Sample records for ubiquitous environmental toxin
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[Environmental toxins in breast milk].
Bratlid, Dag
2009-12-17
Breast milk is very important to ensure infants a well-composed and safe diet during the first year of life. However, the quality of breast milk seems to be affected by an increasing amount of environmental toxins (particularly so-called Persistent, Bioaccumulative Toxins [PBTs]). Many concerns have been raised about the negative effects this may have on infant health. The article is a review of literature (mainly review articles) identified through a non-systematic search in PubMed. The concentration of PBTs in breast milk is mainly caused by man's position as the terminal link in the nutritional chain. Many breast-fed infants have a daily intake of such toxins that exceed limits defined for the population in general. Animal studies demonstrate effects on endocrine function and neurotoxicity in the offspring, and a number of human studies seem to point in the same direction. However the "original" optimal composition of breast milk still seems to protect against long-term effects of such toxicity. There is international consensus about the need to monitor breast milk for the presence of PBTs. Such surveillance will be a good indicator of the population's general exposure to these toxins and may also contribute to identifying groups as risk who should not breast-feed their children for a long time.
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Arsenic (As) is a ubiquitous environmental toxin that causes a wide range of diseases. To date, however, there is no methodology for calculating the impact of cumulative As exposure on health outcomes in the US. The current project will develop and validate the Cumulative Envi...
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Diversity and impact of prokaryotic toxins on aquatic environments: a review.
Valério, Elisabete; Chaves, Sandra; Tenreiro, Rogério
2010-10-01
Microorganisms are ubiquitous in all habitats and are recognized by their metabolic versatility and ability to produce many bioactive compounds, including toxins. Some of the most common toxins present in water are produced by several cyanobacterial species. As a result, their blooms create major threats to animal and human health, tourism, recreation and aquaculture. Quite a few cyanobacterial toxins have been described, including hepatotoxins, neurotoxins, cytotoxins and dermatotoxins. These toxins are secondary metabolites, presenting a vast diversity of structures and variants. Most of cyanobacterial secondary metabolites are peptides or have peptidic substructures and are assumed to be synthesized by non-ribosomal peptide synthesis (NRPS), involving peptide synthetases, or NRPS/PKS, involving peptide synthetases and polyketide synthases hybrid pathways. Besides cyanobacteria, other bacteria associated with aquatic environments are recognized as significant toxin producers, representing important issues in food safety, public health, and human and animal well being. Vibrio species are one of the most representative groups of aquatic toxin producers, commonly associated with seafood-born infections. Some enterotoxins and hemolysins have been identified as fundamental for V. cholerae and V. vulnificus pathogenesis, but there is evidence for the existence of other potential toxins. Campylobacter spp. and Escherichia coli are also water contaminants and are able to produce important toxins after infecting their hosts. Other bacteria associated with aquatic environments are emerging as toxin producers, namely Legionella pneumophila and Aeromonas hydrophila, described as responsible for the synthesis of several exotoxins, enterotoxins and cytotoxins. Furthermore, several Clostridium species can produce potent neurotoxins. Although not considered aquatic microorganisms, they are ubiquitous in the environment and can easily contaminate drinking and irrigation water
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Diversity and Impact of Prokaryotic Toxins on Aquatic Environments: A Review
Valério, Elisabete; Chaves, Sandra; Tenreiro, Rogério
2010-01-01
Microorganisms are ubiquitous in all habitats and are recognized by their metabolic versatility and ability to produce many bioactive compounds, including toxins. Some of the most common toxins present in water are produced by several cyanobacterial species. As a result, their blooms create major threats to animal and human health, tourism, recreation and aquaculture. Quite a few cyanobacterial toxins have been described, including hepatotoxins, neurotoxins, cytotoxins and dermatotoxins. These toxins are secondary metabolites, presenting a vast diversity of structures and variants. Most of cyanobacterial secondary metabolites are peptides or have peptidic substructures and are assumed to be synthesized by non-ribosomal peptide synthesis (NRPS), involving peptide synthetases, or NRPS/PKS, involving peptide synthetases and polyketide synthases hybrid pathways. Besides cyanobacteria, other bacteria associated with aquatic environments are recognized as significant toxin producers, representing important issues in food safety, public health, and human and animal well being. Vibrio species are one of the most representative groups of aquatic toxin producers, commonly associated with seafood-born infections. Some enterotoxins and hemolysins have been identified as fundamental for V. cholerae and V. vulnificus pathogenesis, but there is evidence for the existence of other potential toxins. Campylobacter spp. and Escherichia coli are also water contaminants and are able to produce important toxins after infecting their hosts. Other bacteria associated with aquatic environments are emerging as toxin producers, namely Legionella pneumophila and Aeromonas hydrophila, described as responsible for the synthesis of several exotoxins, enterotoxins and cytotoxins. Furthermore, several Clostridium species can produce potent neurotoxins. Although not considered aquatic microorganisms, they are ubiquitous in the environment and can easily contaminate drinking and irrigation water
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Submission of nucleotide sequence clostridium perfringens alpha-toxin to genbank database
USDA-ARS?s Scientific Manuscript database
Clostridium perfringens (CP) is ubiquitous in the nature, and a normal inhabitant in the intestinal tracts of animals and humans. However, pathogenic CP is also a causative agent of poultry disease necrotic enteritis (NE). Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clo...
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First, Do No Harm: Children's Environmental Health in Schools
ERIC Educational Resources Information Center
Chatham-Stephens, Kevin M.; Mann, Mana; Schwartz, Andrea Wershof; Landrigan, Philip J.
2012-01-01
In the past century, the threats to children's health have shifted radically. Life-threatening infectious diseases--smallpox, polio, and cholera--have been largely conquered. But children are growing up in a world in which environmental toxins are ubiquitous. Measurable levels of hundreds of man-made chemicals are routinely found in the bodies of…
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Development of a quail embryo model for the detection of botulinum toxin type A activity
USDA-ARS?s Scientific Manuscript database
Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...
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Li, Xiaochuang; Dreher, Theo W; Li, Renhui
2016-04-01
The new genus name Dolichospermum, for most of the planktonic former members of the genus Anabaena, is one of the most ubiquitous bloom-forming cyanobacterial genera. Its dominance and persistence have increased in recent years, due to eutrophication from anthropogenic activities and global climate change. Blooms of Dolichospermum species, with their production of secondary metabolites that commonly include toxins, present a worldwide threat to environmental and public health. In this review, recent advances of the genus Dolichospermum are summarized, including taxonomy, genetics, bloom occurrence, and production of toxin and taste-and-odor compounds. The recent and continuing acquisition of genome sequences is ushering in new methods for monitoring and understanding the factors regulating bloom dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.
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Polycystic ovary syndrome and environmental toxins.
Rutkowska, Aleksandra Zofia; Diamanti-Kandarakis, Evanthia
2016-09-15
Polycystic ovary syndrome (PCOS) is the most common, heterogeneous, and multifactorial endocrine disorder in premenopausal women. The pathophysiology of this endocrinopathy is still unclear; however, the heterogeneity of its features within ethnic races, geographic location, and families suggests that environment and lifestyle are of prime importance. This work is mainly focused on the possible role of the most common and studied environmental toxins for this syndrome in the pathogenesis of PCOS. Plasticizers, such as bisphenol A (BPA) or phthalates, which belong to the categories of endocrine disrupting chemicals (EDCs) and advanced glycation end products (AGEs), affect humans' health in everyday, industrialized life; therefore special attention should be paid to such exposure. Timing of exposure to EDCs is crucial for the intensity of adverse health effects. It is now evident that fetuses, infants, and/or young children are the most susceptible groups, especially in the early development periods. Prenatal exposure to EDCs that mimic endogenous hormones may contribute to the altered fetal programming and in consequence lead to PCOS and other adverse health effects, potentially transgenerationally. Acute or prolonged exposure to EDCs and AGEs through different life cycle stages may result in destabilization of the hormonal homeostasis and lead to disruption of reproductive functions. They may also interfere with metabolic alterations such as obesity, insulin resistance, and compensatory hyperinsulinemia that can exacerbate the PCOS phenotype and contribute to PCOS consequences such as type 2 diabetes and cardiovascular disease. Since wide exposure to environmental toxins and their role in the pathophysiology of PCOS are supported by extensive data derived from diverse scientific models, protective strategies and strong recommendations should be considered to reduce human exposure to protect present and future generations from their adverse health effects. Copyright
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Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids.
Forsythe, Steven D; Devarasetty, Mahesh; Shupe, Thomas; Bishop, Colin; Atala, Anthony; Soker, Shay; Skardal, Aleksander
2018-01-01
Environmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S. have suffered from exposures to lead in drinking water or other heavy metals in food or the earth, while there is a high possibility of further places to suffer such exposures in the near future. We employed bioengineered 3D human liver and cardiac organoids to screen a panel of environmental toxins (lead, mercury, thallium, and glyphosate), and charted the response of the organoids to these compounds. Liver and cardiac organoids were exposed to lead (10 µM-10 mM), mercury (200 nM-200 µM), thallium (10 nM-10 µM), or glyphosate (25 µM-25 mM) for a duration of 48 h. The impacts of toxin exposure were then assessed by LIVE/DEAD viability and cytotoxicity staining, measuring ATP activity and determining IC50 values, and determining changes in cardiac organoid beating activity. As expected, all of the toxins induced toxicity in the organoids. Both ATP and LIVE/DEAD assays showed toxicity in both liver and cardiac organoids. In particular, thallium was the most toxic, with IC50 values of 13.5 and 1.35 µM in liver and cardiac organoids, respectively. Conversely, glyphosate was the least toxic of the four compounds, with IC50 values of 10.53 and 10.85 mM in liver and cardiac organoids, respectively. Additionally, toxins had a negative influence on cardiac organoid beating activity as well. Thallium resulting in the most significant decreases in beating rate, followed by mercury, then glyphosate, and finally, lead. These results suggest that the 3D organoids have significant utility to be deployed in additional toxicity screening applications, and future development of treatments to mitigate exposures. 3D organoids have significant utility to be deployed in additional toxicity screening applications, such
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Bhatnagar, Deepak; Yu, Jiujiang; Ehrlich, Kenneth C
2002-01-01
Mycotoxins are low-molecular-weight secondary metabolites of fungi. The most significant mycotoxins are contaminants of agricultural commodities, foods and feeds. Fungi that produce these toxins do so both prior to harvest and during storage. Although contamination of commodities by toxigenic fungi occurs frequently in areas with a hot and humid climate (i.e. conditions favorable for fungal growth), they can also be found in temperate conditions. Production of mycotoxins is dependent upon the type of producing fungus and environmental conditions such as the substrate, water activity (moisture and relative humidity), duration of exposure to stress conditions and microbial, insect or other animal interactions. Although outbreaks of mycotoxicoses in humans have been documented, several of these have not been well characterized, neither has a direct correlation between the mycotoxin and resulting toxic effect been well established in vivo. Even though the specific modes of action of most of the toxins are not well established, acute and chronic effects in prokaryotic and eukaryotic systems, including humans have been reported. The toxicity of the mycotoxins varies considerably with the toxin, the animal species exposed to it, and the extent of exposure, age and nutritional status. Most of the toxic effects of mycotoxins are limited to specific organs, but several mycotoxins affect many organs. Induction of cancer by some mycotoxins is a major concern as a chronic effect of these toxins. It is nearly impossible to eliminate mycotoxins from the foods and feed in spite of the regulatory efforts at the national and international levels to remove the contaminated commodities. This is because mycotoxins are highly stable compounds, the producing fungi are ubiquitous, and food contamination can occur both before and after harvest. Nevertheless, good farm management practices and adequate storage facilities minimize the toxin contamination problems. Current research is
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NASA Astrophysics Data System (ADS)
Nabok, A. V.; Tsargorodskaya, A.; Hassan, A. K.; Starodub, N. F.
2005-06-01
The environmental toxins, such as herbicides simazine and atrazine, and T2 mycotoxin were registered with the optical methods of surface plasmon resonance (SPR) and recently developed total internal reflection ellipsometry (TIRE). The immune assay approach was exploited for in situ registration of the above low molecular weight toxins with specific antibodies immobilised onto the gold surface via (poly)allylamine hydrochloride layer using electrostatic self-assembly (ESA) technique. The comparison of two methods of SPR and TIRE shows a higher sensitivity of the latter.
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Rachael Carson Lecture - Algal Toxins in the Deep Blue Sea: an Environmental Concern?
NASA Astrophysics Data System (ADS)
Silver, M. W.; Bargu, S.
2008-05-01
Many land plants are known to possess toxins, presumably for grazer deterrence, whereas toxins in marine phytoplankton are a much rarer phenomenon, particularly in open ocean (blue water) environments. Several dozen phytoplankton species, frequently dinoflagellates but also some diatoms, form "harmful algal blooms" nearshore: here their toxins can contaminate filter-feeding shellfish resulting in poisoning "syndromes" when humans consume the tainted shellfish. The present rise in such coastal events is a likely consequence of human activities. In blue water, open ocean environments, the filamentous cyanobacterium Trichodesmium (a blue green alga) is one of the few bloom-forming toxin producers and hosts a consortium of microorganisms that may be partially immune to its toxins. Pseudo-nitzschia, a ubiquitous genus of diatoms recently has been shown to include coastal species that produce domoic acid (DA), a neurotoxin that passes through the food web, sometimes with resulting deaths of marine birds and mammals. Oceanic species of Pseudo-nitzschia also exist but are less well known, and DA has not yet been found in them. Here we review some general features of toxic marine phytoplankton, recent studies on DA in coastal ecosystems and describe some of our findings on blue water Pseudo-nitzschia. We will summarize laboratory experiments that show complex patterns of DA retention and release into the water when Fe is added to coastal Pseudo-nitzschia cultures. In oceanic species, equivalent experiments on cell physiology are limited and the natural species and abundance patterns poorly known. Here we present our recent discovery that DA occurs in oceanic Pseudo-nitzschia and review evidence from the literature that this genus may be preferentially enhanced when iron is added to HNLC (high nutrient, low chlorophyll) waters: areas where nitrogen and phosphorus are not yet depleted, but iron concentrations and phytoplankton biomass are low. The rapid growth of these DA
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Polyvalent Recognition of Biopolymers:The Design of Potent Inhibitors of Anthrax Toxin
NASA Astrophysics Data System (ADS)
Kane, Ravi
2007-03-01
Polyvalency -- the simultaneous binding of multiple ligands on one entity to multiple receptors on another -- is a phenomenon that is ubiquitous in nature. We are using a biomimetic approach, inspired by polyvalency, to design potent inhibitors of anthrax toxin. Since the major symptoms and death from anthrax are due primarily to the action of anthrax toxin, the toxin is a prime target for therapeutic intervention. We describe the design of potent polyvalent anthrax toxin inhibitors, and will discuss the role of pattern matching in polyvalent recognition. Pattern-matched polyvalent inhibitors can neutralize anthrax toxin in vivo, and may enable the successful treatment of anthrax during the later stages of the disease, when antibiotic treatment is ineffective.
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Hankett, Jeanne M; Collin, William R; Yang, Pei; Chen, Zhan; Duhaime, Melissa
2016-02-02
Despite the ever-increasing prevalence of plastic debris and endocrine disrupting toxins in aquatic ecosystems, few studies describe their interactions in freshwater environments. We present a model system to investigate the deposition/desorption behaviors of low-volatility lake ecosystem toxins on microplastics in situ and in real time. Molecular interactions of gas-phase nonylphenols (NPs) with the surfaces of two common plastics, poly(styrene) and poly(ethylene terephthalate), were studied using quartz crystal microbalance and sum frequency generation vibrational spectroscopy. NP point sources were generated under two model environments: plastic on land and plastic on a freshwater surface. We found the headspace above calm water provides an excellent environment for NP deposition and demonstrate significant NP deposition on plastic within minutes at relevant concentrations. Further, NP deposits and orders differently on both plastics under humid versus dry environments. We attributed the unique deposition behaviors to surface energy changes from increased water content during the humid deposition. Lastly, nanograms of NP remained on microplastic surfaces hours after initial NP introduction and agitating conditions, illustrating feasibility for plastic-bound NPs to interact with biota and surrounding matter. Our model studies reveal important interactions between low-volatility environmental toxins and microplastics and hold potential to correlate the environmental fate of endocrine disrupting toxins in the Great Lakes with molecular behaviors.
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Kofler, Michael J.; Raiker, Joseph S.; Sarver, Dustin E.; Wells, Erica L.; Soto, Elia F.
2016-01-01
Hyperactivity, or excess gross motor activity, is considered a core and ubiquitous characteristic of ADHD. Alternate models question this premise, and propose that hyperactive behavior reflects, to a large extent, purposeful behavior to cope with environmental demands that interact with underlying neurobiological vulnerabilities. The present review critically evaluates the ubiquity and environmental modifiability of hyperactivity in ADHD through meta-analysis of 63 studies of mechanically measured activity level in children, adolescents, and adults with ADHD relative to typically developing (TD) groups. Random effects models corrected for publication bias confirmed elevated gross motor activity in ADHD (d = 0.86); surprisingly, neither participant age (child vs. adult) nor the proportion of each ADHD sample diagnosed with the Inattentive subtype/presentation moderated this effect. In contrast, activity level assessed during high cognitive load conditions in general (d = 1.14) and high executive functioning demands in particular (d = 1.39) revealed significantly higher effect sizes than activity level during low cognitive load (d = 0.36) and in-class schoolwork (d = 0.50) settings. Low stimulation environments, more rigorous diagnostic practices, actigraph measurement of movement frequency and intensity, and ADHD samples that included fewer females were also associated with larger effects. Overall, the results are inconsistent with DSM-5 and ADHD models that a) describe hyperactivity as ubiquitous behavior, b) predict a developmental decline in hyperactivity, or c) differentiate subtypes/presentations according to perceived differences in hyperactive behavior. Instead, results suggest that the presence and magnitude of hyperactive behavior in ADHD may be influenced to a considerable extent by environmental factors in general, and cognitive/executive functioning demands in particular. PMID:27131918
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[Clostridia: toxin masters. Botulism: from botox to sausages?].
Buzzi, Marta; Rossel, Anne; Coen, Matteo; Kaiser, Laurent; Abbas, Mohamed
2016-04-13
Clostridia are ubiquitous Gram-positive bacteria whose toxins are responsible for serious diseases. In this article we report a case of foodborne botulism we have recently managed. Moreover, we briefly describe the major clinical syndromes caused by different species of Clostridium (except for C. difficile infections, as this subject has been previously extensively reviewed in this journal). Botulism causes a flaccid paralysis starting with cranial nerves. Administration of botulism anti-toxin should be rapidly considered as soon as botulism is suspected, as prognosis is largely dependent on timely treatment; alerting the public health authorities is equally important. In Switzerland botulinum antitoxin can be obtained from the pharmacy of the Swiss Army.
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Antibody-Mediated Inhibition of Ricin Toxin Retrograde Transport
Yermakova, Anastasiya; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J.
2014-01-01
ABSTRACT Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin’s binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases. PMID:24713323
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TOXINS FROM CYANOBACTERIA IN WATER
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 ...
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Ricin detection: tracking active toxin.
Bozza, William P; Tolleson, William H; Rivera Rosado, Leslie A; 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. Published by Elsevier Inc.
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Artificial activation of toxin-antitoxin systems as an antibacterial strategy.
Williams, Julia J; Hergenrother, Paul J
2012-06-01
Toxin-antitoxin (TA) systems are unique modules that effect plasmid stabilization via post-segregational killing of the bacterial host. The genes encoding TA systems also exist on bacterial chromosomes, and it has been speculated that these are involved in a variety of cellular processes. Interest in TA systems has increased dramatically over the past 5 years as the ubiquitous nature of TA genes on bacterial genomes has been revealed. The exploitation of TA systems as an antibacterial strategy via artificial activation of the toxin has been proposed and has considerable potential; however, efforts in this area remain in the early stages and several major questions remain. This review investigates the tractability of targeting TA systems to kill bacteria, including fundamental requirements for success, recent advances, and challenges associated with artificial toxin activation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Hwang, Jeonghwan; Yoe, Hyun
2010-01-01
Many hog farmers are now suffering from high pig mortality rates due to various wasting diseases and increased breeding costs, etc. It is therefore necessary for hog farms to implement systematic and scientific pig production technology to increase productivity and produce high quality pork in order to solve these problems. In this study, we describe such a technology by suggesting a ubiquitous hog farm system which applies WSN (Wireless Sensor Network) technology to the pig industry. We suggest that a WSN and CCTV (Closed-circuit television) should be installed on hog farms to collect environmental and image information which shall then help producers not only in monitoring the hog farm via the Web from outside the farm, but also facilitate the control of hog farm facilities in remote locations. In addition, facilities can be automatically controlled based on breeding environment parameters which are already set up and a SMS notice service to notify of deviations shall provide users with convenience. Hog farmers may increase production and improve pork quality through this ubiquitous hog farm system and prepare a database with information collected from environmental factors and the hog farm control devices, which is expected to provide information needed to design and implement suitable control strategies for hog farm operation.
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Hwang, Jeonghwan; Yoe, Hyun
2010-01-01
Many hog farmers are now suffering from high pig mortality rates due to various wasting diseases and increased breeding costs, etc. It is therefore necessary for hog farms to implement systematic and scientific pig production technology to increase productivity and produce high quality pork in order to solve these problems. In this study, we describe such a technology by suggesting a ubiquitous hog farm system which applies WSN (Wireless Sensor Network) technology to the pig industry. We suggest that a WSN and CCTV (Closed-circuit television) should be installed on hog farms to collect environmental and image information which shall then help producers not only in monitoring the hog farm via the Web from outside the farm, but also facilitate the control of hog farm facilities in remote locations. In addition, facilities can be automatically controlled based on breeding environment parameters which are already set up and a SMS notice service to notify of deviations shall provide users with convenience. Hog farmers may increase production and improve pork quality through this ubiquitous hog farm system and prepare a database with information collected from environmental factors and the hog farm control devices, which is expected to provide information needed to design and implement suitable control strategies for hog farm operation. PMID:22163497
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Meza-Lucas, Antonio; Pérez-Villagómez, María-Fernanda; Martínez-López, José-Patricio; García-Rodea, Ricardo; Martínez-Castelán, María-Guadalupe; Escobar-Gutiérrez, Alejandro; de-la-Rosa-Arana, Jorge-Luis; Villanueva-Zamudio, Altagracia
2016-09-01
A comparison of DOT-ELISA and Standard-ELISA was made for detection of Vibrio cholerae toxin in culture supernatants of bacteria isolated from human and environmental samples. A total of 293 supernatants were tested in a double blind assay. A correlation of 100 % was obtained between both techniques. The cholera toxin was found in 20 Inaba and 3 Ogawa strains. Positive samples were from seafood (17 samples), potable water (1 sample) and sewage (5 samples). The DOT-ELISA was useful as the standard-ELISA to confirm the presence of cholera toxin in the environmental samples.
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Cytotoxic Effects of Environmental Toxins on Human Glial Cells.
D'Mello, Fiona; Braidy, Nady; Marçal, Helder; Guillemin, Gilles; Rossi, Fanny; Chinian, Mirielle; Laurent, Dominique; Teo, Charles; Neilan, Brett A
2017-02-01
Toxins produced by cyanobacteria and dinoflagellates have increasingly become a public health concern due to their degenerative effects on mammalian tissue and cells. In particular, emerging evidence has called attention to the neurodegenerative effects of the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA). Other toxins such as the neurotoxins saxitoxin and ciguatoxin, as well as the hepatotoxic microcystin, have been previously shown to have a range of effects upon the nervous system. However, the capacity of these toxins to cause neurodegeneration in human cells has not, to our knowledge, been previously investigated. This study aimed to examine the cytotoxic effects of BMAA, microcystin-LR (MC-LR), saxitoxin (STX) and ciguatoxin (CTX-1B) on primary adult human astrocytes. We also demonstrated that α-lipoate attenuated MC-LR toxicity in primary astrocytes and characterised changes in gene expression which could potentially be caused by these toxins in primary astrocytes. Herein, we are the first to show that all of these toxins are capable of causing physiological changes consistent with neurodegeneration in glial cells, via oxidative stress and excitotoxicity, leading to a reduction in cell proliferation culminating in cell death. In addition, MC-LR toxicity was reduced significantly in astrocytes-treated α-lipoic acid. While there were no significant changes in gene expression, many of the probes that were altered were associated with neurodegenerative disease pathogenesis. Overall, this is important in advancing our current understanding of the mechanism of toxicity of MC-LR on human brain function in vitro, particularly in the context of neurodegeneration.
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Mutschler, Hannes; Gebhardt, Maike; Shoeman, Robert L; Meinhart, Anton
2011-03-01
Most genomes of bacteria contain toxin-antitoxin (TA) systems. These gene systems encode a toxic protein and its cognate antitoxin. Upon antitoxin degradation, the toxin induces cell stasis or death. TA systems have been linked with numerous functions, including growth modulation, genome maintenance, and stress response. Members of the epsilon/zeta TA family are found throughout the genomes of pathogenic bacteria and were shown not only to stabilize resistance plasmids but also to promote virulence. The broad distribution of epsilon/zeta systems implies that zeta toxins utilize a ubiquitous bacteriotoxic mechanism. However, whereas all other TA families known to date poison macromolecules involved in translation or replication, the target of zeta toxins remained inscrutable. We used in vivo techniques such as microscropy and permeability assays to show that pneumococcal zeta toxin PezT impairs cell wall synthesis and triggers autolysis in Escherichia coli. Subsequently, we demonstrated in vitro that zeta toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) and that this activity is counteracted by binding of antitoxin. After identification of the product we verified the kinase activity in vivo by analyzing metabolite extracts of cells poisoned by PezT using high pressure liquid chromatograpy (HPLC). We further show that phosphorylated UNAG inhibitis MurA, the enzyme catalyzing the initial step in bacterial peptidoglycan biosynthesis. Additionally, we provide what is to our knowledge the first crystal structure of a zeta toxin bound to its substrate. We show that zeta toxins are novel kinases that poison bacteria through global inhibition of peptidoglycan synthesis. This provides a fundamental understanding of how epsilon/zeta TA systems stabilize mobile genetic elements. Additionally, our results imply a mechanism that connects activity of zeta toxin PezT to virulence of pneumococcal infections
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Diodati, Michelle E; Bates, Anne H; Cooley, Michael B; Walker, Samarpita; Mandrell, Robert E; Brandl, Maria T
2015-03-01
Escherichia coli serogroup O111 is among the six most commonly reported non-O157:H7 Shiga toxin-producing E. coli (STEC), which are emerging as important foodborne pathogens. We have assembled a collection of environmental and clinical strains of E. coli O111 from diverse sources and investigated various genotypic and phenotypic characteristics of these strains to gain a better understanding of the epidemiology and biology of this serogroup. Sixty-three percent of the strains (24/38) were of H-type 8, which dominated the environmental- and outbreak-strains group, whereas the sporadic-case strains were more heterogeneous in H-type. All of the environmental and outbreak strains harbored the Shiga toxin 1 gene (stx1), eae, and ehx, and a subset of these also carried the Shiga toxin 2 gene (stx2). Only 9 of 16 sporadic-case strains produced stx1 and/or stx2, and these were mostly of H-type 8 and 10. Pulsed-field gel electrophoresis analysis revealed a cluster of environmental, outbreak, and sporadic illness strains with high phylogenetic similarity. Strains in this pulsogroup were all of the H8 type and STEC pathotype, and carried eae and ehx. Smaller clusters of highly similar STEC O111 strains included outbreak and sporadic illness strains isolated during different time periods or from different geographical locations. A distinct aggregative behavior was observed in the cultures of all environmental and outbreak STEC O111 strains, but not in those of sporadic-case strains. Among environmental and outbreaks strains, aggregation was positively correlated with production of curli fimbriae and RpoS function, and negatively with cellulose synthesis, while the nonaggregative behavior of sporadic-case strains correlated (positively) only with cellulose production. Our results indicate that STEC O111 strains sharing high genotypic similarity and important phenotypic traits with STEC O111 outbreak strains are present in the agricultural environment and may contribute to the
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Williamson, Judy L.; Rocke, Tonie E.; Aiken, Judd M.
1999-01-01
A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.
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Lee, Tammy A; Rollwagen-Bollens, Gretchen; Bollens, Stephen M; Faber-Hammond, Joshua J
2015-04-01
The increasing frequency of harmful cyanobacterial blooms in freshwater systems is a commonly recognized problem due to detrimental effects on water quality. Vancouver Lake, a shallow, tidally influenced lake in the flood plain of the Columbia River within the city of Vancouver, WA, USA, has experienced numerous summertime cyanobacterial blooms, dominated by Aphanizomenon sp. and Anabaena sp. Cyanobacteria abundance and toxin (microcystin) levels have been monitored in this popular urban lake for several years; however, no previous studies have identified which cyanobacteria species produce toxins, nor analyzed how changes in environmental variables contribute to the fluctuations in toxic cyanobacteria populations. We used a suite of molecular techniques to analyze water samples from Vancouver Lake over two summer bloom cycles (2009 and 2010). Both intracellular and extracellular microcystin concentrations were measured using an ELISA kit. Intracellular microcystin concentrations exceeded WHO guidelines for recreational waters several times throughout the sampling period. PCR results demonstrated that Microcystis sp. was the sole microcystin-producing cyanobacteria species present in Vancouver Lake, although Microcystis sp. was rarely detected in microscopical counts. qPCR results indicated that the majority of the Microcystis sp. population contained the toxin-producing gene (mcyE), although Microcystis sp. abundance rarely exceeded 1 percent of overall cyanobacteria abundance. Non-metric multidimensional scaling (NMDS) revealed that PO4-P was the main environmental variable influencing the abundance of toxic and non-toxic cyanobacteria, as well as intracellular microcystin concentrations. Our study underscores the importance of using molecular genetic techniques, in addition to traditional microscopy, to assess the importance of less conspicuous species in the dynamics of harmful algal blooms. Copyright © 2014 Elsevier Inc. All rights reserved.
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Antibody-mediated inhibition of ricin toxin retrograde transport.
Yermakova, Anastasiya; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J
2014-04-08
Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin's binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases. IMPORTANCE Ricin is the prototypic member of the AB family of medically important plant and bacterial toxins that includes cholera and Shiga toxins. Ricin is also a category B biothreat agent. Despite ongoing efforts to develop vaccines and antibody-based therapeutics against ricin, very little is known about the mechanisms by which antibodies neutralize this toxin. In general, it is thought that antibodies simply prevent toxins from attaching to cell surface receptors or promote their clearance through Fc receptor (FcR)-mediated uptake
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The Role of Environmental Toxins on ALS: A Case-Control Study of Occupational Risk Factors
Su, Feng-Chiao.; Goutman, Stephen A.; Chernyak, Sergey; Mukherjee, Bhramar; Callaghan, Brian C.; Batterman, Stuart; Feldman, Eva L.
2016-01-01
Importance Persistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS). Objective To evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan, a state with historically high levels of environmental pollution. Design Case-control study conducted between 2011 and 2014. Setting Tertiary referral center/ALS referral center Participants ALS cases (n=156) with a diagnosis of definitive, probable, probable with laboratory support, or possible ALS by revised El Escorial criteria. Controls (n=128) were excluded if they had a diagnosis of ALS, another neurodegenerative condition, or a family history of ALS in a first- or second-degree blood relative. Additional exclusions included age less than 18 or inability to communicate in English. Main Outcome and Measure(s) Cases and controls completed a survey assessing occupational and residential exposures. Blood concentrations of 122 persistent environmental pollutants, including organochlorine pesticides (OCP), polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs), were measured using gas chromatography/mass spectrometry. Multivariable models with self-reported occupational exposures in various exposure time windows and environmental toxin blood concentrations were separately fit by logistic regression models. Concordance between the survey data and pollutant measurements was assessed using the nonparametric Kendall’s Tau correlation coefficient. Results Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS (OR = 5.09, 95% CI = 1.85–14.0). Military service was also associated with ALS in two time windows. A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of
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Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
Mantzouki, Evanthia; Fastner, Jutta; de Senerpont Domis, Lisette; Wilk-Woźniak, Elżbieta; Koreivienė, Judita; Verstijnen, Yvon; Krztoń, Wojciech; Walusiak, Edward; Karosienė, Jūratė; Kasperovičienė, Jūratė; Savadova, Ksenija; Vitonytė, Irma; Budzyńska, Agnieszka; Szeląg-Wasielewska, Elżbieta; Domek, Piotr; Messyasz, Beata; Pełechata, Aleksandra; Pełechaty, Mariusz; Kokocinski, Mikolaj; García-Murcia, Ana; Real, Monserrat; Romans, Elvira; Noguero-Ribes, Jordi; Duque, David Parreño; Karakaya, Nusret; Häggqvist, Kerstin; Beklioğlu, Meryem; Filiz, Nur; Iskin, Uğur; Bezirci, Gizem; Tavşanoğlu, Ülkü Nihan; Panou, Manthos; Fakioglu, Özden; Avagianos, Christos; Çelik, Kemal; Yilmaz, Mete; Marcé, Rafael; Buck, Moritz; Colom-Montero, William; Mustonen, Kristiina; Pierson, Don; Yang, Yang; Raposeiro, Pedro M.; Antoniou, Maria G.; Tsiarta, Nikoletta; McCarthy, Valerie; Perello, Victor C.; Feldmann, Tõnu; Panksep, Kristel; Tuvikene, Lea; Gagala, Ilona; Çınar, Şakir; Çapkın, Kadir; Yağcı, Abdulkadir; Cesur, Mehmet; Bilgin, Fuat; Bulut, Cafer; Uysal, Rahmi; Boscaini, Adriano; Cerasino, Leonardo; Richardson, Jessica; Visser, Petra M.; Verspagen, Jolanda M. H.; Karan, Tünay; Ochocka, Agnieszka; Pasztaleniec, Agnieszka; Köker, Latife; Albay, Meriç; Maronić, Dubravka Špoljarić; Stević, Filip; Pfeiffer, Tanja Žuna; Fonvielle, Jeremy; Rothhaupt, Karl-Otto; Hansson, Lars-Anders; Bláha, Luděk; Geriš, Rodan; Fránková, Markéta; Koçer, Mehmet Ali Turan; Alp, Mehmet Tahir; Remec-Rekar, Spela; Elersek, Tina; Hiskia, Anastasia; Haande, Sigrid; Skjelbred, Birger; Madrecka, Beata; Nemova, Hana; Drastichova, Iveta; Chomova, Lucia; Edwards, Christine; Sevindik, Tuğba Ongun; Tunca, Hatice; Önem, Burçin; Aleksovski, Boris; Krstić, Svetislav; Vucelić, Itana Bokan; Nawrocka, Lidia; Salmi, Pauliina; Machado-Vieira, Danielle; de Oliveira, Alinne Gurjão; Delgado-Martín, Jordi; García, David; Cereijo, Jose Luís; Trapote, Mari Carmen; Obrador, Biel; Grabowska, Magdalena; Chmura, Damian; Úbeda, Bárbara; Warming, Trine Perlt; Kobos, Justyna; Mazur-Marzec, Hanna; Arvola, Lauri; Alcaraz-Párraga, Pablo; Toporowska, Magdalena; Pawlik-Skowronska, Barbara; Niedźwiecki, Michał; Pęczuła, Wojciech; Moreno-Ostos, Enrique; Blanco, José María; Rodríguez, Valeriano; Montes-Pérez, Jorge Juan; Palomino, Roberto L.; Rodríguez-Pérez, Estela; Carballeira, Rafael; Picazo, Antonio; Santamans, Anna C.; Ferriol, Carmen; Romo, Susana; Dunalska, Julita; Sieńska, Justyna; Szymański, Daniel; Kostrzewska-Szlakowska, Iwona; Jasser, Iwona; Žutinić, Petar; Udovič, Marija Gligora; Plenković-Moraj, Anđelka; Frąk, Magdalena; Bańkowska-Sobczak, Agnieszka; Wasilewicz, Michał; Özkan, Korhan; Kangro, Kersti; Ibelings, Bas W.
2018-01-01
Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains. PMID:29652856
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Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins.
Mantzouki, Evanthia; Lürling, Miquel; Fastner, Jutta; de Senerpont Domis, Lisette; Wilk-Woźniak, Elżbieta; Koreivienė, Judita; Seelen, Laura; Teurlincx, Sven; Verstijnen, Yvon; Krztoń, Wojciech; Walusiak, Edward; Karosienė, Jūratė; Kasperovičienė, Jūratė; Savadova, Ksenija; Vitonytė, Irma; Cillero-Castro, Carmen; Budzyńska, Agnieszka; Goldyn, Ryszard; Kozak, Anna; Rosińska, Joanna; Szeląg-Wasielewska, Elżbieta; Domek, Piotr; Jakubowska-Krepska, Natalia; Kwasizur, Kinga; Messyasz, Beata; Pełechaty, Aleksandra; Pełechaty, Mariusz; Kokocinski, Mikolaj; García-Murcia, Ana; Real, Monserrat; Romans, Elvira; Noguero-Ribes, Jordi; Duque, David Parreño; Fernández-Morán, Elísabeth; Karakaya, Nusret; Häggqvist, Kerstin; Demir, Nilsun; Beklioğlu, Meryem; Filiz, Nur; Levi, Eti E.; Iskin, Uğur; Bezirci, Gizem; Tavşanoğlu, Ülkü Nihan; Özhan, Koray; Gkelis, Spyros; Panou, Manthos; Fakioglu, Özden; Avagianos, Christos; Kaloudis, Triantafyllos; Çelik, Kemal; Yilmaz, Mete; Marcé, Rafael; Catalán, Nuria; Bravo, Andrea G.; Buck, Moritz; Colom-Montero, William; Mustonen, Kristiina; Pierson, Don; Yang, Yang; Raposeiro, Pedro M.; Gonçalves, Vítor; Antoniou, Maria G.; Tsiarta, Nikoletta; McCarthy, Valerie; Perello, Victor C.; Feldmann, Tõnu; Laas, Alo; Panksep, Kristel; Tuvikene, Lea; Gagala, Ilona; Mankiewicz-Boczek, Joana; Yağcı, Meral Apaydın; Çınar, Şakir; Çapkın, Kadir; Yağcı, Abdulkadir; Cesur, Mehmet; Bilgin, Fuat; Bulut, Cafer; Uysal, Rahmi; Obertegger, Ulrike; Boscaini, Adriano; Flaim, Giovanna; Salmaso, Nico; Cerasino, Leonardo; Richardson, Jessica; Visser, Petra M.; Verspagen, Jolanda M. H.; Karan, Tünay; Soylu, Elif Neyran; Maraşlıoğlu, Faruk; Napiórkowska-Krzebietke, Agnieszka; Ochocka, Agnieszka; Pasztaleniec, Agnieszka; Antão-Geraldes, Ana M.; Vasconcelos, Vitor; Morais, João; Vale, Micaela; Köker, Latife; Akçaalan, Reyhan; Albay, Meriç; Špoljarić Maronić, Dubravka; Stević, Filip; Žuna Pfeiffer, Tanja; Fonvielle, Jeremy; Straile, Dietmar; Rothhaupt, Karl-Otto; Hansson, Lars-Anders; Urrutia-Cordero, Pablo; Bláha, Luděk; Geriš, Rodan; Fránková, Markéta; Koçer, Mehmet Ali Turan; Alp, Mehmet Tahir; Remec-Rekar, Spela; Elersek, Tina; Triantis, Theodoros; Zervou, Sevasti-Kiriaki; Hiskia, Anastasia; Haande, Sigrid; Skjelbred, Birger; Madrecka, Beata; Nemova, Hana; Drastichova, Iveta; Chomova, Lucia; Edwards, Christine; Sevindik, Tuğba Ongun; Tunca, Hatice; Önem, Burçin; Aleksovski, Boris; Krstić, Svetislav; Vucelić, Itana Bokan; Nawrocka, Lidia; Salmi, Pauliina; Machado-Vieira, Danielle; de Oliveira, Alinne Gurjão; Delgado-Martín, Jordi; García, David; Cereijo, Jose Luís; Gomà, Joan; Trapote, Mari Carmen; Vegas-Vilarrúbia, Teresa; Obrador, Biel; Grabowska, Magdalena; Karpowicz, Maciej; Chmura, Damian; Úbeda, Bárbara; Gálvez, José Ángel; Özen, Arda; Christoffersen, Kirsten Seestern; Warming, Trine Perlt; Kobos, Justyna; Mazur-Marzec, Hanna; Pérez-Martínez, Carmen; Ramos-Rodríguez, Eloísa; Arvola, Lauri; Alcaraz-Párraga, Pablo; Toporowska, Magdalena; Pawlik-Skowronska, Barbara; Niedźwiecki, Michał; Pęczuła, Wojciech; Leira, Manel; Hernández, Armand; Moreno-Ostos, Enrique; Blanco, José María; Rodríguez, Valeriano; Montes-Pérez, Jorge Juan; Palomino, Roberto L.; Rodríguez-Pérez, Estela; Carballeira, Rafael; Camacho, Antonio; Picazo, Antonio; Rochera, Carlos; Santamans, Anna C.; Ferriol, Carmen; Romo, Susana; Soria, Juan Miguel; Dunalska, Julita; Sieńska, Justyna; Szymański, Daniel; Kruk, Marek; Kostrzewska-Szlakowska, Iwona; Jasser, Iwona; Žutinić, Petar; Gligora Udovič, Marija; Plenković-Moraj, Anđelka; Frąk, Magdalena; Bańkowska-Sobczak, Agnieszka; Wasilewicz, Michał; Özkan, Korhan; Maliaka, Valentini; Kangro, Kersti; Grossart, Hans-Peter; Paerl, Hans W.; Carey, Cayelan C.; Ibelings, Bas W.
2018-04-13
Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
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ERIC Educational Resources Information Center
Schubert, Sandra; Zelinsky, Benjamin
Designed for parents, this primer presents information on threats to children's health that can be found in every American home, including disinfectants, art supplies, pesticides, and toxins in food and drinking water. The primer also provides practical information on safe and environmentally friendly household cleaners and disinfectants, outlines…
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NASA Astrophysics Data System (ADS)
Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J.
2005-05-01
The increasing threat of an intentional (attack) or accidental release of toxins, in particular chemical toxins, including chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) has increased public fear. The major problem in such attacks/accidents is to detect toxins present in very low levels. Indeed, several detection techniques are currently being used for the same. However, none of them meet the most critical requirements of a RISE (Rapid, Inexpensive, Simple and Effective) detect-to-protect class of biosensors. To address this critical demand our group has developed a prototype lab-on-a-chip (LOC) using a colloidal silver-based, surface-enhanced Raman spectroscopy (SERS)-linked immuno-sensor assay (SLISA). The LOC-SLISA was tested for the measurement of RAD54, a stress-marker protein expressed by yeast in response to hydrogen peroxide (H2O2), a toxin in the EPA priority list of chemical toxins. We found SLISA has good correlation in accuracy with the traditional ELISA technique and outperforms the latter by being rapid and easy-to-use. SLISA is more sensitive, provides qualitative information on immuno-sensor's chemical characterization and antigen-antibody binding, and allows direct detection with minimal or no chance of uncertainty, which is a stringent limitation of all label-based biosensor technologies including ELISA. For translational significance of our work, we correlated our results to U.S. EPA (environmental protection agency) defined risk exposure guideline levels of H2O2 to validate the commercial potential of our on-chip SLISA. The label-free, cell-based and RISE detection offered by SERS can allow development of biomedical and environmental sensor technology (BEST) needed for direct, rapid and continuous monitoring of human health and environment
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Environmental toxins and risk of narcolepsy among people with HLA DQB1*0602
Ton, Thanh G.N.; Longstreth, WT; Koepsell, Thomas D.
2010-01-01
One etiologic model for narcolepsy suggests that some environmental toxin selectively and irreversibly destroys hypocretin-producing cells in individuals with human leukocyte antigen (HLA) DQB1*0602. Between 2001-2005, the authors conducted a population-based case-control study in King County, Washington to examine narcolepsy risk in relation to toxins found in jobs, hobbies and other non-vocational activities. Sixty-seven cases and 95 controls were enrolled; all were between ages 18-50 and positive for HLA DQB1*0602. All were administered in-person interviews about jobs, hobbies or other non-vocational activities before age 21. All analyses were adjusted for African American race and income. Risk increased significantly for jobs involving heavy metals (odds ratio [OR]=4.7; 95% confidence interval [CI]: 1.5, 14.5) and for highest levels of exposure to woodwork (OR: 3.0; 95% CI: 1.0, 8.9), fertilizer (OR=3.1; 95% CI: 1.1, 9.1), and bug or weed killer (OR=4.5; 95% CI: 1.5, 13.4). Associations were of borderline significance for activities involving ceramics, pesticides, and painting projects. Significant dose-response relationships were evident for jobs involving metals (p<0.03), paints (p<0.03), and bug or weed killer (p<0.02). Additional studies are needed to replicate these findings and continue the search for specific toxins that could damage hypocretin neurons in genetically susceptible people. PMID:20519130
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Why do we study animal toxins?
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
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USDA-ARS?s Scientific Manuscript database
Shiga toxin-producing Escherichia coli (STEC) serotype O145 is one of the major non-O157 serotypes associated with severe human disease. Here we examined the genetic diversity, population structure, virulence potential, and antibiotic resistance profile of environmental O145 strains isolated from a ...
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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).
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Development of a quail embryo model for the detection of botulinum neurotoxin activity
USDA-ARS?s Scientific Manuscript database
Clostridium botulinum is a ubiquitous microorganism that under anaerobic conditions produces botulinum neurotoxins. In regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or environmental sample e...
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Yu, Fang Fang; Lin, Xia Lu; Yang, Lei; Liu, Huan; Wang, Xi; Fang, Hua; Lammi, ZMikko J; Guo, Xiong
2017-11-01
Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
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Perelle, S; Scalzo, S; Kochi, S; Mock, M; Popoff, M R
1997-01-01
Clostridium perfringens iota and C. spiroforme toxins consist of two separate proteins. One is the binding component and the other the enzymatic component. The two toxins secreted by Bacillus anthracis are composed of binary combinations of three proteins: protective antigen, lethal factor, and edema factor. As shown by Western blotting and ELISA, the binding component of anthrax toxin shares common epitopes with that of iota toxin and C. spiroforme toxin which are closely related immunologically. However, no functional complementation was observed between iota toxin and anthrax toxin components. The binding components can form toxins active on macrophages only in combination with their respective enzymatic components. Agents which prevent acidification of endosomes do not have the same effects on anthrax toxin activity as they do on iota and C. spiroforme toxins. Therefore, the mechanisms of entry into the cells are presumably different. Since the binding components of anthrax toxins and iota toxin share a conserved putative translocation domain, these binding components could have a common mode of insertion into the cell membranes.
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Zittrain, Jonathan
2008-10-28
Ubiquitous computing means network connectivity everywhere, linking devices and systems as small as a drawing pin and as large as a worldwide product distribution chain. What could happen when people are so readily networked? This paper explores issues arising from two possible emerging models of ubiquitous human computing: fungible networked brainpower and collective personal vital sign monitoring.
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Considerations on the role of environmental toxins in idiopathic Parkinson’s disease pathophysiology
2014-01-01
Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system. Often associated with atrophy of the affected central or peripheral nervous structures, they include diseases such as Parkinson’s Disease (PD), Alzheimer’s Disease and other dementias, Genetic Brain Disorders, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s Disease), Huntington’s Disease, Prion Diseases, and others. The prevalence of neurodegenerative diseases has increased over the last years. This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros. Therefore, understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies. While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase, different studies suggest that PD may be due to an increased exposure to environmental toxins. In this article we review epidemiological, sociological and experimental studies to determine which hypothesis is more plausible. Our conclusion is that, at least in idiopathic PD (iPD), the exposure to toxic environmental substances could play an important role in its aetiology. PMID:24826210
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Ferreira, Marcos Roberto A.; Moreira, Gustavo Marçal S. G.; da Cunha, Carlos Eduardo P.; Mendonça, Marcelo; Salvarani, Felipe M.; Moreira, Ângela N.; Conceição, Fabricio R.
