Molecular Analysis of Neurotoxin-Induced Apoptosis

National Research Council Canada - National Science Library

D'Mello, Santosh R

2006-01-01

Apoptosis is a cell-suicide process that is required for the normal development of the nervous system, but that can be aberrantly activated in neurodegenerative diseases and following exposure to neurotoxins...

Therapeutic applications of botulinum neurotoxins in head and neck disorders

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Ahmad Alshadwi

2015-01-01

Conclusion: Botulinum neurotoxin therapy provides viable alternatives to traditional treatment modalities for some conditions affecting the head and neck region that have neurological components. This therapy can overcome some of the morbidities associated with conventional therapy. More research is needed to determine the ideal doses of botulinum neurotoxin to treat different diseases affecting the head and neck regions.

Mechanisms of Resistance to Neurotoxins (Addendum)

National Research Council Canada - National Science Library

Schubert, David

2003-01-01

The toxicity of chemically reactive oxygen species (ROS) is thought to make a significant contribution to the death of nerve cells caused by many neurotoxins as well as in stroke and Parkinson's disease...

Probiotic microorganisms inhibit epithelial cell internalization of botulinum neurotoxin serotype A

Science.gov (United States)

Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that BoNT serotype A (BoNT/A) complex (holotoxin with neurotoxin-associated proteins) bind and transit through the intestinal...

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

Science.gov (United States)

2016-08-26

Each neurotoxin subtype within a serotype cleaves its target substrate at the same single conserved peptide bond, except for BoNT/F5 (Table 2) [55...common for strains of C. botulinum Group III to form a chimeric or hybrid protein that combines elements of BoNT/C and BoNT/D neurotoxin, rather than a...Approved for public release; distribution is unlimited. UNCLASSIFIED 15 reported as BoNT/CD or BoNT/DC chimeric toxins [22]. Two exotoxins

Excitatory amino acid b-N-methylamino-L-alanine is a putative environmental neurotoxin

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VLADIMIR NEDELJKOV

2011-04-01

Full Text Available The amino acid b-N-methylamino-L-alanine (L-BMAA has been associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex in three distinct western Pacific populations. The putative neurotoxin is produced by cyanobacteria, which live symbiotically in the roots of cycad trees. L-BMAA was thought to be a threat only to those few populations whose diet and medicines rely heavily on cycad seeds. However, the recent discovery that cyanobacteria from diverse terrestrial, freshwater, and saltwater ecosystems around the world produce the toxin requires a reassessment of whether it poses a larger health threat. Therefore, it is proposed that monitoring L-BMAA levels in cyanobacteria-contaminated water supplies might be prudent.

Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes

OpenAIRE

Sharma, Shashi K.; Basavanna, Uma; Shukla, Hem D.

2009-01-01

Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among differe...

Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution.

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Skejic, Jure; Steer, David L; Dunstan, Nathan; Hodgson, Wayne C

2015-11-06

This study demonstrates a direct role of venom protein expression alteration in the evolution of snake venom toxicity. Avian skeletal muscle contractile response to exogenously administered acetylcholine is completely inhibited upon exposure to South Australian and largely preserved following exposure to Queensland eastern brown snake Pseudonaja textilis venom, indicating potent postsynaptic neurotoxicity of the former and lack thereof of the latter venom. Label-free quantitative proteomics reveals extremely large differences in the expression of postsynaptic three-finger α-neurotoxins in these venoms, explaining the difference in the muscle contractile response and suggesting that the type of toxicity induced by venom can be modified by altered expression of venom proteins. Furthermore, the onset of neuromuscular paralysis in the rat phrenic nerve-diaphragm preparation occurs sooner upon exposure to the venom (10 μg/mL) with high expression of α-neurotoxins than the venoms containing predominately presynaptic β-neurotoxins. The study also finds that the onset of rat plasma coagulation is faster following exposure to the venoms with higher expression of venom prothrombin activator subunits. This is the first quantitative proteomic study that uses extracted ion chromatogram peak areas (MS1 XIC) of distinct homologous tryptic peptides to directly show the differences in the expression of venom proteins.

New Typical Vector of Neurotoxin β-N-Methylamino-l-Alanine (BMAA in the Marine Benthic Ecosystem

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Aifeng Li

2016-11-01

Full Text Available The neurotoxin β-N-methylamino-l-alanine (BMAA has been identified as an environmental factor triggering neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS and Alzheimer’s disease (AD. We investigated the possible vectors of BMAA and its isomers 2,4-diaminobutyric acid (DAB and N-2(aminoethylglycine (AEG in marine mollusks collected from the Chinese coast. Sixty-eight samples of marine mollusks were collected along the Chinese coast in 2016, and were analyzed by an HILIC-MS/MS (hydrophilic interaction liquid chromatography with tandem quadrupole mass spectrometer method without derivatization. BMAA was detected in a total of five samples from three species: Neverita didyma, Solen strictus, and Mytilus coruscus. The top three concentrations of free-form BMAA (0.99~3.97 μg·g−1 wet weight were detected in N. didyma. DAB was universally detected in most of the mollusk samples (53/68 with no species-specific or regional differences (0.051~2.65 μg·g−1 wet weight. No AEG was detected in any mollusk samples tested here. The results indicate that the gastropod N. didyma might be an important vector of the neurotoxin BMAA in the Chinese marine ecosystem. The neurotoxin DAB was universally present in marine bivalve and gastropod mollusks. Since N. didyma is consumed by humans, we suggest that the origin and risk of BMAA and DAB toxins in the marine ecosystem should be further investigated in the future.

Genotoxic and Cytotoxic Effects on the Immune Cells of the Freshwater Bivalve Dreissena polymorpha Exposed to the Environmental Neurotoxin BMAA.

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Lepoutre, Alexandra; Milliote, Nadia; Bonnard, Marc; Palos-Ladeiro, Mélissa; Rioult, Damien; Bonnard, Isabelle; Bastien, Fanny; Faassen, Elisabeth; Geffard, Alain; Lance, Emilie

2018-03-01

The environmental neurotoxin β- N -Methylamino-l-alanine (BMAA) has been pointed out to be involved in human neurodegenerative diseases. This molecule is known to be bioaccumulated by bivalves. However, little data about its toxic effects on freshwater mussels is available, particularly on the hemolymphatic compartment and its hemocyte cells involved in various physiological processes such as immune defenses, digestion and excretion, tissue repair, and shell production. Here we exposed Dreissena polymorpha to dissolved BMAA, at the environmental concentration of 7.5 µg of /mussel/3 days, during 21 days followed by 14 days of depuration in clear water, with the objective of assessing the BMAA presence in the hemolymphatic compartment, as well as the impact of the hemocyte cells in terms of potential cytotoxicity, immunotoxicity, and genotoxiciy. Data showed that hemocytes were in contact with BMAA. The presence of BMAA in hemolymph did not induce significant effect on hemocytes phagocytosis activity. However, significant DNA damage on hemocytes occurred during the first week (days 3 and 8) of BMAA exposure, followed by an increase of hemocyte mortality after 2 weeks of exposure. Those effects might be an indirect consequence of the BMAA-induced oxidative stress in cells. However, DNA strand breaks and mortality did not persist during the entire exposure, despite the BMAA persistence in the hemolymph, suggesting potential induction of some DNA-repair mechanisms.

Genotoxic and Cytotoxic Effects on the Immune Cells of the Freshwater Bivalve Dreissena polymorpha Exposed to the Environmental Neurotoxin BMAA

Directory of Open Access Journals (Sweden)

Alexandra Lepoutre

2018-03-01

Full Text Available The environmental neurotoxin β-N-Methylamino-l-alanine (BMAA has been pointed out to be involved in human neurodegenerative diseases. This molecule is known to be bioaccumulated by bivalves. However, little data about its toxic effects on freshwater mussels is available, particularly on the hemolymphatic compartment and its hemocyte cells involved in various physiological processes such as immune defenses, digestion and excretion, tissue repair, and shell production. Here we exposed Dreissena polymorpha to dissolved BMAA, at the environmental concentration of 7.5 µg of /mussel/3 days, during 21 days followed by 14 days of depuration in clear water, with the objective of assessing the BMAA presence in the hemolymphatic compartment, as well as the impact of the hemocyte cells in terms of potential cytotoxicity, immunotoxicity, and genotoxiciy. Data showed that hemocytes were in contact with BMAA. The presence of BMAA in hemolymph did not induce significant effect on hemocytes phagocytosis activity. However, significant DNA damage on hemocytes occurred during the first week (days 3 and 8 of BMAA exposure, followed by an increase of hemocyte mortality after 2 weeks of exposure. Those effects might be an indirect consequence of the BMAA-induced oxidative stress in cells. However, DNA strand breaks and mortality did not persist during the entire exposure, despite the BMAA persistence in the hemolymph, suggesting potential induction of some DNA-repair mechanisms.

The neurotoxin BMAA in aquatic systems

NARCIS (Netherlands)

Faassen, E.J.

2016-01-01

Eutrophication is a major water quality issue and in many aquatic systems, it leads to the proliferation of toxic phytoplankton species. The neurotoxin β-N-methylamino-L-alanine (BMAA) is one of the compounds that can be present in phytoplankton. BMAA has been suggested to play a role in

Peg Precipitation Coupled with Chromatography is a New and Sufficient Method for the Purification of Botulinum Neurotoxin Type B

Science.gov (United States)

Zhao, Yao; Kang, Lin; Gao, Shan; Gao, Xing; Xin, Wenwen; Wang, Jinglin

2012-01-01

Clostridium botulinum neurotoxins are used to treat a variety of neuro-muscular disorders, as well as in cosmetology. The increased demand requires efficient methods for the production and purification of these toxins. In this study, a new purification process was developed for purifying type B neurotoxin. The kinetics of C.botulinum strain growth and neurotoxin production were determined for maximum yield of toxin. The neurotoxin was purified by polyethylene glycol (PEG) precipitation and chromatography. Based on design of full factorial experiment, 20% (w/v) PEG-6000, 4°C, pH 5.0 and 0.3 M NaCl were optimal conditions to obtain a high recovery rate of 87% for the type B neurotoxin complex, as indicated by a purification factor of 61.5 fold. Furthermore, residual bacterial cells, impurity proteins and some nucleic acids were removed by PEG precipitation. The following purification of neurotoxin was accomplished by two chromatography techniques using Sephacryl™ S-100 and phenyl HP columns. The neurotoxin was recovered with an overall yield of 21.5% and the purification factor increased to 216.7 fold. In addition, a mouse bioassay determined the purified neurotoxin complex possessed a specific toxicity (LD50) of 4.095 ng/kg. PMID:22761863

Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

Science.gov (United States)

Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

2014-04-01

Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (king cobra).

Science.gov (United States)

Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Dieter; Foo, Chun Shin; Rajagopalan, Nandhakishore; Nirthanan, Selvanayagam; Bertrand, Daniel; Sivaraman, J; Kini, R Manjunatha

2010-03-12

Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.

Injectable neurotoxins and fillers: there is no free lunch.

Science.gov (United States)

Emer, Jason; Waldorf, Heidi

2011-01-01

Injection of neurotoxins and filling agents for the treatment of facial aesthetics has increased dramatically during the past few decades due to an increased interest in noninvasive aesthetic improvements. An aging but still youth-oriented population expects effective treatments with minimal recovery time and limited risk of complications. Injectable neurotoxins and soft tissue stimulators and fillers have filled this niche of "lunch-time" procedures. As demand for these procedures has increased, supply has followed with more noncore cosmetic specialty physicians, as well as unsupervised ancillary staff, becoming providers and advertising them as easy fixes. Despite an excellent record of safety and efficacy demonstrated in scores of published studies, injectable agents do carry risks of complications. These procedures require a physician with in-depth knowledge of facial anatomy and injection techniques to ensure patient safety and satisfaction. In general, adverse events are preventable and technique-dependent. Although most adverse events are minor and temporary, more serious complications can occur. The recognition, management, and treatment of poor outcomes are as important as obtaining the best aesthetic results. This review addresses important considerations regarding the complications of injectable neurotoxins and fillers used for "lunch-time" injectable procedures. Copyright © 2011 Elsevier Inc. All rights reserved.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.

Science.gov (United States)

Tehran, Domenico Azarnia; Pirazzini, Marco

2018-05-10

Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip

Directory of Open Access Journals (Sweden)

Domenico Azarnia Tehran

2018-05-01

Full Text Available Botulinum neurotoxins (BoNTs, the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

What is the risk of aluminium as a neurotoxin?

Science.gov (United States)

Exley, Christopher

2014-06-01

Aluminium is neurotoxic. Its free ion, Al(3+) (aq), is highly biologically reactive and uniquely equipped to do damage to essential cellular (neuronal) biochemistry. This unequivocal fact must be the starting point in examining the risk posed by aluminium as a neurotoxin in humans. Aluminium is present in the human brain and it accumulates with age. The most recent research demonstrates that a significant proportion of individuals older than 70 years of age have a potentially pathological accumulation of aluminium somewhere in their brain. What are the symptoms of chronic aluminium intoxication in humans? What if neurodegenerative diseases such as Alzheimer's disease are the manifestation of the risk of aluminium as a neurotoxin? How might such an (outrageous) hypothesis be tested?

Botulinum neurotoxin type A injections for vaginismus secondary to vulvar vestibulitis syndrome.

Science.gov (United States)

Bertolasi, Laura; Frasson, Emma; Cappelletti, Jee Yun; Vicentini, Silvana; Bordignon, Monia; Graziottin, Alessandra

2009-11-01

To investigate whether botulinum neurotoxin type A improves vaginismus and study its efficacy with repeated treatments. Outpatients were referred because standard cognitive-behavioral and medical treatment for vaginismus and vulvar vestibular syndrome failed. From this group, we prospectively recruited consecutive women (n=39) whose diagnostic electromyogram (EMG) recordings from the levator ani muscle showed hyperactivity at rest and reduced inhibition during straining. These women were followed for a mean (+/-standard deviation) of 105 (+/-50) weeks. Recruited patients underwent repeated cycles of botulinum neurotoxin type A injected into the levator ani under EMG guidance and EMG monitoring thereafter. At enrollment and 4 weeks after each cycle, women were asked about sexual intercourse; underwent EMG evaluation and examinations to grade vaginal resistance according to Lamont; and completed a visual analog scale (VAS) for pain, the Female Sexual Function Index Scale, a quality-of-life questionnaire (Short-Form 12 Health Survey), and bowel and bladder symptom assessment. At 4 weeks after the first botulinum neurotoxin type A cycle, the primary outcome measures (the possibility of having sexual intercourse, and levator ani EMG hyperactivity) both improved, as did the secondary outcomes, Lamont scores, VAS, Female Sexual Function Index Scales, Short-Form 12 Health Survey, and bowel-bladder symptoms. These benefits persisted through later cycles. When follow-up ended, 63.2% of the patients completely recovered from vaginismus and vulvar vestibular syndrome, 15.4% still needed reinjections (censored), and 15.4% had dropped out. Botulinum neurotoxin type A is an effective treatment option for vaginismus secondary to vulvar vestibular syndrome refractory to standard cognitive-behavioral and medical management. After patients received botulinum neurotoxin type A, their sexual activity improved and reinjections provided sustained benefits. III.

RNA aptasensor for rapid detection of natively folded type A botulinum neurotoxin.

Science.gov (United States)

Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Lou, Jianlong; Marks, James D; Cai, Shuowei

2013-12-15

A surface plasmon resonance based RNA aptasensor for rapid detection of natively folded type A botulinum neurotoxin is reported. Using detoxified recombinant type A botulinum neurotoxin as the surrogate, the aptasensor detects active toxin within 90 min. The detection limit of the aptasensor in phosphate buffered saline, carrot juice, and fat free milk is 5.8 ng/ml, 20.3 ng/ml and 23.4 ng/ml, respectively, while that in 5-fold diluted human serum is 22.5 ng/ml. Recovery of toxin from disparate sample matrices are within 91-116%. Most significant is the ability of this aptasensor to effectively differentiate the natively folded toxin from denatured, inactive toxin, which is important for homeland security surveillance and threat assessment. The aptasensor is stable for more than 30 days and over 400 injections/regeneration cycles. Such an aptasensor holds great promise for rapid detection of active botulinum neurotoxin for field surveillance due to its robustness, stability and reusability. © 2013 Elsevier B.V. All rights reserved.

Molecular structures and functional relationships in clostridial neurotoxins.

Science.gov (United States)

Swaminathan, Subramanyam

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structures have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here. Journal compilation © 2011 FEBS. No claim to original US government works.

Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses

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Jorge Lago

2015-10-01

Full Text Available Tetrodotoxin (TTX is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. The ingestion of contaminated pufferfish, considered the most delicious fish in Japan, is the usual route of toxicity. This neurotoxin, reported as a threat to human health in Asian countries, has spread to the Pacific and Mediterranean, due to the increase of temperature waters worldwide. TTX, for which there is no known antidote, inhibits sodium channel producing heart failure in many cases and consequently death. In Japan, a regulatory limit of 2 mg eq TTX/kg was established, although the restaurant preparation of “fugu” is strictly controlled by law and only chefs qualified are allowed to prepare the fish. Due to its paralysis effect, this neurotoxin could be used in the medical field as an analgesic to treat some cancer pains.

An Investigation of Immunogenicity of Chitosan-Based Botulinum Neurotoxin E Binding Domain Recombinant Candidate Vaccine via Mucosal Route

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Mohammad Javad Bagheripour

2017-01-01

Full Text Available Background and Objectives: Botulism syndrome is caused by serotypes A-G of neurotoxins of Clostridium genus. Neurotoxin binding domain is an appropriate vaccine candidate due to its immunogenic activity. In this study, the immunogenicity of chitosan-based botulinum neurotoxin E binding domain recombinant candidate vaccine was investigated via mucosal route of administration. Methods: In this experimental study, chitosan nanoparticles containing rBoNT/E protein were synthesized by ionic gelation method and were administered orally and intranasally to mice. After each administration, IgG antibody titer was measured by ELISA method. Finally, all groups were challenged with active botulinum neurotoxin type E. Data were analyzed using Duncan and repeated ANOVA tests. The significance level was considered as p0.05, even intranasal route reduced the immunogenicity.

Neurotoxins from Marine Dinoflagellates: A Brief Review

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Da-Zhi Wang

2008-06-01

Full Text Available Dinoflagellates are not only important marine primary producers and grazers, but also the major causative agents of harmful algal blooms. It has been reported that many dinoflagellate species can produce various natural toxins. These toxins can be extremely toxic and many of them are effective at far lower dosages than conventional chemical agents. Consumption of seafood contaminated by algal toxins results in various seafood poisoning syndromes: paralytic shellfish poisoning (PSP, neurotoxic shellfish poisoning (NSP, amnesic shellfish poisoning (ASP, diarrheic shellfish poisoning (DSP, ciguatera fish poisoning (CFP and azaspiracid shellfish poisoning (ASP. Most of these poisonings are caused by neurotoxins which present themselves with highly specific effects on the nervous system of animals, including humans, by interfering with nerve impulse transmission. Neurotoxins are a varied group of compounds, both chemically and pharmacologically. They vary in both chemical structure and mechanism of action, and produce very distinct biological effects, which provides a potential application of these toxins in pharmacology and toxicology. This review summarizes the origin, structure and clinical symptoms of PSP, NSP, CFP, AZP, yessotoxin and palytoxin produced by marine dinoflagellates, as well as their molecular mechanisms of action on voltage-gated ion channels.

Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation Procedures

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Katharine E. Alter

2017-12-01

Full Text Available Injections of botulinum neurotoxins (BoNTs are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation. Ultrasound (US based imaging based guidance overcomes some of the limitations of traditional techniques. US and/or US combined with traditional guidance techniques is utilized and or recommended by many expert clinicians; authors and in practice guidelines by professional academies. This article reviews the advantages and disadvantages of available guidance techniques including US as well as technical aspects of US guidance and a focused literature review related to US guidance for chemodenervation procedures including BoNTs injection.

On the translocation of botulinum and tetanus neurotoxins across the membrane of acidic intracellular compartments.

Science.gov (United States)

Pirazzini, Marco; Azarnia Tehran, Domenico; Leka, Oneda; Zanetti, Giulia; Rossetto, Ornella; Montecucco, Cesare

2016-03-01

Tetanus and botulinum neurotoxins are produced by anaerobic bacteria of the genus Clostridium and are the most poisonous toxins known, with 50% mouse lethal dose comprised within the range of 0.1-few nanograms per Kg, depending on the individual toxin. Botulinum neurotoxins are similarly toxic to humans and can therefore be considered for potential use in bioterrorism. At the same time, their neurospecificity and reversibility of action make them excellent therapeutics for a growing and heterogeneous number of human diseases that are characterized by a hyperactivity of peripheral nerve terminals. The complete crystallographic structure is available for some botulinum toxins, and reveals that they consist of four domains functionally related to the four steps of their mechanism of neuron intoxication: 1) binding to specific receptors of the presynaptic membrane; 2) internalization via endocytic vesicles; 3) translocation across the membrane of endocytic vesicles into the neuronal cytosol; 4) catalytic activity of the enzymatic moiety directed towards the SNARE proteins. Despite the many advances in understanding the structure-mechanism relationship of tetanus and botulinum neurotoxins, the molecular events involved in the translocation step have been only partially elucidated. Here we will review recent advances that have provided relevant insights on the process and discuss possible models that can be experimentally tested. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. Copyright © 2015. Published by Elsevier B.V.

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

Science.gov (United States)

Kull, Skadi; Schulz, K Melanie; Weisemann, Jasmin; Kirchner, Sebastian; Schreiber, Tanja; Bollenbach, Alexander; Dabrowski, P Wojtek; Nitsche, Andreas; Kalb, Suzanne R; Dorner, Martin B; Barr, John R; Rummel, Andreas; Dorner, Brigitte G

2015-01-01

Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might

Structure-Function Relationship of Hydrophiidae Postsynaptic Neurotoxins

Science.gov (United States)

1992-03-11

Fulde, G. (1987) Clin. Dermatology 5: 118. Tu, A. T. (1985) Detection of the sulfhydryl group in proteins by raman scattering spectroscopic method. J...properties of novel forms lacking tryptophan. J. Biochem. 85: 379-388. Yu, N. T., Lin, T. S., and Tu, A. T. (1975) Laser Raman scattering uf neurotoxins...hardwickii), binds tightly and specifically to the nicotinic acetylcholine receptor (AChR) inhibiting neumuscular transmission and results in muscular

Interaction of a dinoflagellate neurotoxin with voltage-activated ion channels in a marine diatom.

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Kitchen, Sheila A; Bourdelais, Andrea J; Taylor, Alison R

2018-01-01

. Although membrane excitability and the kinetics of action potential currents were unaffected, the permeation of the channels underlying the diatom action potential was significantly altered in the presence of PbTx-3. However, at environmentally relevant concentrations the effects of PbTx- on diatom voltage activated currents and interference of cell signaling through this pathway may be limited. The relative insensitivity of phytoplankton VGCs may be due to divergence of site-5 (the putative PbTx binding site), and in some cases, such as O. sinensis , resistance to toxin effects may be because of evolutionary loss of the 4-domain eukaryote channel, while retaining a single domain bacterial-like VGC that can substitute in the generation of fast action potentials.

Biochemistry of snake venom neurotoxins and their application to the study of synapse. [Neurotoxins isolated from venom of the Formosan banded krait

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Hanley, M.R.

1978-11-01

The crude venom of the Formosan banded krait, Bungarus multicinctus, was separated into eleven lethal protein fractions. Nine fractions were purified to final homogeneous toxins, designated ..cap alpha..-bungarotoxin, ..beta..-bungarotoxin, and toxins 7, 8, 9A, 11, 12, 13, and 14. Three of the toxins, ..cap alpha..-bungarotoxin, 7, and 8, were identified as post-synaptic curarimimetic neurotoxins. The remaining toxins were identified as pre-synaptic neurotoxins. ..cap alpha..-Bungarotoxin, toxin 7, and toxin 8 are all highly stable basic polypeptides of approx. 8000 daltons molecular weight. The pre-synaptic toxins fell into two structural groups: toxin 9A and 14 which were single basic chains of approx. 14,000 daltons, and ..beta..-bungarotoxin, and toxins 11 thru 13 which were composed of two chains of approx. 8000 and approx. 13,000 daltons covalently linked by disulfides. All the pre-synaptic neurotoxins were shown to have intrinsic calcium-dependent phospholipase A activities. Under certain conditions, intact synaptic membranes were hydrolyzed more rapidly than protein-free extracted synaptic-lipid liposomes which, in turn, were hydrolyzed more rapidly than any other tested liposomes. It was speculated that cell-surface arrays of phosphatidyl serine/glycolipids created high affinity target sites for ..beta..-bungarotoxin. Single-chain toxins were found to be qualitatively different from the two-chain toxins in their ability to block the functioning of acetylcholine receptors, and were quantitatively different in their enzymatic and membrane disruptive activities. ..beta..-Bungarotoxin was shown to be an extremely potent neuronal lesioning agent. There was no apparent selectivity for cholinergic over non-cholinergic neurons, nor for nerve terminals over cell bodies. It was suggested that ..beta..-bungarotoxin can be considered a useful new histological tool, which may exhibit some regional selectivity.

Minimal Essential Domains Specifying Toxicity of the Light Chains of Tetanus Toxin and Botulinum Neurotoxin Type A

NARCIS (Netherlands)

Kurazono, Hisao; Mochida, Sumiko; Binz, Thomas; Eisel, Ulrich; Quanz, Martin; Grebenstein, Oliver; Wernars, Karel; Poulain, Bernard; Tauc, Ladislav; Niemann, Heiner

1992-01-01

To define conserved domains within the light (L) chains of clostridial neurotoxins, we determined the sequence of botulinum neurotoxin type B (BoNT/B) and aligned it with those of tetanus toxin (TeTx) and BoNT/A, BoNT/Cl, BoNT/D, and BoNT/E. The L chains of BoNT/B and TeTx share 51.6% identical

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

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Skadi Kull

Full Text Available Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT. Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed

Assembly and function of the botulinum neurotoxin progenitor complex.

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Gu, Shenyan; Jin, Rongsheng

2013-01-01

Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are high molecular weight (up to ~900 kDa) multiprotein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal (GI) tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream.

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones.

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Moran, Yehu; Genikhovich, Grigory; Gordon, Dalia; Wienkoop, Stefanie; Zenkert, Claudia; Ozbek, Suat; Technau, Ulrich; Gurevitz, Michael

2012-04-07

Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin.

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Kumar, Raj; Kukreja, Roshan V; Cai, Shuowei; Singh, Bal R

2014-06-01

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear. Since the endopeptidase domain (light chain; LC) of toxin apparently survives inside the neuronal cells for months, it is important to examine the structural features of this domain to understand its resistance to intracellular degradation. Published crystal structures (both botulinum neurotoxins and endopeptidase domain) have not provided adequate explanation for the intracellular longevity of the domain. Structural features obtained from spectroscopic analysis of LCA and LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation appears to be responsible for their optimal enzymatic activity at 37°C. LCE, on the other hand, was although optimally active at 37°C, but its active conformation differed from the PRIME conformation of LCA and LCB. This study establishes and confirms our earlier finding that an optimally active conformation of these proteins in the form of PRIME exists for the most poisonous poison, botulinum neurotoxin. There are substantial variations in the structural and functional characteristics of these active molten globule related structures among the three BoNT endopeptidases examined. These differential conformations of LCs are important in understanding the fundamental structural features of proteins, and their possible connection to intracellular longevity could provide significant clues for devising new countermeasures and effective therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

Clostridium botulinum neurotoxin type B is heat-stable in milk and not inactivated by pasteurization.

Science.gov (United States)

Rasooly, Reuven; Do, Paula M

2010-12-08

Foodborne botulism is caused by the ingestion of foods containing botulinum neurotoxins (BoNTs). To study the heat stability of Clostridium botulinum neurotoxins, we needed to measure and compare the activity of botulinum neurotoxins, serotypes A and B, under various pasteurization conditions. Currently, the only accepted assay to detect active C. botulinum neurotoxin is an in vivo mouse bioassay, which raises ethical concerns with regard to the use of experimental animals. In this study, noninvasive methods were used to simultaneously detect and distinguish between active BoNT serotypes A and B in one reaction and sample. We developed an enzymatic activity assay employing internally quenched fluorogenic peptides corresponding to SNAP-25, for BoNT-A, and VAMP2, for BoNT-B, as an alternative method to the mouse bioassay. Because each peptide is labeled with different fluorophores, we were able to distinguish between these two toxins. We used this method to analyze the heat stability of BoNT-A and BoNT-B. This study reports that conventional milk pasteurization (63 °C, 30 min) inactivated BoNT serotype A; however, serotype B is heat-stable in milk and not inactivated by pasteurization. Using this activity assay, we also showed that the commonly used food processes such as acidity and pasteurization, which are known to inhibit C. botulinum growth and toxin production, are more effective in inactivating BoNT serotype A than serotype B when conventional pasteurization (63 °C, 30 min) is used.

Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons

Directory of Open Access Journals (Sweden)

Yiangou Y

2011-10-01

inflammatory bowel disease with abdominal pain (P = 0.023, but not in inflammatory bowel disease without abdominal pain (P = 0.77 or in irritable bowel syndrome (P = 0.13. In vitro studies of botulinum neurotoxin A-treated and botulinum neurotoxin E-treated cultured human sensory neurons showed accumulation of cytoplasmic vesicles, neurite loss, and reduced immunofluorescence for the heat and capsaicin receptor, TRPV1. Functional effects included dose-related inhibition of capsaicin responses on calcium imaging after acute treatment with botulinum neurotoxins A and E.Conclusion: Differential levels of SV2A protein expression in clinical disorders may identify potential new targets for botulinum neurotoxin therapy. In vitro studies indicate that treatment with botulinum neurotoxins A and E may affect receptor expression and nociceptor function in sensory neurons.Keywords: SV2A, human, pain, botulinum neurotoxin, neurons

Inhibiting oral intoxication of botulinum neurotoxin A by carbohydrate receptor mimics

Science.gov (United States)

Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes of BoNT intoxication, where BoNT assembles with several auxiliary proteins to surviv...

Inhibition of the nicotinic acetylcholine receptors by cobra venom α-neurotoxins: is there a perspective in lung cancer treatment?

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Angela Alama

Full Text Available Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated.We determined the activity of α-neurotoxins from Naja atra (short-chain neurotoxin, α-cobrotoxin and Naja kaouthia (long-chain neurotoxin, α-cobratoxin in vitro by cytotoxicity measurements in 5 lung cancer cell lines, by colony formation assay with α7nAChRs expressing and non-expressing cell lines and in vivo by assessing tumor growth in an orthotopic Non-Obese Diabetic/Severe Combined Immunodeficient (NOD/SCID mouse model system utilizing different treatment schedules and dosages.No statistically significant reduction in tumor growth was observed in the treatment arms in comparison to the control for both toxins. Paradoxically α-cobrotoxin from Naja atra showed the tendency to enhance tumor growth although, even in this case, the statistical significance was not reached.In conclusion our results show that, in contrast with other reports, the nAChR inhibitors α-cobratoxin from N. kaouthia and α-cobrotoxin from N. atra neither suppressed tumor growth nor prolonged the survival of the treated animals.

Isolation and amino acid sequence of a short-chain neurotoxin from an Australian elapid snake, Pseudechis australis.

OpenAIRE

Takasaki, C; Tamiya, N

1985-01-01

A short-chain neurotoxin Pseudechis australis a (toxin Pa a) was isolated from the venom of an Australian elapid snake Pseudechis australis (king brown snake) by sequential chromatography on CM-cellulose, Sephadex G-50 and CM-cellulose columns. Toxin Pa a has an LD50 (intravenous) value of 76 micrograms/kg body wt. in mice and consists of 62 amino acid residues. The amino acid sequence of Pa a shows considerable homology with those of short-chain neurotoxins of elapid snakes, especially of tr...

Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity.

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Jin, Rongsheng; Rummel, Andreas; Binz, Thomas; Brunger, Axel T

2006-12-21

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the neuroparalytic syndrome of botulism. With a lethal dose of 1 ng kg(-1), they pose a biological hazard to humans and a serious potential bioweapon threat. BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors), which constitute part of the synaptic vesicle fusion machinery. The molecular details of the toxin-cell recognition have been elusive. Here we report the structure of a BoNT in complex with its protein receptor: the receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution. On binding, a helix is induced in the luminal domain which binds to a saddle-shaped crevice on a distal tip of BoNT/B. This crevice is adjacent to the non-overlapping ganglioside-binding site of BoNT/B. Synaptotagmin II interacts with BoNT/B with nanomolar affinity, at both neutral and acidic endosomal pH. Biochemical and neuronal ex vivo studies of structure-based mutations indicate high specificity and affinity of the interaction, and high selectivity of BoNT/B among synaptotagmin I and II isoforms. Synergistic binding of both synaptotagmin and ganglioside imposes geometric restrictions on the initiation of BoNT/B translocation after endocytosis. Our results provide the basis for the rational development of preventive vaccines or inhibitors against these neurotoxins.

Cyanobacterial Neurotoxin β-N-Methylamino-L-alanine (BMAA in Shark Fins

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John Pablo

2012-02-01

Full Text Available Sharks are among the most threatened groups of marine species. Populations are declining globally to support the growing demand for shark fin soup. Sharks are known to bioaccumulate toxins that may pose health risks to consumers of shark products. The feeding habits of sharks are varied, including fish, mammals, crustaceans and plankton. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA has been detected in species of free-living marine cyanobacteria and may bioaccumulate in the marine food web. In this study, we sampled fin clips from seven different species of sharks in South Florida to survey the occurrence of BMAA using HPLC-FD and Triple Quadrupole LC/MS/MS methods. BMAA was detected in the fins of all species examined with concentrations ranging from 144 to 1836 ng/mg wet weight. Since BMAA has been linked to neurodegenerative diseases, these results may have important relevance to human health. We suggest that consumption of shark fins may increase the risk for human exposure to the cyanobacterial neurotoxin BMAA.

Mass Spectrometric Identification and Differentiation of Botulinum Neurotoxins through Toxin Proteomics.

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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.

Rapid microfluidic assay for the detection of botulinum neurotoxin in animal sera

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The potent botulinum neurotoxins (BoNTs) represent a threat to public health and safety. Botulism is a disease caused by BoNT intoxication that results in muscle paralysis that can be fatal. Sensitive assays capable of detecting BoNTs from different substrates and settings are essential to limit f...

Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

Science.gov (United States)

Popov, Dmitri; Maliev, Slava

Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

Dolichospermum and Aphanizomenon as neurotoxins producers in some Russian freshwaters.

Science.gov (United States)

Chernova, Ekaterina; Sidelev, Sergey; Russkikh, Iana; Voyakina, Ekaterina; Babanazarova, Olga; Romanov, Roman; Kotovshchikov, Anton; Mazur-Marzec, Hanna

2017-05-01

Last decades, cyanobacterial blooms have been commonly reported in Russia. Among the boom-forming species, potential toxin producers have been identified. The aim of this paper was to study the presence of neurotoxic compounds - saxitoxins and anatoxin-a - in water bodies from different regions of Russia. We also made attempts to identify the neurotoxin-producing genera. The good convergence of the results obtained by light microscopy, PCR and LC-MS/MS analyses indicated the presence of active neurotoxin producing species in all investigated water bodies. Saxitoxin was detected in phytoplankton from 4 water bodies in Central European Russia and West Siberia, including lake and reservoirs used as a source for potable water. The water bodies differed with the respect of saxitoxin producers which belonged to Aphanizomenon and/or Dolichospermum genera. For the first time, we obtained quantitative data on the intracellular saxitoxin concentration in Russian freshwaters using LC-MS/MS. Anatoxin-a was detected only in lakes of Northwestern Russia. In the eutrophic shallow Lower Suzdal Lake, Aphanizomenon was the stated anatoxin-a-producing genus. In the large shallow artificial hypertrophic Sestroretskij Razliv Lake, it was very likely that both dominant species - Aphanizomenon flos-aquae and Dolichospermum planctonicum - were anatoxin-a producers. Copyright © 2017 Elsevier Ltd. All rights reserved.

An update on neurotoxin products and administration methods.

Science.gov (United States)

Lanoue, Julien; Dong, Joanna; Do, Timothy; Goldenberg, Gary

2016-09-01

Since onabotulinumtoxinA for nonsurgical aesthetic enhancement of glabellar lines was initially reported, the popularity of botulinum neurotoxin (BoNT) products among both clinicians and consumers has rapidly grown, and we have seen several additional BoNT formulations enter the market. As the demand for minimally invasive cosmetic procedures continues to increase, we will see the introduction of additional formulations of BoNT products as well as new delivery devices and administration techniques. In this article, we provide a brief update on current and upcoming BoNT products and also review the literature on novel administration methods based on recently published studies.

Correction of Malocclusion by Botulinum Neurotoxin Injection into Masticatory Muscles

OpenAIRE

Seok, Hyun; Kim, Seong-Gon

2018-01-01

Botulinum toxin (BTX) is a neurotoxin, and its injection in masticatory muscles induces muscle weakness and paralysis. This paralytic effect of BTX induces growth retardation of the maxillofacial bones, changes in dental eruption and occlusion state, and facial asymmetry. Using masticatory muscle paralysis and its effect via BTX, BTX can be used for the correction of malocclusion after orthognathic surgery and mandible fracture. The paralysis of specific masticatory muscles by BTX injection r...

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

Science.gov (United States)

2009-11-01

simulations; (4) synthesis and evaluation of the molecules from Step 2 or 3 (e.g., synthesizing and testing AHP). From synthetic chemistry point of view...2000) Synthesis of 6H-indolo [2,3-b][1,6]naphthyridines and related compounds as the 5-Aza analogues of ellipticine alkaloids . J Org Chem 65: 7977–7983...Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis -Based Computer-Aided Molecular Design

Systematic analysis of snake neurotoxins' functional classification using a data warehousing approach.

Science.gov (United States)

Siew, Joyce Phui Yee; Khan, Asif M; Tan, Paul T J; Koh, Judice L Y; Seah, Seng Hong; Koo, Chuay Yeng; Chai, Siaw Ching; Armugam, Arunmozhiarasi; Brusic, Vladimir; Jeyaseelan, Kandiah

2004-12-12

Sequence annotations, functional and structural data on snake venom neurotoxins (svNTXs) are scattered across multiple databases and literature sources. Sequence annotations and structural data are available in the public molecular databases, while functional data are almost exclusively available in the published articles. There is a need for a specialized svNTXs database that contains NTX entries, which are organized, well annotated and classified in a systematic manner. We have systematically analyzed svNTXs and classified them using structure-function groups based on their structural, functional and phylogenetic properties. Using conserved motifs in each phylogenetic group, we built an intelligent module for the prediction of structural and functional properties of unknown NTXs. We also developed an annotation tool to aid the functional prediction of newly identified NTXs as an additional resource for the venom research community. We created a searchable online database of NTX proteins sequences (http://research.i2r.a-star.edu.sg/Templar/DB/snake_neurotoxin). This database can also be found under Swiss-Prot Toxin Annotation Project website (http://www.expasy.org/sprot/).

Manganese levels during pregnancy and at birth: relation to environmental factors and smoking in a Southwest Quebec population

International Nuclear Information System (INIS)

Takser, Larissa; Lafond, Julie; Bouchard, Maryse; St-Amour, Genevieve; Mergler, Donna

2004-01-01

Manganese (Mn) is both an essential element and a potent neurotoxin. Higher demand during pregnancy leads to increased blood levels. Previous studies have suggested that environmental factors may influence blood Mn levels. As part of a community-based survey of potentially toxic environmental contaminants among pregnant women, the objective of this exploratory study was to examine the Mn status in pregnant women and their newborns with respect to sociodemographic and environmental variables. Pregnant women from Southwest Quebec were recruited in the first or second trimester through the public health prenatal program Mn was analyzed in mother's blood at entry into the study, in the second trimester (for those who entered during the first trimester), and at delivery, as well as in umbilical cord blood and in placental tissue. Sociodemographic data and information about pregnancy were obtained by two questionnaires; the first was administered at study entry and the second a few weeks following birth. Results showed that mothers' Mn blood levels increased significantly during pregnancy and cord blood Mn levels were significantly higher than those for mothers' blood. There was no relation to age. Smokers had significantly lower Mn blood levels compared to nonsmokers at the second trimester. Those who lived in urban and/or agricultural areas had significantly higher levels compared to those who lived in small villages. Those who reported pesticide spraying less than 1 km from their house likewise had significantly higher levels compared to the others. These findings suggest that lifestyle and environmental factors may interfere with the delicate balance and homeostatic mechanisms required to maintain Mn at optimal levels for physiological changes during pregnancy

Innovative mode of action based in vitro assays for detection of marine neurotoxins

NARCIS (Netherlands)

Nicolas, J.A.Y.

2015-01-01

Innovative mode of action based in vitro assays for detection of marine neurotoxins

J. Nicolas, P.J.M. Hendriksen, T.F.H. Bovee, I.M.C.M. Rietjens

Marine biotoxins are naturally occurring compounds produced by particular phytoplankton species. These toxins often accumulate in

Structural basis of the pH-dependent assembly of a botulinum neurotoxin complex.

Science.gov (United States)

Matsui, Tsutomu; Gu, Shenyan; Lam, Kwok-Ho; Carter, Lester G; Rummel, Andreas; Mathews, Irimpan I; Jin, Rongsheng

2014-11-11

Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and releases it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent conformation with limited domain flexibility. Intriguingly, the free form NTNHA-A adopts pH-dependent conformational changes due to a torsional motion of its C-terminal domain. Once forming a complex at acidic pH, they each adopt a stable conformation that is similar to that observed in the crystal structure of the M-PTC. Our results suggest that assembly of the M-PTC depends on the environmental pH and that the complex form of BoNT/A is induced by interacting with NTNHA-A at acidic pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic Diversity Among Botulinum Neurotoxin Producing Clostridial Strains

Energy Technology Data Exchange (ETDEWEB)

Hill, K K; Smith, T J; Helma, C H; Ticknor, L O; Foley, B T; Svennson, R T; Brown, J L; Johnson, E A; Smith, L A; Okinaka, R T; Jackson, P J; Marks, J D

2006-07-06

Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore forming rod-shaped bacteria which have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and even death in humans and various other animal species. A collection of 174 C. botulinum strains were examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT A-G). Analysis of the16S rRNA sequences confirmed earlier reports of at least four distinct genomic backgrounds (Groups I-IV) each of which has independently acquired one or more BoNT serotypes through horizontal gene transfer. AFLP analysis provided higher resolution, and can be used to further subdivide the four groups into sub-groups. Sequencing of the BoNT genes from serotypes A, B and E in multiple strains confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes, and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven serotypes of BoNT were compared and show varying degrees of interrelatedness and recombination as has been previously noted for the NTNH gene which is linked to BoNT. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for treatment of botulism.

Comparison of Toxicological Properties of Botulinum Neurotoxin Serotypes A and B in Mice

Science.gov (United States)

Botulinum neurotoxins (BoNTs) are among the most toxic biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the human foodborne intoxications. In this study, we compared the toxicological properties of BoNT serotype A and B holotoxins and compl...

Environmental communication in business relations

DEFF Research Database (Denmark)

Holgaard, Jette Egelund

in the way, in which a company organise, communicate and learn in order to succeed in business. The ambition level regarding environmental improvements in each strategy can differ. The three strategies are not mutually exclusive; on the contrary, they supplement and support each other. Empirical data...... is collected by means of environmental reports, qualitative questionnaires, and a case study at Grundfos A/S in Denmark. These data will be discussed in relation to the three strategies of environmental communication. Different trends in environmental communication practise are found, and on this basis......, recommendations are made in order to improve environmental communication in business relations....

Maculotoxin: a neurotoxin from the venom glands of the octopus Hapalochlaena maculosa identified as tetrodotoxin.

Science.gov (United States)

Sheumack, D D; Howden, M E; Spence, I; Quinn, R J

1978-01-13

Maculotoxin, a potent neurotoxin isolated from the posterior salivary glands of the blue-ringed octopus. Hapalochlaena maculosa, has now been identified as tetrodotoxin. This is the first reported case in which tetrodotoxin has been found to occur in a venom.

Toxicology and detection methods of the alkaloid neurotoxin produced by cyanobacteria, anatoxin-a.

Science.gov (United States)

Osswald, Joana; Rellán, Sandra; Gago, Ana; Vasconcelos, Vitor

2007-11-01

Freshwater resources are under stress due to naturally occurring conditions and human impacts. One of the consequences is the proliferation of cyanobacteria, microphytoplankton organisms that are capable to produce toxins called cyanotoxins. Anatoxin-a is one of the main cyanotoxins. It is a very potent neurotoxin that was already responsible for some animal fatalities. In this review we endeavor to divulgate much of the internationally published information about toxicology, occurrence and detection methods of anatoxin-a. Cyanobacteria generalities, anatoxin-a occurrence and production as well as anatoxin-a toxicology and its methods of detection are the aspects focused in this review. Remediation of anatoxin-a occurrence will be addressed with a public health perspective. Final remarks call the attention for some important gaps in the knowledge about this neurotoxin and its implication to public health. Alterations of aquatic ecosystems caused by anatoxin-a is also addressed. Although anatoxin-a is not the more frequent cyanotoxin worldwide, it has to be regarded as a health risk that can be fatal to terrestrial and aquatic organisms because of its high toxicity.

Neuronal targeting, internalization, and biological activity of a recombinant atoxic derivative of botulinum neurotoxin A

Science.gov (United States)

Botulinum neurotoxins (BoNT) have the unique capacity to cross epithelial barriers, target neuromuscular junctions, and translocate active metalloprotease component to the cytosol of motor neurons. We have taken advantage of the molecular carriers responsible for this trafficking to create a family ...

Co-expression Network Approach to Studying the Effects of Botulinum Neurotoxin-A.

Science.gov (United States)

Mukund, Kavitha; Ward, Samuel R; Lieber, Richard L; Subramaniam, Shankar

2017-10-16

Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A. Functional analysis revealed enrichment of group 1 with metabolism; group 5 with contradictory functions of atrophy and cellular recovery; and groups 2 and 3 with extracellular matrix (ECM) and non-fast fiber isoforms. Topological positioning of two highly ranked, significantly expressed genes- Dclk1 and Ostalpha within group 5 suggested possible mechanistic roles in recovery from BoNT-A induced atrophy. Phenotypic correlations of groups with titin and myosin protein content further emphasized the effect of BoNT-A on the sarcomeric contraction machinery in early phase of chemodenervation. In summary, our approach revealed a hierarchical functional response to BoNT-A induced paralysis with early metabolic and later ECM responses and identified putative biomarkers associated with chemodenervation. Additionally, our results provide an unbiased validation of the response documented in our previous workBotulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules

Saxitoxin - neurotoxin produkovaný sinicemi v povrchových vodách České republiky

Czech Academy of Sciences Publication Activity Database

Jančula, Daniel; Babica, Pavel; Straková, Lucie; Sadílek, Jan; Maršálek, Blahoslav

2013-01-01

Roč. 63, č. 12 (2013), s. 406-409 ISSN 1211-0760 Grant - others:European Commission(XE) FP/2007-2013 no.2SGA2858 Institutional support: RVO:67985939 Keywords : cyanobacterial toxins * neurotoxin * hazard Subject RIV: EF - Botanics

Effects of algal-produced neurotoxins on metabolic activity in telencephalon, optic tectum and cerebellum of Atlantic salmon (Salmo salar)

International Nuclear Information System (INIS)

Bakke, Marit Jorgensen; Horsberg, Tor Einar

2007-01-01

Neurotoxins from algal blooms have been reported to cause mortality in a variety of species, including sea birds, sea mammals and fish. Farmed fish cannot escape harmful algal blooms and their potential toxins, thus they are more vulnerable for exposure than wild stocks. Sublethal doses of the toxins are likely to affect fish behaviour and may impair cognitive abilities. In the present study, changes in the metabolic activity in different parts of the Atlantic salmon (Salmo salar) brain involved in central integration and cognition were investigated after exposure to sublethal doses of three algal-produced neurotoxins; saxitoxin (STX), brevetoxin (BTX) and domoic acid (DA). Fish were randomly selected to four groups for i.p. injection of saline (control) or one of the neurotoxins STX (10 μg STX/kg bw), BTX (68 μg BTX/kg bw) or DA (6 mg DA/kg bw). In addition, 14 C-2-deoxyglucose was i.m. injected to measure brain metabolic activity by autoradiography. The three regions investigated were telencephalon (Tel), optic tectum (OT) and cerebellum (Ce). There were no differences in the metabolic activity after STX and BTX exposure compared to the control in these regions. However, a clear increase was observed after DA exposure. When the subregions with the highest metabolic rate were pseudocoloured in the three brain regions, the three toxins caused distinct differences in the respective patterns of metabolic activation. Fish exposed to STX displayed similar patterns as the control fish, whereas fish exposed to BTX and DA showed highest metabolic activity in subregions different from the control group. All three neurotoxins affected subregions that are believed to be involved in cognitive abilities in fish

Botulinum neurotoxin formulations: overcoming the confusion

Directory of Open Access Journals (Sweden)

Samizadeh S

2018-05-01

Full Text Available Souphiyeh Samizadeh,1 Koenraad De Boulle2 1Great British Academy of Aesthetic Medicine, London, UK; 2Aalst Dermatology Clinic, Aalst, Belgium Abstract: Botulinum toxin A is produced by anaerobic spore-forming bacteria and is used for various therapeutic and cosmetic purposes. Botulinum toxin A injections are the most popular nonsurgical procedure worldwide. Despite an increased demand for botulinum toxin A injections, the clinical pharmacology and differences in formulation of commonly available products are poorly understood. The various products available in the market are unique and vary in terms of units, chemical properties, biological activities, and weight, and are therefore not interchangeable. For safe clinical practice and to achieve optimal results, the practitioners need to understand the clinical issues of potency, conversion ratio, and safety issues (toxin spread and immunogenicity. In this paper, the basic clinical pharmacology of botulinum toxin A and differences between onabotulinum toxin A, abobotulinum toxin A, and incobotulinum toxin A are discussed. Keywords: botulinum toxin, botulinum neurotoxin, moiety, protein complexes

Molecular diversity of neurotoxins from Clostridium botulinum type D strains.

