from GenBank. The analysis confirmed the Stx1 and Stx2 divergence, and showed that there is generally more sequence variation among stx2 genes than stx1. The phylograms showed generally flat topologies among our strains' stx1 and stx2 genes. In the stx2 gene, 39.5% of the amino acid sites display very low nonsynonymous to synonymous substitution ratios. Conclusion The stx1 and stx2 genes used in this phylogenetic study show sequence conservation with no significant divergence with respect to place or time. These data could indicate that Shiga toxins are experiencing purifying selection. PMID:18053224

  14. International Typing Study of Toxin A-Negative, Toxin B-Positive Clostridium difficile Variants

    PubMed Central

    Johnson, Stuart; Sambol, Susan P.; Brazier, Jon S.; Delmée, Michel; Avesani, V.; Merrigan, Michelle M.; Gerding, Dale N.

    2003-01-01

    Clinically important strains of Clostridium difficile that do not produce toxin A but produce toxin B and are cytotoxic (A−/B+) have been reported from multiple countries. In order to compare the relatedness of these strains, we typed 23 A−/B+ C. difficile isolates from the United Kingdom (6 isolates), Belgium (11 isolates), and the United States (6 isolates) by three well-described typing methods. Restriction endonuclease analysis (REA), PCR ribotyping, and serogrouping differentiated 11, 4, and 3 different strain types, respectively. Twenty-one of the 23 A−/B+ variants had a 1.8-kb truncation of the toxin A gene characteristic of toxinotype VIII strains; 20 of the 21 toxinotype VIII-like strains were PCR type 17. PCR type 17 isolates could be differentiated into two separate strain groups by serogrouping and by REA. REA further discriminated these isolates into eight subgroups (REA types). PCR type 17-serogroup F-REA group CF isolates were recovered from all three countries, and one specific REA type, CF4, was recovered from patients with C. difficile disease in the United Kingdom and the United States. C. difficile A−/B+ variants of apparent clonal origin are widely distributed in Europe and North America. PMID:12682143

  15. Metabolism of the Fusarium Mycotoxins T-2 Toxin and HT-2 Toxin in Wheat

    PubMed Central

    2015-01-01

    To investigate the metabolic fate of HT-2 toxin (HT2) and T-2 toxin (T2) in wheat (Triticum aestivum L.), an untargeted metabolomics study utilizing stable isotopic labeling and liquid chromatography–high resolution mass spectrometry was performed. In total, 11 HT2 and 12 T2 derived in planta biotransformation products were annotated putatively. In addition to previously reported mono- and diglucosylated forms of HT2, evidence for the formation of HT2-malonyl-glucoside and feruloyl-T2, as well as acetylation and deacetylation products in wheat was obtained for the first time. To monitor the kinetics of metabolite formation, a time course experiment was conducted involving the Fusarium head blight susceptible variety Remus and the resistant cultivar CM-82036. Biotransformation reactions were observed already at the earliest tested time point (6 h after treatment), and formed metabolites showed different kinetic profiles. After ripening, less than 15% of the toxins added to the plants were determined to be unmetabolized. PMID:26278508

  16. Adsorption of organic molecules on silica surface.

    PubMed

    Parida, Sudam K; Dash, Sukalyan; Patel, Sabita; Mishra, B K

    2006-09-13

    The adsorption behaviour of various organic adsorbates on silica surface is reviewed. Most of the structural information on silica is obtained from IR spectral data and from the characteristics of water present at the silica surface. Silica surface is generally embedded with hydroxy groups and ethereal linkages, and hence considered to have a negative charged surface prone to adsorption of electron deficient species. Adsorption isotherms of the adsorbates delineate the nature of binding of the adsorbate with silica. Aromatic compounds are found to involve the pi-cloud in hydrogen bonding with silanol OH group during adsorption. Cationic and nonionic surfactants adsorb on silica surface involving hydrogen bonding. Sometimes, a polar part of the surfactants also contributes to the adsorption process. Styryl pyridinium dyes are found to anchor on silica surface in flat-on position. On modification of the silica by treating with alkali, the adsorption behaviour of cationic surfactant or polyethylene glycol changes due to change in the characteristics of silica or modified silica surface. In case of PEG-modified silica, adsolubilization of the adsorbate is observed. By using a modified adsorption equation, hemimicellization is proposed for these dyes. Adsorptions of some natural macromolecules like proteins and nucleic acids are investigated to study the hydrophobic and hydrophilic binding sites of silica. Artificial macromolecules like synthetic polymers are found to be adsorbed on silica surface due to the interaction of the multifunctional groups of the polymers with silanols. Preferential adsorption of polar adsorbates is observed in case of adsorbate mixtures. When surfactant mixtures are considered to study competitive adsorption on silica surface, critical micelle concentration of individual surfactant also contributes to the adsorption isotherm. The structural study of adsorbed surface and the thermodynamics of adsorption are given some importance in this review

  17. Volumetric interpretation of protein adsorption kinetics

    NASA Astrophysics Data System (ADS)

    Barnthip, Naris

    Protein adsorption is believed to be a very important factor ultimately leading to a predictive basis for biomaterials design and improving biocompatibility. Standard adsorption theories are modified to accommodate experimental observations. Adsorption from single-protein solutions and competitive adsorption from binary solutions are mainly considered. The standard solution-depletion method of measuring protein adsorption is implemented with SDS-gel electrophoresis as a multiplexing, separation-and-quantification tool to measure protein adsorption to hydrophobic octyl sepharose (OS) adsorbent particles. Standard radiometric methods have also been used as a further check on the electrophoresis method mentioned above for purified-protein cases. Experimental results are interpreted in terms of an alternative kinetic model called volumetric interpretation of protein adsorption. A partitioning process between bulk solution and a three-dimensional interphase region that separates bulk solution from the physical adsorbent surface is the concept of the model. Protein molecules rapidly diffuse into an inflating interphase that is spontaneously formed by bringing a protein solution into contact with a physical surface, then follows by rearrangement of proteins within this interphase to achieve the maximum interphase concentration (dictated by energetics of interphase dehydration) within the thinnest (lowest volume) interphase possible. An important role of water in protein adsorption is emphasized and supported by this model. The fundamental aspects including the reversibility/irreversibility of protein adsorption, the multilayer adsorption, the applicability of thermodynamic/computational models, the capacity of protein adsorption, and the mechanism of so called Vroman effect are discussed and compared to the conventional theories. Superhydrophobic effect on the adsorption of human serum albumin is also examined.

  18. Toxin-Antitoxin Systems in Clinical Pathogens.

    PubMed

    Fernández-García, Laura; Blasco, Lucia; Lopez, Maria; Bou, German; García-Contreras, Rodolfo; Wood, Thomas; Tomas, María

    2016-01-01

    Toxin-antitoxin (TA) systems are prevalent in bacteria and archaea. Although not essential for normal cell growth, TA systems are implicated in multiple cellular functions associated with survival under stress conditions. Clinical strains of bacteria are currently causing major human health problems as a result of their multidrug resistance, persistence and strong pathogenicity. Here, we present a review of the TA systems described to date and their biological role in human pathogens belonging to the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and others of clinical relevance (Escherichia coli, Burkholderia spp., Streptococcus spp. and Mycobacterium tuberculosis). Better understanding of the mechanisms of action of TA systems will enable the development of new lines of treatment for infections caused by the above-mentioned pathogens. PMID:27447671

  19. Herbal Compounds and Toxins Modulating TRP Channels

    PubMed Central

    Vriens, Joris; Nilius, Bernd; Vennekens, Rudi

    2008-01-01

    Although the benefits are sometimes obvious, traditional or herbal medicine is regarded with skepticism, because the mechanism through which plant compounds exert their powers are largely elusive. Recent studies have shown however that many of these plant compounds interact with specific ion channels and thereby modulate the sensing mechanism of the human body. Especially members of the Transient Receptor Potential (TRP) channels have drawn large attention lately as the receptors for plant-derived compounds such as capsaicin and menthol. TRP channels constitute a large and diverse family of channel proteins that can serve as versatile sensors that allow individual cells and entire organisms to detect changes in their environment. For this family, a striking number of empirical views have turned into mechanism-based actions of natural compounds. In this review we will give an overview of herbal compounds and toxins, which modulate TRP channels. PMID:19305789

  20. [Use of botulinum toxin for pain therapy].