2016-01-01
Clostridium perfringens is a spore-forming, commensal, ubiquitous bacterium that is present in the gastrointestinal tract of healthy humans and animals. This bacterium produces up to 18 toxins. The species is classified into five toxinotypes (A–E) according to the toxins that the bacterium produces: alpha, beta, epsilon, or iota. Each of these toxinotypes is associated with myriad different, frequently fatal, illnesses that affect a range of farm animals and humans. Alpha, beta, and epsilon toxins are the main causes of disease. Vaccinations that generate neutralizing antibodies are the most common prophylactic measures that are currently in use. These vaccines consist of toxoids that are obtained from C. perfringens cultures. Recombinant vaccines offer several advantages over conventional toxoids, especially in terms of the production process. As such, they are steadily gaining ground as a promising vaccination solution. This review discusses the main strategies that are currently used to produce recombinant vaccines containing alpha, beta, and epsilon toxins of C. perfringens, as well as the potential application of these molecules as vaccines for mammalian livestock animals. PMID:27879630
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Comparative Genomics of the Ubiquitous, Hydrocarbon-degrading Genus Marinobacter
NASA Astrophysics Data System (ADS)
Singer, E.; Webb, E.; Edwards, K. J.
2012-12-01
The genus Marinobacter is amongst the most ubiquitous in the global oceans and strains have been isolated from a wide variety of marine environments, including offshore oil-well heads, coastal thermal springs, Antarctic sea water, saline soils and associations with diatoms and dinoflagellates. Many strains have been recognized to be important hydrocarbon degraders in various marine habitats presenting sometimes extreme pH or salinity conditions. Analysis of the genome of M. aquaeolei revealed enormous adaptation versatility with an assortment of strategies for carbon and energy acquisition, sensation, and defense. In an effort to elucidate the ecological and biogeochemical significance of the Marinobacters, seven Marinobacter strains from diverse environments were included in a comparative genomics study. Genomes were screened for metabolic and adaptation potential to elucidate the strategies responsible for the omnipresence of the Marinobacter genus and their remedial action potential in hydrocarbon-polluted waters. The core genome predominantly encodes for key genes involved in hydrocarbon degradation, biofilm-relevant processes, including utilization of external DNA, halotolerance, as well as defense mechanisms against heavy metals, antibiotics, and toxins. All Marinobacter strains were observed to degrade a wide spectrum of hydrocarbon species, including aliphatic, polycyclic aromatic as well as acyclic isoprenoid compounds. Various genes predicted to facilitate hydrocarbon degradation, e.g. alkane 1-monooxygenase, appear to have originated from lateral gene transfer as they are located on gene clusters of 10-20% lower GC-content compared to genome averages and are flanked by transposases. Top ortholog hits are found in other hydrocarbon degrading organisms, e.g. Alcanivorax borkumensis. Strategies for hydrocarbon uptake encoded by various Marinobacter strains include cell surface hydrophobicity adaptation via capsular polysaccharide biosynthesis and attachment
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ERIC Educational Resources Information Center
McAnear, Anita
2006-01-01
When we planned the editorial calendar with the topic ubiquitous computing, we were thinking of ubiquitous computing as the one-to-one ratio of computers to students and teachers and 24/7 access to electronic resources. At the time, we were aware that ubiquitous computing in the computer science field had more to do with wearable computers. Our…
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Chen, Hsiao Ying; Tran, Hung; Foo, Ling Yann; Sew, Tracey Wenhui; Loke, Weng Keong
2014-08-01
Ricin is a toxin that can be easily extracted from seeds of Ricinus communis plants. Ricin is considered to be a major bio-threat as it can be freely and easily acquired in large quantities. A deliberate release of such toxin in civilian populations would very likely overwhelm existing public health systems, resulting in public fear and social unrest. There is currently no commercially available or FDA-approved prophylaxis such as vaccines, or therapeutic antitoxins or antidotes, available for ricin intoxication. Patient treatment is typically supportive care based on symptoms, often designed to reinforce the body's natural response. This paper describes the development and validation of a robust ELISA test kit, which can be used to screen for ricin in biological specimens such as whole blood and faeces. Faecal specimens are shown in this study to have better diagnostic sensitivity and a wider diagnostic window compared to whole blood. From these results, it is concluded that faeces is the most suitable clinical specimen for diagnosis of ricin poisoning via the oral route. The ELISA test kit can also detect ricin in environmental samples. An advantage of this ELISA kit over other commercial off-the-shelf (COTS) detection kits currently on the market that are developed to screen environmental samples only is its ability to diagnose ricin poisoning from clinical specimens as well as detect ricin from environmental samples.
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Toxin-Antitoxin Systems in the Mobile Genome of Acidithiobacillus ferrooxidans
Bustamante, Paula; Tello, Mario; Orellana, Omar
2014-01-01
Toxin-antitoxin (TA) systems are genetic modules composed of a pair of genes encoding a stable toxin and an unstable antitoxin that inhibits toxin activity. They are widespread among plasmids and chromosomes of bacteria and archaea. TA systems are known to be involved in the stabilization of plasmids but there is no consensus about the function of chromosomal TA systems. To shed light on the role of chromosomally encoded TA systems we analyzed the distribution and functionality of type II TA systems in the chromosome of two strains from Acidithiobacillus ferrooxidans (ATCC 23270 and 53993), a Gram-negative, acidophilic, environmental bacterium that participates in the bioleaching of minerals. As in other environmental microorganisms, A. ferrooxidans has a high content of TA systems (28-29) and in twenty of them the toxin is a putative ribonuclease. According to the genetic context, some of these systems are encoded near or within mobile genetic elements. Although most TA systems are shared by both strains, four of them, which are encoded in the active mobile element ICEAfe1, are exclusive to the type strain ATCC 23270. We demostrated that two TA systems from ICEAfe1 are functional in E. coli cells, since the toxins inhibit growth and the antitoxins counteract the effect of their cognate toxins. All the toxins from ICEAfe1, including a novel toxin, are RNases with different ion requirements. The data indicate that some of the chromosomally encoded TA systems are actually part of the A. ferrooxidans mobile genome and we propose that could be involved in the maintenance of these integrated mobile genetic elements. PMID:25384039
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Hydra, a model system for environmental studies.
Quinn, Brian; Gagné, François; Blaise, Christian
2012-01-01
Hydra have been extensively used for studying the teratogenic and toxic potential of numerous toxins throughout the years and are more recently growing in popularity to assess the impacts of environmental pollutants. Hydra are an appropriate bioindicator species for use in environmental assessment owing to their easily measurable physical (morphology), biochemical (xenobiotic biotransformation; oxidative stress), behavioural (feeding) and reproductive (sexual and asexual) endpoints. Hydra also possess an unparalleled ability to regenerate, allowing the assessment of teratogenic compounds and the impact of contaminants on stem cells. Importantly, Hydra are ubiquitous throughout freshwater environments and relatively easy to culture making them appropriate for use in small scale bioassay systems. Hydra have been used to assess the environmental impacts of numerous environmental pollutants including metals, organic toxicants (including pharmaceuticals and endocrine disrupting compounds), nanomaterials and industrial and municipal effluents. They have been found to be among the most sensitive animals tested for metals and certain effluents, comparing favourably with more standardised toxicity tests. Despite their lack of use in formalised monitoring programmes, Hydra have been extensively used and are regarded as a model organism in aquatic toxicology.
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INVESTIGATOIN OF CYANOBACTERIA TOXINS IN WATER
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... -
Ozcan, Cengiz; Ismi, Onur
2016-08-01
Rhinitis is a common clinical entity. Besides nasal obstruction, itching, and sneezing, one of the most important symptoms of rhinitis is nasal hypersecretion produced by nasal glands and exudate from the nasal vascular bed. Allergic rhinitis is an IgE-mediated inflammatory reaction of nasal mucosa after exposure to environmental allergens. Idiopathic rhinitis describes rhinitis symptoms that occur after non-allergic, noninfectious irritants. Specific allergen avoidance, topical nasal decongestants, nasal corticosteroids, immunotherapy, and sinonasal surgery are the main treatment options. Because the current treatment modalities are not enough for reducing rhinorrhea in some patients, novel treatment options are required to solve this problem. Botulinum toxin is an exotoxin generated by Clostridium botulinum. It disturbs the signal transmission at the neuromuscular and neuroglandular junction by inhibiting the acetylcholine release from the presynaptic nerve terminal. It has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. There have been a lot of published articles concerning the effect of this toxin on rhinitis symptoms. Based on the results of these reports, intranasal botulinum toxin A administration appears to be a safe and effective treatment method for decreasing rhinitis symptoms in rhinitis patients with a long-lasting effect. Botulinum toxin type A will be a good treatment option for the chronic rhinitis patients who are resistant to other treatment methods.
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Learning with Ubiquitous Computing
ERIC Educational Resources Information Center
Rosenheck, Louisa
2008-01-01
If ubiquitous computing becomes a reality and is widely adopted, it will inevitably have an impact on education. This article reviews the background of ubiquitous computing and current research projects done involving educational "ubicomp." Finally it explores how ubicomp may and may not change education in both formal and informal settings and…
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Membrane-aerated biofilm proton and oxygen flux during chemical toxin exposure.
McLamore, E S; Zhang, W; Porterfield, D M; Banks, M K
2010-09-15
Bioreactors containing sessile bacteria (biofilms) grown on hollow fiber membranes have been used for treatment of many wastestreams. Real time operational control of bioreactor performance requires detailed knowledge of the relationship between bulk liquid water quality and physiological transport at the biofilm-liquid interface. Although large data sets exist describing membrane-aerated bioreactor effluent quality, very little real time data is available characterizing boundary layer transport under physiological conditions. A noninvasive, microsensor technique was used to quantify real time (≈1.5 s) changes in oxygen and proton flux for mature Nitrosomonas europaea and Pseudomonas aeruginosa biofilms in membrane-aerated bioreactors following exposure to environmental toxins. Stress response was characterized during exposure to toxins with known mode of action (chlorocarbonyl cyanide phenyl-hydrazone and potassium cyanide), and four environmental toxins (rotenone, 2,4-dinitrophenol, cadmium chloride, and pentachlorophenol). Exposure to sublethal concentrations of all environmental toxins caused significant increases in O(2) and/or H(+) flux (depending on the mode of action). These real time microscale signatures (i.e., fingerprints) of O(2) and H(+) flux can be coupled with bulk liquid analysis to improve our understanding of physiology in counter-diffusion biofilms found within membrane aerated bioreactors; leading to enhanced monitoring/modeling strategies for bioreactor control.
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A Collaborative Model for Ubiquitous Learning Environments
ERIC Educational Resources Information Center
Barbosa, Jorge; Barbosa, Debora; Rabello, Solon
2016-01-01
Use of mobile devices and widespread adoption of wireless networks have enabled the emergence of Ubiquitous Computing. Application of this technology to improving education strategies gave rise to Ubiquitous e-Learning, also known as Ubiquitous Learning. There are several approaches to organizing ubiquitous learning environments, but most of them…
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ERIC Educational Resources Information Center
Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.
This report contains the proceedings of the first of two hearings that explored the risks of environmental toxins to children. Testimony concerned the special vulnerability of children to toxins; the dangers of lead poisoning; instances of childhood cancer, birth defects, and developmental problems; passive smoking; child health in the California…
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Targeted Silencing of Anthrax Toxin Receptors Protects against Anthrax Toxins*
Arévalo, Maria T.; Navarro, Ashley; Arico, Chenoa D.; Li, Junwei; Alkhatib, Omar; Chen, Shan; Diaz-Arévalo, Diana; Zeng, Mingtao
2014-01-01
Anthrax spores can be aerosolized and dispersed as a bioweapon. Current postexposure treatments are inadequate at later stages of infection, when high levels of anthrax toxins are present. Anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2). We hypothesized that host cells would be protected from anthrax toxins if anthrax toxin receptor expression was effectively silenced using RNA interference (RNAi) technology. Thus, anthrax toxin receptors in mouse and human macrophages were silenced using targeted siRNAs or blocked with specific antibody prior to challenge with anthrax lethal toxin. Viability assays were used to assess protection in macrophages treated with specific siRNA or antibody as compared with untreated cells. Silencing CMG2 using targeted siRNAs provided almost complete protection against anthrax lethal toxin-induced cytotoxicity and death in murine and human macrophages. The same results were obtained by prebinding cells with specific antibody prior to treatment with anthrax lethal toxin. In addition, TEM8-targeted siRNAs also offered significant protection against lethal toxin in human macrophage-like cells. Furthermore, silencing CMG2, TEM8, or both receptors in combination was also protective against MEK2 cleavage by lethal toxin or adenylyl cyclase activity by edema toxin in human kidney cells. Thus, anthrax toxin receptor-targeted RNAi has the potential to be developed as a life-saving, postexposure therapy against anthrax. PMID:24742682
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Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu
2012-11-01
Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.
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Continuous evolution of B. thuringiensis toxins overcomes insect resistance
Badran, Ahmed H.; Guzov, Victor M.; Huai, Qing; Kemp, Melissa M.; Vishwanath, Prashanth; Kain, Wendy; Nance, Autumn M.; Evdokimov, Artem; Moshiri, Farhad; Turner, Keith H.; Wang, Ping; Malvar, Thomas; Liu, David R.
2016-01-01
The Bacillus thuringiensis δ-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. We developed a phage-assisted continuous evolution (PACE) selection that rapidly evolves high-affinity protein-protein interactions, and applied this system to evolve variants of the Bt toxin Cry1Ac that bind a cadherin-like receptor from the insect pest Trichoplusia ni (TnCAD) that is not natively targeted by wild-type Cry1Ac. The resulting evolved Cry1Ac variants bind TnCAD with high affinity (Kd = 11–41 nM), kill TnCAD-expressing insect cells that are not susceptible to wild-type Cry1Ac, and kill Cry1Ac-resistant T. ni insects up to 335-fold more potently than wild-type Cry1Ac. Our findings establish that the evolution of Bt toxins with novel insect cell receptor affinity can overcome Bt toxin resistance in insects and confer lethality approaching that of the wild-type Bt toxin against non-resistant insects. PMID:27120167
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A Dynamic Ubiquitous Learning Resource Model with Context and Its Effects on Ubiquitous Learning
ERIC Educational Resources Information Center
Chen, Min; Yu, Sheng Quan; Chiang, Feng Kuang
2017-01-01
Most ubiquitous learning researchers use resource recommendation and retrieving based on context to provide contextualized learning resources, but it is the kind of one-way context matching. Learners always obtain fixed digital learning resources, which present all learning contents in any context. This study proposed a dynamic ubiquitous learning…
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The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis
Park, Kyung-Duck; Pak, Sok Cheon; Park, Kwan-Kyu
2016-01-01
Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%–60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD. PMID:28025545
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Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.
Hettiarachchi, Kalindi D; Zimmet, Paul Z; Myers, Mark A
2008-05-01
The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.
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Epsilon toxin: a fascinating pore-forming toxin.
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. © 2011 The Author Journal compilation © 2011 FEBS.
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... toxin; Colitis - toxin; Pseudomembranous - toxin; Necrotizing colitis - toxin; C difficile - toxin ... be analyzed. There are several ways to detect C difficile toxin in the stool sample. Enzyme immunoassay ( ...
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Trapping toxins within lipid droplets is a resistance mechanism in fungi
Chang, Wenqiang; Zhang, Ming; Zheng, Sha; Li, Ying; Li, Xiaobin; Li, Wei; Li, Gang; Lin, Zhaomin; Xie, Zhiyu; Zhao, Zuntian; Lou, Hongxiang
2015-01-01
Lipid droplets (LDs) act as intracellular storage organelles in most types of cells and are principally involved in energy homeostasis and lipid metabolism. However, the role of LDs in resistance to toxins in fungi remains largely unknown. Here, we show that the trapping of endogenous toxins by LDs is a self-resistance mechanism in the toxin producer, while absorbing external lipophilic toxins is a resistance mechanism in the toxin recipient that acts to quench the production of reactive oxygen species. We found that an endolichenic fungus that generates phototoxic perylenequinones (PQs) trapped the PQs inside LDs. Using a model that incorporates the fungicidal action of hypocrellin A (HA), a PQ derivative, we showed that yeast cells escaped killing by trapping toxins inside LDs. Furthermore, LD-deficient mutants were hypersusceptible to HA-mediated phototoxins and other fungicides. Our study identified a previously unrecognised function of LDs in fungi that has implications for our understanding of environmental adaptation strategies for fungi and antifungal drug discovery. PMID:26463663
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Natural Toxins for Use in Pest Management
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
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Natural toxins for use in pest management.
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.
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USDA-ARS?s Scientific Manuscript database
Investigation of environmental factors on the prevalence of free bacteriophages against Shiga toxin-producing Escherichia coli strains in produce pre-harvest environment in Salinas, California Yen-Te Liaoa, Irwin Quintelab, Kimberly Nguyena, Alexandra Salvadora, Michael Cooleya, and Vivian C.H. Wu*a...
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Technologies for Achieving Field Ubiquitous Computing
NASA Astrophysics Data System (ADS)
Nagashima, Akira
Although the term “ubiquitous” may sound like jargon used in information appliances, ubiquitous computing is an emerging concept in industrial automation. This paper presents the author's visions of field ubiquitous computing, which is based on the novel Internet Protocol IPv6. IPv6-based instrumentation will realize the next generation manufacturing excellence. This paper focuses on the following five key issues: 1. IPv6 standardization; 2. IPv6 interfaces embedded in field devices; 3. Compatibility with FOUNDATION fieldbus; 4. Network securities for field applications; and 5. Wireless technologies to complement IP instrumentation. Furthermore, the principles of digital plant operations and ubiquitous production to support the above key technologies to achieve field ubiquitous systems are discussed.
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Natural toxins for use in pest management
USDA-ARS?s Scientific Manuscript database
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 ...
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A toxin-antitoxin module as a target for antimicrobial development.
Lioy, Virginia S; Rey, Oscar; Balsa, Dolors; Pellicer, Teresa; Alonso, Juan C
2010-01-01
The emergence and spread of pathogenic bacteria that have become resistant to multiple antibiotics through lateral gene transfer have created the need of novel antimicrobials. Toxin-antitoxin (TA) modules, which have been implicated in plasmid maintenance and stress management, are ubiquitous among plasmids from vancomycin or methicillin resistant bacteria. In the Streptococcus pyogenes pSM19035-encoded TA loci, the labile epsilon antitoxin binds to free zeta toxin and neutralizes it. When the zeta toxin is freed from the epsilon antitoxin, it induces a reversible state of growth arrest with a drastic reduction on the rate of replication, transcription and translation. However, upon prolonged zeta toxin action, the cells can no longer be rescued from their stasis state. A compound that disrupts the epsilon.zeta interaction can be considered as an attractive antimicrobial agent. Gene epsilon was fused to luc (Luc-epsilon antitoxin) and zeta to the gfp gene (zeta-GFP). Luc-epsilon or epsilon antitoxin neutralizes the toxic effect of the zeta or zeta-GFP toxin. In the absence of the antitoxin, free zeta or zeta-GFP triggers a reversible loss of cell proliferation, but the zetaK46A-GFP variant fails to block growth. Bioluminescence resonance energy transfer (BRET) assay was developed for high-throughput screening (HTS). To develop the proper controls, molecular dynamics studies were used to predict that the Asp18 and/or Glu22 residues might be relevant for epsilon.zeta interaction. Luc-epsilon efficiently transfers the excited energy to the fluorescent acceptor molecule (zeta-GFP or zetaK46A-GFP) and rendered high bioluminescence BRET signals. The exchange of Asp18 to Ala from zeta (D18A) affects Luc-epsilon.zetaD18A K46A-GFP interaction. In this study, we validate the hypothesis that it is possible to disrupt a TA module and offer a novel and unexploited targets to fight against antibiotic-resistant strains. Copyright 2009 Elsevier Inc. All rights reserved.
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Feng, Peter C H; Delannoy, Sabine; Lacher, David W; Dos Santos, Luis Fernando; Beutin, Lothar; Fach, Patrick; Rivas, Marta; Hartland, Elizabeth L; Paton, Adrienne W; Guth, Beatriz E C
2014-08-01
Shiga toxin-producing Escherichia coli strains of serotype O113:H21 have caused severe human diseases, but they are unusual in that they do not produce adherence factors coded by the locus of enterocyte effacement. Here, a PCR microarray was used to characterize 65 O113:H21 strains isolated from the environment, food, and clinical infections from various countries. In comparison to the pathogenic strains that were implicated in hemolytic-uremic syndrome in Australia, there were no clear differences between the pathogens and the environmental strains with respect to the 41 genetic markers tested. Furthermore, all of the strains carried only Shiga toxin subtypes associated with human infections, suggesting that the environmental strains have the potential to cause disease. Most of the O113:H21 strains were closely related and belonged in the same clonal group (ST-223), but CRISPR analysis showed a great degree of genetic diversity among the O113:H21 strains. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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NASA Astrophysics Data System (ADS)
Hwang, Jeonghwan; Lee, Jiwoong; Lee, Hochul; Yoe, Hyun
The wireless sensor networks (WSN) technology based on low power consumption is one of the important technologies in the realization of ubiquitous society. When the technology would be applied to the agricultural field, it can give big change in the existing agricultural environment such as livestock growth environment, cultivation and harvest of agricultural crops. This research paper proposes the 'Pig Farm Integrated Management System' based on WSN technology, which will establish the ubiquitous agricultural environment and improve the productivity of pig-raising farmers. The proposed system has WSN environmental sensors and CCTV at inside/outside of pig farm. These devices collect the growth-environment related information of pigs, such as luminosity, temperature, humidity and CO2 status. The system collects and monitors the environmental information and video information of pig farm. In addition to the remote-control and monitoring of the pig farm facilities, this system realizes the most optimum pig-raising environment based on the growth environmental data accumulated for a long time.
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Inhibition of cholera toxin and other AB toxins by polyphenolic compounds
USDA-ARS?s Scientific Manuscript database
All AB-type protein toxins have intracellular targets despite an initial extracellular location. These toxins use different methods to reach the cytosol and have different effects on the target cell. Broad-spectrum inhibitors against AB toxins are therefore hard to develop because the toxins use dif...
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Ubiquitous computing in the military environment
NASA Astrophysics Data System (ADS)
Scholtz, Jean
2001-08-01
Increasingly people work and live on the move. To support this mobile lifestyle, especially as our work becomes more intensely information-based, companies are producing various portable and embedded information devices. The late Mark Weiser coined the term, 'ubiquitous computing' to describe an environment where computers have disappeared and are integrated into physical objects. Much industry research today is concerned with ubiquitous computing in the work and home environments. A ubiquitous computing environment would facilitate mobility by allowing information users to easily access and use information anytime, anywhere. As war fighters are inherently mobile, the question is what effect a ubiquitous computing environment would have on current military operations and doctrine. And, if ubiquitous computing is viewed as beneficial for the military, what research would be necessary to achieve a military ubiquitous computing environment? What is a vision for the use of mobile information access in a battle space? Are there different requirements for civilian and military users of this technology? What are those differences? Are there opportunities for research that will support both worlds? What type of research has been supported by the military and what areas need to be investigated? Although we don't yet have all the answers to these questions, this paper discusses the issues and presents the work we are doing to address these issues.
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The Future of Ubiquitous Elearning
ERIC Educational Resources Information Center
Arndt, Timothy
2014-01-01
Post-secondary students are increasingly receiving instruction by eLearning. Many or these are part-time students or are working while taking classes. In such circumstances, students may find themselves short of time to study. One mechanism that can be exploited to make the best use of available time is ubiquitous eLearning. Ubiquitous eLearning…
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Binding of ATP by pertussis toxin and isolated toxin subunits
DOE Office of Scientific and Technical Information (OSTI.GOV)
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;more » 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.« less
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PHARMACEUTICALS AS UBIQUITOUS POLLUTANTS ...
Those chemical pollutants that are regulated under various international, federal, and state programs represent but a small fraction of the universe of chemicals that occur in the environment as a result of both natural processes and human influence. Although this galaxy of targeted chemicals might be minuscule compared with the universe of both known and yet-to-be identified chemicals, an implicit assumption is that these selective lists of chemicals are responsible for the most significant share of risk with respect to environmental or economic impairment or to human health. Pharmaceuticals and personal care products (PPCPs) comprise a particularly large and diverse array of unregulated pollutants that occur in the environment from the combined activities and actions of multitudes of individuals as well as from veterinary and agricultural use. Although the concentration of any individual PPCP rarely ever exceeds the sub-ppm level (if present in drinking water, concentrations of individual PPCPs are generally less than the ppt-ppb level), evidence is accumulating that these trace-Ievel pollutants are ubiquitous, they can have a continuous presence regardless of environmental half-lives ( e.g., where sanitary wastewaters enter the environment), and the numbers of distinct and varied chemical entities could be extremely large (given that thousands are in commercial use). The research focused on in the subtasks is the development and application of state-of the-ar
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Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier
2015-12-01
To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.
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Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology.
Harms, Alexander; Brodersen, Ditlev Egeskov; Mitarai, Namiko; Gerdes, Kenn
2018-06-07
Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules. Copyright © 2018 Elsevier Inc. All rights reserved.
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Toxic shock syndrome toxin-1, not α-toxin, mediated Bundaberg fatalities.
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.
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Tobacco Product Waste: An Environmental Approach to Reduce Tobacco Consumption.
Novotny, Thomas E; Slaughter, Elli
2014-01-01
Cigarette butts and other tobacco product wastes (TPW) are the most common items picked up in urban and beach cleanups worldwide. TPW contains all the toxins, nicotine, and carcinogens found in tobacco products, along with the plastic nonbiodegradable filter attached to almost all cigarettes sold in the United States and in most countries worldwide. Toxicity studies suggest that compounds leached from cigarette butts in salt and fresh water are toxic to aquatic micro-organisms and test fish. Toxic chemicals have also been identified in roadside TPW. With as much as two-thirds of all smoked cigarettes (numbering in the trillions globally) being discarded into the environment each year, it is critical to consider the potential toxicity and remediation of these waste products. This article reviews reports on the toxicity of TPW and recommends several policy approaches to mitigation of this ubiquitous environmental blight.
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Lazarovici, P; Yavin, E
1985-01-25
The properties of tetanus toxin interaction with human erythrocytes supplemented with disialo- and trisialo-gangliosides have been investigated. Binding of toxin is linear with time for 1 h and is 3-4-fold higher at 37 degrees C than at 4 degrees C during incubation of long duration. It exhibits saturation at toxin concentrations between 0.1 and 1 microgram/ml; however, it is nonsaturable between 1 and up to 50 micrograms/ml. It is effectively prevented by free gangliosides and antibodies or by pretreatment with sialidase but is unaffected by a number of closely related ligands including toxoid and toxin fragments. NaCl (1 M) removes a great portion (86%) of cell-associated toxin while Triton X-100 extracts an additional fraction (30%) of the salt-resistant cell-bound toxin. The residual sequestred toxin after detergent extraction is sensitive to proteolytic degradation. The trypsin-stable fraction (1.5%) is biotoxic and may be indicative of internalization of toxin. A macromolecular complex of about 700 kDa containing toxin and gangliosides has been isolated and characterized by Sephacryl S-300 gel permeation chromatography, SDS-gel electrophoresis, immunoprecipitability and biotoxicity. This complex is obtained only in ganglioside-supplemented cells and not when free 3H-labeled GD1b is reacted with 125I-labeled toxin in solution in the absence of cells. The hydrophobicity properties acquired as a result of ganglioside-toxin interaction, presumably at the cell surface, suggest a conformational change of the toxin which may enable its penetration into the bilayer.
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Update on the Role of Environmental Toxins in Neurodevelopmental Disabilities
ERIC Educational Resources Information Center
Kouris, Steven
2007-01-01
Toxic exposures during pregnancy and early childhood continue to play an important role as a preventable cause of neurodevelopmental disabilities in the U.S. and around the world. Identifying and eliminating these toxins should be a priority, but the task is made exceedingly difficult due to the severe limits of scientific knowledge in this area…
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2015-01-01
Parkinson’s disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat “hijacks” the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations
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Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems.
Chan, Wai Ting; Espinosa, Manuel; Yeo, Chew Chieng
2016-01-01
In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I-VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall
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Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems
Chan, Wai Ting; Espinosa, Manuel; Yeo, Chew Chieng
2016-01-01
In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I–VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall
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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
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The Regulatory Networks That Control Clostridium difficile Toxin Synthesis
Martin-Verstraete, Isabelle; Peltier, Johann; Dupuy, Bruno
2016-01-01
The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection. PMID:27187475
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Toxicological Review of Cyanobacterial Toxins: Cylindrospermopsin (External Review Draft)
The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...
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Dashboard for Analyzing Ubiquitous Learning Log
ERIC Educational Resources Information Center
Lkhagvasuren, Erdenesaikhan; Matsuura, Kenji; Mouri, Kousuke; Ogata, Hiroaki
2016-01-01
Mobile and ubiquitous technologies have been applied to a wide range of learning fields such as science, social science, history and language learning. Many researchers have been investigating the development of ubiquitous learning environments; nevertheless, to date, there have not been enough research works related to the reflection, analysis…
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Zebrafish in Toxicology and Environmental Health.
Bambino, Kathryn; Chu, Jaime
2017-01-01
As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of toxicant exposure are emerging as critical public health concerns. Additionally, chemicals that naturally occur in the environment, such as metals, have profound effects on human and animal health. Many of these compounds are in the news: lead, arsenic, and endocrine disruptors such as bisphenol A have all been widely publicized as causing disease or damage to humans and wildlife in recent years. Despite the widespread appreciation that environmental toxins can be harmful, there is limited understanding of how many toxins cause disease. Zebrafish are at the forefront of toxicology research; this system has been widely used as a tool to detect toxins in water samples and to investigate the mechanisms of action of environmental toxins and their related diseases. The benefits of zebrafish for studying vertebrate development are equally useful for studying teratogens. Here, we review how zebrafish are being used both to detect the presence of some toxins as well as to identify how environmental exposures affect human health and disease. We focus on areas where zebrafish have been most effectively used in ecotoxicology and in environmental health, including investigation of exposures to endocrine disruptors, industrial waste byproducts, and arsenic. © 2017 Elsevier Inc. All rights reserved.
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Zebrafish in Toxicology and Environmental Health
Bambino, Kathryn; Chu, Jaime
2018-01-01
As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of toxicant exposure are emerging as critical public health concerns. Additionally, chemicals that naturally occur in the environment, such as metals, have profound effects on human and animal health. Many of these compounds are in the news: lead, arsenic, and endocrine disruptors such as bisphenol A have all been widely publicized as causing disease or damage to humans and wildlife in recent years. Despite the widespread appreciation that environmental toxins can be harmful, there is limited understanding of how many toxins cause disease. Zebrafish are at the forefront of toxicology research; this system has been widely used as a tool to detect toxins in water samples and to investigate the mechanisms of action of environmental toxins and their related diseases. The benefits of zebrafish for studying vertebrate development are equally useful for studying teratogens. Here, we review how zebrafish are being used both to detect the presence of some toxins as well as to identify how environmental exposures affect human health and disease. We focus on areas where zebrafish have been most effectively used in ecotoxicology and in environmental health, including investigation of exposures to endocrine disruptors, industrial waste byproducts, and arsenic. PMID:28335863
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1984-10-26
focused initially on EF because it seemed possible that this component, like cholera toxin, might cause edema in skin through elevation of cellular cAMP...behavior differed from that seen in cells exposed to cholera toxin, where cellular cAMP levels remain elevated upon toxin removal. Studies in CHO cell...LF, the rat bioassay is not likely to be an appropriate system for studying the cellular and molecular mechanisms of action of LF. Therefore, a survey
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Bioterrorism: toxins as weapons.
Anderson, Peter D
2012-04-01
The potential for biological weapons to be used in terrorism is a real possibility. Biological weapons include infectious agents and toxins. Toxins are poisons produced by living organisms. Toxins relevant to bioterrorism include ricin, botulinum, Clostridium perfrigens epsilson toxin, conotoxins, shigatoxins, saxitoxins, tetrodotoxins, mycotoxins, and nicotine. Toxins have properties of biological and chemical weapons. Unlike pathogens, toxins do not produce an infection. Ricin causes multiorgan toxicity by blocking protein synthesis. Botulinum blocks acetylcholine in the peripheral nervous system leading to muscle paralysis. Epsilon toxin damages cell membranes. Conotoxins block potassium and sodium channels in neurons. Shigatoxins inhibit protein synthesis and induce apoptosis. Saxitoxin and tetrodotoxin inhibit sodium channels in neurons. Mycotoxins include aflatoxins and trichothecenes. Aflatoxins are carcinogens. Trichothecenes inhibit protein and nucleic acid synthesis. Nicotine produces numerous nicotinic effects in the nervous system.
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Metabolism of HT-2 Toxin and T-2 Toxin in Oats
Meng-Reiterer, Jacqueline; Bueschl, Christoph; Rechthaler, Justyna; Berthiller, Franz; Lemmens, Marc; Schuhmacher, Rainer
2016-01-01
The Fusarium mycotoxins HT-2 toxin (HT2) and T-2 toxin (T2) are frequent contaminants in oats. These toxins, but also their plant metabolites, may contribute to toxicological effects. This work describes the use of 13C-assisted liquid chromatography–high-resolution mass spectrometry for the first comprehensive study on the biotransformation of HT2 and T2 in oats. Using this approach, 16 HT2 and 17 T2 metabolites were annotated including novel glycosylated and hydroxylated forms of the toxins, hydrolysis products, and conjugates with acetic acid, putative malic acid, malonic acid, and ferulic acid. Further targeted quantitative analysis was performed to study toxin metabolism over time, as well as toxin and conjugate mobility within non-treated plant tissues. As a result, HT2-3-O-β-d-glucoside was identified as the major detoxification product of both parent toxins, which was rapidly formed (to an extent of 74% in HT2-treated and 48% in T2-treated oats within one day after treatment) and further metabolised. Mobility of the parent toxins appeared to be negligible, while HT2-3-O-β-d-glucoside was partly transported (up to approximately 4%) through panicle side branches and stem. Our findings demonstrate that the presented combination of untargeted and targeted analysis is well suited for the comprehensive elucidation of mycotoxin metabolism in plants. PMID:27929394
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Toxin yet not toxic: Botulinum toxin in dentistry.
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.
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Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin.
Popoff, M R; Boquet, P
1988-05-16
We have purified from Clostridium spiroforme strain 246 an heterogeneous population of proteins (Sa) ranging from 43 to 47 kilodaltons exhibiting ADP-ribosyl transferase activity as do C. botulinum C2 toxin component I or the ia chain of C. perfringens E iota toxin. C. spiriforme Sa had alone no activity upon injection in mice or inoculated to Vero cells. When spiroforme ADP ribosyl transferase were mixed with a trypsin activated protein (Sb) separated from C. spiroforme bacterial supernatant, a lethal effect in mice and cytotoxicity on Vero cells were recorded. The Sa cross-reacted immunologically with either the light chain of C. perfringens E iota toxin or the ADP-ribosyl transferase from C. difficile 196 strain. No immunological relatedness was observed between Sa and C2 toxin component I. C. spiroforme toxin is thus another binary toxin close to iota.
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PROSPECTS ON BEHAVIORAL STUDIES OF MARINE AND FRESHWATER TOXINS.
This manuscript is based in large part on an invited presentation. The manuscript provides a brief overview of the growing issue of the human-health and environmental impact of a variety of toxins of marine and freshwater origin, the current (generally crude) state of behavioral...
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Toxin-Induced Experimental Models of Learning and Memory Impairment
More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug
2016-01-01
Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson’s disease dementia and Alzheimer’s disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders. PMID:27598124
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Toxin-Induced Experimental Models of Learning and Memory Impairment.
More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug
2016-09-01
Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.
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Aerosolized red-tide toxins (brevetoxins) and asthma.
Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Bean, Judy A; Wanner, Adam; Reich, Andrew; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William M; Baden, Daniel G
2007-01-01
With the increasing incidence of asthma, there is increasing concern over environmental exposures that may trigger asthma exacerbations. Blooms of the marine microalgae, Karenia brevis, cause red tides (or harmful algal blooms) annually throughout the Gulf of Mexico. K brevis produces highly potent natural polyether toxins, called brevetoxins, which are sodium channel blockers, and possibly histamine activators. In experimental animals, brevetoxins cause significant bronchoconstriction. In humans, a significant increase in self-reported respiratory symptoms has been described after recreational and occupational exposures to Florida red-tide aerosols, particularly among individuals with asthma. Before and after 1 h spent on beaches with and without an active K brevis red-tide exposure, 97 persons >or= 12 years of age with physician-diagnosed asthma were evaluated by questionnaire and spirometry. Concomitant environmental monitoring, water and air sampling, and personal monitoring for brevetoxins were performed. Participants were significantly more likely to report respiratory symptoms after K brevis red-tide aerosol exposure than before exposure. Participants demonstrated small, but statistically significant, decreases in FEV(1), midexpiratory phase of forced expiratory flow, and peak expiratory flow after exposure, particularly among those participants regularly using asthma medications. No significant differences were detected when there was no Florida red tide (ie, during nonexposure periods). This study demonstrated objectively measurable adverse changes in lung function from exposure to aerosolized Florida red-tide toxins in asthmatic subjects, particularly among those requiring regular therapy with asthma medications. Future studies will assess these susceptible subpopulations in more depth, as well as the possible long-term effects of these toxins.
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Aerosolized Red-Tide Toxins (Brevetoxins) and Asthma
Fleming, Lora E.; Kirkpatrick, Barbara; Backer, Lorraine C.; Bean, Judy A.; Wanner, Adam; Reich, Andrew; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William M.; Baden, Daniel G.
2009-01-01
Background With the increasing incidence of asthma, there is increasing concern over environmental exposures that may trigger asthma exacerbations. Blooms of the marine microalgae, Karenia brevis, cause red tides (or harmful algal blooms) annually throughout the Gulf of Mexico. K brevis produces highly potent natural polyether toxins, called brevetoxins, which are sodium channel blockers, and possibly histamine activators. In experimental animals, brevetoxins cause significant bronchoconstriction. In humans, a significant increase in self-reported respiratory symptoms has been described after recreational and occupational exposures to Florida red-tide aerosols, particularly among individuals with asthma. Methods Before and after 1 h spent on beaches with and without an active K brevis red-tide exposure, 97 persons ≥ 12 years of age with physician-diagnosed asthma were evaluated by questionnaire and spirometry. Concomitant environmental monitoring, water and air sampling, and personal monitoring for brevetoxins were performed. Results Participants were significantly more likely to report respiratory symptoms after K brevis red-tide aerosol exposure than before exposure. Participants demonstrated small, but statistically significant, decreases in FEV1, midexpiratory phase of forced expiratory flow, and peak expiratory flow after exposure, particularly among those participants regularly using asthma medications. No significant differences were detected when there was no Florida red tide (ie, during nonexposure periods). Conclusions This study demonstrated objectively measurable adverse changes in lung function from exposure to aerosolized Florida red-tide toxins in asthmatic subjects, particularly among those requiring regular therapy with asthma medications. Future studies will assess these susceptible subpopulations in more depth, as well as the possible long-term effects of these toxins. PMID:17218574
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Wong, A C; Bergdoll, M S
1990-01-01
The kinetics of toxic shock syndrome toxin 1 (TSST-1) production by Staphylococcus aureus was studied in a fermentor in which aeration rate, atmospheric composition, pH, and temperature were controlled. The toxin was synthesized at a maximal rate during the exponential phase. High bacterial populations were not necessarily accompanied by high TSST-1 yields. Aerobiosis increased TSST-1 production, but excessive aeration had an adverse effect. Addition of CO2 enhanced TSST-1 yield by increasing toxin production rate and efficiency. Cultures with no pH control made more TSST-1 than those maintained at pH 5.5 to 7.5. Maximum TSST-1 yields were obtained when cultures were supplied with air (20 cm3/min) and CO2 (5 cm3/min) via a sintered glass sparger. PMID:2108084
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... The toxin that millipedes release keeps away most predators. Some large millipede species can spray these toxins ... Your local poison control center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from ...
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Toxicological Review of Cyanobacterial Toxins: Anatoxin-a (External Review Draft)
The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jenko, Kathryn; Zhang, Yanfeng; Kostenko, Yulia
Plant and microbial toxins are considered bioterrorism threat agents because of their extreme toxicity and/or ease of availability. Additionally, some of these toxins are increasingly responsible for accidental food poisonings. The current study utilized an ELISA-based protein antibody microarray for the multiplexed detection of ten biothreat toxins, botulinum neurotoxins (BoNT) A, B, C, D, E, F, ricin, shiga toxins 1 and 2 (Stx), and staphylococcus enterotoxin B (SEB), in buffer and complex biological matrices. The multiplexed assay displayed a sensitivity of 1.3 pg/mL (BoNT/A, BoNT/B, SEB, Stx-1 and Stx-2), 3.3 pg/mL (BoNT/C, BoNT/E, BoNT/F) and 8.2 pg/mL (BoNT/D, ricin). Allmore » assays demonstrated high accuracy (75-120 percent recovery) and reproducibility (most coefficients of variation < 20%). Quantification curves for the ten toxins were also evaluated in clinical samples (serum, plasma, nasal fluid, saliva, stool, and urine) and environmental samples (apple juice, milk and baby food) with overall minimal matrix effects. The multiplex assays were highly specific, with little crossreactivity observed between the selected toxin antibodies. The results demonstrate a multiplex microarray that improves current immunoassay sensitivity for biological warfare agents in buffer, clinical, and environmental samples.« less
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Shaffer, Howard J; LaBrie, Richard A; LaPlante, Debi
2004-03-01
Exposure and adaptation models provide competing perspectives of the environmental influence on the development of addictive disorders. Exposure theory suggests that the presence of environmental toxins (e.g., casinos) increases the likelihood of related disease (e.g., gambling-related disorders). Adaptation theory proposes that new environmental toxins initially increase adverse reactions; subsequently, symptoms diminish as individuals adapt to such toxins and acquire resistance. The authors describe a new public health regional exposure model (REM) that provides a tool to gather empirical evidence in support of either model. This article demonstrates how the strategic REM, modified to examine gambling exposure, uses standardized indices of exposure to social phenomena at the regional level to quantify social constructs.
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Gui, Qingyuan; Lawson, Tom; Shan, Suyan; Yan, Lu; Liu, Yong
2017-01-01
Various whole cell-based biosensors have been reported in the literature for the last 20 years and these reports have shown great potential for their use in the areas of pollution detection in environmental and in biomedical diagnostics. Unlike other reviews of this growing field, this mini-review argues that: (1) the selection of reporter genes and their regulatory proteins are directly linked to the performance of celllular biosensors; (2) broad enhancements in microelectronics and information technologies have also led to improvements in the performance of these sensors; (3) their future potential is most apparent in their use in the areas of medical diagnostics and in environmental monitoring; and (4) currently the most promising work is focused on the better integration of cellular sensors with nano and micro scaled integrated chips. With better integration it may become practical to see these cells used as (5) real-time portable devices for diagnostics at the bedside and for remote environmental toxin detection and this in situ application will make the technology commonplace and thus as unremarkable as other ubiquitous technologies. PMID:28703749
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Induction of Shiga Toxin-Encoding Prophage by Abiotic Environmental Stress in Food.
Fang, Yuan; Mercer, Ryan G; McMullen, Lynn M; Gänzle, Michael G
2017-10-01
The prophage-encoded Shiga toxin is a major virulence factor in Stx-producing Escherichia coli (STEC). Toxin production and phage production are linked and occur after induction of the RecA-dependent SOS response. However, food-related stress and Stx-prophage induction have not been studied at the single-cell level. This study investigated the effects of abiotic environmental stress on stx expression by single-cell quantification of gene expression in STEC O104:H4 Δ stx2 :: gfp :: amp r In addition, the effect of stress on production of phage particles was determined. The lethality of stressors, including heat, HCl, lactic acid, hydrogen peroxide, and high hydrostatic pressure, was selected to reduce cell counts by 1 to 2 log CFU/ml. The integrity of the bacterial membrane after exposure to stress was measured by propidium iodide (PI). The fluorescent signals of green fluorescent protein (GFP) and PI were quantified by flow cytometry. The mechanism of prophage induction by stress was evaluated by relative gene expression of recA and cell morphology. Acid (pH < 3.5) and H 2 O 2 (2.5 mM) induced the expression of stx 2 in about 18% and 3% of the population, respectively. The mechanism of prophage induction by acid differs from that of induction by H 2 O 2 H 2 O 2 induction but not acid induction corresponded to production of infectious phage particles, upregulation of recA , and cell filamentation. Pressure (200 MPa) or heat did not induce the Stx2-encoding prophage (Stx2-prophage). Overall, the quantification method developed in this study allowed investigation of prophage induction and physiological properties at the single-cell level. H 2 O 2 and acids mediate different pathways to induce Stx2-prophage. IMPORTANCE Induction of the Stx-prophage in STEC results in production of phage particles and Stx and thus relates to virulence as well as the transduction of virulence genes. This study developed a method for a detection of the induction of Stx-prophages at the
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Induction of Shiga Toxin-Encoding Prophage by Abiotic Environmental Stress in Food
Fang, Yuan; Mercer, Ryan G.; McMullen, Lynn M.
2017-01-01
ABSTRACT The prophage-encoded Shiga toxin is a major virulence factor in Stx-producing Escherichia coli (STEC). Toxin production and phage production are linked and occur after induction of the RecA-dependent SOS response. However, food-related stress and Stx-prophage induction have not been studied at the single-cell level. This study investigated the effects of abiotic environmental stress on stx expression by single-cell quantification of gene expression in STEC O104:H4 Δstx2::gfp::ampr. In addition, the effect of stress on production of phage particles was determined. The lethality of stressors, including heat, HCl, lactic acid, hydrogen peroxide, and high hydrostatic pressure, was selected to reduce cell counts by 1 to 2 log CFU/ml. The integrity of the bacterial membrane after exposure to stress was measured by propidium iodide (PI). The fluorescent signals of green fluorescent protein (GFP) and PI were quantified by flow cytometry. The mechanism of prophage induction by stress was evaluated by relative gene expression of recA and cell morphology. Acid (pH < 3.5) and H2O2 (2.5 mM) induced the expression of stx2 in about 18% and 3% of the population, respectively. The mechanism of prophage induction by acid differs from that of induction by H2O2. H2O2 induction but not acid induction corresponded to production of infectious phage particles, upregulation of recA, and cell filamentation. Pressure (200 MPa) or heat did not induce the Stx2-encoding prophage (Stx2-prophage). Overall, the quantification method developed in this study allowed investigation of prophage induction and physiological properties at the single-cell level. H2O2 and acids mediate different pathways to induce Stx2-prophage. IMPORTANCE Induction of the Stx-prophage in STEC results in production of phage particles and Stx and thus relates to virulence as well as the transduction of virulence genes. This study developed a method for a detection of the induction of Stx-prophages at the single
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Privacy-related context information for ubiquitous health.
Seppälä, Antto; Nykänen, Pirkko; Ruotsalainen, Pekka
2014-03-11
Ubiquitous health has been defined as a dynamic network of interconnected systems. A system is composed of one or more information systems, their stakeholders, and the environment. These systems offer health services to individuals and thus implement ubiquitous computing. Privacy is the key challenge for ubiquitous health because of autonomous processing, rich contextual metadata, lack of predefined trust among participants, and the business objectives. Additionally, regulations and policies of stakeholders may be unknown to the individual. Context-sensitive privacy policies are needed to regulate information processing. Our goal was to analyze privacy-related context information and to define the corresponding components and their properties that support privacy management in ubiquitous health. These properties should describe the privacy issues of information processing. With components and their properties, individuals can define context-aware privacy policies and set their privacy preferences that can change in different information-processing situations. Scenarios and user stories are used to analyze typical activities in ubiquitous health to identify main actors, goals, tasks, and stakeholders. Context arises from an activity and, therefore, we can determine different situations, services, and systems to identify properties for privacy-related context information in information-processing situations. Privacy-related context information components are situation, environment, individual, information technology system, service, and stakeholder. Combining our analyses and previously identified characteristics of ubiquitous health, more detailed properties for the components are defined. Properties define explicitly what context information for different components is needed to create context-aware privacy policies that can control, limit, and constrain information processing. With properties, we can define, for example, how data can be processed or how components
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Davis, Catherine C.; Baccam, Mekhine; Mantz, Mary J.
Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable disease that has been associated with tampon use epidemiologically. It involves a confluence of microbial risk factors (Staphylococcus aureus strains that produce the superantigen—TSST-1), as well as environmental characteristics of the vaginal ecosystem during menstruation and host susceptibility factors. This paper describes a series of experiments using the well-characterized model of porcine vaginal mucosa ex-vivo to assess the effect of these factors associated with tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and tritiated water ({sup 3}H{sub 2}O) through porcine vaginal mucosa was determinedmore » at various temperatures, after mechanical disruption of the epithelial surface by tape stripping, after treatment with surfactants or other compounds, and in the presence of microbial virulence factors. Elevated temperatures (42, 47 and 52 °C) did not significantly increase flux of {sup 3}H{sub 2}O. Stripping of the epithelial layers significantly increased the flux of labeled toxin in a dose-dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol (4%) significantly increased the flux of {sup 3}H{sub 2}O but sodium lauryl sulfate at any concentration tested did not. The flux of the labeled toxin was significantly increased in the presence of benzalkonium chloride but not Pluronic® L92 and Tween 20 and significantly increased with addition of α-hemolysin but not endotoxin. These results show that the permeability of porcine vagina ex-vivo to labeled toxin or water can be used to evaluate changes to the vaginal environment and modifications in tampon materials, and thus aid in risk assessment. - Highlights: • Model assessed local effects of tampon use on vaginal mucosa. • Risks were evaluated using two tracers to assess permeability in an ex vivo model. • Mechanical damage to the epithelial surface increased tracer
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Botulinum toxin in parkinsonism: The when, how, and which for botulinum toxin injections.
Cardoso, Francisco
2018-06-01
The aim of this article is to provide a review of the use of injections of botulinum toxin in the management of selected symptoms and signs of Parkinson's disease and other forms of parkinsonism. Sialorrhea is defined as inability to control oral secretions, resulting in excessive saliva in the oropharynx. There is a high level of evidence for the treatment of sialorrhea in parkinsonism with injections of different forms of botulinum toxin type A as well as botulinum toxin type B. Tremor can be improved by the use of botulinum toxin injections but improved tremor control often leads to concomitant motor weakness, limiting its use. Levodopa induced dyskinesias are difficult to treat with botulinum toxin injections because of their variable frequency and direction. Apraxia of eyelid opening, a sign more commonly seen in progressive supranuclear palsy and other tauopathies, often improves after botulinum toxin injections. Recent data suggest that regardless of the underlying mechanism, pain in parkinsonism can be alleviated by botulinum toxin injections. Finally, freezing of gait, camptocormia and Pisa syndrome in parkinsonism almost invariably fail to respond to botulinum toxin injections. Copyright © 2017 Elsevier Ltd. All rights reserved.
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A wearable context aware system for ubiquitous healthcare.
Kang, Dong-Oh; Lee, Hyung-Jik; Ko, Eun-Jung; Kang, Kyuchang; Lee, Jeunwoo
2006-01-01
Recent developments of information technologies are leading the advent of the era of ubiquitous healthcare, which means healthcare services at any time and at any places. The ubiquitous healthcare service needs a wearable system for more continual measurement of biological signals of a user, which gives information of the user from wearable sensors. In this paper, we propose a wearable context aware system for ubiquitous healthcare, and its systematic design process of a ubiquitous healthcare service. Some wearable sensor systems are introduced with Zigbee communication. We develop a context aware framework to send information from wearable sensors to healthcare service entities as a middleware to solve the interoperability problem between sensor makers and healthcare service providers. And, we propose a systematic process of design of ubiquitous healthcare services with the context aware framework. In order to show the feasibility of the proposed system, some application examples are given, which are applied to remote monitoring, and a self check service.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
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.
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Detection Methodologies for Pathogen and Toxins: A Review.
Alahi, Md Eshrat E; Mukhopadhyay, Subhas Chandra
2017-08-16
Pathogen and toxin-contaminated foods and beverages are a major source of illnesses, even death, and have a significant economic impact worldwide. Human health is always under a potential threat, including from biological warfare, due to these dangerous pathogens. The agricultural and food production chain consists of many steps such as harvesting, handling, processing, packaging, storage, distribution, preparation, and consumption. Each step is susceptible to threats of environmental contamination or failure to safeguard the processes. The production process can be controlled in the food and agricultural sector, where smart sensors can play a major role, ensuring greater food quality and safety by low cost, fast, reliable, and profitable methods of detection. Techniques for the detection of pathogens and toxins may vary in cost, size, and specificity, speed of response, sensitivity, and precision. Smart sensors can detect, analyse and quantify at molecular levels contents of different biological origin and ensure quality of foods against spiking with pesticides, fertilizers, dioxin, modified organisms, anti-nutrients, allergens, drugs and so on. This paper reviews different methodologies to detect pathogens and toxins in foods and beverages.
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Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins
DOE Office of Scientific and Technical Information (OSTI.GOV)
Won, JaeSeon; Nam, PilWon; Lee, YongChan
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 Fabmore » 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.« less
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Lopes, Alexandre P. Y.; Lopes, Luana M.; Fraga, Tatiana R.; Chura-Chambi, Rosa M.; Sanson, André L.; Cheng, Elisabeth; Nakajima, Erika; Morganti, Ligia; Martins, Elizabeth A. L.
2014-01-01
The prokaryotic ubiquitous Toxin-Antitoxin (TA) operons encode a stable toxin and an unstable antitoxin. The most accepted hypothesis of the physiological function of the TA system is the reversible cessation of cellular growth under stress conditions. The major TA family, VapBC is present in the spirochaete Leptospira interrogans. VapBC modules are classified based on the presence of a predicted ribonucleasic PIN domain in the VapC toxin. The expression of the leptospiral VapC in E. coli promotes a strong bacterial growth arrestment, making it difficult to express the recombinant protein. Nevertheless, we showed that long term induction of expression in E. coli enabled the recovery of VapC in inclusion bodies. The recombinant protein was successfully refolded by high hydrostatic pressure, providing a new method to obtain the toxin in a soluble and active form. The structural integrity of the recombinant VapB and VapC proteins was assessed by circular dichroism spectroscopy. Physical interaction between the VapC toxin and the VapB antitoxin was demonstrated in vivo and in vitro by pull down and ligand affinity blotting assays, respectively, thereby indicating the ultimate mechanism by which the activity of the toxin is regulated in bacteria. The predicted model of the leptospiral VapC structure closely matches the Shigella's VapC X-ray structure. In agreement, the ribonuclease activity of the leptospiral VapC was similar to the activity described for Shigella's VapC, as demonstrated by the cleavage of tRNAfMet and by the absence of unspecific activity towards E. coli rRNA. This finding suggests that the cleavage of the initiator transfer RNA may represent a common mechanism to a larger group of bacteria and potentially configures a mechanism of post-transcriptional regulation leading to the inhibition of global translation. PMID:25047537
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Lopes, Alexandre P Y; Lopes, Luana M; Fraga, Tatiana R; Chura-Chambi, Rosa M; Sanson, André L; Cheng, Elisabeth; Nakajima, Erika; Morganti, Ligia; Martins, Elizabeth A L
2014-01-01
The prokaryotic ubiquitous Toxin-Antitoxin (TA) operons encode a stable toxin and an unstable antitoxin. The most accepted hypothesis of the physiological function of the TA system is the reversible cessation of cellular growth under stress conditions. The major TA family, VapBC is present in the spirochaete Leptospira interrogans. VapBC modules are classified based on the presence of a predicted ribonucleasic PIN domain in the VapC toxin. The expression of the leptospiral VapC in E. coli promotes a strong bacterial growth arrestment, making it difficult to express the recombinant protein. Nevertheless, we showed that long term induction of expression in E. coli enabled the recovery of VapC in inclusion bodies. The recombinant protein was successfully refolded by high hydrostatic pressure, providing a new method to obtain the toxin in a soluble and active form. The structural integrity of the recombinant VapB and VapC proteins was assessed by circular dichroism spectroscopy. Physical interaction between the VapC toxin and the VapB antitoxin was demonstrated in vivo and in vitro by pull down and ligand affinity blotting assays, respectively, thereby indicating the ultimate mechanism by which the activity of the toxin is regulated in bacteria. The predicted model of the leptospiral VapC structure closely matches the Shigella's VapC X-ray structure. In agreement, the ribonuclease activity of the leptospiral VapC was similar to the activity described for Shigella's VapC, as demonstrated by the cleavage of tRNAfMet and by the absence of unspecific activity towards E. coli rRNA. This finding suggests that the cleavage of the initiator transfer RNA may represent a common mechanism to a larger group of bacteria and potentially configures a mechanism of post-transcriptional regulation leading to the inhibition of global translation.
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Integrating Collaborative and Decentralized Models to Support Ubiquitous Learning
ERIC Educational Resources Information Center
Barbosa, Jorge Luis Victória; Barbosa, Débora Nice Ferrari; Rigo, Sandro José; de Oliveira, Jezer Machado; Rabello, Solon Andrade, Jr.
2014-01-01
The application of ubiquitous technologies in the improvement of education strategies is called Ubiquitous Learning. This article proposes the integration between two models dedicated to support ubiquitous learning environments, called Global and CoolEdu. CoolEdu is a generic collaboration model for decentralized environments. Global is an…
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Antibody-based bacterial toxin detection
NASA Astrophysics Data System (ADS)
Menking, Darrell E.; Heitz, Jonathon M.; Anis, Nabil A.; Thompson, Roy G.
1994-03-01
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 one step assay, antibodies against Cholera toxin or Staphylococcus Enterotoxin B were noncovalently immobilized on quartz fibers and probed with fluorescein-isothiocyanate (FITC)-labeled toxins. In the two-step assay, Cholera toxin or Botulinum toxoid A was immobilized onto the fiber, followed by incubation in an antiserum or partially purified antitoxin IgG. These were then probed with FITC-anti-IgG antibodies. Unlabeled toxins competed with labeled toxins or antitoxin IgG in a dose-dependent manner and the detection of the toxins was in the nanomolar range.
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Toxin Plasmids of Clostridium perfringens
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
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Ubiquitous geospatial concept in evolution of the macro and micro spatial planning
NASA Astrophysics Data System (ADS)
Sabri, S.; Ludin, A. N. M.; Majid, M. R.
2014-02-01
There are many examples of GIS application in planning such as urban land-use planning, cultural heritage conservation, coastal zone management, and the design of structure plans for sustainable economic development. All these applications are dealing with systems in which natural and human factors are interconnected. But an issue that should be addressed is to what extent the current information technology is able to connect all these parts together? Contemporary improvement in information technology made the computer so imbedded in our everyday practices that we use it without having to think about it. Thus, computing is becoming truly ubiquitous and is available anywhere anytime. Advances in the internet facilities and devices, such as high speed wireless networks, mobile middleware, and smart technologies, has pushed the concept of ubiquitous computing to the forefront of GIS research and development. There are developments in this regards, these are such as GeoWeb 2.0, voluntarily geographic Information (VGI), and Mashups, whereby the application of cloud computing was possible in visualizing urban air pollution and emergency responses to ensure the safety and security. These advancements therefore, have changed the conventional facet of macro and micro spatial planning. Every possible information system such as residential, medical, business, environmental, governmental, and the like can be linked through ubiquitous computing technologies and acts as a virtually one system which works for society. However, the journey to achieve a true ubiquitous GIS is not without challenges. Despite the current potentials there are many issues and obstacles need to be addressed before GIS can to be truly ubiquitous in planning context. Perhaps four criteria as explained by Goodchild et al (1997) can be applied to ubiquitous GIS in planning very well: the system must be distributed (data storage, processing and user interaction can occur at locations that are potentially
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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
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The Construction of an Ontology-Based Ubiquitous Learning Grid
ERIC Educational Resources Information Center
Liao, Ching-Jung; Chou, Chien-Chih; Yang, Jin-Tan David
2009-01-01
The purpose of this study is to incorporate adaptive ontology into ubiquitous learning grid to achieve seamless learning environment. Ubiquitous learning grid uses ubiquitous computing environment to infer and determine the most adaptive learning contents and procedures in anytime, any place and with any device. To achieve the goal, an…
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Privacy-Related Context Information for Ubiquitous Health
Nykänen, Pirkko; Ruotsalainen, Pekka
2014-01-01
Background Ubiquitous health has been defined as a dynamic network of interconnected systems. A system is composed of one or more information systems, their stakeholders, and the environment. These systems offer health services to individuals and thus implement ubiquitous computing. Privacy is the key challenge for ubiquitous health because of autonomous processing, rich contextual metadata, lack of predefined trust among participants, and the business objectives. Additionally, regulations and policies of stakeholders may be unknown to the individual. Context-sensitive privacy policies are needed to regulate information processing. Objective Our goal was to analyze privacy-related context information and to define the corresponding components and their properties that support privacy management in ubiquitous health. These properties should describe the privacy issues of information processing. With components and their properties, individuals can define context-aware privacy policies and set their privacy preferences that can change in different information-processing situations. Methods Scenarios and user stories are used to analyze typical activities in ubiquitous health to identify main actors, goals, tasks, and stakeholders. Context arises from an activity and, therefore, we can determine different situations, services, and systems to identify properties for privacy-related context information in information-processing situations. Results Privacy-related context information components are situation, environment, individual, information technology system, service, and stakeholder. Combining our analyses and previously identified characteristics of ubiquitous health, more detailed properties for the components are defined. Properties define explicitly what context information for different components is needed to create context-aware privacy policies that can control, limit, and constrain information processing. With properties, we can define, for example, how
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The Languages Spoken in the Water Body (or the Biological Role of Cyanobacterial Toxins)
Kaplan, Aaron; Harel, Moshe; Kaplan-Levy, Ruth N.; Hadas, Ora; Sukenik, Assaf; Dittmann, Elke
2012-01-01
Although intensification of toxic cyanobacterial blooms over the last decade is a matter of growing concern due to bloom impact on water quality, the biological role of most of the toxins produced is not known. In this critical review we focus primarily on the biological role of two toxins, microcystins and cylindrospermopsin, in inter- and intra-species communication and in nutrient acquisition. We examine the experimental evidence supporting some of the dogmas in the field and raise several open questions to be dealt with in future research. We do not discuss the health and environmental implications of toxin presence in the water body. PMID:22529842
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Toxin-Based Therapeutic Approaches
Shapira, Assaf; Benhar, Itai
2010-01-01
Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564
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Cyanobacteria Toxin and Cell Propagation through Lake Erie Treatment Facilities - proceedings
Harmful algal blooms (HABs), and their associated toxins, in fresh water lakes and reservoirs are drawing the attention of utilities and state regulators nation-wide. Recognizing the potential health and economic consequences, the US Environmental Protection Agency, in partnersh...
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CILT2000: Ubiquitous Computing--Spanning the Digital Divide.
ERIC Educational Resources Information Center
Tinker, Robert; Vahey, Philip
2002-01-01
Discusses the role of ubiquitous and handheld computers in education. Summarizes the contributions of the Center for Innovative Learning Technologies (CILT) and describes the ubiquitous computing sessions at the CILT2000 Conference. (Author/YDS)
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Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study.
Li, Jian; Zhou, Haiying; Zuo, Decheng; Hou, Kun-Mean; De Vaulx, Christophe
2014-01-01
As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor-care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space.
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Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific Endoribonuclease Activity
Masuda, Hisako; Inouye, Masayori
2017-01-01
Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA containing recognition sequences in the absence of ribosome in vitro. However, increasing evidence suggests that in vivo digestion may occur in association with ribosomes. Despite the prevalence of recognition sequences in many mRNA, preferential digestion seems to occur at specific positions within mRNA and also in certain reading frames. In this review, a variety of tools utilized to study the nuclease activities of toxins over the past 15 years will be reviewed. A recent adaptation of an RNA-seq-based technique to analyze entire sets of cellular RNA will be introduced with an emphasis on its strength in identifying novel targets and redefining recognition sequences. The differences in biochemical properties and postulated physiological roles will also be discussed. PMID:28420090
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Wang, Libing; Chen, Wei; Xu, Dinghua; Shim, Bong Sup; Zhu, Yingyue; Sun, Fengxia; Liu, Liqiang; Peng, Chifang; Jin, Zhengyu; Xu, Chuanlai; Kotov, Nicholas A.
2009-01-01
Safety of water was for a long time and still is one of the most pressing needs for many countries and different communities. Despite the fact that there are potentially many methods to evaluate water safety, finding a simple, rapid, versatile, and inexpensive method for detection of toxins in everyday items is still a great challenge. In this study, we extend the concept of composites obtained impregnation of porous fibrous materials, such as fabrics and papers, by single walled carbon-nanotubes (SWNTs) toward very simple but high-performance biosensors. They utilize the strong dependence of electrical conductivity through nanotubes percolation network on the width of nanotubes-nanotube tunneling gap and can potentially satisfy all the requirements outlined above for the routine toxin monitoring. An antibody to the microcystin-LR (MC-LR), one of the common culprits in mass poisonings, was dispersed together with SWNTs. This dispersion was used to dip-coat the paper rendering it conductive. The change in conductivity of the paper was used to sense the MC-LR in the water rapidly and accurately. The method has the linear detection range up to 10 nmol/L and non-linear detection up to 40 nmol/L. The limit of detection was found to be 0.6 nmol/L (0.6 ng/mL), which satisfies the strictest World Health Organization standard for MC-LR content in drinking water (1 ng/mL), and is comparable to the detection limit of traditional ELISA method of MC-LR detection, while drastically reducing the time of analysis by more than an order of magnitude, which is one of the major hurdles in practical applications. Similar technology of sensor preparation can also be used for a variety of other rapid environmental sensors. PMID:19928776
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Jang, Hyun; Kim, Hyo Seung; Kim, Jeong Ah; Seo, Jin Ho; Carbis, Rodney
2009-01-01
A simplified method for the purification of cholera toxin was developed. The 569B strain of Vibrio cholerae, a recognized hyper-producer of cholera toxin, was propagated in a bioreactor under conditions that promote the production of the toxin. The toxin was separated from the bacterial cells using 0.2-microm crossflow microfiltration, the clarified toxin was passed through the membrane into the permeate, and the bacterial cells were retained in the retentate. The 0.2-microm permeate was then concentrated 3-fold and diafiltered against 10 mM phosphate buffer, pH 7.6, using 30-kDa crossflow ultrafiltration. The concentrated toxin was loaded onto a cation exchange column, the toxin was bound to the column, and most of the impurities were passed unimpeded through the column. The toxin was eluted with a salt gradient of phosphate buffer, pH7.0, containing 1.0M NaCl. The peak containing the toxin was assayed for cholera toxin and protein and the purity was determined to be 92%. The toxin peak had a low endotoxin level of 3.1 EU/microg of toxin. The purified toxin was used to prepare antiserum against whole toxin, which was used in a G(M1) ganglioside-binding ELISA to determine residual levels of toxin in an oral inactivated whole-cell cholera vaccine. The G(M1) ganglioside-binding ELISA was shown to be very sensitive and capable of detecting as little as 1 ng/ml of cholera toxin.
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Ferrández-Pastor, Francisco Javier; García-Chamizo, Juan Manuel; Nieto-Hidalgo, Mario; Mora-Pascual, Jerónimo; Mora-Martínez, José
2016-07-22
The application of Information Technologies into Precision Agriculture methods has clear benefits. Precision Agriculture optimises production efficiency, increases quality, minimises environmental impact and reduces the use of resources (energy, water); however, there are different barriers that have delayed its wide development. Some of these main barriers are expensive equipment, the difficulty to operate and maintain and the standard for sensor networks are still under development. Nowadays, new technological development in embedded devices (hardware and communication protocols), the evolution of Internet technologies (Internet of Things) and ubiquitous computing (Ubiquitous Sensor Networks) allow developing less expensive systems, easier to control, install and maintain, using standard protocols with low-power consumption. This work develops and test a low-cost sensor/actuator network platform, based in Internet of Things, integrating machine-to-machine and human-machine-interface protocols. Edge computing uses this multi-protocol approach to develop control processes on Precision Agriculture scenarios. A greenhouse with hydroponic crop production was developed and tested using Ubiquitous Sensor Network monitoring and edge control on Internet of Things paradigm. The experimental results showed that the Internet technologies and Smart Object Communication Patterns can be combined to encourage development of Precision Agriculture. They demonstrated added benefits (cost, energy, smart developing, acceptance by agricultural specialists) when a project is launched.
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Ferrández-Pastor, Francisco Javier; García-Chamizo, Juan Manuel; Nieto-Hidalgo, Mario; Mora-Pascual, Jerónimo; Mora-Martínez, José
2016-01-01
The application of Information Technologies into Precision Agriculture methods has clear benefits. Precision Agriculture optimises production efficiency, increases quality, minimises environmental impact and reduces the use of resources (energy, water); however, there are different barriers that have delayed its wide development. Some of these main barriers are expensive equipment, the difficulty to operate and maintain and the standard for sensor networks are still under development. Nowadays, new technological development in embedded devices (hardware and communication protocols), the evolution of Internet technologies (Internet of Things) and ubiquitous computing (Ubiquitous Sensor Networks) allow developing less expensive systems, easier to control, install and maintain, using standard protocols with low-power consumption. This work develops and test a low-cost sensor/actuator network platform, based in Internet of Things, integrating machine-to-machine and human-machine-interface protocols. Edge computing uses this multi-protocol approach to develop control processes on Precision Agriculture scenarios. A greenhouse with hydroponic crop production was developed and tested using Ubiquitous Sensor Network monitoring and edge control on Internet of Things paradigm. The experimental results showed that the Internet technologies and Smart Object Communication Patterns can be combined to encourage development of Precision Agriculture. They demonstrated added benefits (cost, energy, smart developing, acceptance by agricultural specialists) when a project is launched. PMID:27455265
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Clostridium difficile binary toxin CDT
Gerding, Dale N; Johnson, Stuart; Rupnik, Maja; Aktories, Klaus
2014-01-01
Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed. PMID:24253566
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Graham, Jennifer L.; Loftin, Keith A.; Ziegler, Andrew C.; Meyer, Michael T.
2008-01-01
Cyanobacteria and associated toxins and taste-and-odor compounds are of increasing environmental concern. However, consistent guidelines for the development of studies assessing cyanobacterial toxins and taste-and-odor compounds presently are not available. This report provides guidance for the development of scientific studies of cyanobacteria and associated by-products in lakes and reservoirs. Topics include: background information on cyanobacteria, toxins, and taste-and-odor compounds; spatial and temporal considerations that are unique to the cyanobacteria in lakes and reservoirs; common study types, objectives, and approaches for studies of cyanobacteria and associated toxins and taste-and-odor compounds; general guidelines for collecting samples; and information on sample handling, preparation, processing, and shipping.
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Honda, Kiyoshi; Shrestha, Aadit; Witayangkurn, Apichon; Chinnachodteeranun, Rassarin; Shimamura, Hiroshi
2009-01-01
The fieldserver is an Internet based observation robot that can provide an outdoor solution for monitoring environmental parameters in real-time. The data from its sensors can be collected to a central server infrastructure and published on the Internet. The information from the sensor network will contribute to monitoring and modeling on various environmental issues in Asia, including agriculture, food, pollution, disaster, climate change etc. An initiative called Sensor Asia is developing an infrastructure called Sensor Service Grid (SSG), which integrates fieldservers and Web GIS to realize easy and low cost installation and operation of ubiquitous field sensor networks. PMID:22574018
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Ubiquitous Learning Environments in Higher Education: A Scoping Literature Review
ERIC Educational Resources Information Center
Virtanen, Mari Aulikki; Haavisto, Elina; Liikanen, Eeva; Kääriäinen, Maria
2018-01-01
Ubiquitous learning and the use of ubiquitous learning environments heralds a new era in higher education. Ubiquitous learning environments enhance context-aware and seamless learning experiences available from any location at any time. They support smooth interaction between authentic and digital learning resources and provide personalized…
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New functionalities in abundant element oxides: ubiquitous element strategy
Hosono, Hideo; Hayashi, Katsuro; Kamiya, Toshio; Atou, Toshiyuki; Susaki, Tomofumi
2011-01-01
While most ceramics are composed of ubiquitous elements (the ten most abundant elements within the Earth's crust), many advanced materials are based on rare elements. A ‘rare-element crisis’ is approaching owing to the imbalance between the limited supply of rare elements and the increasing demand. Therefore, we propose a ‘ubiquitous element strategy’ for materials research, which aims to apply abundant elements in a variety of innovative applications. Creation of innovative oxide materials and devices based on conventional ceramics is one specific challenge. This review describes the concept of ubiquitous element strategy and gives some highlights of our recent research on the synthesis of electronic, thermionic and structural materials using ubiquitous elements. PMID:27877391
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Davis, Catherine C; Baccam, Mekhine; Mantz, Mary J; Osborn, Thomas W; Hill, Donna R; Squier, Christopher A
2014-01-15
Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable disease that has been associated with tampon use epidemiologically. It involves a confluence of microbial risk factors (Staphylococcus aureus strains that produce the superantigen-TSST-1), as well as environmental characteristics of the vaginal ecosystem during menstruation and host susceptibility factors. This paper describes a series of experiments using the well-characterized model of porcine vaginal mucosa ex-vivo to assess the effect of these factors associated with tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and tritiated water ((3)H2O) through porcine vaginal mucosa was determined at various temperatures, after mechanical disruption of the epithelial surface by tape stripping, after treatment with surfactants or other compounds, and in the presence of microbial virulence factors. Elevated temperatures (42, 47 and 52°C) did not significantly increase flux of (3)H2O. Stripping of the epithelial layers significantly increased the flux of labeled toxin in a dose-dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol (4%) significantly increased the flux of (3)H2O but sodium lauryl sulfate at any concentration tested did not. The flux of the labeled toxin was significantly increased in the presence of benzalkonium chloride but not Pluronic® L92 and Tween 20 and significantly increased with addition of α-hemolysin but not endotoxin. These results show that the permeability of porcine vagina ex-vivo to labeled toxin or water can be used to evaluate changes to the vaginal environment and modifications in tampon materials, and thus aid in risk assessment. Copyright © 2013 Elsevier Inc. All rights reserved.
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Wu, Yuling; Tabor, David E.; Mok, Hoyin; Sellman, Bret R.; Jenkins, Amy; Yu, Li; Jafri, Hasan S.; Rude, Thomas H.; Ruffin, Felicia; Schell, Wiley A.; Park, Lawrence P.; Yan, Qin; Thaden, Joshua T.; Messina, Julia A.; Esser, Mark T.
2014-01-01
Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 μg/ml, versus failure, 1.09 μg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study. PMID:25392350
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Multi-Toxin Resistance Enables Pink Bollworm Survival on Pyramided Bt Cotton
Fabrick, Jeffrey A.; Unnithan, Gopalan C.; Yelich, Alex J.; DeGain, Ben; Masson, Luke; Zhang, Jie; Carrière, Yves; Tabashnik, Bruce E.
2015-01-01
Transgenic crops producing Bacillus thuringiensis (Bt) proteins kill key insect pests, providing economic and environmental benefits. However, the evolution of pest resistance threatens the continued success of such Bt crops. To delay or counter resistance, transgenic plant “pyramids” producing two or more Bt proteins that kill the same pest have been adopted extensively. Field populations of the pink bollworm (Pectinophora gossypiella) in the United States have remained susceptible to Bt toxins Cry1Ac and Cry2Ab, but field-evolved practical resistance to Bt cotton producing Cry1Ac has occurred widely in India. Here we used two rounds of laboratory selection to achieve 18,000- to 150,000-fold resistance to Cry2Ab in pink bollworm. Inheritance of resistance to Cry2Ab was recessive, autosomal, conferred primarily by one locus, and independent of Cry1Ac resistance. We created a strain with high resistance to both toxins by crossing the Cry2Ab-resistant strain with a Cry1Ac-resistant strain, followed by one selection with Cry2Ab. This multi-toxin resistant strain survived on field-collected Bt cotton bolls producing both toxins. The results here demonstrate the risk of evolution of resistance to pyramided Bt plants, particularly when toxins are deployed sequentially and refuges are scarce, as seen with Bt cotton and pink bollworm in India. PMID:26559899
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Lymphocyte receptors for pertussis toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
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, andmore » 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.« less
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Botulinum toxin: Bioweapon & magic drug
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
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Botulinum toxin: bioweapon & magic drug.
Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi
2010-11-01
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.
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Collins, Ashley; Nasir, Adnan
2010-03-01
Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.
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One gene in diamondback moth confers resistance to four Bacillus thuringiensis toxins
Tabashnik, Bruce E.; Liu, Yong-Biao; Finson, Naomi; Masson, Luke; Heckel, David G.
1997-01-01
Environmentally benign insecticides derived from the soil bacterium Bacillus thuringiensis (Bt) are the most widely used biopesticides, but their success will be short-lived if pests quickly adapt to them. The risk of evolution of resistance by pests has increased, because transgenic crops producing insecticidal proteins from Bt are being grown commercially. Efforts to delay resistance with two or more Bt toxins assume that independent mutations are required to counter each toxin. Moreover, it generally is assumed that resistance alleles are rare in susceptible populations. We tested these assumptions by conducting single-pair crosses with diamondback moth (Plutella xylostella), the first insect known to have evolved resistance to Bt in open field populations. An autosomal recessive gene conferred extremely high resistance to four Bt toxins (Cry1Aa, Cry1Ab, Cry1Ac, and Cry1F). The finding that 21% of the individuals from a susceptible strain were heterozygous for the multiple-toxin resistance gene implies that the resistance allele frequency was 10 times higher than the most widely cited estimate of the upper limit for the initial frequency of resistance alleles in susceptible populations. These findings suggest that pests may evolve resistance to some groups of toxins much faster than previously expected. PMID:9050831
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Garde, Sebastian; Hovenga, Evelyn; Buck, Jasmin; Knaup, Petra
2006-01-01
Ubiquitous computing requires ubiquitous access to information and knowledge. With the release of openEHR Version 1.0 there is a common model available to solve some of the problems related to accessing information and knowledge by improving semantic interoperability between clinical systems. Considerable work has been undertaken by various bodies to standardise Clinical Data Sets. Notwithstanding their value, several problems remain unsolved with Clinical Data Sets without the use of a common model underpinning them. This paper outlines these problems like incompatible basic data types and overlapping and incompatible definitions of clinical content. A solution to this based on openEHR archetypes is motivated and an approach to transform existing Clinical Data Sets into archetypes is presented. To avoid significant overlaps and unnecessary effort during archetype development, archetype development needs to be coordinated nationwide and beyond and also across the various health professions in a formalized process.
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Privacy Policy Enforcement for Ambient Ubiquitous Services
NASA Astrophysics Data System (ADS)
Oyomno, Were; Jäppinen, Pekka; Kerttula, Esa
Ubiquitous service providers leverage miniaturised computing terminals equipped with wireless capabilities to avail new service models. These models are pivoted on personal and inexpensive terminals to customise services to individual preferences. Portability, small sizes and compact keyboards are few features popularising mobile terminals. Features enable storing and carrying of ever increasing proportions of personal data and ability to use them in service adaptations. Ubiquitous services automate deeper soliciting of personal data transparently without the need for user interactions. Transparent solicitations, acquisitions and handling of personal data legitimises privacy concerns regarding disclosures, retention and re-use of the data. This study presents a policy enforcement for ubiquitous services that safeguards handling of users personal data and monitors adherence to stipulated privacy policies. Enforcement structures towards usability and scalability are presented.
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Diversity and distribution of cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae.
Purdy, Alexandra E; Balch, Deborah; Lizárraga-Partida, Marcial Leonardo; Islam, Mohammad Sirajul; Martinez-Urtaza, Jaime; Huq, Anwar; Colwell, Rita R; Bartlett, Douglas H
2010-02-01
Non-toxigenic non-O1, non-O139 Vibrio cholerae strains isolated from both environmental and clinical settings carry a suite of virulence factors aside from cholera toxin. Among V. cholerae strains isolated from coastal waters of southern California, this includes cholix toxin, an ADP-ribosylating factor that is capable of halting protein synthesis in eukaryotic cells. The prevalence of the gene encoding cholix toxin, chxA, was assessed among a collection of 155 diverse V. cholerae strains originating from both clinical and environmental settings in Bangladesh and Mexico and other countries around the globe. The chxA gene was present in 47% of 83 non-O1, non-O139 strains and 16% of 72 O1/O139 strains screened as part of this study. A total of 86 chxA gene sequences were obtained, and phylogenetic analysis revealed that they fall into two distinct clades. These two clades were also observed in the phylogenies of several housekeeping genes, suggesting that the divergence observed in chxA extends to other regions of the V. cholerae genome, and most likely has arisen from vertical descent rather than horizontal transfer. Our results clearly indicate that ChxA is a major toxin of V. cholerae with a worldwide distribution that is preferentially associated with non-pandemic strains. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.
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Fernandez-Miyakawa, Mariano E; Fisher, Derek J; Poon, Rachael; Sayeed, Sameera; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Uzal, Francisco A
2007-03-01
Clostridium perfringens is capable of producing up to 15 toxins, including alpha-toxin (CPA), beta-toxin (CPB), epsilon-toxin (ETX), enterotoxin, beta2-toxin (CPB2), and perfringolysin O. Type B isolates, which must produce CPA, CPB, and ETX, are associated with animal illnesses characterized by sudden death or acute neurological signs, with or without intestinal damage. Type B pathogenesis in ruminants is poorly understood, with some animals showing lesions and clinical signs similar to those caused by either type C or type D infections. It is unknown whether host or environmental conditions are dominant for determining the outcome of type B disease or if disease outcomes are determined by variable characteristics of type B isolates. To help clarify this issue, 19 type B isolates were evaluated for toxin production during late-log-phase growth via quantitative Western blotting and by biological activity assays. Most type B isolates produced CPB levels similar to those produced by type C isolates in vitro and have the potential to produce genotype C-like disease. The lethality of type B isolate supernatants administered intravenously to mice was evaluated with or without prior trypsin treatment, and monoclonal antibody neutralization studies also were performed. Correlation analyses comparing toxin levels in type B supernatants versus lethality and neutralization studies both found that the main contributor to lethality without pretreatment with trypsin was CPB, whereas neutralization studies indicated that CPB and ETX were both important after trypsin pretreatment. At least part of the CPB produced by type B isolates remained active after trypsin treatment. However, the overall lethalities of most supernatants were lower after trypsin pretreatment. Also, there was a significant association between ETX, CPB2, and CPA production in vitro among type B isolates. However, our results suggest that both CPB and ETX are likely the most important contributors to the
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Detecting and discriminating among Shiga toxins
USDA-ARS?s Scientific Manuscript database
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. ...
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Botulinum Toxin and Gastrointestinal Tract Disorders
Weiser, Kirsten; Kennedy, Abigail
2008-01-01
The history of botulinum toxin is fascinating. First recognized as the cause of botulism nearly 200 years ago, it was originally feared as a deadly poison. Over the last 30 years, however, botulinum toxin has been transformed into a readily available medication used to treat a variety of medical disorders. Interest in the use of botulinum toxin has been particularly strong for patients with spastic smooth muscle disorders of the gastrointestinal tract. Patients with achalasia, diffuse esophageal spasm, gastroparesis, sphincter of Oddi dysfunction, and anal fissures have all been treated with botulinum toxin injections, often with impressive results. However, not all patients respond to botulinum toxin therapy, and large randomized controlled trials are lacking for many conditions commonly treated with botulinum toxin. This paper reviews the history, microbiology, and pharmacology of botulinum toxin, discusses its mechanism of action, and then presents recent evidence from the literature regarding the use of botulinum toxin for the treatment of a variety of gastrointestinal tract disorders. PMID:21960915
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Pore-forming activity of clostridial binary toxins.
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. Copyright © 2015 Elsevier B.V. All rights reserved.
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Lysenin Toxin Membrane Insertion Is pH-Dependent but Independent of Neighboring Lysenins.
Munguira, Ignacio L B; Takahashi, Hirohide; Casuso, Ignacio; Scheuring, Simon
2017-11-07
Pore-forming toxins form a family of proteins that act as virulence factors of pathogenic bacteria, but similar proteins are found in all kingdoms of life, including the vertebrate immune system. They are secreted as soluble monomers that oligomerize on target membranes in the so-called prepore state; after activation, they insert into the membrane and adopt the pore state. Lysenin is a pore-forming toxin from the earthworm Eisenida foetida, of which both the soluble and membrane-inserted structures are solved. However, the activation and membrane-insertion mechanisms have remained elusive. Here, we used high-speed atomic force microscopy to directly visualize the membrane-insertion mechanism. Changing the environmental pH from pH 7.5 to below pH 6.0 favored membrane insertion. We detected a short α-helix in the soluble structure that comprised three glutamic acids (Glu92, Glu94, and Glu97) that we hypothesized may represent a pH-sensor (as in similar toxins, e.g., Listeriolysin). Mutant lysenin still can form pores, but mutating these glutamic acids to glutamines rendered the toxin pH-insensitive. On the other hand, toxins in the pore state did not favor insertion of neighboring prepores; indeed, pore insertion breaks the hexagonal ordered domains of prepores and separates from neighboring molecules in the membrane. pH-dependent activation of toxins may represent a common feature of pore-forming toxins. High-speed atomic force microscopy with single-molecule resolution at high temporal resolution and the possibility of exchanging buffers during the experiments presents itself as a unique tool for the study of toxin-state conversion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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Botulinum toxin injection - larynx
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; ...
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Clostridium perfringens epsilon toxin: the third most potent bacterial toxin known.
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. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Oliver, Caitlin J; Softley, Samantha; Williamson, Sally M; Stevenson, Philip C; Wright, Geraldine A
2015-01-01
Sodium channels, found ubiquitously in animal muscle cells and neurons, are one of the main target sites of many naturally-occurring, insecticidal plant compounds and agricultural pesticides. Pyrethroids, derived from compounds found only in the Asteraceae, are particularly toxic to insects and have been successfully used as pesticides including on flowering crops that are visited by pollinators. Pyrethrins, from which they were derived, occur naturally in the nectar of some flowering plant species. We know relatively little about how such compounds--i.e., compounds that target sodium channels--influence pollinators at low or sub-lethal doses. Here, we exposed individual adult forager honeybees to several compounds that bind to sodium channels to identify whether these compounds affect motor function. Using an assay previously developed to identify the effect of drugs and toxins on individual bees, we investigated how acute exposure to 10 ng doses (1 ppm) of the pyrethroid insecticides (cyfluthrin, tau-fluvalinate, allethrin and permethrin) and the nectar toxins (aconitine and grayanotoxin I) affected honeybee locomotion, grooming and wing fanning behaviour. Bees exposed to these compounds spent more time upside down and fanning their wings. They also had longer bouts of standing still. Bees exposed to the nectar toxin, aconitine, and the pyrethroid, allethrin, also spent less time grooming their antennae. We also found that the concentration of the nectar toxin, grayanotoxin I (GTX), fed to bees affected the time spent upside down (i.e., failure to perform the righting reflex). Our data show that low doses of pyrethroids and other nectar toxins that target sodium channels mainly influence motor function through their effect on the righting reflex of adult worker honeybees.
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[Today's threat of ricin toxin].
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. © 2015 MEDPRESS.
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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.
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Purification of the Clostridium spiroforme binary toxin and activity of the toxin on HEp-2 cells.
Popoff, M R; Milward, F W; Bancillon, B; Boquet, P
1989-08-01
The two components Sa (Mr, 44,000) and Sb (Mr, 92,000) of Clostridium spiroforme toxin were identified and characterized. Serological data permitted the identification of two groups of actin ADP-ribosylating clostridial toxins. The first consists of only C. botulinum C2. The second group includes spiroforme toxin, iota toxin of C. perfringens E, and an enzyme called CDT found in one strain of C. difficile, antibodies against which cross-react with all of the members of both groups. C. spiroforme toxin acted on cells by disrupting microfilaments by ADP-ribosylation of G actin. Toxicity was not blocked by 10 or 20 mM ammonium chloride and was only moderately inhibited by 30 mM NH4Cl. Inhibition of coated-pit formation in HEp-2 cells by potassium depletion strongly protected against the effect of C. spiroforme toxin. Toxicity was not blocked by incubation of HEp-2 cells and spiroforme toxin at 15 degrees C. These results suggest that this new binary toxin enters cells via the coated-pit-coated-vesicle pathway and might reach the cytoplasm at the same time as or before transfer to early endosomes.
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Purification of the Clostridium spiroforme binary toxin and activity of the toxin on HEp-2 cells.
Popoff, M R; Milward, F W; Bancillon, B; Boquet, P
1989-01-01
The two components Sa (Mr, 44,000) and Sb (Mr, 92,000) of Clostridium spiroforme toxin were identified and characterized. Serological data permitted the identification of two groups of actin ADP-ribosylating clostridial toxins. The first consists of only C. botulinum C2. The second group includes spiroforme toxin, iota toxin of C. perfringens E, and an enzyme called CDT found in one strain of C. difficile, antibodies against which cross-react with all of the members of both groups. C. spiroforme toxin acted on cells by disrupting microfilaments by ADP-ribosylation of G actin. Toxicity was not blocked by 10 or 20 mM ammonium chloride and was only moderately inhibited by 30 mM NH4Cl. Inhibition of coated-pit formation in HEp-2 cells by potassium depletion strongly protected against the effect of C. spiroforme toxin. Toxicity was not blocked by incubation of HEp-2 cells and spiroforme toxin at 15 degrees C. These results suggest that this new binary toxin enters cells via the coated-pit-coated-vesicle pathway and might reach the cytoplasm at the same time as or before transfer to early endosomes. Images PMID:2545625
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Trust information-based privacy architecture for ubiquitous health.
Ruotsalainen, Pekka Sakari; Blobel, Bernd; Seppälä, Antto; Nykänen, Pirkko
2013-10-08
Ubiquitous health is defined as a dynamic network of interconnected systems that offers health services independent of time and location to a data subject (DS). The network takes place in open and unsecure information space. It is created and managed by the DS who sets rules that regulate the way personal health information is collected and used. Compared to health care, it is impossible in ubiquitous health to assume the existence of a priori trust between the DS and service providers and to produce privacy using static security services. In ubiquitous health features, business goals and regulations systems followed often remain unknown. Furthermore, health care-specific regulations do not rule the ways health data is processed and shared. To be successful, ubiquitous health requires novel privacy architecture. The goal of this study was to develop a privacy management architecture that helps the DS to create and dynamically manage the network and to maintain information privacy. The architecture should enable the DS to dynamically define service and system-specific rules that regulate the way subject data is processed. The architecture should provide to the DS reliable trust information about systems and assist in the formulation of privacy policies. Furthermore, the architecture should give feedback upon how systems follow the policies of DS and offer protection against privacy and trust threats existing in ubiquitous environments. A sequential method that combines methodologies used in system theory, systems engineering, requirement analysis, and system design was used in the study. In the first phase, principles, trust and privacy models, and viewpoints were selected. Thereafter, functional requirements and services were developed on the basis of a careful analysis of existing research published in journals and conference proceedings. Based on principles, models, and requirements, architectural components and their interconnections were developed using system
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Trust Information-Based Privacy Architecture for Ubiquitous Health
2013-01-01
Background Ubiquitous health is defined as a dynamic network of interconnected systems that offers health services independent of time and location to a data subject (DS). The network takes place in open and unsecure information space. It is created and managed by the DS who sets rules that regulate the way personal health information is collected and used. Compared to health care, it is impossible in ubiquitous health to assume the existence of a priori trust between the DS and service providers and to produce privacy using static security services. In ubiquitous health features, business goals and regulations systems followed often remain unknown. Furthermore, health care-specific regulations do not rule the ways health data is processed and shared. To be successful, ubiquitous health requires novel privacy architecture. Objective The goal of this study was to develop a privacy management architecture that helps the DS to create and dynamically manage the network and to maintain information privacy. The architecture should enable the DS to dynamically define service and system-specific rules that regulate the way subject data is processed. The architecture should provide to the DS reliable trust information about systems and assist in the formulation of privacy policies. Furthermore, the architecture should give feedback upon how systems follow the policies of DS and offer protection against privacy and trust threats existing in ubiquitous environments. Methods A sequential method that combines methodologies used in system theory, systems engineering, requirement analysis, and system design was used in the study. In the first phase, principles, trust and privacy models, and viewpoints were selected. Thereafter, functional requirements and services were developed on the basis of a careful analysis of existing research published in journals and conference proceedings. Based on principles, models, and requirements, architectural components and their interconnections
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Mining the preferences of patients for ubiquitous clinic recommendation.
Chen, Tin-Chih Toly; Chiu, Min-Chi
2018-03-06
A challenge facing all ubiquitous clinic recommendation systems is that patients often have difficulty articulating their requirements. To overcome this problem, a ubiquitous clinic recommendation mechanism was designed in this study by mining the clinic preferences of patients. Their preferences were defined using the weights in the ubiquitous clinic recommendation mechanism. An integer nonlinear programming problem was solved to tune the values of the weights on a rolling basis. In addition, since it may take a long time to adjust the values of weights to their asymptotic values, the back propagation network (BPN)-response surface method (RSM) method is applied to estimate the asymptotic values of weights. The proposed methodology was tested in a regional study. Experimental results indicated that the ubiquitous clinic recommendation system outperformed several existing methods in improving the successful recommendation rate.
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Clostridium perfringens type A–E toxin plasmids
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
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Converting a Staphylococcus aureus toxin into effective cyclic pseudopeptide antibiotics.
Solecki, Olivia; Mosbah, Amor; Baudy Floc'h, Michèle; Felden, Brice
2015-03-19
Staphylococcus aureus produces peptide toxins that it uses to respond to environmental cues. We previously characterized PepA1, a peptide toxin from S. aureus, that induces lytic cell death of both bacterial and host cells. That led us to suggest that PepA1 has an antibacterial activity. Here, we demonstrate that exogenously provided PepA1 has activity against both Gram-positive and Gram-negative bacteria. We also see that PepA1 is significantly hemolytic, thus limiting its use as an antibacterial agent. To overcome these limitations, we converted PepA1 into nonhemolytic derivatives. Our most promising derivative is a cyclic heptapseudopeptide with inconsequential toxicity to human cells, enhanced stability in human sera, and sharp antibacterial activity. Mechanistically, linear and helical PepA1 derivatives form pores at the bacterial and erythrocyte surfaces, while the cyclic peptide induces bacterial envelope reorganization, with insignificant action on the erythrocytes. Our work demonstrates that bacterial toxins might be an attractive starting point for antibacterial drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.
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THE PRODUCTION OF DIPHTHERIA TOXIN
Park, W. H.; Williams, A. W.
1896-01-01
Toxin of sufficient strength to kill a 400-gramme guinea-pig in three days and a half in a dose of 0·cubic centimetre developed in suitable bouillon, contained in ordinary Erlenmeyer flasks, within a period of twenty-four hours. In such boullon the toxin reached its greatest strength in from four to seven days (0·005 cubic centimetre killing a 500-gramme guinea-pig in three days). This period of time covered that of the greatest growth of the bacilli, as shown both by the appearance of the culture and by the number of colonies developing an agar plates. The bodies of the diphtheria bacili did not at any time contain toxin in cosiderable amounts. The type of growth of the bacili and the rapidity and extent of the production of toxin depended more on the reaction of the bouillon than upon any other single factor. The best results were obtained in bouillon which, after being neutralized to litmus, had about seven cubic centimetres of normal soda solution added to each litre. An excessive amount of either acid or alkali prevented the development of toxin. Strong toxin was produced in bouillon containing peptone ranging from one to ten per cent. The strength of toxin averaged greater in the two and four-per-cent peptone solutions than in the one-percent. When the stage of acid reaction was brief and the degree of acidity probably slight, strong toxin developed while the culture bouillon was still acid; but when the stage of acid reaction was prolonged, little if any toxin was produced until just before the fluid became alkaline. Glucose is deleterious to the growth of the diphtheria bacillus and to the production of toxin when it is present in sufficient amounts to cause by its disintegration too great a degree of acidity in the fluid culture. When the acid resulting from decomposition of glucose is neutralized by the addition of alkali the diphtheria bacilus again grows abundantly. Glucose is not present, at least as a rule, in sufficient amounts in the meat as
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[Intoxication of botulinum toxin].
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. © 2015 MEDPRESS.