OpenAIRE

Moriishi, K; Syuto, B; Kubo, S; Oguma, K

1989-01-01

The molecular properties of Clostridium botulinum type D South African (D-SA) were compared with those of neurotoxins from type D strain 1873 (D-1873) and type C strains Stockholm and 6813. D-SA toxin, purified 610-fold from the culture supernatant in an overall yield of 30%, consisted of an intact peptide chain with a molecular weight of 140,000. Limited proteolysis of the toxin by trypsin formed a dichain structure consisting of a light chain (Mr, 50,000) and a heavy chain (Mr, 90,000) link...

Challenges in searching for therapeutics against Botulinum Neurotoxins.

Science.gov (United States)

Pirazzini, Marco; Rossetto, Ornella

2017-05-01

Botulinum neurotoxins (BoNTs) are the most potent toxins known. BoNTs are responsible for botulism, a deadly neuroparalytic syndrome caused by the inactivation of neurotransmitter release at peripheral nerve terminals. Thanks to their specificity and potency, BoNTs are both considered potential bio-weapons and therapeutics of choice for a variety of medical syndromes. Several variants of BoNTs have been identified with individual biological properties and little antigenic relation. This expands greatly the potential of BoNTs as therapeutics but poses a major safety problem, increasing the need for finding appropriate antidotes. Areas covered: The authors describe the multi-step molecular mechanism through which BoNTs enter nerve terminals and discuss the many levels at which the toxins can be inhibited. They review the outcomes of the different strategies adopted to limit neurotoxicity and counter intoxication. Potential new targets arising from the last discoveries of the mechanism of action and the approaches to promote neuromuscular junction recovery are also discussed. Expert opinion: Current drug discovery efforts have mainly focused on BoNT type A and addressed primarily light chain proteolytic activity. Development of pan-BoNT inhibitors acting independently of BoNT immunological properties and targeting a common step of the intoxication process should be encouraged.

CRISPR/Cas9-Mediated Genomic Deletion of the Beta-1, 4 N-acetylgalactosaminyltransferase 1 Gene in Murine P19 Embryonal Carcinoma Cells Results in Low Sensitivity to Botulinum Neurotoxin Type C.

Directory of Open Access Journals (Sweden)

Kentaro Tsukamoto

Full Text Available Botulinum neurotoxins produced by Clostridium botulinum cause flaccid paralysis by inhibiting neurotransmitter release at peripheral nerve terminals. Previously, we found that neurons derived from the murine P19 embryonal carcinoma cell line exhibited high sensitivity to botulinum neurotoxin type C. In order to prove the utility of P19 cells for the study of the intracellular mechanism of botulinum neurotoxins, ganglioside-knockout neurons were generated by deletion of the gene encoding beta-1,4 N-acetylgalactosaminyltransferase 1 in P19 cells using the clustered regularly interspaced short palindromic repeats combined with Cas9 (CRISPR/Cas9 system. By using this system, knockout cells could be generated more easily than with previous methods. The sensitivity of the generated beta-1,4 N-acetylgalactosaminyltransferase 1-depleted P19 neurons to botulinum neurotoxin type C was decreased considerably, and the exogenous addition of the gangliosides GD1a, GD1b, and GT1b restored the susceptibility of P19 cells to botulinum neurotoxin type C. In particular, addition of a mixture of these three ganglioside more effectively recovered the sensitivity of knockout cells compared to independent addition of GD1a, GD1b, or GT1b. Consequently, the genome-edited P19 cells generated by the CRISPR/Cas9 system were useful for identifying and defining the intracellular molecules involved in the toxic action of botulinum neurotoxins.

The environmental neurotoxin β-N-methylamino-l-alanine (l-BMAA) is deposited into birds' eggs.

Science.gov (United States)

Andersson, Marie; Karlsson, Oskar; Brandt, Ingvar

2018-01-01

The neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disorders. BMAA is also a known developmental neurotoxin and research indicates that the sources of human and wildlife exposure may be more diverse than previously anticipated. The aim of the present study was therefore to examine whether BMAA can be transferred into birds' eggs. Egg laying quail were dosed with 14 C-labeled BMAA. The distribution of radioactivity in the birds and their laid eggs was then examined at different time points by autoradiography and phosphoimaging analysis. To evaluate the metabolic stability of the BMAA molecule, the distribution of 14 C-methyl- and 14 C-carboxyl-labeled BMAA were compared. The results revealed a pronounced incorporation of radioactivity in the eggs, predominantly in the yolk but also in the albumen. Imaging analysis showed that the concentrations of radioactivity in the liver decreased about seven times between the 24h and the 72h time points, while the concentrations in egg yolk remained largely unchanged. At 72h the egg yolk contained about five times the concentration of radioactivity in the liver. Both BMAA preparations gave rise to similar distribution pattern in the bird tissues and in the eggs, indicating metabolic stability of the labeled groups. The demonstrated deposition into eggs warrants studies of BMAAs effects on bird development. Moreover, birds' eggs may be a source of human BMAA exposure, provided that the laying birds are exposed to BMAA via their diet. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A

NARCIS (Netherlands)

Benoit, Roger M.; Frey, Daniel; Hilbert, Manuel; Kevenaar, Josta T.|info:eu-repo/dai/nl/338771042; Wieser, Mara M.; Stirnimann, Christian U.; McMillan, David; Ceska, Tom; Lebon, Florence; Jaussi, Rolf; Steinmetz, Michel O.; Schertler, Gebhard F X; Hoogenraad, Casper C.|info:eu-repo/dai/nl/227263502; Capitani, Guido; Kammerer, Richard A.

2014-01-01

Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons. Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders. BoNT/A is probably best known for its use as an antiwrinkle

A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food

Science.gov (United States)

Botulism is a serious foodborne neuroparalyic disease caused by botulinum neurotoxin (BoNT) produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We repo...

Explaining human recreational use of 'pesticides': The neurotoxin regulation model of substance use vs. the hijack model and implications for age and sex differences in drug consumption

Directory of Open Access Journals (Sweden)

Edward H Hagen

2013-11-01

Full Text Available Most globally popular drugs are plant neurotoxins or their close chemical analogs. These compounds evolved to deter, not reward or reinforce, consumption. Moreover, they reliably activate virtually all toxin defense mechanisms, and are thus correctly identified by human neurophysiology as toxins. Acute drug toxicity must therefore play a more central role in drug use theory. We accordingly challenge the popular idea that the rewarding and reinforcing properties of drugs "hijack" the brain, and propose instead that the brain evolved to carefully regulate neurotoxin consumption to minimize fitness costs and maximize fitness benefits. This perspective provides a compelling explanation for the dramatic changes in substance use that occur during the transition from childhood to adulthood, and for pervasive sex differences in substance use: because nicotine and many other plant neurotoxins are teratogenic, children, and to a lesser extent women of childbearing age, evolved to avoid ingesting them. However, during the course of human evolution many adolescents and adults reaped net benefits from regulated intake of plant neurotoxins.

A comparative study on three analytical methods for the determination of the neurotoxin BMAA in cyanobacteria

NARCIS (Netherlands)

Faassen, E.J.; Gillissen, F.; Lurling, M.

2012-01-01

The cyanobacterial neurotoxin ß-N-methylamino-L-alanine (BMAA) has been considered a serious health threat because of its putative role in multiple neurodegenerative diseases. First reports on BMAA concentrations in cyanobacteria were alarming: nearly all cyanobacteria were assumed to contain high

Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons.

Directory of Open Access Journals (Sweden)

Laura Restani

2012-12-01

Full Text Available The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to the different fate of the parental neurotoxins once internalised in motor neurons. Tetanus toxin (TeNT is known to undergo transcytosis into inhibitory interneurons and block the release of inhibitory neurotransmitters in the spinal cord, causing a spastic paralysis. In contrast, botulinum neurotoxins (BoNTs block acetylcholine release at the neuromuscular junction, therefore inducing a flaccid paralysis. Whilst overt experimental evidence supports the sorting of TeNT to the axonal retrograde transport pathway, recent findings challenge the established view that BoNT trafficking is restricted to the neuromuscular junction by highlighting central effects caused by these neurotoxins. These results suggest a more complex scenario whereby BoNTs also engage long-range trafficking mechanisms. However, the intracellular pathways underlying this process remain unclear. We sought to fill this gap by using primary motor neurons either in mass culture or differentiated in microfluidic devices to directly monitor the endocytosis and axonal transport of full length BoNT/A and BoNT/E and their recombinant binding fragments. We show that BoNT/A and BoNT/E are internalised by spinal cord motor neurons and undergo fast axonal retrograde transport. BoNT/A and BoNT/E are internalised in non-acidic axonal carriers that partially overlap with those containing TeNT, following a process that is largely independent of stimulated synaptic vesicle endo-exocytosis. Following intramuscular injection in vivo, BoNT/A and TeNT displayed central effects with a similar time course. Central actions paralleled the peripheral spastic paralysis for TeNT, but lagged behind the onset of flaccid paralysis for BoNT/A. These results suggest that the fast axonal retrograde transport compartment is composed of multifunctional trafficking organelles orchestrating the simultaneous transfer

Structural Analysis of Botulinum Neurotoxin Type G Receptor Binding

Energy Technology Data Exchange (ETDEWEB)

Schmitt, John; Karalewitz, Andrew; Benefield, Desire A.; Mushrush, Darren J.; Pruitt, Rory N.; Spiller, Benjamin W.; Barbieri, Joseph T.; Lacy, D. Borden (Vanderbilt); (MCW)

2010-10-19

Botulinum neurotoxin (BoNT) binds peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype (A-G). BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins. We observe conditions under which BoNT/B binds both Syt isoforms, but BoNT/G binds only SytI. Both serotypes bind ganglioside G{sub T1b}. The BoNT/G receptor-binding domain crystal structure provides a context for examining these binding interactions and a platform for understanding the physiological relevance of different Syt receptor isoforms in vivo.

Update on botulinum neurotoxin use in aesthetic dermatology.

Science.gov (United States)

Ibrahim, Omer; Keller, Emily C; Arndt, Kenneth A

2014-12-01

Botulinum toxins are among the most widely studied and versatile drugs in the medicinal market. Since their extraction from Clostridium botulinum, they have been harnessed and incorporated into different formulations with varied properties and actions. These products have been used to treat countless disorders such as musculoskeletal disorders, headaches, and eye disorders, among many others. In the realm of aesthetic cutaneous medicine, the evolution and creativity in the use of botulinum toxins has been swift and ever changing. Knowledge of the science and innovation behind this toxin enables the user to provide the patient with a variety of treatment options founded in evidence-based medicine. This review will highlight the properties and actions of the newer, more recent neurotoxin preparations, as well as some of the latest and novel therapeutic applications of botulinum toxins.

MOLECULAR-BIOLOGY OF CLOSTRIDIAL TOXINS - EXPRESSION OF MESSENGER-RNAS ENCODING TETANUS AND BOTULINUM NEUROTOXINS IN APLYSIA NEURONS

NARCIS (Netherlands)

MOCHIDA, S; POULAIN, B; EISEL, U; BINZ, T; KURAZONO, H; NIEMANN, H; TAUC, L

1990-01-01

mRNAs encoding the light chain of tetanus and botulinum neurotoxins were transcribed, in vitro, from the cloned and specifically truncated genes of Clostridium tetani and Clostridium botulinum, respectively, and injected into presynaptic identified cholinergic neurons of the buccal ganglia of

Current Status and Future Directions of Botulinum Neurotoxins for Targeting Pain Processing

Directory of Open Access Journals (Sweden)

Sabine Pellett

2015-11-01

Full Text Available Current evidence suggests that botulinum neurotoxins (BoNTs A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics.

Safety and administration of treatment with botulinum neurotoxin for sialorrhoea in ALS patients: Review of the litterature and a proposal for tailored treatment

DEFF Research Database (Denmark)

Stokholm, Morten; Bisgård, Carsten; Vilholm, Ole Jakob

2013-01-01

Botulinum neurotoxin (BoNT) is a second-line treatment of sialorrhoea in ALS (amyotrophic lateral sclerosis) patients. This article is a review of the published literature concerning safety and administration of this treatment to ALS patients. A PubMed search was performed. All original publicati......Botulinum neurotoxin (BoNT) is a second-line treatment of sialorrhoea in ALS (amyotrophic lateral sclerosis) patients. This article is a review of the published literature concerning safety and administration of this treatment to ALS patients. A PubMed search was performed. All original...

A protein chip membrane-capture assay for botulinum neurotoxin activity

International Nuclear Information System (INIS)

Marconi, Severine; Ferracci, Geraldine; Berthomieu, Maelys; Kozaki, Shunji; Miquelis, Raymond; Boucraut, Jose; Seagar, Michael

2008-01-01

Botulinum neurotoxins A and B (BoNT/A and B) are neuromuscular blocking agents which inhibit neurotransmission by cleaving the intra-cellular presynaptic SNARE proteins SNAP-25 and VAMP2, localized respectively in plasma membrane and synaptic vesicles. These neurotoxins are both dangerous pathogens and powerful therapeutic agents with numerous clinical and cosmetic applications. Consequently there is a need for in vitro assays of their biological activity to screen for potential inhibitors and to replace the widely used in vivo mouse assay. Surface plasmon resonance (SPR) was used to measure membrane vesicle capture by antibodies against SNAP-25 and VAMP2. Substrate cleavage by BoNTs modified capture providing a method to assay toxin activity. Firstly using synaptic vesicles as a substrate, a comparison of the EC 50 s for BoNT/B obtained by SPR, ELISA or flow cytometry indicated similar sensitivity although SPR assays were more rapid. Sonication of brain or neuronal cultures generated plasma membrane fragments with accessible intra-cellular epitopes adapted to measurement of BoNT/A activity. SPR responses were proportional to antigen concentration permitting detection of as little as 4 pM SNAP-25 in crude lysates. BoNT/A activity was assayed using monoclonal antibodies that specifically recognize a SNAP-25 epitope generated by the proteolytic action of the toxin. Incubation of intact primary cultured neurons with BoNT/A yielded an EC 50 of 0.5 pM. The SPR biosensor method was sensitive enough to monitor BoNT/A and B activity in cells cultured in a 96-well format providing an alternative to experimental animals for toxicological assays

Botulinum Neurotoxin Detection Methods for Public Health Response and Surveillance

Directory of Open Access Journals (Sweden)

Nagarajan Thirunavukkarasu

2018-06-01

Full Text Available Botulism outbreak due to consumption of food contaminated with botulinum neurotoxins (BoNTs is a public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns due to the potential for high mortality and morbidity. Rapid and reliable detection methods are necessary to support clinical diagnosis and surveillance for identifying the source of contamination, performing epidemiological analysis of the outbreak, preventing and responding to botulism outbreaks. This review considers the applicability of various BoNT detection methods and examines their fitness-for-purpose in safeguarding the public health and security goals.

Beltless Translocation Domain of Botulinum Neurotoxin A Embodies a Minimum Ion-conductive Channel*

OpenAIRE

Fischer, Audrey; Sambashivan, Shilpa; Brunger, Axel T.; Montal, Mauricio

2011-01-01

Botulinum neurotoxin, the causative agent of the paralytic disease botulism, is an endopeptidase composed of a catalytic domain (or light chain (LC)) and a heavy chain (HC) encompassing the translocation domain (TD) and receptor-binding domain. Upon receptor-mediated endocytosis, the LC and TD are proposed to undergo conformational changes in the acidic endocytic environment resulting in the formation of an LC protein-conducting TD channel. The mechanism of channel formation and the conformat...

PCR und ELISA - Alternativen zum Maustest für die Analyse des Botulismus-Neurotoxin-C1 Giftbildungspotentiales in Umweltproben? [PCR and ELISA - in vitro alternatives to the mouse-bioassay for assessing the botulinum-neurotoxin-C1 production potential in environmental samples?

Science.gov (United States)

Zechmeister, T.C.; Farnleitner, A.H.; Rocke, T.E.; Pittner, F.; Rosengarten, R.; Mach, R.L.; Herzig, A.; Kirschner, A.K.T.

2002-01-01

Botulism is one of the most important bird diseases world-wide and is caused by the intoxication with Botulinum-Neurotoxin-C1 (BoNt-C1), which is produced by toxigenic clostridia under appropriate conditions. Avian botulism leads regularly to large losses among the migrating bird populations breeding and resting at the saltwater pools of the Austrian national park Neusiedler See-Seewinkel. Despite of its ethical dubiousness and its high technical expense the mouse-bioassay is still used as the routine standard method for the detection of BoNt-C1. According to the 3R-concept, in vitro alternative methods for the qualitative detection of BoNt-C1 (immunostick-ELISA) and a corresponding BoNt-C1 gene fragment (nested-PCR) were established. In order to estimate the BoNt-C1 production potential the methods were tested with sediment samples from different saltwater pools subjected to cultivation conditions appropriate for in vitro BoNt-C1-production. With the mouse-bioassay, 52 out of 77 samples were found to have a positive toxin production potential. The immunostick-ELISA showed a similar sensitivity as the mouse-bioassay and exhibited a highly significant positive correlation (r=0.94; pELISA (r=0.09; p=0.46). Obviously, the PCR approach detected the BoNt-C1 gene fragment in some of the samples where no toxin expression has occurred. Thus it is suggested that the qualitative immunostick-ELISA represents a potential in vitro alternative to the mouse-bioassay for assessing the BoNt-C1 production potential in environmental samples. In contrast, qualitative BoNt-C1 gene fragment detection via PCR led to an overestimation of the actual toxin production potential.

ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

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D. D. Miniaeva

2014-06-01

Full Text Available This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism. The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, targets, tools, processes. Results of research show that the beginning of the XXI century is distinguished by the development of new types of political concepts that explain interaction of elements in modern international relations in the area of environmental protection. The reason of these changes lies in the phenomena of environmentalism integration into Three paradigms of international relations. However, we cannot say that any of the examined paradigms accumulated all features of environmentalism without their modification. Better to say, it's rather similar to adaptation of environmental ideas. Therefore, to understand modern international relations processes, it is necessary to take into account their environmental element. Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-4

In-Vivo Neutralization of Botulinum Neurotoxin Serotype E Using Rabbit Polyclonal Antibody Developed against BoNT/E Light Chain.

Science.gov (United States)

Rani, Sarita; Ponmariappan, S; Sharma, Arti; Kamboj, D V; Jain, A K

2017-01-01

Clostridium botulinum is an obligate anaerobic, Gram positive bacterium that secretes extremely toxic substances known as botulinum neurotoxins (BoNTs) that cause serious paralytic illness called botulism. Based upon the serological properties, these neurotoxin have been classified into seven serotypes designated from A to G. Due to extreme toxicity of BoNTs, these neurotoxins have been designated as category A biowarfare agents. There is no commercial neutralizing antibody available for the treatment of botulism. Hence there is an urgent need to develop therapeutic intervention for prevention and cure of botulism within short period. BoNT antiserum injection is still the effective treatment. In the present study, the recombinant light chain of BoNT/E was successfully purified in soluble form. The purified rBoNT/E LC was used for the generation of polyclonal antibody in rabbit. In order to find out the neutralizing capacity of generated antisera, rabbit antiserum was incubated with 20 LD50 of botulinum neurotoxin type E for 1 hour at 37°C and then injected intraperitoneally (IP) into mice. Further in another set of experiments antiserum was administered in different ways that included administration of - antiserum and BoNT/E toxin simultaneously without preincubation, one after another at the same and different time points for its therapeutic ability. To find out cross neutralization capacity, rBoNT/E LC antiserum was pre-incubated with 5 LD50 of BoNT/A, BoNT/B, BoNT/F and then injected (IP) into mice. In all the cases mice were observed continuously for 96 hours. The results clearly indicate that developed polyclonal rabbit antiserum showed serotype specific neutralization of BoNT/E toxin only but not of BoNT/A, BoNT/B and BoNT/F. The developed antibodies will be used for preventive and therapeutic intervention of type 'E' botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Mechanism of action of neurotoxins acting on the inactivation of voltage-gated sodium channels].

Science.gov (United States)

Benoit, E

1998-01-01

This review focuses on the mechanism(s) of action of neurotoxins acting on the inactivation of voltage-gated Na channels. Na channels are transmembrane proteins which are fundamental for cellular communication. These proteins form pores in the plasma membrane allowing passive ionic movements to occur. Their opening and closing are controlled by gating systems which depend on both membrane potential and time. Na channels have three functional properties, mainly studied using electrophysiological and biochemical techniques, to ensure their role in the generation and propagation of action potentials: 1) a highly selectivity for Na ions, 2) a rapid opening ("activation"), responsible for the depolarizing phase of the action potential, and 3) a late closing ("inactivation") involved in the repolarizing phase of the action potential. As an essential protein for membrane excitability, the Na channel is the specific target of a number of vegetal and animal toxins which, by binding to the channel, alter its activity by affecting one or more of its properties. At least six toxin receptor sites have been identified on the neuronal Na channel on the basis of binding studies. However, only toxins interacting with four of these sites (sites 2, 3, 5 et 6) produce alterations of channel inactivation. The maximal percentage of Na channels modified by the binding of neurotoxins to sites 2 (batrachotoxin and some alkaloids), 3 (alpha-scorpion and sea anemone toxins), 5 (brevetoxins and ciguatoxins) et 6 (delta-conotoxins) is different according to the site considered. However, in all cases, these channels do not inactivate. Moreover, Na channels modified by toxins which bind to sites 2, 5 and 6 activate at membrane potentials more negative than do unmodified channels. The physiological consequences of Na channel modifications, induced by the binding of neurotoxins to sites 2, 3, 5 and 6, are (i) an inhibition of cellular excitability due to an important membrane depolarization (site

Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E.

Science.gov (United States)

Mascher, Gerald; Mertaoja, Anna; Korkeala, Hannu; Lindström, Miia

2017-10-01

Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA-binding domain of Spo0A directly bound to a putative Spo0A-binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C. botulinum type E. Unlike other C. botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C. botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Risk to human health associated with the environmental occurrence of cyanobacterial neurotoxic alkaloids anatoxins and saxitoxins.

Science.gov (United States)

Testai, Emanuela; Scardala, Simona; Vichi, Susanna; Buratti, Franca M; Funari, Enzo

2016-01-01

Cyanobacteria are ubiquitous photosynthetic micro-organisms forming blooms and scums in surface water; among them some species can produce cyanotoxins giving rise to some concern for human health and animal life. To date, more than 65 cyanobacterial neurotoxins have been described, of which the most studied are the groups of anatoxins and saxitoxins (STXs), comprising many different variants. In freshwaters, the hepatotoxic microcystins represent the most frequently detected cyanotoxin: on this basis, it could appear that neurotoxins are less relevant, but the low frequency of detection may partially reflect an a priori choice of target analytes, the low method sensitivity and the lack of certified standards. Cyanobacterial neurotoxins target cholinergic synapses or voltage-gated ion channels, blocking skeletal and respiratory muscles, thus leading to death by respiratory failure. This review reports and analyzes the available literature data on environmental occurrence of cyanobacterial neurotoxic alkaloids, namely anatoxins and STXs, their biosynthesis, toxicology and epidemiology, derivation of guidance values and action limits. These data are used as the basis to assess the risk posed to human health, identify critical exposure scenarios and highlight the major data gaps and research needs.

RPP Environmental Permits and Related Documentation

International Nuclear Information System (INIS)

DEXTER, M.L.

2001-01-01

This document contains the current list of environmental permits and related documentation for RPP facilities and activities. Copies of these permits and related approvals are maintained by RPP Environmental. In addition, notices of Correction and Notices of Violation are issued by State and Federal Regulators which are tracked by RPP Environmental to resolve any recently identified deficiencies. A listing of these recent Notices is provided as an attachment to this document. These permits, approval conditions, and recent regulatory agency notices, constitute an important element of the RPP Authorization Envelope. Permits are issued frequently and the reader is advised to check with RPP environmental for new permits or approval conditions. Interpretation of permit or approval conditions should be coordinated with RPP Environmental. This document is updated on a quarterly basis

RPP Environmental Permits and Related Documentation

International Nuclear Information System (INIS)

DEXTER, M.L.

2000-01-01

This document contains the current list of environmental permits and related documentation for RPP facilities and activities. Copies of these permits and related approvals are maintained by RPP Environmental. In addition, Notices of Correction and Notices of Violation are issued by State and Federal Regulators which are tracked by RPP Environmental to resolve any recently identified deficiencies. A listing of these recent Notices is provided as an attachment to this document. These permits, approval conditions, and recent regulatory agency notices, constitute an important element of the RPP Authorization Envelope. Permits are issued frequently and the reader is advised to check with RPP environmental for new permits or approval conditions. Interpretation of permit or approval conditions should be coordinated with RPP Environmental. This document will be updated on a quarterly basis

Beltless translocation domain of botulinum neurotoxin A embodies a minimum ion-conductive channel.

Science.gov (United States)

Fischer, Audrey; Sambashivan, Shilpa; Brunger, Axel T; Montal, Mauricio

2012-01-13

Botulinum neurotoxin, the causative agent of the paralytic disease botulism, is an endopeptidase composed of a catalytic domain (or light chain (LC)) and a heavy chain (HC) encompassing the translocation domain (TD) and receptor-binding domain. Upon receptor-mediated endocytosis, the LC and TD are proposed to undergo conformational changes in the acidic endocytic environment resulting in the formation of an LC protein-conducting TD channel. The mechanism of channel formation and the conformational changes in the toxin upon acidification are important but less well understood aspects of botulinum neurotoxin intoxication. Here, we have identified a minimum channel-forming truncation of the TD, the "beltless" TD, that forms transmembrane channels with ion conduction properties similar to those of the full-length TD. At variance with the holotoxin and the HC, channel formation for both the TD and the beltless TD occurs independent of a transmembrane pH gradient. Furthermore, acidification in solution induces moderate secondary structure changes. The subtle nature of the conformational changes evoked by acidification on the TD suggests that, in the context of the holotoxin, larger structural rearrangements and LC unfolding occur preceding or concurrent to channel formation. This notion is consistent with the hypothesis that although each domain of the holotoxin functions individually, each domain serves as a chaperone for the others.

Modulation of neurotransmitter release in the region of the caudate nucleus by diet and neurotoxins

Energy Technology Data Exchange (ETDEWEB)

Kurstjens, N P

1987-01-01

In this thesis the effects of dietary manipulation, ethanol and neurotoxins on the basal and electrically evoked release of dopamine and acetylcholine from the caudate nucleus of mature animals are presented together with an evaluation of the presynaptic acetylcholine and dopamine receptors controlling acetylcholine and dopamine release. A standardised superfusion technique was used to monitor the effect of apomorphine, in the presence of (R-S)- sulpiride or haloperidol, on the electrically induced release of (/sup 3/ H)-acetylcholine in slices of rat corpus striatum. The effect of ethanol and dietary manipulation on the basal and electrically evoke release of (/sup 3/H)-acetylfholine from rat striatal slices, in the presence of specific agonists and antagonists was evaluated. From this study it is possible to deduce that diet and neurotoxins exerted a measurable effect on the mechanisms controlling release of neurotransmitters in the region of the caudate nucleus. These changes were determined in mature animals previously considered to have cerebral activity, which was not subject to dietary fluctuaations. No changes in the activity of the presynaptic dopamine receptor of the acetylcholine nerve terminals of the striatal slice could be measured.

Fusion and retrotransposition events in the evolution of the sea anemone Anemonia viridis neurotoxin genes.

Science.gov (United States)

Moran, Yehu; Weinberger, Hagar; Lazarus, Nimrod; Gur, Maya; Kahn, Roy; Gordon, Dalia; Gurevitz, Michael

2009-08-01

Sea anemones are sessile predators that use a variety of toxins to paralyze prey and foe. Among these toxins, Types I, II and III are short peptides that affect voltage-gated sodium channels. Anemonia viridis is the only sea anemone species that produces both Types I and III neurotoxin. Although the two toxin types are unrelated in sequence and three-dimensional structure, cloning and comparative analysis of their loci revealed a highly similar sequence at the 5' region, which encodes a signal peptide. This similarity was likely generated by gene fusion and could be advantageous in transcript stability and intracellular trafficking and secretion. In addition, these analyses identified the processed pseudogenes of the two gene families in the genome of A. viridis, probably resulting from retrotransposition events. As presence of processed pseudogenes in the genome requires transcription in germ-line cells, we analyzed oocyte-rich ovaries and found that indeed they contain Types I and III transcripts. This result raises questions regarding the role of toxin transcripts in these tissues. Overall, the retrotransposition and gene fusion events suggest that the genes of both Types I and III neurotoxins evolved in a similar fashion and share a partial common ancestry.

Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex

OpenAIRE

Matsui, Tsutomu; Gu, Shenyan; Lam, Kwok-ho; Carter, Lester G.; Rummel, Andreas; Mathews, Irimpan I.; Jin, Rongsheng

2014-01-01

Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and release it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent co...

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

Science.gov (United States)

Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Isolation and Pharmacological Characterization of α-Elapitoxin-Ot1a, a Short-Chain Postsynaptic Neurotoxin from the Venom of the Western Desert Taipan, Oxyuranus temporalis

Directory of Open Access Journals (Sweden)

Carmel M. Barber

2016-02-01

Full Text Available Taipans (Oxyuranus spp. are elapids with highly potent venoms containing presynaptic (β and postsynaptic (α neurotoxins. O. temporalis (Western Desert taipan, a newly discovered member of this genus, has been shown to possess venom which displays marked in vitro neurotoxicity. No components have been isolated from this venom. We describe the characterization of α-elapitoxin-Ot1a (α-EPTX-Ot1a; 6712 Da, a short-chain postsynaptic neurotoxin, which accounts for approximately 30% of O. temporalis venom. α-Elapitoxin-Ot1a (0.1–1 µM produced concentration-dependent inhibition of indirect-twitches, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The inhibition of indirect twitches by α-elapitoxin-Ot1a (1 µM was not reversed by washing the tissue. Prior addition of taipan antivenom (10 U/mL delayed the neurotoxic effects of α-elapitoxin-Ot1a (1 µM and markedly attenuated the neurotoxic effects of α-elapitoxin-Ot1a (0.1 µM. α-Elapitoxin-Ot1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA2 value of 8.02 ± 0.05. De novo sequencing revealed the main sequence of the short-chain postsynaptic neurotoxin (i.e., α-elapitoxin-Ot1a as well as three other isoforms found in O. temporalis venom. α-Elapitoxin-Ot1a shows high sequence similarity (i.e., >87% with other taipan short-chain postsynaptic neurotoxins.

Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach

Directory of Open Access Journals (Sweden)

Wanpen Chaicumpa

2011-05-01

Full Text Available Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT derived from heterologous species (immunized animal or mouse hybridoma together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15–20 kDa single domain antibody (VHH that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/VHH phage display library. The VHH has high sequence homology (>80% to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the VHH and the toxin but also an insertion of the VHH CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the VHH to a cell penetrating peptide (CPP, the CPP-VHH fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme.

Identification and Funtional Characterization of Three Postsynaptic Short-chain Neurotoxins from Hydrophiinae, Lapemis hardwickii Gray.

Science.gov (United States)

Zhong, Xiao-Fen; Peng, Li-Sheng; Wu, Wen-Yan; Wei, Jian-Wen; Yang, Hong; Yang, Yan-Zhen; Xu, An-Long

2001-01-01

Three cDNA clones, sn12, sn36 and sn160, encoding isoforms of postsynaptic short-chain neurotoxins, were cloned by screening a cDNA library of the venom from Hydrophiinae, Lapemis hardwickii Gray. The sequences of three cDNA clones encoded proteins consisting of 60 amino acid residues. There was only one amino acid substitution among the three isoforms SN12, SN36 and SN160 at the position 46 of mature proteins, and they were Pro(46), His(46) and Arg(46), respectively. The three molecules were expressed in Escherichia coli and the recombinant proteins were characterized. Different LD(50) were obtained, namely 0.0956 mg/kg, 0.3467 mg/kg and 0.2192 mg/kg, when the SN12, SN36 and SN160 were injected into Kunming mice(i.p.). In analgesic effect assayed by the acetic acid-induced writhing method, SN12 and SN160 showed similar analgesic effect, but SN36 had effects significantly different with the other two. Our studies suggested that the amino acid residues on position 46 could affect the combination between the postsynaptic short-chain neurotoxins and the nicotinic acetylchoine receptor, since different amino acid substitution resulted in different biological activities.

Novel therapeutic uses and formulations of botulinum neurotoxins: a patent review (2012 - 2014).

Science.gov (United States)

Kane, Christopher D; Nuss, Jonathan E; Bavari, Sina

2015-06-01

Botulinum neurotoxins (BoNTs) are among the most toxic of known biological molecules and function as acetylcholine release inhibitors and neuromuscular blocking agents. Paradoxically, these properties also make them valuable therapeutic agents for the treatment of movement disorders, urological conditions and hypersecretory disorders. Greater understanding of their molecular mechanism of action and advances in protein engineering has led to significant efforts to improve and expand their function with a view towards broadening their therapeutic potential. Searches of Espacenet and Google Patent have revealed a number of patents related to BoNTs. This review will focus on novel therapeutic uses and formulations disclosed during 2012 - 2014. The seven patents discussed will include nanoformulations of FDA-approved BoNTs, additional BoNT subtypes and novel BoNT variants and chimeras created through protein engineering. Supporting patents and related publications are also briefly discussed. The clinical and commercial success of BoNTs has prompted investigation into novel BoNTs or BoNT-mediated chimeras with promising in vitro results. Distinct strategies including the use of nanoformulations and targeted delivery have been implemented to identify new indication and improved functionality. Greater understanding of their systemic exposure, efficacy and safety profiles will be required for further development.

Production and characterisation of a neutralising chimeric antibody against botulinum neurotoxin A.

Directory of Open Access Journals (Sweden)

Julie Prigent

Full Text Available Botulinum neurotoxins, produced by Clostridium botulinum bacteria, are the causative agent of botulism. This disease only affects a few hundred people each year, thus ranking it among the orphan diseases. However, botulinum toxin type A (BoNT/A is the most potent toxin known to man. Due to their potency and ease of production, these toxins were classified by the Centers for Disease Control and Prevention (CDC as Category A biothreat agents. For several biothreat agents, like BoNT/A, passive immunotherapy remains the only possible effective treatment allowing in vivo neutralization, despite possible major side effects. Recently, several mouse monoclonal antibodies directed against a recombinant fragment of BoNT/A were produced in our laboratory and most efficiently neutralised the neurotoxin. In the present work, the most powerful one, TA12, was selected for chimerisation. The variable regions of this antibody were thus cloned and fused with the constant counterparts of human IgG1 (kappa light and gamma 1 heavy chains. Chimeric antibody production was evaluated in mammalian myeloma cells (SP2/0-Ag14 and insect cells (Sf9. After purifying the recombinant antibody by affinity chromatography, the biochemical properties of chimeric and mouse antibody were compared. Both have the same very low affinity constant (close to 10 pM and the chimeric antibody exhibited a similar capacity to its parent counterpart in neutralising the toxin in vivo. Its strong affinity and high neutralising potency make this chimeric antibody interesting for immunotherapy treatment in humans in cases of poisoning, particularly as there is a probable limitation of the immunological side effects observed with classical polyclonal antisera from heterologous species.

Recent advances in botulinum neurotoxin inhibitor development.

Science.gov (United States)

Kiris, Erkan; Burnett, James C; Kane, Christopher D; Bavari, Sina

2014-01-01

Botulinum neurotoxins (BoNTs) are endopeptidases that target motor neurons and block acetylcholine neurotransmitter release. This action results in the muscle paralysis that defines the disease botulism. To date, there are no FDA-approved therapeutics to treat BoNT-mediated paralysis after intoxication of the motor neuron. Importantly, the rationale for pursuing treatments to counter these toxins is driven by their potential misuse. Current drug discovery efforts have mainly focused on small molecules, peptides, and peptidomimetics that can directly and competitively inhibit BoNT light chain proteolytic activity. Although this is a rational approach, direct inhibition of the Zn(2+) metalloprotease activity has been elusive as demonstrated by the dearth of candidates undergoing clinical evaluation. Therefore, broadening the scope of viable targets beyond that of active site protease inhibitors represents an additional strategy that could move the field closer to the clinic. Here we review the rationale, and discuss the outcomes of earlier approaches and highlight potential new targets for BoNT inhibition. These include BoNT uptake and processing inhibitors, enzymatic inhibitors, and modulators of neuronal processes associated with toxin clearance, neurotransmitter potentiation, and other pathways geared towards neuronal recovery and repair.

Botulinum neurotoxin: a marvel of protein design.

Science.gov (United States)

Montal, Mauricio

2010-01-01

Botulinum neurotoxin (BoNT), the causative agent of botulism, is acknowledged to be the most poisonous protein known. BoNT proteases disable synaptic vesicle exocytosis by cleaving their cytosolic SNARE (soluble NSF attachment protein receptor) substrates. BoNT is a modular nanomachine: an N-terminal Zn(2+)-metalloprotease, which cleaves the SNAREs; a central helical protein-conducting channel, which chaperones the protease across endosomes; and a C-terminal receptor-binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis. For BoNT, functional complexity emerges from its modular design and the tight interplay between its component modules--a partnership with consequences that surpass the simple sum of the individual component's action. BoNTs exploit this design at each step of the intoxication process, thereby achieving an exquisite toxicity. This review summarizes current knowledge on the structure of individual modules and presents mechanistic insights into how this protein machine evolved to this level of sophistication. Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task.

Peptide inhibitors of botulinum neurotoxin by mRNA display

International Nuclear Information System (INIS)

Yiadom, Kwabena P.A.B.; Muhie, Seid; Yang, David C.H.

2005-01-01

Botulinum neurotoxins (BoNTs) are extremely toxic. The metalloproteases associated with the toxins cleave proteins essential for neurotransmitter secretion. Inhibitors of the metalloprotease are currently sought to control the toxicity of BoNTs. Toward that goal, we produced a synthetic cDNA for the expression and purification of the metalloprotease of BoNT/A in Escherichia coli as a biotin-ubiquitin fusion protein, and constructed a combinatorial peptide library to screen for BoNT/A light chain inhibitors using mRNA display. A protease assay was developed using immobilized intact SNAP-25 as the substrate. The new peptide inhibitors showed a 10-fold increase in affinity to BoNT/A light chain than the parent peptide. Interestingly, the sequences of the new peptide inhibitors showed abundant hydrophobic residues but few hydrophilic residues. The results suggest that mRNA display may provide a general approach in developing peptide inhibitors of BoNTs

Involvement of Cholinergic and Adrenergic Receptors in Pathogenesis and Inflammatory Response Induced by Alpha-Neurotoxin Bot III of Scorpion Venom.

Science.gov (United States)

Nakib, Imene; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

2016-10-01

Bot III neurotoxin is the most lethal α neurotoxin purified from Buthus occitanus tunetanus scorpion venom. This toxin binds to the voltage-gated sodium channel of excitable cells and blocks its inactivation, inducing an increased release of neurotransmitters (acetylcholine and catecholamines). This study aims to elucidate the involvement of cholinergic and adrenergic receptors in pathogenesis and inflammatory response triggered by this toxin. Injection of Bot III to animals induces an increase of peroxidase activities, an imbalance of oxidative status, tissue damages in lung parenchyma, and myocardium correlated with metabolic disorders. The pretreatment with nicotine (nicotinic receptor agonist) or atropine (muscarinic receptor antagonist) protected the animals from almost all disorders caused by Bot III toxin, especially the immunological alterations. Bisoprolol administration (selective β1 adrenergic receptor antagonist) was also efficient in the protection of animals, mainly on tissue damage. Propranolol (non-selective adrenergic receptor antagonist) showed less effect. These results suggest that both cholinergic and adrenergic receptors are activated in the cardiopulmonary manifestations induced by Bot III. Indeed, the muscarinic receptor appears to be more involved than the nicotinic one, and the β1 adrenergic receptor seems to dominate the β2 receptor. These results showed also that the activation of nicotinic receptor leads to a significant protection of animals against Bot III toxin effect. These findings supply a supplementary data leading to better understanding of the mechanism triggered by scorpionic neurotoxins and suggest the use of drugs targeting these receptors, especially the nicotinic one in order to counteract the inflammatory response observed in scorpion envenomation.

Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN). Detection by enzyme-linked immunosorbent assay and purification from normal human urine

DEFF Research Database (Denmark)

Reimert, C M; Minuva, U; Kharazmi, A

1991-01-01

Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) is one of the cationic proteins found in the granules of the human eosinophilic granulocytes. EPX was purified from extracts of granules isolated from blood buffy coat cells of healthy donors. Polyclonal anti-EPX antibodies were...

The Structure of the Neurotoxin- Associated Protein HA33/A from Clostridium botulinum Suggests a Reoccurring Beta-Trefoil Fold in the Progenitor Toxin Complex

National Research Council Canada - National Science Library

Arndt, Joseph W; Gu, Jenny; Jaroszewski, Lukasz; Schwarzenbacher, Robert; Hanson, Michael A; Lebeda, Frank L; Stevens, Raymond C

2004-01-01

The hemagglutinating protein HA33 from Clostridium botulinum is associated with the large botulinum neurotoxin secreted complexes and is critical in toxin protection, internalization, and possibly activation...

1992 yearbook of environmental and technology-related law

International Nuclear Information System (INIS)

Schroeder, M.

1992-01-01

The 1992 and sixth edition of this yearbook contains papers on environmental and technology-related law in the European Communities and the Federal Republic of Germany including among other things information on the latest jurisdiction by the European Court of Justice; insurability of environmental damage; scientific aspects of limit values. There are also treatises on non-German and comparative as well as international environmental and technology- related law which deal among other things with atomic and immission protection law and on harmonization and codification from a general point of view. Finally, some papers report on developments of national and European environmental and technology-related law. Three of the fifteen contributions have been abstracted separately. (HSCH) [de

Selection of RNA Aptamers Against Botulinum Neurotoxin Type A Light Chain Through a Non-Radioactive Approach.

Science.gov (United States)

Chang, Tzuu-Wang; Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Cai, Shuowei

2016-09-01

Botulinum neurotoxin (BoNT), a category A agent, is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, a non-radioactive-based systematic evolution of ligands by exponential enrichment (SELEX) process is developed by utilizing surface plasmon resonance to monitor the binding enrichment. Two RNA aptamers have been identified as strong binders against light chain of botulinum neurotoxin type A. These two aptamers showed strong inhibition activity on LCA, with IC50 in nanomolar range. Inhibition kinetic studies reveal mid nanomolar KI and non-competitive nature of their inhibition, suggesting that they have strong potential as antidotes that can reverse the symptom caused by BoNT/A. More importantly, we observed that the 2'-fluorine-pyrimidine-modified RNA aptamers identified here do not change their binding and biological activities. This observation could lead to a cost-effective way for SELEX, by using regular nucleotide during SELEX, and 2'-fluorine-pyrimidine-modified nucleotide for final application to enhance their RNase-resistance.

In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing

NARCIS (Netherlands)

Nicolas, J.A.Y.; Hendriksen, P.J.M.; Haan, de L.H.J.; Koning, R.; Rietjens, I.M.C.M.; Bovee, T.F.H.

2015-01-01

The present study investigated if and to what extent murine stem cell-derived beating cardiomyocytes within embryoid bodies can be used as a broad screening in vitro assay for neurotoxicity testing, replacing for example in vivo tests for marine neurotoxins. Effect of nine model compounds, acting on

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

OpenAIRE

Moran, Yehu; Genikhovich, Grigory; Gordon, Dalia; Wienkoop, Stefanie; Zenkert, Claudia; Özbek, Suat; Technau, Ulrich; Gurevitz, Michael

2011-01-01

Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficie...

Environmentally related taxes in OECD countries: issues and strategies

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-07-01

Economic instruments, including environmentally related taxes, play an increasing role in the environmental policies of developed countries. This publication addresses the use of environmental taxes and their effectiveness in reducing environmental damage. It finds these taxes are a powerful tool for implementing environmental strategy. It also describes obstacles to increased use of such taxes (e.g. concerns about competitiveness and distributional effects) and suggests ways to overcome such barriers. Particular attention is given to issues and options related to taxes on greenhouse gases. 18 figs., 13 tabs.

Egg yolk antibodies for detection and neutralization of Clostridium botulinum type A neurotoxin.

Science.gov (United States)

Trott, D L; Yang, M; Gonzalez, J; Larson, A E; Tepp, W H; Johnson, E A; Cook, M E

2009-05-01

The objective of this research project was to determine the usefulness of an egg antibody platform for producing materials for the detection and neutralization of botulinum type A neurotoxin. Yield estimates for detection and neutralizing antibodies produced using methods described were calculated. Antibody specific to botulinum toxoid A (aToxoid) and toxin A (aBoNT/A) was produced by immunizing hens with botulinum toxoid A (toxoid) followed by increasing amounts of botulinum neurotoxin A (BoNT/A) in Freund incomplete adjuvant. Egg yolks were extracted with polyethylene glycol (PEG) for antibody detection and neutralization experiments. A model aToxoid/toxoid immunoassay using only egg yolk antibody was developed and had a detection limit of 1 pg/ml of toxoid. In an indirect enzyme-linked immunosorbent assay of BoNT/A-specific antibody, the aBoNT/A contained more BoNT/A-specific antibody than did the aToxoid, and aBoNT/A was as effective as commercial rabbit antibody. The aToxoid provided no protection against BoNT/A in a standard mouse neutralization assay; however, 1 mg of PEG-extracted aBoNT/A neutralized 4,000 lethal doses of BoNT/A injected intraperitoneally. Based on these results, we calculated that in 1 month one hen could produce more than 100 liters of antibody detection reagents or enough antibody to neutralize approximately 11.6 million mouse lethal doses of botulinum toxin. Utilization of an egg antibody platform is potentially rapid (28 to 70 days) and scalable to kilogram quantities using current egg production facilities with as few as 1,000 hens.

In Vivo Toxicity and Immunological Characterization of Detoxified Recombinant Botulinum Neurotoxin Type A.