    PubMed

    Nodera, Hiroyuki

    2008-05-01

    Preventive measures are necessary against contraction of botulism through food intake or due to other factors because the botulinum neurotoxin (BoNT) is one of the strongest toxins. Despite this, given its therapeutic utility in the controll of neuromuscular transmission, BoNT has been utilized to treat diseases related to muscular hyperactivity, such as dystonia and spasticity. Furthermore, it has been recognized that BoNT is also useful in controlling the neurotransmitter release of sensory and autonomic nerve terminals as well. This paper reviews the recent progress in the therapeutic use of BoNT in pain management, for example, in condition such as migraine, myofascial pain syndrome, pelvic pain, and interstitial cystitis. PMID:18516972

  1. Nephrotoxic mechanisms of drugs and environmental toxins

    SciTech Connect

    Porter, G.A.

    1982-01-01

    This book contains 39 contributions divided into five sections each with its own editor and introductory chapter. The first section of nine chapters is concerned with the pathophysiology of acute renal failure. The second section is concerned with the growing problem of renal failure due to the use of antimicrobial agents such as the aminoglycosides. The various causes of tubulointerstitial nephropathy, notably analgesic drugs and environmental toxins such as mycotoxins and lead, are covered in the third section. Environmental and industrial nephrotoxins, such as cadmium, and halogenated aliphatic hydrocarbons, such as chloroform, are the subject of the fourth section. The last section of nine chapters is concerned mainly with a relatively new area of research into immunological mechanisms of nephrotoxicity and the evidence that drugs and other environmental chemicals can serve as antigens for immune complex formation.

  2. Toxin-Antitoxin Systems in Clinical Pathogens

    PubMed Central

    Fernández-García, Laura; Blasco, Lucia; Lopez, Maria; Bou, German; García-Contreras, Rodolfo; Wood, Thomas; Tomas, María

    2016-01-01

    Toxin-antitoxin (TA) systems are prevalent in bacteria and archaea. Although not essential for normal cell growth, TA systems are implicated in multiple cellular functions associated with survival under stress conditions. Clinical strains of bacteria are currently causing major human health problems as a result of their multidrug resistance, persistence and strong pathogenicity. Here, we present a review of the TA systems described to date and their biological role in human pathogens belonging to the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and others of clinical relevance (Escherichia coli, Burkholderia spp., Streptococcus spp. and Mycobacterium tuberculosis). Better understanding of the mechanisms of action of TA systems will enable the development of new lines of treatment for infections caused by the above-mentioned pathogens. PMID:27447671

  3. Botulinum toxin drugs: brief history and outlook.

    PubMed

    Dressler, D

    2016-03-01

    The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur. PMID:26559824

  4. Ozone adsorption on carbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Chassard, Guillaume; Gosselin, Sylvie; Visez, Nicolas; Petitprez, Denis

    2014-05-01

    Carbonaceous particles produced by incomplete combustion or thermal decomposition of hydrocarbons are ubiquitous in the atmosphere. On these particles are adsorbed hundreds of chemical species. Those of great concern to health are polycyclic aromatic hydrocarbons (PAHs). During atmospheric transport, particulate PAHs react with gaseous oxidants. The induced chemical transformations may change toxicity and hygroscopicity of these potentially inhalable particles. The interaction between ozone and carbon particles has been extensively investigated in literature. However ozone adsorption and surface reaction mechanisms are still ambiguous. Some studies described a fast catalytic decomposition of ozone initiated by an atomic oxygen chemisorption followed by a molecular oxygen release [1-3]. Others suggested a reversible ozone adsorption according to Langmuir-type behaviour [4,5]. The aim of this present study is a better understanding of ozone interaction with carbon surfaces. An aerosol of carbon nanoparticles was generated by flowing synthetic air in a glass tube containing pure carbon (primary particles < 50 nm), under magnetic stirring. The aerosol was then mixed with ozone in an aerosol flow tube. Ozone uptake experiments were performed with different particles concentrations with a fixed ozone concentration. The influence of several factors on kinetics was examined: initial ozone concentration, particle size (50 nm ≤ Dp ≤ 200 nm) and competitive adsorption (with probe molecule and water). The effect of initial ozone concentration was first studied. Accordingly to literature, it has been observed that the number of gas-phase ozone molecules lost per unit particle surface area tends towards a plateau for high ozone concentration suggesting a reversible ozone adsorption according to a Langmuir mechanism. We calculated the initial reaction probability between O3 and carbon particles.An initial uptake coefficient of 1.10-4 was obtained. Similar experiments were

  5. Track recording plastic compositions

    NASA Technical Reports Server (NTRS)

    Tarle, Gregory (Inventor)

    1983-01-01

    Improved nuclear track recording plastic compositions are provided which exhibit greatly decreased surface roughness when etched to produce visible tracks of energetic nuclear particles which have passed into and/or through said plastic. The improved compositions incorporate a small quantity of a phthalic acid ester into the major plastic component which is derived from the polymerization of monomeric di-ethylene glycol bis allyl carbonate. Di-substituted phthalic acid esters are preferred as the added component, with the further perference that the ester substituent has a chain length of 2 or more carbon atoms. The inclusion of the phthalic acid ester to an extent of from about 1-2% by weight of the plastic compositions is sufficient to drastically reduce the surface roughness ordinarily produced when the track recording plastic is contacted by etchants.

  6. Tracks to therapy

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.

    1999-01-01

    Studies of the structure of particle tracks have led to models of track effects based on radial dose and radiobiological target theory that have been very successful in describing and predicting track effects in physical, chemical, and biological systems. For describing mammalian cellular inactivation two inactivation modes are required, called gamma-kill and ion-kill, the first due to synergistic effects of delta rays from adjacent ion paths thus resembling the effects from gamma rays, and the second to the effects of single ion transits through a cell nucleus. The ion-kill effect is more severe, where the fraction of cells experiencing ion kill is responsible for a decrease in the oxygen enhancement ratio, and an increase in relative biological effectiveness, but these are accompanied by loss of repair, hence to a reduction in the efficiency of fractionation in high LET therapy, as shown by our calculations for radiobiological effects in the "spread out Bragg Peak".

  7. Controlled Document Tracking Software

    1992-08-24

    MANTRACK is an automated, controlled document tracking system which does the following and reduces staff time required to perform these tasks: generates transmittal letters/receipts for every controlled copy issued (merged from a current distribution list), tracks the return of transmittal receipts, facilitates the check-in of the large number of transmittal receipts returned (using a barcode reader), generates a reminder list which prompts the cyclic review and evaluation of existing documents, generates overdue reminders for themore » return of past-due transmittal receipts, tracks the number of Procedure Change Directives (PCD) currently in effect for each procedure, generates and maintains current distribution lists for each document, generates a current table of contents when updates to the document (usually a procedure manual) are made.« less

  8. Developing a method to scale up production of solanapyrone toxins by Ascochyta rabiei

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ascochyta rabiei, the causal agent of Ascochyta blight of chickpea, produces solanapyrone toxins. The toxins may play a role in pathogenesis. In order to develop toxin assays for screening chickpea genotypes and to investigate the role of the toxins in developing the disease Ascochyta blight, a me...

  9. Anthrax Toxins in Context of Bacillus anthracis Spores and Spore Germination

    PubMed Central

    Cote, Christopher K.; Welkos, Susan L.

    2015-01-01

    The interaction of anthrax toxin or toxin components with B. anthracis spores has been demonstrated. Germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. In this review, we will summarize the work performed that has led to our understanding of toxin and spore interactions and discuss the complexities associated with these interactions. PMID:26287244

  10. Algal toxins alter copepod feeding behavior.

    PubMed

    Hong, Jiarong; Talapatra, Siddharth; Katz, Joseph; Tester, Patricia A; Waggett, Rebecca J; Place, Allen R

    2012-01-01

    Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod's feeding appendages-a "sampling beating" that has short durations (<100 ms) and involves little fluid entrainment and a longer duration "grazing beating" that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod's grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod's feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods. PMID:22629336

  11. Fast Compressive Tracking.

    PubMed

    Zhang, Kaihua; Zhang, Lei; Yang, Ming-Hsuan

    2014-10-01

    It is a challenging task to develop effective and efficient appearance models for robust object tracking due to factors such as pose variation, illumination change, occlusion, and motion blur. Existing online tracking algorithms often update models with samples from observations in recent frames. Despite much success has been demonstrated, numerous issues remain to be addressed. First, while these adaptive appearance models are data-dependent, there does not exist sufficient amount of data for online algorithms to learn at the outset. Second, online tracking algorithms often encounter the drift problems. As a result of self-taught learning, misaligned samples are likely to be added and degrade the appearance models. In this paper, we propose a simple yet effective and efficient tracking algorithm with an appearance model based on features extracted from a multiscale image feature space with data-independent basis. The proposed appearance model employs non-adaptive random projections that preserve the structure of the image feature space of objects. A very sparse measurement matrix is constructed to efficiently extract the features for the appearance model. We compress sample images of the foreground target and the background using the same sparse measurement matrix. The tracking task is formulated as a binary classification via a naive Bayes classifier with online update in the compressed domain. A coarse-to-fine search strategy is adopted to further reduce the computational complexity in the detection procedure. The proposed compressive tracking algorithm runs in real-time and performs favorably against state-of-the-art methods on challenging sequences in terms of efficiency, accuracy and robustness. PMID:26352631

  12. Adsorption of phenol on wood surfaces

    NASA Astrophysics Data System (ADS)

    Mamleeva, N. A.; Lunin, V. V.