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Excitable toxin-antitoxin modules coordinated through intracellular bottlenecks
NASA Astrophysics Data System (ADS)
Mather, William
Chronic infections and pathogenic biofilms present a serious threat to the health of humans by decreasing life expectancy and quality. The resilience of these microbial communities has been attributed to the spontaneous formation of persister cells, which constitute a small fraction of the population capable of surviving a wide range of environmental stressors. Gating of bacterial persistence has recently been linked to toxin-antitoxin (TA) modules, which are operons with an evolutionarily conserved motif that includes a toxin that halts cell growth and a corresponding antitoxin that neutralizes the toxin. While many such modules have been identified and studied in a wide range of organisms, little consideration of the interactions between multiple modules within a single host has been made. Moreover, the multitude of different antitoxin species are degraded by a relatively small number of proteolytic pathways, strongly suggesting competition between antitoxins for degradation machinery, i.e. queueing coupling. Here we present a theoretical understanding of the dynamics of multiple TA modules that are coupled through either proteolytic queueing, a toxic effect on cell growth rate, or both. We conclude that indirect queueing coordination between multiple TA modules may be central to controlling bacterial persistence. NSF Award Number MCB-1330180.
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Construction of Course Ubiquitous Learning Based on Network
ERIC Educational Resources Information Center
Wang, Xue; Zhang, Wei; Yang, Xinhui
2017-01-01
Ubiquitous learning has been more and more recognized, which describes a new generation of learning from a new point of view. Ubiquitous learning will bring the new teaching practice and teaching reform, which will become an essential way of learning in 21st century. Taking translation course as a case study, this research constructed a system of…
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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
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Bordetella Adenylate Cyclase-Hemolysin Toxins
Guiso, Nicole
2017-01-01
Adenylate cyclase-hemolysin toxin is secreted and produced by three classical species of the genus Bordetella: Bordetella pertussis, B. parapertussis and B. bronchiseptica. This toxin has several properties such as: (i) adenylate cyclase activity, enhanced after interaction with the eukaryotic protein, calmodulin; (ii) a pore-forming activity; (iii) an invasive activity. It plays an important role in the pathogenesis of these Bordetella species responsible for whooping cough in humans or persistent respiratory infections in mammals, by modulating host immune responses. In contrast with other Bordetella toxins or adhesins, lack of (or very low polymorphism) is observed in the structural gene encoding this toxin, supporting its importance as well as a potential role as a vaccine antigen against whooping cough. In this article, an overview of the investigations undertaken on this toxin is presented. PMID:28892012
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Pore-forming toxins in Cnidaria.
Podobnik, Marjetka; Anderluh, Gregor
2017-12-01
The ancient phylum of Cnidaria contains many aquatic species with peculiar lifestyle. In order to survive, these organisms have evolved attack and defense mechanisms that are enabled by specialized cells and highly developed venoms. Pore-forming toxins are an important part of their venomous arsenal. Along some other types, the most representative are examples of four protein families that are commonly found in other kingdoms of life: actinoporins, Cry-like proteins, aerolysin-like toxins and MACPF/CDC toxins. Some of the homologues of pore-forming toxins may serve other functions, such as in food digestion, development and response against pathogenic organisms. Due to their interesting physico-chemical properties, the cnidarian pore-forming toxins may also serve as tools in medical research and nanobiotechnological applications. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Plant Insecticidal Toxins in Ecological Networks
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
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NASA Technical Reports Server (NTRS)
Crowley, Sandra L.
2000-01-01
Ubiquitous is a real word. I thank a former Total Quality Coach for my first exposure some years ago to its existence. My version of Webster's dictionary defines ubiquitous as "present, or seeming to be present, everywhere at the same time; omnipresent." While I believe that God is omnipresent, I have come to discover that CM and DM are present everywhere. Oh, yes; I define CM as Configuration Management and DM as either Data or Document Management. Ten years ago, I had my first introduction to the CM world. I had an opportunity to do CM for the Space Station effort at the NASA Lewis Research Center. I learned that CM was a discipline that had four areas of focus: identification, control, status accounting, and verification. I was certified as a CMIl graduate and was indoctrinated about clear, concise, and valid. Off I went into a world of entirely new experiences. I was exposed to change requests and change boards first hand. I also learned about implementation of changes, and then of technical and CM requirements.
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*CYANOBACTERIA AND THEIR TOXINS
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...
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Internet messenger based smart virtual class learning using ubiquitous computing
NASA Astrophysics Data System (ADS)
Umam, K.; Mardi, S. N. S.; Hariadi, M.
2017-06-01
Internet messenger (IM) has become an important educational technology component in college education, IM makes it possible for students to engage in learning and collaborating at smart virtual class learning (SVCL) using ubiquitous computing. However, the model of IM-based smart virtual class learning using ubiquitous computing and empirical evidence that would favor a broad application to improve engagement and behavior are still limited. In addition, the expectation that IM based SVCL using ubiquitous computing could improve engagement and behavior on smart class cannot be confirmed because the majority of the reviewed studies followed instructions paradigms. This article aims to present the model of IM-based SVCL using ubiquitous computing and showing learners’ experiences in improved engagement and behavior for learner-learner and learner-lecturer interactions. The method applied in this paper includes design process and quantitative analysis techniques, with the purpose of identifying scenarios of ubiquitous computing and realize the impressions of learners and lecturers about engagement and behavior aspect and its contribution to learning
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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.
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Gryspeirt, Aiko; Grégoire, Jean-Claude
2012-01-01
To delay resistance development to Bacillus thuringiensis (Bt) plants expressing their own insecticide, the application of the Insect Resistance Management strategy called “High Dose/Refuge Strategy” (HD/R) is recommended by the US Environmental Protection Agency (US EPA). This strategy was developed for Bt plants expressing one toxin. Presently, however, new Bt plants that simultaneously express two toxins are on the market. We used a mathematical model to evaluate the efficiency of the HD/R strategy for both these Bt toxins. As the current two-toxin Bt plants do not express two new Cry toxins but reuse one toxin already in use with a one-toxin plant, we estimated the spread of resistance when the resistance alleles are not rare. This study assesses: (i) whether the two toxins have to be present in high concentration, and (ii) the impact of the relative size of the refuge zone on the evolution of resistance and population density. We concluded that for Bt plants expressing one toxin, a high concentration is an essential condition for resistance management. For the pyramided Bt plants, one toxin could be expressed at a low titer if the two toxins are used for the first time, and a small refuge zone is acceptable. PMID:23162699
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Gryspeirt, Aiko; Grégoire, Jean-Claude
2012-10-01
To delay resistance development to Bacillus thuringiensis (Bt) plants expressing their own insecticide, the application of the Insect Resistance Management strategy called "High Dose/Refuge Strategy" (HD/R) is recommended by the US Environmental Protection Agency (US EPA). This strategy was developed for Bt plants expressing one toxin. Presently, however, new Bt plants that simultaneously express two toxins are on the market. We used a mathematical model to evaluate the efficiency of the HD/R strategy for both these Bt toxins. As the current two-toxin Bt plants do not express two new Cry toxins but reuse one toxin already in use with a one-toxin plant, we estimated the spread of resistance when the resistance alleles are not rare. This study assesses: (i) whether the two toxins have to be present in high concentration, and (ii) the impact of the relative size of the refuge zone on the evolution of resistance and population density. We concluded that for Bt plants expressing one toxin, a high concentration is an essential condition for resistance management. For the pyramided Bt plants, one toxin could be expressed at a low titer if the two toxins are used for the first time, and a small refuge zone is acceptable.
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Cárdenas-Mondragón, María G; Ares, Miguel A; Panunzi, Leonardo G; Pacheco, Sabino; Camorlinga-Ponce, Margarita; Girón, Jorge A; Torres, Javier; De la Cruz, Miguel A
2016-01-01
Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence of H. pylori in the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin-antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome of H. pylori 26695: HP0315-HP0316, HP0892-HP0893, and HP0894-HP0895. Here we characterized a heretofore undescribed type II TA system in H. pylori , HP0967-HP0968, which is encoded by the bicistronic operon hp0968-hp0967 and belongs to the Vap family. The predicted HP0967 protein is a toxin with ribonuclease activity whereas HP0968 is an antitoxin that binds to its own regulatory region. We found that all type II TA systems were expressed in H. pylori during early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, the hp0968-hp0967 pair was the most affected under these environmental conditions. Transcription of hp0968-hp0967 was strongly induced in a mature H. pylori biofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. The hp0968-hp0967 TA system was the most frequent among 317 H. pylori strains isolated from all over the world. This study is the first report on the transcription of type II TA genes in H. pylori under different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute a bona fide type II TA system in H. pylori , whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa.
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Food toxin detection with atomic force microscope
USDA-ARS?s Scientific Manuscript database
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...
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The Interactions of Human Neutrophils with Shiga Toxins and Related Plant Toxins: Danger or Safety?
Brigotti, Maurizio
2012-01-01
Shiga toxins and ricin are well characterized similar toxins belonging to quite different biological kingdoms. Plant and bacteria have evolved the ability to produce these powerful toxins in parallel, while humans have evolved a defense system that recognizes molecular patterns common to foreign molecules through specific receptors expressed on the surface of the main actors of innate immunity, namely monocytes and neutrophils. The interactions between these toxins and neutrophils have been widely described and have stimulated intense debate. This paper is aimed at reviewing the topic, focusing particularly on implications for the pathogenesis and diagnosis of hemolytic uremic syndrome. PMID:22741061
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Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin.
Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro
2017-08-11
Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.
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Conditional Toxin Splicing Using a Split Intein System.
Alford, Spencer C; O'Sullivan, Connor; Howard, Perry L
2017-01-01
Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin. Considerations for the engineering and implementation of conditional toxin splicing (CTS) systems include: choice of toxin split site, split site (extein) chemistry, and temperature sensitivity. The following method outlines design criteria and implementation notes for CTS using a previously engineered system for splicing a toxin called sarcin, as well as for developing alternative CTS systems.
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Mutant with diphtheria toxin receptor and acidification function but defective in entry of toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kohno, Kenji; Hayes, H.; Mekada, Eisuke
1987-09-01
A mutant of Chinese hamster ovary cells, GE1, that is highly resistant to diphtheria toxin was isolated. The mutant contains 50% ADP-ribosylatable elongation factor 2, but its protein synthesis was not inhibited by the toxin even at concentrations above 100 {mu}g/ml. {sup 125}I-labeled diphtheria toxin was associated with GE1 cells as well as with the parent cells but did not block protein synthesis of GE1 cells even when the cells were exposed to low pH in the presence or absence of NH{sub 4}Cl. The infections of GE1 cells and the parent cells by vesicular stomatitis virus were similar. GE1 cellsmore » were cross-resistant to Pseudomonas aeruginosa exotoxin A and so were about 1,000 times more resistant to this toxin than the parent cells. Hybrids of GE1 cells and the parent cells or mutant cells lacking a functional receptor were more sensitive to diphtheria toxin than GE1 cells. These results suggest that entry of diphtheria toxin into cells requires a cellular factor(s) in addition to those involved in receptor function and acidification of endosomes and that GE1 cells do not express this cellular factor. This character is recessive in GE1 cells.« less
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Computational Studies of Snake Venom Toxins
Ojeda, Paola G.; Caballero, Julio; Kaas, Quentin; González, Wendy
2017-01-01
Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin. PMID:29271884
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Structure, Biology, and Therapeutic Application of Toxin-Antitoxin Systems in Pathogenic Bacteria.
Lee, Ki-Young; Lee, Bong-Jin
2016-10-22
Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein-protein interactions. Accumulating knowledge about the structure-function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.
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Clostridial toxins active locally in the gastrointestinal tract.
Wilkins, T; Krivan, H; Stiles, B; Carman, R; Lyerly, D
1985-01-01
Clostridium difficile and Clostridium spiroforme have only in recent years been recognized as intestinal pathogens. They both produce toxins that are also produced by other clostridia. C. difficile toxins A and B are produced by C. sordellii and a few strains of C. perfringens whereas C. spiroforme produces the same toxins as C. perfringens Type E (iota toxin). Iota toxin activity may be the product of two proteins. Toxigenic strains of C. spiroforme and Type E produce two antigens which possess much more biological activity when administered together than when given alone. C. difficile was thought for some time to produce only a single toxin, but then the enterotoxic activity was shown to be due to a separate toxin (toxin A). This toxin increases the oral toxicity of toxin B (the main cytotoxin) and may increase the permeability of the colon. Toxin A binds to a specific receptor in hamster brush border membranes and in the membranes of rabbit erythrocytes. This receptor appears to be a glycoprotein. The receptor can be extracted from the membrane with Triton and binds to immobilized toxin A. The receptor can be extracted and used to coat plastic plates as a first phase in an ELISA assay. Another assay has been developed in which the toxin A binds to the red cells and then the erythrocytes are agglutinated with antitoxin. An even more sensitive assay consists of using rabbit erythrocyte ghosts to bind the toxin and then precipitating the ghosts with antibody to toxin A attached to latex beads. Monoclonal antibodies to toxin A also have been developed and are used in these and other assays.
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NASA Astrophysics Data System (ADS)
Yang, Weidong; Zhang, Naisheng; Cui, Weimin; Xu, Yanyan; Li, Hongye; Liu, Jiesheng
2011-11-01
Karenia mikimotoi (Miyake & Kominami ex Oda) Hansen & Moestrup is associated with harmful algal blooms in temperate and subtropical zones of the world. The hemolytic substances produced by K. mikimotoi are thought to cause mortality in fishes and invertebrates. We evaluated the composition of the hemolytic toxin produced by K. mikimotoi cultured in the laboratory using thin-layer chromatography. In addition, we evaluated the effect of co-occuring algae ( Prorocentrum donghaiense and Alexandrium tamarense) and the cladoceran grazer Moina mongolica on hemolytic toxin production in K. mikimotoi. The hemolytic toxins from K. mikimotoi were a mixture of 2 liposaccharides and 1 lipid. Waterborne clues from P. donghaiense and A. tamarense inhibited the growth of K. mikimotoi but increased the production of hemolytic toxins. Conversely, K. mikimotoi strongly inhibited the growth of caged P. donghaiense and A. tamarense. In addition, the ingestion of K. mikimotoi by M. mongolica induced the production of hemolytic toxins in K. mikimotoi. Taken together, our results suggest that the presence of other microalgae and grazers may be as important as environmental factors for controlling the production of hemolytic substances. K. mikimotoi secreted allelochemicals other than unstable fatty acids with hemolytic activity. The production of hemolytic toxins in dinoflagellates was not only dependent on resource availability, but also on the risk of predation. Hemolytic toxins likely play an important role as chemical deterrents secreted by K. mikimotoi.
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Brown spider dermonecrotic toxin directly induces nephrotoxicity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chaim, Olga Meiri; Sade, Youssef Bacila; Bertoni da Silveira, Rafael
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 proteinaceousmore » 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
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Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin
Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro
2017-01-01
Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins. PMID:28800062
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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
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Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger
2016-04-01
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.
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Implications of Ubiquitous Computing for the Social Studies Curriculum
ERIC Educational Resources Information Center
van Hover, Stephanie D.; Berson, Michael J.; Bolick, Cheryl Mason; Swan, Kathleen Owings
2004-01-01
In March 2002, members of the National Technology Leadership Initiative (NTLI) met in Charlottesville, Virginia to discuss the potential effects of ubiquitous computing on the field of education. Ubiquitous computing, or "on-demand availability of task-necessary computing power," involves providing every student with a handheld computer--a…
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The National Center for Environmental Assessment has prepared the Toxicological Reviews of Cyanobacterial Toxins: Anatoxin-a, Cylindrospermopsin and Microcystins (LR, RR, YR and LA) as a series of dose-response assessments to support the health assessment of unregulated contamina...
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[Biological and toxin terrorism weapons].
Bokan, Slavko
2003-03-01
The use of biological agents and toxins in warfare and terrorism has a long history. Human, animal and plant pathogens and toxins can cause disease and can be used as a threat to humans, animals and staple crops. The same is true for biological agents. Although the use of biological agents and toxins in military conflicts has been a concern of military communities for many years, several recent events have increased the awareness of terrorist use of these weapons against civilian population. A Mass Casualty Biological (Toxin) Weapon (MCBTW) is any biological and toxin weapon capable of causing death or disease on a large scale, such that the military or civilian infrastructure of the state or organization being attacked is overwhelmed. A militarily significant (or terrorist) weapon is any weapon capable of affecting, directly or indirectly, that is physically or psychologically, the outcome of a military operation. Although many biological agents such as toxins and bioregulators can be used to cause diseases, there are only a few that can truly threaten civilian populations on a large scale. Bioregulators or modulators are biochemical compounds, such as peptides, that occur naturally in organisms. They are new class of weapons that can damage nervous system, alter moods, trigger psychological changes and kill. The potential military or terrorist use of bioregulators is similar to that of toxins. Some of these compounds are several hundred times more potent than traditional chemical warfare agents. Important features and military advantages of new bioregulators are novel sites of toxic action; rapid and specific effects; penetration of protective filters and equipment, and militarily effective physical incapacitation. This overview of biological agents and toxins is largely intended to help healthcare providers on all levels to make decisions in protecting general population from these agents.
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Socio-technical Issues for Ubiquitous Information Society in 2010
NASA Astrophysics Data System (ADS)
Funabashi, Motohisa; Homma, Koichi; Sasaki, Toshiro; Sato, Yoshinori; Kido, Kunihiko; Fukumoto, Takashi; Yano, Koujin
Impact of the ubiquitous information technology on our society is so significant that directing technological development and preparing institutional apparatus are quite important and urgent. The present paper elaborates, with the efforts by both humanity and engineering disciplines, to find out the socio-technical issues of ubiquitous information society in 2010 by inspecting social implications of emerging technology as well as social expectations. In order to deliberate the issues, scenarios are developed that describes possible life in ubiquitous information society. The derived issues cover integrating information technology and human body, producing smart sharable environment, protecting individual rights, fostering new service business, and forming community.
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Naturally Occurring Food Toxins
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
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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
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Yermakova, Anastasiya; Klokk, Tove Irene; O'Hara, Joanne M; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J
2016-03-07
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.
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Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles
2017-01-01
ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).
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Trust models in ubiquitous computing.
Krukow, Karl; Nielsen, Mogens; Sassone, Vladimiro
2008-10-28
We recapture some of the arguments for trust-based technologies in ubiquitous computing, followed by a brief survey of some of the models of trust that have been introduced in this respect. Based on this, we argue for the need of more formal and foundational trust models.
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The Status of Ubiquitous Computing.
ERIC Educational Resources Information Center
Brown, David G.; Petitto, Karen R.
2003-01-01
Explains the prevalence and rationale of ubiquitous computing on college campuses--teaching with the assumption or expectation that all faculty and students have access to the Internet--and offers lessons learned by pioneering institutions. Lessons learned involve planning, technology, implementation and management, adoption of computer-enhanced…
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Application of Biosensors Based on Lipid Membranes for the Rapid Detection of Toxins.
Nikoleli, Georgia-Paraskevi; Nikolelis, Dimitrios P; Siontorou, Christina G; Karapetis, Stephanos; Nikolelis, Marianna-Thalia
2018-06-26
Lipid assemblies in the form of two dimensional films have been used extensively as biosensing platforms. These films exhibit certain similarities with cell membranes, thus providing a suitable means for the immobilization of proteinaceous moieties and, further, a number of intrinsic signal amplification mechanisms. Their implementation in the detection of toxins yielded reliable and fast detectors for in field analyses of environmental and clinical samples. Some examples are presented herein, including aflatoxin and cholera toxin detection. The conditions and parameters that determine the analytical specifications of the lipid membrane sensors are discussed, advantages and technology bottlenecks are reviewed, and possible further developments are highlighted.
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Kashiwagi, T; Kunishima, N; Suzuki, C; Tsuchiya, F; Nikkuni, S; Arata, Y; Morikawa, K
1997-01-15
Several strains of yeasts and fungi produce proteinous substances, termed killer toxins, which kill sensitive strains. The SMK toxin, secreted by the halotolerant yeast Pichia farinosa KK1 strain, uniquely exhibits its maximum killer activity under conditions of acidic pH and high salt concentration. The toxin is composed of two distinct subunits, alpha and beta, which tightly interact with each other under acidic conditions. However, they are easily dissociated under neutral conditions and lose the killer activity. The three-dimensional structure of the SMK toxin will provide a better understanding of the mechanism of toxicity of this protein and the cause of its unique pH-dependent stability. Two crystal structures of the SMK toxin have been determined at 1.8 A resolution in different ionic strength conditions. The two subunits, alpha and beta, are jointly folded into an ellipsoidal, single domain structure belonging to the alpha/beta-sandwich family. The folding topology of the SMK toxin is essentially the same as that of the fungal killer toxin, KP4. This shared topology contains two left-handed split betaalphabeta motifs, which are rare in the other proteins. Many acidic residues are clustered at the bottom of the SMK toxin molecule. Some of the carboxyl sidechains interact with each other through hydrogen bonds. The ionic strength difference induces no evident structural change of the SMK toxin except that, in the high ionic strength crystal, a number of sulfate ions are electrostatically bound near the basic residues which are also locally distributed at the bottom of the toxin molecule. The two killer toxins, SMK and KP4, share a unique folding topology which contains a rare structural motif. This observation may suggest that these toxins are evolutionally and/or functionally related. The pH-dependent stability of the SMK toxin is a result of the intensive interactions between the carboxyl groups. This finding is important for protein engineering, for
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Friend, M.
1999-01-01
The previous chapters provide information about some of the chemical toxins that have lethal effects on wild birds. The material presented in Section 7, Chemical Toxins, is far from comprehensive because wild birds are poisoned by a wide variety of toxic substances. Also, monitoring of wild bird mortality is not yet organized so that diagnostic findings can be extended to reflect the relative impacts among the types of toxins, within populations, or among species, geographic areas, and time. The data that are available are not collectively based on random sampling, nor do specimen collection and submission follow methodical assessment methods. Instead, most data simply document individual bird poisoning events. The inherent biases in this information include the species of birds observed dead (large birds in open areas are more likely to be observed dead than small forest birds); the species of birds likely to be submitted for analysis (bald eagles are more likely to be submitted than house sparrows); collection sites (agricultural fields are more likely to be observed than urban environments); geographic area of the country; season; reasons for submissions; and other variables. Nevertheless, findings from individual events reflect the causes of mortality associated with those events and collectively identify chemical toxins that repeatedly cause bird mortalities which result in carcass collection and sub
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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.
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Sea Anemone (Cnidaria, Anthozoa, Actiniaria) Toxins: An Overview
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
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Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: an overview.
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.
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Role of Passive Capturing in a Ubiquitous Learning Environment
ERIC Educational Resources Information Center
Ogata, Hiroaki; Hou, Bin; Li, MengMeng; Uosaki, Noriko; Mouri, Kousuke
2013-01-01
Ubiquitous Learning Log (ULL) is defined as a digital record of what you have learned in the daily life using ubiquitous technologies. This paper focuses on how to capture learning experiences in our daily life for vocabulary learning. In our previous works, we developed a system named SCROLL (System for Capturing and Reminding Of Learning Log) in…
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Ubiquitous Learning Project Using Life-Logging Technology in Japan
ERIC Educational Resources Information Center
Ogata, Hiroaki; Hou, Bin; Li, Mengmeng; Uosaki, Noriko; Mouri, Kosuke; Liu, Songran
2014-01-01
A Ubiquitous Learning Log (ULL) is defined as a digital record of what a learner has learned in daily life using ubiquitous computing technologies. In this paper, a project which developed a system called SCROLL (System for Capturing and Reusing Of Learning Log) is presented. The aim of developing SCROLL is to help learners record, organize,…
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Alam, Syed Imteyaz; Kumar, Bhoj; Kamboj, Dev Vrat
2012-12-04
Protein toxins, such as botulinum neurotoxins (BoNTs), Clostridium perfringens epsilon toxin (ETX), staphylococcal enterotoxin B (SEB), shiga toxin (STX), and plant toxin ricin, are involved in a number of diseases and are considered as potential agents for bioterrorism and warfare. From a bioterrorism and warfare perspective, these agents are likely to cause maximum damage to a civilian or military population through an inhalational route of exposure and aerosol is considered the envisaged mode of delivery. Unambiguous detection of toxin from aerosol is of paramount importance, both for bringing mitigation protocols into operation and for implementation of effective medical countermeasures, in case a "biological cloud" is seen over a population. A multiplex, unambiguous, and qualitative detection of protein toxins is reported here using tandem mass spectrometry with MALDI-TOF-TOF. The methodology involving simple sample processing steps was demonstrated to identify toxins (ETX, Clostridium perfringes phospholipase C, and SEB) from blind spiked samples. The novel directed search approach using a list of unique peptides was used to identify toxins from a complex protein mixture. The bioinformatic analysis of seven protein toxins for elucidation of unique peptides with conservation status across all known sequences provides a high confidence for detecting toxins originating from any geographical location and source organism. Use of tandem MS data with peptide sequence information increases the specificity of the method. A prototype for generation of aerosol using a nebulizer and collection using a cyclone collector was used to provide a proof of concept for unambiguous detection of toxin from aerosol using precursor directed tandem mass spectrometry combined with protein database searching. ETX prototoxin could be detected from aerosol at 0.2 ppb concentration in aerosol.
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Hungerford, James M
2006-01-01
In a very busy and exciting year, 2005 included First Action approval of a much needed official method for paralytic shellfish toxins and multiple international toxin symposia highlighted by groundbreaking research. These are the first-year milestones and activities of the Marine and Freshwater Toxins Task Force and Analytical Community. Inaugurated in 2004 and described in detail in last year's General Referee Report (1) this international toxins group has grown to 150 members from many regions and countries. Perhaps most important they are now making important and global contributions to food safety and to providing alternatives to animal-based assays. Official Method 2005.06 was first approved in late 2004 by the Task Force and subsequently Official First Action in 2005 (2) by the Methods Committee on Natural Toxins and Food Allergens and the Official Methods Board. This nonproprietary method (3) is a precolumn oxidation, liquid chromatographic method that makes good use of fluorescence detection to provide high sensitivity detection of the saxitoxins. It has also proven to be rugged enough for regulatory use and the highest level of validation. As pointed out in the report of method principle investigator and Study Director James Lawrence, approval of 2005.06 now provides the first official alternative to the mouse bioassay after many decades of shellfish monitoring. This past year in April 2005 the group also held their first international conference, "Marine and Freshwater Toxins Analysis: Ist Joint Symposium and AOAC Task Force Meeting," in Baiona, Spain. The 4-day conference consisted of research and stakeholder presentations and symposium-integrated subgroup sessions on ciguatoxins, saxitoxin assays and liquid chromatography (LC) methods for saxitoxins and domoic acids, okadaiates and azaspiracids, and yessotoxins. Many of these subgroups were recently formed in 2005 and are working towards their goals of producing officially validated analytical methods
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Role of Botulinum Toxin in Depression.
Parsaik, Ajay K; Mascarenhas, Sonia S; Hashmi, Aqeel; Prokop, Larry J; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder
2016-03-01
The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression. We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic. Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo. This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.
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Emerging insights into the biology of typhoid toxin
Fowler, Casey C.; Chang, Shu-Jung; Gao, Xiang; Geiger, Tobias; Stack, Gabrielle; Galán, Jorge E.
2017-01-01
Typhoid toxin is a unique A2B5 exotoxin and an important virulence factor for Salmonella Typhi, the cause of typhoid fever. In the decade since its initial discovery, great strides have been made in deciphering the unusual biological program of this toxin, which is fundamentally different from related toxins in many ways. Purified typhoid toxin administered to laboratory animals causes many of the symptoms of typhoid fever, suggesting that typhoid toxin is a central factor in this disease. Further advances in understanding the biology of this toxin will help guide the development of badly needed diagnostics and therapeutic interventions that target this toxin to detect, prevent or treat typhoid fever. PMID:28213043
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Botulinum toxin therapy for limb dystonias.
Yoshimura, D M; Aminoff, M J; Olney, R K
1992-03-01
We investigated the effectiveness of botulinum toxin in 17 patients with limb dystonias (10 with occupational cramps, three with idiopathic dystonia unrelated to activity, and two each with post-stroke and parkinsonian dystonia) in a placebo-controlled, blinded study. We identified affected muscles clinically and by recording the EMG from implanted wire electrodes at rest and during performance of tasks that precipitated abnormal postures. There were three injections given with graded doses of toxin (average doses, 5 to 10, 10 to 20, and 20 to 40 units per muscle) and one with placebo, in random order. Subjective improvement occurred after 53% of injections of botulinum toxin, and this was substantial in 24%. Only one patient (7%) improved after placebo injection. Subjective improvement occurred in 82% of patients with at least one dose of toxin, lasting for 1 to 4 months. Response rates were similar between clinical groups. Objective evaluation failed to demonstrate significant improvement following treatment with toxin compared with placebo. The major side effect was transient focal weakness after 53% of injections of toxin.
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Fusarial toxins: secondary metabolites of Fusarium fungi.
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
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USDA-ARS?s Scientific Manuscript database
Shiga toxin producing Escherichia coli (STEC) represent a continuing threat to the Nation’s food supply and public health. Shiga toxin genes (stx) are encoded in lambda-like bacteriophages whose genome is inserted into the bacterial DNA. Environmental stress can trigger bacteriophage replication a...
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Puntscher, Hannes; Kütt, Mary-Liis; Skrinjar, Philipp; Mikula, Hannes; Podlech, Joachim; Fröhlich, Johannes; Marko, Doris; Warth, Benedikt
2018-05-16
Mycotoxins produced by Alternaria fungi are ubiquitous food contaminants, but analytical methods for generating comprehensive exposure data are rare. We describe the development of an LC-MS/MS method covering 17 toxins for investigating the natural occurrence of free and modified Alternaria toxins in tomato sauce, sunflower seed oil, and wheat flour. Target analytes included alternariol (AOH), AOH-3-glucoside, AOH-9-glucoside, AOH-3-sulfate, alternariol monomethyl ether (AME), AME-3-glucoside, AME-3-sulfate, altenuene, isoaltenuene, tenuazonic acid (TeA), tentoxin (TEN), altertoxin I and II, alterperylenol, stemphyltoxin III, altenusin, and altenuic acid III. Extensive optimization resulted in a time- and cost-effective sample preparation protocol and a chromatographic baseline separation of included isomers. Overall, adequate limits of detection (0.03-9 ng/g) and quantitation (0.6-18 ng/g), intermediate precision (9-44%), and relative recovery values (75-100%) were achieved. However, stemphyltoxin III, AOH-3-sulfate, AME-3-sulfate, altenusin, and altenuic acid III showed recoveries in wheat flour below 70%, while their performance was stable and reproducible. Our pilot study with samples from the Austrian retail market demonstrated that tomato sauces (n = 12) contained AOH, AME, TeA, and TEN in concentrations up to 20, 4, 322, and 0.6 ng/g, while sunflower seed oil (n = 7) and wheat flour samples (n = 9) were contaminated at comparatively lower levels. Interestingly and of relevance for risk assessment, AOH-9-glucoside, discovered for the first time in naturally contaminated food items, and AME-3-sulfate were found in concentrations similar to their parent toxins. In conclusion, the established multi-analyte method proved to be fit for purpose for generating comprehensive Alternaria toxin occurrence data in different food matrices. Graphical abstract ᅟ.
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Bhatnagar, R; Batra, S
2001-01-01
Anthrax is primarily a disease of herbivores caused by gram-positive, aerobic, spore-forming Bacillus anthracis. Humans are accidental hosts through the food of animal origin and animal products. Anthrax is prevelant in most parts of the globe, and cases of anthrax have been reported from almost every country. Three forms of the disease have been recognized: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). The major virulence factors of Bacillus anthracis are a poly-D glutamic acid capsule and a three-component protein exotoxin. The genes coding for the toxin and the enzymes responsible for capsule production are carried on plasmid pXO1 and pXO2, respectively. The three proteins of the exotoxin are protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). The toxins follow the A-B model with PA being the B moeity and LF/EF, the alternative A moeities. LF and EF are individually nontoxic, but in combination with PA form two toxins causing different pathogenic responses in animals and cultured cells. PA + LF forms the lethal toxin and PA + EF forms the edema toxin. During the process of intoxication, PA binds to the cell surface receptor and is cleaved at the sequence RKKR (167) by cell surface proteases such as furin generating a cell-bound, C-terminal 63 kDa protein (PA63). PA63 possesses a binding site to which LF or EF bind with high affinity. The complex is then internalized by receptor-mediated endocytosis. Acidification of the vesicle leads to instertion of PA63 into the endosomal membrane and translocation of LF/EF across the bilayer into the cytosol where they exert their toxic effects. EF has a calcium- and calmodulin-dependent adenylate cyclase activity. Recent reports indicate that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and 2), and this cleavage inactivates MAPKK1 and thus inhibits the
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Humphrey, C D; Condon, C W; Cantey, J R; Pittman, F E
1979-03-01
A toxin with cytotoxic and enterotoxic activities was isolated from cecal contents of hamsters receiving lincomycin. The toxin was partially purified by ultracentrifugation, ultrafiltration, (NH4)2SO4 precipitation, and gel filtration. Cytotoxic activity, assayed on monolayers of HeLa cells, was restricted to material that eluted in the molecular weight range of 107,000 +/- 6,000 daltons. Cytotoxicity of crude AAC toxin could be demonstrated at concentrations as low as 0.04 microgram/ml. The toxin was heat labile (55 degrees-60 degrees C for 0.5 hr) and sensitive to trypsinization, acidification at pH 3, or alkalinization at pH 9. Cytotoxic activity was inhibited by Clostridium sordellii antitoxin. Enterotoxic activity of the crude toxin and the cytotoxic fraction from gel filtration was demonstrated by fluid secretion in ligated rabbit ileal loops. Studies were done in vitro with cholestyramine resin, vancomycin, or gentamicin to determine if the toxin was bound or denatured by these drugs. It was demonstrated that cholestyramine bound the toxin, significantly reducing its cytotoxicity. Reversible binding of the cytotoxic material was demonstrated by salt gradient elution. Neither vancomycin nor gentamicin had any effect on the in vitro cytotoxic activity of the toxin.
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Harmful algal blooms (HABs), and their associated toxins, in fresh water lakes and reservoirs are drawing the attention of utilities and state regulators nation-wide. Recognizing the potential health and economic consequences, the US Environmental Protection Agency, in partnersh...
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Marine Neurotoxins: Ingestible Toxins.
Stommel, Elijah W.; Watters, Michael R.
2004-03-01
Fish and shellfish account for a significant portion of food-borne illnesses throughout the world. In general, three classes of diseases result from seafood consumption--intoxication, allergies, and infections. In this review, the authors discuss several seafood-borne toxins, including domoic acid, which acts on the central nervous system. In addition, the authors discuss ciguatoxin-, brevetoxin-, saxitoxin-, tetrodotoxin-, and scombroid-related histamine toxicity, all of which act primarily on the peripheral nervous system. Fish has become a very popular food in the US mostly related to its potential health benefits. Fish is consumed to such a degree that fishing stocks are reportedly at an all time low from what seemed like an endless supply even 30 years ago. One of the most significant threats to human intoxication is the recreational harvest of shellfish, often times located in remote locations where the harvesters are subsistent on fishery resources and have no monitoring in place. The hazard to intoxication is not as common in purchased seafood, which is more stringently regulated, yet still is a serious problem. Most ingestible toxins are thermo-stable and therefore unaffected by cooking, freezing, or salting. Air transport of consumable products throughout the world makes it easy to obtain exotic edibles from far away countries. A seemingly unusual toxin can be more commonly encountered than previously thought and it is important to consider this when evaluating patients. Recognition and treatment of various neurologic symptoms related to seafood ingestion is paramount in today's mobile, gastronomic world. Specific treatments vary with each individual toxin and with the individual's specific reaction to the toxin. Generally, some degree of medical care is required with all ingestible toxin exposure, ranging from simple administration of medication and hydration to ventilatory and cardiovascular support.
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Novel bacterial ADP-ribosylating toxins: structure and function
Simon, Nathan C.; Aktories, Klaus; Barbieri, Joseph T.
2018-01-01
Preface Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to eukaryotic proteins to promote bacterial pathogenesis. In this review we use prototype bARTTs, such as diphtheria and pertussis toxins, as references for the characterization of several new bARTTs from human, insect, and plant pathogens, which were identified recently through bioinformatic analyses. Several of these toxins, including Cholix toxin from Vibrio cholerae, SpyA from Streptococcus pyogenes, HopU1 from Pseudomonas syringae, and the Tcc toxins from Photorhabdus luminescens, ADP-ribosylate novel substrates and possess unique organizations, which distinguish them from the reference toxins. The characterization of these toxins extends our appreciation for the variety of structure-function properties possessed by bARTTs and their roles in bacterial pathogenesis. PMID:25023120
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Military Importance of Natural Toxins and Their Analogs.
Pitschmann, Vladimír; Hon, Zdeněk
2016-04-28
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.
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Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Brown, Angus M.
2017-01-01
ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood–brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS). PMID:28798954
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Shiga Toxin-Producing Escherichia coli O104:H4: a New Challenge for Microbiology
Muniesa, Maite; Hammerl, Jens A.; Hertwig, Stefan; Appel, Bernd
2012-01-01
In 2011, Germany experienced the largest outbreak with a Shiga toxin-producing Escherichia coli (STEC) strain ever recorded. A series of environmental and trace-back and trace-forward investigations linked sprout consumption with the disease, but fecal-oral transmission was also documented. The genome sequences of the pathogen revealed a clonal outbreak with enteroaggregative E. coli (EAEC). Some EAEC virulence factors are carried on the virulence plasmid pAA. From an unknown source, the epidemic strains acquired a lambdoid prophage carrying the gene for the Shiga toxin. The resulting strains therefore possess two different mobile elements, a phage and a plasmid, contributing essential virulence genes. Shiga toxin is released by decaying bacteria in the gut, migrates through the intestinal barrier, and is transported via the blood to target organs, like the kidney. In a mouse model, probiotic bifidobacteria interfered with transport of the toxin through the gut mucosa. Researchers explored bacteriophages, bacteriocins, and low-molecular-weight inhibitors against STEC. Randomized controlled clinical trials of enterohemorrhagic E. coli (EHEC)-associated hemolytic uremic syndrome (HUS) patients found none of the interventions superior to supportive therapy alone. Antibodies against one subtype of Shiga toxin protected pigs against fatal neurological infection, while treatment with a toxin receptor decoy showed no effect in a clinical trial. Likewise, a monoclonal antibody directed against a complement protein led to mixed results. Plasma exchange and IgG immunoadsoprtion ameliorated the condition in small uncontrolled trials. The epidemic O104:H4 strains were resistant to all penicillins and cephalosporins but susceptible to carbapenems, which were recommended for treatment. PMID:22504816
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Multimodal and ubiquitous computing systems: supporting independent-living older users.
Perry, Mark; Dowdall, Alan; Lines, Lorna; Hone, Kate
2004-09-01
We document the rationale and design of a multimodal interface to a pervasive/ubiquitous computing system that supports independent living by older people in their own homes. The Millennium Home system involves fitting a resident's home with sensors--these sensors can be used to trigger sequences of interaction with the resident to warn them about dangerous events, or to check if they need external help. We draw lessons from the design process and conclude the paper with implications for the design of multimodal interfaces to ubiquitous systems developed for the elderly and in healthcare, as well as for more general ubiquitous computing applications.
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A model for ubiquitous care of noncommunicable diseases.
Vianna, Henrique Damasceno; Barbosa, Jorge Luis Victória
2014-09-01
The ubiquitous computing, or ubicomp, is a promising technology to help chronic diseases patients managing activities, offering support to them anytime, anywhere. Hence, ubicomp can aid community and health organizations to continuously communicate with patients and to offer useful resources for their self-management activities. Communication is prioritized in works of ubiquitous health for noncommunicable diseases care, but the management of resources is not commonly employed. We propose the UDuctor, a model for ubiquitous care of noncommunicable diseases. UDuctor focuses the resources offering, without losing self-management and communication supports. We implemented a system and applied it in two practical experiments. First, ten chronic patients tried the system and filled out a questionnaire based on the technology acceptance model. After this initial evaluation, an alpha test was done. The system was used daily for one month and a half by a chronic patient. The results were encouraging and show potential for implementing UDuctor in real-life situations.
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Navigation studies based on the ubiquitous positioning technologies
NASA Astrophysics Data System (ADS)
Ye, Lei; Mi, Weijie; Wang, Defeng
2007-11-01
This paper summarized the nowadays positioning technologies, such as absolute positioning methods and relative positioning methods, indoor positioning and outdoor positioning, active positioning and passive positioning. Global Navigation Satellite System (GNSS) technologies were introduced as the omnipresent out-door positioning technologies, including GPS, GLONASS, Galileo and BD-1/2. After analysis of the shortcomings of GNSS, indoor positioning technologies were discussed and compared, including A-GPS, Cellular network, Infrared, Electromagnetism, Computer Vision Cognition, Embedded Pressure Sensor, Ultrasonic, RFID (Radio Frequency IDentification), Bluetooth, WLAN etc.. Then the concept and characteristics of Ubiquitous Positioning was proposed. After the ubiquitous positioning technologies contrast and selection followed by system engineering methodology, a navigation system model based on Incorporate Indoor-Outdoor Positioning Solution was proposed. And this model was simulated in the Galileo Demonstration for World Expo Shanghai project. In the conclusion, the prospects of ubiquitous positioning based navigation were shown, especially to satisfy the public location information acquiring requirement.
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Marín, Mercedes; Martín, Adoración; Rupnik, Maja
2014-01-01
Toxins A and B are the main virulence factors of Clostridium difficile and are the targets for molecular diagnostic tests. Here, we describe a new toxin A-negative, toxin B-positive, binary toxin CDT (Clostridium difficile transferase)-negative (A− B+ CDT−) toxinotype (XXXII) characterized by a variant type of pathogenicity locus (PaLoc) without tcdA and with atypical organization of the PaLoc integration site. PMID:25428159
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Therapeutic properties of green tea against environmental insults
Chen, Lixia; Mo, Huanbiao; Zhao, Ling; Gao, Weimin; Wang, Shu; Cromie, Meghan M; Lu, Chuanwen; Wang, Jia-Sheng; Shen, Chwan-Li
2016-01-01
Pesticides, smoke, mycotoxins, polychlorinated biphenyls, and arsenic are the most common environmental toxins and toxicants to humans. These toxins and toxicants may impact on human health at the molecular (DNA, RNA, or protein), organelle (mitochondria, lysosome, or membranes), cellular (growth inhibition or cell death), tissue, organ, and systemic levels. Formation of reactive radicals, lipid peroxidation, inflammation, genotoxicity, hepatotoxicity, embryotoxicity, neurological alterations, apoptosis, and carcinogenic events are some of the mechanisms mediating the toxic effects of the environmental toxins and toxicants. Green tea, the non-oxidized and non-fermented form of tea that contains several polyphenols, including green tea catechins, exhibits protective effects against these environmental toxins and toxicants in preclinical studies and to a much-limited extent, in clinical trials. The protective effects are collectively mediated by antioxidant, anti-inflammatory, anti-mutagenic, hepato- and neuroprotective, and anti-carcinogenic activities. In addition, green tea modulates signaling pathway including NFκB and ERK pathways, preserves mitochondrial membrane potential, inhibits caspase-3 activity, down-regulates pro-apoptotic proteins, and induces the phase II detoxifying pathway. The bioavailability and metabolism of green tea and its protective effects against environmental insults induced by pesticides, smoke, mycotoxins, polychlorinated biphenyls, and arsenic are reviewed in this paper. Future studies with emphasis on clinical trials should identify biomarkers of green tea intake, examine the mechanisms of action of green tea polyphenols, and investigate potential interactions of green tea with other toxicant-modulating dietary factors. PMID:27723473
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Genotypic characterization and biofilm formation of Shiga toxin-producing Escherichia coli.
Picozzi, Claudia; Antoniani, Davide; Vigentini, Ileana; Foschino, Roberto; Kneifel, Wolfgang
2017-01-01
Shiga toxin-producing Escherichia coli (STEC) are recognized as one of the most dangerous foodborne pathogens. The production of Shiga toxins together with intimin protein is among the main virulence factors. However, the ability to form biofilm can protect bacteria against environmental factors (i.e. desiccation, exposure to UV rays, predation, etc.) and sanitization procedures (cleaning, rinsing, chlorination), increasing their survival on food products and in manufacturing plants. Forty-five isolates collected from food and fecal samples were genotyped by pulsed field gel electrophoresis analysis with XbaI restriction enzyme and investigated by searching for toxins (stx1, stx2) and intimin (eae) genes and serogroup (O157, O26, O145, O111, O103 and O104). Afterward, the ability to develop biofilm in microtiter assay and the production of adhesive curli fimbriae and cellulose on agar plates were tested. Our study demonstrated that biofilm formation has a great variability among STEC strains and cannot be related to a specific pulsotype nor even to serogroup or presence of virulence genes. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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2007-02-28
be inter- changed to form biologically-active, hybrid toxins. Thereby, Ib can internalize the enzymatic components from either C. spiroforme or C...since chloro- quine, monensin, nigericin, or ammonium chloride did not in- hibit its activity (Fig. 2A). C. spiroforme toxin, which is very highly...ER [50]. These results are in agreement with a recent report [15], and an earlier finding [45] that there was no effect of C. spiroforme toxin when
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Toxin Detection by Surface Plasmon Resonance
Hodnik, Vesna; Anderluh, Gregor
2009-01-01
Significant efforts have been invested in the past years for the development of analytical methods for fast toxin detection in food and water. Immunochemical methods like ELISA, spectroscopy and chromatography are the most used in toxin detection. Different methods have been linked, e.g. liquid chromatography and mass spectrometry (LC-MS), in order to detect as low concentrations as possible. Surface plasmon resonance (SPR) is one of the new biophysical methods which enables rapid toxin detection. Moreover, this method was already included in portable sensors for on-site determinations. In this paper we describe some of the most common methods for toxin detection, with an emphasis on SPR. PMID:22573957
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Identification of the cellular receptor of Clostridium spiroforme toxin.
Papatheodorou, Panagiotis; Wilczek, Claudia; Nölke, Thilo; Guttenberg, Gregor; Hornuss, Daniel; Schwan, Carsten; Aktories, Klaus
2012-04-01
Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor.
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Azarian, Taj; Ali, Afsar; Johnson, Judith A; Jubair, Mohammad; Cella, Eleonora; Ciccozzi, Massimo; Nolan, David J; Farmerie, William; Rashid, Mohammad H; Sinha-Ray, Shrestha; Alam, Meer T; Morris, J Glenn; Salemi, Marco
2016-10-27
Vibrio cholerae is ubiquitous in aquatic environments, with environmental toxigenic V. cholerae O1 strains serving as a source for recurrent cholera epidemics and pandemic disease. However, a number of questions remain about long-term survival and evolution of V. cholerae strains within these aquatic environmental reservoirs. Through monitoring of the Haitian aquatic environment following the 2010 cholera epidemic, we isolated two novel non-toxigenic (ctxA/B-negative) Vibrio cholerae O1. These two isolates underwent whole-genome sequencing and were investigated through comparative genomics and Bayesian coalescent analysis. These isolates cluster in the evolutionary tree with strains responsible for clinical cholera, possessing genomic components of 6 th and 7 th pandemic lineages, and diverge from "modern" cholera strains around 1548 C.E. [95% HPD: 1532-1555]. Vibrio Pathogenicity Island (VPI)-1 was present; however, SXT/R391-family ICE and VPI-2 were absent. Rugose phenotype conversion and vibriophage resistance evidenced adaption for persistence in aquatic environments. The identification of V. cholerae O1 strains in the Haitian environment, which predate the first reported cholera pandemic in 1817, broadens our understanding of the history of pandemics. It also raises the possibility that these and similar environmental strains could acquire virulence genes from the 2010 Haitian epidemic clone, including the cholera toxin producing CTXϕ.
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Environmental determinants of polycystic ovary syndrome.
Merkin, Sharon Stein; Phy, Jennifer L; Sites, Cynthia K; Yang, Dongzi
2016-07-01
In this review, we summarize existing research on a variety of environmental factors potentially involved in the etiology, prevalence, and modulation of polycystic ovary syndrome (PCOS), and we suggest avenues for future research. The main environmental factors we consider include environmental toxins, diet and nutrition, socioeconomic status, and geography. There is some evidence that environmental toxins play a role in disrupting reproductive health, but there is limited research as to how these toxins may affect the development of PCOS. Although research has also shown that PCOS symptoms are reduced with certain dietary supplements and with weight loss among obese women, additional research is needed to compare various approaches to weight loss, as well as nutritional factors that may play a role in preventing or mitigating the development of PCOS. Limited studies indicate some association of low socioeconomic status with certain PCOS phenotypes, and future research should consider socioeconomic conditions during childhood or adolescence that may be more relevant to the developmental onset of PCOS. Finally, the limited scope of comparable international studies on PCOS needs to be addressed, because global patterns of PCOS are potentially valuable indicators of cultural, environmental, and genetic factors that may contribute to excess risk in certain regions of the world. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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Technologies for detecting botulinum neurotoxins in biological and environmental matrices
USDA-ARS?s Scientific Manuscript database
Biomonitoring of food and environmental matrices is critical for the rapid and sensitive diagnosis, treatment, and prevention of diseases caused by toxins. The United States Centers for Disease Control and Prevention (CDC) has noted that toxins from bacteria, fungi, algae, and plants present an ongo...