Science.gov (United States)

Ravichandran, Easwaran; Janardhanan, Pavithra; Patel, Kruti; Riding, Stephen; Cai, Shuowei; Singh, Bal Ram

2016-03-01

A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT. We determined lethality (LD50) of deactivated recombinant botulinum neurotoxin (drBoNT/A) to be 24.0 μg by intraperitoneal route (i.p). The polypeptide drBoNT/A labeled with near infra-red dye 800 (NIR 800) was used to examine its distribution to different organs using whole body imaging when administered to mice via intravenous (i.v) or i.p route. Also, drBoNT/A was used to evaluate its immunogenicity in Balb/C mice model. drBoNT/A was found to be highly immunogenic when tested under various in vivo conditions in Balb/C mice model. For the first time we have demonstrated that a full length 150 kDa drBoNT/A, by administering via inhalation route in mice model, has evoked both circulating immunoglobulin levels of IgG and secretory IgA at the mucosal surface. The immunoglobulin levels were sufficient enough to protect against the challenge dose of native BoNT toxin in mice model. Tissue distribution of drBoNT/A seems to be similar to that of native toxin. Based on the characteristics described in this report this nontoxic holotoxin protein will assist us to explore the window of opportunity available for therapeutic treatment in case of unnatural poisoning, and also it can be an effective vaccine candidate.

The Metal Neurotoxins: An Important Role in Current Human Neural Epidemics?

Directory of Open Access Journals (Sweden)

Keith Schofield

2017-12-01

Full Text Available Many published studies have illustrated that several of the present day neurological epidemics (autism, attention deficit disorder, Alzheimer’s cannot be correlated to any single neurotoxicant. However, the present scientific examination of the numerous global blood monitoring databases for adults that include the concentrations of the neurotoxic elements, aluminum (Al, arsenic (As, lead (Pb, manganese (Mn, mercury (Hg, and selenium (Se clearly indicate that, when considered in combination, for some, the human body may become easily over-burdened. This can be explained by changes in modern lifestyles. Similar data, solely for pregnant women, have been examined confirming this. All these elements are seen to be present in the human body and at not insignificant magnitudes. Currently suggested minimum risk levels (MRL for humans are discussed and listed together with averages of the reported distributions, together with their spread and maximum values. One observation is that many distributions for pregnant women are not too dissimilar from those of general populations. Women obviously have their individual baseline of neurotoxin values before pregnancy and any efforts to modify this to any significant degree is not yet clearly apparent. For any element, distribution shapes are reasonably similar showing broad distributions with extended tails with numerous outlier values. There are a certain fraction of people that lie well above the MRL values and may be at risk, especially if genetically susceptible. Additionally, synergistic effects between neurotoxins and with other trace metals are now also being reported. It appears prudent for women of child-bearing age to establish their baseline values well before pregnancy. Those at risk then can be better identified. Adequate instrumental testing now is commercially available for this. In addition, directives are necessary for vaccination programs to use only non-neurotoxic adjuvants, especially for

The Deployment of Product-Related Environmental Legislation into Product Requirements

Directory of Open Access Journals (Sweden)

Daniela C. A. Pigosso

2016-04-01

Full Text Available Environmental legislation is increasingly changing its focus from manufacturing-oriented to product-oriented instruments. Compliance with product-related environmental legislation is achieved by the incorporation of environmental requirements into the early phases of the product development process (PDP. Nevertheless, the deployment of product-related environmental legislation into product requirements is still a challenge. This study followed an inductive approach to propose a guideline to support the identification, analysis and deployment of product requirements based on product-related environmental legislation. The guideline is composed of nine steps, clustered into three groups according to their main objective: (A identification of environmental product-related legislation; (B identification of legislative topics to be considered for the deployment of requirements; and (C creation and validation of product requirements. The product requirements deployed are to be considered during the PDP. The guideline was evaluated in an expert consultation in a large manufacturing company, suggesting that it can be used to support the systematization and deployment of product-related environmental requirements.

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

Science.gov (United States)

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

2017-04-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

32 CFR 536.35 - Unique issues related to environmental claims.

Science.gov (United States)

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Unique issues related to environmental claims... issues related to environmental claims. Claims for property damage, personal injury, or death arising in... reported by USARCS to the Environmental Law Division of the Army Litigation Center and the Environmental...

EARTH RESOURCE PROBLEMS AND RELATED ENVIRONMENTAL CONSIDERATIONS

Directory of Open Access Journals (Sweden)

Orlitová Erika

1997-10-01

Full Text Available The paper discusses some of the problems of geology and earth resources management in relation to environmental problems of the technosphere. It deals also with some aspects of environmental monitoring of areas where surveying or mining operations are planned or in progress.

78 FR 8964 - Environmental Impact and Related Procedures

Science.gov (United States)

2013-02-07

... Administration 49 CFR Part 622 [Docket No. FTA-2011-0056] RIN 2132-AB03 Environmental Impact and Related... an environmental impact statement. DATES: Effective on February 7, 2013. FOR FURTHER INFORMATION... the list of project types that normally result in the preparation of an Environmental Impact Statement...

Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: Insight into the ganglioside binding mechanism

Energy Technology Data Exchange (ETDEWEB)

Nuemket, Nipawan [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Tanaka, Yoshikazu [Creative Research Institution ' Sousei,' Hokkaido University, Sapporo 001-0021 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Tsukamoto, Kentaro; Tsuji, Takao [Department of Microbiology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192 (Japan); Nakamura, Keiji; Kozaki, Shunji [Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531 (Japan); Yao, Min [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Tanaka, Isao, E-mail: tanaka@castor.sci.hokudai.ac.jp [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan)

2011-07-29

Highlights: {yields} We determined the crystal structure of the receptor binding domain of BoNT in complex with 3'-sialyllactose. {yields} An electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. {yields} Alanine site-directed mutagenesis showed that GBS and GBL are important for ganglioside binding. {yields} A cell binding mechanism, which involves cooperative contribution of two sites, was proposed. -- Abstract: Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinum neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0 A. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.

Epitopic Profiling of Antibody Response against Neurotoxins from the Black Mamba (Dendroaspis polylepis)

DEFF Research Database (Denmark)

Jespersen, Martin Closter; Engmark, Mikael; Laustsen, Andreas Hougaard

The black mamba (Dendroaspis Polylepis) is among the most dangerous snakes in the world, with a venom dominated by three-finger toxins and dendrotoxins. Among the three-finger toxins, the α-neurotoxins (α-NT) are the most important, and these are conserved between snake species. Cross......-reactivity between threefinger toxins is known to occur, and understanding this phenomenon in depth may help guide future design of antivenoms to obtain optimal specificity against medically important toxins from different snake species. Using a bioinformatic approach, we investigated the cross-reactivity be- tween...

A Label Free Colorimetric Assay for the Detection of Active Botulinum Neurotoxin Type A by SNAP-25 Conjugated Colloidal Gold

Directory of Open Access Journals (Sweden)

Christopher Gwenin

2013-08-01

Full Text Available Botulinum neurotoxins are one of the most potent toxins known to man. Current methods of detection involve the quantification of the toxin but do not take into account the percentage of the toxin that is active. At present the assay used for monitoring the activity of the toxin is the mouse bioassay, which is lengthy and has ethical issues due to the use of live animals. This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. The results show clear differences between the toxin product and the placebo, which contains the pharmaceutical excipients human serum albumin and lactose, showing that the assay detects the active form of the toxin.

Environmental considerations related to mining of nonfuel minerals

Science.gov (United States)

Seal, Robert R.; Piatak, Nadine M.; Kimball, Bryn E.; Hammarstrom, Jane M.; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.

2017-12-19

Throughout most of human history, environmental stewardship during mining has not been a priority partly because of the lack of applicable laws and regulations and partly because of ignorance about the effects that mining can have on the environment. In the United States, the National Environmental Policy Act of 1969, in conjunction with related laws, codified a more modern approach to mining, including the responsibility for environmental stewardship, and provided a framework for incorporating environmental protection into mine planning. Today, similar frameworks are in place in the other developed countries of the world, and international mining companies generally follow similar procedures wherever they work in the world. The regulatory guidance has fostered an international effort among all stakeholders to identify best practices for environmental stewardship.The modern approach to mining using best practices involves the following: (a) establishment of a pre-mining baseline from which to monitor environmental effects during mining and help establish geologically reasonable closure goals; (b) identification of environmental risks related to mining through standardized approaches; and (c) formulation of an environmental closure plan before the start of mining. A key aspect of identifying the environmental risks and mitigating those risks is understanding how the risks vary from one deposit type to another—a concept that forms the basis for geoenvironmental mineral-deposit models.Accompanying the quest for best practices is the goal of making mining sustainable into the future. Sustainable mine development is generally considered to be development that meets the needs of the present generation without compromising the ability of future generations to meet their own needs. The concept extends beyond the availability of nonrenewable mineral commodities and includes the environmental and social effects of mine development.Global population growth, meanwhile, has

Environmental Values related to fish and wildlife lands

Science.gov (United States)

David N. Bengston

2000-01-01

THe purpose of this paper is to provide an overview of key concepts related to environmental values and their importance for public land managers. The following section defines environmental values and discusses their relationship to environmnetal attitudes and beliefs. This is followed by presentation of a broad system for classifying environmental values and...

Effects of atomoxetine on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)

NARCIS (Netherlands)

Hauser, J.; Reissmann, A.; Sontag, T.A.; Tucha, Oliver; Lange, K.W.

2017-01-01

The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In

Research gaps related to the environmental impacts of electronic cigarettes

OpenAIRE

Chang, Hoshing

2014-01-01

Objective To consider the research gaps related to the environmental impacts of electronic cigarettes due to their manufacture, use and disposal. Methods Literature searches were conducted through December 2013. Studies were included in this review if they related to the environmental impacts of e-cigarettes. Results Scientific information on the environmental impacts of e-cigarette manufacturing, use and disposal is very limited. No studies formally evaluated the environmental impacts of the...

Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its central analgesic effects under red light

Directory of Open Access Journals (Sweden)

Yang Q

2017-05-01

Full Text Available Qian Yang, Chuang Zhao, Jun Zhao, Yong Ye Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: Cobra neurotoxin (CNT, a peptide isolated from snake venom of Naja naja atra, shows central analgesic effects in our previous research. In order to help CNT pass through blood–brain barrier (BBB and improve its central analgesic effects, a new kind of CNT nanocapsules were prepared by double emulsification with soybean lecithin and cholesterol as the shell, and pheophorbide as the photosensitizer added to make it photoresponsive. The analgesic effects were evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT nanocapsules had an average particle size of 229.55 nm, zeta potential of -53.00 mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly distributed in outer layer of the CNT nanocapsules and increased the release of the CNT nanocapsules after 650 nm illumination. The central analgesic effects were improved after intraperitoneal injection of CNT at 25 and 50 µg·kg-1 under 650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by red light generated reactive oxygen species which opened the nanocapsules and BBB and helped the CNT enter the brain. This research provides a new drug delivery for treatment of central pain. Keywords: cobra neurotoxin, nanocapsules, photoresponsive, central analgesic effects, red light, drug delivery, photosensitizer

Comparison of the catalytic properties of the botulinum neurotoxin subtypes A1 and A5.

Science.gov (United States)

Wang, Dongxia; Krilich, Joan; Pellett, Sabine; Baudys, Jakub; Tepp, William H; Barr, John R; Johnson, Eric A; Kalb, Suzanne R

2013-12-01

Clostridium botulinum neurotoxins (BoNTs) cause the life-threatening disease botulism through the inhibition of neurotransmitter release by cleaving essential SNARE proteins. There are seven serologically distinctive types of BoNTs and many subtypes within a serotype have been identified. BoNT/A5 is a recently discovered subtype of type A botulinum neurotoxin which possesses a very high degree of sequence similarity and identity to the well-studied A1 subtype. In the present study, we examined the endopeptidase activity of these two BoNT/A subtypes and our results revealed significant differences in substrate binding and cleavage efficiency between subtype A5 and A1. Distinctive hydrolysis efficiency was observed between the two toxins during cleavage of the native substrate SNAP-25 versus a shortened peptide mimic. N-terminal truncation studies demonstrated that a key region of the SNAP-25, including the amino acid residues at 151 through 154 located in the remote binding region of the substrate, contributed to the differential catalytic properties between A1 and A5. Elevated binding affinity of the peptide substrate resulted from including these important residues and enhanced BoNT/A5's hydrolysis efficiency. In addition, mutations of these amino acid residues affect the proteolytic performance of the two toxins in different ways. This study provides a better understanding of the biological activity of these toxins, their performance characteristics in the Endopep-MS assay to detect BoNT in clinical samples and foods, and is useful for the development of peptide substrates. © 2013. Published by Elsevier B.V. All rights reserved.

Statistics and Corporate Environmental Management: Relations and Problems

DEFF Research Database (Denmark)

Madsen, Henning; Ulhøi, John Parm

1997-01-01

Statistical methods have long been used to analyse the macroeconomic consequences of environmentally damaging activities, political actions to control, prevent, or reduce these damages, and environmental problems in the natural environment. Up to now, however, they have had a limited and not very...... specific use in corporate environmental management systems. This paper will address some of the special problems related to the use of statistical techniques in corporate environmental management systems. One important aspect of this is the interaction of internal decisions and activities with conditions...

Accelerated Intoxication of GABAergic Synapses by Botulinum Neurotoxin A Disinhibits Stem Cell-Derived Neuron Networks Prior to Network Silencing

Science.gov (United States)

2015-04-23

administered BoNT can lead to central nervous system intoxication is currently being debated. Recent findings in vitro and in vivo suggest that BoNT...Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Accelerated intoxication of GABAergic synapses by botulinum neurotoxin A disinhibits 5a...April 2015 Published: 23 April 2015 Citation: Beske PH, Scheeler SM, AdlerM and McNutt PM (2015) Accelerated intoxication of GABAergic synapses by

Review of Research on Environmental Public Relations

Science.gov (United States)

Grunig, James E.

1977-01-01

Reviews existing knowledge on the behavior of public relations practitioners in environmental problems, public concern and media coverage of pollution and deterioation of the natural environment. Available from: Public Relations Review, Ray Hiebert, Dean, College of Journalism, University of Maryland, College Park, MD 20742. (MH)

Molecular cloning of the human eosinophil-derived neurotoxin: A member of the ribonuclease gene family

International Nuclear Information System (INIS)

Rosenberg, H.F.; Tenen, D.G.; Ackerman, S.J.

1989-01-01

The authors have isolated a 725-base-pair cDNA clone for human eosinophil-derived neurotoxin (EDN). EDN is a distinct cationic protein of the eosinophil's large specific granule known primarily for its ability to induce ataxia, paralysis, and central nervous system cellular degeneration in experimental animals (Gordon phenomenon). The open reading frame encodes a 134-amino acid mature polypeptide with a molecular mass of 15.5 kDa and a 27-residue amino-terminal hydrophobic leader sequence. The sequence of the mature polypeptide is identical to that reported for human urinary ribonuclease, and to the amino-terminal sequence of human liver ribonuclease; the cDNA encodes a tryptophan in position 7. Both EDN and the related granule protein, eosinophil cationic protein, have ribonucleolytic activity; sequence similarities among EDN, eosinophil cationic protein, ribonucleases from liver, urine, and pancreas, and angiogenin define a ribonuclease multigene family. mRNA encoding EDN was detected in uninduced HL-60 cells and was up-regulated in cells induced toward eosinophilic differentiation with B-cell growth factor 2/interleukin 5 and toward neutrophilic differentiation with dimethyl sulfoxide. EDN mRNA was detected in mature neutrophils even though EDN-like neurotoxic activity is not found neutrophil extracts. These results suggest that neutrophils contain a protein that is closely related or identical to EDN

Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

OpenAIRE

Yao, G; Lam, KH; Perry, K; Weisemann, J; Rummel, A; Jin, R

2017-01-01

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established Bo...

The relation between proactive environmental strategies and competitive advantage

Science.gov (United States)

Butnariu, A.; Avasilcăi, S.

2015-11-01

There are two distinct orientations of the environmental management that companies may adopt: the model of compliance and the strategic model. The strategic model treats environmental expenses as investments that will lead to competitive advantage for the company. Nevertheless, there are few scientific works that prove the relation between corporate environmental investments and competitive advantage. Thereby, in order to bring clarifications about the profound implications of environmental investments, in the first stage of our research we have proposed the hypothesis that the environmental investments would probably lead to competitive advantage by creating capabilities that are mediators of this relation. In the second stage we have tested this hypothesis, using the research method of survey. A questionnaire was sent to managers in textile Romanian industry, and 109 answers were received. The data was analysed using the linear multiple regression method and the results confirm our hypothesis.

Research gaps related to the environmental impacts of electronic cigarettes

Science.gov (United States)

Chang, Hoshing

2014-01-01

Objective To consider the research gaps related to the environmental impacts of electronic cigarettes due to their manufacture, use and disposal. Methods Literature searches were conducted through December 2013. Studies were included in this review if they related to the environmental impacts of e-cigarettes. Results Scientific information on the environmental impacts of e-cigarette manufacturing, use and disposal is very limited. No studies formally evaluated the environmental impacts of the manufacturing process or disposal of components, including batteries. Four studies evaluated potential exposure to secondhand e-cigarette aerosol, an indication of impacts on indoor air quality. A 2010 survey of six e-cigarette models found that none of the products provided disposal instructions for spent cartridges containing nicotine. Notably, some e-cigarette manufacturers claim their e-cigarettes are ‘eco-friendly’ or ‘green’, despite the lack of any supporting data or environmental impact studies. Some authors argue that such advertising may boost sales and increase e-cigarette appeal, especially among adolescents. Conclusions Little is known about the environmental impacts of e-cigarettes, and a number of topics could be further elucidated by additional investigation. These topics include potential environmental impacts related to manufacturing, use and disposal. The environmental impacts of e-cigarette manufacturing will depend upon factory size and the nicotine extracting method used. The environmental impacts of e-cigarette use will include chemical and aerosol exposure in the indoor environment. The environmental impacts of disposal of e-cigarette cartridges (which contain residual nicotine) and disposal of e-cigarettes (which contain batteries) represent yet another environmental concern. PMID:24732165

Research gaps related to the environmental impacts of electronic cigarettes.

Science.gov (United States)

Chang, Hoshing

2014-05-01

To consider the research gaps related to the environmental impacts of electronic cigarettes due to their manufacture, use and disposal. Literature searches were conducted through December 2013. Studies were included in this review if they related to the environmental impacts of e-cigarettes. Scientific information on the environmental impacts of e-cigarette manufacturing, use and disposal is very limited. No studies formally evaluated the environmental impacts of the manufacturing process or disposal of components, including batteries. Four studies evaluated potential exposure to secondhand e-cigarette aerosol, an indication of impacts on indoor air quality. A 2010 survey of six e-cigarette models found that none of the products provided disposal instructions for spent cartridges containing nicotine. Notably, some e-cigarette manufacturers claim their e-cigarettes are 'eco-friendly' or 'green', despite the lack of any supporting data or environmental impact studies. Some authors argue that such advertising may boost sales and increase e-cigarette appeal, especially among adolescents. Little is known about the environmental impacts of e-cigarettes, and a number of topics could be further elucidated by additional investigation. These topics include potential environmental impacts related to manufacturing, use and disposal. The environmental impacts of e-cigarette manufacturing will depend upon factory size and the nicotine extracting method used. The environmental impacts of e-cigarette use will include chemical and aerosol exposure in the indoor environment. The environmental impacts of disposal of e-cigarette cartridges (which contain residual nicotine) and disposal of e-cigarettes (which contain batteries) represent yet another environmental concern.

The decline and revival of environmentally-related taxation in Europe

DEFF Research Database (Denmark)

Andersen, Mikael Skou

2013-01-01

The EU Energy Taxation Directive's low minimum tax rate for diesel along with a general dieselisation of Europe's vehicle fleet explains why revenues from environmentally-related taxes gradually declined from 1999-2008. After the financial crisis environmentally-related taxation is resuming its...

Statistics and Corporate Environmental Management: Relations and Problems

DEFF Research Database (Denmark)

Madsen, Henning; Ulhøi, John Parm

1997-01-01

Statistical methods have long been used to analyse the macroeconomic consequences of environmentally damaging activities, political actions to control, prevent, or reduce these damages, and environmental problems in the natural environment. Up to now, however, they have had a limited and not very...... in the external environment. The nature and extent of the practical use of quantitative techniques in corporate environmental management systems is discussed on the basis of a number of company surveys in four European countries.......Statistical methods have long been used to analyse the macroeconomic consequences of environmentally damaging activities, political actions to control, prevent, or reduce these damages, and environmental problems in the natural environment. Up to now, however, they have had a limited and not very...... specific use in corporate environmental management systems. This paper will address some of the special problems related to the use of statistical techniques in corporate environmental management systems. One important aspect of this is the interaction of internal decisions and activities with conditions...

Transport-related lifestyle and environmentally-friendly travel mode choices

DEFF Research Database (Denmark)

Thøgersen, John

2018-01-01

. Finally, a multivariate GLM analysis reveals that three behavioral tendencies of importance for transport-related environmental impacts vary significantly and substantially between lifestyle segments: vehicle ownership, everyday travel-mode choice and environmentally-friendly transport innovativeness...

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H

OpenAIRE

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-01-01

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed Bo...

Botulinum neurotoxin: unique folding of enzyme domain of the most-poisonous poison.

Science.gov (United States)

Kumar, Raj; Kukreja, Roshan V; Li, Li; Zhmurov, Artem; Kononova, Olga; Cai, Shuowei; Ahmed, Syed A; Barsegov, Valeri; Singh, Bal Ram

2014-01-01

Botulinum neurotoxin (BoNT), the most toxic substance known to mankind, is the first example of the fully active molten globule state. To understand its folding mechanism, we performed urea denaturation experiments and theoretical modeling using BoNT serotype A (BoNT/A). We found that the extent of BoNT/A denaturation from the native state (N) shows a nonmonotonic dependence on urea concentration indicating a unique multistep denaturation process, N → I1 [Formula: see text] I2 [Formula: see text] U, with two intermediate states I1 and I2. BoNT/A loses almost all its secondary structure in 3.75 M urea (I1), yet it displays a native-like secondary structure in 5 M urea (I2). This agrees with the results of theoretical modeling, which helped to determine the molecular basis of unique behavior of BoNT/A in solution. Except for I2, all the states revert back to full enzymatic activity for SNAP-25 including the unfolded state U stable in 7 M urea. Our results stress the importance of structural flexibility in the toxin's mechanism of survival and action, an unmatched evolutionary trait from billion-year-old bacteria, which also correlates with the long-lasting enzymatic activity of BoNT inside neuronal cells. BoNT/A provides a rich model to explore protein folding in relation to functional activity.

ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

OpenAIRE

D. D. Miniaeva

2014-01-01

This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism) into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism). The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, ta...

Cyanobacteria, neurotoxins and water resources: are there implications for human neurodegenerative disease?

Science.gov (United States)

Metcalf, James S; Codd, Geoffrey A

2009-01-01

Cyanobacteria are cosmopolitan microbes that inhabit marine, freshwater and terrestrial environments. Under favourable conditions in waterbodies, they can form massive populations (blooms and scums), which present hazards to human and animal health. Such cyanobacteria often contain a variety of toxic substances (cyanotoxins) that can exist as both cell-associated and free forms in the surrounding water. Some cyanotoxins are highly neurotoxic and act through a variety of mechanisms. Recent findings of the production of the neurotoxin beta-N-methylamino-L-alanine (BMAA) by cyanobacteria in aquatic environments, and of BMAA in brain and cerebrospinal fluid samples of amyotrophic lateral sclerosis and Alzheimer's disease victims, raises the possibility that people may be exposed to waterborne BMAA of cyanobacterial origin and that this may contribute to human neurodegenerative disease. An understanding of the risks presented by waterborne BMAA and of available mitigation strategies to reduce this potential exposure is needed.

Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli.

OpenAIRE

Clayton, M A; Clayton, J M; Brown, D R; Middlebrook, J L

1995-01-01

A completely synthetic gene encoding fragment C, a approximately 50-kDa fragment, of botulinum neurotoxin serotype A was constructed from oligonucleotides. The gene was expressed in Escherichia coli, and full-sized product was produced as judged by Western blot (immunoblot) analysis. Crude extracts of E. coli expressing the gene were used to vaccinate mice and evaluate their survival against challenge with active toxin. Mice given three subcutaneous vaccinations were protected against an intr...

International Relations and the environment: practical examples of environmental multilateralism

Directory of Open Access Journals (Sweden)

Filipa Tiago Gomes

2012-01-01

Full Text Available The “environmental crisis” we experience today and the international community’s struggle to develop environmental standards to reach the epic “sustainable development” are widely known topics. What is needed, then, is an urgent and determined practice, which is only possible if international governance is structured, coherent and effective. The optimization of Environmental Multilateralism (the joining of what are considered the “driving forces” of Environmental International Relations: Law, Politics and international Diplomacy contributes greatly to this end. To understand its basic concepts and systems, as for example, its actors, negotiation and implementation of Multilateral Environmental Agreements (MEAs and the carrying out of their Regimes, as well as their development in the United Nations, these are all crucial elements for its improvement and optimization. The United Nations Conference on Environment and Development (Rio de Janeiro, 1992 and “its” Conventions are important examples in the history of Environmental Multilateralism, still very up-to-date not only due to the 20th anniversary of the “Rio Conference” but also due to the continuity and importance that the “Rio Conventions” and their Conferences of Parties (COP still have. This papers aims to analyze this area of studies transversal to International Relations and to the Environment, namely by studying the relation between the theory of Environmental Multilateralism and its practice.

Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

Science.gov (United States)

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2010-01-01

Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

Characterization of the binding of the Ptychodiscus brevis neurotoxin T17 to sodium channels in rat brain synaptosomes

International Nuclear Information System (INIS)

Poli, M.A.

1985-01-01

The lipid-soluble polyether neurotoxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique receptor site associated with the voltage-sensitive sodium channel in rat brain synaptosomes. Reduction of the C 42 aldehyde function of T34 to the alcohol function of T17 using NaB 3 H 4 yielded 3 H-T17 with a specific activity of 15 Ci;/mmol. Using this specific probe, binding to sodium channels was measured at 4 0 CC, 22 0 C, and 37 0 C. Rosenthal analysis of the binding data yielded a K/sub d/ of 2.9 nM and B/sub max/ of 6.8 pmoles 3 H-T17 per mg of synaptosomal protein at 4 0 C. Both K/sub d/ and B/sub max/ were found to be temperature dependent. Depolarization of the synaptosomes by osmotic lysis resulted in the loss of 34% of the available receptor sites, with no decrease in binding affinity. Unlabeled T17, T34, and synthetic T17 (reduced T34) were equipotent in their ability to displace 3 H-T17 from its specific receptor site. Competition experiments using natural toxin probes specific for sites I-IV on the voltage-sensitive sodium channel demonstrate that 3 H-T17 does not bind to any of the previously-described neurotoxin receptor sites. A fifth site is proposed

Characterization of the binding of the Ptychodiscus brevis neurotoxin T17 to sodium channels in rat brain synaptosomes

Energy Technology Data Exchange (ETDEWEB)

Poli, M.A.

1985-01-01

The lipid-soluble polyether neurotoxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique receptor site associated with the voltage-sensitive sodium channel in rat brain synaptosomes. Reduction of the C/sub 42/ aldehyde function of T34 to the alcohol function of T17 using NaB/sup 3/H/sub 4/ yielded /sup 3/H-T17 with a specific activity of 15 Ci;/mmol. Using this specific probe, binding to sodium channels was measured at 4/sup 0/CC, 22/sup 0/C, and 37/sup 0/C. Rosenthal analysis of the binding data yielded a K/sub d/ of 2.9 nM and B/sub max/ of 6.8 pmoles /sup 3/H-T17 per mg of synaptosomal protein at 4/sup 0/C. Both K/sub d/ and B/sub max/ were found to be temperature dependent. Depolarization of the synaptosomes by osmotic lysis resulted in the loss of 34% of the available receptor sites, with no decrease in binding affinity. Unlabeled T17, T34, and synthetic T17 (reduced T34) were equipotent in their ability to displace /sup 3/H-T17 from its specific receptor site. Competition experiments using natural toxin probes specific for sites I-IV on the voltage-sensitive sodium channel demonstrate that /sup 3/H-T17 does not bind to any of the previously-described neurotoxin receptor sites. A fifth site is proposed.

Epitope-Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent in Cell Inhibitor of Botulinum Neurotoxin**

OpenAIRE

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M.; Das, Samir; Nag, Arundhati; Agnew, Heather D.; Heath, James R.

2015-01-01

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ ...

Researchers unmask secret to long-lasting effects of botulinum neurotoxin A in motor neurons | Center for Cancer Research

Science.gov (United States)

A team of scientists led by the Center for Cancer Research's Allan M. Weissman, M.D., and Yien Che Tsai, Ph.D., has discovered a molecular mechanism that explains the extreme toxicity of botulinum neurotoxin A (BoNT/A), the most potent BoNT strain. The discovery, published June 5 in PNAS, also identifies a molecular target that the researchers hope will eventually lead to improved therapies to treat exposure and severely undermine the potential use of BoNTs as bioweapons.  Read more...  

Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments

Directory of Open Access Journals (Sweden)

Sheng Chen

2012-10-01

Full Text Available Botulinum neurotoxins (BoNTs cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, and hemificial spasm as early as 1989 and then for treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis, chronic migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT therapies are limited to neuronal indications with the requirement of periodic injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs.

High-level expression, purification, crystallization and preliminary X-ray crystallographic studies of the receptor-binding domain of botulinum neurotoxin serotype D

International Nuclear Information System (INIS)

Zhang, Yanfeng; Gao, Xiaoli; Qin, Ling; Buchko, Garry W.; Robinson, Howard; Varnum, Susan M.

2010-01-01

The receptor-binding domain of botulinum neurotoxin serotype D was expressed in E. coli using a codon-optimized cDNA. The highly purified protein crystallized in space group P2 1 2 1 2 1 , with unit-cell parameters a = 60.8, b = 89.7, c = 93.9 Å, and the crystals diffracted to 1.65 Å resolution. Botulinum neurotoxins (BoNTs) are highly toxic proteins for humans and animals that are responsible for the deadly neuroparalytic disease botulism. Here, details of the expression and purification of the receptor-binding domain (HCR) of BoNT/D in Escherichia coli are presented. Using a codon-optimized cDNA, BoNT/D-HCR was expressed at a high level (150–200 mg per litre of culture) in the soluble fraction. Following a three-step purification protocol, very pure (>98%) BoNT/D-HCR was obtained. The recombinant BoNT/D-HCR was crystallized and the crystals diffracted to 1.65 Å resolution. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 60.8, b = 89.7, c = 93.9 Å. Preliminary crystallographic data analysis revealed the presence of one molecule in the asymmetric unit

Effect of nitrogen on cellular production and release of the neurotoxin anatoxin-a in a nitrogen-fixing cyanobacterium

Directory of Open Access Journals (Sweden)

Alexis eGagnon

2012-06-01

Full Text Available Anatoxin-a (ANTX is a neurotoxin produced by several freshwater cyanobacteria and implicated in lethal poisonings of domesticated animals and wildlife. The factors leading to its production in nature and in culture are not well understood. Resource availability may influence its cellular production as suggested by the carbon-nutrient hypothesis, which links the amount of secondary metabolites produced by plants or microbes to the relative abundance of nutrients. We tested the effects of nitrogen supply on ANTX production and release in a toxic strain of the cyanobacterium Aphanizomenon issatschenkoi (Nostocales. We hypothesized that nitrogen deficiency might constrain the production of ANTX. However, the total concentration and more significantly the cellular content of anatoxin-a peaked (max. 146 µg/L and 1683 µg•g-1 dry weight at intermediate levels of nitrogen supply when N-deficiency was evident based on phycocyanin to chlorophyll a and carbon to nitrogen ratios. The results suggest that the cellular production of anatoxin-a may be stimulated by moderate nutrient stress as described recently for another cyanotoxin (microcystin.

Mass Spectrometric Detection of Botulinum Neurotoxin by Measuring its Activity in Serum and Milk

Science.gov (United States)

Kalb, Suzanne R.; Pirkle, James L.; Barr, John R.

Botulinum neurotoxins (BoNTs) are bacterial protein toxins which are considered likely agents for bioterrorism due to their extreme toxicity and high availability. A new mass spectrometry based assay called Endopep MS detects and defines the toxin serotype in clinical and food matrices via toxin activity upon a peptide substrate which mimics the toxin's natural target. Furthermore, the subtype of the toxin is differentiated by employing mass spectrometry based proteomic techniques on the same sample. The Endopep-MS assay selectively detects active BoNT and defines the serotype faster and with sensitivity greater than the mouse bioassay. One 96-well plate can be analyzed in under 7 h. On higher level or "hot" samples, the subtype can then be differentiated in less than 2 h with no need for DNA.

Metabolic solutions to the biosynthesis of some diaminomonocarboxylic acids in nature: Formation in cyanobacteria of the neurotoxins 3-N-methyl-2,3-diaminopropanoic acid (BMAA) and 2,4-diaminobutanoic acid (2,4-DAB).

Science.gov (United States)

Nunn, Peter B; Codd, Geoffrey A

2017-12-01

The non-encoded diaminomonocarboxylic acids, 3-N-methyl-2,3-diaminopropanoic acid (syn: α-amino-β-methylaminopropionic acid, MeDAP; β-N-methylaminoalanine, BMAA) and 2,4-diaminobutanoic acid (2,4-DAB), are distributed widely in cyanobacterial species in free and bound forms. Both amino acids are neurotoxic in whole animal and cell-based bioassays. The biosynthetic pathway to 2,4-DAB is well documented in bacteria and in one higher plant species, but has not been confirmed in cyanobacteria. The biosynthetic pathway to BMAA is unknown. This review considers possible metabolic routes, by analogy with reactions used in other species, by which these amino acids might be biosynthesised by cyanobacteria, which are a widespread potential environmental source of these neurotoxins. Where possible, the gene expression that might be implicated in these biosyntheses is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Environmental problems relating to uranium mining and milling

International Nuclear Information System (INIS)

Friedman, F.B.

1979-01-01

The regulations of the mining and milling of uranium as they relate to the environment are discussed. The industry is primarily under the jurisdiction of the federal government and administered by the Nuclear Regulatory Commission (NRC). This authority can in some instances be relegated to the states. Certain areas of jurisdiction have been given over to Environmental Protection Agency (EPA) by the courts. The Safe Drinking Water Act is discussed as it relates to in situ leach mining. The role of the Department of Interior in the regulating of uranium mining, as described in the Federal Land Policy Management Act of 1976, is discussed. The requirement for environmental impact statements prior to licensing by the NRC or the individual states is also discussed. Air quality and radioactive waste disposal as they relate to uranium mining are also discussed

Potential of mediation for resolving environmental disputes related to energy facilities

Energy Technology Data Exchange (ETDEWEB)

None

1979-12-01

This study assesses the potential of mediation as a tool for resolving disputes related to the environmental regulation of new energy facilities and identifies possible roles the Federal government might play in promoting the use of mediation. These disputes result when parties challenge an energy project on the basis of its potential environmental impacts. The paper reviews the basic theory of mediation, evaluates specific applications of mediation to recent environmental disputes, discusses the views of environmental public-interest groups towards mediation, and identifies types of energy facility-related disputes where mediation could have a significant impact. Finally, potential avenues for the Federal government to encourage use of this tool are identified.

What Causes Environmental Inequalities and Related Health Effects? An Analysis of Evolving Concepts

Science.gov (United States)

Kruize, Hanneke; Droomers, Mariël; van Kamp, Irene; Ruijsbroek, Annemarie

2014-01-01

Early environmental justice studies were exposure-oriented, lacked an integrated approach, and did not address the health impact of environmental inequalities. A coherent conceptual framework, needed to understand and tackle environmental inequalities and the related health effects, was lacking. We analyzed the more recent environmental justice literature to find out how conceptual insights have evolved. The conceptual framework of the WHO Commission on Social Determinants of Health (CSDH) was analyzed for additional explanations for environmental inequalities and the related health effects. This paper points out that recent environmental justice studies have broadened their scope by incorporating a broader set of physical and social environmental indicators, and by focusing on different geographic levels and on health impacts of environmental inequalities. The CSDH framework provided additional elements such as the role of structural determinants, the role of health-related behavior in relation to the physical and social environment, access to health care, as well as the life course perspective. Incorporating elements of the CSDH framework into existing environmental justice concepts, and performing more empirical research on the interactions between the different determinants at different geographical levels would further improve our understanding of environmental inequalities and their health effects and offer new opportunities for policy action. PMID:24886752

What Causes Environmental Inequalities and Related Health Effects? An Analysis of Evolving Concepts

Directory of Open Access Journals (Sweden)

Hanneke Kruize

2014-05-01

Full Text Available Early environmental justice studies were exposure-oriented, lacked an integrated approach, and did not address the health impact of environmental inequalities. A coherent conceptual framework, needed to understand and tackle environmental inequalities and the related health effects, was lacking. We analyzed the more recent environmental justice literature to find out how conceptual insights have evolved. The conceptual framework of the WHO Commission on Social Determinants of Health (CSDH was analyzed for additional explanations for environmental inequalities and the related health effects. This paper points out that recent environmental justice studies have broadened their scope by incorporating a broader set of physical and social environmental indicators, and by focusing on different geographic levels and on health impacts of environmental inequalities. The CSDH framework provided additional elements such as the role of structural determinants, the role of health-related behavior in relation to the physical and social environment, access to health care, as well as the life course perspective. Incorporating elements of the CSDH framework into existing environmental justice concepts, and performing more empirical research on the interactions between the different determinants at different geographical levels would further improve our understanding of environmental inequalities and their health effects and offer new opportunities for policy action.

Leading product-related environmental performance indicators: a selection guide and database

DEFF Research Database (Denmark)

Issa, Isabela I.; Pigosso, Daniela Cristina Antelmi; McAloone, Tim C.

2015-01-01

Ecodesign is a proactive environmental management and improvement approach employed in the product development process, which aims to minimize the environmental impacts caused during a product's life cycle and thus improve its environmental performance. The establishment of measurable environmental...... in the selection and application of environmental performance indicators - a more structured approach is still lacking. This paper presents the efforts made to identify and systematize existing leading product-related environmental performance indicators, based on a systematic literature review, and to develop...

Uncertainty related to Environmental Data and Estimated Extreme Events

DEFF Research Database (Denmark)

Burcharth, H. F.

The design loads on rubble mound breakwaters are almost entirely determined by the environmental conditions, i.e. sea state, water levels, sea bed characteristics, etc. It is the objective of sub-group B to identify the most important environmental parameters and evaluate the related uncertainties...... including those corresponding to extreme estimates typically used for design purposes. Basically a design condition is made up of a set of parameter values stemming from several environmental parameters. To be able to evaluate the uncertainty related to design states one must know the corresponding joint....... Consequently this report deals mainly with each parameter separately. Multi parameter problems are briefly discussed in section 9. It is important to notice that the quantified uncertainties reported in section 7.7 represent what might be regarded as typical figures to be used only when no more qualified...

Neurotoxins in a water supply reservoir: An alert to environmental and human health.

Science.gov (United States)

Calado, Sabrina Loise de Morais; Wojciechowski, Juliana; Santos, Gustavo Souza; Magalhães, Valéria Freitas de; Padial, André Andrian; Cestari, Marta Margarete; Silva de Assis, Helena Cristina da

2017-02-01

Reservoirs are important source of power generation, recreation, and water supply. Nevertheless, human activities have favored the bloom of toxic cyanobacteria in many reservoirs, which has resulted in environmental, social, and economic problems. This study aims to evaluate the water quality of a reservoir in South Brazil through the analysis of cyanobacteria and cyanotoxins PSTs (Paralytic Shellfish Toxins) and biomarkers of environmental contamination in fish. For this purpose, water samples and fish (Geophagus brasiliensis) (Perciformes: Cichlidae) were collected from September 2013 to May 2014. The fish G. brasiliensis were separated in two groups. The first one "site group" was euthanized after the sampling and their weight and length were measured. The blood, brain, muscle and liver were collected for chemical, biochemical and genetics biomarkers analysis. The second group "depuration group" was submitted to depuration experiment for 40 days in clean water. After that, the same procedures as for the first group were carried out. Cylindrospermopsis raciborskii was the dominant cyanobacteria found in the reservoir, and it showed a density above the recommended limit by Brazilian legislation of 20,000 cells/mL. Results showed that the fish accumulate PSTs in the Reservoir and these were not eliminated after 40 days. The biochemical and genotoxic biomarkers showed a significant difference between "site groups" and "depuration groups", which suggests a recovery of the antioxidant system and a reduction of cellular damage after 40 days in clean water. In conjunction with results reported earlier by others, Alagados Reservoir, in South Brazil, appears to have a persistent contamination of cyanotoxins. Moreover, the mixture of contaminants which may be present in the water body can explain the seasonal differences in fish at the sampled points. Copyright © 2016 Elsevier Ltd. All rights reserved.

USER principle as relating the human environmental management

International Nuclear Information System (INIS)

Kernakis

2005-01-01

The environmental variable can be understood as the resulting biosphere space that has suffered the occurrence of pre-biotic, biotic and anthropic processes. This necessary expansion of the environmental frontier allows understand clearly the magnitude the great complexity of the process immersed in the current environmental problematic. This, taking into account the analysis of the reference systems used by the different species to face their interaction with the nature. Hence, it is necessary to evaluate the human referential process of reality, as a responsible specie of the derange shown by the Environmental Mother Eve. The latest hominid development of an Artificial Reference System (ARS) (linguistic symbols), points to the constitution of the casual factor that triggers such an environmental problematic. The expansive dynamics accomplished by the ARS has not always made reference to the natural ambience that created them. The formulation of the Unprivilegeness of Symbolic Endogenous Referents (USER) Principle (Kernakis 1986, 1997), as a necessary epistemological consequence of the Special Relativity from Einstein, entails to the reversion of the local privileges created by the ARS, stating a referential crisis as alternative to a potential environmental collapse. AII these could lead to the most intra-specific understanding with the nature, antonomastical fragmented by the privileges of the ARS. Such integration species-nature would allow to make possible an spontaneous natural-cultural arranging of the environmental balance

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

Directory of Open Access Journals (Sweden)

Stéphanie Simon

2015-11-01

Full Text Available Botulinum neurotoxins (BoNTs cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G, of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples.

Science.gov (United States)

Simon, Stéphanie; Fiebig, Uwe; Liu, Yvonne; Tierney, Rob; Dano, Julie; Worbs, Sylvia; Endermann, Tanja; Nevers, Marie-Claire; Volland, Hervé; Sesardic, Dorothea; Dorner, Martin B

2015-11-26

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A-G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as "category A" bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Using llama derived single domain antibodies to target botulinum neurotoxins

Science.gov (United States)

Swain, Marla D.; Anderson, George P.; Bernstein, Rachael D.; Liu, Jinny L.; Goldman, Ellen R.

2010-04-01

Llama serum contains both conventional IgG as well as unique forms of antibody that contain only heavy chains where antigen binding is mediated through a single variable domain. These variable domains can be expressed recombinantly and are referred to as single domain antibodies (sdAb). SdAb are among the smallest known naturally derived antigen binding fragments, possess good solubility, thermal stability, and can refold after heat and chemical denaturation. Llamas were immunized with either BoNT A or B toxoid and phage display libraries prepared. Single domain antibodies (sdAb) that were able to detect botulinum neurotoxin (BoNT) serotypes A and B were selected from their respective libraries. Here, the binders obtained by panning the BoNT B library on either BoNT B toxoid or BoNT B complex toxoid coated plates or BoNT B toxin coupled microspheres are described. Using these panning methods, we selected for binders that showed specificity for BoNT B. Phage displayed binders were screened, moved to a protein expression vector and soluble sdAb was produced. Using a Luminex flow cytometer binders were evaluated in direct binding assays. We have exploited the unique properties of sdAb and used them as biological recognition elements in immuno-based sensors that can detect BoNT B.

Environmental issues related to commercialization of CulnSe2- based photovoltaics

International Nuclear Information System (INIS)

Eberspacher, C.; Fthenakis, V.M.; Moskowitz, P.D.

1996-01-01

One of the most promising materials for low-cost thin film photovoltaic cells is copper indium selenide (CuInSe 2 or CIS). As with any new material, successful commercialization of CIS photovoltaic (PV) technology will require attention to environmental issues related to the sources of raw materials, their usage, and the disposal and/or recycling of products at the end of their useful life. This paper focuses on three specific environmental issues related to CIS technology: (i) Economics of the use and re-use of materials; (ii) regulations on environmental disposal and waste handling, and (iii) logistics and economics of recycling and disposing of products by industries faced with comparable environmental issues

Environmental remediation: Addressing public concerns through effective community relations

International Nuclear Information System (INIS)

Davis, S.; Heywood, J.; Wood, M.B.; Arellano, M.; Pfister, S.

1998-01-01

The public's perception of risk drives their response to any potential environmental remediation project. Even if the actual environmental and health risks may be relatively low, public perception of high risk may doom the project to an uphill struggle characterized by heated public meetings, negative media coverage, reluctant regulators, project delays and increased costs. The ultimate Catch 22 in such a case is that the contamination remains in-place until the public drama is concluded. This paper explores the development and implementation of a Community Relations Plan for the clean up of a Manufactured Gas Plant (MGP) site owned and operated by corporate predecessors of Arizona Public Service Company (APS) near the turn of the century. The unique challenges associated with this project were that the former MGP was located in downtown Phoenix at the site of a future federal courthouse. Although the MGP site had been under investigation for some time, the clean-up schedule was driven by a tight courthouse construction schedule. Compounding these challenges were the logistics associated with conducting a large-scale cleanup in a congested, highly visible downtown location. An effective Community Relations Plan can mean the difference between the success and failure of an environmental remediation project. Elements of an effective plan are: identifying key stakeholders and involving them in the project from the beginning; providing timely information and being open and honest about the potential environmental and health risks; involving your company's community relations and media staff; and educating affected company employees. The Community Relations Plan developed for this project was designed to alleviate public concern about potential risks (perceived or real) associated with the project by keeping key stakeholders informed of all activities well in advance

Tiger team findings related to DOE environmental restoration activities

International Nuclear Information System (INIS)

Levitan, W.M.

1991-01-01

Tiger Team Assessments were implemented in June 1989 as part of a strategy to ensure that DOE facilities fully comply with Federal, state, local and DOE environment, safety, and health (ES ampersand H) requirements. The Tiger Teams provide the Secretary of Energy with information on current ES ampersand H compliance status of each DOE facility and causes for noncompliance. To date, Tiger Team Assessments have been completed at 25 DOE facilities. With regard to assessments of environmental restoration activities, the performance of DOE facilities was evaluated against the requirements of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended, the National Contingency Plan (NCP), and DOE Order 5400.4, CERCLA Requirements, among others. Five major categories of environmental restoration-related findings were identified: (1) environmental restoration program planning and management (found at 60 percent of the sites assessed); (2) community relations/administrative record (60 percent); (3) characterization of extent of contamination (56 percent); (4) identification and evaluation of inactive waste sites (56 percent); and (5) DOE and NCP requirements for response action studies (44 percent). Primary causal factors for these findings were inadequate procedures, resources, supervision, and policy implementation

Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

Science.gov (United States)

Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

2017-07-01

Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical

Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

Science.gov (United States)

Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

2018-03-15

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Seeking environmental causes of neurodegenerative disease and envisioning primary prevention.