    2016-03-01

    Adsorption of phenol on aspen and pine wood is investigated. It is shown that adsorption isotherms are described by the Langmuir model. The woods' specific surface areas and adsorption interaction constants are determined. It is found that the sorption of phenol on surfaces of aspen and pine is due to Van der Waals interactions ( S sp = 45 m2/godw for aspen and 85 m2/godw for pine). The difference between the adsorption characteristics is explained by properties of the wood samples' microstructures.

  13. Adsorption of water vapor on reservoir rocks

    SciTech Connect

    Not Available

    1993-07-01

    Progress is reported on: adsorption of water vapor on reservoir rocks; theoretical investigation of adsorption; estimation of adsorption parameters from transient experiments; transient adsorption experiment -- salinity and noncondensible gas effects; the physics of injection of water into, transport and storage of fluids within, and production of vapor from geothermal reservoirs; injection optimization at the Geysers Geothermal Field; a model to test multiwell data interpretation for heterogeneous reservoirs; earth tide effects on downhole pressure measurements; and a finite-difference model for free surface gravity drainage well test analysis.

  14. Adsorption interactions of humic acids with biocides

    NASA Astrophysics Data System (ADS)

    Mal'Tseva, E. V.; Ivanov, A. A.; Yudina, N. V.

    2009-11-01

    The chemical composition of humic acids from brown coal (Aldrich) was determined by element analysis, 13C NMR spectroscopy, and potentiometric titration. The adsorption ability of humic acids with different biocides (cyproconasol, propiconasol, tebuconasol, irgarol 1051, and DCOIT) was studied. The adsorption ability of a mixture of biocides in aqueous solutions was higher than that of the individual components. The limiting concentration of humic acids at which adsorption of biocides was maximum was determined. Adsorption constants were calculated by the Freundlich equation for each biocide in aqueous solution.

  15. Adsorption and isotopic fractionation of Xe

    NASA Technical Reports Server (NTRS)

    Bernatowicz, T. J.; Podosek, F. A.

    1986-01-01

    A theoretical description of the mechanisms of isotopic fractionation arising during adsorption of noble gases in a Henry's Law pressure regime is given. Experimental data on the isotopic composition of Xe adsorbed on activated charcoal in the temperature range 220 K to 350 K are presented. Both theoretical considerations and the experimental data indicate that equilibrium adsorption does not significantly alter the isotopic structure of adsorbed structure of adsorbed noble gases. Therefore, if adsorption is responsible for the elemental noble gas pattern in meteorites and the earth, the heavy noble gas isotopic fractionation between them must have been produced prior to and by a different process than equilibrium adsorption.

  16. Moisture adsorption in optical coatings

    NASA Technical Reports Server (NTRS)

    Macleod, H. Angus

    1988-01-01

    The thin film filter is a very large aperture component which is exceedingly useful because of its small size, flexibility and ease of mounting. Thin film components, however, do have defects of performance and especially of stability which can cause problems in systems, particularly where long-term measurements are being made. Of all of the problems, those associated with moisture absorption are the most serious. Moisture absorption occurs in the pore-shaped voids inherent in the columnar structure of the layers. Ion-assisted deposition is a promising technique for substantially reducing moisture adsorption effects in thin film structures.

  17. Charcoal/Nitrogen Adsorption Cryocooler

    NASA Technical Reports Server (NTRS)

    Bard, Steven

    1987-01-01

    Refrigerator with no wear-related moving parts produces 0.5 W of cooling at 118 K. When fully developed, refrigerator needs no electrical power, and life expectancy of more than 10 yr, operates unattended to cool sensitive infrared detectors for long periods. Only moving parts in adsorption cryocooler are check valves. As charcoal is cooled in canister, gas pressure drops, allowing inlet check valve to open and admit more nitrogen. When canister is heated, pressure rises, closing inlet valve and eventually opening outlet valve.

  18. Enthalpy of adsorption and isotherms for adsorption of naphthenic acid onto clays

    SciTech Connect

    Zou, L.; Han, B.; Yan, H.; Kasperski, K.L.; Xu, Y.; Hepler, L.G.

    1997-06-15

    The enthalpies of adsorption and the isotherms for adsorption of naphthenic acid onto Na-montmorillonite, Na-kaolinite, and Na-illite were studied by means of calorimetry and the static method at 298.15 K. The results show that the enthalpies of adsorption and saturated adsorption amounts of naphthenic acid on different clays change in the order Na-montmorillonite > Na-illite > Na-kaolinite. The interaction between naphthenic acid and clays is discussed.

  19. Hazardous waste tracking issues

    SciTech Connect

    Marvin, R. )

    1993-08-01

    The concept of cradle-to-grave oversight of hazardous waste was established in 1976 under RCRA. Since then, the multicopy Uniform Hazardous Waste Manifest has been a key component in the federal tracking system. The manifests ensure that generators, transporters and TSDFs maintain documentation of hazardous waste shipments. To a large extent, the tracking system has served its intended purpose; nevertheless, certain shortcomings exist. Anyone involved in shipping hazardous waste should be aware of the system's weaknesses and take appropriate measures to compensate for them.

  20. Automatic crack propagation tracking

    NASA Technical Reports Server (NTRS)

    Shephard, M. S.; Weidner, T. J.; Yehia, N. A. B.; Burd, G. S.

    1985-01-01

    A finite element based approach to fully automatic crack propagation tracking is presented. The procedure presented combines fully automatic mesh generation with linear fracture mechanics techniques in a geometrically based finite element code capable of automatically tracking cracks in two-dimensional domains. The automatic mesh generator employs the modified-quadtree technique. Crack propagation increment and direction are predicted using a modified maximum dilatational strain energy density criterion employing the numerical results obtained by meshes of quadratic displacement and singular crack tip finite elements. Example problems are included to demonstrate the procedure.

  1. Computationally efficient Bayesian tracking

    NASA Astrophysics Data System (ADS)

    Aughenbaugh, Jason; La Cour, Brian

    2012-06-01

    In this paper, we describe the progress we have achieved in developing a computationally efficient, grid-based Bayesian fusion tracking system. In our approach, the probability surface is represented by a collection of multidimensional polynomials, each computed adaptively on a grid of cells representing state space. Time evolution is performed using a hybrid particle/grid approach and knowledge of the grid structure, while sensor updates use a measurement-based sampling method with a Delaunay triangulation. We present an application of this system to the problem of tracking a submarine target using a field of active and passive sonar buoys.

  2. Health Risk Assessment for Cyanobacterial Toxins in Seafood

    PubMed Central

    Mulvenna, Vanora; Dale, Katie; Priestly, Brian; Mueller, Utz; Humpage, Andrew; Shaw, Glen; Allinson, Graeme; Falconer, Ian

    2012-01-01

    Cyanobacteria (blue-green algae) are abundant in fresh, brackish and marine waters worldwide. When toxins produced by cyanobacteria are present in the aquatic environment, seafood harvested from these waters may present a health hazard to consumers. Toxicity hazards from seafood have been internationally recognised when the source is from marine algae (dinoflagellates and diatoms), but to date few risk assessments for cyanobacterial toxins in seafood have been presented. This paper estimates risk from seafood contaminated by cyanobacterial toxins, and provides guidelines for safe human consumption. PMID:22690165

  3. Ten Mistakes To Avoid When Injecting Botulinum Toxin.

    PubMed

    Ruiz-Rodriguez, R; Martin-Gorgojo, A

    2015-01-01

    Injection of botulinum toxin is currently the most common cosmetic procedure in the United States, and in recent years it has become-together with dermal fillers-the mainstay of therapy for the prevention and treatment of facial aging. However, in some cases the treatment may lead to a somewhat unnatural appearance, usually caused by loss of facial expression or other telltale signs. In the present article, we review the 10 mistakes that should be avoided when injecting botulinum toxin. We also reflect on how treatment with botulinum toxin influences us through our facial expressions, both in terms of how we feel and what others perceive. PMID:25956528

  4. Botulinum toxin type A for the management of glabellar rhytids

    PubMed Central

    Tremaine, Anne Marie; McCullough, Jerry L

    2010-01-01

    There is an increasing demand for minimally-invasive cosmetic procedures to arrest the aging process. Botulinum toxin type A injections are the most commonly used nonsurgical cosmetic procedures in the United States. There has been research spanning over two decades dedicated to safety, efficacy, dosing, and complications of botulinum toxin type A. There are now two Food and Drug Administration (FDA) approved botulinum toxin type A options in the United States: Botox® and Dysport™, with new advances being made in the field. PMID:21437056

  5. [Detection of Staphylococcus aureus toxins using immuno-PCR].