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NASA Astrophysics Data System (ADS)
Tu, Shu-I.; Uknalis, Joseph; He, Yiping
2009-05-01
We have developed a sandwiched immuno assay to detect sensitively Shiga-like toxins (SLTs) produced by Escherichia coli O157:H7. The method involved the capture of toxins by specific immuno magnetic beads followed by tagging the toxins with peroxidase-labeled anti E. coli O157:H7 antibody. Upon addition of proper substrate, peroxidase induced luminescence was used to measure the presence of SLTs. We have previously demonstrated that co-incubation of shiga toxin (SLT) producing E. coli O157:H7 with certain other bacteria can inhibit toxin production but does not affect the growth of the E. coli. We show here that media in which the cells have grown been centrifuged from (conditioned media) have similar effects on cell growth and SLT production. Adjusting the pH and adding nutrients to the conditioned media did not have any effect on the reduction of SLT produced. Bacteria communicate with each other via secreted sensing molecules. Several types of the molecules have been identified. However, the mechanisms of control remain to be established. This pattern for bacteria growth and toxin production is also observed when quorum-sensing molecules of homoserine lactone and indole are added to the media prior to inoculation.
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Use of Ubiquitous Technologies in Military Logistic System in Iran
NASA Astrophysics Data System (ADS)
Jafari, P.; Sadeghi-Niaraki, A.
2013-09-01
This study is about integration and evaluation of RFID and ubiquitous technologies in military logistic system management. Firstly, supply chain management and the necessity of a revolution in logistic systems especially in military area, are explained. Secondly RFID and ubiquitous technologies and the advantages of their use in supply chain management are introduced. Lastly a system based on these technologies for controlling and increasing the speed and accuracy in military logistic system in Iran with its unique properties, is presented. The system is based on full control of military logistics (supplies) from the time of deployment to replenishment using sensor network, ubiquitous and RFID technologies.
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Identification of the Cellular Receptor of Clostridium spiroforme Toxin
Papatheodorou, Panagiotis; Wilczek, Claudia; Nölke, Thilo; Guttenberg, Gregor; Hornuss, Daniel; Schwan, Carsten
2012-01-01
Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor. PMID:22252869
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Toxin-Antitoxin Systems as Multilevel Interaction Systems
Goeders, Nathalie; Van Melderen, Laurence
2014-01-01
Toxin-antitoxin (TA) systems are small genetic modules usually composed of a toxin and an antitoxin counteracting the activity of the toxic protein. These systems are widely spread in bacterial and archaeal genomes. TA systems have been assigned many functions, ranging from persistence to DNA stabilization or protection against mobile genetic elements. They are classified in five types, depending on the nature and mode of action of the antitoxin. In type I and III, antitoxins are RNAs that either inhibit the synthesis of the toxin or sequester it. In type II, IV and V, antitoxins are proteins that either sequester, counterbalance toxin activity or inhibit toxin synthesis. In addition to these interactions between the antitoxin and toxin components (RNA-RNA, protein-protein, RNA-protein), TA systems interact with a variety of cellular factors, e.g., toxins target essential cellular components, antitoxins are degraded by RNAses or ATP-dependent proteases. Hence, TA systems have the capacity to interact with each other at different levels. In this review, we will discuss the different interactions in which TA systems are involved and their implications in TA system functions and evolution. PMID:24434905
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Ubiquitous Computing: The Universal Use of Computers on College Campuses.
ERIC Educational Resources Information Center
Brown, David G., Ed.
This book is a collection of vignettes from 13 universities where everyone on campus has his or her own computer. These 13 institutions have instituted "ubiquitous computing" in very different ways at very different costs. The chapters are: (1) "Introduction: The Ubiquitous Computing Movement" (David G. Brown); (2) "Dartmouth College" (Malcolm…
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Ubiquitous Learning: Determinants Impacting Learners' Satisfaction and Performance with Smartphones
ERIC Educational Resources Information Center
Jung, Hee-Jung
2014-01-01
Although the concept of ubiquitous technologies has been introduced to many parts of society, there have been limited applications, and little is known about learners' behavior toward ubiquitous technologies, particularly in the context of English learning. This study considers a sample of Korean students to identify the key factors that influence…
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Proteomic Methods of Detection and Quantification of Protein Toxins.
Duracova, Miloslava; Klimentova, Jana; Fucikova, Alena; Dresler, Jiri
2018-02-28
Biological toxins are a heterogeneous group of compounds that share commonalities with biological and chemical agents. Among them, protein toxins represent a considerable, diverse set. They cover a broad range of molecular weights from less than 1000 Da to more than 150 kDa. This review aims to compare conventional detection methods of protein toxins such as in vitro bioassays with proteomic methods, including immunoassays and mass spectrometry-based techniques and their combination. Special emphasis is given to toxins falling into a group of selected agents, according to the Centers for Disease Control and Prevention, such as Staphylococcal enterotoxins , Bacillus anthracis toxins, Clostridium botulinum toxins, Clostridium perfringens epsilon toxin, ricin from Ricinus communis , Abrin from Abrus precatorius or control of trade in dual-use items in the European Union, including lesser known protein toxins such as Viscumin from Viscum album . The analysis of protein toxins and monitoring for biological threats, i.e., the deliberate spread of infectious microorganisms or toxins through water, food, or the air, requires rapid and reliable methods for the early identification of these agents.
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Proteomic Methods of Detection and Quantification of Protein Toxins
Klimentova, Jana; Fucikova, Alena
2018-01-01
Biological toxins are a heterogeneous group of compounds that share commonalities with biological and chemical agents. Among them, protein toxins represent a considerable, diverse set. They cover a broad range of molecular weights from less than 1000 Da to more than 150 kDa. This review aims to compare conventional detection methods of protein toxins such as in vitro bioassays with proteomic methods, including immunoassays and mass spectrometry-based techniques and their combination. Special emphasis is given to toxins falling into a group of selected agents, according to the Centers for Disease Control and Prevention, such as Staphylococcal enterotoxins, Bacillus anthracis toxins, Clostridium botulinum toxins, Clostridium perfringens epsilon toxin, ricin from Ricinus communis, Abrin from Abrus precatorius or control of trade in dual-use items in the European Union, including lesser known protein toxins such as Viscumin from Viscum album. The analysis of protein toxins and monitoring for biological threats, i.e., the deliberate spread of infectious microorganisms or toxins through water, food, or the air, requires rapid and reliable methods for the early identification of these agents. PMID:29495560
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Crystallization of isoelectrically homogeneous cholera toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spangler, B.D.; Westbrook, E.M.
1989-02-07
Past difficulty in growing good crystals of cholera toxin has prevented the study of the crystal structure of this important protein. The authors have determined that failure of cholera toxin to crystallize well has been due to its heterogeneity. They have now succeeded in overcoming the problem by isolating a single isoelectric variant of this oligomeric protein (one A subunit and five B subunits). Cholera toxin purified by their procedure readily forms large single crystals. The crystal form has been described previously. They have recorded data from native crystals of cholera toxin to 3.0-{angstrom} resolution with our electronic area detectors.more » With these data, they have found the orientation of a 5-fold symmetry axis within these crystals, perpendicular to the screw dyad of the crystal. They are now determining the crystal structure of cholera toxin by a combination of multiple heavy-atom isomorphous replacement and density modification techniques, making use of rotational 5-fold averaging of the B subunits.« less
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Botulinum toxin in trigeminal neuralgia.
Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia
2017-01-06
Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
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Collaborative Research Program on Seafood Toxins
1988-08-14
Crystallographic Structures of Saxitoxins Cl and C2 Appendix C: Collaborative Research Program an Seafcod Toxins Progress Report on Ciguatera and Related...radioimmunoassay for PSP were also evalumted. The Hokama stick test for ciguatera toxin was also evaluated. 4. initiate Studies on the Accumulation...tco•d which caie a form of b-mnn poisoning referred to as ciguatera . The respcnsible toxins originate from ll1ular rine algae of the division
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Legionella pneumophila Toxin, Isolation and Purification
1981-01-01
which dis- plays an in vivo lethality. The purification procedures involve acid precipitation, gel chromatography, and preparative isotachophoresis. The...Chymotrypsinogen A, Ribonuclease A, and Apoprotinin as markers. Preparation of antiserum One milliqram amounts of protein from Le jonella acid ...RESULTS Toxin isolation Step 1: Acid precipitation of crude toxin. 1.0 N HCl acid was slowly added to rapidly stirred crude toxin until pH 3.5 was
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Creekmore, Lynn H.
1999-01-01
Periodic blooms of algae, including true algae, dinoflagellates, and cyanobacteria or blue-green algae have been reported in marine and freshwater bodies throughout the world. Although many blooms are merely an aesthetic nuisance, some species of algae produce toxins that kill fish, shellfish, humans, livestock and wildlife. Pigmented blooms of toxinproducing marine algae are often referred to as “red tides” (Fig. 36.1). Proliferations of freshwater toxin-producing cyanobacteria are simply called “cyanobacterial blooms” or “toxic algal blooms.” Cyanobacterial blooms initially appear green and may later turn blue, sometimes forming a “scum” in the water (Fig. 36.2).Although algal blooms historically have been considered a natural phenomenon, the frequency of occurrence of harmful algae appears to have increased in recent years. Agricultural runoff and other pollutants of freshwater and marine wetlands and water bodies have resulted in increased nutrient loading of phosphorus and nitrogen, thus providing conditions favorable to the growth of potentially toxic algae. The detrimental impact of red tides and cyanobacterial blooms on wetland, shore, and pelagic species has long been suspected but not often been substantiated because information on the effects of these toxins in fish and wildlife species is lacking and diagnostic tools are limited.
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Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.
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.
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Tumor Targeting and Drug Delivery by Anthrax Toxin.
Bachran, Christopher; Leppla, Stephen H
2016-07-01
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.
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Subburaj, Yamunadevi; Ros, Uris; Hermann, Eduard; Tong, Rudi; García-Sáez, Ana J.
2015-01-01
α-Pore-forming toxins (α-PFTs) are ubiquitous defense tools that kill cells by opening pores in the target cell membrane. Despite their relevance in host/pathogen interactions, very little is known about the pore stoichiometry and assembly pathway leading to membrane permeabilization. Equinatoxin II (EqtII) is a model α-PFT from sea anemone that oligomerizes and forms pores in sphingomyelin-containing membranes. Here, we determined the spatiotemporal organization of EqtII in living cells by single molecule imaging. Surprisingly, we found that on the cell surface EqtII did not organize into a unique oligomeric form. Instead, it existed as a mixture of oligomeric species mostly including monomers, dimers, tetramers, and hexamers. Mathematical modeling based on our data supported a new model in which toxin clustering happened in seconds and proceeded via condensation of EqtII dimer units formed upon monomer association. Furthermore, altering the pathway of EqtII assembly strongly affected its toxic activity, which highlights the relevance of the assembly mechanism on toxicity. PMID:25525270
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Garvey, Mark I; Bradley, Craig W; Wilkinson, Martyn A C; Holden, Elisabeth
2017-01-01
Diagnosis of C. difficile infection (CDI) is controversial because of the many laboratory methods available and their lack of ability to distinguish between carriage, mild or severe disease. Here we describe whether a low C. difficile toxin B nucleic acid amplification test (NAAT) cycle threshold (CT) can predict toxin EIA, CDI severity and mortality. A three-stage algorithm was employed for CDI testing, comprising a screening test for glutamate dehydrogenase (GDH), followed by a NAAT, then a toxin enzyme immunoassay (EIA). All diarrhoeal samples positive for GDH and NAAT between 2012 and 2016 were analysed. The performance of the NAAT CT value as a classifier of toxin EIA outcome was analysed using a ROC curve; patient mortality was compared to CTs and toxin EIA via linear regression models. A CT value ≤26 was associated with ≥72% toxin EIA positivity; applying a logistic regression model we demonstrated an association between low CT values and toxin EIA positivity. A CT value of ≤26 was significantly associated ( p = 0.0262) with increased one month mortality, severe cases of CDI or failure of first line treatment. The ROC curve probabilities demonstrated a CT cut off value of 26.6. Here we demonstrate that a CT ≤26 indicates more severe CDI and is associated with higher mortality. Samples with a low CT value are often toxin EIA positive, questioning the need for this additional EIA test. A CT ≤26 could be used to assess the potential for severity of CDI and guide patient treatment.
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Guo, Yunxue; Yao, Jianyun; Sun, Chenglong; Wen, Zhongling; Wang, Xiaoxue
2016-07-01
Toxin-antitoxin (TA) systems are small genetic elements that are ubiquitous in prokaryotes. Most studies on TA systems have focused on commensal and pathogenic bacteria; yet very few studies have focused on TAs in marine bacteria, especially those isolated from a deep sea environment. Here, we characterized a type II VapC/VapB TA system from the deep-sea derived Streptomyces sp. SCSIO 02999. The VapC (virulence-associated protein) protein belongs to the PIN (PilT N-terminal) superfamily. Overproduction of VapC strongly inhibited cell growth and resulted in a bleb-containing morphology in E. coli. The toxicity of VapC was neutralized through direct protein-protein interaction by a small protein antitoxin VapB encoded by a neighboring gene. Antitoxin VapB alone or the VapB/VapC complex negatively regulated the vapBC promoter activity. We further revealed that three conserved Asp residues in the PIN domain were essential for the toxic effect of VapC. Additionally, the VapC/VapB TA system stabilized plasmid in E. coli. Furthermore, VapC cross-activated transcription of several TA operons via a partially Lon-dependent mechanism in E. coli, and the activated toxins accumulated more preferentially than their antitoxin partners. Collectively, we identified and characterized a new deep sea TA system in the deep sea Streptomyces sp. and demonstrated that the VapC toxin in this system can cross-activate TA operons in E. coli.
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Monoclonal antibodies and toxins--a perspective on function and isotype.
Chow, Siu-Kei; Casadevall, Arturo
2012-06-01
Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins--Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)--and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.
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Aktories, Klaus; Barth, Holger
2004-04-01
Clostridium botulinum C2 toxin is a member of the family of binary actin-ADP-ribosylating toxins. It consists of the enzyme component C2I, and the separated binding/translocation component C2II. Proteolytically activated C2II forms heptamers and binds to a carbohydrate cell surface receptor. After attachment of C2I, the toxin complex is endocytosed to reach early endosomes. At low pH of endosomes, C2II-heptamers insert into the membrane, form pores and deliver C2I into the cytosol. Here, C2I ADP-ribosylates actin at Arg177 to block actin polymerization and to induce depolymerization of actin filaments. The mini-review describes main properties of C2 toxin and discusses new findings on the involvement of chaperones in the up-take process of the toxin.
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Ubiquitous technologies in health: new challenges of opportunity, expectation, and responsibility.
Rigby, Michael
2006-01-01
In spite of their name, 'ubiquitous' technologies are not yet ubiquitous in the true sense of the word, but rather are 'novel', being at the research, pilot, and selective use stages. In future, the proliferation in types of application, the major increase in cases and data volumes, and above all the dependence on ubiquitous technologies will raise practical, ethical, and liability issues. Equally significantly, it will require health service redesign, including new response services. Health informaticians need to be active in stimulating consideration of all these issues, as part of both social and professional responsibility.
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Using SWE Standards for Ubiquitous Environmental Sensing: A Performance Analysis
Tamayo, Alain; Granell, Carlos; Huerta, Joaquín
2012-01-01
Although smartphone applications represent the most typical data consumer tool from the citizen perspective in environmental applications, they can also be used for in-situ data collection and production in varied scenarios, such as geological sciences and biodiversity. The use of standard protocols, such as SWE, to exchange information between smartphones and sensor infrastructures brings benefits such as interoperability and scalability, but their reliance on XML is a potential problem when large volumes of data are transferred, due to limited bandwidth and processing capabilities on mobile phones. In this article we present a performance analysis about the use of SWE standards in smartphone applications to consume and produce environmental sensor data, analysing to what extent the performance problems related to XML can be alleviated by using alternative uncompressed and compressed formats.
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Toxins That Affect Voltage-Gated Sodium Channels.
Ji, Yonghua
2017-10-26
Voltage-gated sodium channels (VGSCs) are critical in generation and conduction of electrical signals in multiple excitable tissues. Natural toxins, produced by animal, plant, and microorganisms, target VGSCs through diverse strategies developed over millions of years of evolutions. Studying of the diverse interaction between VGSC and VGSC-targeting toxins has been contributing to the increasing understanding of molecular structure and function, pharmacology, and drug development potential of VGSCs. This chapter aims to summarize some of the current views on the VGSC-toxin interaction based on the established receptor sites of VGSC for natural toxins.
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Botulinum toxin for the treatment of bruxism.
Tinastepe, Neslihan; Küçük, Burcu Bal; Oral, Koray
2015-10-01
Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.
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Botulinum toxin for the treatment of bruxism.
Tinastepe, Neslihan; Küçük, Burcu Bal; Oral, Koray
2014-08-14
Aims: Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. Methodology: An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Results: Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Conclusion: Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.
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Cyanobacterial toxins: risk management for health protection
DOE Office of Scientific and Technical Information (OSTI.GOV)
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 riskmore » 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.« less
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USDA-ARS?s Scientific Manuscript database
Shiga toxin-producing Escherichia coli (STEC) strains of the O91: H21 serotype have caused severe infections, including hemolytic-uremic syndrome. Strains of the O91 serogroup have been isolated from food, animals, and the environment worldwide but are not well characterized. We used a microarray an...
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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
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Narayanaswami, Pushpa; Geisbush, Thomas; Tarulli, Andrew; Raynor, Elizabeth; Gautam, Shiva; Tarsy, Daniel; Gronseth, Gary
2016-09-01
Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD. 1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models. 1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: -0.194 ± 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands. This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful. Copyright © 2016 Elsevier Ltd. All rights reserved.
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An improved anonymous authentication scheme for roaming in ubiquitous networks.
Lee, Hakjun; Lee, Donghoon; Moon, Jongho; Jung, Jaewook; Kang, Dongwoo; Kim, Hyoungshick; Won, Dongho
2018-01-01
With the evolution of communication technology and the exponential increase of mobile devices, the ubiquitous networking allows people to use our data and computing resources anytime and everywhere. However, numerous security concerns and complicated requirements arise as these ubiquitous networks are deployed throughout people's lives. To meet the challenge, the user authentication schemes in ubiquitous networks should ensure the essential security properties for the preservation of the privacy with low computational cost. In 2017, Chaudhry et al. proposed a password-based authentication scheme for the roaming in ubiquitous networks to enhance the security. Unfortunately, we found that their scheme remains insecure in its protection of the user privacy. In this paper, we prove that Chaudhry et al.'s scheme is vulnerable to the stolen-mobile device and user impersonation attacks, and its drawbacks comprise the absence of the incorrect login-input detection, the incorrectness of the password change phase, and the absence of the revocation provision. Moreover, we suggest a possible way to fix the security flaw in Chaudhry et al's scheme by using the biometric-based authentication for which the bio-hash is applied in the implementation of a three-factor authentication. We prove the security of the proposed scheme with the random oracle model and formally verify its security properties using a tool named ProVerif, and analyze it in terms of the computational and communication cost. The analysis result shows that the proposed scheme is suitable for resource-constrained ubiquitous environments.
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Morales-Menchén, Ana; Navarro-García, Federico; Guirao-Abad, José P.; Román, Elvira; Prieto, Daniel; Coman, Ioana V.; Pla, Jesús; Alonso-Monge, Rebeca
2018-01-01
Certain yeasts secrete peptides known as killer toxins or mycocins with a deleterious effect on sensitive yeasts or filamentous fungi, a common phenomenon in environmental species. In a recent work, different Debaryomyces hansenii (Dh) strains isolated from a wide variety of cheeses were identified as producing killer toxins active against Candida albicans and Candida tropicalis. We have analyzed the killer activity of these toxins in C. albicans mutants defective in MAPK signaling pathways and found that the lack of the MAPK Hog1 (but not Cek1 or Mkc1) renders cells hypersensitive to Dh mycocins while mutants lacking other upstream elements of the pathway behave as the wild type strain. Point mutations in the phosphorylation site (T174A-176F) or in the kinase domain (K52R) of HOG1 gene showed that both activities were relevant for the survival of C. albicans to Dh killer toxins. Moreover, Hog1 phosphorylation was also required to sense and adapt to osmotic and oxidative stress while the kinase activity was somehow dispensable. Although the addition of supernatant from the killer toxin- producing D. hansenii 242 strain (Dh-242) induced a slight intracellular increase in Reactive Oxygen Species (ROS), overexpression of cytosolic catalase did not protect C. albicans against this mycocin. This supernatant induced an increase in intracellular glycerol concentration suggesting that this toxin triggers an osmotic stress. We also provide evidence of a correlation between sensitivity to Dh-242 killer toxin and resistance to Congo red, suggesting cell wall specific alterations in sensitive strains. PMID:29774204
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Context Aware Ubiquitous Learning Environments for Peer-to-Peer Collaborative Learning
ERIC Educational Resources Information Center
Yang, Stephen J. H.
2006-01-01
A ubiquitous learning environment provides an interoperable, pervasive, and seamless learning architecture to connect, integrate, and share three major dimensions of learning resources: learning collaborators, learning contents, and learning services. Ubiquitous learning is characterized by providing intuitive ways for identifying right learning…
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Botulinum toxin for the treatment of strabismus.
Rowe, Fiona J; Noonan, Carmel P
2017-03-02
The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further
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Mechanisms of the cytopathic action of actin-ADP-ribosylating toxins.
Aktories, K; Wegner, A
1992-10-01
Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin, and Clostridium spiroforme toxin ADP-ribosylate actin monomers. Toxin-induced ADP-ribosylation disturbs the cellular equilibrium between monomeric and polymeric actin and traps monomeric actin in its unpolymerized form, thereby depolymerizing actin filaments and destroying the microfilament network. Furthermore, the toxins ADP-ribosylate gelsolin actin complexes. These modifications may contribute to the cytopathic action of the toxins.
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Botulinum Toxin Use in Pediatric Plastic Surgery.
Fu, Katherine J; Teichgraeber, John F; Greives, Matthew R
2016-11-01
Botulinum toxin has increasingly become a prevalent treatment option for a wide range of conditions, many of which have their roots in plastic surgery and have been well studied. In adults, chronic headache, hyperhidrosis, and facial muscular hypertrophy have been effectively treated with botulinum toxin, and emerging studies have begun looking at its efficacy in children, as well. Successful treatment of spasticity and muscular contraction has allowed for the creation of safety profiles and dosage guidelines for botulinum toxin usage in children. The expanded indications for its use have since flourished in all arenas of pediatric care, including plastic surgery. Recent studies have described the use of botulinum toxin as an adjunct to the treatment of congenital torticollis and cleft lip. This review discusses the various applications of botulinum toxin for pediatric patients in the field of plastic surgery.
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Short toxin-like proteins abound in Cnidaria genomes.
Tirosh, Yitshak; Linial, Itai; Askenazi, Manor; Linial, Michal
2012-11-16
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.
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Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice.
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. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Molecular basis of toxicity of Clostridium perfringens epsilon toxin.
Bokori-Brown, Monika; Savva, Christos G; Fernandes da Costa, Sérgio P; Naylor, Claire E; Basak, Ajit K; Titball, Richard W
2011-12-01
Clostridium perfringens ε-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats, calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. The relatively inactive 32.9 kDa prototoxin is converted to active mature toxin by proteolytic cleavage, either by digestive proteases of the host, such as trypsin and chymotrypsin, or by C. perfringens λ-protease. In vivo, the toxin appears to target the brain and kidneys, but relatively few cell lines are susceptible to the toxin, and most work has been carried out using Madin-Darby canine kidney (MDCK) cells. The binding of ε-toxin to MDCK cells and rat synaptosomal membranes is associated with the formation of a stable, high molecular weight complex. The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins, ε-toxin appears to form heptameric pores in target cell membranes. The exquisite specificity of the toxin for specific cell types suggests that it binds to a receptor found only on these cells. © 2011 The Authors Journal compilation © 2011 FEBS.
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Botulinum toxin for vaginismus treatment.
Ferreira, Juliana Rocha; Souza, Renan Pedra
2012-01-01
Vaginismus is characterized by recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina when penile, finger, tampon, or speculum penetration is attempted. Recent results have suggested the use of botulinum toxin for the treatment of vaginismus. Here, we assessed previously published data to evaluate the therapeutic effectiveness of botulinum toxin for vaginismus. We have carried out a systematic review followed by a meta-analysis. Our results indicate that botulinum toxin is an effective therapeutic option for patients with vaginismus (pooled odds ratio of 8.723 with 95% confidence interval limits of 1.942 and 39.162, p = 0.005). This may hold particularly true in treatment-refractory patients because most of the studies included in this meta-analysis have enrolled these subjects in their primary analysis. Botulinum toxin appears to bea reasonable intervention for vaginismus. However, this conclusion should be read carefully because of the deficiency of placebo-controlled randomized clinical trials and the quality issues presented in the existing ones.
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Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases
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
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An improved anonymous authentication scheme for roaming in ubiquitous networks
Lee, Hakjun; Lee, Donghoon; Moon, Jongho; Jung, Jaewook; Kang, Dongwoo; Kim, Hyoungshick
2018-01-01
With the evolution of communication technology and the exponential increase of mobile devices, the ubiquitous networking allows people to use our data and computing resources anytime and everywhere. However, numerous security concerns and complicated requirements arise as these ubiquitous networks are deployed throughout people’s lives. To meet the challenge, the user authentication schemes in ubiquitous networks should ensure the essential security properties for the preservation of the privacy with low computational cost. In 2017, Chaudhry et al. proposed a password-based authentication scheme for the roaming in ubiquitous networks to enhance the security. Unfortunately, we found that their scheme remains insecure in its protection of the user privacy. In this paper, we prove that Chaudhry et al.’s scheme is vulnerable to the stolen-mobile device and user impersonation attacks, and its drawbacks comprise the absence of the incorrect login-input detection, the incorrectness of the password change phase, and the absence of the revocation provision. Moreover, we suggest a possible way to fix the security flaw in Chaudhry et al’s scheme by using the biometric-based authentication for which the bio-hash is applied in the implementation of a three-factor authentication. We prove the security of the proposed scheme with the random oracle model and formally verify its security properties using a tool named ProVerif, and analyze it in terms of the computational and communication cost. The analysis result shows that the proposed scheme is suitable for resource-constrained ubiquitous environments. PMID:29505575
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Single toxin dose-response models revisited
DOE Office of Scientific and Technical Information (OSTI.GOV)
Demidenko, Eugene, E-mail: eugened@dartmouth.edu
The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the fourmore » models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.« less
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Dinoflagellate Toxins Responsible for Ciguatera Food Poisoning
1988-12-10
0 AD DINOFLAGELLATE TOXINS RESPONSIBLE FOR CIGUATERA FOOD POISONING Annual Summary Report Donald M. Miller December 10, 1988 Supported by US ARMY...Maryland 21701-5012 62770A 62770A871 AA 377 11. TITLE (Include Security Classification) Dinoflagellate Toxins Responsible for Ciguatera Poisoning 12...block number) FIELD GROUP SUB-GROUP Ciguatera ; Toxins; Inhibitor; RA I; Dinoflagellates; 06 03 Mass Culture; Purification j 01 19 ABSTRACT
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Clostridial binary toxins: iota and C2 family portraits.
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.
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Clostridial Binary Toxins: Iota and C2 Family Portraits
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
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Short Toxin-like Proteins Abound in Cnidaria Genomes
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
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In vitro reconstitution of the Clostridium botulinum type D progenitor toxin.
Kouguchi, Hirokazu; Watanabe, Toshihiro; Sagane, Yoshimasa; Sunagawa, Hiroyuki; Ohyama, Tohru
2002-01-25
Clostridium botulinum type D strain 4947 produces two different sizes of progenitor toxins (M and L) as intact forms without proteolytic processing. The M toxin is composed of neurotoxin (NT) and nontoxic-nonhemagglutinin (NTNHA), whereas the L toxin is composed of the M toxin and hemagglutinin (HA) subcomponents (HA-70, HA-17, and HA-33). The HA-70 subcomponent and the HA-33/17 complex were isolated from the L toxin to near homogeneity by chromatography in the presence of denaturing agents. We were able to demonstrate, for the first time, in vitro reconstitution of the L toxin formed by mixing purified M toxin, HA-70, and HA-33/17. The properties of reconstituted and native L toxins are indistinguishable with respect to their gel filtration profiles, native-PAGE profiles, hemagglutination activity, binding activity to erythrocytes, and oral toxicity to mice. M toxin, which contained nicked NTNHA prepared by treatment with trypsin, could no longer be reconstituted to the L toxin with HA subcomponents, whereas the L toxin treated with proteases was not degraded into M toxin and HA subcomponents. We conclude that the M toxin forms first by assembly of NT with NTNHA and is subsequently converted to the L toxin by assembly with HA-70 and HA-33/17.
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Botulinum toxin in pain treatment.
Colhado, Orlando Carlos Gomes; Boeing, Marcelo; Ortega, Luciano Bornia
2009-01-01
Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known. However, the efficacy of some of its indications is still in the process of being confirmed. The objective of this study was to review the history, pharmacological properties, and clinical applications of BTX in the treatment of pain of different origins. Botulinum toxin is produced by fermentation of Clostridium botulinum, a Gram-positive, anaerobic bacterium. Commercially, BTX comes in two presentations, types A and B. Botulinum toxin, a neurotoxin with high affinity for cholinergic synapses, blocks the release of acetylcholine by nerve endings without interfering with neuronal conduction of electrical signals or synthesis and storage of acetylcholine. It has been proven that BTX can selectively weaken painful muscles, interrupting the spasm-pain cycle. Several studies have demonstrated the efficacy and safety of BTX-A in the treatment of tension headaches, migraines, chronic lumbar pain, and myofascial pain. Botulinum toxin type A is well tolerated in the treatment of chronic pain disorders in which pharmacotherapy regimens can cause side effects. The reduction in the consumption of analgesics and length of action of 3 to 4 months per dose represent other advantages of its use. However, further studies are necessary to establish the efficacy of BTX-A in chronic pain disorders and its exact mechanism of action, as well as its potential in multifactorial treatments.
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UBIQUITOUS POLLUTION FROM HEALTH AND COSMETIC ...
Those chemical pollutants that are regulated under various international, federal, and state programs represent but a small fraction of the universe of chemicals that occur in the environment as a result of both natural processses and human influence. Although this galaxy of targeted chemicals might be miniuscule compared with the universe of both known and yet-to-be identified chemicals, an implicit assumption is that these selective lists of chemicals are responsible for the most significant share of risk with respect to environmental or economic impairment or to human health.Pharmaceuticals and person care products (PPCPs) comprise a particularly large and diverse array of unregulated pollutants that occur in the environment from the combined activities and actions of multitudes of individuals as well as from veterinary and agricultural use. Although the concentration of any individual PPCP are generally less than ppt-ppb), evidence is accumulateing that these trace-level pollutants are ubiquitous, they can have a continuous presence regardless of environment half-lives (especially where sanitary wastewaters enter the environment), and the numbers of distinct and varied chemical entities could be extremely large (given that thousands are in commerical use). The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Locat
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The role of toxins in Clostridium difficile infection.
Chandrasekaran, Ramyavardhanee; Lacy, D Borden
2017-11-01
Clostridium difficile is a bacterial pathogen that is the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. The incidence, severity, mortality and healthcare costs associated with C. difficile infection (CDI) are rising, making C. difficile a major threat to public health. Traditional treatments for CDI involve use of antibiotics such as metronidazole and vancomycin, but disease recurrence occurs in about 30% of patients, highlighting the need for new therapies. The pathogenesis of C. difficile is primarily mediated by the actions of two large clostridial glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a third toxin, the binary toxin C. difficile transferase, which can also contribute to C. difficile virulence and disease. These toxins act on the colonic epithelium and immune cells and induce a complex cascade of cellular events that result in fluid secretion, inflammation and tissue damage, which are the hallmark features of the disease. In this review, we summarize our current understanding of the structure and mechanism of action of the C. difficile toxins and their role in disease. Published by Oxford University Press on behalf of FEMS 2017.
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Interactions of cnidarian toxins with the immune system.
Suput, Dusan
2011-10-01
Cnidarians comprise four classes of toxic marine animals: Anthozoa, Cubozoa, Scyphozoa and Hydrozoa. They are the largest and probably the oldest phylum of toxic marine animals. Any contact with a cnidarian, especially the box jellyfish (Chironex fleckeri), can be fatal, but most cnidarians do not possess sufficiently strong venomous apparatus to penetrate the human skin, whereas others rarely come into contact with human beings. Only a small, almost negligible percentage of the vast wealth of cnidarian toxins has been studied in detail. Many polypeptide cnidarian toxins are immunogenic, and cross-reactivity between several jellyfish venoms has been reported. Cnidarians also possess components of innate immunity, and some of those components have been preserved in evolution. On the other hand, cnidarian toxins have already been used for the design of immunotoxins to treat cancer, whereas other cnidarian toxins can modulate the immune system in mammals, including man. This review will focus on a short overview of cnidarian toxins, on the innate immunity of cnidarians, and on the mode of action of cnidarian toxins which can modulate the immune system in mammals. Emphasis is palced on those toxins which block voltage activated potassium channels in the cells of the immune system.
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Environmental Exposures and Children's Health Challenges
ERIC Educational Resources Information Center
Landrigan, Philip J.
2005-01-01
The author looks at the sharp increase in a number of childhood disorders--including asthma, certain cancers, and learning/behavioral disabilities--and the role environmental toxins may play in this increase. He describes the need to train many more health professionals in prenatal and children's environmental health and the national network of…
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Dinoflagellate Toxins Responsible for Ciguatera Food Poisoning
1987-12-10
the occurrence and importance of secondary toxins (12, 13, 14, 15, 16 and 17). Hutner and McLaughlin (18) suggested that the zooxanthellae ...argued that zooxanthellae were unlikely prospects because very few fishes eat coral and saxitoxin (STX = a paralytic shellfish poison which originates...of the toxins was not based on tests of zooxanthellae species but rather on the assumption that all dinoflagellate toxins would be expected to be
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Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten
2005-04-08
Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to lowmore » pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids.« less
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Formation and Control of Cyanobacterial Toxins
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...
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Natural toxins of plant origin (phytotoxins)
USDA-ARS?s Scientific Manuscript database
Over 100,000 secondary compounds have been identified in plants including alkaloids, glycosides, proteins, polypeptides, amines and non-protein amino acids, organic acids, alcohols, polyacetylenes, resinous toxins and mineral toxins. For thousands of years man has used some of these compounds as fl...
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Ubiquitous Robotic Technology for Smart Manufacturing System.
Wang, Wenshan; Zhu, Xiaoxiao; Wang, Liyu; Qiu, Qiang; Cao, Qixin
2016-01-01
As the manufacturing tasks become more individualized and more flexible, the machines in smart factory are required to do variable tasks collaboratively without reprogramming. This paper for the first time discusses the similarity between smart manufacturing systems and the ubiquitous robotic systems and makes an effort on deploying ubiquitous robotic technology to the smart factory. Specifically, a component based framework is proposed in order to enable the communication and cooperation of the heterogeneous robotic devices. Further, compared to the service robotic domain, the smart manufacturing systems are often in larger size. So a hierarchical planning method was implemented to improve the planning efficiency. A test bed of smart factory is developed. It demonstrates that the proposed framework is suitable for industrial domain, and the hierarchical planning method is able to solve large problems intractable with flat methods.
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Ubiquitous Robotic Technology for Smart Manufacturing System
Zhu, Xiaoxiao; Wang, Liyu; Qiu, Qiang; Cao, Qixin
2016-01-01
As the manufacturing tasks become more individualized and more flexible, the machines in smart factory are required to do variable tasks collaboratively without reprogramming. This paper for the first time discusses the similarity between smart manufacturing systems and the ubiquitous robotic systems and makes an effort on deploying ubiquitous robotic technology to the smart factory. Specifically, a component based framework is proposed in order to enable the communication and cooperation of the heterogeneous robotic devices. Further, compared to the service robotic domain, the smart manufacturing systems are often in larger size. So a hierarchical planning method was implemented to improve the planning efficiency. A test bed of smart factory is developed. It demonstrates that the proposed framework is suitable for industrial domain, and the hierarchical planning method is able to solve large problems intractable with flat methods. PMID:27446206
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The life history of a botulinum toxin molecule.
Simpson, Lance
2013-06-01
There is an emerging literature describing the absorption, distribution, metabolism and elimination of botulinum toxin. This work reveals that the toxin can be absorbed by both the oral and inhalation routes. The primary mechanism for absorption is binding and transport across epithelial cells. Toxin that enters the body undergoes a distribution phase, which is quite short, and an elimination phase, which is comparatively long. During the distribution phase, botulinum toxin migrates to the peri-neuronal microcompartment in the vicinity of vulnerable cells, such as cholinergic nerve endings. Only these cells have the ability to selectively accumulate the molecule. When the toxin moves from the cell membrane to the cell interior, it undergoes programmed death. This is coincident with release of the catalytically active light chain that paralyzes transmission. Intraneuronal metabolism of light chain is via the ubiquitination-proteasome pathway. Systemic metabolism and elimination is assumed to be via the liver. The analysis of absorption, distribution, metabolism and elimination of the toxin helps to create a life history of the molecule in the body. This has many benefits, including: a) clarifying the mechanisms that underlie the disease botulism, b) providing insights for development of medical countermeasures against the toxin, and c) helping to explain the meaning of a lethal dose of toxin. It is likely that work intended to enhance understanding of the fate of botulinum toxin in the body will intensify. These efforts will include new and powerful analytic tools, such as single molecule-single cell analyses in vitro and real time, 3-dimensional pharmacokinetic studies in vivo. Copyright © 2013 Elsevier Ltd. All rights reserved.
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U-ALS: A Ubiquitous Learning Environment
ERIC Educational Resources Information Center
Piovesan, Sandra Dutra; Passerino, Liliana Maria; Medina, Roseclea Duarte
2012-01-01
The diffusion of the use of the learning virtual environments presents a great potential for the development of an application which meet the necessities in the education area. In view of the importance of a more dynamic application and that can adapt itself continuously to the students' necessities, the "U-ALS" (Ubiquitous Adapted Learning…
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Rocker, Andrea; Peschke, Madeleine; Kittilä, Tiia; Sakson, Roman; Brieke, Clara; Meinhart, Anton
2018-04-27
Bacterial toxin-antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin-antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.
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Using Context-Aware Ubiquitous Learning to Support Students' Understanding of Geometry
ERIC Educational Resources Information Center
Crompton, Helen
2015-01-01
In this study, context-aware ubiquitous learning was used to support 4th grade students as they learn angle concepts. Context-aware ubiquitous learning was provided to students primarily through the use of iPads to access real-world connections and a Dynamic Geometry Environment. Gravemeijer and van Eerde's (2009), design-based research (DBR)…
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Zhu, Luchang; Olsen, Randall J; Horstmann, Nicola; Shelburne, Samuel A; Fan, Jia; Hu, Ye; Musser, James M
2016-07-01
Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Risk Assessment of Shellfish Toxins
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
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CD44 Promotes intoxication by the clostridial iota-family toxins.
Wigelsworth, Darran J; Ruthel, Gordon; Schnell, Leonie; Herrlich, Peter; Blonder, Josip; Veenstra, Timothy D; Carman, Robert J; Wilkins, Tracy D; Van Nhieu, Guy Tran; Pauillac, Serge; Gibert, Maryse; Sauvonnet, Nathalie; Stiles, Bradley G; Popoff, Michel R; Barth, Holger
2012-01-01
Various pathogenic clostridia produce binary protein toxins associated with enteric diseases of humans and animals. Separate binding/translocation (B) components bind to a protein receptor on the cell surface, assemble with enzymatic (A) component(s), and mediate endocytosis of the toxin complex. Ultimately there is translocation of A component(s) from acidified endosomes into the cytosol, leading to destruction of the actin cytoskeleton. Our results revealed that CD44, a multifunctional surface protein of mammalian cells, facilitates intoxication by the iota family of clostridial binary toxins. Specific antibody against CD44 inhibited cytotoxicity of the prototypical Clostridium perfringens iota toxin. Versus CD44(+) melanoma cells, those lacking CD44 bound less toxin and were dose-dependently resistant to C. perfringens iota, as well as Clostridium difficile and Clostridium spiroforme iota-like, toxins. Purified CD44 specifically interacted in vitro with iota and iota-like, but not related Clostridium botulinum C2, toxins. Furthermore, CD44 knockout mice were resistant to iota toxin lethality. Collective data reveal an important role for CD44 during intoxication by a family of clostridial binary toxins.
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CD44 Promotes Intoxication by the Clostridial Iota-Family Toxins
Wigelsworth, Darran J.; Ruthel, Gordon; Schnell, Leonie; Herrlich, Peter; Blonder, Josip; Veenstra, Timothy D.; Carman, Robert J.; Wilkins, Tracy D.; Van Nhieu, Guy Tran; Pauillac, Serge; Gibert, Maryse; Sauvonnet, Nathalie; Stiles, Bradley G.; Popoff, Michel R.; Barth, Holger
2012-01-01
Various pathogenic clostridia produce binary protein toxins associated with enteric diseases of humans and animals. Separate binding/translocation (B) components bind to a protein receptor on the cell surface, assemble with enzymatic (A) component(s), and mediate endocytosis of the toxin complex. Ultimately there is translocation of A component(s) from acidified endosomes into the cytosol, leading to destruction of the actin cytoskeleton. Our results revealed that CD44, a multifunctional surface protein of mammalian cells, facilitates intoxication by the iota family of clostridial binary toxins. Specific antibody against CD44 inhibited cytotoxicity of the prototypical Clostridium perfringens iota toxin. Versus CD44+ melanoma cells, those lacking CD44 bound less toxin and were dose-dependently resistant to C. perfringens iota, as well as Clostridium difficile and Clostridium spiroforme iota-like, toxins. Purified CD44 specifically interacted in vitro with iota and iota-like, but not related Clostridium botulinum C2, toxins. Furthermore, CD44 knockout mice were resistant to iota toxin lethality. Collective data reveal an important role for CD44 during intoxication by a family of clostridial binary toxins. PMID:23236484
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Structural Insights into Clostridium perfringens Delta Toxin Pore Formation
Huyet, Jessica; Naylor, Claire E.; Savva, Christos G.; Gibert, Maryse; Popoff, Michel R.; Basak, Ajit K.
2013-01-01
Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins. PMID:23805259
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[Staphylococcal toxin of toxic shock syndrome].
Fluer, F S
2007-01-01
Literature data on toxic shock syndrome staphylococcal toxin (TSST-1) are summarized; properties of Staphylococcus aureus strains producing TSST-1, nutrient media, and factors influencing on production of TSST-1 are reviewed. Physical and chemical properties of the toxin, its molecular characteristics, genetic regulation of its production, mechanism of action, and diseases which it causes are also discussed. Clinical and histologic signs of toxic shock syndrome (TSS), its diagnostic criteria, susceptibility of people to TSS, antigenic and serologic properties of the toxin, epidemiology of the infection caused by TSST-1-producing strains of staphylococci, methods of TSST-1 extraction and identification are described.
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Structural Basis of Clostridium perfringens Toxin Complex Formation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adams,J.; Gregg, K.; Bayer, E.
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 themore » 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.« less
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Voltage-dependent blockade of muscle Na+ channels by guanidinium toxins
1984-01-01
Na+ channels from rat muscle plasma membrane vesicles were inserted into neutral planar phospholipid bilayers and were activated by batrachotoxin. Single channel blocking events induced by the addition of various guanidinium toxins were analyzed to derive the rates of channel-toxin association and dissociation. Blocking by tetrodotoxin, saxitoxin, and six natural saxitoxin derivatives containing sulfate or hydroxyl groups were studied. Although the binding affinities vary over 2,000-fold, all of the toxins exhibit identical voltage dependence of the blocking reactions, regardless of the toxin's net charge. The results suggest that the voltage dependence of toxin binding is due to a voltage-dependent conformational equilibrium of the toxin receptor, rather than to direct entry of the charged toxin molecule into the applied transmembrane electric field. PMID:6096479
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ERIC Educational Resources Information Center
Drayton, Brian; Falk, Joni K.; Stroud, Rena; Hobbs, Kathryn; Hammerman, James
2010-01-01
There are few studies of the impact of ubiquitous computing on high school science, and the majority of studies of ubiquitous computing report only on the early stages of implementation. The present study presents data on 3 high schools with carefully elaborated ubiquitous computing systems that have gone through at least one "obsolescence cycle"…
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Sokolosky, Melissa L.; Wargovich, Michael J.
2012-01-01
The advent of modern medicine has allowed for significant advances within the fields of emergency care, surgery, and infectious disease control. Health threats that were historically responsible for immeasurable tolls on human life are now all but eradicated within certain populations, specifically those that enjoy higher degrees of socio-economic status and access to healthcare. However, modernization and its resulting lifestyle trends have ushered in a new era of chronic illness; one in which an unprecedented number of people are estimated to contract cancer and other inflammatory diseases. Here, we explore the idea that homeostasis has been redefined within just a few generations, and that diseases such as colorectal cancer are the result of fluctuating physiological and molecular imbalances. Phytochemical-deprived, pro-inflammatory diets combined with low-dose exposures to environmental toxins, including bisphenol-A (BPA) and other endocrine disruptors, are now linked to increasing incidences of cancer in westernized societies and developing countries. There is recent evidence that disease determinants are likely set in utero and further perpetuated into adulthood dependent upon the innate and environmentally-acquired phenotype unique to each individual. In order to address a disease as multi-factorial, case-specific, and remarkably adaptive as cancer, research must focus on its root causes in order to elucidate the molecular mechanisms by which they can be prevented or counteracted via plant-derived compounds such as epigallocatechin-3-gallate (EGCG) and resveratrol. The significant role of epigenetics in the regulation of these complex processes is emphasized here to form a comprehensive view of the dynamic interactions that influence modern-day carcinogenesis, and how sensibly restoring homeostatic balance may be the key to the cancer riddle. PMID:22675672
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Sokolosky, Melissa L; Wargovich, Michael J
2012-01-01
The advent of modern medicine has allowed for significant advances within the fields of emergency care, surgery, and infectious disease control. Health threats that were historically responsible for immeasurable tolls on human life are now all but eradicated within certain populations, specifically those that enjoy higher degrees of socio-economic status and access to healthcare. However, modernization and its resulting lifestyle trends have ushered in a new era of chronic illness; one in which an unprecedented number of people are estimated to contract cancer and other inflammatory diseases. Here, we explore the idea that homeostasis has been redefined within just a few generations, and that diseases such as colorectal cancer are the result of fluctuating physiological and molecular imbalances. Phytochemical-deprived, pro-inflammatory diets combined with low-dose exposures to environmental toxins, including bisphenol-A (BPA) and other endocrine disruptors, are now linked to increasing incidences of cancer in westernized societies and developing countries. There is recent evidence that disease determinants are likely set in utero and further perpetuated into adulthood dependent upon the innate and environmentally acquired phenotype unique to each individual. In order to address a disease as multi-factorial, case-specific, and remarkably adaptive as cancer, research must focus on its root causes in order to elucidate the molecular mechanisms by which they can be prevented or counteracted via plant-derived compounds such as epigallocatechin-3-gallate (EGCG) and resveratrol. The significant role of epigenetics in the regulation of these complex processes is emphasized here to form a comprehensive view of the dynamic interactions that influence modern-day carcinogenesis, and how sensibly restoring homeostatic balance may be the key to the cancer riddle.
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Toxin gene determination and evolution in scorpaenoid fish.