Science.gov (United States)

Spencer, Peter S; Palmer, Valerie S; Kisby, Glen E

2016-09-01

Pathological changes of the aging brain are expressed in a range of neurodegenerative disorders that will impact increasing numbers of people across the globe. Research on the causes of these disorders has focused heavily on genetics, and strategies for prevention envision drug-induced slowing or arresting disease advance before its clinical appearance. We discuss a strategic shift that seeks to identify the environmental causes or contributions to neurodegeneration, and the vision of primary disease prevention by removing or controlling exposure to culpable agents. The plausibility of this approach is illustrated by the prototypical neurodegenerative disease amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long-latency disease, once thought to be an inherited genetic disorder but now known to have a predominant or exclusive environmental origin, is in the process of disappearing from the three heavily affected populations, namely Chamorros of Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure via traditional food and/or medicine (the only common exposure in all three geographic isolates) to one or more neurotoxins in seed of cycad plants is the most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at exposure might explain the stratified epidemic of neurodegenerative disease on Guam in which high-incidence ALS peaked and declined before that of PD, only to be replaced today by a dementing disorder comparable to Alzheimer's disease. Exposure to the Guam environment is also linked to the delayed development of ALS among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of which is reported here for the first time. Lessons learned from this study and from 65 years of research on ALS-PDC include the exceptional value of initial, field-based informal investigation of

An analysis of students’ cognitive structures in relation to their environmental sensitivity

Directory of Open Access Journals (Sweden)

Gercek Cem

2017-01-01

Full Text Available One of the basic aims of environment-related subjects included in the biology curriculum is to raise environmental awareness. Yet, the fact that the concepts taught especially in the context of environmental issues are abstract influences meaningful learning. This, in turn, influences behaviours displayed. Exhibiting students’ cognitive structures in assuring effective and meaningful concept teaching increases the importance of studies conducted. Unavailability of studies in the literature analysing students’ cognitive structures in relation to their sensitivity to the environment demonstrates the importance of this current study. This study aims to analyse students’ cognitive structures in relation to their environmental sensitivity. The study employs survey model- one of the qualitative research designs. The study group was composed of 56 high school students in the 2016-2017 academic year. The study group was formed through purposeful sampling. Word Association Test (WAT was prepared in order to uncover students’ cognitive structures in relation to their environmental sensitivity. Having transcribed the data obtained, they were put to content analysis and were transferred to the medium of computer. The results showed that students’ cognitive structure concerning their environmental sensitivity was divided into categories.

Environmental radiological surveillance in perspective: the relative importance of environmental media as a function of effluent pathway and radionuclides

International Nuclear Information System (INIS)

Denham, D.H.

1977-01-01

Most published guidelines for environmental surveillance emphasize the collection and analysis of specific media (e.g. air, water, milk, direct radiation) without total regard for the potential dose impact of the radionuclides expected in or actually present in the effluent streams FR-om nuclear facilities. To determine the relative importance of medium/nuclide combinations in environmental surveillance, the experience at major ERDA sites and at operating nuclear power plants was reviewed. Typical release rates for nuclide groupings (tritium, noble gases, radioiodine, mixed fission or activation products, and transuranics) in those effluent streams were followed through various environmental pathways. By using this scheme the environmental medium which is most prominent in the critical dose pathway to man was determined. It was also possible to determine points of short-or long-term contaminant accumulation. Following these combination providing the relative importance of sampling specific environmental media with emphasis on the radiation dose to a critical population group. Finally, the results of these environmental pathway studies are presented in tabular form to provide ready reference for environmental surveillance program design or evaluation

Botulinum neurotoxin type-A when utilized in animals with trigeminal sensitization induced a antinociceptive effect

Directory of Open Access Journals (Sweden)

Elcio J Piovesan

2016-06-01

Full Text Available ABSTRACT Purpose of the study was evaluate the possible antinociceptive effect of botulinum neurotoxin type-A (BoNT/A in an experimental model of trigeminal neuralgia. Method Neuropathic pain was induced by surgical constriction of the infraorbital nerve in rats. A control group underwent a sham procedure consisting of surgical exposure of the nerve. Subgroups of each group received either BoNT/A or isotonic saline solution. The clinical response was assessed with the -20°C test. Animals that underwent nerve constriction developed sensitization; the sham group did not. Results The sensitization was reversed by BoNT/A treatment evident 24 hours following application. Pronociceptive effect was observed in the sham group following BoNT/A. Conclusion BoNT/A has an antinociceptive effect in sensitized animals and a pronociceptive effect in non-sensitized animals.

78 FR 18562 - Economic and Environmental Principles and Guidelines for Water and Related Land Resources...

Science.gov (United States)

2013-03-27

... COUNCIL ON ENVIRONMENTAL QUALITY Economic and Environmental Principles and Guidelines for Water... the Army to revise the ``Economic and Environmental Principles and Guidelines for Water and Related... Army to revise the ``Economic and Environmental Principles and Guidelines for Water and Related Land...

Environmental issues related to commercialization of CulnSe{sub 2}- based photovoltaics

Energy Technology Data Exchange (ETDEWEB)

Eberspacher, C. [UNISUN, Newbury Park, CA (United States); Fthenakis, V.M.; Moskowitz, P.D.

1996-07-01

One of the most promising materials for low-cost thin film photovoltaic cells is copper indium selenide (CuInSe{sub 2} or CIS). As with any new material, successful commercialization of CIS photovoltaic (PV) technology will require attention to environmental issues related to the sources of raw materials, their usage, and the disposal and/or recycling of products at the end of their useful life. This paper focuses on three specific environmental issues related to CIS technology: (i) Economics of the use and re-use of materials; (ii) regulations on environmental disposal and waste handling, and (iii) logistics and economics of recycling and disposing of products by industries faced with comparable environmental issues.

Environmental radiological surveillance in perspective: the relative importance of environmental media as a function of effluent pathway and radionuclides

International Nuclear Information System (INIS)

Denham, D.H.

1977-10-01

Most published guidelines for environmental surveillance emphasize the collection and analysis of specific media (e.g. air, water, milk, direct radiation) without total regard for the potential dose impact of the radionuclides expected in or actually present in the effluent streams from nuclear facilities. To determine the relative importance of medium/nuclide combinations in environmental surveillance, the experience at major ERDA sites and at operating nuclear power plants was reviewed. Typical release rates for nuclide groupings (tritium, noble gases, radioiodine, mixed fission or activation products, and transuranics) in those effluent streams were followed through various environmental pathways. By using this scheme the environmental medium which is most prominent in the critical dose pathway to man was determined. It was also possible to determine points of short-or long-term contaminant accumulation. Following these calculations, each medium was ranked for a given nuclide/effluent pathway combination providing the relative importance of sampling specific environmental media with emphasis on the radiation dose to a critical population group. Finally, the results of these environmental pathway studies are presented in tabular form to provide ready reference for environmental surveillance program design or evaluation

[Prophylaxis of recurring low-flow priapism : Experimental botulinum neurotoxin injection into the ischiocavernosus muscle].

Science.gov (United States)

Reichel, G; Stenner, A

2018-01-01

The treatment of recurring low-flow priapism with the usual medications is still unsatisfactory. The case of an otherwise healthy young man experiencing low-flow priapism at the age of 31 is presented. A reason for his condition could not be identified. Over the course of several months, he required emergency urological treatment more than ten times. Treatment with cyproterone acetate (Androcur® 50 mg/day) stopped the spontaneous erections, but resulted in erectile impotence, reduced motivation, decreased interest in sex, weight gain of 10 kg, breast enlargement combined with touch sensitivity on both sides, and hair loss on both legs. In addition, the patient complained about painful cramps in his pelvic muscles. After appropriate explanations he agreed to try botulinum neurotoxin injections into both ischiocavernosus muscles. The objective was to reduce muscle tone in order to improve venous drainage of blood from the penis. The latest relapse of priapism occurred more than 6 months ago.

Rational design of botulinum neurotoxin A1 mutants with improved oxidative stability.

Science.gov (United States)

López de la Paz, Manuela; Scheps, Daniel; Jurk, Marcel; Hofmann, Fred; Frevert, Jürgen

2018-06-01

Botulinum neurotoxins (BoNTs) are the most potent toxic proteins to mankind known but applied in low doses trigger a localized muscle paralysis that is beneficial for the therapy of several neurological disorders and aesthetic treatment. The paralytic effect is generated by the enzymatic activity of the light chain (LC) that cleaves specifically one of the SNARE proteins responsible for neurotransmitter exocytosis. The activity of the LC in a BoNT-containing therapeutic can be compromised by denaturing agents present during manufacturing and/or in the cell. Stabilization of the LC by reducing vulnerability towards denaturants would thus be advantageous for the development of BoNT-based therapeutics. In this work, we focused on increasing the stability of LC of BoNT/A1 (LC/A1) towards oxidative stress. We tackled this task by rational design of mutations at cysteine and methionine LC/A1 sites. Designed mutants showed improved oxidative stability in vitro and equipotency to wildtype toxin in vivo. Our results suggest that suitable modification of the catalytic domain can lead to more stable BoNTs without impairing their therapeutic efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

78 FR 20074 - Environmental Impact and Related Procedures

Science.gov (United States)

2013-04-03

... DEPARTMENT OF TRANSPORTATION Federal Highway Administration 23 CFR Part 771 Federal Transit Administration 49 CFR Part 622 [Docket No. FHWA-2013-0007] FHWA RIN 2125-AF48 FTA RIN 2132-AB05 Environmental Impact and Related Procedures Correction The correction that appeared on page 15925, Wednesday, March 13...

78 FR 15925 - Environmental Impact and Related Procedures

Science.gov (United States)

2013-03-13

... DEPARTMENT OF TRANSPORTATION Federal Highway Administration 23 CFR Part 771 Federal Transit Administration 49 CFR Part 622 [Docket No. FHWA-2012-2013] FHWA RIN 2125-AF48 FTA RIN 2132-AB05 Environmental Impact and Related Procedures Correction In proposed rule document 2013-4678 beginning on page 13609 in...

The relative contributions of climatic elements and environmental ...

African Journals Online (AJOL)

The aim of this paper was to determine the relative contributions of climatic elements and environmental factors to urban flooding in Awka urban area of Anambra State. Towards achieving this aim, 10 year (2000-2009) meteorological data of temperature and rainfall of the study area were collected from synoptic ...

Status of health and environmental research relative to coal gasification 1976 to the present

Energy Technology Data Exchange (ETDEWEB)

Wilzbach, K.E.; Reilly, C.A. Jr. (comps.)

1982-10-01

Health and environmental research relative to coal gasification conducted by Argonne National Laboratory, the Inhalation Toxicology Research Institute, and Oak Ridge National Laboratory under DOE sponsorship is summarized. The studies have focused on the chemical and toxicological characterization of materials from a range of process streams in five bench-scale, pilot-plant and industrial gasifiers. They also address ecological effects, industrial hygiene, environmental control technology performance, and risk assessment. Following an overview of coal gasification technology and related environmental concerns, integrated summaries of the studies and results in each area are presented and conclusions are drawn. Needed health and environmental research relative to coal gasification is identified.

[The reaction of the neuroblastoma cells in the culture on the influence of tretionine and neurotoxine].

Science.gov (United States)

Magakian, Iu A; Karalian, Z A; Karalova, E M; Abroian, L O; Akopian, L A; Avetisian, A C; Semerdzhian, Z B

2011-01-01

Effect of the tretionine (retinoid) and aluminum chloride (neurotoxin) on the growth and differentiation of neuroblastoma cells in culture after their introduction into the medium separately and in combination was studied. The introduction of these substances creates a new information field in the medium, which becomes apparent by the reactions of neuroblastoma found on the populational and cellular levels of its organization. The presence of tretionine stimulates proliferation and induces differentiation of the cells into astrocytes. Aluminum chloride inhibits cell proliferation and enhances the process of their destruction in the monolayer. The variety of the reactions of neuroblastoma cells to the presence of these substances in the medium indicates the existence and functioning of a mechanism that selects from the information introduced only the portion which may contribute to adaptation of neuroblastoma cells to the changed culture conditions.

Recommendations related to the strategic environmental assessment. Methodological note

International Nuclear Information System (INIS)

Le Bris, Charlotte; Brivadier, Isabelle; Fournie, Sebastien; Godart, Angelique; Hubert, Severine; Ille, Yann-Mikiel; Le Mitouard, Eric; Phelep, Michele; Delduc, Paul; Poitevin, Florent; Lemaitre, Valery; Bataille, Tristan; Noulin, Alice; Fevre, Cecile; Kervella, Frederic; Orefici, Christine; Rambaud, Lucile; Antoine, Stephanie; Wormser, Veronique; Garrigou, Olivier; Vinay, Catherine; Cretin, Benedicte; Le Saout, Michaele; Pagnucco, Fabrice; Meinier, Yves; Nicolas, Veronique; Thiolliere, Blandine; Guilbert, Sebastien; Billant, Claude; Saingenest, Patrick

2015-05-01

This methodological note aims at giving commissioners and project managers of plans, schemes and programmes or other planning documents related to strategic environmental assessment a comprehensive vision of the approach to be adopted, as well as useful advices and operational recommendations. The first part recalls the main principles of environmental assessment, addresses general issues of organisation of the approach, and clarifies its articulation with the plan/scheme/programme elaboration or other approaches such as the assessment of incidences on the Natura 2000 network. The second part addresses the different chapters which are foreseen by the regulation for the environmental report. Some sheets are proposed on SDAGEs (Water Development and Management Master Plans) and PGIRs (flood risk management plans), on SRCs (quarry regional plan) and SAGEs (Water Development and Management Scheme)

The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes.

Directory of Open Access Journals (Sweden)

Sara Marinelli

Full Text Available In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25, the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A, could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw's nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC. We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients' quality of life.

Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

Directory of Open Access Journals (Sweden)

Witchuda Danpaiboon

2014-05-01

Full Text Available Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase. N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv.

Science.gov (United States)

Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

2014-05-13

Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

Glossary of CERCLA, RCRA and TSCA related terms and acronyms. Environmental Guidance

Energy Technology Data Exchange (ETDEWEB)

1993-10-01

This glossary contains CERCLA, RCRA and TSCA related terms that are most often encountered in the US Department of Energy (DOE) Environmental Restoration and Emergency Preparedness activities. Detailed definitions are included for key terms. The CERCLA definitions included in this glossary are taken from the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), as amended and related federal rulemakings. The RCRA definitions included in this glossary are taken from the Resource Conservation and Recovery Act (RCRA) and related federal rulemakings. The TSCA definitions included in this glossary are taken from the Toxic Substances and Control Act (TSCA) and related federal rulemakings. Definitions related to TSCA are limited to those sections in the statute and regulations concerning PCBs and asbestos.Other sources for definitions include additional federal rulemakings, assorted guidance documents prepared by the US Environmental Protection Agency (EPA), guidance and informational documents prepared by the US Department of Energy (DOE), and DOE Orders. The source of each term is noted beside the term. Terms presented in this document reflect revised and new definitions published before July 1, 1993.

Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A

Science.gov (United States)

Lam, Tina I.; Tam, Christina C.; Stanker, Larry H.; Cheng, Luisa W.

2016-01-01

Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins. In this study, we evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Several probiotics tested (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri) blocked BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain of Escherichia coli did not. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A binding and internalization in vitro and may lead to the development of new therapies. PMID:27999281

Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A

Directory of Open Access Journals (Sweden)

Tina I. Lam

2016-12-01

Full Text Available Botulinum neurotoxins (BoNTs are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins. In this study, we evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Several probiotics tested (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri blocked BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain of Escherichia coli did not. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A binding and internalization in vitro and may lead to the development of new therapies.

Amino acid neurotoxins in feathers of the Lesser Flamingo, Phoeniconaias minor.

Science.gov (United States)

Metcalf, J S; Banack, S A; Kotut, K; Krienitz, L; Codd, G A

2013-01-01

The Lesser Flamingo (Phoeniconaias minor) is known to use cyanobacteria (primarily Arthrospira) as a major food source in the East African Rift Valley lakes. Periodically, mass mortalities have occurred, associated with the cyanobacterial toxins (cyanotoxins), microcystins and anatoxin-a. Deposition of these cyanotoxins into P. minor feathers has been shown to occur, consistent with the presence of cyanotoxins in the livers, stomach and faecal contents after dietary intake. As cyanobacteria have been shown to also produce the neurotoxins β-N-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB), stored wing feathers, previously recovered from flamingos which had been exposed to microcystins and anatoxin-a and had subsequently died, were analysed for these neurotoxic amino acids. Trace amounts of BMAA were detected in extracts from Lake Nakuru flamingo feathers, with DAB also present at concentrations between 3.5 and 8.5 μg g(-1) dry weight in feathers from both lakes. Toxin recovery by solid-phase extraction of feather digests was tested with spiked deuterated BMAA and showed good recovery when analysed by LC-MS/MS (80-94%). This is the first report of these neurotoxic amino acids in birds. We discuss the origin and significance of DAB, alongside other cyanotoxins of dietary origin, in the feathers of the Lesser Flamingo. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vitro detection and quantification of botulinum neurotoxin type E activity in avian blood

Science.gov (United States)

Piazza, Timothy M.; Blehert, David S.; Dunning, F. Mark; Berlowski-Zier, Brenda M.; Zeytin, Fusun N.; Samuel, Michael D.; Tucker, Ward C.

2011-01-01

Botulinum neurotoxin serotype E (BoNT/E) outbreaks in the Great Lakes region cause large annual avian mortality events, with an estimated 17,000 bird deaths reported in 2007 alone. During an outbreak investigation, blood collected from bird carcasses is tested for the presence of BoNT/E using the mouse lethality assay. While sensitive, this method is labor-intensive and low throughput and can take up to 7 days to complete. We developed a rapid and sensitive in vitro assay, the BoTest Matrix E assay, that combines immunoprecipitation with high-affinity endopeptidase activity detection by Förster resonance energy transfer (FRET) to rapidly quantify BoNT/E activity in avian blood with detection limits comparable to those of the mouse lethality assay. On the basis of the analysis of archived blood samples (n = 87) collected from bird carcasses during avian mortality investigations, BoTest Matrix E detected picomolar quantities of BoNT/E following a 2-h incubation and femtomolar quantities of BoNT/E following extended incubation (24 h) with 100% diagnostic specificity and 91% diagnostic sensitivity.

Resourceful Thinking about Printing and Related Industries: Economic Considerations and Environmental Sustainability

Science.gov (United States)

Wikina, Suanu Bliss; Thompson, Cynthia Carlton; Blackwell, Elinor

2010-01-01

Increasing population, total economic volume, and human consumption levels have resulted in problems of resource shortages, climate change, ozone layer depletion, land regression, and deteriorating environmental pollution. Printing and related industries constitute one of the major sources of environmental pollution due to heavy energy and…

Energy saving in Swedish households. The (relative) importance of environmental attitudes

International Nuclear Information System (INIS)

Martinsson, Johan; Lundqvist, Lennart J.; Sundstroem, Aksel

2011-01-01

The objectives for energy saving in the housing sector set by recent Swedish energy and climate policies are quite demanding. This article uses nation-wide Swedish survey data from 2004 to 2007 to explore the potential for achieving those targets. Earlier findings that socio-economic characteristics such as age, housing type and income are strongly linked to higher propensities to save on heating and hot water usage are confirmed by ordered logistic regression models. However, general environmental attitudes are also found to play a crucial role. When assessing the relative importance of socio-economic factors and environmental attitudes, the effect on energy saving is generally greater for the former than the latter. In addition, important interaction effects are identified. In relative terms, the effect of environmental attitudes is clearly stronger among households in apartment blocks than among those in detached housing, and stronger among households with higher income than among those with lower income. We end by discussing the implications for the selection and targeting of policy measures to tap the energy savings potential in the population. - Highlights: → We use Swedish survey data to analyse the determinants of household energy saving. → Housing type plays a crucial role for individuals' propensity to save energy. → Environmental attitudes are clearly more important in high-income households. → Environmental attitudes are clearly more important for people in apartment blocks.

Several issues related to regional environmental investigation to inland nuclear power plant

International Nuclear Information System (INIS)

Tian Xinshan; Zhang Xiaofeng

2010-01-01

Based on the goal of carrying out regional environmental investigation and review of recent environmental investigations toward inland nuclear power plant(NPP) site, and combined with the characteristics between inland and coastal sites, this paper is to make deeply analysis on population distribution, environmental characteristics, feasibility of performing emergency plan, characteristics of received water and external human-induced incident of NPP vicinity, then advance several significant issues related regional environmental investigation to inland sites, and make comparison with the investigation to coastal sites. Meantime, on guarantee of the integrity of collected materials during investigation, this paper also makes several proposals to provide reference for carrying out regional environmental investigation to inland NPP site. (authors)

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography.

Science.gov (United States)

Kumaran, Desigan; Adler, Michael; Levit, Matthew; Krebs, Michael; Sweeney, Richard; Swaminathan, Subramanyam

2015-11-15

The seven antigenically distinct serotypes (A-G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins consisting of a ∼ 100 kDa heavy chain and a ∼ 50 kDa light chain; the former is responsible for neurospecific binding, internalization and translocation, and the latter for cleavage of neuronal SNARE proteins. Because of their extreme toxicity and history of weaponization, the BoNTs are regarded as potential biowarfare/bioterrorism agents. No post-symptomatic therapeutic interventions are available for BoNT intoxication other than intensive care; therefore it is imperative to develop specific antidotes against this neurotoxin. To this end, a cyclic peptide inhibitor (CPI-1) was evaluated in a FRET assay for its ability to inhibit BoNT/A light chain (Balc). CPI was found to be highly potent, exhibiting a Ki of 12.3 nM with full-length Balc448 and 39.2 nM using a truncated crystallizable form of the light chain (Balc424). Cocrystallization studies revealed that in the Balc424-CPI-1 complex, the inhibitor adopts a helical conformation, occupies a high percentage of the active site cavity and interacts in an amphipathic manner with critical active site residues. The data suggest that CPI-1 prevents SNAP-25 from accessing the Balc active site by blocking both the substrate binding path at the surface and the Zn(2+) binding region involved in catalysis. This differs from linear peptide inhibitors described to date which block only the latter. Published by Elsevier Ltd.

How Do Learners in Developed and Developing Countries Relate to Environmental Issues?

Science.gov (United States)

Trumper, Ricardo

2010-01-01

The present study was carried out in the framework of earlier research on environmental education for sustainability, using data collected in the ROSE Project. Attention was focused mainly on students' responses to sections and items related to environmental issues, regarding their countries' degree of development. The research questions dealt…

78 FR 18562 - Economic and Environmental Principles and Requirements for Water and Related Land Resources...

Science.gov (United States)

2013-03-27

... COUNCIL ON ENVIRONMENTAL QUALITY Economic and Environmental Principles and Requirements for Water... ``Economic and Environmental Principles and Guidelines for Water and Related Land Resources Implementation... Secretary of the Army to revise the ``Economic and Environmental Principles and Guidelines for Water and...

78 FR 31521 - Economic and Environmental Principles and Guidelines for Water and Related Land Resources...

Science.gov (United States)

2013-05-24

... COUNCIL ON ENVIRONMENTAL QUALITY Economic and Environmental Principles and Guidelines for Water... the Army to revise the ``Economic and Environmental Principles and Guidelines for Water and Related.... L. 110-114) directed the Secretary of the Army to revise the ``Economic and Environmental Principles...

Environmental quality rehabilitation relating to the cessation of a thermal plant

International Nuclear Information System (INIS)

Pauna, Gheorghe; Budulan, Pompiliu; Pavel, Adina Mariana

2004-01-01

The paper describes the environmental requirements as a result of the IANCA Thermal Plant running on coal, taking out of operation and turning it to better account by selling or dismantling it. Thus, in agreement with the Environmental Protection Law No. 137/29.12.1995- modified and republished on 17.02.2000//Article 15 specifies that when the investment changes its owner or destination or the activities generating an impact on the environment cease to exist, it is mandatory that the former owner develop an environmental study, with a view to establishing the requirements obligations relating to environmental quality restoration in the area the respective activity had an impact on. In the paper will be presented the following issues: environmental obligations resulting from the objective putting out of operation. Legislative specifications; specific works and environmental protection measures: installation, equipment, sub assemblies, spare parts turning to better account; general conditions (prerequisites) for waste management,, categories of waste resulting from the IANCA Thermal Plant dismantling. Its storage and turning to better account. (Author)

Multimodal aspects of CSR communication related to gender empowerment and environmental protection

DEFF Research Database (Denmark)

Maier, Carmen Daniela

Purpose – This paper explores how the multimodal persuasive strategies of CSR communication related to Coca-Cola’s “5 by 20” succeed to highlight the company’s continuous commitment to gender empowerment and environmental protection. Launched in 2010, “5 by 20” is a program designed to empower 5...... million female entrepreneurs throughout the company’s global business system by 2020. The program has recently received 2013 Catalyst Award for its accomplishments. According to the company’s homepage, hundreds of thousands of women around the world are building stronger businesses, families...... and communities due to the implementation of this program. The environmental concerns are embedded in their activities. Approach – Drawing on an interdisciplinary methodological framework related to CSR communication, multimodal discourse analysis, gender theory and environmental communication, the paper proposes...

Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: synthesis, crystallography, modeling, kinetic and cellular based studies.

Science.gov (United States)

Šilhár, Peter; Silvaggi, Nicholas R; Pellett, Sabine; Čapková, Kateřina; Johnson, Eric A; Allen, Karen N; Janda, Kim D

2013-03-01

Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind and are responsible for the neuroparalytic disease botulism. Current treatments for botulinum poisoning are all protein based and thus have a limited window of treatment opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a therapeutic strategy for the treatment of botulism as it may provide an effective post exposure remedy. Using a combination of crystallographic and modeling studies a series of hydroxamates derived from 1-adamantylacetohydroxamic acid (3a) were prepared. From this group of compounds, an improved potency of about 17-fold was observed for two derivatives. Detailed mechanistic studies on these structures revealed a competitive inhibition model, with a K(i)=27 nM, which makes these compounds some of the most potent small molecule, non-peptidic BoNT/A LC inhibitors reported to date. Copyright © 2012 Elsevier Ltd. All rights reserved.

Socially related fears following exposure to trauma: environmental and genetic influences.

Science.gov (United States)

Collimore, Kelsey C; Asmundson, Gordon J G; Taylor, Steven; Jang, Kerry L

2009-03-01

Few studies have examined why socially related fears and posttraumatic stress commonly, but not invariably, co-occur. It may be that only traumata of human agency (e.g., sexual assault), for which there is an interpersonal component, give rise to co-occurring socially related fears. These symptoms might also co-occur because of shared genetic factors. We investigated these issues using a sample of 882 monozygotic and dizygotic twins. No significant differences in socially related fear (i.e., fear of negative evaluation, fear of socially observable arousal symptoms) were found between participants reporting assaultive or nonassaultive trauma. However, significant differences in socially related fear were found when participants were grouped into probable PTSD and no PTSD groups. Participants with probable PTSD exhibited greater socially related fear (i.e., fear of negative evaluation) than those without PTSD. Using biometric structural equation modeling, trauma exposure was best explained by shared and nonshared environmental influences. The fear of socially observable arousal symptoms was influenced by genetic and nonshared environmental influences. Implications and directions for future research are discussed.

Emergence of collective action and environmental networking in relation to radioactive waste management

International Nuclear Information System (INIS)

Williams, R.G.; Payne, B.A.

1985-01-01

This paper explores the relationship between the national environmental movement and nuclear technology in relation to a local emergent group. The historical development of nuclear technology in this conutry has followed a path leading to continued fear and mistrust of waste management by a portion of the population. At the forefront of opposition to nuclear technology are people and groups endorsing environmental values. Because of the antinuclear attitudes of environmentalists and the value orientation of appropriate technologists in the national environmental movement, it seems appropriate for local groups to call on these national groups for assistance regarding nuclear-related issues. A case study is used to illustrate how a local action group, once integrated into a national environmental network, can become an effective, legitimate participant in social change. The formation, emergence, mobilization, and networking of a local group opposed to a specific federal radioactive waste management plan is described based on organizational literature. However, inherent contradictions in defining the local versus national benefits plus inherent problems within the environmental movement could be acting to limit the effectiveness of such networks. 49 refs

125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection

International Nuclear Information System (INIS)

Wiegand, H.; Erdmann, G.; Wellhoener, H.H.

1976-01-01

On unilateral injection of sublethal doses of 125 I-botulinum A neurotoxin (BTA) into one gastrocnemius muscle of the cat we found after 48 h: a disto-proximal gradient of radioactivity (RA) hat developed in the sciatic nerve of the injected side. The ventral roots of the spinal cord half segments supplying the injected muscle showed a higher RA than the ventral roots of the contralateral control side. The spinal cord half segments innervating the injected muscle had a RA much higher than the corresponding segments of the contralateral side. However, a small rise of RA was also observed in the contralateral half segments. In histoautoradiographs of the (ligatured) ventral roots the RA was strictly confined to the intraaxonal space of a few nerve fibres. On injection of equal doses of 125 I-BTA into either gastrocnemius muscle we found after 38 h: direct stimulation of only one of the injected muscles caused the RA to reach a higher level in the spinal cord half segments ipsilateral to the stimulated muscle than in the spinal cord half segments of the non-stimulated side. Unilateral stimulation of one gastrocnemius nerve under the influence of gallamine or unilateral antidromic stimulation of the dorsal roots L7, S1 failed to cause a difference in RA between stimulated and non-stimulated side. (orig.) [de

Multiplex Biosensing Based on Highly Sensitive Magnetic Nanolabel Quantification: Rapid Detection of Botulinum Neurotoxins A, B, and E in Liquids.

Science.gov (United States)

Orlov, Alexey V; Znoyko, Sergey L; Cherkasov, Vladimir R; Nikitin, Maxim P; Nikitin, Petr I

2016-11-01

We present a multiplex quantitative lateral flow (LF) assay for simultaneous on-site detection of botulinum neurotoxin (BoNT) types A, B, and E in complex matrixes, which is innovative by virtually no sacrifice in performance while transition from the single-plex assays and by characteristics on the level of laboratory quantitative methods. The novel approach to easy multiplexing is realized via joining an on-demand set of single-plex LF strips, which employ magnetic nanolabels, into a miniature cylinder cartridge that mimics LF strip during all assay stages. The cartridge is read out by an original portable multichannel reader based on the magnetic particle quantification technique. The developed reader offers the unmatched 60 zmol detection limit and 7-order linear dynamic range for volumetric registration of magnetic labels inside a cartridge of several millimeters in diameter regardless of its optical transparency. Each of the test strips, developed here as building blocks for the multiplex assay, can be used "as is" for autonomous quantitative single-plex detection with the same measuring setup, exhibiting the limits of detection (LOD) of 0.22, 0.11, and 0.32 ng/mL for BoNT-A, -B, and -E, respectively. The proposed multiplex assay has demonstrated the remarkably similar LOD values of 0.20, 0.12, 0.35 ng/mL under the same conditions. The multiplex assay performance was successfully validated by BoNT detection in milk and apple and orange juices. The developed methods can be extended to other proteins and used for rapid multianalyte tests for point-of-care in vitro diagnostics, food analysis, biosafety and environmental monitoring, forensics, and security, etc.

Binding sites and actions of Tx1, a neurotoxin from the venom of the spider Phoneutria nigriventer, in guinea pig ileum

Directory of Open Access Journals (Sweden)

R.G. Santos

1999-12-01

Full Text Available Tx1, a neurotoxin isolated from the venom of the South American spider Phoneutria nigriventer, produces tail elevation, behavioral excitation and spastic paralysis of the hind limbs after intracerebroventricular injection in mice. Since Tx1 contracts isolated guinea pig ileum, we have investigated the effect of this toxin on acetylcholine release, as well as its binding to myenteric plexus-longitudinal muscle membranes from the guinea pig ileum. [125I]-Tx1 binds specifically and with high affinity (Kd = 0.36 ± 0.02 nM to a single, non-interacting (nH = 1.1, low capacity (Bmax 1.1 pmol/mg protein binding site. In competition experiments using several compounds (including ion channel ligands, only PhTx2 and PhTx3 competed with [125I]-Tx1 for specific binding sites (K0.5 apparent = 7.50 x 10-4 g/l and 1.85 x 10-5 g/l, respectively. PhTx2 and PhTx3, fractions from P. nigriventer venom, contain toxins acting on sodium and calcium channels, respectively. However, the neurotoxin PhTx2-6, one of the isoforms found in the PhTx2 pool, did not affect [125I]-Tx1 binding. Tx1 reduced the [3H]-ACh release evoked by the PhTx2 pool by 33%, but did not affect basal or KCl-induced [3H]-ACh release. Based on these results, as well as on the homology of Tx1 with toxins acting on calcium channels (w-Aga IA and IB and its competition with [125I]-w-Cono GVIA in the central nervous system, we suggest that the target site for Tx1 may be calcium channels.

Experience on environmental qualification of safety-related components for Darlington Nuclear Generating Station

International Nuclear Information System (INIS)

Yu, A.S.; Kukreti, B.M.

1987-01-01

The proliferation of Nuclear Power Plant safety concerns has lead to increasing attention over the Environmental Qualification (EQ) of Nuclear Power Plant Safety-Related Components to provide the assurance that the safety related equipment will meet their intended functions during normal operation and postulated accident conditions. The environmental qualification of these components is also a Licensing requirement for Darlington Nuclear Generating Station. This paper provides an overview of EQ and the experience of a pilot project, in the qualification of the Main Moderator System safety-related functions for the Darlington Nuclear Generating Station currently under construction. It addresses the various phases of qualification from the identification of the EQ Safety-Related Components List, definition of location specific service conditions (normal, adbnormal and accident), safety-related functions, Environmental Qualification Assessments and finally, an EQ system summary report for the Main Moderator System. The results of the pilot project are discussed and the methodology reviewed. The paper concludes that the EQ Program developed for Darlington Nuclear Generating Station, as applied to the qualification of the Main Moderator System, contained all the elements necessary in the qualification of safety-related equipment. The approach taken in the qualification of the Moderator safety-related equipment proves to provide a sound framework for the qualification of other safety-related components in the station

Presence of the Neurotoxin BMAA in Aquatic Ecosystems: What Do We Really Know?

Science.gov (United States)

Faassen, Elisabeth J.

2014-01-01

The neurotoxin β-N-methylamino-l-alanine (BMAA) is suspected to play a role in the neurological diseases amyotrophic lateral sclerosis, Alzheimer’s disease, and Parkinson’s disease. BMAA production by cyanobacteria has been reported and contact with cyanobacteria infested waters or consumption of aquatic organisms are possible pathways to human exposure. However, there is little consensus regarding whether BMAA is present in cyanobacteria or not, and if so, at what concentrations. The aim of this review is to indicate the current state of knowledge on the presence of BMAA in aquatic ecosystems. Some studies have convincingly shown that BMAA can be present in aquatic samples at the µg/g dry weight level, which is around the detection limit of some equally credible studies in which no BMAA was detected. However, for the majority of the reviewed articles, it was unclear whether BMAA was correctly identified, either because inadequate analytical methods were used, or because poor reporting of analyses made it impossible to verify the results. Poor analysis, reporting and prolific errors have shaken the foundations of BMAA research. First steps towards estimation of human BMAA exposure are to develop and use selective, inter-laboratory validated methods and to correctly report the analytical work. PMID:24662480

Global environmental policy strategies. ''Environment and development'' in north-south relations

International Nuclear Information System (INIS)

Bruckmeier, K.

1994-01-01

Global environmental policy has hardly made headway after the United Nations World Conference on Environment and Development (UNCED) in Rio in June 1992, despite there being no shortage of programmes, institutions, and actors. Obviously, formal structures for political action based on the system of institutions of the United Nations do not suffice. Global environmental policy strategies must reach further, overcoming system-immanent obstacles to sustainable development. This necessitates analyzing the causes of environmental destruction and making a critical evaluation of the relations between the societies of the North and South that received their imprint from development policies. Only after such a preliminary elucidation by interdisciplinary approaches in the light of political and ecological economy and human ecology does an empirical analysis of politically controlled processes in environmental and development policy make sense. The analysis points to strategies for this international political field that rely on non-governmental actors and social movements, and question the traditional European model of an environmental policy determined by government institutions. (orig./UA) [de

Food-Related Environmental Beliefs and Behaviours among University Undergraduates: A Mixed-Methods Study

Science.gov (United States)

Campbell-Arvai, Victoria

2015-01-01

Purpose: The purpose of this paper was to document the food-related environmental beliefs and behaviours of undergraduate university students. More specifically, this research was focussed on determining if environmental sustainability is a consideration in students' food choices, identifying the specific choices and behaviours adopted to reduce…

Modelling the relative stability of carbon nanotubes exposed to environmental adsorbates and air

International Nuclear Information System (INIS)

Barnard, Amanda S

2009-01-01

In parallel with the development of technological applications for carbon nanotubes, issues related to toxicology and environmental impact are also under increased scrutiny. It is clear from the available literature that the integrity of future carbon nanotube-based devices, our ability to anticipate failure of these devices, and our ability to manage the toxicological and environmental impacts require a detailed understanding of the stability of pure and functionalized carbon nanotubes under a full range of environmental conditions. Motivated by this endeavour, the present study uses a general thermodynamic model to predict the relative stability of carbon nanotubes exposed to a variety of atmospheric adsorbates, and uses them to examine the stability of nanotubes in air, as a function of the relative humidity. In general the results indicate that the adsorption of a sparse coverage of air is thermodynamically favoured, depending on the humidity, and the stability of small diameter nanotubes may be improved by exposure to humid air.

The first venomous crustacean revealed by transcriptomics and functional morphology: remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin.

Science.gov (United States)

von Reumont, Björn M; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A

2014-01-01

Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.

Environmental Survey preliminary report, Laboratory for Energy-Related Health Research, Davis, California

International Nuclear Information System (INIS)

1988-03-01

This report presents the preliminary findings from the first phase of the Survey of the United States Department of Energy (DOE) Laboratory for Energy-Related Health Research (LEHR) at the University of California, Davis (UC Davis), conducted November 16 through 20, 1987. The Survey is being conducted by an interdisciplinary team of environmental specialists, led and managed by the Office of Environment, Safety and Health's Office of Environmental Audit. Individual team components are being supplied by a private contractor. The objective of the Survey is to identify environmental problems and areas of environmental risk associated with the LEHR. The Survey covers all environmental media and all areas of environmental regulation, and is being performed in accordance with the DOE Environmental Survey Manual. This phase of the Survey involves the review of existing site environmental data, observations of the operations at the LEHR and interviews with site personnel. The Survey team developed a Sampling and Analysis Plan to assist in further assessing certain of the environmental problems identified during its on-site activities. The Sampling and Analysis Plan will be executed by a DOE National Laboratory or a support contractor. When completed, the results will be incorporated into the Environmental Survey Interim Report for the LEHR at UC Davis. The Interim Report will reflect the final determinations of the LEHR Survey. 75 refs., 26 figs., 23 tabs

Guidelines for the Deployment of Product-Related Environmental Legislation into Requirements for the Product Development Process

DEFF Research Database (Denmark)

Ferraz, Mariana; Pigosso, Daniela Cristina Antelmi; Teixeira, Cláudia Echevenguá

2013-01-01

Environmental legislation is increasingly changing its focus from end-of-pipe approaches to a life cycle perspective. Therefore, manufacturing companies are increasingly identifying the need of deploying and incorporating product-related environmental requirements into the product development...... process. This paper presents twelve guidelines, clustered into three groups, to support companies in the identification, analysis and deployment of product requirements from product-related environmental legislation....

Evaluating the relative environmental impact of countries.

Science.gov (United States)

Bradshaw, Corey J A; Giam, Xingli; Sodhi, Navjot S

2010-05-03

Environmental protection is critical to maintain ecosystem services essential for human well-being. It is important to be able to rank countries by their environmental impact so that poor performers as well as policy 'models' can be identified. We provide novel metrics of country-specific environmental impact ranks - one proportional to total resource availability per country and an absolute (total) measure of impact - that explicitly avoid incorporating confounding human health or economic indicators. Our rankings are based on natural forest loss, habitat conversion, marine captures, fertilizer use, water pollution, carbon emissions and species threat, although many other variables were excluded due to a lack of country-specific data. Of 228 countries considered, 179 (proportional) and 171 (absolute) had sufficient data for correlations. The proportional index ranked Singapore, Korea, Qatar, Kuwait, Japan, Thailand, Bahrain, Malaysia, Philippines and Netherlands as having the highest proportional environmental impact, whereas Brazil, USA, China, Indonesia, Japan, Mexico, India, Russia, Australia and Peru had the highest absolute impact (i.e., total resource use, emissions and species threatened). Proportional and absolute environmental impact ranks were correlated, with mainly Asian countries having both high proportional and absolute impact. Despite weak concordance among the drivers of environmental impact, countries often perform poorly for different reasons. We found no evidence to support the environmental Kuznets curve hypothesis of a non-linear relationship between impact and per capita wealth, although there was a weak reduction in environmental impact as per capita wealth increases. Using structural equation models to account for cross-correlation, we found that increasing wealth was the most important driver of environmental impact. Our results show that the global community not only has to encourage better environmental performance in less

Evaluating the relative environmental impact of countries.

Directory of Open Access Journals (Sweden)

Corey J A Bradshaw

Full Text Available Environmental protection is critical to maintain ecosystem services essential for human well-being. It is important to be able to rank countries by their environmental impact so that poor performers as well as policy 'models' can be identified. We provide novel metrics of country-specific environmental impact ranks - one proportional to total resource availability per country and an absolute (total measure of impact - that explicitly avoid incorporating confounding human health or economic indicators. Our rankings are based on natural forest loss, habitat conversion, marine captures, fertilizer use, water pollution, carbon emissions and species threat, although many other variables were excluded due to a lack of country-specific data. Of 228 countries considered, 179 (proportional and 171 (absolute had sufficient data for correlations. The proportional index ranked Singapore, Korea, Qatar, Kuwait, Japan, Thailand, Bahrain, Malaysia, Philippines and Netherlands as having the highest proportional environmental impact, whereas Brazil, USA, China, Indonesia, Japan, Mexico, India, Russia, Australia and Peru had the highest absolute impact (i.e., total resource use, emissions and species threatened. Proportional and absolute environmental impact ranks were correlated, with mainly Asian countries having both high proportional and absolute impact. Despite weak concordance among the drivers of environmental impact, countries often perform poorly for different reasons. We found no evidence to support the environmental Kuznets curve hypothesis of a non-linear relationship between impact and per capita wealth, although there was a weak reduction in environmental impact as per capita wealth increases. Using structural equation models to account for cross-correlation, we found that increasing wealth was the most important driver of environmental impact. Our results show that the global community not only has to encourage better environmental performance in

Evaluating the Relative Environmental Impact of Countries

Science.gov (United States)

Bradshaw, Corey J. A.; Giam, Xingli; Sodhi, Navjot S.

2010-01-01

Environmental protection is critical to maintain ecosystem services essential for human well-being. It is important to be able to rank countries by their environmental impact so that poor performers as well as policy ‘models’ can be identified. We provide novel metrics of country-specific environmental impact ranks – one proportional to total resource availability per country and an absolute (total) measure of impact – that explicitly avoid incorporating confounding human health or economic indicators. Our rankings are based on natural forest loss, habitat conversion, marine captures, fertilizer use, water pollution, carbon emissions and species threat, although many other variables were excluded due to a lack of country-specific data. Of 228 countries considered, 179 (proportional) and 171 (absolute) had sufficient data for correlations. The proportional index ranked Singapore, Korea, Qatar, Kuwait, Japan, Thailand, Bahrain, Malaysia, Philippines and Netherlands as having the highest proportional environmental impact, whereas Brazil, USA, China, Indonesia, Japan, Mexico, India, Russia, Australia and Peru had the highest absolute impact (i.e., total resource use, emissions and species threatened). Proportional and absolute environmental impact ranks were correlated, with mainly Asian countries having both high proportional and absolute impact. Despite weak concordance among the drivers of environmental impact, countries often perform poorly for different reasons. We found no evidence to support the environmental Kuznets curve hypothesis of a non-linear relationship between impact and per capita wealth, although there was a weak reduction in environmental impact as per capita wealth increases. Using structural equation models to account for cross-correlation, we found that increasing wealth was the most important driver of environmental impact. Our results show that the global community not only has to encourage better environmental performance in less

Predicting Improvement in Writer's Cramp Symptoms following Botulinum Neurotoxin Injection Therapy

Directory of Open Access Journals (Sweden)

Mallory Jackman

2016-09-01

Full Text Available Introduction: Writer's cramp is a specific focal hand dystonia causing abnormal posturing and tremor in the upper limb. The most popular medical intervention, botulinum neurotoxin type A (BoNT-A therapy, is variably effective for 50–70% of patients. BoNT-A non-responders undergo ineffective treatment and may experience significant side effects. Various assessments have been used to determine response prediction to BoNT-A, but not in the same population of patients. Methods: A comprehensive assessment was employed to measure various symptom aspects. Clinical scales, full upper-limb kinematic measures, self-report, and task performance measures were assessed for nine writer's cramp patients at baseline. Patients received two BoNT-A injections then were classified as responders or non-responders based on a quantified self-report measure. Baseline scores were compared between groups, across all measures, to determine which scores predicted a positive BoNT-A response. Results: Five of nine patients were responders. No kinematic measures were predictably different between groups. Analyses revealed three features that predicted a favorable response and separated the two groups: higher than average cramp severity and cramp frequency, and below average cramp latency. Discussion: Non-kinematic measures appear to be superior in making such predictions. Specifically, measures of cramp severity, frequency, and latency during performance of a specific set of writing and drawing tasks were predictive factors. Since kinematic was not used to determine the injection pattern and the injections were visually guided, it may still be possible to use individual patient kinematics for better outcomes. 

Trade Liberalization and Optimal Environmental Policies in Vertical Related Markets

Directory of Open Access Journals (Sweden)

Yan-Shu Lin

2012-12-01

Full Text Available This paper establishes a symmetric two-country model with vertically related markets. In the downstream market, there is one firm in each country selling a homogeneous good, whose production generates pollution, to its home and the foreign markets a la Brander (1981. In the intermediate good market, there is also one upstream firm in each country, supplying the intermediate good only to its own country’s downstream market. The upstream firms can choose either price or quantity to maximize their profits. With this setting, the paper examines the optimal environmental policy and how it is affected by the tariff on the final good. It is found that, under free trade, the optimal final-good output with imperfect intermediate-good market will have the same output level as that with perfect intermediate-good market after imposing the optimal emission tax. The optimal environmental tax is smaller and the optimal environmental policy is less likely to be a green strategy under trade liberalization if the market structure in the intermediate good market is imperfect than perfect competition. On the other hand, the optimal environmental tax is necessarily higher if the upstream firm chooses price than quantity. Moreover, the optimal environmental policy is less likely to be a green strategy under trade liberalization if the upstream firms choose quantity than price to maximize their profits.

Environmental flow assessments in estuaries related to preference of phytoplankton

Science.gov (United States)

Yang, Z. F.; Sun, T.; Zhao, R.

2014-01-01

We developed an approach to assess environmental flows in estuaries related to preference of phytoplankton considering the complex relationship between hydrological modification and biomass in ecosystems. As a first step, a relationship was established between biomass requirements for organisms of primary and higher nutritional levels based on the principle of nutritional energy flow of ecosystem. Then, diagnostic pigments were employed to represent phytoplankton community biomass, which indicated competition between two groups of phytoplankton in the biochemistry process. Considering empirical relationships between diagnostic pigments and critical environmental factors, responses of biomass to river discharges were established based on a convection-diffusion model by simulating distributions of critical environmental factors under action of river discharges and tide currents. Consequently, environmental flows could be recommended for different requirements of fish biomass. In the case study in the Yellow River estuary, May and October were identified as critical months for fish reproduction and growth during dry years. Artificial hydrological regulation strategies should carefully consider the temporal variations of natural flow regime, especially for a high-amplitude flood pulse, which may cause negative effects on phytoplankton groups and higher organism biomass.