    PubMed

    Maerle, A V; Riazantsev, D Iu; Dmitrenko, O A; Petrova, E Ia; Komaleva, R L; Sergeev, I V; Trofimov, D Iu; Zavriev, S K

    2014-01-01

    A highly sensitive test system, based on the method of immuno-PCR, was developed for the detection of two staphylococcal toxins: enterotoxin A (SEA) and toxic shock syndrome toxin (TSST). A key element of the developed systems was obtaining supramolecular complexes of bisbiotinylated oligodeoxynucleotides and streptavidin, which were used as DNA tags. Specificity studies showed no cross-reactivity when determining SEA and TSST. The sensitivity of detection of these toxins in the culture supernatants S. aureus was not less than 10 pg/mL. PMID:25895352

  6. Locus of the Pseudomonas aeruginosa toxin A gene.

    PubMed Central

    Hanne, L F; Howe, T R; Iglewski, B H

    1983-01-01

    The gene for Pseudomonas aeruginosa toxin A has been mapped in the late region of the chromosome of strain PAO. Strain PAO-PR1, which produces parental levels of toxin A antigen that is enzymatically inactive and nontoxic, was used as the donor for R68.45 plasmid-mediated genetic exchange. Strain PAO-PR1 (toxA1) was mated with toxin A-producing strains, and exconjugates for selected prototrophic markers were tested for the transfer of toxA1. The toxA1 gene was located between cnu-9001 and pur-67 at approximately 85 min on the PAO chromosome. PMID:6403508

  7. Occurrence of paralytic toxin in Taiwanese crab Atergatopsis germaini.

    PubMed

    Tsai, Y H; Hwang, D F; Chai, T J; Jeng, S S

    1996-04-01

    Paralytic toxicity was detected by paralytic shellfish poison bioassay for all 17 specimens of the xanthid crab A. germaini collected from northern Taiwan in November 1993. The average toxicity of crab specimens was 3809 +/- 2591 mouse units (mean +/- S.D.). The toxin was partially purified from ethanolic extract of the crab by ultrafiltration and Bio-Gel P-2 column chromatography. Electrophoresis, TLC, HPLC, ultraviolet spectrum and GC-MS analyses indicated that the crab toxin was composed of gonyautoxin 3 (50%), neosaxitoxin and saxitoxin (7%), a novel paralytic shellfish poison-like toxin (40%) and tetrodotoxin (3%). PMID:8735246

  8. Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases.

    PubMed

    Uzal, F A; Vidal, J E; McClane, B A; Gurjar, A A

    2010-01-01

    Clostridium perfringens is a gram-positive anaerobic rod that is classified into 5 toxinotypes (A, B, C, D, and E) according to the production of 4 major toxins, namely alpha (CPA), beta (CPB), epsilon (ETX) and iota (ITX). However, this microorganism can produce up to 16 toxins in various combinations, including lethal toxins such as perfringolysin O (PFO), enterotoxin (CPE), and beta2 toxin (CPB2). Most diseases caused by this microorganism are mediated by one or more of these toxins. The role of CPA in intestinal disease of mammals is controversial and poorly documented, but there is no doubt that this toxin is essential in the production of gas gangrene of humans and several animal species. CPB produced by C. perfringens types B and C is responsible for necrotizing enteritis and enterotoxemia mainly in neonatal individuals of several animal species. ETX produced by C. perfringens type D is responsible for clinical signs and lesions of enterotoxemia, a predominantly neurological disease of sheep and goats. The role of ITX in disease of animals is poorly understood, although it is usually assumed that the pathogenesis of intestinal diseases produced by C. perfringens type E is mediated by this toxin. CPB2, a necrotizing and lethal toxin that can be produced by all types of C. perfringens, has been blamed for disease in many animal species, but little information is currently available to sustain or rule out this claim. CPE is an important virulence factor for C. perfringens type A gastrointestinal disease in humans and dogs; however, the data implicating CPE in other animal diseases remains ambiguous. PFO does not seem to play a direct role as the main virulence factor for animal diseases, but it may have a synergistic role with CPA-mediated gangrene and ETX-mediated enterotoxemia. The recent improvement of animal models for C. perfringens infection and the use of toxin gene knock-out mutants have demonstrated the specific pathogenic role of several toxins of C

  9. From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules

    PubMed Central

    Nasiripourdori, Adak; Taly, Valérie; Grutter, Thomas; Taly, Antoine

    2011-01-01

    Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted. PMID:22069709

  10. Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases

    PubMed Central

    Uzal, F. A.; Vidal, J. E.; McClane, B. A.; Gurjar, A. A.

    2013-01-01

    Clostridium perfringens is a gram-positive anaerobic rod that is classified into 5 toxinotypes (A, B, C, D, and E) according to the production of 4 major toxins, namely alpha (CPA), beta (CPB), epsilon (ETX) and iota (ITX). However, this microorganism can produce up to 16 toxins in various combinations, including lethal toxins such as perfringolysin O (PFO), enterotoxin (CPE), and beta2 toxin (CPB2). Most diseases caused by this microorganism are mediated by one or more of these toxins. The role of CPA in intestinal disease of mammals is controversial and poorly documented, but there is no doubt that this toxin is essential in the production of gas gangrene of humans and several animal species. CPB produced by C. perfringens types B and C is responsible for necrotizing enteritis and enterotoxemia mainly in neonatal individuals of several animal species. ETX produced by C. perfringens type D is responsible for clinical signs and lesions of enterotoxemia, a predominantly neurological disease of sheep and goats. The role of ITX in disease of animals is poorly understood, although it is usually assumed that the pathogenesis of intestinal diseases produced by C. perfringens type E is mediated by this toxin. CPB2, a necrotizing and lethal toxin that can be produced by all types of C. perfringens, has been blamed for disease in many animal species, but little information is currently available to sustain or rule out this claim. CPE is an important virulence factor for C. perfringens type A gastrointestinal disease in humans and dogs; however, the data implicating CPE in other animal diseases remains ambiguous. PFO does not seem to play a direct role as the main virulence factor for animal diseases, but it may have a synergistic role with CPA-mediated gangrene and ETX-mediated enterotoxemia. The recent improvement of animal models for C. perfringens infection and the use of toxin gene knock-out mutants have demonstrated the specific pathogenic role of several toxins of C

  11. Biosecurity reference : CFR-listed agent and toxin summaries.

    SciTech Connect

    Barnett, Natalie Beth

    2003-09-01

    This reference document provides summary information on the animal, plant, zoonotic, and human pathogens and toxins regulated and categorized by 9 CFR 331 and 7 CFR 121, 'Agricultural Bioterrorism Protection Act of 2002; Possession, Use and Transfer of Biological Agents and Toxins,' and 42 CFR 73, 'Possession, Use, and Transfer of Select Agents and Toxins.' Summary information includes, at a minimum, a description of the agent and its associated symptoms; often additional information is provided on the diagnosis, treatment, geographic distribution, transmission, control and eradication, and impacts on public health.

  12. Novel Structure and Function of Typhoid Toxin

    MedlinePlus

    ... excellent track record of success,” Galán says. — by Carol Torgan, Ph.D. Related Links Salmonella Are Armed, ... Assistant Editors: Vicki Contie, Tianna Hicklin, Ph.D., Carol Torgan, Ph.D. NIH Research Matters is a ...

  13. Three-component competitive adsorption model for fixed-bed and moving-bed granular activated carbon adsorbers. Part I. Model development.