Chuang, Po-Shun; Shiao, Jen-Chieh
2014-09-01
In this study, we determine the toxin genes from both cDNA and genomic DNA of four scorpaenoid fish and reconstruct their evolutionary relationship. The deduced protein sequences of the two toxin subunits in Sebastapistes strongia, Scorpaenopsis oxycephala, and Sebastiscus marmoratus are about 700 amino acid, similar to the sizes of the stonefish (Synanceia horrida, and Synanceia verrucosa) and lionfish (Pterois antennata and Pterois volitans) toxins previously published. The intron positions are highly conserved among these species, which indicate the applicability of gene finding by using genomic DNA template. The phylogenetic analysis shows that the two toxin subunits were duplicated prior to the speciation of Scorpaenoidei. The precedence of the gene duplication over speciation indicates that the toxin genes may be common to the whole family of Scorpaeniform. Furthermore, one additional toxin gene has been determined in the genomic DNA of Dendrochirus zebra. The phylogenetic analysis suggests that an additional gene duplication occurred before the speciation of the lionfish (Pteroinae) and a pseudogene may be generally present in the lineage of lionfish. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Discovery of novel bacterial toxins by genomics and computational biology.
Doxey, Andrew C; Mansfield, Michael J; Montecucco, Cesare
2018-06-01
Hundreds and hundreds of bacterial protein toxins are presently known. Traditionally, toxin identification begins with pathological studies of bacterial infectious disease. Following identification and cultivation of a bacterial pathogen, the protein toxin is purified from the culture medium and its pathogenic activity is studied using the methods of biochemistry and structural biology, cell biology, tissue and organ biology, and appropriate animal models, supplemented by bioimaging techniques. The ongoing and explosive development of high-throughput DNA sequencing and bioinformatic approaches have set in motion a revolution in many fields of biology, including microbiology. One consequence is that genes encoding novel bacterial toxins can be identified by bioinformatic and computational methods based on previous knowledge accumulated from studies of the biology and pathology of thousands of known bacterial protein toxins. Starting from the paradigmatic cases of diphtheria toxin, tetanus and botulinum neurotoxins, this review discusses traditional experimental approaches as well as bioinformatics and genomics-driven approaches that facilitate the discovery of novel bacterial toxins. We discuss recent work on the identification of novel botulinum-like toxins from genera such as Weissella, Chryseobacterium, and Enteroccocus, and the implications of these computationally identified toxins in the field. Finally, we discuss the promise of metagenomics in the discovery of novel toxins and their ecological niches, and present data suggesting the existence of uncharacterized, botulinum-like toxin genes in insect gut metagenomes. Copyright © 2018. Published by Elsevier Ltd.
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Clostridium perfringens epsilon toxin is absorbed from different intestinal segments of mice.
Losada-Eaton, D M; Uzal, F A; Fernández Miyakawa, M E
2008-06-01
Clostridium perfringens epsilon toxin is a potent toxin responsible for a rapidly fatal enterotoxaemia in several animal species. The pathogenesis of epsilon toxin includes toxicity to endothelial cells and neurons. Although epsilon toxin is absorbed from the gastrointestinal tract, the intestinal regions where the toxin is absorbed and the conditions favoring epsilon toxin absorption are unknown. The aim of this paper was to determine the toxicity of epsilon toxin absorbed from different gastrointestinal segments of mice and to evaluate the influence of the intestinal environment in the absorption of this toxin. Epsilon toxin diluted in one of several different saline solutions was surgically introduced into ligated stomach or intestinal segments of mice. Comparison of the toxicity of epsilon toxin injected in different sections of the gastrointestinal tract showed that this toxin can be absorbed from the small and the large intestine but not from the stomach of mice. The lethality of epsilon toxin was higher when this toxin was injected in the colon than in the small intestine. Low pH, and Na(+) and glucose added to the saline solution increased the toxicity of epsilon toxin injected into the small intestine. This study shows that absorption of epsilon toxin can occur in any intestinal segment of mice and that the physicochemical characteristics of the intestinal content can affect the absorption of this toxin.
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A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure
Luoma, Sarah E.; St. Armour, Genevieve E.; Thakkar, Esha
2017-01-01
The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag. Drosophila melanogaster is a powerful model that enables genome-wide studies for the identification of allelic variants that contribute to variation in susceptibility to environmental toxins, since the genetic background, environmental rearing conditions and toxic exposure can be precisely controlled. Here, we used extreme QTL mapping in an outbred population derived from the D. melanogaster Genetic Reference Panel to identify alleles associated with resistance to lead and/or cadmium, two ubiquitous environmental toxins that present serious health risks. We identified single nucleotide polymorphisms (SNPs) associated with variation in resistance to both heavy metals as well as SNPs associated with resistance specific to each of them. The effects of these SNPs were largely sex-specific. We applied mutational and RNAi analyses to 33 candidate genes and functionally validated 28 of them. We constructed networks of candidate genes as blueprints for orthologous networks of human genes. The latter not only provided functional contexts for known human targets of heavy metal toxicity, but also implicated novel candidate susceptibility genes. These studies validate Drosophila as a translational toxicogenomics gene discovery system. PMID:28732062
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Kreidler, Anna-Maria; Benz, Roland; Barth, Holger
2017-03-01
The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B 7 ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B 7 components of C2 toxin and LT, C2IIa and PA 63 , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA 63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA 63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA 63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA 63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.
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The Effects of Environmental Toxins on Allergic Inflammation
Yang, San-Nan; Hsieh, Chong-Chao; Kuo, Hsuan-Fu; Lee, Min-Sheng; Huang, Ming-Yii
2014-01-01
The prevalence of asthma and allergic disease has increased worldwide over the last few decades. Many common environmental factors are associated with this increase. Several theories have been proposed to account for this trend, especially those concerning the impact of environmental toxicants. The development of the immune system, particularly in the prenatal period, has far-reaching consequences for health during early childhood, and throughout adult life. One underlying mechanism for the increased levels of allergic responses, secondary to exposure, appears to be an imbalance in the T-helper function caused by exposure to the toxicants. Exposure to environmental endocrine-disrupting chemicals can result in dramatic changes in cytokine production, the activity of the immune system, the overall Th1 and Th2 balance, and in mediators of type 1 hypersensitivity mediators, such as IgE. Passive exposure to tobacco smoke is a common risk factor for wheezing and asthma in children. People living in urban areas and close to roads with a high volume of traffic, and high levels of diesel exhaust fumes, have the highest exposure to environmental compounds, and these people are strongly linked with type 1 hypersensitivity disorders and enhanced Th2 responses. These data are consistent with epidemiological research that has consistently detected increased incidences of allergies and asthma in people living in these locations. During recent decades more than 100,000 new chemicals have been used in common consumer products and are released into the everyday environment. Therefore, in this review, we discuss the environmental effects on allergies of indoor and outside exposure. PMID:25374746
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The effects of environmental toxins on allergic inflammation.
Yang, San-Nan; Hsieh, Chong-Chao; Kuo, Hsuan-Fu; Lee, Min-Sheng; Huang, Ming-Yii; Kuo, Chang-Hung; Hung, Chih-Hsing
2014-11-01
The prevalence of asthma and allergic disease has increased worldwide over the last few decades. Many common environmental factors are associated with this increase. Several theories have been proposed to account for this trend, especially those concerning the impact of environmental toxicants. The development of the immune system, particularly in the prenatal period, has far-reaching consequences for health during early childhood, and throughout adult life. One underlying mechanism for the increased levels of allergic responses, secondary to exposure, appears to be an imbalance in the T-helper function caused by exposure to the toxicants. Exposure to environmental endocrine-disrupting chemicals can result in dramatic changes in cytokine production, the activity of the immune system, the overall Th1 and Th2 balance, and in mediators of type 1 hypersensitivity mediators, such as IgE. Passive exposure to tobacco smoke is a common risk factor for wheezing and asthma in children. People living in urban areas and close to roads with a high volume of traffic, and high levels of diesel exhaust fumes, have the highest exposure to environmental compounds, and these people are strongly linked with type 1 hypersensitivity disorders and enhanced Th2 responses. These data are consistent with epidemiological research that has consistently detected increased incidences of allergies and asthma in people living in these locations. During recent decades more than 100,000 new chemicals have been used in common consumer products and are released into the everyday environment. Therefore, in this review, we discuss the environmental effects on allergies of indoor and outside exposure.
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Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity
Pigott, Craig R.; Ellar, David J.
2007-01-01
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
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Cellular Uptake of the Clostridium perfringens Binary Iota-Toxin
Blöcker, Dagmar; Behlke, Joachim; Aktories, Klaus; Barth, Holger
2001-01-01
The binary iota-toxin is produced by Clostridium perfringens type E strains and consists of two separate proteins, the binding component iota b (98 kDa) and an actin-ADP-ribosylating enzyme component iota a (47 kDa). Iota b binds to the cell surface receptor and mediates the translocation of iota a into the cytosol. Here we studied the cellular uptake of iota-toxin into Vero cells. Bafilomycin A1, but not brefeldin A or nocodazole, inhibited the cytotoxic effects of iota-toxin, indicating that toxin is translocated from an endosomal compartment into the cytoplasm. Acidification (pH ≤ 5.0) of the extracellular medium enabled iota a to directly enter the cytosol in the presence of iota b. Activation by chymotrypsin induced oligomerization of iota b in solution. An average mass of 530 ± 28 kDa for oligomers was determined by analytical ultracentrifugation, indicating heptamer formation. The entry of iota-toxin into polarized CaCo-2 cells was studied by measuring the decrease in transepithelial resistance after toxin treatment. Iota-toxin led to a significant decrease in resistance when it was applied to the basolateral surface of the cells but not following application to the apical surface, indicating a polarized localization of the iota-toxin receptor. PMID:11292715
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Song, Lei; Seeger, Achim; Santos-Sacchi, Joseph
2005-01-01
The outer hair cell (OHC) underlies mammalian cochlea amplification, and its lateral membrane motor, prestin, which drives the cell's mechanical activity, is modulated by intracellular chloride ions. We have previously described a native nonselective conductance (GmetL) that influences OHC motor activity via Cl flux across the lateral membrane. Here we further investigate this conductance and use the environmental toxin tributyltin (TBT) to better understand Cl-prestin interactions. Capitalizing on measures of prestin-derived nonlinear capacitance to gauge Cl flux across the lateral membrane, we show that the Cl ionophore TBT, which affects neither the motor nor GmetL directly, is capable of augmenting the native flux of Cl in OHCs. These observations were confirmed using the chloride-sensitive dye MQAE. Furthermore, the compound's potent ability, at nanomolar concentrations, to equilibrate intra- and extracellular Cl concentrations is shown to surpass the effectiveness of GmetL in promoting Cl flux, and secure a quantitative analysis of Cl-prestin interactions in intact OHCs. Using malate as an anion replacement, we quantify chloride effects on the nonlinear charge density and operating voltage range of prestin. Our data additionally suggest that ototoxic effects of organotins can derive from their disruption of OHC Cl homeostasis, ultimately interfering with anionic modulation of the mammalian cochlear amplifier. Notably, this observation identifies a new environmental threat for marine mammals by TBT, which is known to accumulate in the food chain. PMID:15596517
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Ahmed, W; Gyawali, P; Toze, S
2015-03-03
Quantitative PCR (qPCR) assays were used to determine the concentrations of E. coli including shiga toxin-producing E. coli (STEC) associated virulence genes (eaeA, stx1, stx2, and hlyA) in ten animal species (fecal sources) and environmental water samples in Southeast Queensland, Australia. The mean Log10 concentrations and standard deviations of E. coli 23S rRNA across fecal sources ranged from 1.3 ± 0.1 (horse) to 6.3 ± 0.4 (cattle wastewater) gene copies at a test concentration of 10 ng of DNA. The differences in mean concentrations of E. coli 23S rRNA gene copies among fecal source samples were significantly different from each other (P < 0.0001). Among the virulence genes, stx2 (25%, 95% CI, 17-33%) was most prevalent among fecal sources, followed by eaeA (19%, 95% CI, 12-27%), stx1 (11%, 95% CI, 5%-17%) and hlyA (8%, 95% CI, 3-13%). The Log10 concentrations of STEC virulence genes in cattle wastewater samples ranged from 3.8 to 5.0 gene copies at a test concentration of 10 ng of DNA. Of the 18 environmental water samples tested, three (17%) were positive for eaeA and two (11%) samples were also positive for the stx2 virulence genes. The data presented in this study will aid in the estimation of quantitative microbial risk assessment (QMRA) from fecal pollution of domestic and wild animals in drinking/recreational water catchments.
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Toxin activity assays, devices, methods and systems therefor
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.
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Clostridium perfringens iota toxin: synergism between two proteins.
Stiles, B G; Wilkins, T D
1986-01-01
The iota toxin of Clostridium perfringens type E is a guinea pig dermonecrotic, mouse lethal toxin which cross-reacts with the iota-like toxin of Clostridium spiroforme. Antiserum raised against C. spiroforme or C. perfringens type E neutralizes the toxin from both species. By using C. spiroforme antiserum and crossed immunoelectrophoresis, we have found that there are two cross-reacting proteins, designated iota a (ia) and iota b (ib) in the culture filtrate of C. perfringens type E. Both proteins of C. perfringens were separated by preparative isoelectric focusing and had very little toxic activity when tested alone. However, when they were recombined there were 8- and 25-fold increases in bioactivity as determined by mouse lethal and guinea pig dermonecrotic assays, respectively. These results demonstrate that the iota toxin of C. perfringens requires two immunologically and biochemically different proteins for maximum activity.
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Diarrhetic Shellfish Toxins and Other Lipophilic Toxins of Human Health Concern in Washington State
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
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Diarrhetic shellfish toxins and other lipophilic toxins of human health concern in Washington State.
Trainer, Vera L; Moore, Leslie; Bill, Brian D; Adams, Nicolaus G; Harrington, Neil; Borchert, Jerry; da Silva, Denis A M; Eberhart, Bich-Thuy L
2013-05-28
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.
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X Irradiation and Toxin Neutralization by Antitoxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kahn, R. L.; Kim, S. H.; Curtis, A. C.
1960-11-01
A small area of the skin of normal rabbits was exposed to 1000 r and, after a given interval, 15 units of horse serum diphtheria antitoxin were injected subcutaneously in that area and simultaneously a lethal (25 MLD) dose of homologous toxin in another area. As controls, non-irradiated rabbits of similar weight were injected with the same quantities of antitoxin and of toxin at the same time as the irradiated rabbits and under identical conditions. Five intervals following the irradiation were employed for the injection of the antitoxin and the toxin: 1 to 3 hours, 24 hours, 7 days, 14more » days, and 90 days. It was found that, of the irradiated rabbits, 55% survived the toxin when the antitoxin was injected 1 to 3 hours after the exposure, 100% survived when the antitoxin was injected 24 hours after, 47% survived when the antitoxin was injected 7 days after, 27% survived when the antitoxin was injected 14 days after and none of the rabbits survived when the antitoxin was injected 90 days after. Of the non-irradiated controls, an average of 20% survived the toxin. The results indicated that a restricted amount of antitoxin injected subcutaneously in an irradiated area up to 7 days after exposure to 1000 r was more effective in the neutralization of a lethal dose of toxin than the same amount injected into a corresponding area of non-irradiated rabbits and the most marked neutralization occurred 24 hours after the exposure. By 14 days after the exposure, the neutralization of the toxin reached the control level, but 90 days after, no neutralization of the toxin was observed. The basis for the non-neutralization of the toxin in any of the rabbits was apparently not an insufficiency of the subcutaneouslyinjected antitoxin, which consisted of 15 units, since 5 units injected intravenously were found to be ample for neutralization of the same dose of toxin. The non-protection was due most likely to the localization of the proteins of the antitoxin, consisting of 0
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EFFECTS OF MARINE ALGAL TOXINS ON THERMOREGULATION IN MICE.
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...
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Inland Transport of Aerosolized Florida Red Tide Toxins.
Kirkpatrick, Barbara; Pierce, Richard; Cheng, Yung Sung; Henry, Michael S; Blum, Patricia; Osborn, Shannon; Nierenberg, Kate; Pederson, Bradley A; Fleming, Lora E; Reich, Andrew; Naar, Jerome; Kirkpatrick, Gary; Backer, Lorraine C; Baden, Daniel
2010-02-01
Florida red tides, an annual event off the west coast of Florida, are caused by the toxic dinoflagellate, Karenia brevis. K. brevis produces a suite of potent neurotoxins, brevetoxins, which kill fish, sea birds, and marine mammals, as well as sickening humans who consume contaminated shellfish. These toxins become part of the marine aerosol, and can also be inhaled by humans and other animals. Recent studies have demonstrated a significant increase in symptoms and decrease lung function in asthmatics after only one hour of beach exposure during an onshore Florida red tide bloom.This study constructed a transect line placing high volume air samplers to measure brevetoxins at sites beginning at the beach, moving approximately 6.4 km inland. One non-exposure and 2 exposure studies, each of 5 days duration, were conducted. No toxins were measured in the air during the non-exposure period. During the 2 exposure periods, the amount of brevetoxins varied considerably by site and by date. Nevertheless, brevetoxins were measured at least 4.2 kilometers from the beach and/or 1.6 km from the coastal shoreline. Therefore, populations sensitive to brevetoxins (such as asthmatics) need to know that leaving the beach may not discontinue their environmental exposure to brevetoxin aerosols.
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ERIC Educational Resources Information Center
Peng, Hsinyi; Chou, Chien; Chang, Chun-Yu
2008-01-01
Computing devices and applications are now used beyond the desktop, in diverse environments, and this trend toward ubiquitous computing is evolving. In this study, we re-visit the interactivity concept and its applications for interactive function design in a ubiquitous-learning system (ULS). Further, we compare interactivity dimensions and…
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2009-01-01
neuroblastomas and rat gliomas, but not to human neuroblastoma cell lines ( Yokosawa et ai., 1989). Yokosawa et ai. (1989) suggested that reduced...12764-72. Yndestad, M., Loftsgard, G. (1970). Susceptibility of mink to Clostridium botulinum type C toxin. Acta Vet. Scand. 11: 594-9. Yokosawa , N
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Cellular vacuolation induced by Clostridium perfringens epsilon-toxin.
Nagahama, Masahiro; Itohayashi, Yukari; Hara, Hideki; Higashihara, Masahiro; Fukatani, Yusuke; Takagishi, Teruhisa; Oda, Masataka; Kobayashi, Keiko; Nakagawa, Ichiro; Sakurai, Jun
2011-09-01
The epsilon-toxin of Clostridium perfringens forms a heptamer in the membranes of Madin-Darby canine kidney cells, leading to cell death. Here, we report that it caused the vacuolation of Madin-Darby canine kidney cells. The toxin induced vacuolation in a dose-dependent and time-dependent manner. The monomer of the toxin formed oligomers on lipid rafts in membranes of the cells. Methyl-β-cyclodextrin and poly(ethylene glycol) 4000 inhibited the vacuolation. Epsilon-toxin was internalized into the cells. Confocal microscopy revealed that the internalized toxin was transported from early endosomes (early endosome antigen 1 staining) to late endosomes and lysosomes (lysosomal-associated membrane protein 2 staining) and then distributed to the membranes of vacuoles. Furthermore, the vacuolation was inhibited by bafilomycin A1, a V-type ATPase inhibitor, and colchicine and nocodazole, microtubule-depolymerizing agents. The early endosomal marker green fluorescent protein-Rab5 and early endosome antigen 1 did not localize to vacuolar membranes. In contrast, the vacuolar membranes were specifically stained by the late endosomal and lysosomal marker green fluorescent protein-Rab7 and lysosomal-associated membrane protein 2. The vacuoles in the toxin-treated cells were stained with LysoTracker Red DND-99, a marker for late endosomes and lysosomes. A dominant negative mutant of Rab7 prevented the vacuolization, whereas a mutant form of Rab5 was less effective. These results demonstrate, for the first time, that: (a) oligomers of epsilon-toxin formed in lipid rafts are endocytosed; and (b) the vacuoles originating from late endosomes and lysosomes are formed by an oligomer of epsilon-toxin. © 2011 The Authors Journal compilation © 2011 FEBS.
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Ubiquitous Mobile Knowledge Construction in Collaborative Learning Environments
Baloian, Nelson; Zurita, Gustavo
2012-01-01
Knowledge management is a critical activity for any organization. It has been said to be a differentiating factor and an important source of competitiveness if this knowledge is constructed and shared among its members, thus creating a learning organization. Knowledge construction is critical for any collaborative organizational learning environment. Nowadays workers must perform knowledge creation tasks while in motion, not just in static physical locations; therefore it is also required that knowledge construction activities be performed in ubiquitous scenarios, and supported by mobile and pervasive computational systems. These knowledge creation systems should help people in or outside organizations convert their tacit knowledge into explicit knowledge, thus supporting the knowledge construction process. Therefore in our understanding, we consider highly relevant that undergraduate university students learn about the knowledge construction process supported by mobile and ubiquitous computing. This has been a little explored issue in this field. This paper presents the design, implementation, and an evaluation of a system called MCKC for Mobile Collaborative Knowledge Construction, supporting collaborative face-to-face tacit knowledge construction and sharing in ubiquitous scenarios. The MCKC system can be used by undergraduate students to learn how to construct knowledge, allowing them anytime and anywhere to create, make explicit and share their knowledge with their co-learners, using visual metaphors, gestures and sketches to implement the human-computer interface of mobile devices (PDAs). PMID:22969333
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Ubiquitous mobile knowledge construction in collaborative learning environments.
Baloian, Nelson; Zurita, Gustavo
2012-01-01
Knowledge management is a critical activity for any organization. It has been said to be a differentiating factor and an important source of competitiveness if this knowledge is constructed and shared among its members, thus creating a learning organization. Knowledge construction is critical for any collaborative organizational learning environment. Nowadays workers must perform knowledge creation tasks while in motion, not just in static physical locations; therefore it is also required that knowledge construction activities be performed in ubiquitous scenarios, and supported by mobile and pervasive computational systems. These knowledge creation systems should help people in or outside organizations convert their tacit knowledge into explicit knowledge, thus supporting the knowledge construction process. Therefore in our understanding, we consider highly relevant that undergraduate university students learn about the knowledge construction process supported by mobile and ubiquitous computing. This has been a little explored issue in this field. This paper presents the design, implementation, and an evaluation of a system called MCKC for Mobile Collaborative Knowledge Construction, supporting collaborative face-to-face tacit knowledge construction and sharing in ubiquitous scenarios. The MCKC system can be used by undergraduate students to learn how to construct knowledge, allowing them anytime and anywhere to create, make explicit and share their knowledge with their co-learners, using visual metaphors, gestures and sketches to implement the human-computer interface of mobile devices (PDAs).
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42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... such agent or toxin or destroys the agent or toxin by a recognized sterilization or inactivation...
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Ubiquitous computing in shared-care environments.
Koch, S
2006-07-01
In light of future challenges, such as growing numbers of elderly, increase in chronic diseases, insufficient health care budgets and problems with staff recruitment for the health-care sector, information and communication technology (ICT) becomes a possible means to meet these challenges. Organizational changes such as the decentralization of the health-care system lead to a shift from in-hospital to both advanced and basic home health care. Advanced medical technologies provide solutions for distant home care in form of specialist consultations and home monitoring. Furthermore, the shift towards home health care will increase mobile work and the establishment of shared care teams which require ICT-based solutions that support ubiquitous information access and cooperative work. Clinical documentation and decision support systems are the main ICT-based solutions of interest in the context of ubiquitous computing for shared care environments. This paper therefore describes the prerequisites for clinical documentation and decision support at the point of care, the impact of mobility on the documentation process, and how the introduction of ICT-based solutions will influence organizations and people. Furthermore, the role of dentistry in shared-care environments is discussed and illustrated in the form of a future scenario.
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Cellular Uptake and Mode-of-Action of Clostridium difficile Toxins.
Papatheodorou, Panagiotis; Barth, Holger; Minton, Nigel; Aktories, Klaus
2018-01-01
Research on the human gut pathogen Clostridium difficile and its toxins has gained much attention, particularly as a consequence of the increasing threat to human health presented by emerging hypervirulent strains. Toxin A (TcdA) and B (TcdB) are the two major virulence determinants of C. difficile. Both are single-chain proteins with a similar multidomain architecture. Certain hypervirulent C. difficile strains also produce a third toxin, namely binary toxin CDT (Clostridium difficile transferase). As C. difficile toxins are the causative agents of C. difficile-associated diseases (CDAD), such as antibiotics-associated diarrhea and pseudomembranous colitis, considerable efforts have been expended to unravel their molecular mode-of-action and the cellular mechanisms responsible for their uptake. Notably, a high proportion of studies on C. difficile toxins were performed in European laboratories. In this chapter we will highlight important recent advances in C. difficile toxins research.
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Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress
Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ)induce oxidative stress by redox cycling, which generates hydrogen peroxide (H202). Cysteinylthio...
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Phage Display of a Biologically Active Bacillus thuringiensis Toxin
Kasman, Laura M.; Lukowiak, Andrew A.; Garczynski, Stephen F.; McNall, Rebecca J.; Youngman, Phil; Adang, Michael J.
1998-01-01
Activated forms of Bacillus thuringiensis insecticidal toxins have consistently been found to form insoluble and inactive precipitates when they are expressed in Escherichia coli. Genetic engineering of these proteins to improve their effectiveness as biological pesticides would be greatly facilitated by the ability to express them in E. coli, since the molecular biology tools available for Bacillus are limited. To this end, we show that activated B. thuringiensis toxin (Cry1Ac) can be expressed in E. coli as a translational fusion with the minor phage coat protein of filamentous phage. Phage particles displaying this fusion protein were viable, infectious, and as lethal as pure toxin on a molar basis when the phage particles were fed to insects susceptible to native Cry1Ac. Enzyme-linked immunosorbent assay and Western blot analysis showed the fusion protein to be antigenically equivalent to native toxin, and micropanning with anti-Cry1Ac antibody was positive for the toxin-expressing phage. Phage display of B. thuringiensis toxins has many advantages over previous expression systems for these proteins and should make it possible to construct large libraries of toxin variants for screening or biopanning. PMID:9687463
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Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish
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
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Permpoonpattana, Patima; Hong, Huynh A.; Phetcharaburanin, Jutarop; Huang, Jen-Min; Cook, Jenny; Fairweather, Neil F.; Cutting, Simon M.
2011-01-01
Clostridium difficile is a leading cause of nosocomial infection in the developed world. Two toxins, A and B, produced by most strains of C. difficile are implicated as virulence factors, yet only recently has the requirement of these for infection been investigated by genetic manipulation. Current vaccine strategies are focused mostly on parenteral delivery of toxoids. In this work, we have used bacterial spores (Bacillus subtilis) as a delivery vehicle to evaluate the carboxy-terminal repeat domains of toxins A and B as protective antigens. Our findings are important and show that oral immunization of the repeat domain of toxin A is sufficient to confer protection in a hamster model of infection designed to closely mimic the human course of infection. Importantly, neutralizing antibodies to the toxin A repeat domain were shown to be cross-reactive with the analogous domain of toxin B and, being of high avidity, provided protection against challenge with a C. difficile strain producing toxins A and B (A+B+). Thus, although many strains produce both toxins, antibodies to only toxin A can mediate protection. Animals vaccinated with recombinant spores were fully able to survive reinfection, a property that is particularly important for a disease with which patients are prone to relapse. We show that mucosal immunization, not parenteral delivery, is required to generate secretory IgA and that production of these neutralizing polymeric antibodies correlates with protection. This work demonstrates that an effective vaccine against C. difficile can be designed around two attributes, mucosal delivery and the repeat domain of toxin A. PMID:21482682
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Wu, Wenda; Zhou, Hui-Ren; Pan, Xiao; Pestka, James J
Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON) and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g., T-2 toxin, HT-2 toxin), airborne Type D trichothecenes (e.g. satratoxin G [SG]) or functionally analogous metabolites that impair protein synthesis. Here, we utilized a well-described mouse model of food intake to compare the anorectic potencies of T-2 toxin, HT-2 toxin, and SG to that of emetine, a medicinal alkaloid derived from ipecac that inhibits translation. Intraperitoneal (IP) administration with T-2 toxin, HT-2 toxin, emetine and SG evoked anorectic responses that occurred within 0.5 h that lasted up to 96, 96, 3 and 96 h, respectively, with lowest observed adverse effect levels (LOAELs) being 0.1, 0.1, 2.5 and 0.25 mg/kg BW, respectively. When delivered via natural routes of exposure, T-2 toxin, HT-2 toxin, emetine (oral) and SG (intranasal) induced anorectic responses that lasted up to 48, 48, 3 and 6 h, respectively with LOAELs being 0.1, 0.1, 0.25, and 0.5 mg/kg BW, respectively. All four compounds were generally much more potent than DON which was previously observed to have LOAELs of 1 and 2.5 mg/kg BW after IP and oral dosing, respectively. Taken together, these anorectic potency data will be valuable in discerning the relative risks from trichothecenes and other translational inhibitors of natural origin.
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Han, Jeong-Sun; Lee, Jae Jin; Anandan, Tripti; Zeng, Minghui; Sripathi, Srinivas; Jahng, Wan Jin; Lee, Sang Hee; Suh, Joo-Won; Kang, Choong-Min
2010-09-24
Toxin-antitoxin systems, ubiquitous in prokaryotic genomes, have been proposed to play an important role in several stress responses. While Mycobacterium tuberculosis contains more than 80 putative TA loci, the roles they play in this pathogen are yet to be studied. Here, we characterize a chromosomal Rv1102c-Rv1103c TA system in M. tuberculosis. We found that the Rv1102c toxin interacts with the Rv1103c antitoxin in a pull-down assay and the yeast two-hybrid system. Rv1102c cleaved the era mRNA in Escherichia coli, and cleavage was inhibited by co-expression of Rv1103c. Heterologous expression of Rv1102c led to growth arrest in E. coli, which was fully recovered only when Rv1103c was co-expressed in cis with Rv1102c, suggesting that the production and assembly of Rv1102c and Rv1103c are tightly linked. Our additional results indicate that translational coupling of the Rv1102c and Rv1103c genes is important for Rv1102c-Rv1103c binding. Finally, we discovered that the expression of Rv1102c induced growth arrest and increased the level of persister cells in Mycobacterium smegmatis. These results suggest that the Rv1102c-Rv1103c TA system could play a role in M. tuberculosis pathogenesis via generating bacilli that survive in the face of multidrug therapy. Copyright © 2010. Published by Elsevier Inc.
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Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle.
James, Arlene N; Ryan, James P; Parkman, Henry P
2003-08-01
Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis. Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle. The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle. Guinea pig pyloric muscle strips were studied in vitro. Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h. ACh (100 microM)-induced contractile responses were determined before and after 6 h. Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS. At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 +/- 9% without affecting ACh-induced contractions. At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 +/- 7% and decreased ACh-induced contraction by 79 +/- 9%. In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility. At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves. At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh.
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42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... an entity eligible to receive such agent or toxin or destroys the agent or toxin by a recognized...
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A Conserved Mode of Protein Recognition and Binding in a ParD−ParE Toxin−Antitoxin Complex
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dalton, Kevin M.; Crosson, Sean
2010-05-06
Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and bindingmore » groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.« less
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AB toxins: a paradigm switch from deadly to desirable.
Odumosu, Oludare; Nicholas, Dequina; Yano, Hiroshi; Langridge, William
2010-07-01
To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity.
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AB Toxins: A Paradigm Switch from Deadly to Desirable
Odumosu, Oludare; Nicholas, Dequina; Yano, Hiroshi; Langridge, William
2010-01-01
To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity. PMID:22069653
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Overview of Scorpion Species from China and Their Toxins
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
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Botulinum toxin A for the Treatment of Overactive Bladder.
Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung
2016-02-29
The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.
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Botulinum toxin type a for chronic migraine.
Ashkenazi, Avi
2010-03-01
Chronic migraine (CM) is the leading cause of chronic daily headache, a common and debilitating headache syndrome. The management of CM patients is challenging, with only limited benefit from available oral preventive medications. Botulinum neurotoxin (BoNT) has been used extensively to treat disorders associated with increased muscle tone. More recent scientific data support an analgesic effect of the toxin. The pharmacokinetic and pharmacodynamic profiles of BoNT make it an appealing candidate for migraine prevention. Results from older clinical trials on the efficacy of the toxin in CM were inconclusive. However, recent trials using more stringent inclusion criteria have shown positive results, supporting the use of the toxin in some patients with this disorder. This review summarizes the scientific data on the analgesic properties of BoNT, as well as the clinical data on the efficacy of the toxin in treating CM.
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Commentary: Ubiquitous Computing Revisited--A New Perspective
ERIC Educational Resources Information Center
Bull, Glen; Garofalo, Joe
2006-01-01
In 2002, representatives from the teacher educator associations representing the core content areas (science, mathematics, language arts, and social studies) and educational technology met at the National Technology Leadership Retreat (NTLR) to discuss potential implications of ubiquitous computing for K-12 schools. This paper re-examines some of…
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Towards ubiquitous access of computer-assisted surgery systems.
Liu, Hui; Lufei, Hanping; Shi, Weishong; Chaudhary, Vipin
2006-01-01
Traditional stand-alone computer-assisted surgery (CAS) systems impede the ubiquitous and simultaneous access by multiple users. With advances in computing and networking technologies, ubiquitous access to CAS systems becomes possible and promising. Based on our preliminary work, CASMIL, a stand-alone CAS server developed at Wayne State University, we propose a novel mobile CAS system, UbiCAS, which allows surgeons to retrieve, review and interpret multimodal medical images, and to perform some critical neurosurgical procedures on heterogeneous devices from anywhere at anytime. Furthermore, various optimization techniques, including caching, prefetching, pseudo-streaming-model, and compression, are used to guarantee the QoS of the UbiCAS system. UbiCAS enables doctors at remote locations to actively participate remote surgeries, share patient information in real time before, during, and after the surgery.
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Binding of epsilon-toxin from Clostridium perfringens in the nervous system.
Dorca-Arévalo, Jonatan; Soler-Jover, Alex; Gibert, Maryse; Popoff, Michel R; Martín-Satué, Mireia; Blasi, Juan
2008-09-18
Epsilon-toxin (epsilon-toxin), produced by Clostridium perfringens type D, is the main agent responsible for enterotoxaemia in livestock. Neurological disorders are a characteristic of the onset of toxin poisoning. Epsilon-Toxin accumulates specifically in the central nervous system, where it produces a glutamatergic-mediated excitotoxic effect. However, no detailed study of putative binding structures in the nervous tissue has been carried out to date. Here we attempt to identify specific acceptor moieties and cell targets for epsilon-toxin, not only in the mouse nervous system but also in the brains of sheep and cattle. An epsilon-toxin-GFP fusion protein was produced and used to incubate brain sections, which were then analyzed by confocal microscopy. The results clearly show specific binding of epsilon-toxin to myelin structures. epsilon-Prototoxin-GFP and epsilon-toxin-GFP, the inactive and active forms of the toxin, respectively, showed identical results. By means of pronase E treatment, we found that the binding was mainly associated to a protein component of the myelin. Myelinated peripheral nerve fibres were also stained by epsilon-toxin. Moreover, the binding to myelin was not only restricted to rodents, but was also found in humans, sheep and cattle. Curiously, in the brains of both sheep and cattle, the toxin strongly stained the vascular endothelium, a result that may explain the differences in potency and effect between species. Although the binding of epsilon-toxin to myelin does not directly explain its neurotoxic effect, this feature opens up a new line of enquiry into its mechanism of toxicity and establishes the usefulness of this toxin for the study of the mammalian nervous system.
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Song, Kejing; Mize, R Ranney; Marrero, Luis; Corti, Miriam; Kirk, Jason M; Pincus, Seth H
2013-01-01
Mechanisms of antibody-mediated neutralization are of much interest. For plant and bacterial A-B toxins, A chain mediates toxicity and B chain binds target cells. It is generally accepted and taught that antibody (Ab) neutralizes by preventing toxin binding to cells. Yet for some toxins, ricin included, anti-A chain Abs afford greater protection than anti-B. The mechanism(s) whereby Abs to the A chain neutralize toxins are not understood. We use quantitative confocal imaging, neutralization assays, and other techniques to study how anti-A chain Abs function to protect cells. Without Ab, ricin enters cells and penetrates to the endoplasmic reticulum within 15 min. Within 45-60 min, ricin entering and being expelled from cells reaches equilibrium. These results are consistent with previous observations, and support the validity of our novel methodology. The addition of neutralizing Ab causes ricin accumulation at the cell surface, delays internalization, and postpones retrograde transport of ricin. Ab binds ricin for >6hr as they traffic together through the cell. Ab protects cells even when administered hours after exposure. CONCLUSIONS/KEY FINDINGS: We demonstrate the dynamic nature of the interaction between the host cell and toxin, and how Ab can alter the balance in favor of the cell. Ab blocks ricin's entry into cells, hinders its intracellular routing, and can protect even after ricin is present in the target organelle, providing evidence that the major site of neutralization is intracellular. These data add toxins to the list of pathogenic agents that can be neutralized intracellularly and explain the in vivo efficacy of delayed administration of anti-toxin Abs. The results encourage the use of post-exposure passive Ab therapy, and show the importance of the A chain as a target of Abs.
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Song, Kejing; Mize, R. Ranney; Marrero, Luis; Corti, Miriam; Kirk, Jason M.; Pincus, Seth H.
2013-01-01
Background Mechanisms of antibody-mediated neutralization are of much interest. For plant and bacterial A-B toxins, A chain mediates toxicity and B chain binds target cells. It is generally accepted and taught that antibody (Ab) neutralizes by preventing toxin binding to cells. Yet for some toxins, ricin included, anti-A chain Abs afford greater protection than anti-B. The mechanism(s) whereby Abs to the A chain neutralize toxins are not understood. Methodology/Principal Findings We use quantitative confocal imaging, neutralization assays, and other techniques to study how anti-A chain Abs function to protect cells. Without Ab, ricin enters cells and penetrates to the endoplasmic reticulum within 15 min. Within 45–60 min, ricin entering and being expelled from cells reaches equilibrium. These results are consistent with previous observations, and support the validity of our novel methodology. The addition of neutralizing Ab causes ricin accumulation at the cell surface, delays internalization, and postpones retrograde transport of ricin. Ab binds ricin for >6hr as they traffic together through the cell. Ab protects cells even when administered hours after exposure. Conclusions/Key Findings We demonstrate the dynamic nature of the interaction between the host cell and toxin, and how Ab can alter the balance in favor of the cell. Ab blocks ricin’s entry into cells, hinders its intracellular routing, and can protect even after ricin is present in the target organelle, providing evidence that the major site of neutralization is intracellular. These data add toxins to the list of pathogenic agents that can be neutralized intracellularly and explain the in vivo efficacy of delayed administration of anti-toxin Abs. The results encourage the use of post-exposure passive Ab therapy, and show the importance of the A chain as a target of Abs. PMID:23638075
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Drug-, toxin-, and radiation therapy-induced eosinophilic pneumonia.
Solomon, Joshua; Schwarz, Marvin
2006-04-01
A significant number of drugs and toxins have been associated with eosinophilic pneumonia. Antibiotics and NSAID, are the most commonly reported drugs. Toxins suspected to cause eosinophilic pneumonia include cigarette smoke and illicit drugs. Drug- or toxin-induced eosinophilic pneumonia is indistinguishable from idiopathic acute or chronic eosinophilic pneumonia by clinical, radiographic, and histopathologic criteria. The diagnosis is supported by a temporal relationship to a drug or toxin. The condition usually resolves with removal from the agent and recurs with rechallenge. Treatment involves discontinuation of the offending drug or toxin and treatment with corticosteroids in severe respiratory failure. There are also mass outbreaks of eosinophilic pneumonia reported, such as the toxic-oil syndrome in 1981 and the eosinophilia-myalgia syndrome related to the ingestion of L-tryptophan in 1989. A recent report has described an outbreak of acute eosinophilic pneumonia found in soldiers in Iraq. Radiation therapy has also been associated with the development of eosinophilic pneumonia in patients receiving this treatment for breast cancer.
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Use of lactose against the deadly biological toxin ricin.
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.
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Structural Insights into Bacillus thuringiensis Cry, Cyt and Parasporin Toxins
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
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Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin.
Nagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko
2018-05-20
Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca 2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca 2+ . Ib induced the extracellular release of ASMase in the presence of Ca 2+ . ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells.
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Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin
Nagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko
2018-01-01
Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca2+. Ib induced the extracellular release of ASMase in the presence of Ca2+. ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells. PMID:29783772
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From Many-to-One to One-to-Many: The Evolution of Ubiquitous Computing in Education
ERIC Educational Resources Information Center
Chen, Wenli; Lim, Carolyn; Tan, Ashley
2011-01-01
Personal, Internet-connected technologies are becoming ubiquitous in the lives of students, and ubiquitous computing initiatives are already expanding in educational contexts. Historically in the field of education, the terms one-to-one (1:1) computing and ubiquitous computing have been interpreted in a number of ways and have at times been used…
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Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin.
Pelish, Teal M; McClain, Mark S
2009-10-23
The Clostridium perfringens epsilon-toxin is responsible for a severe, often lethal intoxication. In this study, we characterized dominant-negative inhibitors of the epsilon-toxin. Site-specific mutations were introduced into the gene encoding epsilon-toxin, and recombinant proteins were expressed in Escherichia coli. Paired cysteine substitutions were introduced at locations predicted to form a disulfide bond. One cysteine in each mutant was introduced into the membrane insertion domain of the toxin; the second cysteine was introduced into the protein backbone. Mutant proteins with cysteine substitutions at amino acid positions I51/A114 and at V56/F118 lacked detectable cytotoxic activity in a MDCK cell assay. Cytotoxic activity could be reconstituted in both mutant proteins by incubation with dithiothreitol, indicating that the lack of cytotoxic activity was attributable to the formation of a disulfide bond. Fluorescent labeling of the cysteines also indicated that the introduced cysteines participated in a disulfide bond. When equimolar mixtures of wild-type epsilon-toxin and mutant proteins were added to MDCK cells, the I51C/A114C and V56C/F118C mutant proteins each inhibited the activity of wild-type epsilon-toxin. Further analysis of the inhibitory activity of the I51C/A114C and V56C/F118C mutant proteins indicated that these proteins inhibit the ability of the active toxin to form stable oligomeric complexes in the context of MDCK cells. These results provide further insight into the properties of dominant-negative inhibitors of oligomeric pore-forming toxins and provide the basis for developing new therapeutics for treating intoxication by epsilon-toxin.
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Cellular and molecular actions of binary toxins possessing ADP-ribosyltransferase activity.
Considine, R V; Simpson, L L
1991-01-01
Clostridial organisms produce a number of binary toxins. Thus far, three complete toxins (botulinum, perfringens and spiroforme) and one incomplete toxin (difficile) have been identified. In the case of complete toxins, there is a heavy chain component (Mr approximately 100,000) that binds to target cells and helps create a docking site for the light chain component (Mr approximately 50,000). The latter is an enzyme that possesses mono(ADP-ribosyl)transferase activity. The toxins appear to proceed through a three step sequence to exert their effects, including a binding step, an internalization step and an intracellular poisoning step. The substrate for the toxins is G-actin. By virtue of ADP-ribosylating monomeric actin, the toxins prevent polymerization as well as promoting depolymerization. The most characteristic cellular effect of the toxins is alteration of the cytoskeleton, which leads directly to changes in cellular morphology and indirectly to changes in cell function (e.g. release of chemical mediators). Binary toxins capable of modifying actin are likely to be useful tools in the study of cell biology.
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Ubiquitous Green Computing Techniques for High Demand Applications in Smart Environments
Zapater, Marina; Sanchez, Cesar; Ayala, Jose L.; Moya, Jose M.; Risco-Martín, José L.
2012-01-01
Ubiquitous sensor network deployments, such as the ones found in Smart cities and Ambient intelligence applications, require constantly increasing high computational demands in order to process data and offer services to users. The nature of these applications imply the usage of data centers. Research has paid much attention to the energy consumption of the sensor nodes in WSNs infrastructures. However, supercomputing facilities are the ones presenting a higher economic and environmental impact due to their very high power consumption. The latter problem, however, has been disregarded in the field of smart environment services. This paper proposes an energy-minimization workload assignment technique, based on heterogeneity and application-awareness, that redistributes low-demand computational tasks from high-performance facilities to idle nodes with low and medium resources in the WSN infrastructure. These non-optimal allocation policies reduce the energy consumed by the whole infrastructure and the total execution time. PMID:23112621
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Ubiquitous green computing techniques for high demand applications in Smart environments.
Zapater, Marina; Sanchez, Cesar; Ayala, Jose L; Moya, Jose M; Risco-Martín, José L
2012-01-01
Ubiquitous sensor network deployments, such as the ones found in Smart cities and Ambient intelligence applications, require constantly increasing high computational demands in order to process data and offer services to users. The nature of these applications imply the usage of data centers. Research has paid much attention to the energy consumption of the sensor nodes in WSNs infrastructures. However, supercomputing facilities are the ones presenting a higher economic and environmental impact due to their very high power consumption. The latter problem, however, has been disregarded in the field of smart environment services. This paper proposes an energy-minimization workload assignment technique, based on heterogeneity and application-awareness, that redistributes low-demand computational tasks from high-performance facilities to idle nodes with low and medium resources in the WSN infrastructure. These non-optimal allocation policies reduce the energy consumed by the whole infrastructure and the total execution time.
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Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin.
McClain, Mark S; Cover, Timothy L
2007-04-01
The Clostridium perfringens epsilon-toxin causes a severe, often fatal illness (enterotoxemia) characterized by cardiac, pulmonary, kidney, and brain edema. In this study, we examined the activities of two neutralizing monoclonal antibodies against the C. perfringens epsilon-toxin. Both antibodies inhibited epsilon-toxin cytotoxicity towards cultured MDCK cells and inhibited the ability of the toxin to form pores in the plasma membranes of cells, as shown by staining cells with the membrane-impermeant dye 7-aminoactinomycin D. Using an antibody competition enzyme-linked immunosorbent assay (ELISA), a peptide array, and analysis of mutant toxins, we mapped the epitope recognized by one of the neutralizing monoclonal antibodies to amino acids 134 to 145. The antibody competition ELISA and analysis of mutant toxins suggest that the second neutralizing monoclonal antibody also recognizes an epitope in close proximity to this region. The region comprised of amino acids 134 to 145 overlaps an amphipathic loop corresponding to the putative membrane insertion domain of the toxin. Identifying the epitopes recognized by these neutralizing antibodies constitutes an important first step in the development of therapeutic agents that could be used to counter the effects of the epsilon-toxin.
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Staphylococcus Alpha-Toxin Action on the Rabbit Iris: Toxic Effects and Their Inhibition.
Arana, Angela M; Bierdeman, Michael A; Balzli, Charles L; Tang, Aihua; Caballero, Armando R; Patel, Rupesh; O'Callaghan, Richard J
2015-01-01
Staphylococcus aureus infection of the anterior chamber can occur after cataract surgery, causing inflammation and extensive damage to the iris. Alpha-toxin, the most potent S. aureus corneal toxin, was tested as a possible mediator of damage to the iris, and alpha-toxin anti-serum and a chemical toxin inhibitor were tested as potential pathology-reducing agents. The hemolytic activity of alpha-toxin and its inhibition by a chemical inhibitor or anti-serum were quantified in vitro. Purified alpha-toxin, heat-inactivated toxin, or alpha-toxin plus normal serum, alpha-toxin anti-serum, or the chemical inhibitor, methyl-β-cyclodextrin-cholesterol (CD-cholesterol), was injected into the rabbit anterior chamber. Pathological changes were photographed, quantified by slit-lamp examination (SLE) scoring, and further documented by histopathological analysis. At five hours post-injection, eyes injected with alpha-toxin or heat-inactivated toxin had a mean SLE score of 7.3 ± 0.59 or 0.84 ± 0.19, respectively. Active toxin caused moderate to severe iris edema, severe erosion of the iris, and mild to moderate fibrin accumulation in the anterior chamber. Alpha-toxin plus anti-serum or CD-cholesterol, in contrast to alpha-toxin alone, caused less iris edema and epithelium sloughing as well as significantly lower SLE scores than eyes receiving alpha-toxin alone (p ≤ 0.019). Alpha-toxin caused extensive iris damage and inflammation, and either anti-alpha-toxin anti-serum or CD-cholesterol was able to significantly reduce toxin-mediated damage and inflammation.
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Dysport: pharmacological properties and factors that influence toxin action.