The ENDORSE study: Research into environmental determinants of obesity related behaviors in Rotterdam schoolchildren

Directory of Open Access Journals (Sweden)

Looij-Jansen Petra

2008-04-01

Full Text Available Abstract Background Children and adolescents are important target groups for prevention of overweight and obesity as overweight is often developed early in life and tracks into adulthood. Research into behaviors related to overweight (energy balance-related behaviors and the personal and environmental determinants of these behaviors is fundamental to inform prevention interventions. In the Netherlands and in other countries systematic research into environmental determinants of energy balance related behaviors in younger adolescents is largely lacking. This protocol paper describes the design, the components and the methods of the ENDORSE study (Environmental Determinants of Obesity in Rotterdam SchoolchildrEn, that aims to identify important individual and environmental determinants of behaviors related to overweight and obesity and the interactions between these determinants among adolescents. Methods The ENDORSE study is a longitudinal study with a two-year follow-up of a cohort of adolescents aged 12–15 years. Data will be collected at baseline (2005/2006 and at two years follow-up (2007/2008. Outcome measures are body mass index (BMI, waist circumference, time spent in physical activity and sedentary behaviors, and soft drink, snack and breakfast consumption. The ENDORSE study consists of two phases, first employing qualitative research methods to inform the development of a theoretical framework to examine important energy balance related behaviors and their determinants, and to inform questionnaire development. Subsequently, the hypothetical relationships between behavioral determinants, energy balance related behaviors and BMI will be tested in a quantitative study combining school-based surveys and measurements of anthropometrical characteristics at baseline and two-year follow-up. Discussion The ENDORSE project is a comprehensive longitudinal study that enables investigation of specific environmental and individual determinants of

The thioredoxin reductase--Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles.

Science.gov (United States)

Pirazzini, Marco; Azarnia Tehran, Domenico; Zanetti, Giulia; Lista, Florigio; Binz, Thomas; Shone, Clifford C; Rossetto, Ornella; Montecucco, Cesare

2015-12-01

Botulinum neurotoxins (BoNTs) are Janus toxins, as they are at the same time the most deadly substances known and one of the safest drugs used in human therapy. They specifically block neurotransmission at peripheral nerves through the proteolysis of SNARE proteins, i.e. the essential proteins which are the core of the neuroexocytosis machinery. Even if BoNTs are traditionally known as seven main serotypes, their actual number is much higher as each serotype exists in many different subtypes, with individual biological properties and little antigenic relations. Since BoNTs can be used as biological weapons, and the only currently available therapy is based on immunological approaches, the existence of so many different subtypes is a major safety problem. Nevertheless, all BoNT isoforms are structurally similar and intoxicate peripheral nerve endings via a conserved mechanism. They consist of two chains linked by a unique disulphide bond which must be reduced to enable their toxicity. We found that thioredoxin 1 and its reductase compose the cell redox system responsible for this reduction, and its inhibition via specific chemicals significantly reduces BoNTs activity, in vitro as well as in vivo. Such molecules can be considered as lead compounds for the development of pan-inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Community Relations Plan for Lawrence Berkeley Laboratory. Environmental Restoration Program

Energy Technology Data Exchange (ETDEWEB)

1993-07-01

The Lawrence Berkeley Laboratory (LBL) has applied to the California Environmental Protection Agency, Department of Toxic Substances Control (DTSC), for renewal of its Hazardous Waste Handling Facility Permit. A permit is required under Resource Conservation and Recovery Act (RCRA) regulations. The permit will allow LBL to continue using its current hazardous waste handling facility, upgrade the existing facility, and construct a replacement facility. The new facility is scheduled for completion in 1995. The existing facility will be closed under RCRA guidelines by 1996. As part of the permitting process, LBL is required to investigate areas of soil and groundwater contamination at its main site in the Berkeley Hills. The investigations are being conducted by LBL`s Environmental Restoration Program and are overseen by a number of regulatory agencies. The regulatory agencies working with LBL include the California Environmental Protection Agency`s Department of Toxic Substances Control, the California Regional Water Quality Control Board, the Bay Area Air Quality Management District, the East Bay Municipal Utilities District, and the Berkeley Department of Environmental Health. RCRA requires that the public be informed of LBL`s investigations and site cleanup, and that opportunities be available for the public to participate in making decisions about how LBL will address contamination issues. LBL has prepared this Community Relations Plan (CRP) to describe activities that LBL will use to keep the community informed of environmental restoration progress and to provide for an open dialogue with the public on issues of importance. The CRP documents the community`s current concerns about LBL`s Environmental Restoration Program. Interviews conducted between February and April 1993 with elected officials, agency staff, environmental organizations, businesses, site neighbors, and LBL employees form the basis for the information contained in this document.

The application of nuclear and nuclear-related techniques for environmental pollution studies in Vietnam

International Nuclear Information System (INIS)

Nguyen Mong Sinh

1992-01-01

The applicability of neutron activation analysis, X-ray fluorescence and other related techniques to environmental samples from Viet Nam has been investigated. Results show that multielemental analysis of environmental samples and the determination of heavy metal pollution in the environment is best performed by a combination of techniques. Preliminary results of studying the environmental pollution associated with solid wastes are reported. 4 refs, 5 figs, 17 tabs

Proceedings of the fifth national symposium on environment: focal theme environmental issues related to mining, milling and metallurgy

International Nuclear Information System (INIS)

Sastry, V.N.; Bapat, V.N.; Desai, M.V.M.

1996-02-01

The fifth National Symposium on Environment was held in Calcutta from February 28 to March 1, 1996. It focused on environmental issues related to mining, milling and metallurgy. Some of the topics covered are coal mining and related environmental issues, chromium mining and associated environmental problems, heavy metals especially nuclear materials and the environmental management strategies, arsenic contamination in water in West Bengal areas and radiological issues related to fertilizers and gypsum industries. Papers relevant to INIS are indexed separately. refs., figs., tabs

Botulinum Neurotoxin Type-A for the Treatment of Atypical Odontalgia.

Science.gov (United States)

Cuadrado, María-Luz; García-Moreno, Héctor; Arias, José-Antonio; Pareja, Juan A

2016-09-01

Atypical odontalgia (AO), a subform of persistent idiopathic facial pain, is defined as a continuous toothache in which a thorough examination reveals no dental pathology. AO is believed to be a neuropathic condition, given that some cases are preceded by dental procedures. Different topical and systemic medications have been used for the treatment of AO, but their effect is often unsatisfactory. The authors aimed to assess the effect and safety of botulinum neurotoxin type-A (BoNTA) in a series of patients with AO. Four patients with refractory AO (2 males and 2 females, aged 31-72) were treated with local injections of BoNTA to the painful area. BoNTA was injected at various sites into the gums, and two patients had additional injections in the hard palate or the upper lip. The total dose of BoNTA for each procedure was 15-30 U, and the total number of injection points was 6-12. The follow-up ranged from 6 to 20 months. Two patients received two cycles of BoNTA, while the remaining patients received three and five cycles each, respectively. All patients obtained significant relief with complete or almost complete reduction of pain. The analgesic effect was apparent after a latency period of 3-14 days, and the effect persisted for 2-6 months. There were no adverse events reported from any of the interventions. The responses to BoNTA injections in this series agree with those previously observed in neuropathic pain. BoNTA injections may be a safe and effective option for the treatment of AO. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Radiation-related monitoring and environmental research at the Nevada Test Site

International Nuclear Information System (INIS)

Anspaugh, L.R.; Patton, S.E.; Shinn, J.H.; Black, S.C.; Costa, C.F.; Elle, D.R.; Essington, E.H.; Gilbert, R.O.; Gonzalez, D.A.; Hunter, R.B.; Medica, P.A.; McArthur, R.D.; Thompson, C.B.; O'Farrell, T.P.; Romney, E.M.

1990-01-01

Beginning with the first nuclear-weapons-related tests at the Nevada Test Site (NTS) in 1951, a radiation-related monitoring program was established to determine the levels and distribution of radionuclides released. Primary methods involved survey-meter-equipped field-monitoring teams and placement of film badges and air-sampling devices at fixed locations. Beginning in the mid-1950s, more stringent standards, the results of this monitoring program, and the results of related research programs led to increased engineering efforts to reduce local fallout. With passage of the National Environmental Policy Act and increased concern about possible effects of radiation exposure, environmental activities related to the NTS increased. There is now an extensive monitoring program at the NTS to assess radiological conditions resulting from past tests and from continued testing of nuclear-weapons devices. In populated areas near NTS, there is also a monitoring effort that relies on assistance from local communities. Other efforts include reconstruction of radiation doses received by offsite residents during the 1950s and 1960s, determination of the current inventory and distribution of radionuclides in surface soil, and studies of the movement of radionuclides in the desert ecosystem

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

Energy Technology Data Exchange (ETDEWEB)

Weingart, Oliver G., E-mail: Oliver.Weingart@hest.ethz.ch; Loessner, Martin J.

2016-12-15

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

International Nuclear Information System (INIS)

Weingart, Oliver G.; Loessner, Martin J.

2016-01-01

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A

Science.gov (United States)

Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan; Lam, Kwok-ho; Stern, Daniel; Bagramyan, Karine; Perry, Kay; Kalkum, Markus; Rummel, Andreas; Dong, Min; Jin, Rongsheng

2016-01-01

Botulinum neurotoxin serotype A1 (BoNT/A1) is one of the most dangerous potential bioterrorism agents, and exerts its action by invading motoneurons. It is also a licensed drug widely used for medical and cosmetic applications. Here we report a 2.0 Å resolution crystal structure of BoNT/A1 receptor-binding domain in complex with its neuronal receptor, the glycosylated human SV2C. We find that the neuronal tropism of BoNT/A1 requires recognition of both the peptide moiety and an N-linked glycan on SV2. This N-glycan—conserved in all SV2 isoforms across vertebrates—is essential for BoNT/A1 binding to neurons and its potent neurotoxicity. The glycan-binding interface on SV2 is targeted by a human BoNT/A1-neutralizing antibody currently licensed as an anti-botulism drug. Our studies reveal a new paradigm of host-pathogen interactions, in which pathogens exploit conserved host post-translational modifications to achieve highly specific receptor binding while also tolerating genetic changes across multiple isoforms of receptors. PMID:27294781

Paresthesias Among Community Members Exposed to the World Trade Center Disaster

Science.gov (United States)

Marmor, Michael; Shao, Yongzhao; Bhatt, D. Harshad; Stecker, Mark M.; Berger, Kenneth I.; Goldring, Roberta M.; Rosen, Rebecca L.; Caplan-Shaw, Caralee; Kazeros, Angeliki; Pradhan, Deepak; Wilkenfeld, Marc; Reibman, Joan

2017-01-01

Objective: Paresthesias can result from metabolic disorders, nerve entrapment following repetitive motions, hyperventilation pursuant to anxiety, or exposure to neurotoxins. We analyzed data from community members exposed to the World Trade Center (WTC) disaster of September 11, 2001, to evaluate whether exposure to the disaster was associated with paresthesias. Methods: Analysis of data from 3141 patients of the WTC Environmental Health Center. Results: Fifty-six percent of patients reported paresthesias at enrollment 7 to 15 years following the WTC disaster. After controlling for potential confounders, paresthesias were associated with severity of exposure to the WTC dust cloud and working in a job requiring cleaning of WTC dust. Conclusions: This study suggests that paresthesias were commonly associated with WTC-related exposures or post-WTC cleaning work. Further studies should objectively characterize these paresthesias and seek to identify relevant neurotoxins or paresthesia-inducing activities. PMID:28157767

The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) induces neuronal and behavioral changes in honeybees

Energy Technology Data Exchange (ETDEWEB)

Okle, Oliver, E-mail: oliver.okle@uni-konstanz.de [Human and Environmental Toxicology, University of Konstanz, Jacob-Burckhardt-Strasse 25, 78457 Konstanz (Germany); Rath, Lisa; Galizia, C. Giovanni [Zoology and Neurobiology, University of Konstanz, Universitätsstraße 10, 78457 Konstanz (Germany); Dietrich, Daniel R., E-mail: daniel.dietrich@uni-konstanz.de [Human and Environmental Toxicology, University of Konstanz, Jacob-Burckhardt-Strasse 25, 78457 Konstanz (Germany)

2013-07-01

The cyanobacterially produced neurotoxin beta-N-methylamino-L-alanine (BMAA) is thought to induce amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC)-like symptoms. However, its mechanism of action and its pathway of intoxication are yet unknown. In vivo animal models suitable for investigating the neurotoxic effect of BMAA with applicability to the human are scarce. Hence, we used the honeybee (Apis mellifera) since its nervous system is relatively simple, yet having cognitive capabilities. Bees fed with BMAA-spiked sugar water had an increased mortality rate and a reduced ability to learn odors in a classical conditioning paradigm. Using {sup 14}C-BMAA we demonstrated that BMAA is biologically available to the bee, and is found in the head, thorax and abdomen with little to no excretion. BMAA is also transferred from one bee to the next via trophallaxis resulting in an exposure of the whole beehive. BMAA bath application directly onto the brain leads to an altered Ca{sup 2+} homeostasis and to generation of reactive oxygen species. These behavioral and physiological observations suggest that BMAA may have effects on bee brains similar to those assumed to occur in humans. Therefore the bee could serve as a surrogate model system for investigating the neurological effects of BMAA. - Highlights: • Investigating of neurotoxic effects of BMAA in honeybees • BMAA impairs ALS markers (ROS, Ca{sup 2+}, learning, memory, odor) in bees. • A method for the observation of ROS development in living bees brain was established. • Honeybees are a suitable model to explore neurodegenerative processes. • Neurotoxic BMAA can be spread in bee populations by trophallaxis.

The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) induces neuronal and behavioral changes in honeybees

International Nuclear Information System (INIS)

Okle, Oliver; Rath, Lisa; Galizia, C. Giovanni; Dietrich, Daniel R.

2013-01-01

The cyanobacterially produced neurotoxin beta-N-methylamino-L-alanine (BMAA) is thought to induce amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC)-like symptoms. However, its mechanism of action and its pathway of intoxication are yet unknown. In vivo animal models suitable for investigating the neurotoxic effect of BMAA with applicability to the human are scarce. Hence, we used the honeybee (Apis mellifera) since its nervous system is relatively simple, yet having cognitive capabilities. Bees fed with BMAA-spiked sugar water had an increased mortality rate and a reduced ability to learn odors in a classical conditioning paradigm. Using 14 C-BMAA we demonstrated that BMAA is biologically available to the bee, and is found in the head, thorax and abdomen with little to no excretion. BMAA is also transferred from one bee to the next via trophallaxis resulting in an exposure of the whole beehive. BMAA bath application directly onto the brain leads to an altered Ca 2+ homeostasis and to generation of reactive oxygen species. These behavioral and physiological observations suggest that BMAA may have effects on bee brains similar to those assumed to occur in humans. Therefore the bee could serve as a surrogate model system for investigating the neurological effects of BMAA. - Highlights: • Investigating of neurotoxic effects of BMAA in honeybees • BMAA impairs ALS markers (ROS, Ca 2+ , learning, memory, odor) in bees. • A method for the observation of ROS development in living bees brain was established. • Honeybees are a suitable model to explore neurodegenerative processes. • Neurotoxic BMAA can be spread in bee populations by trophallaxis

Relating the environmental impact of consumption to household expenditures. An input-output analysis

International Nuclear Information System (INIS)

Kerkhof, Annemarie C.; Nonhebel, Sanderine; Moll, Henri C.

2009-01-01

In this paper we evaluate the relationships between household expenditures and the environmental impact categories climate change, acidification, eutrophication and smog formation, by combining household expenditures with environmentally extended input-output analysis. Expenditure elasticities are examined with regression analysis, and are compared and interpreted on the basis of insight at the product level. With data from the Netherlands in the year 2000, we find that environmental impact increases with increasing household expenditures, although the degree to which the environmental impact increases differs per impact category. Climate change and eutrophication increase less than proportionally with increasing expenditures. Acidification increases nearly proportionally with increasing expenditures, whereas smog formation increases more than proportionally. It appears that the mix of necessities and luxuries to which an environmental impact is related is essential in explaining the relationship. (author)

Final environmental statement related to operation of White Mesa Uranium Project, Energy Fuels Nuclear, Inc

International Nuclear Information System (INIS)

1979-05-01

Environmental impact statements are presented under the following headings: the existing environment; mining and milling operations; air quality; land use; mineral resources; soils; radiological impacts; socioeconomic impacts; environmental effects of accidents; monitoring programs; unavoidable adverse environmental impacts; relation between short-term uses of the environment and long-term productivity; irreversible and irretrievable commitments

/sup 125/I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection

Energy Technology Data Exchange (ETDEWEB)

Wiegand, H; Erdmann, G; Wellhoener, H H [Giessen Univ. (Germany, F.R.). Pharmakologisches Inst.

1976-01-01

On unilateral injection of sublethal doses of /sup 125/I-botulinum A neurotoxin (BTA) into one gastrocnemius muscle of the cat we found after 48 h: a disto-proximal gradient of radioactivity (RA) hat developed in the sciatic nerve of the injected side. The ventral roots of the spinal cord half segments supplying the injected muscle showed a higher RA than the ventral roots of the contralateral control side. The spinal cord half segments innervating the injected muscle had a RA much higher than the corresponding segments of the contralateral side. However, a small rise of RA was also observed in the contralateral half segments. In histoautoradiographs of the (ligatured) ventral roots the RA was strictly confined to the intraaxonal space of a few nerve fibres. On injection of equal doses of /sup 125/I-BTA into either gastrocnemius muscle we found after 38 h: direct stimulation of only one of the injected muscles caused the RA to reach a higher level in the spinal cord half segments ipsilateral to the stimulated muscle than in the spinal cord half segments of the non-stimulated side. Unilateral stimulation of one gastrocnemius nerve under the influence of gallamine or unilateral antidromic stimulation of the dorsal roots L7, S1 failed to cause a difference in RA between stimulated and non-stimulated side.

78 FR 11593 - Environmental Impact and Related Procedures

Science.gov (United States)

2013-02-19

... (EA) or environmental impact statement (EIS) under 23 CFR part 771, the repair or reconstruction of... unusual circumstances include significant environmental impacts, substantial controversy on environmental... the action normally has significant environmental impacts either individually or cumulatively and may...

Urban-Related Environmental Variables and Their Relation with Patterns in Biological Community Structure in the Fountain Creek Basin, Colorado, 2003-2005

Science.gov (United States)

Zuellig, Robert E.; Bruce, James F.; Evans, Erin E.; Stogner, Sr., Robert W.

2007-01-01

In 2003, the U.S. Geological Survey, in cooperation with Colorado Springs City Engineering, began a study to evaluate the influence of urbanization on stream ecosystems. To accomplish this task, invertebrate, fish, stream discharge, habitat, water-chemistry, and land-use data were collected from 13 sites in the Fountain Creek basin from 2003 to 2005. The Hydrologic Index Tool was used to calculate hydrologic indices known to be related to urbanization. Response of stream hydrology to urbanization was evident among hydrologic variables that described stormflow. These indices included one measurement of high-flow magnitude, two measurements of high-flow frequency, and one measurement of stream flashiness. Habitat and selected nonstormflow water chemistry were characterized at each site. Land-use data were converted to estimates of impervious surface cover and used as the measure of urbanization annually. Correlation analysis (Spearman?s rho) was used to identify a suite of nonredundant streamflow, habitat, and water-chemistry variables that were strongly associated (rho > 0.6) with impervious surface cover but not strongly related to elevation (rho analysis (BIO-ENV, PRIMER ver 6.1, Plymouth, UK) was used to create subsets of eight urban-related environmental variables that described patterns in biological community structure. The strongest and most parsimonious subset of variables describing patterns in invertebrate community structure included high flood pulse count, lower bank capacity, and nutrients. Several other combinations of environmental variables resulted in competing subsets, but these subsets always included the three variables found in the most parsimonious list. This study found that patterns in invertebrate community structure from 2003 to 2005 in the Fountain Creek basin were associated with a variety of environmental characteristics influenced by urbanization. These patterns were explained by a combination of hydrologic, habitat, and water

Health-related disparities: influence of environmental factors.

Science.gov (United States)

Olden, Kenneth; White, Sandra L

2005-07-01

Racial disparities in health cannot be explained solely on the basis of poverty, access to health care, behavior, or environmental factors. Their complex etiology is dependent on interactions between all these factors plus genetics. Scientists have been slow to consider genetics as a risk factor because genetic polymorphisms tend to be more variable within a race than between races. Now that studies are demonstrating the existence of racial differences in allelic frequencies for multiple genes affecting a single biologic mechanism, the present argument for a significant genetic role in contributing to health disparities is gaining support. Individuals vary, often significantly, in their response to environmental agents. This variability provides a high "background noise" when scientists examine human populations to identify environmental links to disease. This variability often masks important environmental contributors to disease risk and is a major impediment to efforts to investigate the causes of diseases.Fortunately, investments in the various genome projects have led to the development of tools and databases that can be used to help identify the genetic variations in environmental response genes that can lead to such wide differences in disease susceptibility. NIEHS developed the environ-mental genome project to catalog these genetic variants (polymorphisms)and to identify the ones that play a major role in human susceptibility to environmental agents. This information is being used in epidemiologic studies to pinpoint environmental contributors to disease better. The research summarized in this article is critically important for tying genetics and the environment to health disparities, and for the development of a rational approach to gauge environmental threats. Common variants in genes play pivotal roles in determining if or when illness or death result from exposure to drugs or environmental xenobiotics. Most common variants exist in all human

Investigating the traffic-related environmental impacts of hydraulic-fracturing (fracking) operations.

Science.gov (United States)

Goodman, Paul S; Galatioto, Fabio; Thorpe, Neil; Namdeo, Anil K; Davies, Richard J; Bird, Roger N

2016-01-01

Hydraulic fracturing (fracking) has been used extensively in the US and Canada since the 1950s and offers the potential for significant new sources of oil and gas supply. Numerous other countries around the world (including the UK, Germany, China, South Africa, Australia and Argentina) are now giving serious consideration to sanctioning the technique to provide additional security over the future supply of domestic energy. However, relatively high population densities in many countries and the potential negative environmental impacts that may be associated with fracking operations has stimulated controversy and significant public debate regarding if and where fracking should be permitted. Road traffic generated by fracking operations is one possible source of environmental impact whose significance has, until now, been largely neglected in the available literature. This paper therefore presents a scoping-level environmental assessment for individual and groups of fracking sites using a newly-created Traffic Impacts Model (TIM). The model produces estimates of the traffic-related impacts of fracking on greenhouse gas emissions, local air quality emissions, noise and road pavement wear, using a range of hypothetical fracking scenarios to quantify changes in impacts against baseline levels. Results suggest that the local impacts of a single well pad may be short duration but large magnitude. That is, whilst single digit percentile increases in emissions of CO2, NOx and PM are estimated for the period from start of construction to pad completion (potentially several months or years), excess emissions of NOx on individual days of peak activity can reach 30% over baseline. Likewise, excess noise emissions appear negligible (fracking water and flowback waste requirements. The TIM model is designed to be adaptable to any geographic area where the required input data are available (such as fleet characteristics, road type and quality), and we suggest could be deployed as a

Evaluating the Relative Environmental Impact of Countries

OpenAIRE

Bradshaw, Corey J. A.; Giam, Xingli; Sodhi, Navjot Singh

2010-01-01

Environmental protection is critical to maintain ecosystem services essential for human well-being. It is important to be able to rank countries by their environmental impact so that poor performers as well as policy ?models? can be identified. We provide novel metrics of country-specific environmental impact ranks ? one proportional to total resource availability per country and an absolute (total) measure of impact ? that explicitly avoid incorporating confounding human health or economic i...

Spatial analysis of freshwater lake cyanobacteria blooms, 2008-2011

Science.gov (United States)

Background/Question/Methods Cyanobacteria and associated harmful algal blooms cause significant social, economic, and environmental impacts. Cyanobacteria synthesize hepatotoxins, neurotoxins, and dermatotoxins, affecting the health of humans and other species. The Cyanobacteria ...

Altered pairing behaviour and reproductive success in white ibises exposed to environmentally relevant concentrations of methylmercury.

Science.gov (United States)

Frederick, Peter; Jayasena, Nilmini

2011-06-22

Methylmercury (MeHg) is the most biologically available and toxic form of mercury, and can act as a powerful teratogen, neurotoxin and endocrine disruptor in vertebrates. However, mechanisms of endocrine impairment and net effects on demography of biota are poorly understood. Here, we report that experimental exposure of an aquatic bird over 3 years to environmentally relevant dietary MeHg concentrations (0.05-0.3 ppm wet weight) resulted in dose-related increases in male-male pairing behaviour (to 55% of males), and decreases in egg productivity (to 30%). Dosed males showed decreased rates of key courtship behaviours, and were approached less by courting females in comparison to control males. Within dosed groups, homosexual males showed a similar reduction when compared with dosed heterosexual males. We found an average 35 per cent decrease in fledgling production in high-dose birds over the study duration. These results are of interest because (i) MeHg exposure is experimentally tied to demographically important reproductive deficits, (ii) these effects were found at low, chronic exposure levels commonly experienced by wildlife, and (iii) effects on reproductive behaviour and sexual preference mediated by endocrine disruption represent a novel and probably under-reported mechanism by which contaminants may influence wild populations of birds.

Long term energy-related environmental issues of copper production

International Nuclear Information System (INIS)

Alvarado, S.; Maldonado, P.; Barrios, A.; Jaques, I.

2002-01-01

Primary copper production is a major activity in the mining sector of several countries. However, it is highly energy-intensive and poses important environmental hazards. In the case of Chile, the world's largest copper producer (40% of world total), we examine its energy consumption and energy-related environmental implications over a time horizon of 25 years. Concerning the latter, we focus on greenhouse-gas (GHG) emissions, one of the most debated environmental issues. This paper follows up our previous report in which the current situation was analyzed and a particular technical option for improving the energy efficiency and concurrently reducing GHG emissions was discussed. Estimated reference or base (BS) and mitigation (MS) scenarios are developed for the period ending in 2020. The former assesses the energy demand projected in accordance with production forecasts and specific energy consumption patterns (assuming that energy efficiency measures are adopted 'spontaneously') with their resultant GHG emissions, while the latter assumes induced actions intended to reduce emissions by adopting an aggressive policy of efficient energy use. For the year 2020, the main results are: (i) BS, 1214 t of CO 2 /ton of refined copper content (49% lower than in 1994); (ii) MS, 1037 t of CO 2 /t of refined copper content (56% lower than in 1994). CO 2 emissions have been estimated considering both fuel and electricity process requirements. (author)

Environmental accounts. Environmentally related taxes, subsidies and emission permits; Miljoerelaterade skatter, subventioner och utslaeppsraetter

Energy Technology Data Exchange (ETDEWEB)

Cederlund, Maja; Brolinson, Hanna; Palm, Viveka

2010-12-15

Environmental Economic instruments is seen as an important component towards a sustainable society. In Prop. (proposition) 2009/10:155 'Swedish environmental objectives - for a more effective environmental' the Ministry of the Environment says that 'We must therefore work to improve the price signals by internalising external environmental costs and increase the use of economic instruments in environmental policy.' Statistics Sweden have now for the first time quantified the environmental economic instruments, both individually and together. In addition, the results are broken down by industry and for most time series can be presented. The result of this work is presented in this report

Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E in Pichia pastoris.

Science.gov (United States)

Baghban, Roghayyeh; Gargari, Seyed Latif Mousavi; Rajabibazl, Masoumeh; Nazarian, Shahram; Bakherad, Hamid

2016-01-01

Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism. Common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies (VHH) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. The Pichia pastoris is suitable for expression of recombinant antibody fragments. Disulfide bond formation and correct folds of protein with a high yield are some of the advantages of this eukaryotic host. In this study, we have expressed and purified the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris-expressed antibody was estimated to be 16 mg/l, which is higher than that expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized 4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in E. coli extended the mice's survival to 1.5-fold compared to the control. This experiment indicated that the quality of expressed protein in the yeast is superior to that of the bacterial expression. Favorable protein folding by P. pastoris seems to play a role in its better toxin-binding property. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats

Science.gov (United States)

Kim, Hye-Jin; Lee, Geun-Woo; Kim, Min-Ji; Yang, Kui-Ye; Kim, Seong-Taek; Bae, Yong-Cheol

2015-01-01

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions. PMID:26170739

Molecular bases of protective immune responses against botulinum neurotoxin A--how antitoxin antibodies block its action.

Science.gov (United States)

Atassi, M Zouhair; Dolimbek, Behzod Z; Steward, Lance E; Aoki, K Roger

2007-01-01

In studies from this laboratory, we localized the regions on the H chain of botulinum neurotoxin A (BoNT/A) that are recognized by anti-BoNT/A antibodies (Abs) and block the activity of the toxin in vivo. These Abs were obtained from cervical dystonia patients who had been treated with BoNT/A and had become unresponsive to the treatment, as well as blocking Abs raised in mouse, horse, and chicken. We also localized the regions involved in BoNT/A binding to mouse brain synaptosomes (snp). Comparison of spatial proximities in the three-dimensional structure of the Ab-binding regions and the snp binding showed that except for one, the Ab-binding regions either coincide or overlap with the snp regions. It should be folly expected that protective Abs when bound to the toxin at sites that coincide or overlap with snp binding would prevent the toxin from binding to nerve synapse and therefore block toxin entry into the neuron. Thus, analysis of the locations of the Ab-binding and the snp-binding regions provides a molecular rationale for the ability of protecting Abs to block BoNT/A action in vivo.

Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson's disease.

Science.gov (United States)

Triadafilopoulos, George; Gandhy, Rita; Barlow, Carrolee

2017-11-01

Gastrointestinal symptoms, such as dysphagia, postprandial bloating, and defecatory straining are common in Parkinson's Disease (PD) and they impact quality of life. Endoscopic botulinum neurotoxin (BoNT) injection has been used in the treatment of dysphagia, gastroparesis and chronic anismus. To examine the feasibility, safety and efficacy of endoscopically delivered BoNT injection to distal esophagus, pylorus or anal canal aiming at relieving regional gastrointestinal symptoms in patients with PD. This is a retrospective open cohort pilot study to assess the clinical response to endoscopic BoNT injection on selected PD patients with symptoms and identifiable abnormalities on high-resolution manometry and wireless motility capsule, to generate early uncontrolled data on feasibility, tolerability, safety and efficacy. Baseline symptoms and response to therapy were assessed by questionnaires. Fourteen PD patients (10 M:4 F), mean age 73 (range: 62-93) were treated. Three patients had esophageal Botox for ineffective esophageal motility (IEM) (n = 1), esophago-gastric junction outlet obstruction (EGJOO) & IEM (n = 1), and diffuse esophageal spasm (DES) (n = 1). Nine patients were treated with pyloric BoNT injection for gastroparesis with mean gastric transit time of 21.2 h; range 5.2-44.2 h. Two patients received anal Botox for defecatory dyssynergia ((Type I) (n = 1) and overlap (slow-transit and dyssynergic) constipation (n = 1). Endoscopic BoNT injection (100-200 units) was well tolerated and there were no significant adverse events. Endoscopic BoNT injection to esophagus, pylorus or anal canal is safe, well-tolerated and leads to symptomatic improvement that lasts up to several months. The procedure can be repeated as needed and combined with other therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

77 FR 59875 - Environmental Impact and Related Procedures

Science.gov (United States)

2012-10-01

... repair project that do not typically involve significant environmental impacts. Specifically, the FHWA... damaged facility to address concerns such as safety and environmental impacts. The agencies also seek... kinds of projects and activities described in this paragraph and the environmental impacts of such...

A gender perspective on environmentally related family consumption

DEFF Research Database (Denmark)

Grønhøj, Alice; Ølander, Folke

2007-01-01

Studies of 'green' consumer behavior have often reported differences in male and female environmental concern and participation. This paper looks into the nature of such differences within the family. Husband-wife differences with regard to family participation in a number of environmentally...... for this could be discerned. Most notably, the division of household and consumption roles within families often made sub-activities of pro-environmental practices the prime responsibility of either one of the partners. Thus, a gender-based inside-outside division of household responsibilities with regard to pro......-environmental practices could be noted. It is suggested that the processes whereby environmentally oriented consumer practices are adopted and transmitted among family members receive closer research attention....

Environmental Factors Related to Fungal Wound Contamination after Combat Trauma in Afghanistan, 2009-2011.

Science.gov (United States)

Tribble, David R; Rodriguez, Carlos J; Weintrob, Amy C; Shaikh, Faraz; Aggarwal, Deepak; Carson, M Leigh; Murray, Clinton K; Masuoka, Penny

2015-10-01

During the recent war in Afghanistan (2001-2014), invasive fungal wound infections (IFIs) among US combat casualties were associated with risk factors related to the mechanism and pattern of injury. Although previous studies recognized that IFI patients primarily sustained injuries in southern Afghanistan, environmental data were not examined. We compared environmental conditions of this region with those of an area in eastern Afghanistan that was not associated with observed IFIs after injury. A larger proportion of personnel injured in the south (61%) grew mold from wound cultures than those injured in the east (20%). In a multivariable analysis, the southern location, characterized by lower elevation, warmer temperatures, and greater isothermality, was independently associated with mold contamination of wounds. These environmental characteristics, along with known risk factors related to injury characteristics, may be useful in modeling the risk for IFIs after traumatic injury in other regions.

Staff report on the environmental qualification of safety-related electrical equipment

International Nuclear Information System (INIS)

1977-12-01

The current NRC safety review process for nuclear power plants includes criteria related to the qualification of certain electrical equipment. These criteria require that electrical equipment important to safety must be qualified to function in the environment that might result from various accident conditions. Although such criteria have been applied since the early days of commercial nuclear power, the details of these criteria have been changed over the years. The evolution of environmental qualification of safety-related electrical equipment is described in Appendix A

Unscrambling cyanobacteria community dynamics related to environmental factors

Directory of Open Access Journals (Sweden)

Mireia eBertos-Fortis

2016-05-01

Full Text Available Future climate scenarios in the Baltic Sea project an increase of cyanobacterial bloom frequency and duration, attributed to eutrophication and climate change. Some cyanobacteria can be toxic and their impact on ecosystem services is relevant for a sustainable sea. Yet, there is limited understanding of the mechanisms regulating cyanobacterial diversity and biogeography. Here we unravel successional patterns and changes in cyanobacterial community structure using a two-year monthly time-series during the productive season in a 100 km coastal-offshore transect using microscopy and high-throughput sequencing of 16S rRNA gene fragments. A total of 565 cyanobacterial OTUs were found, of which 231 where filamentous/colonial and 334 picocyanobacterial. Spatial differences in community structure between coastal and offshore waters were minor. An epidemic population structure (dominance of a single cluster was found for Aphanizomenon/Dolichospermum within the filamentous/colonial cyanobacterial community. In summer, this cluster simultaneously occurred with opportunistic clusters/OTUs e.g. Nodularia spumigena and Pseudanabaena. Picocyanobacteria, Synechococcus/Cyanobium, formed a consistent but highly diverse group. Overall, the potential drivers structuring summer cyanobacterial communities were temperature and salinity. However, the different responses to environmental factors among and within genera suggest high niche specificity for individual OTUs. The recruitment and occurrence of potentially toxic filamentous/colonial clusters was likely related to disturbance such as mixing events and short-term shifts in salinity, and not solely dependent on increasing temperature and nitrogen-limiting conditions. Nutrients did not explain further the changes in cyanobacterial community composition. Novel occurrence patterns were identified as a strong seasonal succession revealing a tight coupling between the emergence of opportunistic picocyanobacteria and

The Relation between Sustainable Innovation Strategy and Financial Performance Mediated By Environmental Performance

Directory of Open Access Journals (Sweden)

Hariyati Hariyati

2015-06-01

Full Text Available This study aims to examine the relationship of sustainable innovation strategy and financial performance through the mediation environmental performance. The hypothesis in this study is sustainable innovation strategy affect the financial performance which is mediated by environmental performance. This study is quantitative research in the explanatory level. The population of this study is all the manufacturer companies in East Java. The data is collected through questionnaire. The unit of analysis is a business unit. The respondent of this study is the manager of a business unit manufacturing company in East Java. The results showed that the environmental performance mediates partially the relation between sustainable innovation strategy and financial performance.

Long term energy-related environmental issues of copper production

Energy Technology Data Exchange (ETDEWEB)

Alvarado, S. [University of Chile, Santiago (Chile). Dept. of Mechanical Engineering; Maldonado, P.; Barrios, A.; Jaques, I. [University of Chile, Santiago (Chile). Energy Research Program

2002-02-01

Primary copper production is a major activity in the mining sector of several countries. However, it is highly energy-intensive and poses important environmental hazards. In the case of Chile, the world's largest copper producer (40% of world total), we examine its energy consumption and energy-related environmental implications over a time horizon of 25 years. Concerning the latter, we focus on greenhouse-gas (GHG) emissions, one of the most debated environmental issues. This paper follows up our previous report in which the current situation was analyzed and a particular technical option for improving the energy efficiency and concurrently reducing GHG emissions was discussed. Estimated reference or base (BS) and mitigation (MS) scenarios are developed for the period ending in 2020. The former assesses the energy demand projected in accordance with production forecasts and specific energy consumption patterns (assuming that energy efficiency measures are adopted 'spontaneously') with their resultant GHG emissions, while the latter assumes induced actions intended to reduce emissions by adopting an aggressive policy of efficient energy use. For the year 2020, the main results are: (i) BS, 1214 t of CO{sub 2}/ton of refined copper content (49% lower than in 1994); (ii) MS, 1037 t of CO{sub 2}/t of refined copper content (56% lower than in 1994). CO{sub 2} emissions have been estimated considering both fuel and electricity process requirements. (author)

Inventory of environmental impact models related to energy technologies

Energy Technology Data Exchange (ETDEWEB)

Owen, P.T.; Dailey, N.S.; Johnson, C.A.; Martin, F.M. (eds.)

1979-02-01

The purpose of this inventory is to identify and collect data on computer simulations and computational models related to the environmental effects of energy source development, energy conversion, or energy utilization. Information for 33 data fields was sought for each model reported. All of the information which could be obtained within the time alloted for completion of the project is presented for each model listed. Efforts will be continued toward acquiring the needed information. Readers who are interested in these particular models are invited to contact ESIC for assistance in locating them. In addition to the standard bibliographic information, other data fields of interest to modelers, such as computer hardware and software requirements, algorithms, applications, and existing model validation information, are included. Indexes are provided for contact person, acronym, keyword, and title. The models are grouped into the following categories: atmospheric transport, air quality, aquatic transport, terrestrial food chains, soil transport, aquatic food chains, water quality, dosimetry, and human effects, animal effects, plant effects, and generalized environmental transport. Within these categories, the models are arranged alphabetically by last name of the contact person.

Inventory of environmental impact models related to energy technologies

International Nuclear Information System (INIS)

Owen, P.T.; Dailey, N.S.; Johnson, C.A.; Martin, F.M.

1979-02-01

The purpose of this inventory is to identify and collect data on computer simulations and computational models related to the environmental effects of energy source development, energy conversion, or energy utilization. Information for 33 data fields was sought for each model reported. All of the information which could be obtained within the time alloted for completion of the project is presented for each model listed. Efforts will be continued toward acquiring the needed information. Readers who are interested in these particular models are invited to contact ESIC for assistance in locating them. In addition to the standard bibliographic information, other data fields of interest to modelers, such as computer hardware and software requirements, algorithms, applications, and existing model validation information, are included. Indexes are provided for contact person, acronym, keyword, and title. The models are grouped into the following categories: atmospheric transport, air quality, aquatic transport, terrestrial food chains, soil transport, aquatic food chains, water quality, dosimetry, and human effects, animal effects, plant effects, and generalized environmental transport. Within these categories, the models are arranged alphabetically by last name of the contact person

Epidemiologic Tools to Study the Influence of Environmental Factors on Fecundity and Pregnancy-related Outcomes

Science.gov (United States)

Slama, Rémy; Ballester, Ferran; Casas, Maribel; Cordier, Sylvaine; Eggesbø, Merete; Iniguez, Carmen; Nieuwenhuijsen, Mark; Philippat, Claire; Rey, Sylvie; Vandentorren, Stéphanie; Vrijheid, Martine

2014-01-01

Adverse pregnancy outcomes entail a large health burden for the mother and offspring; a part of it might be avoided by better understanding the role of environmental factors in their etiology. Our aims were to review the assessment tools to characterize fecundity troubles and pregnancy-related outcomes in human populations and their sensitivity to environmental factors. For each outcome, we reviewed the possible study designs, main sources of bias, and their suggested cures. In terms of study design, for most pregnancy outcomes, cohorts with recruitment early during or even before pregnancy allow efficient characterization of pregnancy-related events, time-varying confounders, and in utero exposures that may impact birth outcomes and child health. Studies on congenital anomalies require specific designs, assessment of anomalies in medical pregnancy terminations, and, for congenital anomalies diagnosed postnatally, follow-up during several months after birth. Statistical analyses should take into account environmental exposures during the relevant time windows; survival models are an appropriate approach for fecundity, fetal loss, and gestational duration/preterm delivery. Analysis of gestational duration could distinguish pregnancies according to delivery induction (and possibly pregnancy-related conditions). In conclusion, careful design and analysis are required to better characterize environmental effects on human reproduction. PMID:24363355

76 FR 70169 - Draft Supplement 2 to Final Environmental Statement Related to the Operation of Watts Bar Nuclear...

Science.gov (United States)

2011-11-10

... Environmental Statement Related to the Operation of Watts Bar Nuclear Plant, Unit 2; Tennessee Valley Authority... on NUREG-0498, ``Final Environmental Statement, Supplement 2, Related to the Operation of Watts Bar... the Nuclear Regulatory Commission. Stephen J. Campbell, Chief, Watts Bar Special Projects Branch...

Product-related Environmental Performance Indicators: a systematic literature review

DEFF Research Database (Denmark)

Issa, Isabela I.; Pigosso, Daniela Cristina Antelmi; McAloone, Tim C.

2013-01-01

Ecodesign is a proactive environmental management approach employed in the product development process (PDP) which aims to minimize the environmental impacts caused during products’ life-cycle, improving its environmental performance. The establishment of measurable environmental performance...

Environmental quality as a public health issue.

Science.gov (United States)

2001-03-01

Mercury is a persistent, bio-accumulative toxin that has been linked to numerous health effects in wildlife and humans. Mercury is a potent neurotoxin which may also harm the brain, kidneys and lungs. The unborn child and young infants are at special risk of brain damage from mercury exposure. Hospitals' use of mercury in chemical solutions, thermometers, blood pressure gauges, batteries, and fluorescent lamps make them large contributors to the overall mercury emission into the environment. Most hospitals recognize the dangers of mercury. In a recent survey, 4 out of 5 hospitals asked have policies in place to eliminate the use of mercury containing products and 62% require vendors to disclose the presence of mercury in chemicals that the hospital purchases. Only 12% distribute mercury-containing thermometers to new parent. Ninety two percent teach their employees about the health and environmental effects of mercury and 46 percent teach all employees how to clean up mercury spills. However, the same study showed that many hospitals have not implemented those policies. Forty two percent were not aware if they still purchased items containing mercury. In addition, 49% still purchase mercury thermometers, 44% purchase mercury gastrointestinal diagnostic equipment, and 64% still purchase mercury lab thermometers.

Environmental issues related to biomass: An overview

International Nuclear Information System (INIS)

Hughes, M.; Ranney, J.W.

1993-01-01

With public attention increasingly focused on environmentalism and climate change, there is enormous potential for the commercial use of biomass to accelerate. Renewable feedstocks such as biomass can provide more environmentally balanced sources of energy and other non-food products than fossil fuels. Biomass utilization is in a precarious position, however, with public attention increasingly focused on both its potential and the strength of the challenges it faces. The paper is divided into five sections. Section 2 briefly addresses economic environmental issues. The extent to which externalities are accounted for in the market price of fuels plays a significant role in determining both the ultimate size of biofuel markets and the extent of the environmental benefits of feedstock cultivation and conversion processes. Sections 3 through 4 catalogue the main hazards and benefits that are likely to arise in the large scale commercialization of biomass fuel and note where the major uncertainties lay. Environmental issues arise with the cultivation of each feedstock and with each step in the process of its conversion to fuel. Feedstocks are discussed in Section 3 in terms of three main groups; wastes, energy crops, and traditional agricultural crops. In Section 4, conversion processes are also divided into three groups, on the basis of the end energy carrier; gas, liquid, and solid and electricity. Section 5 is devoted to a conclusion and summary

Challenging Ingrained Thoughts? The Joint Effect of Stereotypes and Awareness of Related Information on Pro-Environmental Behavior in China

Directory of Open Access Journals (Sweden)

Majid Ghorbani

2018-06-01

Full Text Available This research applies a positive stereotype perspective to test the effect of individuals’ choices between pro-environmental versus pro-safety behavior, while considering the role of media exposure. We test our hypotheses in China, where both food-safety and environment are major issues and are widely covered by the media and government reports. Based on a quasi-experiments and survey questionnaires focused on attitudes towards disposable chopsticks, we find that individuals form cognitive perceptions in ways that either have stronger positive environmental or safety stereotypes. Based on these stereotypes, they either believe that reusable chopsticks are more environmentally friendly or that disposable chopsticks are safer, each impacting individuals’ choices differently. In addition, awareness of information related to the environment augments the link between environmental stereotypes and pro-environmental behavior, while having no influence on the effect of safety stereotypes on pro-safety behavior. On the other hand, while awareness of safety-related information accentuates the link between safety-related stereotypes and pro-safety behavior, it has no impact on the effect of environmental stereotypes on pro-environmental behavior.

Weed Control in Maize-Cowpea Intercropping System Related to Environmental Resources Consumption

Directory of Open Access Journals (Sweden)

Hamdollah ESKANDARI

2011-03-01

Full Text Available A field experiment was carried out in Ramhormoz, Iran during the 2008-2009 growing season to investigate the effects of different planting pattern of intercropping on environmental resource consumption and weed biomass. A randomized complete block design (RCBD with three replications was employed to compare the treatments. Treatments included maize sole crop (M, cow pea sole crop (C, within row intercropping (I1, row intercropping (I2 and mix cropping (I3. The density of intercropping was according to replacement design (one maize replaced by three cow pea plants. The results showed that environmental resource consumption was significantly (P?0.05 affected by cropping system, where PAR interception, moisture and nutrients uptake were higher in intercropping systems compared to sole crop systems. Regarding to weed control, intercrops were more effective than sole crops and it was related to lower availability of environmental resources for weeds in intercropping systems.

Forecasting the relative influence of environmental and anthropogenic stressors on polar bears

Science.gov (United States)

Todd C. Atwood; Bruce G. Marcot; David C. Douglas; Steven C. Amstrup; Karyn D. Rode; George M. Durner; Jeffrey F. Bromaghin

2016-01-01

Effective conservation planning requires understanding and ranking threats to wildlife populations. We developed a Bayesian network model to evaluate the relative influence of environmental and anthropogenic stressors, and their mitigation, on the persistence of polar bears (Ursus maritimus). Overall sea ice conditions, affected by rising global...

Development of the Environmental Strategies Instrument to Measure Adolescent Alcohol Prevention-Related Outcomes in Community Settings

Science.gov (United States)

Cervantes, Richard C.; Goldbach, Jeremy; Yeung, Albert; Rey, Antonio

2012-01-01

Recently, evidence-based community policy approaches to preventing substance use and alcohol abuse, called environmental strategies, have gained in popularity. The environmental survey instrument (ESI) was developed to evaluate perceptions around drinking and related problems. Specifically, the authors were interested in assessing community…

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes

Directory of Open Access Journals (Sweden)

Consuelo Garcia-Rodriguez

2018-03-01

Full Text Available Human botulism is most commonly caused by botulinum neurotoxin (BoNT serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS. A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD. By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633 is in pre-clinical development with an investigational new drug (IND application filing expected in 2018.

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Science.gov (United States)

Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

2018-03-01

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

Assessment of elements in coal related to environmental concern

International Nuclear Information System (INIS)

Diah Dwiana Lestiani; Muhayatun Santoso; Natalia Adventini

2010-01-01

National energy consumption increases rapidly in line with the economic growth and population. Indonesian government plans to develop electrical power plant 10 000 MW program to anticipate this matter, first step of which is focused on coal power plant. In this study, coal combustion was assessed on its environmental impact. Determination of trace and toxic elements was applied by instrumental neutron activation analysis. Samples were irradiated in Rabbit System at GA Siwabessy, Serpong, in reactor with neutron flux ~10 13 n.cm -2 .s -1 , then counted using HPGe detector. The method was validated by analysis of standard reference material NIST SRM 1633b coal fly ash. The results showed that Al and Cr concentrations were 2.1 0±0.80 and 7.63±1.45 mg/kg, respectively, and other elements such as Al, Co, Cs, Ce, Fe, K, La, Mn, Na, Sc, Sm, Ti, and V were still in the range of those in other world coals. Comparison the elements in coal with the elements in fly ash and bottom ash for relative enrichment index, mass balance calculation and mass flow estimation using assumption was also carried out to estimate the total emission estimation related the environmental concerned elements. The total emission of As, Co and Cr were in the range of 0.84-2.28 kg/day or equivalent to 0.49-1.23 % of total elemental mass content in coal. This also indicated that these elements were captured 98-99 % before released to the environment. (author)

Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

Science.gov (United States)

Hauser, Joachim; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

2017-05-01

The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats' performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats.