    PubMed

    Schideman, Lance C; Mariñas, Benito J; Snoeyink, Vernon L; Campos, Carlos

    2006-11-01

    Heterogeneous natural organic matter (NOM) present in all natural waters impedes trace organic contaminant adsorption, and predictive modeling of granular activated carbon (GAC) adsorber performance is often compromised by inadequate accounting forthese competitive effects. Thus, a 3-component adsorption model, COMPSORB-GAC, is developed that separately tracks NOM adsorption and its competitive effects as a function of NOM surface loading. In this model, NOM is simplified into two fictive fractions with distinct competitive effects on trace compound adsorption: a smaller, strongly competing fraction that reduces equilibrium capacity and a larger pore-blocking fraction that reduces adsorption kinetics (both external film mass transfer and surface diffusion). COMPSORB-GAC tracks these two NOM fractions, along with the trace compound, and changes adsorption parameters according to the local surface loading of the two NOM fractions. Model parameters are allowed to vary both temporally and spatially to reflect differences in the NOM preloading conditions that occur in GAC columns. This dual-resistance model is based on homogeneous surface diffusion with external film mass-transfer limitations. The governing equations are expressed in a moving-grid finite-difference formulation to accommodate the modeling of spatially varying parameters and moving-bed reactors with counter-current adsorbent flow. A series of short-term adsorption tests with fresh and preloaded GAC is proposed to determine the necessary model input parameters. The accompanying manuscript demonstrates the parameterization procedure and verifies the model with experimental data. PMID:17144314

  14. Staphylococcus aureus β-toxin Production is Common in Strains With the β-toxin Gene Inactivated by Bacteriophage

    PubMed Central

    Salgado-Pabón, Wilmara; Herrera, Alfa; Vu, Bao G.; Stach, Christopher S.; Merriman, Joseph A.; Spaulding, Adam R.; Schlievert, Patrick M.

    2014-01-01

    Background. Staphylococcus aureus causes life-threatening infections, including infective endocarditis, sepsis, and pneumonia. β-toxin is a sphingomyelinase encoded for by virtually all S. aureus strains and exhibits human immune cell cytotoxicity. The toxin enhances S. aureus phenol-soluble modulin activity, and its activity is enhanced by superantigens. The bacteriophage φSa3 inserts into the β-toxin gene in human strains, inactivating it in the majority of S. aureus clonal groups. Hence, most strains are reported not to secrete β-toxin. Methods. This dynamic was investigated by examining β-toxin production by multiple clonal groups of S. aureus, both in vitro and in vivo during infections in rabbit models of infective endocarditis, sepsis, and pneumonia. Results. β-toxin phenotypic variants are common among strains containing φSa3. In vivo, φSa3 is differentially induced in heart vegetations, kidney abscesses, and ischemic liver compared to spleen and blood, and in vitro growth in liquid culture. Furthermore, in pneumonia, wild-type β-toxin production leads to development of large caseous lesions, and in infective endocarditis, increases the size of pathognomonic vegetations. Conclusions. This study demonstrates the dynamic interaction between S. aureus and the infected host, where φSa3 serves as a regulator of virulence gene expression, and increased fitness and virulence in new environments. PMID:24620023

  15. The elimination of DNA from the Cry toxin-DNA complex is a necessary step in the mode of action of the Cry8 toxin.

    PubMed

    Ai, Bingjie; Li, Jie; Feng, Dongmei; Li, Feng; Guo, Shuyuan

    2013-01-01

    Several crystal (Cry) proteins are known to occur as DNA-protein complexes. However, the role of the DNA associated with the activated toxin in the mechanism of action of the Cry toxin has long been ignored. Here, we focused on the DNA-activated Cry toxin complex. Both forms of the Cry8Ca2 and Cry8Ea1 toxins, i.e., with or without bound DNA, were separately obtained. Size-exclusion chromatography analysis indicated that the Cry8Ca2 toxin-DNA complex has a tight or compact structure. The Cry8Ca2 toxin-DNA complex is more likely to move toward the air/water interface and is more hydrophobic than the toxin without DNA. Competitive binding assays indicated that the Cry8Ca2 and Cry8Ea1 toxins without DNA specifically bind to the midgut of Anomala corpulenta and Holotrichia parallela larvae, respectively. In contrast, the association of DNA with each toxin might result in the nonspecific recognition of the Cry toxin and its target receptor in the insect midgut. The association of the DNA fragment with the Cry8 toxin was shown to protect the Cry protein from digestion by proteases. Based on our results, we propose an additional step in the mechanism of action of the Cry8 toxin and elucidate the function of the associated DNA as well as the importance of the removal of this DNA for the insecticidal activity of the toxin. PMID:24324685

  16. The Elimination of DNA from the Cry Toxin-DNA Complex Is a Necessary Step in the Mode of Action of the Cry8 Toxin

    PubMed Central

    Ai, Bingjie; Li, Jie; Feng, Dongmei; Li, Feng; Guo, Shuyuan

    2013-01-01

    Several crystal (Cry) proteins are known to occur as DNA-protein complexes. However, the role of the DNA associated with the activated toxin in the mechanism of action of the Cry toxin has long been ignored. Here, we focused on the DNA-activated Cry toxin complex. Both forms of the Cry8Ca2 and Cry8Ea1 toxins, i.e., with or without bound DNA, were separately obtained. Size-exclusion chromatography analysis indicated that the Cry8Ca2 toxin-DNA complex has a tight or compact structure. The Cry8Ca2 toxin-DNA complex is more likely to move toward the air/water interface and is more hydrophobic than the toxin without DNA. Competitive binding assays indicated that the Cry8Ca2 and Cry8Ea1 toxins without DNA specifically bind to the midgut of Anomala corpulenta and Holotrichia parallela larvae, respectively. In contrast, the association of DNA with each toxin might result in the nonspecific recognition of the Cry toxin and its target receptor in the insect midgut. The association of the DNA fragment with the Cry8 toxin was shown to protect the Cry protein from digestion by proteases. Based on our results, we propose an additional step in the mechanism of action of the Cry8 toxin and elucidate the function of the associated DNA as well as the importance of the removal of this DNA for the insecticidal activity of the toxin. PMID:24324685

  17. Development of a Diphtheria Toxin-Based Recombinant Porcine IL-2 Fusion Toxin for Depleting Porcine CD25+ Cells

    PubMed Central

    Peraino, Jaclyn Stromp; Schenk, Marian; Li, Guoying; Zhang, Huiping; Farkash, Evan A.; Sachs, David H.; Huang, Christene A.; Duran-Struuck, Raimon; Wang, Zhirui

    2013-01-01

    Regulatory T cells (Tregs) have been widely recognized as crucial players in controlling immune responses. Because their major role is to ensure that the immune system is not over reactive, Tregs have been the focus of multiple research studies including those investigating transplantation tolerance, autoimmunity and cancer treatment. On their surface Tregs constitutively express CD25, a high affinity receptor for the cytokine interleukin-2 (IL-2). The reagents constructed in this study were generated by genetically linking porcine IL-2 to the truncated diphtheria toxin (DT390). This reagent functions by first binding to the cell surface via the porcine IL-2/porcine CD25 interaction then the DT390 domain facilitates internalization followed by inhibition of protein synthesis resulting in cell death. Four versions of the porcine IL-2 fusion toxin were designed in an interest to find the most effective isoform: 1) monovalent glycosylated porcine IL-2 fusion toxin (Gly); 2) monovalent non-N-glycosylated porcine IL-2 fusion toxin (NonGly); 3) bivalent glycosylated porcine IL-2 fusion toxin (Bi-Gly); 4) bivalent non-N-glycosylated porcine IL-2 fusion toxin (Bi-NonGly). Using a porcine CD25+ B cell lymphoma cell line (LCL13271) in vitro analysis of the fusion toxins’ ability to inhibit protein synthesis demonstrated that the Bi-NonGly fusion toxin is the most efficient reagent. These in vitro results are consistent with binding affinity as the Bi-NonGly fusion toxin binds strongest to CD25 on the same LCL13271 cells. The Bi-Gly fusion toxin significantly prolonged the survival (p=0.028) of tumor-bearing NOD/SCID IL-2 receptor γ−/− (NSG) mice injected with LCL13271 cells compared with untreated controls. This recombinant protein has great potential to function as a useful tool for in vivo depletion of porcine CD25+ cells for studying immune regulation. PMID:24055128

  18. Surfactant adsorption to soil components and soils.

    PubMed

    Ishiguro, Munehide; Koopal, Luuk K

    2016-05-01

    Soils are complex and widely varying mixtures of organic matter and inorganic materials; adsorption of surfactants to soils is therefore related to the soil composition. We first discuss the properties of surfactants, including the critical micelle concentration (CMC) and surfactant adsorption on water/air interfaces, the latter gives an impression of surfactant adsorption to a hydrophobic surface and illustrates the importance of the CMC for the adsorption process. Then attention is paid to the most important types of soil particles: humic and fulvic acids, silica, metal oxides and layered aluminosilicates. Information is provided on their structure, surface properties and primary (proton) charge characteristics, which are all important for surfactant binding. Subsequently, the adsorption of different types of surfactants on these individual soil components is discussed in detail, based on mainly experimental results and considering the specific (chemical) and electrostatic interactions, with hydrophobic attraction as an important component of the specific interactions. Adsorption models that can describe the features semi-quantitatively are briefly discussed. In the last part of the paper some trends of surfactant adsorption on soils are briefly discussed together with some complications that may occur and finally the consequences of surfactant adsorption for soil colloidal stability and permeability are considered. When we seek to understand the fate of surfactants in soil and aqueous environments, the hydrophobicity and charge density of the soil or soil particles, must be considered together with the structure, hydrophobicity and charge of the surfactants, because these factors affect the adsorption. The pH and ionic strength are important parameters with respect to the charge density of the particles. As surfactant adsorption influences soil structure and permeability, insight in surfactant adsorption to soil particles is useful for good soil management. PMID