Pickett, Andy
2009-10-01
The pharmacological properties of Dysport that influence toxin action are reviewed and compared with other botulinum toxin products. In particular, the subject of diffusion is examined and discussed based upon the evidence that currently exists, both from laboratory studies and from clinical data. Diffusion of botulinum toxin products is not related to the size of the toxin complex in the product since the complex dissociates under physiological conditions, releasing the naked neurotoxin to act. The active neurotoxin in Type A products is the same and therefore diffusion is equal when equal doses are administered.
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Ubiquitous Accessibility for People with Visual Impairments: Are We There Yet?
Billah, Syed Masum; Ashok, Vikas; Porter, Donald E.; Ramakrishnan, IV
2017-01-01
Ubiquitous access is an increasingly common vision of computing, wherein users can interact with any computing device or service from anywhere, at any time. In the era of personal computing, users with visual impairments required special-purpose, assistive technologies, such as screen readers, to interact with computers. This paper investigates whether technologies like screen readers have kept pace with, or have created a barrier to, the trend toward ubiquitous access, with a specific focus on desktop computing as this is still the primary way computers are used in education and employment. Towards that, the paper presents a user study with 21 visually-impaired participants, specifically involving the switching of screen readers within and across different computing platforms, and the use of screen readers in remote access scenarios. Among the findings, the study shows that, even for remote desktop access—an early forerunner of true ubiquitous access—screen readers are too limited, if not unusable. The study also identifies several accessibility needs, such as uniformity of navigational experience across devices, and recommends potential solutions. In summary, assistive technologies have not made the jump into the era of ubiquitous access, and multiple, inconsistent screen readers create new practical problems for users with visual impairments. PMID:28782061
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Ubiquitous Accessibility for People with Visual Impairments: Are We There Yet?
Billah, Syed Masum; Ashok, Vikas; Porter, Donald E; Ramakrishnan, I V
2017-05-01
Ubiquitous access is an increasingly common vision of computing, wherein users can interact with any computing device or service from anywhere, at any time. In the era of personal computing, users with visual impairments required special-purpose, assistive technologies, such as screen readers, to interact with computers. This paper investigates whether technologies like screen readers have kept pace with, or have created a barrier to, the trend toward ubiquitous access, with a specific focus on desktop computing as this is still the primary way computers are used in education and employment. Towards that, the paper presents a user study with 21 visually-impaired participants, specifically involving the switching of screen readers within and across different computing platforms, and the use of screen readers in remote access scenarios. Among the findings, the study shows that, even for remote desktop access-an early forerunner of true ubiquitous access-screen readers are too limited, if not unusable. The study also identifies several accessibility needs, such as uniformity of navigational experience across devices, and recommends potential solutions. In summary, assistive technologies have not made the jump into the era of ubiquitous access, and multiple, inconsistent screen readers create new practical problems for users with visual impairments.
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Towards Ubiquitous Blood Pressure Monitoring via Pulse Transit Time: Theory and Practice
Hahn, Jin-Oh; Inan, Omer T.; Mestha, Lalit K.; Kim, Chang-Sei; Töreyin, Hakan; Kyal, Survi
2015-01-01
Ubiquitous blood pressure (BP) monitoring is needed to improve hypertension detection and control and is becoming feasible due to recent technological advances such as in wearable sensing. Pulse transit time (PTT) represents a well-known, potential approach for ubiquitous BP monitoring. The goal of this review is to facilitate the achievement of reliable, ubiquitous BP monitoring via PTT. We explain the conventional BP measurement methods and their limitations; present models to summarize the theory of the PTT-BP relationship; outline the approach while pinpointing the key challenges; overview the previous work towards putting the theory to practice; make suggestions for best practice and future research; and discuss realistic expectations for the approach. PMID:26057530
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How Parkinsonian Toxins Dysregulate the Autophagy Machinery
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
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Expanding horizons. Integrating environmental health in occupational health nursing.
Rogers, B; Cox, A R
1998-01-01
1. Environmental hazards are ubiquitous. Many exist in the workplace or occur as a result of work process exposures. 2. Environmental health is a natural component of the expanding practice of occupational health nursing. 3. AAOHN's vision for occupational and environmental health will continue to set the standard and provide leadership in the specialty.
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Schneider, B; Weigel, W; Sztukowska, M; Demuth, D R
2018-06-01
Type II toxin/antitoxin (TA) systems contribute to the formation of persister cells and biofilm formation for many organisms. Aggregatibacter actinomycetemcomitans thrives in the complex oral microbial community subjected to continual environmental flux. Little is known regarding the presence and function of type II TA systems in this organism or their contribution to adaptation and persistence in the biofilm. We identified 11 TA systems that are conserved across all seven serotypes of A. actinomycetemcomitans and represent the RelBE, MazEF and HipAB families of type II TA systems. The systems selectively responded to various environmental conditions that exist in the oral cavity. Two putative RelBE-like TA systems, D11S_1194-1195 and D11S_1718-1719 were induced in response to low pH and deletion of D11S_1718-1719 significantly reduced metabolic activity of stationary phase A. actinomycetemcomitans cells upon prolonged exposure to acidic conditions. The deletion mutant also exhibited reduced biofilm biomass when cultured under acidic conditions. The D11S_1194 and D11S_1718 toxin proteins inhibited in vitro translation of dihydrofolate reductase (DHFR) and degraded ribosome-associated, but not free, MS2 virus RNA. In contrast, the corresponding antitoxins (D11S_1195 and D11S_1719), or equimolar mixtures of toxin and antitoxin, had no effect on DHFR production or RNA degradation. Together, these results suggest that D11S_1194-1195 and D11S_1718-1719 are RelBE-like type II TA systems that are activated under acidic conditions and may function to cleave ribosome-associated mRNA to inhibit translation in A. actinomycetemcomitans. In vivo, these systems may facilitate A. actinomycetemcomitans adaptation and persistence in acidic local environments in the dental biofilm. © 2018 The Authors. Molecular Oral Microbiology Published by John Wiley & Sons Ltd.
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Dover, Nir; Barash, Jason R.; Burke, Julianne N.; ...
2014-05-22
Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bontmore » gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ 70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.« less
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Crystal structure of Clostridium difficile toxin A
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chumbler, Nicole M.; Rutherford, Stacey A.; Zhang, Zhifen
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. The toxins are large (308 and 270 kDa, respectively), homologous (47% amino acid identity) glucosyltransferases that target small GTPases within the host. 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 eventmore » 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 (TcdA 1832), 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.« less
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Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.
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. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.
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Potent antitumor activity of a urokinase-activated engineered anthrax toxin
NASA Astrophysics Data System (ADS)
Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.
2003-01-01
The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.
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9 CFR 121.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-01-01
... select agent or toxin to APHIS or CDC. (i) The seizure of any of the following overlap select agents and.... This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after seizure of the overlap select agent or toxin. (ii) For all other overlap select agents or toxins, APHIS/CDC Form...
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USDA-ARS?s Scientific Manuscript database
Environmental indicators are powerful tools for tracking environmental changes, measuring environmental performance, and informing policy makers. With the ubiquitous nature of environmental assets and within the broad themes of environmental disciplines, many diverse environmental indicators, inclu...
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Ubiquitous Computing--Are We Crazy? Point/Counterpoint
ERIC Educational Resources Information Center
DeWitt, Scott W.; Horn, Patricia S.
2005-01-01
The push for ubiquitous computing (UC) relies on an understandable and well-intentioned belief that teaching and schooling need to be transformed. This view appears credible based on large-scale criteria, such as test scores relative to other countries, drop-out rates, and economic changes. And the use of technology to achieve this goal is…
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Fernandez-Miyakawa, Mariano E; Jost, B Helen; Billington, Stephen J; Uzal, Francisco A
2008-03-18
Epsilon toxin (ETX) is the most important virulence factor of Clostridium perfringens type D. Two other important toxins, alpha toxin (CPA) and perfringolysin-O (PFO), are encoded and potentially produced by most C. perfringens type D isolates. The biological effects of these toxins are dissimilar although they are all lethal. Since the possible interaction of these toxins during infection is unknown, the effects of CPA and PFO on the lethal activity of ETX were studied in a mouse model. Mice were injected intravenously or intragastrically with CPA or PFO with or without ETX. Sublethal doses of CPA or PFO did not affect the lethality of ETX when either was injected together with the latter intravenously. However, sublethal or lethal doses of CPA or PFO resulted in reduction of the survival time of mice injected simultaneously with ETX when compared with the intravenous effect of ETX injected alone. When PFO was inoculated intragastrically with ETX, a reduction of the survival time was observed. CPA did not alter the survival time when inoculated intragastrically with ETX. The results of the present study suggest that both CPA and PFO have the potential to enhance the ETX lethal effects during enterotoxemia in natural hosts such as sheep and goats.
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Modification of opiate agonist binding by pertussis toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abood, M.E.; Lee, N.M.; Loh, H.H.
1986-03-05
Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin.more » This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.« less
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Isolation of isoelectrically pure cholera toxin for crystallization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spangler, B.D.; Westbrook, E.M.
1989-01-01
We have determined that the failure of cholera toxin to crystallize well results from its isoelectric heterogeneity, which is probably due to a post-translational process such as deamidation of its B subunit. Every sample of cholera toxin we have examined from commercial or academic suppliers has been heterogeneous; heterogeneous cholera toxin does not crystallize satisfactorily. We have overcome this problem by using ion-exchange fast protein liquid chromatography (FPLC) to obtain an isoelectrically homogeneous species of cholera toxin. Homogeneous cholera toxin crystallizes readily, forming single, nonmosaic crystals suitable for x-ray diffraction studies. For this process, protein was applied to a MonoQmore » ion-exchange column, then eluted with an isocratic low salt buffer followed by a linear salt gradient (0-100 mM NaCl). Column fractions were analyzed on isoelectric focusing gels, and those fractions containing the desired homogeneous species were pooled and concentrated. Crystals formed within 24 to 48 hours in a MOPS/PEG buffer, which made use of slow isoelectric precipitation to induce crystallization. 23 refs., 6 figs.« less
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ERIC Educational Resources Information Center
Huang, Yueh-Min; Huang, Yong-Ming; Huang, Shu-Hsien; Lin, Yen-Ting
2012-01-01
English vocabulary learning and ubiquitous learning have separately received considerable attention in recent years. However, research on English vocabulary learning in ubiquitous learning contexts has been less studied. In this study, we develop a ubiquitous English vocabulary learning (UEVL) system to assist students in experiencing a systematic…
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Botulinum toxin treatment of hemifacial spasm.
Elston, J S
1986-01-01
Six patients with hemifacial spasm were treated with injections of botulinum toxin A into the orbicularis oculi; the abnormal movements around the eye were relieved for an average of 15 weeks. There were no systemic or significant local side effects, and in view of the risks involved in neurosurgical treatment, a trial of botulinum toxin injections is recommended in the first instance in this condition. PMID:3746313
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ADP-ribosylation of transducin by pertussis toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Watkins, P.A.; Burns, D.L.; Kanaho, Y.
1985-11-05
Transducin, the guanyl nucleotide-binding regulatory protein of retinal rod outer segments that couples the photon receptor, rhodopsin, with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, T alpha and T beta gamma. T alpha (39 kDa), which is (TSP)ADP-ribosylated by pertussis toxin and (TSP)NAD in rod outer segments and in purified transducin, was also labeled by the toxin after separation from T beta gamma (36 kDa and approximately 10 kDa); neither component of T beta gamma was a pertussis toxin substrate. Labeling of T alpha was enhanced by T beta gamma and was maximal at approximately 1:1more » molar ratio of T alpha : T beta gamma. Limited proteolysis by trypsin of T alpha in the presence of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) resulted in the sequential appearance of proteins of 38 and TS kDa. The amino terminus of both 38- and TS-kDa proteins was leucine, whereas that of T alpha could not be identified and was assumed to be blocked. The TS-kDa peptide was not a pertussis toxin substrate. Labeling of the 38-kDa protein was poor and was not enhanced by T beta gamma. Trypsin treatment of (TSP)ADP-ribosyl-T alpha produced a labeled 37-38-kDa doublet followed by appearance of radioactivity at the dye front. It appears, therefore, that, although the 38-kDa protein was poor toxin substrate, it contained the ADP-ribosylation site. Without rhodopsin, labeling of T alpha (in the presence of T beta gamma) was unaffected by Gpp(NH)p, guanosine 5'-O-(thiotriphosphate) (GTP gamma S), GTP, GDP, and guanosine 5'-O-(thiodiphosphate) (GDP beta S) but was increased by ATP. When photolyzed rhodopsin and T beta gamma were present, Gpp(NH)p and GTP gamma S decreased (TSP)ADP-ribosylation by pertussis toxin. Thus, pertussis toxin-catalyzed (TSP)ADP-ribosylation of T alpha was affected by nucleotides, rhodopsin and light in addition to T beta gamma.« less
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Modelling the Stoichiometric Regulation of C-Rich Toxins in Marine Dinoflagellates.
Pinna, Adriano; Pezzolesi, Laura; Pistocchi, Rossella; Vanucci, Silvana; Ciavatta, Stefano; Polimene, Luca
2015-01-01
Toxin production in marine microalgae was previously shown to be tightly coupled with cellular stoichiometry. The highest values of cellular toxin are in fact mainly associated with a high carbon to nutrient cellular ratio. In particular, the cellular accumulation of C-rich toxins (i.e., with C:N > 6.6) can be stimulated by both N and P deficiency. Dinoflagellates are the main producers of C-rich toxins and may represent a serious threat for human health and the marine ecosystem. As such, the development of a numerical model able to predict how toxin production is stimulated by nutrient supply/deficiency is of primary utility for both scientific and management purposes. In this work we have developed a mechanistic model describing the stoichiometric regulation of C-rich toxins in marine dinoflagellates. To this purpose, a new formulation describing toxin production and fate was embedded in the European Regional Seas Ecosystem Model (ERSEM), here simplified to describe a monospecific batch culture. Toxin production was assumed to be composed by two distinct additive terms; the first is a constant fraction of algal production and is assumed to take place at any physiological conditions. The second term is assumed to be dependent on algal biomass and to be stimulated by internal nutrient deficiency. By using these assumptions, the model reproduced the concentrations and temporal evolution of toxins observed in cultures of Ostreopsis cf. ovata, a benthic/epiphytic dinoflagellate producing C-rich toxins named ovatoxins. The analysis of simulations and their comparison with experimental data provided a conceptual model linking toxin production and nutritional status in this species. The model was also qualitatively validated by using independent literature data, and the results indicate that our formulation can be also used to simulate toxin dynamics in other dinoflagellates. Our model represents an important step towards the simulation and prediction of marine algal
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NASA Astrophysics Data System (ADS)
Jacobson, Mark Joseph; Johnson, Eric A.
The clostridia have a rich history and contemporary importance in industrial, environmental, and medical microbiology. Due to their ability to form endospores, clostridia are ubiquitous in nature and are found in many environments, especially in soils and the intestinal tract of animals including humans. Many clostridia cause devastating diseases of humans and animals, such as botulism, tetanus, and gas gangrene, through the production of protein toxins. The clostridia produce more protein toxins that are lethal for humans and animals than any other bacterial genus (Johnson, 2005; Van Heyningen, 1950). Other species are important in the formation of solvents and organic acids by anaerobic fermentations or as a source of unique enzymes for biocatalysis (Bradshaw and Johnson, 2010; Hatheway and Johnson, 1998).
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Kalb, Suzanne R; Barr, John R
2013-08-01
Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A-G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence and immunogenic properties, and some subtypes are further differentiated into toxin variants. Toxin characterization is important as different types of BoNT can respond differently to medical countermeasures for botulism, and characterization of the toxin can aid in epidemiologic and forensic investigations. Proteomic techniques have been established to determine the serotype, subtype, or toxin variant of BoNT. These techniques involve digestion of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the peptides, and database searching to identify the BoNT protein. These techniques demonstrate the capability to detect BoNT and its neurotoxin-associated proteins, and differentiate the toxin from other toxins which are up to 99.9% identical in some cases. This differentiation can be accomplished from toxins present in a complex matrix such as stool, food, or bacterial cultures and no DNA is required.
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USDA-ARS?s Scientific Manuscript database
Like common bacteriophages, Shiga toxin-producing Escherichia coli (STEC) bacteriophages are viruses that recognize and bind to specific bacterial host (STEC) for propagation. They co-exist with STEC hosts, which cause epidemic food and waterborne illnesses, but may act as host populations limiting ...
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Integrated Environment for Ubiquitous Healthcare and Mobile IPv6 Networks
NASA Astrophysics Data System (ADS)
Cagalaban, Giovanni; Kim, Seoksoo
The development of Internet technologies based on the IPv6 protocol will allow real-time monitoring of people with health deficiencies and improve the independence of elderly people. This paper proposed a ubiquitous healthcare system for the personalized healthcare services with the support of mobile IPv6 networks. Specifically, this paper discusses the integration of ubiquitous healthcare and wireless networks and its functional requirements. This allow an integrated environment where heterogeneous devices such a mobile devices and body sensors can continuously monitor patient status and communicate remotely with healthcare servers, physicians, and family members to effectively deliver healthcare services.
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The Biology of Pichia membranifaciens Killer Toxins
Belda, Ignacio; Ruiz, Javier; Alonso, Alejandro; Marquina, Domingo; Santos, Antonio
2017-01-01
The killer phenomenon is defined as the ability of some yeast to secrete toxins that are lethal to other sensitive yeasts and filamentous fungi. Since the discovery of strains of Saccharomyces cerevisiae capable of secreting killer toxins, much information has been gained regarding killer toxins and this fact has substantially contributed knowledge on fundamental aspects of cell biology and yeast genetics. The killer phenomenon has been studied in Pichia membranifaciens for several years, during which two toxins have been described. PMKT and PMKT2 are proteins of low molecular mass that bind to primary receptors located in the cell wall structure of sensitive yeast cells, linear (1→6)-β-d-glucans and mannoproteins for PMKT and PMKT2, respectively. Cwp2p also acts as a secondary receptor for PMKT. Killing of sensitive cells by PMKT is characterized by ionic movements across plasma membrane and an acidification of the intracellular pH triggering an activation of the High Osmolarity Glycerol (HOG) pathway. On the contrary, our investigations showed a mechanism of killing in which cells are arrested at an early S-phase by high concentrations of PMKT2. However, we concluded that induced mortality at low PMKT2 doses and also PMKT is indeed of an apoptotic nature. Killer yeasts and their toxins have found potential applications in several fields: in food and beverage production, as biocontrol agents, in yeast bio-typing, and as novel antimycotic agents. Accordingly, several applications have been found for P. membranifaciens killer toxins, ranging from pre- and post-harvest biocontrol of plant pathogens to applications during wine fermentation and ageing (inhibition of Botrytis cinerea, Brettanomyces bruxellensis, etc.). PMID:28333108
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Oligomerization of Clostridium perfringens Epsilon Toxin Is Dependent upon Caveolins 1 and 2
Fennessey, Christine M.; Sheng, Jinsong; Rubin, Donald H.; McClain, Mark S.
2012-01-01
Evidence from multiple studies suggests that Clostridium perfringens ε-toxin is a pore-forming toxin, assembling into oligomeric complexes in the plasma membrane of sensitive cells. In a previous study, we used gene-trap mutagenesis to identify mammalian factors contributing to toxin activity, including caveolin-2 (CAV2). In this study, we demonstrate the importance of caveolin-2 and its interaction partner, caveolin-1 (CAV1), in ε-toxin-induced cytotoxicity. Using CAV2-specific shRNA in a toxin-sensitive human kidney cell line, ACHN, we confirmed that cells deficient in CAV2 exhibit increased resistance to ε-toxin. Similarly, using CAV1-specific shRNA, we demonstrate that cells deficient in CAV1 also exhibit increased resistance to the toxin. Immunoprecipitation of CAV1 and CAV2 from ε-toxin-treated ACHN cells demonstrated interaction of both CAV1 and -2 with the toxin. Furthermore, blue-native PAGE indicated that the toxin and caveolins were components of a 670 kDa protein complex. Although ε-toxin binding was only slightly perturbed in caveolin-deficient cells, oligomerization of the toxin was dramatically reduced in both CAV1- and CAV2-deficient cells. These results indicate that CAV1 and -2 potentiate ε-toxin induced cytotoxicity by promoting toxin oligomerization – an event which is requisite for pore formation and, by extension, cell death. PMID:23056496
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Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2.
Fennessey, Christine M; Sheng, Jinsong; Rubin, Donald H; McClain, Mark S
2012-01-01
Evidence from multiple studies suggests that Clostridium perfringens ε-toxin is a pore-forming toxin, assembling into oligomeric complexes in the plasma membrane of sensitive cells. In a previous study, we used gene-trap mutagenesis to identify mammalian factors contributing to toxin activity, including caveolin-2 (CAV2). In this study, we demonstrate the importance of caveolin-2 and its interaction partner, caveolin-1 (CAV1), in ε-toxin-induced cytotoxicity. Using CAV2-specific shRNA in a toxin-sensitive human kidney cell line, ACHN, we confirmed that cells deficient in CAV2 exhibit increased resistance to ε-toxin. Similarly, using CAV1-specific shRNA, we demonstrate that cells deficient in CAV1 also exhibit increased resistance to the toxin. Immunoprecipitation of CAV1 and CAV2 from ε-toxin-treated ACHN cells demonstrated interaction of both CAV1 and -2 with the toxin. Furthermore, blue-native PAGE indicated that the toxin and caveolins were components of a 670 kDa protein complex. Although ε-toxin binding was only slightly perturbed in caveolin-deficient cells, oligomerization of the toxin was dramatically reduced in both CAV1- and CAV2-deficient cells. These results indicate that CAV1 and -2 potentiate ε-toxin induced cytotoxicity by promoting toxin oligomerization - an event which is requisite for pore formation and, by extension, cell death.
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Anthrax toxin-induced rupture of artificial lipid bilayer membranes
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.
2013-01-01
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. PMID:23947891
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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.
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A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity
Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.
2012-01-01
The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.
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A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.
Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J
2012-01-01
The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.
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Structure and Orientation of a Voltage-Sensor Toxin in Lipid Membranes
Jung, Hyun Ho; Jung, Hoi Jong; Milescu, Mirela; Lee, Chul Won; Lee, Seungkyu; Lee, Ju Yeon; Eu, Young-Jae; Kim, Ha Hyung; Swartz, Kenton J.; Kim, Jae Il
2010-01-01
Abstract Amphipathic protein toxins from tarantula venom inhibit voltage-activated potassium (Kv) channels by binding to a critical helix-turn-helix motif termed the voltage sensor paddle. Although these toxins partition into membranes to bind the paddle motif, their structure and orientation within the membrane are unknown. We investigated the interaction of a tarantula toxin named SGTx with membranes using both fluorescence and NMR spectroscopy. Depth-dependent fluorescence-quenching experiments with brominated lipids suggest that Trp30 in SGTx is positioned ∼9 Å from the center of the bilayer. NMR spectra reveal that the inhibitor cystine knot structure of the toxin does not radically change upon membrane partitioning. Transferred cross-saturation NMR experiments indicate that the toxin's hydrophobic protrusion contacts the hydrophobic core of the membrane, whereas most surrounding polar residues remain at interfacial regions of the bilayer. The inferred orientation of the toxin reveals a twofold symmetry in the arrangement of basic and hydrophobic residues, a feature that is conserved among tarantula toxins. These results have important implications for regions of the toxin involved in recognizing membranes and voltage-sensor paddles, and for the mechanisms by which tarantula toxins alter the activity of different types of ion channels. PMID:20643084
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Kiriake, Aya; Suzuki, Yasuko; Nagashima, Yuji; Shiomi, Kazuo
2013-08-01
The crude toxins from three species of venomous fish (lionfish Pterois lunulata, devil stinger Inimicus japonicus and waspfish Hypodytes rubripinnis) belonging to the order Scorpaeniformes exhibited mouse-lethal, hemolytic, edema-forming and nociceptive activities. In view of the antigenic cross-reactivity with the stonefish toxins, the primary structures of the stonefish toxin-like toxins from the three scorpaeniform fish were determined by cDNA cloning using primers designed from the highly conserved sequences of the stonefish toxins. Based on the data obtained in gel filtration, immunoblotting and cDNA cloning, each toxin was judged to be a 160 kDa heterodimer composed of 80 kDa α- and β-subunits. The three scorpaeniform fish toxins contain a B30.2/SPRY domain (∼200 amino acid residues) in the C-terminal region of each subunit, as reported for the toxins from two species of lionfish and two species of stonefish. With respect to the amino acid sequence similarity, the scorpaeniform fish toxins are divided into the following two groups: toxins from three species of lionfish and those from devil stinger, two species of stonefish and waspfish. The phylogenetic tree generated also clearly supports the classification of the toxins. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Cry1Ab toxin production of MON 810 transgenic maize.
Székács, András; Lauber, Eva; Juracsek, Judit; Darvas, Béla
2010-01-01
Levels of Cry1Ab toxin were detected in genetically modified maize of genetic event MON 810 against near isogenic maize as negative control by two commercial immunoassays. The immunoassays were characterized for their cross-reactivity (CR) between Cry1Ab protoxin and activated toxin, and were compared with each other for toxin detection in a reference plant sample. Cry1Ab toxin levels, corrected for active toxin content using the CR values obtained, were monitored in maize DK-440 BTY through the entire vegetation period. The toxin concentration was found to show a rapid rise in the leaves to 17.15 +/- 1.66 microg/g by the end of the fifth week of cultivation, followed by a gradual decline to 9.61 +/- 2.07 microg/g by the 16th week and a slight increase again to 13.51 +/- 1.96 microg/g during the last 2 weeks due to partial desiccation. Similar but lesser fluctuation of toxin levels was seen in the roots between 5.32 +/- 0.49 microg/g at the less differentiated V1 stage and 2.25 +/- 0.30 microg/g during plant development. In contrast, Cry1Ab toxin levels appeared to be stably 1.36 +/- 0.45, 4.98 +/- 0.31, 0.47 +/- 0.03, and 0.83 +/- 0.15 microg/g in the stem, anther wall, pollen, and grain, respectively. Toxin concentrations produced at the VT-R4 phenological stages under actual cultivation conditions were compared with each other in three different years within an 8-year period.
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Detoxification of toxins by bacillithiol in Staphylococcus aureus
Newton, Gerald L.; Fahey, Robert C.
2012-01-01
Bacillithiol (BSH), an α-anomeric glycoside of l-cysteinyl-d-glucosaminyl-l-malate, is a major low-molecular-mass thiol found in bacteria such as Bacillus sp., Staphylococcus aureus and Deinococcus radiodurans. Like other low-molecular-mass thiols such as glutathione and mycothiol, BSH is likely to be involved in protection against environmental toxins including thiol-reactive antibiotics. We report here a BSH-dependent detoxification mechanism in S. aureus. When S. aureus Newman strain was treated with monobromobimane and monochlorobimane, the cellular BSH was converted to the fluorescent S-conjugate BS-bimane. A bacillithiol conjugate amidase activity acted upon the BS-bimane to produce Cys-bimane, which was then acetylated by an N-acetyltransferase to generate N-acetyl-Cys-bimane, a mercapturic acid. An S. aureus mutant lacking BSH did not produce mercapturic acid when treated with monobromobimane and monochlorobimane, confirming the involvement of bacillithiol. Furthermore, treatment of S. aureus Newman with rifamycin, the parent compound of the first-line anti-tuberculosis drug, rifampicin, indicated that this thiol-reactive antibiotic is also detoxified in a BSH-dependent manner, since mercapturic acids of rifamycin were observed in the culture medium. These data indicate that toxins and thiol-reactive antibiotics are detoxified to less potent mercapturic acids in a BSH-dependent manner and then exported out of the cell in S. aureus. PMID:22262099
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From Learning Object to Learning Cell: A Resource Organization Model for Ubiquitous Learning
ERIC Educational Resources Information Center
Yu, Shengquan; Yang, Xianmin; Cheng, Gang
2013-01-01
The key to implementing ubiquitous learning is the construction and organization of learning resources. While current research on ubiquitous learning has primarily focused on concept models, supportive environments and small-scale empirical research, exploring ways to organize learning resources to make them available anywhere on-demand is also…
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Tetanus toxin is labeled with photoactivatable phospholipids at low pH
DOE Office of Scientific and Technical Information (OSTI.GOV)
Montecucco, C.; Schiavo, G.; Brunner, J.
1986-02-25
The mechanism of cell penetration by tetanus toxin is unknown; it has been suggested that the toxin may penetrate into the lipid bilayer from a low-pH vesicular compartment. In this work, the interaction of tetanus toxin with liposomal model membranes has been studied by following its photoinduced cross-linking with either a nitrene or a carbene photolytically generated from corresponding light-sensitive phosphatidylcholine analogues. The toxin was labeled only at pHs lower than 5.5. The low pH acquired hydrophobicity of tetanus toxin appears to be confined to its light chain and to the 45-kDa NH2-terminal fragment of the heavy chain. Negatively chargedmore » lipids promote the interaction of this toxin with the hydrocarbon chain of phospholipids. The relevance of the present findings to the possible mechanism of nerve cell penetration by tetanus toxin is discussed.« less
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ERIC Educational Resources Information Center
Liu, Tsung-Yu; Chu, Yu-Ling
2010-01-01
This paper reports the results of a study which aimed to investigate how ubiquitous games influence English learning achievement and motivation through a context-aware ubiquitous learning environment. An English curriculum was conducted on a school campus by using a context-aware ubiquitous learning environment called the Handheld English Language…
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Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jorgensen, Rene; Purdy, Alexandra E.; Fieldhouse, Robert J.
2008-07-15
The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC50 = 4.6 {+-} 0.4 ng/ml) and crustaceans (Artemia nauplii LD50 = 10 {+-} 2 {mu}g/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity againstmore » ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-{angstrom} resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.« less
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Russo, Lisa M.; Melton-Celsa, Angela R.; Smith, Michael J.; O'Brien, Alison D.
2014-01-01
Shiga toxin (Stx)-producing E. coli (STEC) cause food-borne outbreaks of hemorrhagic colitis. The main virulence factor expressed by STEC, Stx, is an AB5 toxin that has two antigenically distinct forms, Stx1a and Stx2a. Although Stx1a and Stx2a bind to the same receptor, globotriaosylceramide (Gb3), Stx2a is more potent than Stx1a in mice, whereas Stx1a is more cytotoxic than Stx2a in cell culture. In this study, we used chimeric toxins to ask what the relative contribution of individual Stx subunits is to the differential toxicity of Stx1a and Stx2a in vitro and in vivo. Chimeric stx1/stx2 operons were generated by PCR such that the coding regions for the A2 and B subunits of one toxin were combined with the coding region for the A1 subunit of the heterologous toxin. The toxicities of purified Stx1a, Stx2a, and the chimeric Stxs were determined on Vero and HCT-8 cell lines, while polarized HCT-8 cell monolayers grown on permeable supports were used to follow toxin translocation. In all in vitro assays, the activity of the chimeric toxin correlated with that of the parental toxin from which the B subunit originated. The origin of the native B subunit also dictated the 50% lethal dose of toxin after intraperitoneal intoxication of mice; however, the chimeric Stxs exhibited reduced oral toxicity and pH stability compared to Stx1a and Stx2a. Taken together, these data support the hypothesis that the differential toxicity of the chimeric toxins for cells and mice is determined by the origin of the B subunit. PMID:24671194
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Binary toxin and its clinical importance in Clostridium difficile infection, Belgium.
Pilate, T; Verhaegen, J; Van Ranst, M; Saegeman, V
2016-11-01
Binary toxin-producing Clostridium difficile strains such as ribotypes 027 and 078 have been associated with increased Clostridium difficile infection (CDI) severity. Our objective was to investigate the association between presence of the binary toxin gene and CDI severity and recurrence. We performed a laboratory-based retrospective study including patients between January 2013 and March 2015 whose fecal samples were analyzed by polymerase chain reaction (PCR) for the presence of the genes for toxin B and binary toxin and a deletion in the tcdC gene, specific for ribotype 027. Clinical and epidemiological characteristics were compared between 33 binary toxin-positive CDI patients and 33 binary toxin-negative CDI patients. Subsequently, the characteristics of 66 CDI patients were compared to those of 66 diarrhea patients who were carriers of non-toxigenic C. difficile strains. Fifty-nine of 1034 (5.7 %) fecal samples analyzed by PCR were binary toxin-positive, belonging to 33 different patients. No samples were positive for ribotype 027. Binary toxin-positive CDI patients did not differ from binary toxin-negative CDI patients in terms of disease recurrence, morbidity, or mortality, except for a higher peripheral leukocytosis in the binary toxin-positive group (16.30 × 10 9 /L vs. 11.65 × 10 9 /L; p = 0.02). The second part of our study showed that CDI patients had more severe disease, but not a higher 30-day mortality rate than diarrhea patients with a non-toxicogenic C. difficile strain. In our setting with a low prevalence of ribotype 027, the presence of the binary toxin gene is not associated with poor outcome.
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Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.
Duarte, Gonçalo S; Castelão, Mafalda; Rodrigues, Filipe B; Marques, Raquel E; Ferreira, Joaquim; Sampaio, Cristina; Moore, Austen P; Costa, João
2016-10-26
This is an update of a Cochrane review first published in 2003. Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterised by painful involuntary head posturing. There are two available formulations of botulinum toxin, with botulinum toxin type A (BtA) usually considered the first line therapy for this condition. Botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason why it might not be as- or even more effective - than BtA. To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia. To identify studies for this review we searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were last run in October 2016. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia. Two independent authors assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed meta-analyses using the random-effects model, for the comparison BtA versus BtB to estimate pooled effects and corresponding 95% confidence intervals (95% CI). No prespecified subgroup analyses were carried out. The primary efficacy outcome was improvement on any validated symptomatic rating scale, and the primary safety outcome was the proportion of participants with adverse events. We included three RCTs, all new to this update, of very low to low methodological quality, with a total of 270 participants.Two studies exclusively enrolled participants with a known positive response to BtA treatment. This raises concerns of population enrichment
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[Botulism: structure and function of botulinum toxin and its clinical application].
Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko
2012-08-01
Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.
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Botulinum toxin in the treatment of vocal fold nodules.
Allen, Jacqui E; Belafsky, Peter C
2009-12-01
Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.
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Discovery of a widely distributed toxin biosynthetic gene cluster
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
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Herrera, Cristina; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J
2016-01-01
JJX12 is an engineered bispecific antibody against ricin, a member of the medically important A-B family of toxins that exploits retrograde transport as means to gain entry into the cytosol of target cells. JJX12 consists of RTA-D10, a camelid single variable domain (VHH) antibody directed against an epitope on ricin's enzymatic subunit (RTA), linked via a 15-mer peptide to RTB-B7, a VHH against ricin's bivalent galactose binding subunit (RTB). We previously reported that JJX12, but not an equimolar mixture of RTA-D10 and RTB-B7 monomers, was able to passively protect mice against a lethal dose ricin challenge, demonstrating that physically linking RTB-B7 and RTA-D10 is critical for toxin-neutralizing activity in vivo. We also reported that JJX12 promotes aggregation of ricin in solution, presumably through the formation of intermolecular crosslinking. In the current study, we now present evidence that JJX12 affects the dynamics of ricin uptake and trafficking in human epithelial cells. Confocal microscopy, as well as live cell imaging coupled with endocytosis pathway-specific inhibitors, revealed that JJX12-toxin complexes are formed on the surfaces of mammalian cells and internalized via a pathway sensitive to amiloride, a known inhibitor of macropinocytosis. Moreover, in the presence of JJX12, retrograde transport of ricin to the trans-Golgi network was significantly reduced, while accumulation of the toxin in late endosomes was significantly enhanced. In summary, we propose that JJX12, by virtue of its ability to crosslink ricin toxin, alters the route of toxin uptake and trafficking within cells.
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Herrera, Cristina; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten
2016-01-01
JJX12 is an engineered bispecific antibody against ricin, a member of the medically important A-B family of toxins that exploits retrograde transport as means to gain entry into the cytosol of target cells. JJX12 consists of RTA-D10, a camelid single variable domain (VHH) antibody directed against an epitope on ricin’s enzymatic subunit (RTA), linked via a 15-mer peptide to RTB-B7, a VHH against ricin’s bivalent galactose binding subunit (RTB). We previously reported that JJX12, but not an equimolar mixture of RTA-D10 and RTB-B7 monomers, was able to passively protect mice against a lethal dose ricin challenge, demonstrating that physically linking RTB-B7 and RTA-D10 is critical for toxin-neutralizing activity in vivo. We also reported that JJX12 promotes aggregation of ricin in solution, presumably through the formation of intermolecular crosslinking. In the current study, we now present evidence that JJX12 affects the dynamics of ricin uptake and trafficking in human epithelial cells. Confocal microscopy, as well as live cell imaging coupled with endocytosis pathway-specific inhibitors, revealed that JJX12-toxin complexes are formed on the surfaces of mammalian cells and internalized via a pathway sensitive to amiloride, a known inhibitor of macropinocytosis. Moreover, in the presence of JJX12, retrograde transport of ricin to the trans-Golgi network was significantly reduced, while accumulation of the toxin in late endosomes was significantly enhanced. In summary, we propose that JJX12, by virtue of its ability to crosslink ricin toxin, alters the route of toxin uptake and trafficking within cells. PMID:27300140
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Network architecture test-beds as platforms for ubiquitous computing.
Roscoe, Timothy
2008-10-28
Distributed systems research, and in particular ubiquitous computing, has traditionally assumed the Internet as a basic underlying communications substrate. Recently, however, the networking research community has come to question the fundamental design or 'architecture' of the Internet. This has been led by two observations: first, that the Internet as it stands is now almost impossible to evolve to support new functionality; and second, that modern applications of all kinds now use the Internet rather differently, and frequently implement their own 'overlay' networks above it to work around its perceived deficiencies. In this paper, I discuss recent academic projects to allow disruptive change to the Internet architecture, and also outline a radically different view of networking for ubiquitous computing that such proposals might facilitate.
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Synthesis of protein in intestinal cells exposed to cholera toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.
1987-11-01
The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells andmore » Chinese hamster ovary cells exposed to cholera toxin. An increase in (/sup 3/H) leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of (/sup 35/S) methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed.« less
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A system for ubiquitous health monitoring in the bedroom via a Bluetooth network and wireless LAN.
Choi, J M; Choi, B H; Seo, J W; Sohn, R H; Ryu, M S; Yi, W; Park, K S
2004-01-01
Advances in information technology have enabled ubiquitous health monitoring at home, which is particularly useful for patients, who have to live alone. We have focused on the automatic and unobtrusive measurement of biomedical signals and activities of patients. We have constructed wireless communication networks in order to transfer data. The networks consist of Bluetooth and Wireless Local Area Network (WLAN). In this paper, we present the concept of a ubiquitous-Bedroom (u-Bedroom) which is a part of a ubiquitous-House (u-House) and we present our systems for ubiquitous health monitoring.
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A vision for ubiquitous sequencing
Erlich, Yaniv
2015-01-01
Genomics has recently celebrated reaching the $1000 genome milestone, making affordable DNA sequencing a reality. With this goal successfully completed, the next goal of the sequencing revolution can be sequencing sensors—miniaturized sequencing devices that are manufactured for real-time applications and deployed in large quantities at low costs. The first part of this manuscript envisions applications that will benefit from moving the sequencers to the samples in a range of domains. In the second part, the manuscript outlines the critical barriers that need to be addressed in order to reach the goal of ubiquitous sequencing sensors. PMID:26430149
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Santussi, Welligton M.; Bordon, Karla C. F.; Rodrigues Alves, Ana P. N.; Cologna, Camila T.; Said, Suraia; Arantes, Eliane C.
2017-01-01
Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A. nidulans, A. niger, A. terreus, Neurospora crassa, Penicillium corylophilum, P. ochrochloron, P. verrucosum, P. viridicatum, P. waksmanii, and Talaromyces flavus) was evaluated by quantitative microplate reader assay. Tsv (100 and 500 μg/well, which correspond to 1 and 5 mg/mL, respectively, of total soluble protein) was active in inhibiting growth of A. nidulans, A. terreus, P. corylophilum, and P. verrucosum, especially in the higher concentration used and at the first 30 h. After this period, fungi might have used Tsv components as alternative sources of nutrients, and therefore, increased their growth tax. Only fractions IX, X, XI, XIIA, XIIB (3 and 7.5 μg/well, which correspond to 30 and 75 μg/mL, respectively, of total soluble protein) and Ts1 (1.5, 3, and 6 μg/well, which correspond to 2.18, 4.36, and 8.72 μM, respectively) showed antifungal activity. Ts1 showed to be a non-morphogenic toxin with dose-dependent activity against A. nidulans, inhibiting 100% of fungal growth from 3 μg/well (4.36 μM). The inhibitory effect of Ts1 against A. nidulans growth was accompanied by fungistatic effects and was not amended by 1 mM CaCl2 or tetrodotoxin (46.98 and 93.96 μM). The structural differences between Ts1 and drosomycin, a potent cysteine-rich antifungal peptide, are discussed here. Our results highlight the antifungal potential of the first cysteine
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Schmidt, Daniel; MacKinnon, Roderick
2008-12-09
Voltage-dependent K(+) (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K(+) channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.
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Evidence of paralytic shellfish poisoning toxin in milkfish in South Taiwan.
Chou, H-N; Chung, Y-C; Cho, W-C; Chen, C-Y
2003-06-01
Natural phytoplankton blooms of the dinoflagellate Alexandrium minutum, milkfish (Chanos chanos) exposed to natural blooms, sediment and mangrove crab (Scylla serrata) were analysed for paralytic shellfish poisoning toxins by high-performance liquid chromatography. The toxin profiles of milkfish and mangrove crab were similar to that of A. minutum collected from blooming fishponds. In a laboratory A. minutum-blooming environment, the stomach and intestine of milkfish accumulated paralytic shellfish poisoning toxins during the exposure period. The non-visceral tissues were non-toxic. However, milkfish lost their entire body burden of toxin on the first day of transferring to a toxic algae-free environment. The result shows that milkfish concentrate paralytic shellfish poisoning toxins in digestive organs and did not retain toxins.
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Environmental Inequality and Pollution Advantage among Immigrants in the United States.
Bakhtsiyarava, Maryia; Nawrotzki, Raphael J
2017-04-01
Environmental inequality scholarship has paid little attention to the disproportional exposure of immigrants in the United States (U.S.) to unfavorable environmental conditions. This study investigates whether new international migrants in the U.S. are exposed to environmental hazards and how this pattern varies among immigrant subpopulations (e.g., Hispanics, Asian, European). We combine sociodemographic information from the American Community Survey with toxicity-weighted chemical concentrations (Toxics Release Inventory) to model the relationship between toxin exposure and the relative population of recent immigrants across Public Use Microdata Areas (PUMAs, n=2,054) during 2005-2011. Results from spatial panel models show that immigrants tend to be less exposed to toxins, suggesting resilience instead of vulnerability. This pattern was pronounced among immigrants from Europe and Latin America (excluding Mexico). However, our results revealed that Mexican immigrants are disproportionately exposed to environmental hazards in wealthy regions.
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Diphtheria toxin-induced channels in Vero cells selective for monovalent cations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sandvig, K.; Olsnes, S.
1988-09-05
Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of /sup 45/Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+,more » K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed.« less
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Fate of Fusarium Toxins during Brewing.
Habler, Katharina; Geissinger, Cajetan; Hofer, Katharina; Schüler, Jan; Moghari, Sarah; Hess, Michael; Gastl, Martina; Rychlik, Michael
2017-01-11
Some information is available about the fate of Fusarium toxins during the brewing process, but only little is known about the single processing steps in detail. In our study we produced beer from two different barley cultivars inoculated with three different Fusarium species, namely, Fusarium culmorum, Fusarium sporotrichioides, and Fusarium avenaceum, producing a wide range of mycotoxins such as type B trichothecenes, type A trichothecenes, and enniatins. By the use of multi-mycotoxin LC-MS/MS stable isotope dilution methods we were able to follow the fate of Fusarium toxins during the entire brewing process. In particular, the type B trichothecenes deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol showed similar behaviors. Between 35 and 52% of those toxins remained in the beer after filtration. The contents of the potentially hazardous deoxynivalenol-3-glucoside and the type A trichothecenes increased during mashing, but a rapid decrease of deoxynivalenol-3-glucoside content was found during the following steps of lautering and wort boiling. The concentration of enniatins greatly decreased with the discarding of spent grains or finally with the hot break. The results of our study show the retention of diverse Fusarium toxins during the brewing process and allow for assessing the food safety of beer regarding the monitored Fusarium mycotoxins.
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Type II toxin: antitoxin systems. More than small selfish entities?
Rocker, Andrea; Meinhart, Anton
2016-05-01
Toxin-antitoxin (TA) modules regulate metabolism and viability of bacteria and archaea. In type II TA systems these functions are generally thought to be performed by two small proteins. However, evidence is increasing that the toxins are much more diverse and can form multi-domain proteins. Recently, we published a novel type II TA system in which toxin and antitoxin are covalently linked into a single polypeptide chain. In this review we summarize the current knowledge on these elongated toxin homologs and provide perspectives for future study.
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Mihaylov, Nikolay L.; Perkins, Douglas D.
2015-01-01
Local environmental grassroots activism is robust and globally ubiquitous despite the ebbs and flows of the general environmental movement. In this review we synthesize social movement, environmental politics, and environmental psychology literatures to answer the following questions: How does the environment emerge as a topic for community action and how a particular environmental discourse (preservation, conservation, public health, Deep Ecology, justice, localism and other responses to modernization and development) becomes dominant? How does a community coalesce around the environmental issue and its particular framing? What is the relationship between local and supralocal (regional, national, global) activism? We contrast “Not in My Back Yard” (NIMBY) activism and environmental liberation and discuss the significance of local knowledge and scale, nature as an issue for activism, place attachment and its disruption, and place-based power inequalities. Environmental psychology contributions to established scholarship on environmental activism are proposed: the components of place attachment are conceptualized in novel ways and a continuous dweller and activist place attachment is elaborated. PMID:25806672
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Mihaylov, Nikolay L; Perkins, Douglas D
2015-03-23
Local environmental grassroots activism is robust and globally ubiquitous despite the ebbs and flows of the general environmental movement. In this review we synthesize social movement, environmental politics, and environmental psychology literatures to answer the following questions: How does the environment emerge as a topic for community action and how a particular environmental discourse (preservation, conservation, public health, Deep Ecology, justice, localism and other responses to modernization and development) becomes dominant? How does a community coalesce around the environmental issue and its particular framing? What is the relationship between local and supralocal (regional, national, global) activism? We contrast "Not in My Back Yard" (NIMBY) activism and environmental liberation and discuss the significance of local knowledge and scale, nature as an issue for activism, place attachment and its disruption, and place-based power inequalities. Environmental psychology contributions to established scholarship on environmental activism are proposed: the components of place attachment are conceptualized in novel ways and a continuous dweller and activist place attachment is elaborated.
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Evolution of Bacillus thuringiensis Cry toxins insecticidal activity.
Bravo, Alejandra; Gómez, Isabel; Porta, Helena; García-Gómez, Blanca Ines; Rodriguez-Almazan, Claudia; Pardo, Liliana; Soberón, Mario
2013-01-01
Insecticidal Cry proteins produced by Bacillus thuringiensis are use worldwide in transgenic crops for efficient pest control. Among the family of Cry toxins, the three domain Cry family is the better characterized regarding their natural evolution leading to a large number of Cry proteins with similar structure, mode of action but different insect specificity. Also, this group is the better characterized regarding the study of their mode of action and the molecular basis of insect specificity. In this review we discuss how Cry toxins have evolved insect specificity in nature and analyse several cases of improvement of Cry toxin action by genetic engineering, some of these examples are currently used in transgenic crops. We believe that the success in the improvement of insecticidal activity by genetic evolution of Cry toxins will depend on the knowledge of the rate-limiting steps of Cry toxicity in different insect pests, the mapping of the specificity binding regions in the Cry toxins, as well as the improvement of mutagenesis strategies and selection procedures. © 2012 The Authors. Microbial Biotechnology © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.
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Modelling toxin effects on protein biosynthesis in eukaryotic cells.