Reconciling Trade and Environmental Protection in ASEAN-China Relations: More than Political Window Dressing?

Directory of Open Access Journals (Sweden)

Joern Dosch

2011-01-01

Full Text Available Has the growing pro-environment rhetoric in ASEAN-China relations resulted in the effective mainstreaming of environmental issue into trade agreements and multilateral cooperation frameworks? The article discusses the cases of the ASEAN China Free Trade Area (ACFTA and the Greater Mekong Subregion (GMS and argues that there is no shortage of national and regional policy agendas that visibly link trade growth and environmental considerations. However, this nexus is still a weak one in terms of implementation and effectiveness. The most promising initiatives towards an effective reconciliation of trade growth and environmental sustainability are promoted and often driven by foreign donors, most prominently the European Union (EU.

Brevetoxin, the Dinoflagellate Neurotoxin, Localizes to Thylakoid Membranes and Interacts with the Light-Harvesting Complex II (LHCII) of Photosystem II.

Science.gov (United States)

Cassell, Ryan T; Chen, Wei; Thomas, Serge; Liu, Li; Rein, Kathleen S

2015-05-04

The brevetoxins are neurotoxins that are produced by the "Florida red tide" dinoflagellate Karenia brevis. They bind to and activate the voltage-gated sodium channels in higher organisms, specifically the Nav 1.4 and Nav 1.5 channel subtypes. However, the native physiological function that the brevetoxins perform for K. brevis is unknown. By using fluorescent and photoactivatable derivatives, brevetoxin was shown to localize to the chloroplast of K. brevis where it binds to the light-harvesting complex II (LHCII) and thioredoxin. The LHCII is essential to non-photochemical quenching (NPQ), whereas thioredoxins are critical to the maintenance of redox homeostasis within the chloroplast and contribute to the scavenging of reactive oxygen. A culture of K. brevis producing low levels of toxin was shown to be deficient in NPQ and produced reactive oxygen species at twice the rate of the toxic culture, implicating a role in NPQ for the brevetoxins. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Airway metaplasia related to smoking and environmental pollution through sputum].

Science.gov (United States)

Ferman-Cano, Floribel; Padilla-Santamaría, Fernando; Moreno-Venegas, Luis; Torner-Aguilar, Carlos Alejandro; Molina-Medina, Miguel Angel

2018-01-01

Both environmental pollution and smoking affect the respiratory epithelium, causing cellular adaptation changes. Therefore, this work explores the presence of metaplasia in smokers compared with non-smokers from Mexico City. A prospective cohort study was performed. The sample was performed through a home interview covering the five Mexico City zones delimited to the study and monitoring of air quality. We searched metaplastic cells and inflammation in sputum cytology stained with Papanicolaou technique, and we assessed the air quality in Mexico City. We calculated relative risk (RR) and attributable risk (AR) in relation to the presence of metaplasia and smoking. We performed 1897 home interviews obtaining a final sample of 30 participants. There were no significant differences between smokers and non-smokers with the presence of metaplastic cells (p = 0.269), although the association of metaplastic cells and inflammation showed a significant difference in the non-smokers group (p = 0.010). The RR in association with the presence of metaplasia in sputum cytology and smoking was 1.6, and the RA was 0.2. The air quality in this city has led the population to undergo changes of cellular adaptation in the respiratory epithelium by the simple fact of being exposed to environmental pollution. Metaplastic changes in non-smokers suggest strongly that pollution causes the same effect as smoking.

Botulinum Neurotoxins: Qualitative and Quantitative Analysis Using the Mouse Phrenic Nerve Hemidiaphragm Assay (MPN

Directory of Open Access Journals (Sweden)

Hans Bigalke

2015-11-01

Full Text Available The historical method for the detection of botulinum neurotoxin (BoNT is represented by the mouse bioassay (MBA measuring the animal survival rate. Since the endpoint of the MBA is the death of the mice due to paralysis of the respiratory muscle, an ex vivo animal replacement method, called mouse phrenic nerve (MPN assay, employs the isolated N. phrenicus-hemidiaphragm tissue. Here, BoNT causes a dose-dependent characteristic decrease of the contraction amplitude of the indirectly stimulated muscle. Within the EQuATox BoNT proficiency 13 test samples were analysed using the MPN assay by serial dilution to a bath concentration resulting in a paralysis time within the range of calibration curves generated with BoNT/A, B and E standards, respectively. For serotype identification the diluted samples were pre-incubated with polyclonal anti-BoNT/A, B or E antitoxin or a combination of each. All 13 samples were qualitatively correctly identified thereby delivering superior results compared to single in vitro methods like LFA, ELISA and LC-MS/MS. Having characterized the BoNT serotype, the final bath concentrations were calculated using the calibration curves and then multiplied by the respective dilution factor to obtain the sample concentration. Depending on the source of the BoNT standards used, the quantitation of ten BoNT/A containing samples delivered a mean z-score of 7 and of three BoNT/B or BoNT/E containing samples z-scores <2, respectively.

Compensation for environmental asbestos-related diseases in South Africa: a neglected issue.

Science.gov (United States)

Ndlovu, Ntombizodwa; Naude, Jim teWater; Murray, Jill

2013-01-24

Environmentally acquired asbestos-related diseases (ARDs) are of concern globally. In South Africa, there is widespread contamination of the environment due to historical asbestos mining operations that were poorly regulated. Although the law makes provision for the compensation of occupationally acquired ARDs, compensation for environmentally acquired ARDs is only available through the Asbestos Relief Trust (ART) and Kgalagadi Relief Trust, both of which are administered by the ART. This study assessed ARDs and compensation outcomes of environmental claims submitted to the Trusts. The personal details, medical diagnoses, and exposure information of all environmental claims considered by the Trusts from their inception in 2003 to April 2010 were used to calculate the numbers and proportions of ARDs and compensation awards. There were 146 environmental claimants of whom 35 (23.9%) had fibrotic pleural disease, 1 (0.7%) had lung cancer, and 77 (52.7%) had malignant mesothelioma. 53 (36.3%) claimants were compensated: 20 with fibrotic pleural disease and 33 with mesothelioma. Of the 93 (63.7%) claimants who were not compensated, 33 had no ARDs, 18 had fibrotic pleural disease, 1 had lung cancer, and 44 had mesothelioma. In addition to having ARDs, those that were compensated had qualifying domestic (33; 62.2%) or neighbourhood (20; 37.8%) exposures to asbestos. Most of the claimants who were not compensated had ARDs but their exposures did not meet the Trusts' exposure criteria. This study demonstrates the environmental impact of asbestos mining on the burden of ARDs. Mesothelioma was the most common disease diagnosed, but most cases were not compensated. This highlights that there is little redress for individuals with environmentally acquired ARDs in South Africa. To stop this ARD epidemic, there is a need for the rehabilitation of abandoned asbestos mines and the environment. These issues may not be unique to South Africa as many countries continue to mine and use

[Environmental and genetic variables related with alterations in language acquisition in early childhood].

Science.gov (United States)

Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

2017-01-01

A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

Preliminary analysis of environmental regulations related to remedial action activities at the Oak Ridge National Laboratory: Environmental Sciences Division Publication No. 2695

International Nuclear Information System (INIS)

Voorhees, L.D.; Saylor, R.E.

1986-11-01

Past research and development activities at Oak Ridge National Laboratory (ORNL) have resulted in the presence of several areas where low-level radioactive and/or hazardous waste have been disposed of or that have been contaminated through accidental spills or planned releases of radionuclides. Although these areas have been monitored and controlled to ensure that on-site and off-site releases of contaminants are within applicable Department of Energy (DOE) guidelines, ORNL established the Environmental Restoration and Facilities Upgrade (ERFU) Program to address formally the immediate and long-range needs of meeting all applicable federal and state regulations regarding waste disposal. The environmental laws, regulations, and DOE Orders governing the cleanup activities are numerous and complex. Hence, a synthesis of the principal regulations related to the ERFU Program is presented to facilitate efficient planning for characterization and cleanup of contaminated sites. Because of regulatory decisions made after this report was finalized, several statements presented herein may no longer apply to the ERFU Program. Nevertheless, the report is issued as originally written so that ORNL's early planning efforts to comply with environmental laws and legislation are formally documented. Several general principles to consider when developing a plan for environmental compliance - which would be of use to others who must comply with legislation related to the cleanup of sites contaminated with radionuclides and hazardous chemicals - are also discussed

Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B

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Luisa W. Cheng

2015-11-01

Full Text Available Botulinum neurotoxins (BoNT are some of nature’s most potent toxins. Due to potential food contamination, and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are of urgent interest. Recently, we have developed a sensitive electrochemiluminescent (ECL immunoassay for BoNT/B, using monoclonal antibodies (mAbs MCS6-27 and anti-BoNT/B rabbit polyclonal antibodies as the capture and detector. The ECL assay detected as little as 1 pg/mL BoNT/B in the buffer matrix, surpassing the detection sensitivities of the gold standard mouse bioassays. The ECL assay also allowed detection of BoNT/B in sera matrices of up to 100% sera with negligible matrix effects. This highly-sensitive assay allowed the determination of the biological half-lives of BoNT/B holotoxin in vivo. We further tested the toxin neutralization potential of our monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs protected mice in both pre- and post-exposure models to lethal doses of BoNT/B. MAbs were capable of increasing survival of animals when administered even 10 h post-intoxication in an oral model, suggesting a likely time for BoNT/B complexes to reach the blood stream. More sensitive detection assays and treatments against BoNT intoxication will greatly enhance efforts to combat botulism.

Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain.

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Sharad P Adekar

2008-08-01

Full Text Available Botulinum neurotoxins (BoNT are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC, a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A. The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro.An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components of an antibody antidote for BoNT exposure.

Implementing the Bruker MALDI Biotyper in the Public Health Laboratory for C. botulinum Neurotoxin Detection

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Michael J. Perry

2017-03-01

Full Text Available Currently, the gold standard method for active botulinum neurotoxin (BoNT detection is the mouse bioassay (MBA. A Centers for Disease Control and Prevention-developed mass spectrometry (MS-based assay that detects active BoNT was successfully validated and implemented in a public health laboratory in clinical matrices using the Bruker MALDI-TOF MS (Matrix-assisted laser desorption ionization–time of flight mass spectrometry Biotyper. For the first time, a direct comparison with the MBA was performed to determine MS-based assay sensitivity using the Bruker MALDI Biotyper. Mice were injected with BoNT/A, /B, /E, and /F at concentrations surrounding the established MS assay limit of detection (LOD and analyzed simultaneously. For BoNT/B, /E, and /F, MS assay sensitivity was equivalent or better than the MBA at 25, 0.3, and 8.8 mLD50, respectively. BoNT/A was detected by the MBA between 1.8 and 18 mLD50, somewhat more sensitive than the MS method of 18 mLD50. Studies were performed to compare assay performance in clinical specimens. For all tested specimens, the MS method rapidly detected BoNT activity and serotype in agreement with, or in the absence of, results from the MBA. We demonstrate that the MS assay can generate reliable, rapid results while eliminating the need for animal testing.

A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food

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Larry H. Stanker

2013-11-01

Full Text Available Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT, produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A–H have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D., ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule and readily detects toxin in those food samples tested.

A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food.

Science.gov (United States)

Stanker, Larry H; Scotcher, Miles C; Cheng, Luisa; Ching, Kathryn; McGarvey, Jeffery; Hodge, David; Hnasko, Robert

2013-11-18

Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD's) for individual antibodies ranging from 10 to 48 × 10-11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested.

Evaluation of the patient with an exposure-related disease: the occupational and environmental history.

Science.gov (United States)

Papali, Alfred; Hines, Stella E

2015-03-01

Although the process of taking an occupational and environmental history has remained largely the same, the context in which it is done has changed dramatically over recent years. This review examines the role of the occupational and environmental history in the context of the changing nature of medical practice and discusses methods for evaluating patients with contemporary exposure-related respiratory illnesses. Surveillance for occupational lung disease using mnemonic devices, screening questions and the use of structured questionnaires can significantly increase the likelihood and accuracy of detection. Electronic health records likewise can be adapted to include the most important elements of the occupational and environmental history. The emergence of new technologies and industries will lead to respiratory diseases in novel occupational and environmental contexts. Using the methods described herein can make detecting these diseases easier and less time-consuming.

Relation of Environmental Impact Assessment (EIA and Strategic Environmental Assessment (SEA and the Importance of Strategic Environmental Assessment in Landscape Planning Process

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Gizem CENGİZ GÖKÇE

2015-07-01

Full Text Available The main goal in the countries which have not completed their development progress is industrialization and development just as soon as possible. Therefore, negative effects of industrialization and development on envi ronment and/or nature cannot be mostly discussed adequately. One of the planning approach instruments that targets sustainability, Environmental Impact Assessment (EIA is used in many countries effectively. But in recent years, that has understood; EIA is an impact assessment instrument that contains defensive preventions only on the basis of projects and this situation has caused some concerns against EIA. In this direction, Strategical Environmental Assessment (SEA exists as the final point of the instruments which are formed to provide sustainable development . In this study; the importance and the requirement of effectively taking a role of landscape architectures that have ecological based job, in the SEA workings which isn’t have got a legal status in Turkey yet, are emphasized by reviewing the relations between EIA and SEA concepts.

Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages.

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Yun Jeong Kim

Full Text Available Botulinum neurotoxin type A (BoNT/A is the most potent protein toxin and causes fatal flaccid muscle paralysis by blocking neurotransmission. Application of BoNT/A has been extended to the fields of therapeutics and biodefense. Nevertheless, the global response of host immune cells to authentic BoNT/A has not been reported. Employing microarray analysis, we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment. The altered genes were mainly involved in signal transduction, immunity and defense, protein metabolism and modification, neuronal activities, intracellular protein trafficking, and muscle contraction. Microarray data were validated with real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi, stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO and tumor necrosis factor alpha (TNFα were induced in a dose-dependent manner in BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was inhibited by monoclonal anti-Toll-like receptor 2 (TLR2 and inhibitors specific to intracellular proteins such as c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, and p38 mitogen-activated protein kinase (MAPK. BoNT/A also suppressed lipopolysaccharide-induced NO and TNFα production from RAW264.7 macrophages at the transcription level by blocking activation of JNK, ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results suggest that BoNT/A induces global gene expression changes in host immune cells and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which is modulated by JNK, ERK, and p38 MAPK.

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

NARCIS (Netherlands)

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-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.

2018-01-01

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

Environmental heterogeneity generates opposite gene-by-environment interactions for two fitness-related traits within a population.

Science.gov (United States)

Culumber, Zachary W; Schumer, Molly; Monks, Scott; Tobler, Michael

2015-02-01

Theory predicts that environmental heterogeneity offers a potential solution to the maintenance of genetic variation within populations, but empirical evidence remains sparse. The live-bearing fish Xiphophorus variatus exhibits polymorphism at a single locus, with different alleles resulting in up to five distinct melanistic "tailspot" patterns within populations. We investigated the effects of heterogeneity in two ubiquitous environmental variables (temperature and food availability) on two fitness-related traits (upper thermal limits and body condition) in two different tailspot types (wild-type and upper cut crescent). We found gene-by-environment (G × E) interactions between tailspot type and food level affecting upper thermal limits (UTL), as well as between tailspot type and thermal environment affecting body condition. Exploring mechanistic bases underlying these G × E patterns, we found no differences between tailspot types in hsp70 gene expression despite significant overall increases in expression under both thermal and food stress. Similarly, there was no difference in routine metabolic rates between the tailspot types. The reversal of relative performance of the two tailspot types under different environmental conditions revealed a mechanism by which environmental heterogeneity can balance polymorphism within populations through selection on different fitness-related traits. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.

Science.gov (United States)

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M; Das, Samir; Nag, Arundhati; Agnew, Heather D; Heath, James R

2015-06-08

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A systematic review of environmental correlates of obesity-related dietary behaviors in youth

NARCIS (Netherlands)

K. van der Horst (Klazine); A. Oenema (Anke); A. Ferreira (Isabel); G.C.W. Wendel-Vos (Wanda); K. Giskes (Katrina); F.J. van Lenthe (Frank); J. Brug (Hans)

2007-01-01

textabstractThere is increasing interest in the role the environment plays in shaping the dietary behavior of youth, particularly in the context of obesity prevention. An overview of environmental factors associated with obesity-related dietary behaviors among youth is needed to inform the

Purification and characterization of a novel subtype a3 botulinum neurotoxin.

Science.gov (United States)

Tepp, William H; Lin, Guangyun; Johnson, Eric A

2012-05-01

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are of considerable importance due to their being the cause of human and animal botulism, their potential as bioterrorism agents, and their utility as important pharmaceuticals. Type A is prominent due to its high toxicity and long duration of action. Five subtypes of type A BoNT are currently recognized; BoNT/A1, -/A2, and -/A5 have been purified, and their properties have been studied. BoNT/A3 is intriguing because it is not effectively neutralized by polyclonal anti-BoNT/A1 antibodies, and thus, it may potentially replace BoNT/A1 for patients who have become refractive to treatment with BoNT/A1 due to antibody formation or other modes of resistance. Purification of BoNT/A3 has been challenging because of its low levels of production in culture and the need for innovative purification procedures. In this study, modified Mueller-Miller medium was used in place of traditional toxin production medium (TPM) to culture C. botulinum A3 (CDC strain) and boost toxin production. BoNT/A3 titers were at least 10-fold higher than those produced in TPM. A purification method was developed to obtain greater than 95% pure BoNT/A3. The specific toxicity of BoNT/A3 as determined by mouse bioassay was 5.8 × 10(7) 50% lethal doses (LD(50))/mg. Neutralization of BoNT/A3 toxicity by a polyclonal anti-BoNT/A1 antibody was approximately 10-fold less than the neutralization of BoNT/A1 toxicity. In addition, differences in symptoms were observed between mice that were injected with BoNT/A3 and those that were injected with BoNT/A1. These results indicate that BoNT/A3 has novel biochemical and pharmacological properties compared to those of other subtype A toxins.

Environmental planning related to the oil industry activities at Maracaibo Lake Venezuela

International Nuclear Information System (INIS)

German, F.

1993-01-01

Maracaibo Lake has been the center of most of the hydrocarbon exploration and production activities in Venezuela since the early twenties, with a total cumulative oil extraction of nearly 40 billion barrels. The intensive activities related to production have brought a wide variety of ecosystem perturbations, as a consequence of the construction of facilities for exploration, transport, treatment, storage, and oil refining, as well as the generation of effluents, emissions, and solid wastes therein associated. The Venezuelan Petroleum Corporation (PDVSA) has recognized the importance of preventing further potential damage from its current operations and future expansions, with an additional concern for restoring affected areas. Herein, actual and future restoration/mitigation environmental planning will be discussed, emphasizing a research program focused on the Maracaibo Lake region, being conducted by PDVSA's R ampersand D Corporative branch. Research main objective is to gather, for PDVSA operating companies, a priority setting, as a function of environmental or ecological risks, related to the oil industry activities. To this end, efforts will be directed from a multidisciplinary approach, taking into account some of the major links structuring ecosystem complexity

Phosphatase Inhibitors Function as Novel, Broad Spectrum Botulinum Neurotoxin Antagonists in Mouse and Human Embryonic Stem Cell-Derived Motor Neuron-Based Assays.

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Erkan Kiris

Full Text Available There is an urgent need to develop novel treatments to counter Botulinum neurotoxin (BoNT poisoning. Currently, the majority of BoNT drug development efforts focus on directly inhibiting the proteolytic components of BoNT, i.e. light chains (LC. Although this is a rational approach, previous research has shown that LCs are extremely difficult drug targets and that inhibiting multi-serotype BoNTs with a single LC inhibitor may not be feasible. An alternative approach would target neuronal pathways involved in intoxication/recovery, rather than the LC itself. Phosphorylation-related mechanisms have been implicated in the intoxication pathway(s of BoNTs. However, the effects of phosphatase inhibitors upon BoNT activity in the physiological target of BoNTs, i.e. motor neurons, have not been investigated. In this study, a small library of phosphatase inhibitors was screened for BoNT antagonism in the context of mouse embryonic stem cell-derived motor neurons (ES-MNs. Four inhibitors were found to function as BoNT/A antagonists. Subsequently, we confirmed that these inhibitors protect against BoNT/A in a dose-dependent manner in human ES-MNs. Additionally, these compounds provide protection when administered in post-intoxication scenario. Importantly, the inhibitors were also effective against BoNT serotypes B and E. To the best of our knowledge, this is the first study showing phosphatase inhibitors as broad-spectrum BoNT antagonists.

LOUISIANA ENVIRONMENTAL MODELING SYSTEM FOR HYPOXIA RELATED ISSUES

Science.gov (United States)

An environmental assessment tool to evaluate the impacts of nonpoint source (NPS) pollutants discharged from Mississippi River basins into the Gulf of Mexico and to assess their effects on receiving water quality will be described. This system (Louisiana Environmental Modeling S...

A Relational Database Model and Tools for Environmental Sound Recognition

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Yuksel Arslan

2017-12-01

Full Text Available Environmental sound recognition (ESR has become a hot topic in recent years. ESR is mainly based on machine learning (ML and ML algorithms require first a training database. This database must comprise the sounds to be recognized and other related sounds. An ESR system needs the database during training, testing and in the production stage. In this paper, we present the design and pilot establishment of a database which will assists all researchers who want to establish an ESR system. This database employs relational database model which is not used for this task before. We explain in this paper design and implementation details of the database, data collection and load process. Besides we explain the tools and developed graphical user interface for a desktop application and for the WEB.

Functional influence of botulinum neurotoxin type A treatment (Xeomin® of multifocal upper and lower limb spasticity on chronic hemiparetic gait

Directory of Open Access Journals (Sweden)

Maurizio Falso

2012-05-01

Full Text Available This report describes the modification of hemiplegic shoulder pain and walking velocity through injections of Xeomin®, a new botulinum neurotoxin type A formulation, in a 67-year-old woman with chronic residual left hemiparesis and hemiparetic gait attributable to stroke. Clinical evaluation included upper and lower limb spasticity, upper and lower limb pain, trunk control, upper and lower limb motricity index, visual gait analysis, and gait velocity. Assessments were performed before, 1 week after, and 1 month after treatment. Improvement was observed in all clinical parameters assessed. Amelioration of spasticity of the upper and lower limbs and shoulder pain was observed after 1 month. Trunk postural attitude and paraxial muscle recruitment recovered. No adverse events were observed and the patient shows significant improvement of functional impairment derived from chronic spasticity after treatment with Xeomin®. We also provide a simple and useful protocol for clinical evaluation of the treatment.

Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

Science.gov (United States)

Leonetti, D L; Bergstrom, R W; Shuman, W P; Wahl, P W; Jenner, D A; Harrison, G A; Fujimoto, W Y

1991-05-01

The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus

EI Scale: an environmental impact assessment scale related to the construction materials used in the reinforced concrete

OpenAIRE

Gilson Morales; Antonio Edésio Jungles; Sheila Elisa Scheidemantel Klein; Juliana Guarda

2010-01-01

This study aimed to create EI Scal, an environmental impact assessment scal, related to construction materials used in the reinforced concrete structure production. The main reason for that was based on the need to classify the environmental impact levels through indicators to assess the damage level process. The scale allowed converting information to estimate the environmental impact caused. Indicators were defined trough the requirements and classification criteria of impact aspects consid...

Environment, Agriculture and Sustainability Relations: From the Environmental Degradation to the Necessity of Conservation of Natural Resources.

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Flórida Rosa Mali Assêncio

2015-01-01

Full Text Available This paper presents a brief approach on environmental aspects related to the development of agriculture in the world and especially in Brazil, detaching some historical aspects. Some characteristics of the social and environmental degradation generated by the processes of production of modern agriculture, based on studies of Environmental Sciences, in general, and, more specifically, of Agroecology, are presented, as well as the necessity of searching for new models of development according to the recent paradigm of sustainability (social, economic and environmental, debated in international conferences on 'environment and development'.

Compensation for environmental asbestos-related diseases in South Africa: a neglected issue

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Ntombizodwa Ndlovu

2013-01-01

Full Text Available Background: Environmentally acquired asbestos-related diseases (ARDs are of concern globally. In South Africa, there is widespread contamination of the environment due to historical asbestos mining operations that were poorly regulated. Although the law makes provision for the compensation of occupationally acquired ARDs, compensation for environmentally acquired ARDs is only available through the Asbestos Relief Trust (ART and Kgalagadi Relief Trust, both of which are administered by the ART. This study assessed ARDs and compensation outcomes of environmental claims submitted to the Trusts. Methods: The personal details, medical diagnoses, and exposure information of all environmental claims considered by the Trusts from their inception in 2003 to April 2010 were used to calculate the numbers and proportions of ARDs and compensation awards. Results: There were 146 environmental claimants of whom 35 (23.9% had fibrotic pleural disease, 1 (0.7% had lung cancer, and 77 (52.7% had malignant mesothelioma. 53 (36.3% claimants were compensated: 20 with fibrotic pleural disease and 33 with mesothelioma. Of the 93 (63.7% claimants who were not compensated, 33 had no ARDs, 18 had fibrotic pleural disease, 1 had lung cancer, and 44 had mesothelioma. In addition to having ARDs, those that were compensated had qualifying domestic (33; 62.2% or neighbourhood (20; 37.8% exposures to asbestos. Most of the claimants who were not compensated had ARDs but their exposures did not meet the Trusts’ exposure criteria. Conclusions: This study demonstrates the environmental impact of asbestos mining on the burden of ARDs. Mesothelioma was the most common disease diagnosed, but most cases were not compensated. This highlights that there is little redress for individuals with environmentally acquired ARDs in South Africa. To stop this ARD epidemic, there is a need for the rehabilitation of abandoned asbestos mines and the environment. These issues may not be unique to

The shaping of environmental concern in product chains: analysing Danish case studies on environmental aspects in product chain relations

DEFF Research Database (Denmark)

Forman, Marianne; Hansen, Anne Grethe; Jørgensen, Michael Søgaard

indirect demand for greening activities. The analysis shows the co-construction of environmental concerns and demands, companies’ environmental practices and technological developments, and their stabilisation in the supply chain. The case studies also point to how the greening of frontrunners might make...... the systems of production, consumption, knowledge and regulation are discussed. The role of boundary objects is discussed with eco-labelling as case. The role of and the impact on the product chain relations are analysed as part of these mechanisms. From the case studies, green innovations in the product...... chain, which the case company represents, are identified. Direct customer and regulatory demands, as well as indirect societal and regulatory demands are mapped, and their role for product chain greening analysed. The case studies point to the importance of customer demand, regulation and potentially...

Handling of Environmental Related Requirements : Awareness and Ability to Act at Small and Medium Sized Electric and Electronic Companies

OpenAIRE

Lin, Han-Hsuan

2008-01-01

Environmental related product requirements are increasing worldwide from government authorities, customers and other stakeholders. For small and medium sized companies manufacturing electric and electronic products it is more difficult compared to bigger companies to meet new product related requirements due to smaller budget, resources and knowledge. This research studies the awareness and ability to act upon changes when small and medium sized companies in Sweden face environmental related ...

Environmental influences on neural systems of relational complexity

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Layne eKalbfleisch

2013-09-01

Full Text Available Constructivist learning theory contends that we construct knowledge by experience and that environmental context influences learning. To explore this principle, we examined the cognitive process relational complexity (RC, defined as the number of visual dimensions considered during problem solving on a matrix reasoning task and a well-documented measure of mature reasoning capacity. We sought to determine how the visual environment influences RC by examining the influence of color and visual contrast on RC in a neuroimaging task. To specify the contributions of sensory demand and relational integration to reasoning, our participants performed a non-verbal matrix task comprised of color, no-color line, or black-white visual contrast conditions parametrically varied by complexity (relations 0, 1, 2. The use of matrix reasoning is ecologically valid for its psychometric relevance and for its potential to link the processing of psychophysically specific visual properties with various levels of relational complexity during reasoning. The role of these elements is important because matrix tests assess intellectual aptitude based on these seemingly context-less exercises. This experiment is a first step toward examining the psychophysical underpinnings of performance on these types of problems. The importance of this is increased in light of recent evidence that intelligence can be linked to visual discrimination. We submit three main findings. First, color and black-white visual contrast add demand at a basic sensory level, but contributions from color and from black-white visual contrast are dissociable in cortex such that color engages a reasoning heuristic and black-white visual contrast engages a sensory heuristic. Second, color supports contextual sense-making by boosting salience resulting in faster problem solving. Lastly, when visual complexity reaches 2-relations, color and visual contrast relinquish salience to other dimensions of problem

Facilitating relative comparisons of health impacts from postulated accidents in environmental impact statements

International Nuclear Information System (INIS)

Mueller, C.J.

1996-01-01

Current US Department of Energy (DOE) guidance on the performance of accident analyses supported an environmental impact statement (EIS) stresses a graded approach that emphasizes the most important risks, calls for the evaluation of frequencies as well as consequences for severe accident scenarios, and discourages the use of bounding analyses that confound risk comparisons among EIS alternatives. This paper discusses methods in probabilistic risk analysis that were developed and applied in defining accidents and generating radiological source terms for the DOE Draft Waste Management Programmatic Environmental Impact Statement (WM PEIS); publication of the Final WM PEIS is due in late summer 1996. The strengths and shortcomings of the cited probabilistic risk analysis methods used to evaluate facility accidents are addressed, both as they relate to the WM PEIS and as they relate to more general EIS applications. Key guidance is discussed that was developed by DOE and used in shaping the techniques cited herein for application in an EIS. Related perceptions on accidents observed from the public comment process for the WM PEIS are cited. Finally, recommendations are made on the basis of needs as well as lessons learned in implementing the accident analysis for the WM PEIS

Meaning From Environmental Sounds: Types of Signal-Referent Relations and Their Effect on Recognizing Auditory Icons

Science.gov (United States)

Keller, Peter; Stevens, Catherine

2004-01-01

This article addresses the learnability of auditory icons, that is, environmental sounds that refer either directly or indirectly to meaningful events. Direct relations use the sound made by the target event whereas indirect relations substitute a surrogate for the target. Across 3 experiments, different indirect relations (ecological, in which…

Molecular basis of immunogenicity to botulinum neurotoxins and uses of the defined antigenic regions.

Science.gov (United States)

Atassi, M Z

2015-12-01

Intensive research in this laboratory over the last 19 years has aimed at understanding the molecular bases for immune recognition of botulinum neurotoxin, types A and B and the role of anti-toxin immune responses in defense against the toxin. Using 92 synthetic 19-residue peptides that overlapped by 5 residues and comprised an entire toxin (A or B) we determined the peptides' ability to bind anti-toxin Abs of human, mouse, horse and chicken. We also localized the epitopes recognized by Abs of cervical dystonia patients who developed immunoresistance to correlate toxin during treatment with BoNT/A or BoNT/B. For BoNT/A, patients' blocking Abs bound to 13 regions (5 on L and 8 on H subunit) on the surface and the response to each region was under separate MHC control. The responses were defined by the structure of the antigen and by the MHC of the host. The antigenic regions coincided or overlapped with synaptosomes (SNPS) binding regions. Antibody binding blocked the toxin's ability to bind to neuronal cells. In fact selected synthetic peptides were able to inhibit the toxin's action in vivo. A combination of three synthetic strong antigenic peptides detected blocking Abs in 88% of immunoresistant patients' sera. Administration of selected epitopes, pre-linked at their N(α) group to monomethoxyployethylene glycol, into mice with ongoing blocking anti-toxin Abs, reduced blocking Ab levels in the recipients. This may be suitable for clinical applications. Defined epitopes should also be valuable in synthetic vaccines design. Copyright © 2015 Elsevier Ltd. All rights reserved.

Psychometric evaluation of the Environmental Reality Shock-Related Issues and Concerns instrument for newly graduated nurses.

Science.gov (United States)

Kim, Eun-Young; Yeo, Jung Hee; Park, Hyunjeong; Sin, Kyung Mi; Jones, Cheryl B

2018-02-01

Reality shock is a critical representation of the gap between nursing education and clinical practice and it is important to explore the level of reality shock among nurses. However, there is no relevant instrument to assess the level of reality shock in South Korea. The purpose of this is to determine the validity and reliability of the Korean version of the Environmental Reality Shock-Related Issues and Concerns instrument. A cross-sectional study design was used in this study. The data collection was conducted in selected 15 hospitals in South Korea. A convenience sample of 216 newly graduated nurses participated in the study. The Korean version of the Environmental Reality Shock-Related Issues and Concerns instrument was developed through the forward-backward translation technique, and revision based on feedback from expert groups. The internal consistency reliability was assessed using Cronbach's alpha, and the construct validity was determined via exploratory and confirmatory factor analysis. The Korean version of the Environmental Reality Shock-Related Issues and Concerns has reliable internal consistency (Cronbach's alpha=0.91). Exploratory factor analysis revealed five factors including job, relationships, expectations, private life, and performance, which explained 61.92% of variance. The factor loadings ranged from 0.451 to 0.832. The five-factor structure was validated by confirmatory factor analysis (RMR0.9). It was concluded that the Korean version of the Environmental Reality Shock-Related Issues and Concerns instrument has satisfactory construct validity and reliability to measure the reality shock of newly graduated nurses in South Korea. Copyright © 2017 Elsevier Ltd. All rights reserved.

Indoor environmental and air quality characteristics, building-related health symptoms, and worker productivity in a federal government building complex.

Science.gov (United States)

Lukcso, David; Guidotti, Tee Lamont; Franklin, Donald E; Burt, Allan

2016-01-01

Building Health Sciences, Inc. (BHS), investigated environmental conditions by many modalities in 71 discreet areas of 12 buildings in a government building complex that had experienced persistent occupant complaints despite correction of deficiencies following a prior survey. An online health survey was completed by 7,637 building occupants (49% response rate), a subset of whom voluntarily wore personal sampling apparatus and underwent medical evaluation. Building environmental measures were within current standards and guidelines, with few outliers. Four environmental factors were consistently associated with group-level building-related health complaints: physical comfort/discomfort, odor, job stress, and glare. Several other factors were frequently commented on by participants, including cleanliness, renovation and construction activities, and noise. Low relative humidity was significantly associated with lower respiratory and "sick building syndrome"-type symptoms. No other environmental conditions (including formaldehyde, PM10 [particulate matter with an aerodynamic diameter work but at reduced capacity), and increase in reported symptom-days, including symptoms not related to respiratory disease. We found that in buildings without unusual hazards and with environmental and air quality indicators within the range of acceptable indoor air quality standards, there is an identifiable population of occupants with a high prevalence of asthma and allergic disease who disproportionately report discomfort and lost productivity due to symptoms and that in "normal" buildings these outcome indicators are more closely associated with host factors than with environmental conditions. We concluded from the experience of this study that building-related health complaints should be investigated at the work-area level and not at a building-wide level. An occupant-centric medical evaluation should guide environmental investigations, especially when screening results of building

Partitioning the Relative Importance of Phylogeny and Environmental Conditions on Phytoplankton Fatty Acids

Science.gov (United States)

Galloway, Aaron W. E.; Winder, Monika

2015-01-01

Essential fatty acids (EFA), which are primarily generated by phytoplankton, limit growth and reproduction in diverse heterotrophs. The biochemical composition of phytoplankton is well-known to be governed both by phylogeny and environmental conditions. Nutrients, light, salinity, and temperature all affect both phytoplankton growth and fatty acid composition. However, the relative importance of taxonomy and environment on algal fatty acid content has yet to be comparatively quantified, thus inhibiting predictions of changes to phytoplankton food quality in response to global environmental change. We compiled 1145 published marine and freshwater phytoplankton fatty acid profiles, consisting of 208 species from six major taxonomic groups, cultured in a wide range of environmental conditions, and used a multivariate distance-based linear model to quantify the total variation explained by each variable. Our results show that taxonomic group accounts for 3-4 times more variation in phytoplankton fatty acids than the most important growth condition variables. The results underscore that environmental conditions clearly affect phytoplankton fatty acid profiles, but also show that conditions account for relatively low variation compared to phylogeny. This suggests that the underlying mechanism determining basal food quality in aquatic habitats is primarily phytoplankton community composition, and allows for prediction of environmental-scale EFA dynamics based on phytoplankton community data. We used the compiled dataset to calculate seasonal dynamics of long-chain EFA (LCEFA; ≥C20 ɷ-3 and ɷ-6 polyunsaturated fatty acid) concentrations and ɷ-3:ɷ-6 EFA ratios in Lake Washington using a multi-decadal phytoplankton community time series. These analyses quantify temporal dynamics of algal-derived LCEFA and food quality in a freshwater ecosystem that has undergone large community changes as a result of shifting resource management practices, highlighting diatoms

Review: Groundwater resources and related environmental issues in China

Science.gov (United States)

Hao, Aibing; Zhang, Yilong; Zhang, Eryong; Li, Zhenghong; Yu, Juan; Wang, Huang; Yang, Jianfeng; Wang, Yao

2018-05-01

As an important component of water resources, groundwater plays a crucial role in water utilization in China and an irreplaceable role in supporting economic and social development, especially in the northern arid and semi-arid plains and basin areas, which are densely populated and relatively short of surface-water resources. This paper comprehensively reviews and discusses the regional hydrogeological conditions, the temporal and spatial distribution of groundwater, the groundwater quality, and the actuality of groundwater exploitation and utilization in China. Meanwhile, aiming at the environmental problems induced by overexploitation to meet the sharply increasing water demand, this paper puts forward the major tasks for the next few years in terms of groundwater exploitation control, conservation and management.

Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin.

Science.gov (United States)

Ayyar, B Vijayalakshmi; Tajhya, Rajeev B; Beeton, Christine; Atassi, M Zouhair

2015-10-28

Botulinum neurotoxins (BoNTs) are the most toxic substances known. BoNT intoxicates cells in a highly programmed fashion initiated by binding to the cell surface, internalization and enzymatic cleavage of substrate, thus, inhibiting synaptic exocytosis. Over the past two decades, immunological significance of BoNT/A C-terminal heavy chain (HC) and light chain (LC) domains were investigated extensively leading to important findings. In the current work, we explored the significance of BoNT/A heavy chain N-terminal (HN) region as a vaccine candidate. Mice were immunized with recombinant HN519-845 generating antibodies (Abs) that were found to be protective against lethal dose of BoNT/A. Immuno-dominant regions of HN519-845 were identified and individually investigated for antibody response along with synthetic peptides within those regions, using in vivo protection assays against BoNT/A. Results were confirmed by patch-clamp analysis where anti-HN antibodies were studied for the ability to block toxin-induced channel formation. This data strongly indicated that HN519-593 is an important region in generating protective antibodies and should be valuable in a vaccine design. These results are the first to describe and dissect the protective activity of the BoNT/A HN domain.

Clostridium botulinum serotype D neurotoxin and toxin complex bind to bovine aortic endothelial cells via sialic acid.

Science.gov (United States)

Yoneyama, Tohru; Miyata, Keita; Chikai, Tomoyuki; Mikami, Akifumi; Suzuki, Tomonori; Hasegawa, Kimiko; Ikeda, Toshihiko; Watanabe, Toshihiro; Ohyama, Tohru; Niwa, Koichi

2008-12-01

Botulinum neurotoxin (BoNT) is produced as a large toxin complex (L-TC) associated with nontoxic nonhemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, -33 and -17). The binding properties of BoNT to neurons and L-TC to intestinal epithelial cells are well documented, while those to other tissues are largely unknown. Here, to obtain novel insights into the pathogenesis of foodborne botulism, we examine whether botulinum toxins bind to vascular endothelial cells. BoNT and 750 kDa L-TC (a complex of BoNT, NTNHA and HAs) of Clostridium botulinum serotype D were incubated with bovine aortic endothelial cells (BAECs), and binding to the cells was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Both BoNT and L-TC bound to BAECs, with L-TC showing stronger binding. Binding of BoNT and L-TC to BAECs was significantly inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, galactose, lactose or N-acetyl galactosamine did not significantly inhibit toxin binding to the cells. This is the first report demonstrating that BoNT and L-TC bind to BAECs via sialic acid, and this mechanism may be important in the trafficking pathway of BoNT in foodborne botulism.

Cleavage of SNAP25 and its shorter versions by the protease domain of serotype A botulinum neurotoxin.

Directory of Open Access Journals (Sweden)

Rahman M Mizanur

Full Text Available Various substrates, catalysts, and assay methods are currently used to screen inhibitors for their effect on the proteolytic activity of botulinum neurotoxin. As a result, significant variation exists in the reported results. Recently, we found that one source of variation was the use of various catalysts, and have therefore evaluated its three forms. In this paper, we characterize three substrates under near uniform reaction conditions using the most active catalytic form of the toxin. Bovine serum albumin at varying optimum concentrations stimulated enzymatic activity with all three substrates. Sodium chloride had a stimulating effect on the full length synaptosomal-associated protein of 25 kDa (SNAP25 and its 66-mer substrates but had an inhibitory effect on the 17-mer substrate. We found that under optimum conditions, full length SNAP25 was a better substrate than its shorter 66-mer or 17-mer forms both in terms of kcat, Km, and catalytic efficiency kcat/Km. Assay times greater than 15 min introduced large variations and significantly reduced the catalytic efficiency. In addition to characterizing the three substrates, our results identify potential sources of variations in previous published results, and underscore the importance of using well-defined reaction components and assay conditions.

An overview of public health service health-related activities as they relate to the Department of Energy's environmental restoration program

International Nuclear Information System (INIS)

Kocher, P.L.; Bashor, M.M.

1991-01-01

The Agency for Toxic Substances and Disease Registry (ATSDR) was created by the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) as an agency of the Public Health Service. Under the Superfund Amendments and Reauthorization Act of 1986 (SARA; CERCLA as amended), the public health responsibilities of ATSDR were greatly expanded. Among the responsibilities are (1) preparing health assessments for each site proposed for or listed on the National Priorities List (NPL) established by the US Environmental Protection Agency; (2) conducting epidemiologic and other health studies around NPL sites; (3) establishing registries of exposed individuals; (4) establishing health surveillance programs; (5) developing toxicological profiles for hazardous substances; (6) performing health and emergency response consultations; and (7) performing other health-related activities (e.g., health education). In October 1990, ATSDR signed a memorandum of understanding (MOU) with the Department of Energy (DOE) headquarters requiring that DOE operations offices sign interagency agreements (IAGs) with ATSDR for its conduct of 104(i) health activities at DOE sites. These activities include health assessments, related health studies such as surveillance programs, epidemiologic studies, and registries of exposed persons, and toxicological profiles of hazardous substances unique to DOE sites. ATSDR's studies will focus more on an assessment of the health risk to human populations residing in and around DOE sites than on an evaluation of the health risk to workers on site. Nevertheless, CERCLA, the MOU, and site-specific IAGs authorize ATSDR's access to health and environmental data concerning each site. The IAGs contemplate that ATSDR work closely with DOE operations offices in their implementation of their respective environmental restoration programs

Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

Energy Technology Data Exchange (ETDEWEB)

Ha, Mi-Hee; Pflugmacher, Stephan, E-mail: stephan.pflugmacher@tu-berlin.de

2013-08-15

Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H{sub 2}O{sub 2}, which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

International Nuclear Information System (INIS)

Ha, Mi-Hee; Pflugmacher, Stephan

2013-01-01

Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H 2 O 2 , which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

Directory of Open Access Journals (Sweden)

Irene Vergara

2016-03-01

Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.

The destructive effect of botulinum neurotoxins on the SNARE protein: SNAP-25 and synaptic membrane fusion

Directory of Open Access Journals (Sweden)

Bin Lu

2015-06-01

Full Text Available Synaptic exocytosis requires the assembly of syntaxin 1A and SNAP-25 on the plasma membrane and synaptobrevin 2 (VAMP2 on the vesicular membrane to bridge the two opposite membranes. It is believed that the three SNARE proteins assemble in steps along the dynamic assembly pathway. The C-terminus of SNAP-25 is known to be the target of botulinum neurotoxins (BoNT/A and BoNT/E that block neurotransmitters release in vivo. In this study, we employed electron paramagnetic resonance (EPR spectroscopy to investigate the conformation of the SNAP-25 C-terminus in binary and ternary SNARE complexes. The fluorescence lipid mixing assay shows that the C-terminal of SNAP-25 is essential for membrane fusion, and that the truncated SNAP-25 mutants cleaved by BoNT/A and BoNT/E display different inhibition effects on membrane fusion: SNAP-25E (Δ26 abolishes the fusion activity of the SNARE complex, while SNAP-25A (Δ9 loses most of its function, although it can still form a SDS-resistant SNARE complex as the wild-type SNAP-25. CW-EPR spectra validate the unstable structures of the SNARE complex formed by SNAP-25 mutants. We propose that the truncated SNAP-25 mutants will disrupt the assembly of the SNARE core complex, and then inhibit the synaptic membrane fusion accordingly.

Quality and environmental aspects in relation to the application of pulverized fuel ash

International Nuclear Information System (INIS)

Berg, J.W. van den

1991-01-01

In the Netherlands pulverised coal from different parts of the world is used in 5 coalfired power stations which each have 1 to 3 boilers, which in turn are equipped with various types of burners. This causes a large variation in the composition of the pulverized fuel ash (PFA). The PFA is marketed in several areas, each of which has its own specific quality requirements. These requirements are partially dictated in standard specifications. In order to obtain insight into the quality of the PFA, samples are taken and analysed daily. Rules for certification, concerning the quality and the quality control of PFA for use in concrete in The Netherlands have been agreed upon. The environmental aspects in relation to the application of PFA concern the working conditions and health aspects during processing and the environmental impact when PFA is used as a building material. The Dutch legislation concerning the environmental consequences of the application of PFA and other secondary materials is currently under review. 3 tabs

A Systematic Review of Environmental Correlates of Obesity-Related Dietary Behaviors in Youth

Science.gov (United States)

van der Horst, Klazine; Oenema, A.; Ferreira, I.; Wendel-Vos, W.; Giskes, K.; van Lenthe, F.; Brug, J.

2007-01-01

There is increasing interest in the role the environment plays in shaping the dietary behavior of youth, particularly in the context of obesity prevention. An overview of environmental factors associated with obesity-related dietary behaviors among youth is needed to inform the development of interventions. A systematic review of observational…

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

OpenAIRE

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

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 li...

Temperature effects explain continental scale distribution of cyanobacterial toxins

OpenAIRE

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

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 li...

Botulinum neurotoxin type A radiolabeled at either the light or the heavy chain

International Nuclear Information System (INIS)

Dekleva, M.L.; DasGupta, B.R.; Sathyamoorthy, V.

1989-01-01

Botulinum neurotoxin (NT) has two distinct structural regions called L and H chains (approximately 50 and approximately 100 kDa, respectively). Although the H chain is responsible for binding of the NT to neuronal cells, it is not known which of the subunits is internalized and therefore responsible for causing the blockage of acetylcholine release in susceptible neuronal cells. In this report we describe for the first time the preparation of type A NT which is selectively radiolabeled at either the L or the H chain subunit. Such NT preparations will be useful as tools for determining the distribution of L and H chains in poisoned neuronal cells and the role that each subunit plays in inducing toxicity. The L and H chains of the NT (approximately 150 kDa) were separated, purified, and then individually radiolabeled by reductive methylation of the lysine residues using [3H]- or [14C]formaldehyde. The labeled L and H chains were reconjugated with the complementary unlabeled L and H chains. Formation of -S-S- and noncovalent bonds between the L and H chains regenerated the approximately 150 kDa NT. Autoradiographs of sodium dodecyl sulfate polyacrylamide gels confirmed that each reconstituted NT preparation was labeled at only one subunit chain. NT selectively labeled at either the L or the H chain had specific radioactivities of ca. 25-30 and 45-55 microCi/mumol, respectively, and toxicity (mouse LD50/mg protein) values of 2.2 +/- 1.1 X 10(7) and 3.0 +/- 1.0 X 10(7), respectively. A linear increase in the specific radioactivity of L and H chain subunits was observed with increasing concentrations of 3H- or 14C-labeled formaldehyde in the reaction mixture and with increasing concentrations of L or H chain in the reaction mixture

Motivators and barriers to incorporating climate change-related health risks in environmental health impact assessment.