  19. Hydrogen adsorption on functionalized nanoporous activated carbons.

    PubMed

    Zhao, X B; Xiao, B; Fletcher, A J; Thomas, K M

    2005-05-12

    There is considerable interest in hydrogen adsorption on carbon nanotubes and porous carbons as a method of storage for transport and related energy applications. This investigation has involved a systematic investigation of the role of functional groups and porous structure characteristics in determining the hydrogen adsorption characteristics of porous carbons. Suites of carbons were prepared with a wide range of nitrogen and oxygen contents and types of functional groups to investigate their effect on hydrogen adsorption. The porous structures of the carbons were characterized by nitrogen (77 K) and carbon dioxide (273 K) adsorption methods. Hydrogen adsorption isotherms were studied at 77 K and pressure up to 100 kPa. All the isotherms were Type I in the IUPAC classification scheme. Hydrogen isobars indicated that the adsorption of hydrogen is very temperature dependent with little or no hydrogen adsorption above 195 K. The isosteric enthalpies of adsorption at zero surface coverage were obtained using a virial equation, while the values at various surface coverages were obtained from the van't Hoff isochore. The values were in the range 3.9-5.2 kJ mol(-1) for the carbons studied. The thermodynamics of the adsorption process are discussed in relation to temperature limitations for hydrogen storage applications. The maximum amounts of hydrogen adsorbed correlated with the micropore volume obtained from extrapolation of the Dubinin-Radushkevich equation for carbon dioxide adsorption. Functional groups have a small detrimental effect on hydrogen adsorption, and this is related to decreased adsorbate-adsorbent and increased adsorbate-adsorbate interactions. PMID:16852056

  20. Diphtheria toxin-based bivalent human IL-2 fusion toxin with improved efficacy for targeting human CD25(+) cells.

    PubMed

    Peraino, Jaclyn Stromp; Zhang, Huiping; Rajasekera, Priyani V; Wei, Min; Madsen, Joren C; Sachs, David H; Huang, Christene A; Wang, Zhirui

    2014-03-01

    Regulatory T cells (Treg) constitute a major inhibitory cell population which suppresses immune responses. Thus, Treg have proven to be key players in the induction of transplantation tolerance, protection from autoimmune disease and prevention of the development of effective anti-tumor immune reactions. Treg express high levels of the high affinity interleukin-2 receptor (IL-2R) consisting of IL-2Rα (CD25) together with IL-2Rβ (CD122) and the common γ-chain (CD132). An effective reagent capable of depleting Treg in vivo would facilitate better cancer treatment and allow mechanistic studies of the role of Treg in transplantation tolerance and the development of autoimmune disease. In this study, we have developed a novel bivalent human IL-2 fusion toxin along with an Ontak®-like monovalent human IL-2 fusion toxin and compared the functional ability of these reagents in vitro. Here we show that genetically linking two human IL-2 domains in tandem, thereby generating a bivalent fusion toxin, results in significantly improved capacity in targeting human CD25(+) cells in vitro. Binding analysis by flow cytometry showed that the bivalent human IL-2 fusion toxin has notably increased affinity for human CD25(+) cells. In vitro functional analysis demonstrated that the bivalent isoform has an increased potency of approximately 2 logs in inhibiting cellular proliferation and protein synthesis in human CD25(+) cells compared to the monovalent human IL-2 fusion toxin. Additionally, we performed two inhibition assays in order to verify that the fusion toxins target the cells specifically through binding of the human IL-2 domain of the fusion toxin to the human IL-2 receptor on the cell surface. These results demonstrated that 1) both monovalent and bivalent human IL-2 fusion toxins are capable of blocking the binding of biotinylated human IL-2 to human CD25 by flow cytometry; and 2) human IL-2 blocked the fusion toxins from inhibiting protein synthesis and cellular

  1. Dust Devil Tracks

    NASA Technical Reports Server (NTRS)

    2002-01-01

    (Released 8 May 2002) The Science This image, centered near 50.0 S and 17.7 W displays dust devil tracks on the surface. Most of the lighter portions of the image likely have a thin veneer of dust settled on the surface. As a dust devil passes over the surface, it acts as a vacuum and picks up the dust, leaving the darker substrate exposed. In this image there is a general trend of many of the tracks running from east to west or west to east, indicating the general wind direction. There is often no general trend present in dust devil tracks seen in other images. The track patterns are quite ephemeral and can completely change or even disappear over the course of a few months. Dust devils are one of the mechanisms that Mars uses to constantly pump dust into the ubiquitously dusty atmosphere. This atmospheric dust is one of the main driving forces of the present Martian climate. The Story Vrrrrooooooooom. Think of a tornado, the cartoon Tasmanian devil, or any number of vacuum commercials that powerfully suck up swirls of dust and dirt. That's pretty much what it's like on the surface of Mars a lot of the time. Whirlpools of wind called

  2. Tracking Speech Sound Acquisition

    ERIC Educational Resources Information Center

    Powell, Thomas W.

    2011-01-01

    This article describes a procedure to aid in the clinical appraisal of child speech. The approach, based on the work by Dinnsen, Chin, Elbert, and Powell (1990; Some constraints on functionally disordered phonologies: Phonetic inventories and phonotactics. "Journal of Speech and Hearing Research", 33, 28-37), uses a railway idiom to track gains in…

  3. Energy rays tracking device

    SciTech Connect

    Monk, R.J.

    1981-05-12

    An energy rays tracking device includes a receiver for fixing a position relative to the direction of maximum energy rays, a prime mover for maintaining the alignment of the receiver and an energy rays user, an energy rays tracker for controlling the power to the prime mover in response to the receiver, a timed tracker for controlling the prime mover when the energy rays tracker is not functioning due to energy rays being too diffused, an energy sensitive element for detecting the presence or absence of energy rays, and a power controller responsive to the energy sensitive element for repositioning the receiver and the energy rays user for the following period of tracking is disclosed. The receiver includes an enclosure which only allows a selected pattern of direct rays to penetrate into the enclosure. A razor sharp edge at the opening of the enclosure maintains the outermost direct energy rays undiffused. A differential sensor sensitive to direct energy rays is installed inside the enclosure for determining the direction of the direct energy rays. In an application for tracking the sun, the time tracker uses a piecewise linear method of tracking. In the return cycle during the night, the return is interspersed with a wash cycle for cleaning the energy rays user.

  4. Personal Tracking Charts

    MedlinePlus

    ... only on Monday, Wednesday, and Friday. Keep an eye out for allergic reactions. I should take Prezista with food. year keeping track of my periods month mark the Type of Flow in the boxes below L =exceptionally light N =normal h =exceptionally heavy S =spotting O =none ...

  5. Manure Tracking Book

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This document provides an example of the ‘Manure Tracking Book’ that was used by the fifty-four Wisconsin dairy farmers who participated in the “On Farmers’ Ground” nutrient management research project. This Book was used to systematically tract how, when and where farmers spread manure, and factors...

  6. General defocusing particle tracking.

    PubMed

    Barnkob, Rune; Kähler, Christian J; Rossi, Massimiliano

    2015-09-01

    A General Defocusing Particle Tracking (GDPT) method is proposed for tracking the three-dimensional motion of particles in Lab-on-a-chip systems based on a set of calibration images and the normalized cross-correlation function. In comparison with other single-camera defocusing particle-tracking techniques, GDPT possesses a series of key advantages: it is applicable to particle images of arbitrary shapes, it is intuitive and easy to use, it can be used without advanced knowledge of optics and velocimetry theory, it is robust against outliers and overlapping particle images, and it requires only equipment which is standard in microfluidic laboratories. We demonstrate the method by tracking the three-dimensional motion of 2 μm spherical particles in a microfluidic channel using three different optical arrangements. The position of the particles was measured with an estimated uncertainty of 0.1 μm in the in-plane direction and 2 μm in the depth direction for a measurement volume of 1510 × 1270 × 160 μm(3). A ready-to-use GUI implementation of the method can be acquired on . PMID:26201498

  7. Spiral track oven

    SciTech Connect

    Drobilisch, Sandor

    1998-12-20

    Final report on development of a continuously operating oven system in which the parts are progressing automatically on a spiral track for in-line service installation for the production of electronic and/or other components to be heat cured or dried.