Skakauskas, Vladas; Katauskis, Pranas
2017-08-01
We present a rather generic model for toxin (ricin) inhibition of protein biosynthesis in eukaryotic cells. We also study reduction of the ricin toxic effects with application of antibodies against the RTB subunit of ricin molecules. Both species initially are delivered extracellularly. The model accounts for the pinocytotic and receptor-mediated toxin endocytosis and the intact toxin exocytotic removal out of the cell. The model also includes the lysosomal toxin destruction, the intact toxin motion to the endoplasmic reticulum (ER) for separation of its molecules into the RTA and RTB subunits, and the RTA chain translocation into the cytosol. In the cytosol, one portion of the RTA undergoes degradation via the ERAD. The other its portion can inactivate ribosomes at a large rate. The model is based on a system of deterministic ODEs. The influence of the kinetic parameters on the protein concentration and antibody protection factor is studied in detail. Copyright © 2017 Elsevier Ltd. All rights reserved.
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The Role of Typhoid Toxin in Salmonella Typhi Virulence
Chong, Alexander; Lee, Sohyoung; Yang, Yi-An; Song, Jeongmin
2017-01-01
Unlike many of the nontyphoidal Salmonella serovars such as S. Typhimurium that cause restricted gastroenteritis, Salmonella Typhi is unique in that it causes life-threatening typhoid fever in humans. Despite the vast difference in disease outcomes that S. Typhi and S. Typhimurium cause in humans, there are few genomic regions that are unique to S. Typhi. Of these regions, the most notable is the small locus encoding typhoid toxin, an AB toxin that has several distinct characteristics that contribute to S. Typhi’s pathogenicity. As a result, typhoid toxin and its role in S. Typhi virulence have been studied in an effort to gain insight into potential treatment and prevention strategies. Given the rise of multidrug-resistant strains, research in this area has become increasingly important. This article discusses the current understanding of typhoid toxin and potential directions for future research endeavors in order to better understand the contribution of typhoid toxin to S. Typhi virulence. PMID:28656014
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Treatment of Gastrointestinal Sphincters Spasms with Botulinum Toxin A
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
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Biosecurity reference : CFR-listed agent and toxin summaries.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barnett, Natalie Beth
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.
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The resurgence of botulinum toxin injection for strabismus in children.
Mahan, Marielle; Engel, J Mark
2017-09-01
The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.
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[Toxins of Clostridium perfringens as a natural and bioterroristic threats].
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. © 2015 MEDPRESS.
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Ubiquitous Fast Propagating Intensity Disturbances in Solar Chromosphere
NASA Technical Reports Server (NTRS)
Kubo, M.; Katsukawa, Y.; Suematsu, Y.; Kano, R.; Bando, T.; Narukage, N.; Ishikawa, R.; Hara, H.; Giono, G.; Winebarger, A.;
2016-01-01
High cadence observations by the slit-jaw (SJ) optics system of the sounding rocket experiment "the Chromospheric Lyman Alpha SpectroPolarimeter (CLASP)" reveal ubiquitous intensity disturbances that recurrently propagate in either the chromosphere, transition region, or both at a speed much higher than the sound speed.
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USDA-ARS?s Scientific Manuscript database
Shiga toxin producing Escherichia coli (STEC) is one of the major foodborne pathogens causing serious illnesses, leading to hospitalizations in the United States. Bacteria that are exposed to environmental stresses during food processing may exhibit different growth patterns in subsequent growth env...
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USDA-ARS?s Scientific Manuscript database
Background Shiga toxin (Stx) is a common virulence factor of all Shiga toxin producing E. coli (STEC) that cause a wide spectrum of disease, including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Although several commercial kits are available for detection of Stx produced by STEC, none o...
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Potentiometric chemical sensors for the detection of paralytic shellfish toxins.
Ferreira, Nádia S; Cruz, Marco G N; Gomes, Maria Teresa S R; Rudnitskaya, Alisa
2018-05-01
Potentiometric chemical sensors for the detection of paralytic shellfish toxins have been developed. Four toxins typically encountered in Portuguese waters, namely saxitoxin, decarbamoyl saxitoxin, gonyautoxin GTX5 and C1&C2, were selected for the study. A series of miniaturized sensors with solid inner contact and plasticized polyvinylchloride membranes containing ionophores, nine compositions in total, were prepared and their characteristics evaluated. Sensors displayed cross-sensitivity to four studied toxins, i.e. response to several toxins together with low selectivity. High selectivity towards paralytic shellfish toxins was observed in the presence of inorganic cations with selectivity coefficients ranging from 0.04 to 0.001 for Na + and K + and 3.6*10 -4 to 3.4*10 -5 for Ca 2+ . Detection limits were in the range from 0.25 to 0.9 μmolL -1 for saxitoxin and decarbamoyl saxitoxin, and from 0.08 to 1.8 μmolL -1 for GTX5 and C1&C2, which allows toxin detection at the concentration levels corresponding to the legal limits. Characteristics of the developed sensors allow their use in the electronic tongue multisensor system for simultaneous quantification of paralytic shellfish toxins. Copyright © 2018 Elsevier B.V. All rights reserved.
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Voronina, Olga L.; Kunda, Marina S.; Aksenova, Ekaterina I.; Ryzhova, Natalia N.; Semenov, Andrey N.; Petrov, Evgeny M.; Didenko, Lubov V.; Lunin, Vladimir G.; Ananyina, Yuliya V.; Gintsburg, Alexandr L.
2014-01-01
Background and Aim. Leptospira, the causal agent of leptospirosis, has been isolated from the environment, patients, and wide spectrum of animals in Russia. However, the genetic diversity of Leptospira in natural and anthropurgic foci was not clearly defined. Methods. The recent MLST scheme was used for the analysis of seven pathogenic species. 454 pyrosequencing technology was the base of the whole genome sequencing (WGS). Results. The most wide spread and prevalent Leptospira species in Russia were L. interrogans, L. kirschneri, and L. borgpetersenii. Five STs, common for Russian strains: 37, 17, 199, 110, and 146, were identified as having a longtime and ubiquitous distribution in various geographic areas. Unexpected properties were revealed for the environmental Leptospira strain Bairam-Ali. WGS of this strain genome suggested that it combined the features of the pathogenic and nonpathogenic strains and may be a reservoir of the natural resistance genes. Results of the comparative analysis of rrs and rpoB genes and MLST loci for different Leptospira species strains and phenotypic and serological properties of the strain Bairam-Ali suggested that it represented separate Leptospira species. Conclusions. Thus, the natural and anthropurgic foci supported ubiquitous Leptospira species and the pool of genes important for bacterial adaptivity to various conditions. PMID:25276806
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Peyronnet, Benoit; Castel-Lacanal, Evelyne; Roumiguie, Mathieu; Even, Lucie; Marque, Philippe; Soulié, Michel; Rischmann, Pascal; Game, Xavier
2017-03-01
To compare the outcomes of the first intradetrusor injections of abobotulinum toxin 750 U and onabotulinum toxin 200 and 300 U in patients with neurogenic detrusor overactivity (NDO). A retrospective case-control study was conducted including 211 NDO patients treated in three consecutives eras with onabotulinum toxin 300 U (2004-2006; 80 patients), abobotulinum toxin 750 U (2007-2011; 78 patients) or onabotulinum toxin 200 U (2011-2014; 53 patients). Urodynamic and clinical parameters were compared between groups. The primary endpoint was the rates of success defined as the combination of urgency, urinary incontinence, and detrusor overactivity resolution. When comparing abobotulinum toxin to onabotulinum toxin any doses (200 or 300 U; n = 133), success rates were similar (65.4% vs. 55.6%; P = 0.16). Patients treated with abobotulinum toxin 750 U had higher success rate (65.4% vs. 41.5%; P = 0.007) compared to those who received onabotulinum toxin 200 U. In contrast, there were similar success rates in abobotulinum toxin 750 U and onabotulinum toxin 300 U groups (65.4% vs. 65%; P = 0.91) but with a trend towards longer interval between the first and the second injection in the onabotulinum toxin 300 U group (12.4 vs. 9.3 months; P = 0.09). Intradetrusor injections of abobotulinum toxin 750 U for NDO provided better outcomes than injections of onabotulinum toxin 200 U. Success rates of abobotulinum toxin 750 U and onabotulinum toxin 300 U were similar but interval between injections tended to be longer with onabotulinum toxin 300 U. Neurourol. Urodynam. 36:734-739, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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A Ubiquitous Blood Pressure Sensor Worn at the Ear
NASA Astrophysics Data System (ADS)
Koizumi, Hiroshi; Shimada, Junichi; Uenishi, Yuji; Tochikubo, Osamu
2009-12-01
Blood pressure (BP) measurement and BP control are important for the prevention of lifestyle diseases, especially hypertension, which can lead to more serious conditions, such as cardiac infarction and cerebral apoplexy. The purpose of our study is to develop a ubiquitous blood pressure sensor that is more comfortable and less disruptive of users' daily activities than conventional blood pressure sensors. Our developed sensor is worn at an ear orifice and measures blood pressure at the tragus. This paper describes the concept, configuration, and the optical and electronic details of the developed ear-worn blood pressure sensor and presents preliminary evaluation results. The developed sensor causes almost no discomfort and produces signals whose quality is high enough for detecting BP at an ear, making it suitable for ubiquitous usage.
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Function-based Biosensor for Hazardous Waste Toxin Detection
DOE Office of Scientific and Technical Information (OSTI.GOV)
James J Hickman
There is a need for new types of toxicity sensors in the DOE and other agencies that are based on biological function as the toxins encountered during decontamination or waste remediation may be previously unknown or their effects subtle. Many times the contents of the environmental waste, especially the minor components, have not been fully identified and characterized. New sensors of this type could target unknown toxins that cause death as well as intermediate levels of toxicity that impair function or cause long term impairment that may eventually lead to death. The primary question posed in this grant was tomore » create an electronically coupled neuronal cellular circuit to be used as sensor elements for a hybrid non-biological/biological toxin sensor system. A sensor based on the electrical signals transmitted between two mammalian neurons would allow the marriage of advances in solid state electronics with a functioning biological system to develop a new type of biosensor. Sensors of this type would be a unique addition to the field of sensor technology but would also be complementary to existing sensor technology that depends on knowledge of what is to be detected beforehand. We integrated physics, electronics, surface chemistry, biotechnology, and fundamental neuroscience in the development of this biosensor. Methods were developed to create artificial surfaces that enabled the patterning of discrete cells, and networks of cells, in culture; the networks were then aligned with transducers. The transducers were designed to measure electromagnetic fields (EMF) at low field strength. We have achieved all of the primary goals of the project. We can now pattern neurons routinely in our labs as well as align them with transducers. We have also shown the signals between neurons can be modulated by different biochemicals. In addition, we have made another significant advance where we have repeated the patterning results with adult hippocampal cells. Finally, we
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USDA-ARS?s Scientific Manuscript database
Escherichia coli O111 is an emerging non-O157:H7 Shiga toxin-producing E. coli (STEC). We previously reported that outbreak and environmental, but not sporadic case, strains of STEC O111 share a distinct aggregation phenotype (M. E. Diodati, A. H. Bates, M. B. Cooley, S. Walker, R. E. Mandrell, and ...
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The Sensorial Effect: Dynamics of Emotion in Pro-Environmental Behavior
ERIC Educational Resources Information Center
Hipolito, Joana
2011-01-01
In this article, sensorial effects are introduced as emotional stimuli for shaping environmentally significant behaviors. This research provides a link between sensorial effect as ubiquitous environmental behavior feedback and the effect of sensorial stimuli on emotions that trigger individuals' pro-environment behavior. A case study of using…
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Development of HIHM (Home Integrated Health Monitor) for ubiquitous home healthcare.
Kim, Jung Soo; Kim, Beom Oh; Park, Kwang Suk
2007-01-01
Home Integrated Health Monitor (HIHM) was developed for ubiquitous home healthcare. From quantitative analysis, we have elicited modal of chair. The HIHM could detect Electrocardiogram (ECG) and Photoplethysmography (PPG) non-intrusively. Also, it could estimate blood pressure (BP) non-intrusively, measure blood glucose and ear temperature. Detected signals and information were transmitted to home gateway and home server through Zigbee communication technology. Home server carried them to Healthcare Center, and specialists such as medical doctors could monitor by Internet. There was also feedback system. This device has a potential to study about ubiquitous home healthcare.
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Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro
2010-01-01
The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.
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Binding properties of Clostridium botulinum type C progenitor toxin to mucins.
Nakamura, Toshio; Takada, Noriko; Tonozuka, Takashi; Sakano, Yoshiyuki; Oguma, Keiji; Nishikawa, Atsushi
2007-04-01
It has been reported that Clostridium botulinum type C 16S progenitor toxin (C16S toxin) first binds to the sialic acid on the cell surface of mucin before invading cells [A. Nishikawa, N. Uotsu, H. Arimitsu, J.C. Lee, Y. Miura, Y. Fujinaga, H. Nakada, T. Watanabe, T. Ohyama, Y. Sakano, K. Oguma, The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells, Biochem. Biophys. Res. Commun. 319 (2004) 327-333]. In this study we investigated the binding properties of the C16S toxin to glycoproteins. Although the toxin bound to membrane blotted mucin derived from the bovine submaxillary gland (BSM), which contains a lot of sialyl oligosaccharides, it did not bind to neuraminidase-treated BSM. The binding of the toxin to BSM was inhibited by N-acetylneuraminic acid, N-glycolylneuraminic acid, and sialyl oligosaccharides strongly, but was not inhibited by neutral oligosaccharides. Both sialyl alpha2-3 lactose and sialyl alpha2-6 lactose prevented binding similarly. On the other hand, the toxin also bound well to porcine gastric mucin. In this case, neutral oligosaccharides might play an important role as ligand, since galactose and lactose inhibited binding. These results suggest that the toxin is capable of recognizing a wide variety of oligosaccharide structures.
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Pufferfish mortality associated with novel polar marine toxins in Hawaii
Work, Thierry M.; Moeller, Perer D. R.; Beauchesne, Kevin R.; Dagenais, Julie; Breeden, Renee; Rameyer, Robert; Walsh, Willliam A.; Abecassis, Melanie; Kobayashi, Donald R.; Conway, Carla M.; Winton, James
2017-01-01
Fish die-offs are important signals in tropical marine ecosystems. In 2010, a mass mortality of pufferfish in Hawaii (USA) was dominated by Arothron hispidus showing aberrant neurological behaviors. Using pathology, toxinology, and field surveys, we implicated a series of novel, polar, marine toxins as a likely cause of this mass mortality. Our findings are striking in that (1) a marine toxin was associated with a kill of a fish species that is itself toxic; (2) we provide a plausible mechanism to explain clinical signs of affected fish; and (3) this epizootic likely depleted puffer populations. Whilst our data are compelling, we did not synthesize the toxin de novo, and we were unable to categorically prove that the polar toxins caused mortality or that they were metabolites of an undefined parent compound. However, our approach does provide a template for marine fish kill investigations associated with marine toxins and inherent limitations of existing methods. Our study also highlights the need for more rapid and cost-effective tools to identify new marine toxins, particularly small, highly polar molecules.
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Pufferfish mortality associated with novel polar marine toxins in Hawaii.
Work, Thierry M; Moeller, Peter D R; Beauchesne, Kevin R; Dagenais, Julie; Breeden, Renee; Rameyer, Robert; Walsh, William J; Abecassis, Melanie; Kobayashi, Donald R; Conway, Carla; Winton, James
2017-03-06
Fish die-offs are important signals in tropical marine ecosystems. In 2010, a mass mortality of pufferfish in Hawaii (USA) was dominated by Arothron hispidus showing aberrant neurological behaviors. Using pathology, toxinology, and field surveys, we implicated a series of novel, polar, marine toxins as a likely cause of this mass mortality. Our findings are striking in that (1) a marine toxin was associated with a kill of a fish species that is itself toxic; (2) we provide a plausible mechanism to explain clinical signs of affected fish; and (3) this epizootic likely depleted puffer populations. Whilst our data are compelling, we did not synthesize the toxin de novo, and we were unable to categorically prove that the polar toxins caused mortality or that they were metabolites of an undefined parent compound. However, our approach does provide a template for marine fish kill investigations associated with marine toxins and inherent limitations of existing methods. Our study also highlights the need for more rapid and cost-effective tools to identify new marine toxins, particularly small, highly polar molecules.
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Nanoparticle-conjugated animal venom-toxins and their possible therapeutic potential
Biswas, Archita; Gomes, Aparna; Sengupta, Jayeeta; Datta, Poulami; Singha, Santiswarup; Dasgupta, Anjan Kr; Gomes, Antony
2012-01-01
Nano-medical approaches to develop drugs have attracted much attention in different arenas to design nanoparticle conjugates for better efficacy of the potential bio-molecules. A group of promising candidates of this category would be venom-toxins of animal origin of potential medicinal value. Traditional systems of medicine as well as folklores mention the use of venom-toxins for the treatment of various diseases. Research has led to scientific validation of medicinal applications of venoms-toxins and many active constituents derived from venoms-toxins are already in clinical use or under clinical trial. Nanomedicine is an emerging field of medicine where nanotechnology is used to develop molecules of nano-scale dimension, so that these molecules can be taken up by the cells more easily and have better efficacy, as compared to large molecules that may tend to get eliminated. This review will focus on some of the potential venoms and toxins along with nanoparticle conjugated venom-toxins of snakes, amphibians, scorpions and bees, etc., for possible therapeutic clues against emerging diseases. PMID:23236583
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Naturally acquired antibodies against Clostridium perfringens epsilon toxin in goats.
Veschi, Josir Laine A; Bruzzone, Octavio A; Losada-Eaton, Daniela M; Dutra, Iveraldo S; Fernandez-Miyakawa, Mariano E
2008-09-15
Clostridium perfringens type D-producing epsilon toxin is a common cause of death in sheep and goats worldwide. Although anti-epsilon toxin serum antibodies have been detected in healthy non-vaccinated sheep, the information regarding naturally acquired antibodies in ruminants is scanty. The objective of the present report was to characterize the development of naturally acquired antibodies against C. perfringens epsilon toxin in goats. The levels of anti-epsilon toxin antibodies in blood serum of goat kids from two different herds were examined continuously for 14 months. Goats were not vaccinated against any clostridial disease and received heterologous colostrums from cows that were not vaccinated against any clostridial disease. During the survey one of these flocks suffered an unexpectedly severe C. perfringens type D enterotoxemia outbreak. The results showed that natural acquired antibodies against C. perfringens epsilon toxin can appear as early as 6 weeks in young goats and increase with the age without evidence of clinical disease. The enterotoxemia outbreak was coincident with a significant increase in the level of anti-epsilon toxin antibodies.
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Environmental Toxicity and Poor Cognitive Outcomes in Children and Adults
Liu, Jianghong; Lewis, Gary
2014-01-01
Extensive literature has already documented the deleterious effects of heavy metal toxins on the human brain and nervous system. These toxins, however, represent only a fraction of the environmental hazards that may pose harm to cognitive ability in humans. Lead and mercury exposure, air pollution, and organic compounds all have the potential to damage brain functioning yet remain understudied. In order to provide comprehensive and effective public health and health care initiatives for prevention and treatment, we must first fully understand the potential risks, mechanisms of action, and outcomes surrounding exposure to these elements in the context of neurocognitive ability. This article provides a review of the negative effects on cognitive ability of these lesser-studied environmental toxins, with an emphasis on delineating effects observed in child versus adult populations. Possible differential effects across sociodemographic populations (e.g., urban versus rural residents; ethnic minorities) are discussed as important contributors to risk assessment and the development of prevention measures. The public health and clinical implications are significant and offer ample opportunities for clinicians and researchers to help combat this growing problem. PMID:24645424
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Environmental toxicity and poor cognitive outcomes in children and adults.
Liu, Jianghong; Lewis, Gary
2014-01-01
Extensive literature has already documented the deleterious effects of heavy metal toxins on the human brain and nervous system. These toxins, however, represent only a fraction of the environmental hazards that may pose harm to cognitive ability in humans. Lead and mercury exposure, air pollution, and organic compounds all have the potential to damage brain functioning yet remain understudied. In order to provide comprehensive and effective public health and health care initiatives for prevention and treatment, we must first fully understand the potential risks, mechanisms of action, and outcomes surrounding exposure to these elements in the context of neurocognitive ability. This article provides a review of the negative effects on cognitive ability of these lesser-studied environmental toxins, with an emphasis on delineating effects observed in child versus adult populations. Possible differential effects across sociodemographic populations (e.g., urban versus rural residents; ethnic minorities) are discussed as important contributors to risk assessment and the development of prevention measures. The public health and clinical implications are significant and offer ample opportunities for clinicians and researchers to help combat this growing problem.
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Fungal toxins bind to the URF13 protein in maize mitochondria and Escherichia coli.
Braun, C J; Siedow, J N; Levings, C S
1990-01-01
Expression of the maize mitochondrial T-urf13 gene results in a sensitivity to a family of fungal pathotoxins and to methomyl, a structurally unrelated systemic insecticide. Similar effects of pathotoxins and methomyl are observed when T-urf13 is cloned and expressed in Escherichia coli. An interaction between these compounds and the membrane-bound URF13 protein permeabilizes the inner mitochondrial and bacterial plasma membranes. To understand the toxin-URF13 effects, we have investigated whether toxin specifically binds to the URF13 protein. Our studies indicate that toxin binds to the URF13 protein in maize mitochondria and in E. coli expressing URF13. Binding analysis in E. coli reveals cooperative toxin binding. A low level of specific toxin binding is also demonstrated in cms-T and cms-T-restored mitochondria; however, binding does not appear to be cooperative in maize mitochondria. Competition and displacement studies in E. coli demonstrate that toxin binding is reversible and that the toxins and methomyl compete for the same, or for overlapping, binding sites. Two toxin-insensitive URF13 mutants display a diminished capability to bind toxin in E. coli, which identifies residues of URF13 important in toxin binding. A third toxin-insensitive URF13 mutant shows considerable toxin binding in E. coli, demonstrating that toxin binding can occur without causing membrane permeabilization. Our results indicate that toxin-mediated membrane permeabilization only occurs when toxin or methomyl is bound to URF13. PMID:2136632
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Prisilla, A; Prathiviraj, R; Sasikala, R; Chellapandi, P
2016-10-01
Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 and C3 toxins in addition to botulinum neurotoxins in avian and mammalian cells. C2 and C3 toxins are members of bacterial ADP-ribosyltransferase superfamily, which modify the eukaryotic cell surface proteins by ADP-ribosylation reaction. Herein, the mutant proteins with lack of catalytic and pore forming function derived from C2 (C2I and C2II) and C3 toxins were computationally evaluated to understand their structure-function integrity. We have chosen many structural constraints including local structural environment, folding process, backbone conformation, conformational dynamic sub-space, NAD-binding specificity and antigenic determinants for screening of suitable avirulent toxins. A total of 20 avirulent mutants were identified out of 23 mutants, which were experimentally produced by site-directed mutagenesis. No changes in secondary structural elements in particular to α-helices and β-sheets and also in fold rate of all-β classes. Structural stability was maintained by reordered hydrophobic and hydrogen bonding patterns. Molecular dynamic studies suggested that coupled mutations may restrain the binding affinity to NAD(+) or protein substrate upon structural destabilization. Avirulent toxins of this study have stable energetic backbone conformation with a common blue print of folding process. Molecular docking studies revealed that avirulent mutants formed more favorable hydrogen bonding with the side-chain of amino acids near to conserved NAD-binding core, despite of restraining NAD-binding specificity. Thus, structural constraints in the avirulent toxins would determine their immunogenic nature for the prioritization of protein-based subunit vaccine/immunogens to avian and veterinary animals infected with C. botulinum. Copyright © 2016 Elsevier B.V. All rights reserved.
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Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease
Martinez, Terina N.
2012-01-01
Abstract Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide disease-modifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920–934. PMID:21554057
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Haug, Gerd; Wilde, Christian; Leemhuis, Jost; Meyer, Dieter K; Aktories, Klaus; Barth, Holger
2003-12-30
The Clostridium botulinum C2 toxin is the prototype of the family of binary actin-ADP-ribosylating toxins. C2 toxin is composed of two separated nonlinked proteins. The enzyme component C2I ADP-ribosylates actin in the cytosol of target cells. The binding/translocation component C2II mediates cell binding of the enzyme component and its translocation from acidic endosomes into the cytosol. After proteolytic activation, C2II forms heptameric pores in endosomal membranes, and most likely, C2I translocates through these pores into the cytosol. For this step, the cellular heat shock protein Hsp90 is essential. We analyzed the effect of methotrexate on the cellular uptake of a fusion toxin in which the enzyme dihydrofolate reductase (DHFR) was fused to the C-terminus of C2I. Here, we report that unfolding of C2I-DHFR is required for cellular uptake of the toxin via the C2IIa component. The C2I-DHFR fusion toxin catalyzed ADP-ribosylation of actin in vitro and was able to intoxicate cultured cells when applied together with C2IIa. Binding of the folate analogue methotrexate favors a stable three-dimensional structure of the dihydrofolate reductase domain. Pretreatment of C2I-DHFR with methotrexate prevented cleavage of C2I-DHFR by trypsin. In the presence of methotrexate, intoxication of cells with C2I-DHFR/C2II was inhibited. The presence of methotrexate diminished the translocation of the C2I-DHFR fusion toxin from endosomal compartments into the cytosol and the direct C2IIa-mediated translocation of C2I-DHFR across cell membranes. Methotrexate had no influence on the intoxication of cells with C2I/C2IIa and did not alter the C2IIa-mediated binding of C2I-DHFR to cells. The data indicate that methotrexate prevented unfolding of the C2I-DHFR fusion toxin, and thereby the translocation of methotrexate-bound C2I-DHFR from endosomes into the cytosol of target cells is inhibited.
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Xylella fastidiosa plasmid-encoded PemK toxin is an endoribonuclease.
USDA-ARS?s Scientific Manuscript database
Stable inheritance of pXF-RIV11 in Xylella fastidiosa is conferred by the pemI/pemK plasmid addiction system. PemK serves as a toxin inhibiting bacterial growth; PemI is the corresponding antitoxin that blocks activity of PemK toxin by direct binding. PemK toxin and PemI antitoxin were over-expre...
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Properties of dermonecrotic toxin prepared from sonic extracts Bordetella bronchiseptica.
Kume, K; Nakai, T; Samejima, Y; Sugimoto, C
1986-05-01
A toxin with dermonecrotic activity (DNT) was purified from sonic extracts of Bordetella bronchiseptica L3 of pig origin at phase I by chromatographic and electrophoretic methods. The purification procedure was one developed for obtaining the Pasteurella multocida DNT from sonic extracts with some modifications. Dermonecrotizing activity of B. bronchiseptica-purified DNT was increased by 600-fold compared with that of the crude extract, and the average yield was about 3%. The toxin was homogeneous, as determined by Ouchterlony double immunodiffusion, crossed immunoelectrophoresis, and disk isoelectric focusing in polyacrylamide gels. The toxin gave a single band on polyacrylamide disk gel electrophoresis (PAGE) and sodium dodecyl sulfate-SDS PAGE. The molecular weight of the toxin was ca. 190,000 +/- 5,000, as determined by SDS-PAGE. The isoelectric point of the toxin was ca. 6.5 to 6.6. The minimal necrotizing dose of the toxin for guinea pigs was about 2 ng of protein per 0.1 ml, the 50% lethal dose per mouse was about 0.3 micrograms, and the minimal cytotoxic dose for embryonic bovine lung cells was about 2 ng/ml. The toxin was heat labile and sensitive to inactivation by trypsin, Formalin, and glutaraldehyde. The mildly trypsinized B. bronchiseptica DNT preparation dissociated into two polypeptide chains, with molecular weights of ca. 75,000 +/- 4,000 (fragment 1) and ca. 118,000 +/- 5,000 (fragment 2), after treatment with dithiothreitol-SDS or urea. Upon removal of dithiothreitol and urea from the dissociated DNT preparation, the fragments reassociated, and the DNT that was formed was indistinguishable from the native toxin.
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Characterization of Botulinum Progenitor Toxins by Mass Spectrometry
2005-08-01
and proteases by NTNH to HA-33 assistance in binding to and translocating progenitor toxin(s) through alimentary epithelial barriers (11, 12, 24...performed using peak list files generated by MassLynx (v3.5) and the following parameters: the National Center for Biotechnology Information
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Intragenome Diversity of Gene Families Encoding Toxin-like Proteins in Venomous Animals.
Rodríguez de la Vega, Ricardo C; Giraud, Tatiana
2016-11-01
The evolution of venoms is the story of how toxins arise and of the processes that generate and maintain their diversity. For animal venoms these processes include recruitment for expression in the venom gland, neofunctionalization, paralogous expansions, and functional divergence. The systematic study of these processes requires the reliable identification of the venom components involved in antagonistic interactions. High-throughput sequencing has the potential of uncovering the entire set of toxins in a given organism, yet the existence of non-venom toxin paralogs and the misleading effects of partial census of the molecular diversity of toxins make necessary to collect complementary evidence to distinguish true toxins from their non-venom paralogs. Here, we analyzed the whole genomes of two scorpions, one spider and one snake, aiming at the identification of the full repertoires of genes encoding toxin-like proteins. We classified the entire set of protein-coding genes into paralogous groups and monotypic genes, identified genes encoding toxin-like proteins based on known toxin families, and quantified their expression in both venom-glands and pooled tissues. Our results confirm that genes encoding toxin-like proteins are part of multigene families, and that these families arise by recruitment events from non-toxin genes followed by limited expansions of the toxin-like protein coding genes. We also show that failing to account for sequence similarity with non-toxin proteins has a considerable misleading effect that can be greatly reduced by comparative transcriptomics. Our study overall contributes to the understanding of the evolutionary dynamics of proteins involved in antagonistic interactions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.
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Ubiquitous Learning Ecologies for a Critical Cyber-Citizenship
ERIC Educational Resources Information Center
Díez-Gutiérrez, Enrique; Díaz-Nafría, José-María
2018-01-01
The aim of this research is to identify and analyse the ubiquitous learning acquired through blending education settings devoted to the "lifelong training of trainers" and how these contribute to the development of a conscious, critic and engaged citizenship. Through active exploration of the learning process, the study analyses the…
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Fleming, Lora E.; Kirkpatrick, Barbara; Backer, Lorraine C.; Bean, Judy A.; Wanner, Adam; Dalpra, Dana; Tamer, Robert; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William; Clark, Richard; Zhou, Yue; Henry, Michael S.; Johnson, David; Van De Bogart, Gayl; Bossart, Gregory D.; Harrington, Mark; Baden, Daniel G.
2005-01-01
Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic
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Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Bean, Judy A; Wanner, Adam; Dalpra, Dana; Tamer, Robert; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William; Clark, Richard; Zhou, Yue; Henry, Michael S; Johnson, David; Van De Bogart, Gayl; Bossart, Gregory D; Harrington, Mark; Baden, Daniel G
2005-05-01
Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic
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Office-based endoscopic botulinum toxin injection in laryngeal movement disorders.
Kaderbay, A; Righini, C A; Castellanos, P F; Atallah, I
2018-06-01
Botulinum toxin injection is widely used for the treatment of laryngeal movement disorders. Electromyography-guided percutaneous injection is the technique most commonly used to perform intralaryngeal botulinum toxin injection. We describe an endoscopic approach for intralaryngeal botulinum toxin injection under local anaesthesia without using electromyography. A flexible video-endoscope with an operating channel is used. After local anaesthesia of the larynx by instillation of lidocaine, a flexible needle is inserted into the operating channel in order to inject the desired dose of botulinum toxin into the vocal and/or vestibular folds. Endoscopic botulinum toxin injection under local anaesthesia is a reliable technique for the treatment of laryngeal movement disorders. It can be performed by any laryngologist without the need for electromyography. It is easy to perform for the operator and comfortable for the patient. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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Takagishi, Teruhisa; Oda, Masataka; Takehara, Masaya; Kobayashi, Keiko; Nagahama, Masahiro
2016-11-01
Clostridium perfringens epsilon-toxin is responsible for fatal enterotoxemia in ungulates. The toxin forms a heptamer in the lipid rafts of Madin-Darby Canine Kidney (MDCK) cells, leading to cell death. Here, we showed that epsilon-toxin requires neutral sphingomyelinase (nSMase) activity during oligomerization. We tested the role of nSMase in the oligomerization of epsilon-toxin using specific inhibitors, knockdown of nSMase, formation of ceramide, and localization of epsilon-toxin and ceramide by immunofluorescence staining. Epsilon-toxin induced the production of ceramide is a dose- and time-dependent manner in ACHN cells. GW4869, an inhibitor of nSMase, inhibited ceramide production induced by the toxin. GW4869 and knockdown of nSMase blocked toxin-induced cell death and oligomer formation of epsilon-toxin. Confocal microscopy images showed that the toxin induced ceramide clustering and colocalized with ceramide. These results demonstrated that oligomer formation of epsilon-toxin is facilitated by the production of ceramide through activation of nSMase caused by the toxin. Inhibitors of nSMase may confer protection against infection. Copyright © 2016 Elsevier B.V. All rights reserved.
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Molecular cloning of toxins expressed by the venom gland of Lasiodora sp.
Vieira, A L G; Moura, M B; Babá, E H; Chávez-Olórtegui, C; Kalapothakis, E; Castro, I M
2004-12-15
The present work describes the identification of toxins expressed by the venom gland of the spider Lasiodora sp. The toxins LTx1, LTx2 and LTx3 were identified by the screening of a cDNA library. These toxins showed significant similarity at the amino acid level with spider toxins from Lasiodora parahybana, Eurypelma californicum, Brachypelma smithii, Selenocosmia huwena.
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Effects of Clostridium perfringens iota toxin in the small intestine of mice.
Redondo, Leandro M; Redondo, Enzo A; Dailoff, Gabriela C; Leiva, Carlos L; Díaz-Carrasco, Juan M; Bruzzone, Octavio A; Cangelosi, Adriana; Geoghegan, Patricia; Fernandez-Miyakawa, Mariano E
2017-12-01
Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases. Published by Elsevier Ltd.
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Anti-idiotypic antibodies that protect cells against the action of diphtheria toxin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rolf, J.M.; Gaudin, H.M.; Tirrell, S.M.
1989-03-01
An anti-idiotypic serum prepared against the combining site (idiotype) of specific anti-diphtheria toxoid antibodies was characterized with respect to its interaction with highly diphtheria toxin-sensitive Vero cells. Although the anti-idiotypic serum protected Vero cells against the cytotoxic action of diphtheria toxin, it did not prevent the binding of /sup 125/I-labeled diphtheria toxin to the cells but did inhibit the internalization and degradation of /sup 125/I-labeled toxin. This anti-idiotypic serum immunoprecipitated a cell-surface protein from radiolabeled Vero cells with an apparent Mr of approximately 15,000. These results are consistent with the hypothesis that the anti-idiotypic serum contains antibodies that carry anmore » internal image of an internalization site on the toxin and that a cell-surface protein involved in toxin internalization possesses a complementary site recognized by both the toxin and the anti-idiotypic antibodies.« less
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EFFECT OF MARINE TOXINS ON THERMOREGULATION IN MICE.
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...
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Linden, Jennifer R.; Ma, Yinghua; Zhao, Baohua; Harris, Jason Michael; Rumah, Kareem Rashid; Schaeren-Wiemers, Nicole
2015-01-01
ABSTRACT Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes white matter damage is poorly understood. In this study, we sought to determine the molecular and cellular mechanisms by which ε-toxin causes pathological changes to white matter. In primary CNS cultures, ε-toxin binds to and kills oligodendrocytes but not astrocytes, microglia, or neurons. In cerebellar organotypic culture, ε-toxin induces demyelination, which occurs in a time- and dose-dependent manner, while preserving neurons, astrocytes, and microglia. ε-Toxin specificity for oligodendrocytes was confirmed using enriched glial culture. Sensitivity to ε-toxin is developmentally regulated, as only mature oligodendrocytes are susceptible to ε-toxin; oligodendrocyte progenitor cells are not. ε-Toxin sensitivity is also dependent on oligodendrocyte expression of the proteolipid myelin and lymphocyte protein (MAL), as MAL-deficient oligodendrocytes are insensitive to ε-toxin. In addition, ε-toxin binding to white matter follows the spatial and temporal pattern of MAL expression. A neutralizing antibody against ε-toxin inhibits oligodendrocyte death and demyelination. This study provides several novel insights into the action of ε-toxin in the CNS. (i) ε-Toxin causes selective oligodendrocyte death while preserving all other neural elements. (ii) ε-Toxin-mediated oligodendrocyte death is a cell autonomous effect. (iii) The effects of ε-toxin on the oligodendrocyte lineage are restricted to mature oligodendrocytes. (iv) Expression of the developmentally regulated proteolipid MAL is required for the cytotoxic effects. (v) The cytotoxic effects of ε-toxin can be abrogated by an ε-toxin neutralizing antibody. PMID:26081637
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Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity.
Kalb, Suzanne R; Boyer, Anne E; Barr, John R
2015-08-31
Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A-G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin.
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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.
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Bacterial toxin-antitoxin systems: more than selfish entities?
Van Melderen, Laurence; Saavedra De Bast, Manuel
2009-03-01
Bacterial toxin-antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.
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Botulinum toxin for treatment of the focal dystonia.
Nakamura, Yusaku
2017-07-29
Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.
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Occurrence and sequestration of toxins in food chains.
Mebs, D
1998-11-01
Animals may acquire toxicity by absorbing toxic compounds from their food, e.g. from plants or other animals. Sequestration and accumulation of toxins may provide protection from predators, which learn to avoid this prey because of unpleasant experiences such as bitter taste. This is a common phenomenon in marine as well as in terrestrial ecosystems. Moreover, toxins may enter food chains where they accumulate reaching high, often lethal concentrations. Palytoxin which had been primarily detected in marine zoanthids (Palythoa sp.), occurs also in a wide range of other animals, e.g. in sponges, corals, shellfish, polychaetes and crustaceans, but also in fish, which feed on crustaceans and zoanthids as well. These animals exhibit a high resistance to the toxin's action. The mechanisms which protect the Na+, K+-ATPase of their cell membranes, the primary target of palytoxin, is unknown. Sequestration of the toxin by other animals may cause health problems due to food poisoning.
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Neutralization of B. anthracis toxins during ex vivo phagocytosis.
Tarasenko, Olga; Scott, Ashley; Jones, April; Soderberg, Lee; Alusta, Pierre
2013-07-01
Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.
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Botulinum toxin treatment for facial palsy: A systematic review.
Cooper, Lilli; Lui, Michael; Nduka, Charles
2017-06-01
Facial palsy may be complicated by ipsilateral synkinesis or contralateral hyperkinesis. Botulinum toxin is increasingly used in the management of facial palsy; however, the optimum dose, treatment interval, adjunct therapy and performance as compared with alternative treatments have not been well established. This study aimed to systematically review the evidence for the use of botulinum toxin in facial palsy. The Cochrane central register of controlled trials (CENTRAL), MEDLINE(R) (1946 to September 2015) and Embase Classic + Embase (1947 to September 2015) were searched for randomised studies using botulinum toxin in facial palsy. Forty-seven studies were identified, and three included. Their physical and patient-reported outcomes are described, and observations and cautions are discussed. Facial asymmetry has a strong correlation to subjective domains such as impairment in social interaction and perception of self-image and appearance. Botulinum toxin injections represent a minimally invasive technique that is helpful in restoring facial symmetry at rest and during movement in chronic, and potentially acute, facial palsy. Botulinum toxin in combination with physical therapy may be particularly helpful. Currently, there is a paucity of data; areas for further research are suggested. A strong body of evidence may allow botulinum toxin treatment to be nationally standardised and recommended in the management of facial palsy. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
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Targeting Metastasis with Snake Toxins: Molecular Mechanisms
Urra, Félix A.
2017-01-01
Metastasis involves the migration of cancer cells from a primary tumor to invade and establish secondary tumors in distant organs, and it is the main cause for cancer-related deaths. Currently, the conventional cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. This highlights the need to find new anti-metastatic drugs. Toxins isolated from snake venoms are a natural source of potentially useful molecular scaffolds to obtain agents with anti-migratory and anti-invasive effects in cancer cells. While there is greater evidence concerning the mechanisms of cell death induction of several snake toxin classes on cancer cells; only a reduced number of toxin classes have been reported (i.e., disintegrins/disintegrin-like proteins, C-type lectin-like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells. Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing three targets, which involve (1) inhibition of extracellular matrix components-dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal transition, and (3) inhibition of migration by alterations in the actin/cytoskeleton network. PMID:29189742
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Special issue: engineering toxins for 21st-century therapies: introduction.
Acharya, K Ravi
2011-12-01
This special issue on 'Engineering toxins for 21st century therapies' provides a critical review of the current state of multifaceted aspects of toxin research by some of the leading researchers in the field. It also highlights the clinical potential and challenges for development of novel biologics based on engineered toxin derived products. © 2011 The Author Journal compilation © 2011 FEBS.
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Recent progress in the analysis of uremic toxins by mass spectrometry.
Niwa, Toshimitsu
2009-09-01
Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on recent progress in the analysis of uremic toxins by using MS. Uremic toxins include low-molecular-weight compounds (e.g., indoxyl sulfate, p-cresol sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, asymmetric dimethylarginine), middle-molecular-weight peptides, and proteins modified with advanced glycation and oxidation. These uremic toxins are considered to be involved in a variety of symptoms which may appear in patients with stage 5 chronic kidney disease. Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms.
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Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum
Koon, Hon Wai; Ho, Samantha; Hing, Tressia C.; Cheng, Michelle; Chen, Xinhua; Ichikawa, Yoshi; Kelly, Ciarán P.
2014-01-01
Clostridium difficile infection (CDI) is a common, debilitating infection with high morbidity and mortality. C. difficile causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters C. difficile toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements. C. difficile toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against C. difficile, fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of C. difficile toxins. PMID:24890583
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Conjoint Analysis for Mobile Devices for Ubiquitous Learning in Higher Education: The Korean Case
ERIC Educational Resources Information Center
Lee, Hyeongjik
2013-01-01
Despite the increasing importance of mobile devices in education, the essential features of these devices for ubiquitous learning have not been empirically addressed. This study empirically investigated the necessary conditions for using mobile devices as an educational tool for ubiquitous learning in higher education by a conjoint method. The…
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ERIC Educational Resources Information Center
Wu, Po-Han; Hwang, Gwo-Jen; Tsai, Wen-Hung
2013-01-01
Context-aware ubiquitous learning has been recognized as being a promising approach that enables students to interact with real-world learning targets with supports from the digital world. Several researchers have indicated the importance of providing learning guidance or hints to individual students during the context-aware ubiquitous learning…
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Ubiquitous Health in Korea: Progress, Barriers, and Prospects
Lee, Yountae
2012-01-01
Objectives Korea has one of the most advanced information technology (IT) infrastructures in the world, and the application of IT in health systems is rapidly progressing from computerization to information systems, ubiquitous systems, and smart systems. This study aims to analyze Korean environments in regards to the development of their u-Health industry and propose directions for u-Healthcare services based on this analysis. Methods This paper reviews the background, progress history, and current status of u-Health in Korea, and suggests strategies for the u-Health industry based on an analysis of its barriers and obstacles. Results When u-Health was introduced to Koreans, their policies and approaches focused mainly on environmental factors, yet these efforts have not progressed further to impact the u-Healthcare service industry itself. To develop the u-Healthcare industry, four points need to be considered: the development and support of the practical service model, institutional support, support of core technology and industry, and the institutionalization of health management service. Conclusions Korea is at a strategic point to start building u-Healthcare service delivery models. u-Healthcare is a healthcare service that provides added value through u-Health environments. By identifying critical success factors in u-Healthcare, we can strengthen the u-Health industry and implement policies to coordinate our efforts in the process of value chains to which we belong. PMID:23346474
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Anomericity of T-2 toxin-glucosides; masked mycotoxins in cereal crops
USDA-ARS?s Scientific Manuscript database
T-2 toxin is a trichothecene mycotoxin produced when the fungus Fusarium infects small grains, especially oats. Ingestion of T-2 toxin contaminated grain can cause diarrhea, hemorrhaging, and feed refusal. Cereal crops infected with mycotoxin-producing fungi form toxin glycosides, sometimes called m...
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Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium Channels
Salari, Autoosa; Vega, Benjamin S.; Milescu, Lorin S.; Milescu, Mirela
2016-01-01
Few gating-modifier toxins have been reported to target low-voltage-activated (LVA) calcium channels, and the structural basis of toxin sensitivity remains incompletely understood. Studies of voltage-gated potassium (Kv) channels have identified the S3b–S4 “paddle motif,” which moves at the protein-lipid interface to drive channel opening, as the target for these amphipathic neurotoxins. Voltage-gated calcium (Cav) channels contain four homologous voltage sensor domains, suggesting multiple toxin binding sites. We show here that the S3–S4 segments within Cav3.1 can be transplanted into Kv2.1 to examine their individual contributions to voltage sensing and pharmacology. With these results, we now have a more complete picture of the conserved nature of the paddle motif in all three major voltage-gated ion channel types (Kv, Nav, and Cav). When screened with tarantula toxins, the four paddle sequences display distinct toxin binding properties, demonstrating that gating-modifier toxins can bind to Cav channels in a domain specific fashion. Domain III was the most commonly and strongly targeted, and mutagenesis revealed an acidic residue that is important for toxin binding. We also measured the lipid partitioning strength of all toxins tested and observed a positive correlation with their inhibition of Cav3.1, suggesting a key role for membrane partitioning. PMID:27045173
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Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.
Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi
2014-09-03
The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.
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Ubiquitous Mobile Technologies and the Transformation of Schooling
ERIC Educational Resources Information Center
Bjerede, Marie; Atkins, Kristin; Dede, Chris
2010-01-01
This article explores how the Internet and mobile broadband technologies that are transforming the work of business professionals may be applied to the work of teachers and students in K-20 schooling, with similarly transformative outcomes. First, they discuss the ways in which ubiquitous mobile technologies are changing 21st century business.…
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Di Bella, Stefano; Ascenzi, Paolo; Siarakas, Steven; Petrosillo, Nicola; di Masi, Alessandra
2016-01-01
Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies. PMID:27153087
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Study on the context-aware middleware for ubiquitous greenhouses using wireless sensor networks.
Hwang, Jeonghwang; Yoe, Hyun
2011-01-01
Wireless Sensor Network (WSN) technology is one of the important technologies to implement the ubiquitous society, and it could increase productivity of agricultural and livestock products, and secure transparency of distribution channels if such a WSN technology were successfully applied to the agricultural sector. Middleware, which can connect WSN hardware, applications, and enterprise systems, is required to construct ubiquitous agriculture environment combining WSN technology with agricultural sector applications, but there have been insufficient studies in the field of WSN middleware in the agricultural environment, compared to other industries. This paper proposes a context-aware middleware to efficiently process data collected from ubiquitous greenhouses by applying WSN technology and used to implement combined services through organic connectivity of data. The proposed middleware abstracts heterogeneous sensor nodes to integrate different forms of data, and provides intelligent context-aware, event service, and filtering functions to maximize operability and scalability of the middleware. To evaluate the performance of the middleware, an integrated management system for ubiquitous greenhouses was implemented by applying the proposed middleware to an existing greenhouse, and it was tested by measuring the level of load through CPU usage and the response time for users' requests when the system is working.
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Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting α-toxin expression.
Teng, Zihao; Shi, Dongxue; Liu, Huanyu; Shen, Ziying; Zha, Yonghong; Li, Wenhua; Deng, Xuming; Wang, Jianfeng
2017-09-01
α-Toxin, one of the best known pore-forming proteins produced by Staphylococcus aureus (S. aureus), is a critical virulence factor in multiple infections. The necessity of α-toxin for S. aureus pathogenicity suggests that this toxin is an important target for the development of a potential treatment strategy. In this study, we showed that lysionotin, a natural compound, can inhibit the hemolytic activity of culture supernatants by S. aureus by reducing α-toxin expression. Using real-time PCR analysis, we showed that transcription of hla (the gene encoding α-toxin) and agr (the locus regulating hla) was significantly inhibited by lysionotin. Lactate dehydrogenase and live/dead assays indicated that lysionotin effectively protected human alveolar epithelial cells against S. aureus, and in vivo studies also demonstrated that lysionotin can protect mice from pneumonia caused by S. aureus. These findings suggest that lysionotin is an efficient inhibitor of α-toxin expression and shows significant protection against S. aureus in vitro and in vivo. This study supports a potential strategy for the treatment of S. aureus infection by inhibiting the expression of virulence factors and indicates that lysionotin may be a potential treatment for S. aureus pneumonia.