Science.gov (United States)

Turner, Lyle R; Alderman, Katarzyna; Connell, Des; Tong, Shilu

2013-03-22

Climate change presents risks to health that must be addressed by both decision-makers and public health researchers. Within the application of Environmental Health Impact Assessment (EHIA), there have been few attempts to incorporate climate change-related health risks as an input to the framework. This study used a focus group design to examine the perceptions of government, industry and academic specialists about the suitability of assessing the health consequences of climate change within an EHIA framework. Practitioners expressed concern over a number of factors relating to the current EHIA methodology and the inclusion of climate change-related health risks. These concerns related to the broad scope of issues that would need to be considered, problems with identifying appropriate health indicators, the lack of relevant qualitative information that is currently incorporated in assessment and persistent issues surrounding stakeholder participation. It was suggested that improvements are needed in data collection processes, particularly in terms of adequate communication between environmental and health practitioners. Concerns were raised surrounding data privacy and usage, and how these could impact on the assessment process. These findings may provide guidance for government and industry bodies to improve the assessment of climate change-related health risks.

A new approach to determine the environmental qualification requirements for the safety related equipment

International Nuclear Information System (INIS)

Hasnaoui, C.; Parent, G.

2000-01-01

The objective of the environmental qualification of safety related equipment is to ensure that the plant defense-in-depth is not compromised by common mode failures following design basis accidents with a harsh environment. A new approach based on safety functions has been developed to determine what safety-related equipment is required to function during and after a design basis accident, as well as their environmental qualification requirements. The main feature of this approach is to use auxiliary safety functions established from safety requirements as credited in the safety analyses. This approach is undertaken in three steps: identification of the auxiliary safety functions of each main safety function; determination of the main equipment groups required for each auxiliary safety function; and review of the safety analyses for design basis accidents in order to determine the credited auxiliary safety functions and their mission times for each accident scenario. Some of the benefits of the proposed approach for the determination of the safety environmental qualification requirements are: a systematic approach for the review of safety analyses based on a safety function check list, and the insurance, with the availability of the safety functions, that Gentilly-2 defense-in-depth would not be compromised by design basis accidents with a harsh environment. (author)

Environmental Characteristics of Carbonatite and Alkaline Intrusion-related Rare Earth Element (REE) Deposits

Science.gov (United States)

Seal, R. R., II; Piatak, N. M.

2017-12-01

Carbonatites and alkaline intrusions are important sources of REEs. Environmental risks related to these deposit types have been assessed through literature review and evaluation of the geochemical properties of representative samples of mill tailings and their leachates. The main ore mineral in carbonatite deposits is bastnasite [(Ce,La)(CO3)F], which is found with dolomite and calcite ( 65 %), barite (20 - 25 %), plus a number of minor accessory minerals including sulfides such as galena and pyrite. Generally, alkaline intrusion-related REE deposits either occur in layered complexes or with dikes and veins cutting alkaline intrusions. Such intrusions have a more diverse group of REE ore minerals that include fluorcarbonates, oxides, silicates, and phosphates. Ore also can include minor calcite and iron (Fe), lead (Pb), and zinc (Zn) sulfides. The acid-generating potential of both deposit types is low because of a predominance of carbonate minerals in the carbonatite deposits, the presence of feldspars and minor calcite in alkaline intrusion-related deposits, and to only minor to trace occurrence of potentially acid-generating sulfide minerals. Both deposit types, however, are produced by igneous and hydrothermal processes that enrich high-field strength, incompatible elements, which typically are excluded from common rock-forming minerals. Elements such as yttrium (Y), niobium Nb), zirconium (Zr), hafnium (Hf), tungsten (W), titanium (Ti), tantalum (Ta), scandium (Sc), thorium (Th), and uranium (U) can be characteristic of these deposits and may be of environmental concern. Most of these elements, including the REEs, but with the exception of U, have low solubilities in water at the near-neutral pH values expected around these deposits. Mill tailings from carbonatite deposits can exceed residential soil and sediment criteria for Pb, and leachates from mill tailings can exceed drinking water guidelines for Pb. The greatest environmental challenges, however, are

Environmental factors related to water level regulation - a comparative study in northern Finland

International Nuclear Information System (INIS)

Hellsten, S.K.

1997-01-01

The environmental conditions of the littoral zone were studied in the regulated Lake Ontojaervi and the unregulated Lake Lentua in northern Finland. The general aims of the study were to analyse the environmental factors related to water level regulation in the littoral zone and to produce information for assessing the effects of hydroelectric development in northern lakes. The study was basically carried out by comparing the littoral environments of the two study lakes. The most visible effects of water level regulation were related to the raised water level, which yielded erosion of sandy shores at the beginning of the regulation. Another effect of lake regulation was the altered fluctuation of the water level, which led to bottom instability and increased the size of the frozen and ice penetration zones. The effect of ice penetration was also easy to recognize on the shores of Lake Ontojaervi, where the surface sediment was frozen to a greater depth and across wider areas than in Lake Lentua. Below the freezing zone, the ice just pressed down on the sediment. The shores of Lake Ontojaervi were steeper than those of Lake Lentua, which affected the distribution of bottom types, with sandy bottoms being more common in Lake Lentua than in Lake Ontojaervi. The factors related to site exposure included effective fetch and the shape of the shoreline. The sedimentation level correlated only with the slope and was not predicted by the fetch or shape. The vertical reduction of light was estimated on the basis of water colour. The main environmental factors from the two lakes were used in a discriminant analysis to predict the bottom type distribution of the littoral (r 2 = 0.41). (orig.) 66 refs

Environmental factors related to water level regulation - a comparative study in northern Finland

Energy Technology Data Exchange (ETDEWEB)

Hellsten, S K [VTT Communities and Infrastructure. Water Engineering and Ecotechnology, Oulu (Finland)

1998-12-31

The environmental conditions of the littoral zone were studied in the regulated Lake Ontojaervi and the unregulated Lake Lentua in northern Finland. The general aims of the study were to analyse the environmental factors related to water level regulation in the littoral zone and to produce information for assessing the effects of hydroelectric development in northern lakes. The study was basically carried out by comparing the littoral environments of the two study lakes. The most visible effects of water level regulation were related to the raised water level, which yielded erosion of sandy shores at the beginning of the regulation. Another effect of lake regulation was the altered fluctuation of the water level, which led to bottom instability and increased the size of the frozen and ice penetration zones. The effect of ice penetration was also easy to recognize on the shores of Lake Ontojaervi, where the surface sediment was frozen to a greater depth and across wider areas than in Lake Lentua. Below the freezing zone, the ice just pressed down on the sediment. The shores of Lake Ontojaervi were steeper than those of Lake Lentua, which affected the distribution of bottom types, with sandy bottoms being more common in Lake Lentua than in Lake Ontojaervi. The factors related to site exposure included effective fetch and the shape of the shoreline. The sedimentation level correlated only with the slope and was not predicted by the fetch or shape. The vertical reduction of light was estimated on the basis of water colour. The main environmental factors from the two lakes were used in a discriminant analysis to predict the bottom type distribution of the littoral (r{sup 2} = 0.41). (orig.) 66 refs.

Group contribution modelling for the prediction of safety-related and environmental properties

DEFF Research Database (Denmark)

Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

warming potential and ozone depletion potential. Process safety studies and environmental assessments rely on accurate property data. Safety data such as flammability limits, heat of combustion or auto ignition temperature play an important role in quantifying the risk of fire and explosions among others......We present a new set of property prediction models based on group contributions to predict major safety-related and environmental properties for organic compounds. The predicted list of properties includes lower and upper flammability limits, heat of combustion, auto ignition temperature, global...... models like group contribution (GC) models can estimate data. However, the estimation needs to be accurate, reliable and as little time-consuming as possible so that the models can be used on the fly. In this study the Marrero and Gani group contribution (MR GC) method has been used to develop the models...

The Relation of Environmental Quality and Fishery Sector in Indonesia

Science.gov (United States)

Oktavilia, Shanty; Habibah Yusfi, Reikha; Firmansyah; Sugiyanto, FX

2018-02-01

The condition of fishery sector is currently stagnating, even tending to decline, which is indicated by the decrease of production in some areas in Indonesia. Environmental degradation in marine waters is due to global climate change and uncontrolled fish exploitation impact on the decline of marine fisheries production. While in aquaculture, the environmental quality is also indicated to influence the production. Nevertheless, the increase of production of both marine and terrestrial fisheries has an effect on the quality of the environment. This study aims to analyze the interrelationship between the influence of environmental quality on the production of fishery sub-sector and the influence of fishery subsector production on environmental quality. This research employs environmental quality data and output of fishery of 34 provinces in Indonesia during 2011-2015. The study finds that output of fishery sector affects the environmental quality, which proves the Environment Kuznets Curve in the fishery sector in Indonesia. Since a certain threshold is achieved, the increase in revenue followed by the increase in environmental quality. The study also finds that the environmental quality has a positive effect on the production of fishery. Implication of the study is the increase of income of fishery households can be encouraged the ability of the community to protect the environment and increases the willingness of households to sacrifice other goods to environmental protection.

Quantification of mold contamination in multi-level buildings using the Environmental Relative Moldiness Index

Science.gov (United States)

The goal of this study was to evaluate the possible use of the Environmental Relative Moldiness Index (ERMI) to quantify mold contamination in multi-level, office buildings. Settled-dust samples were collected in multi-level, office buildings and the ERMI value for each sample de...

A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding

Energy Technology Data Exchange (ETDEWEB)

Yao, Guorui; Lam, Kwok-ho; Weisemann, Jasmin; Peng, Lisheng; Krez, Nadja; Perry, Kay; Shoemaker, Charles B.; Dong, Min; Rummel, Andreas; Jin, Rongsheng (BCH); (Cornell); (Tufts CTSI); (UCI); (MHH)

2017-08-07

Antibody treatment is currently the only available countermeasure for botulism, a fatal illness caused by flaccid paralysis of muscles due to botulinum neurotoxin (BoNT) intoxication. Among the seven major serotypes of BoNT/A-G, BoNT/A poses the most serious threat to humans because of its high potency and long duration of action. Prior to entering neurons and blocking neurotransmitter release, BoNT/A recognizes motoneurons via a dual-receptor binding process in which it engages both the neuron surface polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Previously, we identified a potent neutralizing antitoxin against BoNT/A1 termed ciA-C2, derived from a camelid heavy-chain-only antibody (VHH). In this study, we demonstrate that ciA-C2 prevents BoNT/A1 intoxication by inhibiting its binding to neuronal receptor SV2. Furthermore, we determined the crystal structure of ciA-C2 in complex with the receptor-binding domain of BoNT/A1 (HCA1) at 1.68 Å resolution. The structure revealed that ciA-C2 partially occupies the SV2-binding site on H_CA1, causing direct interference of HCA1 interaction with both the N-glycan and peptide-moiety of SV2. Interestingly, this neutralization mechanism is similar to that of a monoclonal antibody in clinical trials, despite that ciA-C2 is more than 10-times smaller. Taken together, these results enlighten our understanding of BoNT/A1 interactions with its neuronal receptor, and further demonstrate that inhibiting toxin binding to the host receptor is an efficient countermeasure strategy.

Scorpion neurotoxin AaIT-expressing Beauveria bassiana enhances the virulence against Aedes albopictus mosquitoes.

Science.gov (United States)

Deng, Sheng-Qun; Cai, Qun-Di; Deng, Ming-Zhi; Huang, Qiang; Peng, Hong-Juan

2017-12-01

To improve the insecticidal efficacy of this entomopathogen Beauveria bassiana, the fungus was genetically modified to express an insect-specific scorpion neurotoxin AaIT. The virulence of the recombinant B. bassiana strain (Bb-AaIT) against Aedes albopictus adults (which occurs via penetration through the cuticle during spore germination or by conidia ingestion), and the larvae (by conidia ingestion) was measured with bioassays. The median lethal concentration (LC 50 ) of Bb-AaIT against A. albopictus larvae was 313.3-fold lower on day 4 and 11.3-fold lower on day 10 than that of the wild type (WT). Through conidia feeding or body contact, Bb-AaIT killed 50% of adult female mosquitoes at 3.9- or 1.9-fold reduced concentrations on day 4 and at 2.1- or 2.4-fold reduced concentrations on day 10. Compared with the results for the WT, the median lethal time (LT 50 ) of Bb-AaIT was reduced by 28.6% at 1 × 10 7 conidia ml -1 and 34.3% at 1 × 10 6 conidia ml -1 in the larvae bioassay by conidia ingestion, while it decreased 32.3% at 1 × 10 7 conidia ml -1 by conidia ingestion and 24.2% at 1 × 10 8 conidia ml -1 by penetrating through the cuticle in the adult bioassay. All the differences were significant. Our findings indicated that Bb-AaIT had higher virulence and faster action than the WT in killing the larval and adult mosquitoes, and therefore, it is valuable for development as a commercial mosquito pesticide.

Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

Directory of Open Access Journals (Sweden)

Jack Xie

2010-08-01

Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

Experiments related to marine environmental science using a tandem Pelletron

International Nuclear Information System (INIS)

Kitamura, A.; Hamamoto, S.; Ohtani, Y.; Furuyama, Y.; Taniike, A.; Kubota, N.; Yamauchi, T.; Mimura, H.

2003-01-01

Activities related to marine environmental science, which have been made in our laboratory using a 1.7MV Pelletron 5SDH2 accelerator, are reviewed. One is successful application of proton beams to radiation-induced graft polymerization for making amidoxime-type adsorbents that are very effective for collecting doubly charged ions of metal elements, such as uranium and vanadium, abundantly dissolved in seawater. The other is effective application of accelerator analyses to investigation of interaction of tributyltin (TBT) chloride, which had been used in self-polishing antifouling paints and are endocrine disrupter having mutagenicity, with a TBT resistant marine microorganism newly isolated from sediment of a ship's ballast water tank. (author)

Botulinum Neurotoxin A Injections Influence Stretching of the Gastrocnemius Muscle-Tendon Unit in an Animal Model

Directory of Open Access Journals (Sweden)

Christopher J. Tuohy

2012-08-01

Full Text Available Botulinum Neurotoxin A (BoNT-A injections have been used for the treatment of muscle contractures and spasticity. This study assessed the influence of (BoNT-A injections on passive biomechanical properties of the muscle-tendon unit. Mouse gastrocnemius muscle (GC was injected with BoNT-A (n = 18 or normal saline (n = 18 and passive, non-destructive, in vivo load relaxation experimentation was performed to examine how the muscle-tendon unit behaves after chemical denervation with BoNT-A. Injection of BoNT-A impaired passive muscle recovery (15% vs. 35% recovery to pre-stretching baseline, p < 0.05 and decreased GC stiffness (0.531 ± 0.061 N/mm vs. 0.780 ± 0.037 N/mm, p < 0.05 compared to saline controls. The successful use of BoNT-A injections as an adjunct to physical therapy may be in part attributed to the disruption of the stretch reflex; thereby modulating in vivo passive muscle properties. However, it is also possible that BoNT-A injection may alter the structure of skeletal muscle; thus modulating the in vivo passive biomechanical properties of the muscle-tendon unit.

The Environmental Scanning Function of Public Relations Practitioners and Participation in Management Decision Making.

Science.gov (United States)

Dozier, David M.

Focusing on the concepts of scanning (gathering information about segments of the public, their reactions to the organization, and their opinions about issues important to the organization), decision making, and roles, a study examined the relationship between environmental scanning and the participation of public relations practitioners in…

The relative efficiency of market-based environmental policy instruments with imperfect compliance

OpenAIRE

Rousseau, Sandra; Proost, Stef

2004-01-01

This paper examines to what extent incomplete compliance of environmental regulation mitigates the distortions caused by pre-existing labour taxes. We study the relative cost efficiency of three market-based instruments: emission taxes, tradable permits and output taxes. In a first-best setting and given that monitoring and enforcement is costless, we find that the same utility levels can be reached with and without incomplete compliance. However, allowing for violations makes the policy i...

Botulinum Neurotoxin Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation with and without Neurogenic Muscular Hyperactivity

Directory of Open Access Journals (Sweden)

Kazuya Yoshida

2018-04-01

Full Text Available The aim of this study was to compare treatment outcomes following intramuscular injection of botulinum neurotoxin (BoNT in patients with recurrent temporomandibular joint dislocation, with and without muscle hyperactivity due to neurological diseases. Thirty-two patients (19 women and 13 men, mean age: 62.3 years with recurrent temporomandibular joint dislocation were divided into two groups: neurogenic (8 women and 12 men and habitual (11 women and 1 man. The neurogenic group included patients having neurological disorders, such as Parkinson’s disease or oromandibular dystonia, that are accompanied by muscle hyperactivity. BoNT was administered via intraoral injection to the inferior head of the lateral pterygoid muscle. In total, BoNT injection was administered 102 times (mean 3.2 times/patient. The mean follow-up duration was 29.5 months. The neurogenic group was significantly (p < 0.001 younger (47.3 years than the habitual group (84.8 years and required significantly (p < 0.01 more injections (4.1 versus 1.7 times to achieve a positive outcome. No significant immediate or delayed complications occurred. Thus, intramuscular injection of BoNT into the lateral pterygoid muscle is an effective and safe treatment for habitual temporomandibular joint dislocation. More injections are required in cases of neurogenic temporomandibular joint dislocation than in those of habitual dislocation without muscle hyperactivity.

Qualitative and Quantitative Detection of Botulinum Neurotoxins from Complex Matrices: Results of the First International Proficiency Test

Directory of Open Access Journals (Sweden)

Sylvia Worbs

2015-11-01

Full Text Available In the framework of the EU project EQuATox, a first international proficiency test (PT on the detection and quantification of botulinum neurotoxins (BoNT was conducted. Sample materials included BoNT serotypes A, B and E spiked into buffer, milk, meat extract and serum. Different methods were applied by the participants combining different principles of detection, identification and quantification. Based on qualitative assays, 95% of all results reported were correct. Successful strategies for BoNT detection were based on a combination of complementary immunological, MS-based and functional methods or on suitable functional in vivo/in vitro approaches (mouse bioassay, hemidiaphragm assay and Endopep-MS assay. Quantification of BoNT/A, BoNT/B and BoNT/E was performed by 48% of participating laboratories. It turned out that precise quantification of BoNT was difficult, resulting in a substantial scatter of quantitative data. This was especially true for results obtained by the mouse bioassay which is currently considered as “gold standard” for BoNT detection. The results clearly demonstrate the urgent need for certified BoNT reference materials and the development of methods replacing animal testing. In this context, the BoNT PT provided the valuable information that both the Endopep-MS assay and the hemidiaphragm assay delivered quantitative results superior to the mouse bioassay.

Multimodal aspects of CSR communication related to gender empowerment and environmental protection

DEFF Research Database (Denmark)

Maier, Carmen Daniela

Purpose – This paper explores how the multimodal persuasive strategies of CSR communication related to Coca-Cola’s “5 by 20” succeed to highlight the company’s continuous commitment to gender empowerment and environmental protection. Launched in 2010, “5 by 20” is a program designed to empower 5...... as the usual textual focus is extended to a multimodal one. Shedding light on how the multimodal interplay contributes to communicate corporate commitment to gender empowerment and environmental protection, this model can also be employed in order to explore multimodally other areas of CSR communication....... a multimodal analysis model through which it is possible to map and explain the multimodal persuasive strategies employed by the company in their CSR communication. The paper is focused on the analysis of the video series that can be accessed at: http://www.coca-colacompany.com/stories/5by20. Based on a social...

The role of environmental smoking in smoking-related cognitions and susceptibility to smoking in never-smoking 9-12 year-old children

NARCIS (Netherlands)

Schuck, K.; Otten, R.; Engels, R.C.M.E.; Kleinjan, M.

2012-01-01

Environmental smoking has numerous adverse effects on child health, and children are frequently exposed to environmental smoking. In the present study, we investigated the role of environmental smoking (parental smoking, sibling smoking, peer smoking) in smoking-related cognitions (pros of smoking,

Motivators and Barriers to Incorporating Climate Change-Related Health Risks in Environmental Health Impact Assessment

Directory of Open Access Journals (Sweden)

Shilu Tong

2013-03-01

Full Text Available Climate change presents risks to health that must be addressed by both decision-makers and public health researchers. Within the application of Environmental Health Impact Assessment (EHIA, there have been few attempts to incorporate climate change-related health risks as an input to the framework. This study used a focus group design to examine the perceptions of government, industry and academic specialists about the suitability of assessing the health consequences of climate change within an EHIA framework. Practitioners expressed concern over a number of factors relating to the current EHIA methodology and the inclusion of climate change-related health risks. These concerns related to the broad scope of issues that would need to be considered, problems with identifying appropriate health indicators, the lack of relevant qualitative information that is currently incorporated in assessment and persistent issues surrounding stakeholder participation. It was suggested that improvements are needed in data collection processes, particularly in terms of adequate communication between environmental and health practitioners. Concerns were raised surrounding data privacy and usage, and how these could impact on the assessment process. These findings may provide guidance for government and industry bodies to improve the assessment of climate change-related health risks.

EI Scale: an environmental impact assessment scale related to the construction materials used in the reinforced concrete

Directory of Open Access Journals (Sweden)

Gilson Morales

2010-12-01

Full Text Available This study aimed to create EI Scal, an environmental impact assessment scal, related to construction materials used in the reinforced concrete structure production. The main reason for that was based on the need to classify the environmental impact levels through indicators to assess the damage level process. The scale allowed converting information to estimate the environmental impact caused. Indicators were defined trough the requirements and classification criteria of impact aspects considering the eco-design theory. Moreover, the scale allowed classifying the materials and processes environmental impact through four score categories which resulted in a single final impact score. It was concluded that the EI scale could be cheap, accessible, and relevant tool for environmental impact controlling and reduction, allowing the planning and material specification to minimize the construction negative effects caused in the environment.

Trend of environmental radiation protection and its current related studies

International Nuclear Information System (INIS)

Yoshida, Satoshi

2011-01-01

Reviewed are the international trend of environmental radiation protection (ERP), Japanese studies of radiation effects on environmental livings from aspects of ecosystem to molecular level, and the future view. ERP is particularly closed up toward promotion after its first involvement in the general global conference, UN Conference on Environment and Development (1992). International Commission of Radiological Protection (ICRP) has conducted such actions for the environment as establishing protection essentials for non-human species (2003), organizing Committee 5 (2005), and defining Reference Animals and Plants (2008) where Derived Consideration Reference Levels of 0.1-100 mGy/d are proposed, together with cooperative actions by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), International Atomic Energy Agency (IAEA), The Organization for Economic Co-operation and Development (OECD)/Nuclear Energy Agency (NEA) and European projects. Japanese NIRS is now enrolled in the project of Environmental Modeling for Radiation Safety-II (IAEA). Major Japanese studies of radiation effects on environmental livings have utilized killifish (medaka: Oryzias latipes), springtail, earthworm, nematode, cultured plant cell (cedar), poplar, etc. Studies of the radiation effect on microcosm consisting of 3 livings have led to establishing a model for mathematical analysis and of 8 livings, have defined 50% affect dose of 5600 Gy gamma-ray. Irradiation of gamma-ray at 1 Gy/d for 5-10 days to the soil has been shown to result in alteration of the composition of natural earth bacterial population by denaturant gradient gel electrophoresis, which being a promising tool for evaluating the alteration of soil composition and function. At molecular levels, transcriptome analysis of various cells from yeast to man, is performed after irradiation of gamma-ray, neutron, heavy particles and others to reveal radiation-induced gene expression; and Hi-CEP (high

Evaluating the Environmental Dimension of Material Efficiency Strategies Relating to the Circular Economy

Directory of Open Access Journals (Sweden)

Stuart Walker

2018-03-01

Full Text Available Material efficiency is a key element of new thinking to address the challenges of reducing impacts on the environment and of resource scarcity, whilst at the same time meeting service and functionality demands on materials. Directly related to material efficiency is the concept of the Circular Economy, which is based on the principle of optimising the utility embodied in materials and products through the life-cycle. Although materials such as steel, on account of high recycling rates at end-of-life, are amongst the most ‘circular’ of manufactured materials, significant opportunities for greater material efficiency exist, which are yet to be widely implemented. Life Cycle Assessment (LCA is commonly used to assess the environmental benefits of recovering and recycling materials through the manufacturing supply chain and at end-of-life. Using an example taken from renewable energy generation, this paper explores the correlation between product circularity and the environmental case for strategies designed to improve material efficiency. An LCA-based methodology for accounting for the recovery and reuse of materials from the supply chain and at end-of-life is used as the basis for calculating the carbon footprint benefits of five material efficiency scenarios. The results are compared with a number of proposed material circularity indicators. Two conclusions from this exercise are that (i LCA methodologies based around end-of-life approaches are well placed for quantifying the environmental benefits of material efficiency and circular economy strategies and (ii when applying indicators relating to the circularity of materials these should also be supported by LCA-based studies.

Trust and cooperation relations in environmental management of Lebanon

NARCIS (Netherlands)

Abbas, Nivine; van der Molen, I.; Nader, M.R.; Lovett, Jonathan Cranidge

2014-01-01

This paper investigates trust and cooperation in the context of environmental management in Lebanon. Literature already indicated increasing environmental problems in this area that suffered from repeated episodes of armed conflict. The Lebanese government has been faced by many difficulties to

Gender differences in environmental related behaviour

Energy Technology Data Exchange (ETDEWEB)

Dalen, Hanne Marit; Halvorsen, Bente

2011-11-15

This report discusses gender differences in the data collected in the OECD household survey on environmental behaviour. The survey asked a sample of 10 000 respondents from 10 countries (Norway, Sweden, Canada, France, Italy, the Netherlands, the Czech Republic, Mexico, Australia and Korea) concerning household behaviour with respect to five areas: recycling, energy and water saving, organic food consumption and transportation. This report identifies and describes gender differences in behaviour, in underlying preferences and in household characteristics in this data. We use regression analyses to identify and test for significant gender differences in preferences, and we use differences in means to test for gender differences in background variables and the total effect of gender on behaviour. In our estimations, where we test for significant gender differences in preferences, we find many significant differences with respect to several of the explanatory variables affecting behaviour. However, there was no clear pattern for most of these gender differences. The only systematic gender difference we found in the estimations was that the belief that they can actually contribute to a better environment seems to be a more important motivator for environmental friendly behaviour for men than it is for women. There are also many significant differences between the genders in the distribution of key background variables, in particular with respect to income, car ownership, participation in the workforce, education and choice of residence. However, these gender differences in preferences and background variables only result in pronounced gender differences in behaviour to a small degree. The exception is transportation, where gender differences are large and significant. Men have a higher probability of owning a car or a motorcycle than women. And given that the respondent owns a car, men drive significantly more than women. For the rest of the behaviour measured in this

Applying real options in investment decisions relating to environmental pollution

Energy Technology Data Exchange (ETDEWEB)

Lin, Tyrone T. [Department of International Business, National Dong Hwa University, 1, Sec. 2, Da Hsueh Road, Shou-Feng, Hualien 974, Taiwan (China)]. E-mail: tjlin@mail.ndhu.edu.tw; Ko, C.-C. [Department of International Trade, Jin Wen Institute of Technology, Taiwan (China); Yeh, H.-N. [Graduate School of Management, Ming Chuan University, Taiwan (China)

2007-04-15

This study focuses on how to assess the optimal environmental investment decisions under economic and ecological uncertainty, and establishes the continuous time model using the real option approach to optimize environmental pollution policy. Unlike traditional cost benefit analysis, this work extends the model of [Pindyck, R.S., 2002. Optimal timing problems in environmental economics. Journal of Economic Dynamics and Control 26(9-10), 1677-1697], and attempts to identify the storage threshold of pollution stocks and the optimal timing for implementing environmental pollution decisions.

Applying real options in investment decisions relating to environmental pollution

International Nuclear Information System (INIS)

Lin, Tyrone T.; Ko, C.-C.; Yeh, H.-N.

2007-01-01

This study focuses on how to assess the optimal environmental investment decisions under economic and ecological uncertainty, and establishes the continuous time model using the real option approach to optimize environmental pollution policy. Unlike traditional cost benefit analysis, this work extends the model of [Pindyck, R.S., 2002. Optimal timing problems in environmental economics. Journal of Economic Dynamics and Control 26(9-10), 1677-1697], and attempts to identify the storage threshold of pollution stocks and the optimal timing for implementing environmental pollution decisions

Environmental and geomagnetic factors in relation to self-destructive ideation and behaviour

Science.gov (United States)

Bergiannaki, J. D.; Psarros, C.; Nastos, P. Th.; Paparigopoulos, T.; Paliatsos, A. G.; Tritakis, V. P.; Stefanis, C. N.

2001-09-01

Besides the individual factors such as the reaction to conflicts, several exogenous factors environmental and social may exert a pathogenic influence on suicidal behavior, suicide attempts and complete suicide on predisposed individuals. In the turn of the century many reports accord for the seasonality of suicides, which seems to have a bimodal distribution with a major peak around the spring-summer (April-May) and a second minor in autumn. On the other hand, the seasonal variation of environmental factors (daylight, sunlight duration, weather, temperature, air pressure, humidity, geomagnetism, solar activity, etc), of biological factors (melatonin, serotonin, serotonin precursors, etc) as also of sociological factors (ethnic events, major holidays, weekends etc) possibly influences the seasonal pattern of self-destructive behavior. Bimodal seasonal variation is also reported for biochemical parameters (L-tryptophan, serotonin, endorphin I fraction) that matches seasonal pattern in the prevalence of violent suicide in the total population and also in the incidence of the affective disorders. The aim of this study is to investigate the relation of environmental factors expressed by the Discomfort Index (DI) and geomagnetic factors expressed by the geomagnetic field Index DST in relation to suicidal behavior. The total number (4803) of patients recorded in the Ambulance of a Phychiatric Hospital (Eginition) throughout 1994 was used along with the records of 2750 patients of the year 1989. The Index DI is a function of dry and wet-bulb temperature. DST is probably one of the geomagnetic indices that expresses and monitors with the greatest accuracy the equatorial ring current variations. Our results show that there is a seasonal variation of suicidal behavior (Fourier analysis) with a major peak during summer (July) and a minor one during spring. A difference in the occurrence of the peaks was observed among genders. A relation of self-destructive behavior and the

Medical Isotopes Production Project: Molybdenum-99 and related isotopes: Environmental Impact Statement, Volume I

International Nuclear Information System (INIS)

1996-04-01

This Environmental Impact Statement (EIS) provides environmental and technical information concerning the U.S. Department of Energy's (DOE) proposal to establish a domestic source to produce molybdenum-99 (Mo-99) and related medical isotopes (iodine-131, xenon-133 and iodine-125). Mo-99, a radioactive isotope of the element molybdenum, decays to form metastable technetium-99 (Tc-99m), a radioactive isotope used thousands of times daily in medical diagnostic procedures in the U.S. Currently, all Mo-99 used in the U.S. is obtained from a single Canadian source. DOE is pursuing the Medical Isotopes Production Project in order to ensure that a reliable supply of Mo-99 is available to the U.S. medical community. Under DOE's preferred alternative, the Chemistry and Metallurgy Research Facility at the Los Alamos National Laboratory (LANL) and the Annular Core Research Reactor and Hot Cell Facility at Sandia National Laboratories/New Mexico (SNL/NM) would be used for production of the medical isotopes. In addition to the preferred alternative, three other reasonable alternatives and a no action alternative are analyzed in detail. The sites for the three reasonable alternatives are LANL, Oak Ridge National Laboratory (ORNL), and Idaho National Engineering Laboratory (INEL). The analyses in this EIS indicate no significant difference in the potential environmental impacts among the alternatives. Each of the alternatives would use essentially the same technology for the production of the medical isotopes. Minor differences in environmental impacts among alternatives relate to the extent of activity necessary to modify and restart (as necessary) existing reactors and hot cell facilities at each of the sites, the quantities, of low-level radioactive waste generated, how such waste would be managed, and the length of time needed for initial and full production capacity

The Relative Importance of Spatial and Local Environmental Factors in Determining Beetle Assemblages in the Inner Mongolia Grassland.

Directory of Open Access Journals (Sweden)

Xiao-Dong Yu

Full Text Available The aim of this paper is to increase understanding of the relative importance of the input of geographic and local environmental factors on richness and composition of epigaeic steppe beetles (Coleoptera: Carabidae and Tenebrionidae along a geographic (longitudinal/precipitation gradient in the Inner Mongolia grassland. Specifically, we evaluate the associations of environmental variables representing climate and environmental heterogeneity with beetle assemblages. Beetles were sampled using pitfall traps at 25 sites scattered across the full geographic extent of the study biome in 2011-2012. We used variance partitioning techniques and multi-model selection based on the Akaike information criterion to assess the relative importance of the spatial and environmental variables on beetle assemblages. Species richness and abundance showed unimodal patterns along the geographic gradient. Together with space, climate variables associated with precipitation, water-energy balance and harshness of climate had strong explanatory power in richness pattern. Abundance pattern showed strongest association with variation in temperature and environmental heterogeneity. Climatic factors associated with temperature and precipitation variables and the interaction between climate with space were able to explain a substantial amount of variation in community structure. In addition, the turnover of species increased significantly as geographic distances increased. We confirmed that spatial and local environmental factors worked together to shape epigaeic beetle communities along the geographic gradient in the Inner Mongolia grassland. Moreover, the climate features, especially precipitation, water-energy balance and temperature, and the interaction between climate with space and environmental heterogeneity appeared to play important roles on controlling richness and abundance, and species compositions of epigaeic beetles.

Environmental taxes and subsidies 2002

International Nuclear Information System (INIS)

Anon.

2003-01-01

The statistics presents statements of environmental taxes for the period 1970 - 2002 and statements of environmentally related subsidies for the years 1996 - 2002. Environmental taxes are a concept for pollution, energy, transportation, and resource related taxes. The State's revenue from environmental taxes have increased from 4,0 billions DKK in 1970 to 65,7 billions DKK in 2002. The environmental taxes' part of the GNP has increased from 3,2 % in 1970 to 4,8 % in 2002. The part of the environmental taxes of the total taxes and tariffs has increased from 8,2 % in 1970 to 9,8 % in 2002. >From 2001 to 2002 the environmental taxes increased with 5,6 %, primarily because the taxes in the transportation sector increased with 13,5 % due to more new cars. The pollution taxes increased with 6 % while the environmental taxes for energy increased with only 0,8 %. In 2002 the energy related taxes amounted to 54 %, the transport related taxes to 39 %, and pollution and resource related taxes amounted to 7 % of the total environmental taxes. The public environmentally related subsidies to companies and households has been on a stable level of a little more than 10 billions DKK through the latest years. The energy related subsidies have, however, been transferred to transport related subsidies, i.e. primarily subsidies to the public transport. (ln)

Metabolic syndrome-related composite factors over 5 years in the STANISLAS family study: genetic heritability and common environmental influences.

Science.gov (United States)

Herbeth, Bernard; Samara, Anastasia; Ndiaye, Coumba; Marteau, Jean-Brice; Berrahmoune, Hind; Siest, Gérard; Visvikis-Siest, Sophie

2010-06-03

We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters "risk lipids" and "protective lipids". Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: "liver enzymes", "adiposity/blood pressure" and "inflammation". Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits. Copyright 2010 Elsevier B.V. All rights reserved.

The Effects of an Environmental Studies Course on Selected Variables Related To Environmentally Responsible Behavior.

Science.gov (United States)

Smith-Sebasto, N. J.

1995-01-01

Reports that students completing an environmental studies course displayed significant gains when compared with students not completing such a course. These gains were made in acquiring a more internally-oriented locus of control of reinforcement for environmentally responsible behavior, a higher perception of their knowledge of and skill in using…

Environmental issues related to uranium mining

International Nuclear Information System (INIS)

Gorber, D.M.; Chambers, D.B.

1983-01-01

This paper introduces the environmental issues (both real and perceived) associated with uranium exploration, mining, milling, and tailings management. As well, some of the issues pertaining to the closeout of uranium tailings areas are discussed. These issues have received considerable attention in Canada in public inquiries and hearings that have been held across the country. The major conclusions of some of these hearings are also noted

Report on a fiscal 1995 basic survey of the environmental engineering. Investigational study on the systematization of the environmental business related information; 1995 nendo kankyo business no engineering ka kiso chosa hokokusho. Kankyo business kanren joho no system ka ni kansuru chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-05-01

An investigational study was conducted on directionality of arranging the environmental business related information, based on the analysis of the status of arrangement of the environmental business related information and the examination of the needs for the environmental business related information. As the directionality of arranging the environmental business related information which is most suitable for enterprises and research institutes to use, the following were considered: (1) arrangement of a system for effective use of the information owned by environmental related organs; (2) arrangement of a system for supply of the environmental business related information mainly to medium and small companies; (3) arrangement of the environmental business related information forum. In (1), it is necessary to arrange the system for the joint use of information owned by each institute. In (2), the tackling with the environmental business should be supported by arranging the system for information supply from big companies to medium and small companies. In (3), it is necessary to arrange the information forum, and it is necessary to control information thoroughly for the management for prevention of bad deeds of brokers. 7 refs., 19 figs., 21 tabs.

Environmental issues related to oil and gas access

International Nuclear Information System (INIS)

Antoniuk, T.

1998-01-01

This presentation discussed the environmental issues that petroleum companies face in northeast British Columbia. Petroleum exploration, development, production, abandonment and transportation activities in the province must follow provincial and federal regulations as well as government policies and guidelines which define environmental assessment, protection, and mitigation standards. A discussion about the regulatory framework in British Columbia can be found in the 'British Columbia Oil and Gas Handbook' which is available on the INTERNET at http://natural.gov.bc.ca/handpubs/oilgashb/bcoghb.htm. It was suggested that companies wishing to conduct drilling or exploration activities in sensitive areas should allow extra time (up to one year) to obtain approval for such activities. British Columbia's environmental setting includes five zones - the Alpine Tundra, the Spruce-Willow-Birch zone, the Engelmannn Spruce-Subalpine Fir forests, the Sub-Boreal Spruce zone, and the Boreal White and Black Spruce zone. Four discrete oil and gas guideline zones with differing standards have been developed. These are: (1) the Northern Rocky Mountains, (2) the Northeastern Slopes, (3) the Southeastern Slopes, and (4) the Northern Plains. A set of interim environmental guidelines are in effect to direct activity away from any sensitive area. Three sub-regional land use planning areas have also been established in the Prince George Forest Region which includes Dawson Creek, Fort St. John and Fort Nelson. Petroleum operators in these regions are obliged to deal with issues regarding aboriginal involvement, stream crossings, access management, and air quality. 40 refs

Assessing environmental features related to mental health: a reliability study of visual streetscape images.

Science.gov (United States)

Wu, Yu-Tzu; Nash, Paul; Barnes, Linda E; Minett, Thais; Matthews, Fiona E; Jones, Andy; Brayne, Carol

2014-10-22

An association between depressive symptoms and features of built environment has been reported in the literature. A remaining research challenge is the development of methods to efficiently capture pertinent environmental features in relevant study settings. Visual streetscape images have been used to replace traditional physical audits and directly observe the built environment of communities. The aim of this work is to examine the inter-method reliability of the two audit methods for assessing community environments with a specific focus on physical features related to mental health. Forty-eight postcodes in urban and rural areas of Cambridgeshire, England were randomly selected from an alphabetical list of streets hosted on a UK property website. The assessment was conducted in July and August 2012 by both physical and visual image audits based on the items in Residential Environment Assessment Tool (REAT), an observational instrument targeting the micro-scale environmental features related to mental health in UK postcodes. The assessor used the images of Google Street View and virtually "walked through" the streets to conduct the property and street level assessments. Gwet's AC1 coefficients and Bland-Altman plots were used to compare the concordance of two audits. The results of conducting the REAT by visual image audits generally correspond to direct observations. More variations were found in property level items regarding physical incivilities, with broad limits of agreement which importantly lead to most of the variation in the overall REAT score. Postcodes in urban areas had lower consistency between the two methods than rural areas. Google Street View has the potential to assess environmental features related to mental health with fair reliability and provide a less resource intense method of assessing community environments than physical audits.

The relation between environmental pollution and trade: a panel data analysis

Directory of Open Access Journals (Sweden)

Selahattin Bekmez

2016-06-01

Full Text Available Human and environment relations began to change with agricultural revolution at first. This change was followed by the industrial revolution. As a result of the increase in the world's population, production, trade with the industrial revolution, environment has been effected negatively by accelerating the consumption of natural resources. Some of the factors such as industrialization, rapid population growth and excessive consumption of natural resources has been caused environmental pollution. In this context, this paper explains the dilemma between environmental pollution and trade for various countries with different income levels. This study aims to analyze the relationship between environment, economic growth and Trade Openness Rate. For this reason, CO2 emissions per capita, GDP and Trade Openness Rate have been used for the period from 1960 to 2010. The data has been obtained from the World Bank and analyzed by the Panel Data Method. To conclude, Trade Openness Rate of developed countries has a negative effect on the level of CO2 emission while Trade Openness Rate of developing and less developed countries has positive effect. The results may be evidence that the Pollution Haven Hypothesis is still valid for the developing and/or less developed countries.

Environmental report 1993-94

International Nuclear Information System (INIS)

1993-01-01

This environmental report for 1993-1994, sets out Nuclear Electric plc's environmental policy relating to its nuclear-powered power stations in England and Wales, and to its various other sites. The report looks at the environmental benefits of nuclear power in a world increasingly concerned about global warming as well as addressing areas of public concern relating to radioactive waste management, reactor decommissioning and environmental contamination. Nuclear Electric claims high safety standards and a commitment to open and honest reporting of failures and successes relating to these standards. The report also documents continuing improvements to the company's environmental protection performance. (UK)

Diurnal flight behavior of Ichneumonoidea (Insecta: Hymenoptera) related to environmental factors in a tropical dry forest.

Science.gov (United States)

González-Moreno, A; Bordera, S; Leirana-Alcocer, J; Delfín-González, H

2012-06-01

The biology and behavior of insects are strongly influenced by environmental conditions such as temperature and precipitation. Because some of these factors present a within day variation, they may be causing variations on insect diurnal flight activity, but scant information exists on the issue. The aim of this work was to describe the patterns on diurnal variation of the abundance of Ichneumonoidea and their relation with relative humidity, temperature, light intensity, and wind speed. The study site was a tropical dry forest at Ría Lagartos Biosphere Reserve, Mexico; where correlations between environmental factors (relative humidity, temperature, light, and wind speed) and abundance of Ichneumonidae and Braconidae (Hymenoptera: Ichneumonoidea) were estimated. The best regression model for explaining abundance variation was selected using the second order Akaike Information Criterion. The optimum values of temperature, humidity, and light for flight activity of both families were also estimated. Ichneumonid and braconid abundances were significantly correlated to relative humidity, temperature, and light intensity; ichneumonid also showed significant correlations to wind speed. The second order Akaike Information Criterion suggests that in tropical dry conditions, relative humidity is more important that temperature for Ichneumonoidea diurnal activity. Ichneumonid wasps selected toward intermediate values of relative humidity, temperature and the lowest wind speeds; while Braconidae selected for low values of relative humidity. For light intensity, braconids presented a positive selection for moderately high values.

Quantifying The Relative Importance Of Phylogeny And Environmental Preferences As Drivers Of Gene Content In Prokaryotic Microorganisms

Directory of Open Access Journals (Sweden)

Javier eTamames

2016-03-01

Full Text Available Two complementary forces shape microbial genomes: vertical inheritance of genes by phylogenetic descent, and acquisition of new genes related to adaptation to particular habitats and lifestyles. Quantification of the relative importance of each driving force proved difficult. We determined the contribution of each factor, and identified particular genes or biochemical/cellular processes linked to environmental preferences (i.e., propensity of a taxon to live in particular habitats. Three types of data were confronted: [i] complete genomes, which provide gene content of different taxa; [ii] phylogenetic information, via alignment of 16S rRNA sequences, which allowed determination of the distance between taxa, and [iii] distribution of species in environments via 16S rRNA sampling experiments, reflecting environmental preferences of different taxa. The combination of these three datasets made it possible to describe and quantify the relationships among them. We found that, although phylogenetic descent was responsible for shaping most genomes, a discernible part of the latter was correlated to environmental adaptations. Particular families of genes were identified as environmental markers, as supported by direct studies such as metagenomic sequencing. These genes are likely important for adaptation of bacteria to particular conditions or habitats, such as carbohydrate or glycan metabolism genes being linked to host-associated environments.

Individual and Environmental determinants of Health Related Quality of Life in Iranian patients with type II diabetes

Directory of Open Access Journals (Sweden)

Maryam Hadipour

2014-01-01

Full Text Available Abstract Background: In recent two past decades prevalence of Type II diabetes has increased dramatically. Despite its financial costs, one of its consequence outcomes is decreasing quality of life of Diabetic patients. So it seems to be more useful to evaluate the influential personal and also environmental factors on patient’s quality of life. The purpose of this study was to assess effects of personal and environmental factors on Health Related Quality of Life (HRQoL of Iranian type II diabetic patients. Material and Methods: We worked on some parts of data form a national cross sectional study conducted in 2006. Sampling technique was random cluster sampling. Data collection method was face to face interview based on EQ-5D questionnaire. Interview form, also measured personal factors include: gender, age, duration of diseases from diagnosis, educational and family economic status. We collected our environmental factors such as literacy rate, urbanization rate, number of medical clinics and endocrinologists from latest national census, 1385. For data analysis we used multilevel regression analysis by Ml-win software. Results: Available data were analyses for 3472 diabetic patients. Gender, age, duration of disease, economic status and educational level in personal level and urbanization rate as an environmental factor were statistically significant factors in relation with health related quality of life. Conclusion: Based on study results, gender, and age, duration of illness, family economic and educational status of patients and the rate of urbanization affect on the HRQoL of type II diabetic patients.

Botulinum neurotoxin type A versus punctal plug insertion in the management of dry eye disease

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Amal A Bukhari

2014-01-01

Full Text Available Purpose: To compare the efficacies of punctal plug insertion and Botulinum toxin injection in dry eye disease not responding to topical medications. Materials and Methods: A non-controlled randomized clinical trial of two parallel groups of 60 dry eye patients seen in the clinic not responding to topical medications were divided into two groups. One group received punctal plugs and the other group received Botulinum toxin injections to prevent lacrimal tear drainage. Results: Of a total of 36 patients with a mean age of 44.5 years who received punctal plugs, 50% of them experienced improvements in the clinical manifestations of their disease. 12/36 (33.3% developed plug extrusion, and 6/36 (16.7% patients developed conjunctival erosions with irritation that necessitated plug removal within one week of insertion. A total of 24 patients with a mean age of 47.5 years received injections of Botulinum toxin. Of these, 83.3% had improvement in all of the clinical manifestations of dry eye. 4/24 (16.7% had no improvement in the degrees to which they experienced foreign body sensations, 33.3% reported shampoo entering the eye while showering. All of the patients who received Botulinum toxin injections were satisfied with the results of their treatment, whereas only 72.3% of the patients who received punctal plugs were satisfied with their results. Conclusion: Botulinum neurotoxin A injections can be a very good alternative to punctal plugs in improving the clinical manifestations of dry eye disease They are associated with the development of fewer and milder complications and with higher levels of patient satisfaction.

Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

Directory of Open Access Journals (Sweden)

Sharad P Adekar

2011-03-01

Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

Environmental management in public hospitals: Environmental management in Colombia

OpenAIRE

Juan Pablo Rodríguez-Miranda; César Augusto García-Ubaque; María Camila García-Vaca

2016-01-01

Introduction: Activities in hospitals have environmental impacts which may pose risks to human and environmental health if they are not managed correctly. For this reason, it is necessary to implement an environmental management plan in hospitals that not only focuses on solid waste management but includes all aspects associated with health within institutions. Objective: To review environmental management aspects related to public hospitals in order to identify environmental management a...