  8. Tracking the Invisible Faculty

    ERIC Educational Resources Information Center

    Gravois, John

    2006-01-01

    For decades it has been happening everywhere in academe, but nowhere in particular. The sweeping shift toward non-tenure-track academic labor has been one of the most worried-over trends in American higher education. But it has been charted mostly with broad-brush data, which give little indication of the trend's progress at the institutional…

  9. Dust Devil Tracks

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Context image for PIA03052 Dust Devil Tracks

    These dust devil tracks are located in the region surrounding Hooke Crater.

    Image information: VIS instrument. Latitude 46.6S, Longitude 316.1E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  10. Asset tracking systems.

    PubMed

    2006-11-01

    Asset tracking systems are used in healthcare to find objects--medical devices and other hospital equipment--and to record the physical location of those objects over time. Interest in asset tracking is growing daily, but the technology is still evolving, and so far very few systems have been implemented in hospitals. This situation is likely to change over the next few years, at which point many hospitals will be faced with choosing a system. We evaluated four asset tracking systems from four suppliers: Agility Healthcare Solutions, Ekahau, Radianse, and Versus Technology. We judged the systems' performance for two "levels" of asset tracking. The first level is basic locating--simply determining where in the facility an item can be found. This may be done because the equipment needs routine inspection and preventive maintenance or because it is required for recall purposes; or the equipment may be needed, often urgently, for clinical use. The second level, which is much more involved, is inventory optimization and workflow improvement. This entails analyzing asset utilization based on historical location data to improve the use, distribution, and processing of equipment. None of the evaluated products is ideal for all uses--each has strengths and weaknesses. In many cases, hospitals will have to select a product based on their specific needs. For example, they may need to choose between a supplier whose system is easy to install and a supplier whose tags have a long battery operating life. PMID:17278873

  11. TRACKING Trounces Test Scores

    ERIC Educational Resources Information Center

    Education Digest: Essential Readings Condensed for Quick Review, 2004

    2004-01-01

    This article presents an adaptation of an article from School Board News, January 6, 2004 edition. The article describes the effort of de-tracking students of varying ability levels, made by officials of South Side High School, in Rockville Centre, New York, and Noble High School, in North Berwick, Maine. Officials from both schools say that the…

  12. Energy Tracking Diagrams

    ERIC Educational Resources Information Center

    Scherr, Rachel E.; Harrer, Benedikt W.; Close, Hunter G.; Daane, Abigail R.; DeWater, Lezlie S.; Robertson, Amy D.; Seeley, Lane; Vokos, Stamatis

    2016-01-01

    Energy is a crosscutting concept in science and features prominently in national science education documents. In the "Next Generation Science Standards," the primary conceptual learning goal is for learners to conserve energy as they "track" the transfers and transformations of energy within, into, or out of the system of…

  13. Tracking Politics with POWER

    ERIC Educational Resources Information Center

    Moreira, Silvio; Batista, David S.; Carvalho, Paula; Couto, Francisco M.; Silva, Mario J.

    2013-01-01

    Purpose: POWER is an ontology of political processes and entities. It is designed for tracking politicians, political organizations and elections, both in mainstream and social media. The aim of this paper is to propose a data model to describe political agents and their relations over time. Design/methodology/approach: The authors propose a data…

  14. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms:...

  15. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of...

  16. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... have been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria..., and Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the...

  17. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... have been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria..., and Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the...

  18. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... have been genetically modified. (d) Overlap select agents or toxins that meet any of the following... Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic Organisms:...

  19. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are...) Genetic Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic...

  20. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms:...

  1. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms:...

  2. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms:...

  3. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... have been genetically modified. (d) Overlap select agents or toxins that meet any of the following... Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic Organisms:...

  4. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... have been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria..., and Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the...

  5. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms:...

  6. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms:...

  7. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are...) Genetic Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic...

  8. Shellfish Toxins Targeting Voltage-Gated Sodium Channels

    PubMed Central

    Zhang, Fan; Xu, Xunxun; Li, Tingting; Liu, Zhonghua

    2013-01-01

    Voltage-gated sodium channels (VGSCs) play a central role in the generation and propagation of action potentials in excitable neurons and other cells and are targeted by commonly used local anesthetics, antiarrhythmics, and anticonvulsants. They are also common targets of neurotoxins including shellfish toxins. Shellfish toxins are a variety of toxic secondary metabolites produced by prokaryotic cyanobacteria and eukaryotic dinoflagellates in both marine and fresh water systems, which can accumulate in marine animals via the food chain. Consumption of shellfish toxin-contaminated seafood may result in potentially fatal human shellfish poisoning. This article provides an overview of the structure, bioactivity, and pharmacology of shellfish toxins that act on VGSCs, along with a brief discussion on their pharmaceutical potential for pain management. PMID:24287955

  9. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke

    PubMed Central

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-01-01

    Abstract Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases. This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance. During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization. The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia. PMID:26266368

  10. Identification of the cellular receptor for anthrax toxin

    NASA Astrophysics Data System (ADS)

    Bradley, Kenneth A.; Mogridge, Jeremy; Mourez, Michael; Collier, R. John; Young, John A. T.

    2001-11-01

    The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.

  11. Treatment of Nystagmus in Brainstem Cavernous Malformation with Botulinum Toxin

    PubMed Central

    Fredrick, Douglas; Steinberg, Gary K; Liao, Yaping J

    2016-01-01

    We report a long-term eye movement study of a 68-year-old female with pontomedullary junction cavernous malformation whose dysconjugate nystagmus was treated with retrobulbar botulinum toxin A injections. Sequential, bilateral retrobulbar injections of botulinum toxin A were performed. Injections immediately decreased oscillopsia and nystagmus, and improved visual acuities. One to three months following injection, three-dimensional infrared oculography measured a significant 39-100% (P = 0.001) decrease in nystagmus amplitudes at multiple dimensions. This improvement diminished by six months in the right eye but sustained for about one year in the left eye. Over two years, botulinum toxin A injections were performed twice in the left eye and five times in the right eye. Our study supported the safe and effective use of repetitive retrobulbar botulinum toxin A injections in symptomatic nystagmus that failed medical therapy. PMID:27182467

  12. DEVELOPMENT OF A HUMAN BIOMARKER FOR CYANOBACTERIAL TOXINS- MICROCYSTINS

    EPA Science Inventory

    Increasingly, cyanobacterial blooms are being reported worldwide due to several factors: eutrophication, climate change, and potentially greater scientific awareness and detection. During 1996, an outbreak of fatal cyanobacterial toxin intoxications occurred among a group of dia...

  13. Interactions between Autophagy and Bacterial Toxins: Targets for Therapy?

    PubMed Central

    Mathieu, Jacques

    2015-01-01

    Autophagy is a physiological process involved in defense mechanisms for clearing intracellular bacteria. The autophagic pathway is finely regulated and bacterial toxins interact with this process in a complex manner. Bacterial toxins also interact significantly with many biochemical processes. Evaluations of the effects of bacterial toxins, such as endotoxins, pore-forming toxins and adenylate cyclases, on autophagy could support the development of new strategies for counteracting bacterial pathogenicity. Treatment strategies could focus on drugs that enhance autophagic processes to improve the clearance of intracellular bacteria. However, further in vivo studies are required to decipher the upregulation of autophagy and potential side effects limiting such approaches. The capacity of autophagy activation strategies to improve the outcome of antibiotic treatment should be investigated in the future. PMID:26248079

  14. How Safe Is Safe for Marine Toxins Monitoring?

    PubMed Central

    Botana, Luis M.; Alfonso, Amparo; Rodríguez, Ines; Botana, Ana M.; Louzao, Maria del Carmen; Vieytes, Mercedes R.

    2016-01-01

    Current regulation for marine toxins requires a monitoring method based on mass spectrometric analysis. This method is pre-targeted, hence after searching for pre-assigned masses, it identifies those compounds that were pre-defined with available calibrants. Therefore, the scope for detecting novel toxins which are not included in the monitoring protocol are very limited. In addition to this, there is a poor comprehension of the toxicity of some marine toxin groups. Also, the validity of the current approach is questioned by the lack of sufficient calibrants, and by the insufficient coverage by current legislation of the toxins reported to be present in shellfish. As an example, tetrodotoxin, palytoxin analogs, or cyclic imines are mentioned as indicators of gaps in the system that require a solid comprehension to assure consumers are protected. PMID:27399774

  15. The setting of a botulinum toxin treatment service.

    PubMed

    Cavallini, Maurizio

    2014-05-01

    The administration of botulinum toxin is an activity performed mostly by a specialist service for the management of a wide range of neurological conditions. For therapeutic purposes botulinum toxin type A is used, although in selected patients who develop antibodies specific for the serotype A botulinum toxin B can be used for the treatment. Hereby, we describe the organizational arrangements for the botulinum toxin treatment service at the Department of Neurology of Hospital Cardinal Massaia based in Asti. The diseases most frequently treated are movement disorders (primary and secondary focal dystonia, blepharospasm, facial emispasmo) spasticity and, more recently, chronic migraine. In particular, the latter application is one of the most promising expansions of the use of this drug in the few past years, although a larger number of patients are required to determine its efficacy and the related tolerability profile. PMID:24867836

  16. GPS Metric Tracking Unit

    NASA Technical Reports Server (NTRS)

    2008-01-01

    As Global Positioning Satellite (GPS) applications become more prevalent for land- and air-based vehicles, GPS applications for space vehicles will also increase. The Applied Technology Directorate of Kennedy Space Center (KSC) has developed a lightweight, low-cost GPS Metric Tracking Unit (GMTU), the first of two steps in developing a lightweight, low-cost Space-Based Tracking and Command Subsystem (STACS) designed to meet Range Safety's link margin and latency requirements for vehicle command and telemetry data. The goals of STACS are to improve Range Safety operations and expand tracking capabilities for space vehicles. STACS will track the vehicle, receive commands, and send telemetry data through the space-based asset, which will dramatically reduce dependence on ground-based assets. The other step was the Low-Cost Tracking and Data Relay Satellite System (TDRSS) Transceiver (LCT2), developed by the Wallops Flight Facility (WFF), which allows the vehicle to communicate with a geosynchronous relay satellite. Although the GMTU and LCT2 were independently implemented and tested, the design collaboration of KSC and WFF engineers allowed GMTU and LCT2 to be integrated into one enclosure, leading to the final STACS. In operation, GMTU needs only a radio frequency (RF) input from a GPS antenna and outputs position and velocity data to the vehicle through a serial or pulse code modulation (PCM) interface. GMTU includes one commercial GPS receiver board and a custom board, the Command and Telemetry Processor (CTP) developed by KSC. The CTP design is based on a field-programmable gate array (FPGA) with embedded processors to support GPS functions.

  17. Tracking Virtual Trajectories

    NASA Technical Reports Server (NTRS)

    Stone, Leland S.; Beutter, Brent R.; Lorenceau, Jean D.; Null, Cynthia H. (Technical Monitor)

    1996-01-01

    Current models of smooth pursuit eye movements assume that it is largely driven by retinal image motion. We tested this hypothesis by measuring pursuit of elliptical motion (3.2s, 0.9 Hz, 1.4 deg x 1.6 deg, 4 randomly interleaved phases) of either a small spot ("real" motion) or of a line-figure diamond viewed through apertures such that only the motion of four isolated oblique line segments was visible ("virtual" motion). Each segment moved sinusoidally along a linear trajectory yet subjects perceived a diamond moving along an elliptical path behind the aperture. We found, as expected, that real motion produced accurate tracking (N = 2) with mean gain (over horizontal and vertical) of 0.9, mean phase of -6 deg (lag), mean relative phase (H vs V) of 90 +/- 8 deg (RMS error). Virtual motion behind an X-shaped aperture (N= 4 with one naive) yielded a mean gain of 0.7, mean phase of -11 deg, mean relative phase of 87 +/- 15 deg. We also measured pursuit with the X-shaped aperture using a higher segment luminance which prevents the segments from being grouped into a coherently moving diamond while keeping the motion otherwise identical. In this incoherent case, the same four subjects no longer showed consistent elliptical tracking (RMS error in relative phase rose to 60 deg) suggesting that perceptual coherence is critical. Furthermore, to rule out tracking of the centroid, we also used vertical apertures so that all segment motion was vertical (N = 3). This stimulus still produced elliptical tracking (mean relative phase of 84 +/- 19 deg), albeit with a lower gain (0.6). These data show that humans can track moving objects reasonably accurately even when the trajectory can only be derived by spatial integration of motion signals. Models that merely seek to minimize retinal or local stimulus motion cannot explain these results.

  18. Anomericity of T-2 Toxin-glucoside: Masked Mycotoxin in Cereal Crops

    PubMed Central

    2015-01-01

    T-2 toxin is a trichothecene mycotoxin produced when Fusarium fungi infect grains, especially oats and wheat. Ingestion of T-2 toxin contaminated grain can cause diarrhea, hemorrhaging, and feed refusal in livestock. Cereal crops infected with mycotoxin-producing fungi form toxin glycosides, sometimes called masked mycotoxins, which are a potential food safety concern because they are not detectable by standard approaches and may be converted back to the parent toxin during digestion or food processing. The work reported here addresses four aspects of T-2 toxin-glucosides: phytotoxicity, stability after ingestion, antibody detection, and the anomericity of the naturally occurring T-2 toxin-glucoside found in cereal plants. T-2 toxin-β-glucoside was chemically synthesized and compared to T-2 toxin-α-glucoside prepared with Blastobotrys muscicola cultures and the T-2 toxin-glucoside found in naturally contaminated oats and wheat. The anomeric forms were separated chromatographically and differ in both NMR and mass spectrometry. Both anomers were significantly degraded to T-2 toxin and HT-2 toxin under conditions that mimic human digestion, but with different kinetics and metabolic end products. The naturally occurring T-2 toxin-glucoside from plants was found to be identical to T-2 toxin-α-glucoside prepared with B. muscicola. An antibody test for the detection of T-2 toxin was not effective for the detection of T-2 toxin-α-glucoside. This anomer was produced in sufficient quantity to assess its animal toxicity. PMID:25520274

  19. Tracking bacterial virulence: global modulators as indicators.

    PubMed

    Prieto, Alejandro; Urcola, Imanol; Blanco, Jorge; Dahbi, Ghizlane; Muniesa, Maite; Quirós, Pablo; Falgenhauer, Linda; Chakraborty, Trinad; Hüttener, Mário; Juárez, Antonio

    2016-01-01

    The genomes of Gram-negative bacteria encode paralogues and/or orthologues of global modulators. The nucleoid-associated H-NS and Hha proteins are an example: several enterobacteria such as Escherichia coli or Salmonella harbor H-NS, Hha and their corresponding paralogues, StpA and YdgT proteins, respectively. Remarkably, the genome of the pathogenic enteroaggregative E. coli strain 042 encodes, in addition to the hha and ydgT genes, two additional hha paralogues, hha2 and hha3. We show in this report that there exists a strong correlation between the presence of these paralogues and the virulence phenotype of several E. coli strains. hha2 and hha3 predominate in some groups of intestinal pathogenic E. coli strains (enteroaggregative and shiga toxin-producing isolates), as well as in the widely distributed extraintestinal ST131 isolates. Because of the relationship between the presence of hha2/hha3 and some virulence factors, we have been able to provide evidence for Hha2/Hha3 modulating the expression of the antigen 43 pathogenic determinants. We show that tracking global modulators or their paralogues/orthologues can be a new strategy to identify bacterial pathogenic clones and propose PCR amplification of hha2 and hha3 as a virulence indicator in environmental and clinical E. coli isolates. PMID:27169404

  20. Tracking bacterial virulence: global modulators as indicators

    PubMed Central

    Prieto, Alejandro; Urcola, Imanol; Blanco, Jorge; Dahbi, Ghizlane; Muniesa, Maite; Quirós, Pablo; Falgenhauer, Linda; Chakraborty, Trinad; Hüttener, Mário; Juárez, Antonio

    2016-01-01

    The genomes of Gram-negative bacteria encode paralogues and/or orthologues of global modulators. The nucleoid-associated H-NS and Hha proteins are an example: several enterobacteria such as Escherichia coli or Salmonella harbor H-NS, Hha and their corresponding paralogues, StpA and YdgT proteins, respectively. Remarkably, the genome of the pathogenic enteroaggregative E. coli strain 042 encodes, in addition to the hha and ydgT genes, two additional hha paralogues, hha2 and hha3. We show in this report that there exists a strong correlation between the presence of these paralogues and the virulence phenotype of several E. coli strains. hha2 and hha3 predominate in some groups of intestinal pathogenic E. coli strains (enteroaggregative and shiga toxin-producing isolates), as well as in the widely distributed extraintestinal ST131 isolates. Because of the relationship between the presence of hha2/hha3 and some virulence factors, we have been able to provide evidence for Hha2/Hha3 modulating the expression of the antigen 43 pathogenic determinants. We show that tracking global modulators or their paralogues/orthologues can be a new strategy to identify bacterial pathogenic clones and propose PCR amplification of hha2 and hha3 as a virulence indicator in environmental and clinical E. coli isolates. PMID:27169404