Heavy metals exposures among Mexican farmworkers in eastern North Carolina

International Nuclear Information System (INIS)

Quandt, Sara A.; Jones, Bradley T.; Talton, Jennifer W.; Whalley, Lara E.; Galvan, Leonardo; Vallejos, Quirina M.; Grzywacz, Joseph G.; Chen, Haiying; Pharr, Kathryn E.; Isom, Scott; Arcury, Thomas A.

2010-01-01

Background: Immigrant farmworkers are a population at risk for numerous environmental and occupational exposures. The metals arsenic, lead, mercury, and cadmium are known neurotoxins to which workers can be exposed both in the US and in their country of origin. Because farmworkers are exposed to neurotoxic pesticides, they may be at risk for adverse health effects from the combined exposure. Objectives: To examine the relationship between exposure to metals, as measured in urine, with personal and work-related characteristics of Mexican migrant and seasonal farmworkers in the US. Methods: We analyzed data on metals found in urine of 258 farmworkers recruited from 44 camps in eastern North Carolina in 2007. Geometric means and 95% confidence intervals (CI) were used to compare data with data from the National Health and Nutrition Examination Survey (NHANES). We used multivariate regression models fitted for each metal to estimate the association of creatinine-corrected urinary metals and worker characteristics related to environmental and occupational exposures. Results: Geometric mean urinary metals concentrations (μg/g creatinine) exceeded NHANES reference values for arsenic (13.23 [CI 11.11, 15.35] vs. 8.55 [CI 7.23, 9.86]) and lead (1.26 [CI 1.08, 1.43] vs. 0.63 [CI 0.60, 0.66]). Age, being from the central region of Mexico, and pack years of cigarette smoking were significant predictors of metals exposure; being a current smoker and years worked in US agriculture were not. Conclusions: This first study to examine indicators of worker body burdens of metals shows that workers have body burdens related to exposures other than work in the US. Further research should address their risk for adverse health outcomes due to combined exposures to neurotoxins in pesticides.

Heavy metals exposures among Mexican farmworkers in eastern North Carolina

Energy Technology Data Exchange (ETDEWEB)

Quandt, Sara A., E-mail: squandt@wfubmc.edu [Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157 (United States); Jones, Bradley T. [Department of Chemistry, Wake Forest University, Winston-Salem, NC (United States); Talton, Jennifer W. [Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Whalley, Lara E. [Department of Family and Community Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Galvan, Leonardo [North Carolina Farmworkers Project, Benson, NC (United States); Vallejos, Quirina M.; Grzywacz, Joseph G. [Department of Family and Community Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chen, Haiying [Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Pharr, Kathryn E. [Department of Chemistry, Wake Forest University, Winston-Salem, NC (United States); Isom, Scott [Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Arcury, Thomas A. [Department of Family and Community Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

2010-01-15

Background: Immigrant farmworkers are a population at risk for numerous environmental and occupational exposures. The metals arsenic, lead, mercury, and cadmium are known neurotoxins to which workers can be exposed both in the US and in their country of origin. Because farmworkers are exposed to neurotoxic pesticides, they may be at risk for adverse health effects from the combined exposure. Objectives: To examine the relationship between exposure to metals, as measured in urine, with personal and work-related characteristics of Mexican migrant and seasonal farmworkers in the US. Methods: We analyzed data on metals found in urine of 258 farmworkers recruited from 44 camps in eastern North Carolina in 2007. Geometric means and 95% confidence intervals (CI) were used to compare data with data from the National Health and Nutrition Examination Survey (NHANES). We used multivariate regression models fitted for each metal to estimate the association of creatinine-corrected urinary metals and worker characteristics related to environmental and occupational exposures. Results: Geometric mean urinary metals concentrations ({mu}g/g creatinine) exceeded NHANES reference values for arsenic (13.23 [CI 11.11, 15.35] vs. 8.55 [CI 7.23, 9.86]) and lead (1.26 [CI 1.08, 1.43] vs. 0.63 [CI 0.60, 0.66]). Age, being from the central region of Mexico, and pack years of cigarette smoking were significant predictors of metals exposure; being a current smoker and years worked in US agriculture were not. Conclusions: This first study to examine indicators of worker body burdens of metals shows that workers have body burdens related to exposures other than work in the US. Further research should address their risk for adverse health outcomes due to combined exposures to neurotoxins in pesticides.

Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

International Nuclear Information System (INIS)

Inui, Ken; Sagane, Yoshimasa; Miyata, Keita; Miyashita, Shin-Ichiro; Suzuki, Tomonori; Shikamori, Yasuyuki; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro

2012-01-01

Highlights: ► BoNT and NTNHA proteins share a similar protein architecture. ► NTNHA and BoNT were both identified as zinc-binding proteins. ► NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. ► Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structure classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X 35 -D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.

Concerted evolution of sea anemone neurotoxin genes is revealed through analysis of the Nematostella vectensis genome.

Science.gov (United States)

Moran, Yehu; Weinberger, Hagar; Sullivan, James C; Reitzel, Adam M; Finnerty, John R; Gurevitz, Michael

2008-04-01

Gene families, which encode toxins, are found in many poisonous animals, yet there is limited understanding of their evolution at the nucleotide level. The release of the genome draft sequence for the sea anemone Nematostella vectensis enabled a comprehensive study of a gene family whose neurotoxin products affect voltage-gated sodium channels. All gene family members are clustered in a highly repetitive approximately 30-kb genomic region and encode a single toxin, Nv1. These genes exhibit extreme conservation at the nucleotide level which cannot be explained by purifying selection. This conservation greatly differs from the toxin gene families of other animals (e.g., snakes, scorpions, and cone snails), whose evolution was driven by diversifying selection, thereby generating a high degree of genetic diversity. The low nucleotide diversity at the Nv1 genes is reminiscent of that reported for DNA encoding ribosomal RNA (rDNA) and 2 hsp70 genes from Drosophila, which have evolved via concerted evolution. This evolutionary pattern was experimentally demonstrated in yeast rDNA and was shown to involve unequal crossing-over. Through sequence analysis of toxin genes from multiple N. vectensis populations and 2 other anemone species, Anemonia viridis and Actinia equina, we observed that the toxin genes for each sea anemone species are more similar to one another than to those of other species, suggesting they evolved by manner of concerted evolution. Furthermore, in 2 of the species (A. viridis and A. equina) we found genes that evolved under diversifying selection, suggesting that concerted evolution and accelerated evolution may occur simultaneously.

Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin.

Science.gov (United States)

Ye, Yong; Li, Yue; Fang, Fei

2014-05-05

Cobra neurotoxin (NT) has central analgesic effects, but it is difficult to pass through brain blood barrier (BBB). A novel method of red light induction is designed to help NT across BBB, which is based on photosensitizer activation by red light to generate reactive oxygen species (ROS) to open BBB. The effects were evaluated on cell models and animals in vivo with illumination by semiconductor laser at 670nm on photosensitizer pheophorbide isolated from silkworm excrement. Brain microvascular endothelial cells and astrocytes were co-cultured to build up BBB cell model. The radioactivity of (125)I-NT was measured in cells and tissues for NT permeation. Three ways of cranial irradiation, nasal cavity and intravascular irradiation were tested with combined injection of (125)I-NT 20μg/kg and pheophorbide 100μg/kg to rats, and organs of rats were separated and determined the radioactivity. Paw pressure test in rats, hot plate and writhing test in mice were applied to appraise the analgesic effects. NT across BBB cell model increased with time of illumination, and reached stable level after 60min. So did ROS in cells. NT mainly distributed in liver and kidney of rats, significantly increased in brain after illumination, and improved analgesic effects. Excitation of pheophorbide at red light produces ROS to open BBB, help NT enter brain, and enhance its central action. This research provides a new method for drug across BBB to improve its central role. Copyright © 2014 Elsevier B.V. All rights reserved.

Environmental law

International Nuclear Information System (INIS)

Kloepfer, M.

1989-01-01

This comprehensive reference book on environmental law and practice also is a valuable textbook for students specializing in the field. The entire law on pollution control and environmental protection is presented in an intelligent system, covering the latest developments in the Federal and Land legislation, public environmental law, and the related provisions in the fields of civil law and criminal law. The national survey is rounded up by information concerning the international environmental law, environmental law of the European Communities, and of other foreign countries as e.g. Austria and Switzerland. The author also reviews conditions in neighbouring fields such as technology and labour law, environmental economy, environmental policy. Special attention is given to current topics, as e.g. relating to genetic engineering, disused landfills or industrial sites, soil protection, transport of hazardous goods, liability for damage to forests, atomic energy law, and radiation protection law. The latest publishing dates of literature and court decisions considered in the book are in the first months of 1989. (RST) [de

Consumers' environmental and ethical consciousness and the use of the related food products information: The role of perceived consumer effectiveness.

Science.gov (United States)

Ghvanidze, Sophie; Velikova, Natalia; Dodd, Tim H; Oldewage-Theron, Wilna

2016-12-01

Consumers can be important active contributors to a sustainable society by selecting food choices that are both healthy and produced respecting environmental and socially ethical standards. The current study investigates five consumer behavioural factors - namely, perceived consumer effectiveness (PCE); environmental conscious behaviour; concerns for ethical food production; health conscious lifestyle; and healthy dietary patterns. The key interest of the study lies in exploring the moderating role of PCE - the extent to which the consumer believes that his/her own efforts can make a difference - in these interrelationships. The empirical analysis was conducted through an online survey of food consumers implemented in three markets - the US, the UK and Germany. Findings indicate that for individuals with higher levels of PCE, who are environmental conscious and ethically concerned, information on food labels relating to environmental and social issues represents value by itself. Interestingly, health and nutrition information on food labels was not perceived valuable by consumers with high PCE. The predictive effects of various socio-demographic variables on PCE, consumer environmental and health consciousness are discussed. Cross-cultural differences are also outlined. The results of this research may contribute to the development of environmental policies and communication strategies of the food industry to enhance perceived consumer effectiveness among consumers. Improved PCE, in turn, may catalyze consumers' environmental behaviour and ethical concerns in relation to consumption of food products with environmental and social information. Copyright © 2016 Elsevier Ltd. All rights reserved.

Status of health and environmental research relative to direct coal liquefaction: 1976 to the present

Energy Technology Data Exchange (ETDEWEB)

Gray, R.H.; Cowser, K.E. (eds.)

1982-06-01

This document describes the status of health and environmental research efforts, supported by the US Department of Energy (DOE), to assist in the development of environmentally acceptable coal liquefaction processes. Four major direct coal liquefaction processes are currently in (or have been investigated at) the pilot plant stage of development. Two solvent refined coal processes (SRC-I and -II), H-coal (a catalytic liquefaction process) and Exxon donor solvent (EDS). The Pacific Northwest Laboratory was assigned responsibility for evaluating SRC process materials and prepared comprehensive health and environmental effects research program plans for SRC-I and -II. A similar program plan was prepared for H-coal process materials by the Oak Ridge National Laboratory. A program has been developed for EDS process materials by Exxon Research and Engineering Co. The program includes short-term screening of coal-derived materials for potential health and ecological effects. Longer-term assays are used to evaluate materials considered most representative of potential commercial practice and with greatest potential for human exposure or release to the environment. Effects of process modification, control technologies and changing operational conditions on potential health and ecological effects are also being evaluated. These assessments are being conducted to assist in formulating cost-effective environmental research programs and to estimate health and environmental risks associated with a large-scale coal liquefaction industry. Significant results of DOE's health and environmental research efforts relative to coal liquefaction include the following: chemical characterization, health effects, ecological fate and effects, amelioration and risk assessment.

Incorporating environmental justice into environmental decision making

Energy Technology Data Exchange (ETDEWEB)

Wolfe, A.K.; Vogt, D.P.; Hwang, Ho-Ling [Oak Ridge National Lab., TN (United States)] [and others

1995-07-01

Executive Order 12898, signed on February 11, 1994, broadly states that federal activities, programs, and policies should not produce disproportionately high and adverse impacts on minority and low-income populations. Moreover, the Order indicates that these populations should not be denied the benefits of, or excluded from participation in, these activities, programs, and policies. Because a presidential memorandum accompanying the order said that National Environmental Policy Act (NEPA) documents should begin to address environmental justice immediately, much attention has been paid to assessment-related issues. Also important, a topic that appears to have received relatively little attention, is how decision makers should be expected to use information about environmental justice in their decision making. This paper discusses issues surrounding the use of environmental justice information in the decision-making process by focusing on the following five main topics: (1) the importance, or weight, attached to environmental justice within larger decision-making contexts; (2) the potential tension between localized environmental justice issues and regional or national issues and needs; (3) the use of environmental justice information to develop (perhaps in concert with affected minority and low-income communities) appropriate mitigation strategies, or to establish conditions under which activities, programs, and policies may be accepted locally; (4) the general implications of shifting the distribution of broadly defined risks, costs, and benefits among different population groups; and (5) the implications of implementing environmental justice on an individual, ad hoc basis rather than within a larger environmental justice framework. This paper raises the issues and discusses the implications of alternative approaches to them.

A Nationwide View of Undergraduates' Interest in Earth-related Careers and Motivation to Tackle Environmental Challenges

Science.gov (United States)

Kastens, K. A.; Mara, V.; Turrin, M.

2016-12-01

The InTeGrate Attitudinal Instrument (IAI) is an on-line survey that probes students' interest in Earth-related careers, their concern about environmental issues, and their motivation to tackle grand challenges of environmental sustainability and resource limitations. The survey has been taken by several thousand students, at the beginning and end of more than a hundred different undergraduate courses throughout the United States. All courses include some Earth/environmental content, but not all in are geoscience departments. Although results vary somewhat between subpopulations, taken in the aggregate the data paint a nation-wide picture of the state of undergraduates' environmental interests and concerns. Regardless of intended career path, respondents place a high value on working for an organization that is committed to environmentally sustainable practices. Respondents consistently indicate that developments such as global climate change, loss of biodiversity, and water resource limitations are a problem; however, these same students are much less consistent when it comes to engaging in personal behaviors that would help mitigate environmental problems, such as washing clothes in cold water or using recyclable bags when shopping. When asked what factors or sources of information influence their decisions to engage in the specified environmentally sustainable behaviors, the factor most often cited, by a wide margin, is "desire to save money," followed by "concern about pollution." A final open-ended question asked students if they can envision using what they have learned in this course to help society overcome problems of environmental degradation, natural resources limitations, or other environmental issues; if yes, how, and if no, why not. Strong majorities said yes. Among the minority who said no, commonly cited reasons include lack of empowerment (I'm only one person, the problems are too big); course was too general and didn't address solutions; and

Environmental reporting as a strategic issue

DEFF Research Database (Denmark)

Larsen, Lars Bjørn

1997-01-01

Organisations are facing ever increasing demands or pressures from various stakeholder to raise their environmental standards. Raising the environmental standards includes improving and documenting the environmental performance in relation to production processes, products and logistics.This pape...... adresses environmental reporting as an important issue in strategic management, since many of environmental management are related to the availability of environmental information both inside and outside the company.......Organisations are facing ever increasing demands or pressures from various stakeholder to raise their environmental standards. Raising the environmental standards includes improving and documenting the environmental performance in relation to production processes, products and logistics.This paper...

The Prototype Plume Busters Software: A New Tool for Exploring Issues Related to Environmental Policy in Undergraduate-level Earth and Environmental Science Courses

Science.gov (United States)

Macfarlane, P. A.

2006-12-01

Students seldom have an opportunity to explore the issues related to the environmental impact of contamination on water resources. With NSF support we have developed the prototype Plume Busters, in which students take on the role of an environmental consultant. The software consists of an interactive, Java application and accompanying HTML linked pages. Following a pipeline spill, the environmental consultant is hired by the pipeline owner to locate the resulting plume created by the spill and remediate the contaminated aquifer at minimum monetary and time cost. The contamination must be removed from the aquifer before it reaches the river and eventually a downstream public water supply. The application simulates movement of a plume from a pipeline break through a shallow alluvial aquifer towards the river upstream from a municipal water supply intake. To locate the plume, the student places observation wells on a gridded map of the study area and the simulation returns the contaminant concentrations at those locations on the appropriate sample dates. Once the plume is located, the student is able to site pumping and injection wells on the map for aquifer remediation using a simple pump-and-treat technique. The simulation then computes the movement of particles to the pumping wells and returns the cumulative mass removed by the production remediation well. Plume Busters also provides teachers with a means to initiate student exploration of a wide range of environmental issues, including (1) source-water assessment and ground-water and wellhead protection zones, (2) the impact of human activities and technology on the hydrosphere and the biosphere, (3) the role of technology in the resolution of environmental issues (4) legal, social, political, and economic implications of environmental issues, and (5) risk assessment resulting from human activities.

Multinationals and international environmental policy

International Nuclear Information System (INIS)

Dam, L.; Scholtens, B.

2009-01-01

Multinationals with relatively poor environmental policy establish themselves in countries with weak environmental regulation. These activities are not undertaken in the poorest or most corrupt countries though. The question arises if multinationals with relatively developed environmental behavior settle less or more often in countries with environmental legislation. [mk] [nl

Familial aggregation of gout and relative genetic and environmental contributions: a nationwide population study in Taiwan.

Science.gov (United States)

Kuo, Chang-Fu; Grainge, Matthew J; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Valdes, Ana M; Zhang, Weiya; Doherty, Michael

2015-02-01

To examine familial aggregation of gout and to estimate the heritability and environmental contributions to gout susceptibility in the general population. Using data from the National Health Insurance (NHI) Research Database in Taiwan, we conducted a nationwide cross-sectional study of data collected from 22 643 748 beneficiaries of the NHI in 2004; among them 1 045 059 individuals had physician-diagnosed gout. We estimated relative risks (RR) of gout in individuals with affected first-degree and second-degree relatives and relative contributions of genes (heritability), common environment shared by family members and non-shared environment to gout susceptibility. RRs for gout were significantly higher in individuals with affected first-degree relatives (men, 1.91 (95% CI 1.90 to 1.93); women, 1.97 (95% CI 1.94 to 1.99)) and also in those with affected second-degree relatives (men, 1.27 (95% CI 1.23 to 1.31); women, 1.40 (95% CI 1.35 to 1.46)). RRs (95% CIs) for individuals with an affected twin, sibling, offspring, parent, grandchild, nephew/niece, uncle/aunt and grandparent were 8.02 (6.95 to 9.26), 2.59 (2.54 to 2.63), 1.96 (1.95 to 1.97), 1.93 (1.91 to 1.94), 1.48 (1.43 to 1.53), 1.40 (1.32 to 1.47), 1.31 (1.24 to 1.39), and 1.26 (1.21 to 1.30), respectively. The relative contributions of heritability, common and non-shared environmental factors to phenotypic variance of gout were 35.1, 28.1 and 36.8% in men and 17.0, 18.5 and 64.5% in women, respectively. This population-based study confirms that gout aggregates within families. The risk of gout is higher in people with a family history. Genetic and environmental factors contribute to gout aetiology, and the relative contributions are sexually dimorphic. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Determinants of palm species distributions across Africa: the relative roles of climate, non-climatic environmental factors, and spatial constraints

DEFF Research Database (Denmark)

Overgaard, Anne Blach; Svenning, J.-C.; Dransfield, John

2010-01-01

-climatic environmental predictors, the latter having no discernible effect beyond the climatic control. Hence, at the continental scale, climate constitutes the only strong environmental control of palm species distributions in Africa. With regard to the most important climatic predictors of African palm distributions......, water-related factors were most important for 25 of the 29 species analysed. The strong response of palm distributions to climate in combination with the importance of non-environmental spatial constraints suggests that African palms will be sensitive to future climate changes, but that their ability...

Relating Magnetic Parameters to Heavy Metal Concentrations and Environmental Factors at Formosa Mine Superfund Site, Douglas County, OR

Science.gov (United States)

Upton, T. L.

2016-12-01

Advances in the field of environmental magnetism have led to exciting new applications for this field. Magnetic minerals are ubiquitous in the environment and tend to have an affinity for heavy metals. Hence, it has been demonstrated that magnetic properties are often significantly related to concentrations of heavy metals and other pollutants. As a result, magnetic techniques have been used as proxy for determining hot spots of several types of pollution produced from a diversity of anthropogenic sources. Magnetic measurements are non-destructive and relatively inexpensive compared to geochemical analyses. The utility of environmental magnetic methods varies widely depending on biological, chemical and physical processes that create and transform soils and sediments. Applications in the direction of mapping heavy metals have been studied and shown to be quite useful in countries such as China and India but to date, little research has been done in the US. As such, there is need to expand the scope of research to a wider range of soil types and land uses, especially within the US. This study investigates the application of environmental magnetic techniques to mapping of heavy metal concentrations at the Formosa Mine Superfund Site, an abandoned mine about 25 miles southwest of Roseburg, OR. The soils and sediment at this site are derived from pyrite-rich bedrock which is weak in terms of magnetic susceptibility. Using hotspot analysis, correlation and cluster analyses, interactions between metals and magnetic parameters are investigated in relation to environmental factors such as proximity to seeps and adits. Preliminary results suggest significant correlation of magnetic susceptibility with certain heavy metals, signifying that magnetic methods may be useful in mapping heavy metal hotspots at this site. Further analysis examines the relation of various land use differences in magnetic signatures obtained throughout the Cow Creek watershed.

76 FR 80409 - Draft Supplement 2 to Final Environmental Statement Related to the Operation of Watts Bar Nuclear...

Science.gov (United States)

2011-12-23

... Environmental Statement Related to the Operation of Watts Bar Nuclear Plant, Unit 2; Tennessee Valley Authority..., Related to the Operation of Watts Bar Nuclear Plant [WBN], Unit 2--Draft Report for Comment'' (draft SFES.... Stephen J. Campbell, Chief, Watts Bar Special Projects Branch, Division of Operating Reactor Licensing...

The regulatory instruments for the correction of energy-related environmental externalities

International Nuclear Information System (INIS)

Labanderia Villot, X.; Lopez Otero, X.; Rodriguez Mendez, M.

2007-01-01

In this paper we deal with the different regulatory instruments for the correction of energy-related environmental externalities. This objective is justified by the size and general occurrence of this type of externalities in contemporary societies. In this sense, we distinguish between three main generations of instruments: conventional regulations, market mechanisms and voluntary approaches. In all cases, some practical examples of their application are presented, albeit emphasizing the experience with the so-called market instruments and the results of hypothetical simulations for the Spanish case. As a general conclusion we underline the role of economic analysis in the design, choice and evaluation of those mechanisms, which also explains the structure and contents of the article. (Author)

The relation between product innovation and strategic environmental goals

DEFF Research Database (Denmark)

Gerstlberger, Wolfgang; Pedrosa, Alex; Atlason, Reynir Smari

2017-01-01

Innovation management in manufacturing firms including its environmental dimension is currently on top of the political agenda of the European Union. Existing studies only provide limited findings in this research field. By using cross-sectional data, this study investigates firms’ internal capab...... Policies (IPPs). IPPs combine the support of product innovations in general and environmental innovations in particular. Future research could apply mixed-method studies in single or multiple countries which combine different types of data....

Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

Energy Technology Data Exchange (ETDEWEB)

Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

2008-02-10

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences.

Science.gov (United States)

Fujimi, T J; Nakajyo, T; Nishimura, E; Ogura, E; Tsuchiya, T; Tamiya, T

2003-08-14

The genes encoding erabutoxin (short chain neurotoxin) isoforms (Ea, Eb, and Ec), LsIII (long chain neurotoxin) and a novel long chain neurotoxin pseudogene were cloned from a Laticauda semifasciata genomic library. Short and long chain neurotoxin genes were also cloned from the genome of Laticauda laticaudata, a closely related species of L. semifasciata, by PCR. A putative matrix attached region (MAR) sequence was found in the intron I of the LsIII gene. Comparative analysis of 11 structurally relevant snake toxin genes (three-finger-structure toxins) revealed the molecular evolution of these toxins. Three-finger-structure toxin genes diverged from a common ancestor through two types of evolutionary pathways (long and short types), early in the course of evolution. At a later stage of evolution in each gene, the accumulation of mutations in the exons, especially exon II, by accelerated evolution may have caused the increased diversification in their functions. It was also revealed that the putative MAR sequence found in the LsIII gene was integrated into the gene after the species-level divergence.

Environmental law

International Nuclear Information System (INIS)

Ketteler, G.; Kippels, K.

1988-01-01

In section I 'Basic principles' the following topics are considered: Constitutional-legal aspects of environmental protection, e.g. nuclear hazards and the remaining risk; European environmental law; international environmental law; administrative law, private law and criminal law relating to the environment; basic principles of environmental law, the instruments of public environmental law. Section II 'Special areas of law' is concerned with the law on water and waste, prevention of air pollution, nature conservation and care of the countryside. Legal decisions and literature up to June 1988 have been taken into consideration. (orig./RST) [de

The economic, energy, and environmental impacts of the Energy-Related Inventions Program

International Nuclear Information System (INIS)

Brown, M.A.; Wilson, C.R.; Franchuk, C.A.; Cohn, S.M.; Jones, D.

1994-07-01

This report provides information on the economic, energy, and environmental impacts of inventions supported by the Energy-Related Inventions Program (ERIP) -- a program jointly operated by the US Department of Energy and the National Institute of Standards and Technology (NIST). It describes the results of the latest in a series of ERIP evaluation projects that have been completed since 1980. The period of interest is 1980 through 1992. The evaluation is based on data collected in 1993 through mail and telephone surveys of 253 program participants, and historical data collected during previous evaluations for an additional 189 participants

The economic, energy, and environmental impacts of the Energy-Related Inventions Program

Energy Technology Data Exchange (ETDEWEB)

Brown, M.A.; Wilson, C.R.; Franchuk, C.A.; Cohn, S.M.; Jones, D.

1994-07-01

This report provides information on the economic, energy, and environmental impacts of inventions supported by the Energy-Related Inventions Program (ERIP) -- a program jointly operated by the US Department of Energy and the National Institute of Standards and Technology (NIST). It describes the results of the latest in a series of ERIP evaluation projects that have been completed since 1980. The period of interest is 1980 through 1992. The evaluation is based on data collected in 1993 through mail and telephone surveys of 253 program participants, and historical data collected during previous evaluations for an additional 189 participants.

Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

Energy Technology Data Exchange (ETDEWEB)

Inui, Ken [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Sagane, Yoshimasa [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Miyata, Keita [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Miyashita, Shin-Ichiro [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Suzuki, Tomonori [Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikamori, Yasuyuki [Agilent Technologies International Japan, Ltd. Takaura-cho 9-1, Hachioji-shi, Tokyo 192-0033 (Japan); Ohyama, Tohru; Niwa, Koichi [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Watanabe, Toshihiro, E-mail: t-watana@bioindustry.nodai.ac.jp [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan)

2012-03-16

Highlights: Black-Right-Pointing-Pointer BoNT and NTNHA proteins share a similar protein architecture. Black-Right-Pointing-Pointer NTNHA and BoNT were both identified as zinc-binding proteins. Black-Right-Pointing-Pointer NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. Black-Right-Pointing-Pointer Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structure classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X{sub 35}-D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.

Beyond Precipitation: Physiographic Gradients Dictate the Relative Importance of Environmental Drivers on Savanna Vegetation

Science.gov (United States)

Campo-Bescós, Miguel A.; Muñoz-Carpena, Rafael; Kaplan, David A.; Southworth, Jane; Zhu, Likai; Waylen, Peter R.

2013-01-01

Background Understanding the drivers of large-scale vegetation change is critical to managing landscapes and key to predicting how projected climate and land use changes will affect regional vegetation patterns. This study aimed to improve our understanding of the role, magnitude and spatial distribution of the key environmental factors driving vegetation change in southern African savanna, and how they vary across physiographic gradients. Methodology/Principal Findings We applied Dynamic Factor Analysis (DFA), a multivariate times series dimension reduction technique to ten years of monthly remote sensing data (MODIS-derived normalized difference vegetation index, NDVI) and a suite of environmental covariates: precipitation, mean and maximum temperature, soil moisture, relative humidity, fire and potential evapotranspiration. Monthly NDVI was described by cyclic seasonal variation with distinct spatiotemporal patterns in different physiographic regions. Results support existing work emphasizing the importance of precipitation, soil moisture and fire on NDVI, but also reveal overlooked effects of temperature and evapotranspiration, particularly in regions with higher mean annual precipitation. Critically, spatial distributions of the weights of environmental covariates point to a transition in the importance of precipitation and soil moisture (strongest in grass-dominated regions with precipitation950 mm). Conclusions/Significance We quantified the combined spatiotemporal effects of an available suite of environmental drivers on NDVI across a large and diverse savanna region. The analysis supports known drivers of savanna vegetation but also uncovers important roles of temperature and evapotranspiration. Results highlight the utility of applying the DFA approach to remote sensing products for regional analyses of landscape change in the context of global environmental change. With the dramatic increase in global change research, this methodology augurs well for

Photoperiodism and circadian rhythms in relation to the hazards of environmental pollutants

International Nuclear Information System (INIS)

Attia, A.M.; Ali, M.M.; Abdou, M.M.

1999-01-01

The duration, intensity and wavelengths of light to which vertebrates and invertebrates are exposed vary widely over a 24-hour period as well as throughout the year. Species, by means of their behavioral patterns, differentially control in part the photoperiodic environment to which they are exposed. It is essential that mammals, probably including humans, adjust their physiology with changes in the makeup of the photoperiod. Numerous body functions undergo variations recurring at about 24-hour intervals in the presence or absence of known environmental changes with similar periods. This applies to continuos but rhythmic phenomena, with a peak and trough repeating itself every 24-hours, as well as to discrete events occurring about once a day. The time intervals separating these consecutive periodic events are similar but often not identical. Such periods are called circadian. Rhythms have been reported in cell growth, hormonal levels, and so on. Rhythms are generally resistant to a variety of chemical substances including stimulants and depressants. photoperiodism and circadian rhythms, in relation to the hazardous effects of environmental pollutants, as pesticides; which may directly or indirectly affect or alter physiologocal processes in living things, are summarized

Environmental pediatrics: an emerging issue.

Science.gov (United States)

Valenzuela, Patricia M; Matus, M Soledad; Araya, Gabriela I; Paris, Enrique

2011-01-01

To review the most relevant articles regarding environmental pediatrics, its potential effects on health, and especially its advances in prevention. A literature search was conducted using MEDLINE/PubMed and SciELO databases. Articles from 1990 to 2010 were reviewed, in addition to book chapters related to environmental pediatrics. There is a significant variety of factors that make children highly vulnerable to environmental hazard exposure, which are mainly associated with children's comparatively greater consumption of water, food, and air in relation to body weight. According to the World Health Organization, every year more than 3 million children under the age of 5 die because of environment-related conditions. Approximately 30 to 40% of pediatric diseases are related to environmental factors. Children are constantly exposed to various environmental health hazards, among which the following stand out: contaminated water, lack of adequate sanitation facilities, air pollution, disease vectors, chemical hazards, injuries, and accidents. Nowadays, pediatricians are challenged to address environmental pediatrics health care needs. The pediatric health history needs to be more comprehensive by adding pointed questions to help identify potential environmental risks. Awareness and understanding of the noxious effects of various environmental conditions and knowledge of the related prevention measures will result in timely and adequate interventions that will improve our children's health and development.

Environmental, health and safety issues related to commercializing CuInSe{sub 2}-based photovoltaics

Energy Technology Data Exchange (ETDEWEB)

Eberspacher, C. [UNISUN, Newbury Park, CA (United States); Fthenakis, V.M.; Moskowtiz, P.D. [Brookhaven National Lab., Upton, NY (United States)

1996-07-01

Photovoltaics technology is rapidly evolving towards a new generation of low-cost thin film technologies. One of the most promising materials in this new generation is copper indium selenide (CuInSe{sub 2} or CIS). As with any new material, successful commercialization of CIS photovoltaic (PV) technology will require attention to environmental, health and safety issues, including consideration of the sources, usage, and end-of-product-life disposal and/or recycling of the constituent materials. This work focuses on three specific environmental, health and safety (EH and S) issues related to CIS PV: (1) economics are analyzed to determine their impact on materials use and re-use; (2) Federal and California State environmental disposal and waste handling regulations are analyzed to evaluate their impact on PV module manufacturing and end-of-life module handling; and (3) the logistics and economics of product recycling and waste disposal by industries with comparable EH and S issues are examined to quantify the corresponding options available for handling, disposing of and/or recycling manufacturing by-products and end-of-life modules.

Human comfort and self-estimated performance in relation to indoor environmental parameters and building features

DEFF Research Database (Denmark)

Frontczak, Monika Joanna

The main objective of the Ph.D. study was to examine occupants’ perception of comfort and self-estimated job performance in non-industrial buildings (homes and offices), in particular how building occupants understand comfort and which parameters, not necessarily related to indoor environments...... and storage, noise level and visual privacy. However, if job performance is considered, then satisfaction with the main indoor environmental parameters should be addressed first as they affected self-estimated job performance to the highest extent. The present study showed that overall satisfaction...... with personal workspace affected significantly the self-estimated job performance. Increasing overall satisfaction with the personal workspace by about 15% would correspond to an increase of self-estimated job performance by 3.7%. Among indoor environmental parameters and building features, satisfaction...

The relative contributions of climatic elements and environmental ...

African Journals Online (AJOL)

SEJUP

2013-08-01

Aug 1, 2013 ... environmental factors to urban flooding in Awka urban area of Anambra State. Towards ... city, while Geoffrey (2001) employed time series analysis ..... Street Flooding in Calabar Municipality, Cross River State in Bisong.

Meeting United States re-licensing requirements related to environmental protection using innovative technologies

International Nuclear Information System (INIS)

Taft, E.P.; Winchell, F.C.; Cook, T.C.

1998-01-01

Procedure for meeting re-licensing requirements related to environmental protection and an overview of several new and emerging technologies regarding the development of ways to prevent fish passage through hydraulic turbines at hydroelectric power dams is described. Fish mortality and injury has long been a concern in the hydroelectric industry and research and development efforts have been ongoing since the 1970s to prevent fish passage through turbines. Several new and emerging technologies are examined that have the potential for wide-spread cost-effective applications

Llama Single Domain Antibodies Specific for the 7 Botulinum Neurotoxin Serotypes as Heptaplex Immunoreagents

Science.gov (United States)

Collazo, M. Thelma; Garza, John A.; Hayhurst, Andrew

2010-01-01

Background There are currently 7 known serotypes of botulinum neurotoxin (BoNT) classified upon non-cross reactivity of neutralizing immunoglobulins. Non-neutralizing immunoglobulins, however, can exhibit cross-reactivities between 2 or more serotypes, particularly mosaic forms, which can hamper the development of highly specific immunoassays, especially if based on polyclonal antisera. Here we employ facile recombinant antibody technology to subtractively select ligands to each of the 7 BoNT serotypes, resulting in populations with very high specificity for their intended serotype. Methods and Findings A single llama was immunized with a cocktail of 7 BoNT toxoids to generate a phage display library of single domain antibodies (sdAb, VHH or nanobodies) which were selected on live toxins. Resulting sdAb were capable of detecting both toxin and toxin complex with the best combinations able to detect 100s-10s of pg per 50 µL sample in a liquid bead array. The most sensitive sdAb were combined in a heptaplex assay to identify each of the BoNT serotypes in buffer and milk and to a lesser extent in carrot juice, orange juice and cola. Several anti-A(1) sdAb recognized A2 complex, showing that subtype cross-reactivity within a serotype was evident. Many of our sdAb could act as both captor and tracer for several toxin and toxin complexes suggesting sdAb can be used as architectural probes to indicate BoNT oligomerisation. Six of 14 anti-A clones exhibited inhibition of SNAP-25 cleavage in the neuro-2A assay indicating some sdAb had toxin neutralizing capabilities. Many sdAb were also shown to be refoldable after exposure to high temperatures in contrast to polyclonal antisera, as monitored by circular dichroism. Conclusions Our panel of molecularly flexible antibodies should not only serve as a good starting point for ruggedizing assays and inhibitors, but enable the intricate architectures of BoNT toxins and complexes to be probed more extensively. PMID:20098614

Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A

Science.gov (United States)

Benoit, Roger M.; Frey, Daniel; Hilbert, Manuel; Kevenaar, Josta T.; Wieser, Mara M.; Stirnimann, Christian U.; McMillan, David; Ceska, Tom; Lebon, Florence; Jaussi, Rolf; Steinmetz, Michel O.; Schertler, Gebhard F. X.; Hoogenraad, Casper C.; Capitani, Guido; Kammerer, Richard A.

2014-01-01

Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons. Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders. BoNT/A is probably best known for its use as an antiwrinkle agent in cosmetic applications (including Botox and Dysport). BoNT/A application causes long-lasting flaccid paralysis of muscles through inhibiting the release of the neurotransmitter acetylcholine by cleaving synaptosomal-associated protein 25 (SNAP-25) within presynaptic nerve terminals. Two types of BoNT/A receptor have been identified, both of which are required for BoNT/A toxicity and are therefore likely to cooperate with each other: gangliosides and members of the synaptic vesicle glycoprotein 2 (SV2) family, which are putative transporter proteins that are predicted to have 12 transmembrane domains, associate with the receptor-binding domain of the toxin. Recently, fibroblast growth factor receptor 3 (FGFR3) has also been reported to be a potential BoNT/A receptor. In SV2 proteins, the BoNT/A-binding site has been mapped to the luminal domain, but the molecular details of the interaction between BoNT/A and SV2 are unknown. Here we determined the high-resolution crystal structure of the BoNT/A receptor-binding domain (BoNT/A-RBD) in complex with the SV2C luminal domain (SV2C-LD). SV2C-LD consists of a right-handed, quadrilateral β-helix that associates with BoNT/A-RBD mainly through backbone-to-backbone interactions at open β-strand edges, in a manner that resembles the inter-strand interactions in amyloid structures. Competition experiments identified a peptide that inhibits the formation of the complex. Our findings provide a strong platform for the development of novel antitoxin agents and for the rational design of BoNT/A variants with improved therapeutic properties.

Utilizing Ayurvedic literature for the identification of novel phytochemical inhibitors of botulinum neurotoxin A.

Science.gov (United States)

Yalamanchili, Chinni; Manda, Vamshi K; Chittiboyina, Amar G; Guernieri, Rebecca L; Harrell, William A; Webb, Robert P; Smith, Leonard A; Khan, Ikhlas A

2017-02-02

Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to identify novel phytochemicals for the inhibition of bacterial exotoxin, botulinum neurotoxin A (BoNT/A) based on Ayurvedic literature. BoNT/A is released by Clostridium species, which when ingested, inhibits the release of acetylcholine by concentrating at the neuromuscular junction and causes flaccid paralysis, resulting in a condition termed as botulism, and may also lead to death due to respiratory arrest. Fifteen plants were selected from the book 'Diagnosis and treatment of diseases in Ayurveda' by Vaidya Bhagwan Dash and Lalitesh Kashyap, based on their frequency of use in the formulations used for the treatment of six diseases with neuromuscular symptoms similar to botulism. Phytochemicals from these plants were screened using in silico, and in vitro methods. Structures of 570 reported phytochemicals from 14 plants were docked inside six reported BoNT/A light chain crystal structures using ensemble docking module in Maestro (Schrödinger, LLE). From the docking scores and structural diversity, nine compounds including acoric acid 1, three flavonoids, three coumarins derivatives, one kava lactone were selected and screened using an in vitro HPLC-based protease assay. The bioassay results showed that several compounds possess BoNT/A LC inhibition of 50-60% when compared to positive controls NSC 84094 and CB7967495 (80-95%). Further testing of the active compounds identified from Ayurvedic literature and structure-activity studies of acoric acid 1 using more sensitive bioassays is under way. The identification of acoric acid 1, a novel scaffold against BoNT/A, exemplifies the utility of Ayurvedic literature for the discovery of novel drug leads. Copyright © 2016 Elsevier Ireland Ltd. All rights

Detection, concentrations and distribution of paxilline, an animal neurotoxin, in mouse brain: an application of ultra-high sensitivity detection of 14C by accelerator mass spectrometry

International Nuclear Information System (INIS)

Roberts, P.B.; Kim, K.

1999-01-01

Full text: Paxilline is an intermediate in the biosynthesis of lolitrem neurotoxins that cause the disorder rye grass staggers in livestock grazing on pastures infected with certain fungi. Paxilline itself produces similar symptoms and the 14 C-labelled compound has been produced bio-synthetically at low specific activity. Using conventional liquid scintillation counting it was not possible to detect the labelled compound in the brain of mice sacrificed at the time they displayed physiological symptoms. Accelerator mass spectrometry (AMS) counts 14 C atoms, not decays, and provides sensitivity 10,000-100,000 times greater than conventional scintillation counting of radioactive decays. Measurements are easily obtained at the level of the natural abundance of 14 C in living tissue of 6fCi or 10 -16 moles 14 C per mg total carbon. Extraction of the labelled compound from the tissue is unnecessary and sample size can be 0.01-10mg. Paxilline (8mg/kg ip) was given to 25g mice. The total activity injected was 11,000 dpm though the results showed that 1,000dpm would have been sufficient. The concentration of paxilline in homogenised whole brain was determined to be 985 pg or 0.0075 dpm mg dry tissue. The concentration in the major brain segments ranged from 893-1137 pgmg dry tissue. The spinal cord contained 719 pg/mg dry tissue. Our results suggest that toxicologists and pharmacologists should consider what new information may be obtained by combining tracer studies with the power of AMS detection. The AMS method makes possible great reductions in the amount of label and sample sizes, plus wider ranges in concentration/time course studies. In particular, it opens up new possibilities such as: studies at true dietary or environmental levels; tracer studies in large animal or plant systems; field trials; human studies where radiation dose must be considered; and studies with compounds that can only be synthesised with low specific activity. Copyright (1999) Australasian

Corporate environmental responsibility. Conference papers

International Nuclear Information System (INIS)

1992-01-01

The European and U.S. industrial participants presented their environmental policies and programs. There is a difference of opinion between the European and U.S. industry representatives with regard to disclosure of environmental data. The coalition for Environmentally Responsible Economies (CERES) had played a role in the recent evolution of industry environmental programs, especially as they relate to environmental performance measurement, communication of environmental issues and concerns with shareholders and the public, and issues related to public accountability and disclosure. An overview of accomplishments is given and a common agenda is offered. (DG)

The environmental science and law II. The short development of the environmental science and environmental law

International Nuclear Information System (INIS)

Klinda, J.

1998-01-01

This book contains the basic documents about environmental laws and related documents approved in the world and in the Slovak Republic. The system of the environmental laws and organizations in the world and in the Slovak Republic are reviewed. A review of a selected environmental laws of the Slovak Republic are included. The significant world acts (declarations, charters and other documents) are reviewed

Supplement to Final Environmental Statement related to construction and operation of Clinch River Breeder Reactor Plant, Docket No. 50-537

International Nuclear Information System (INIS)

1982-10-01

In February 1977, the Office of Nuclear Reactor Regulation issued a Final Environmental Statement (FES) (NUREG-0139) related to the construction and operation of the proposed Clinch River Breeder Reactor Plant (CRBRP). Since the FES was issued, additional data relative to the site and its environs have been collected, several modifications have been made to the CRBRP design, and its fuel cycle, and the timing of the plant construction and operation has been affected in accordance with deferments under the DOE Liquid Metal Fast Breeder Reactor (LMFBR) program. These changes are summarized and their environmental significance is assessed in this document. The reader should note that this document generally does not repeat the substantial amount of information in the FES which is still current; hence, the FES should be consulted for a comprehensive understanding of the staff's environmental review of the CRBRP project

A thesis investigating the impact of energy related environmental factors on domestic window design

Science.gov (United States)

McEvoy, Michael Edward

In recent years the extent of glazing in houses has been tightly controlled by the Building Regulations in order to save energy. In addition guidelines derived from passive solar principles prescribe the distribution of domestic windows between elevations according to their orientation. This thesis studies the impact of these energy-related environmental factors on domestic window design. The first of these investigations determined the degree to which limitations on the area and arrangement of windows are significant in terms of daylighting. The experiments measured the effect that passive solar requirements and detailed aspects of window design have on the quality of daylighting in houses. The volume of background ventilation required for domestic accommodation has recently been increased. As a result, in a well-sealed construction, heat loss due to background ventilation becomes a larger part of the total heat loss and larger air movements become a potential cause of draughts. The ventilation experiment sought to establish the impact of these more onerous requirements on comfort within rooms. The third experiment combines these factors and asks the question: Could windows be actively involved in overcoming some of these difficulties by being used to preheat ventilation air in order to diminish the extent of heat loss and to alleviate the problem of cold draughts? Also by designing the window to reclaim heat from the room might it be possible to offset the window's thermal inadequacy? Through analysis of responses to a questionnaire and the use of optimisation techniques, scenarios were suggested for the future modification of windows in relation to energy and health expectations. The conclusions form a commentary on recent and future revisions to the Building Regulations and determine whether or not the Regulations facilitate the environmental engineering of windows as an active component of a building's whole environmental system.

Smoking-related knowledge, attitude, social pressure, and environmental constraints among new undergraduates in Chongqing, China.

Science.gov (United States)

Xu, Xianglong; Leung, Doris Yin Ping; Li, Bing; Wang, Pengfei; Zhao, Yong

2015-01-19

Smoking has resulted in numerous deaths in China. Data indicate that 21% of college students in China are smokers. This study aimed to examine the smoking-related behaviors of undergraduates, as influenced by knowledge, attitude, social pressure, and environmental constraints. A convenience sampling of 412 fresh undergraduates from two universities in the University Town in Chongqing, China was recruited. Chi-square tests were used to compare the smoking-related variables between smokers and non-smokers. Moreover, logistic regression was used to examine the factors that associated with smoking status in undergraduates. Smokers and non-smokers differ in terms of knowledge, attitudes toward smoking, participation in tobacco promotional activities, and sources of social pressure. Logistic regression model identified that sex, living cost, five smoking-related attitudes of "Smoking is pleasurable, Smoking relaxes me, Smoking makes me look strong, Smoking is a waste of money, Smoking can help me study better", the social pressure "Smoking brings comfort during celebration", and the environmental constraints "How did you get your cigarettes in the past 30 days?" are significantly associated with smoking. The findings provide a better understanding of the epidemic of smoking among fresh undergraduates in Chongqing, China. This study provides more detailed consideration of the implications for the WHO Framework Convention on Tobacco Control (FCTC) policies, especially on restriction of retail sales outlets and tobacco promotion activities near universities in China.

Relations between protein production, protein quality and environmental factors in Pisum mutants

International Nuclear Information System (INIS)

Gottschalk, W.; Mueller, H.P.; Wolff, G.

1975-01-01

The seed protein content of 138 radiation-induced Pisum mutants was determined. The variability of this genetically well-defined material agrees approximately with that of the world collection of Pisum sativum. Some environmental factors to a great extent influence the protein production of the mutants and the initial line. Therefore, it is necessary to consider the relations between the genetically controlled protein production and its dependence upon the environmental factors. This is especially evident if the protein situation of the same genotypes cultivated under the moderate climatic conditions of middle Europe is compared with the subtropical conditions of India. A generally firm correlation between seed size and protein content could not be found in material regarding 148 different mutants of our assortment. Therefore, the selection of small-grained mutants does not result in a selection of protein-rich genotypes in Pisum sativum. Considering all the criteria positively and negatively influencing the protein production, a positive situation could be found in some mutants, especially in the fasciated ones. Furthermore, an improvement of the protein quality could be reached by a genetically conditioned alteration of the globulin-albumin ratio leading to an increase of some essential amino acids such as methionine and lysine. The combined action of mutant genes results in unexpected changes of the protein quantity as well as the quality of the recombinants in relation to their parental mutants. The comparison of some essential amino acids of our useful mutants with those of the varieties of other genera of the Leguminosae shows certain trends of biochemical alterations realized during evolutionary development of the family. (author)

A comparison of ISO 14001 to other related environmental management systems and tools

International Nuclear Information System (INIS)

White, S.E.; Byron, D.F.; Livingston, B.L.

1995-08-01

Efficient environmental management is of increasing priority for the industrial sector. The achievement of ISO 14001 certification will demonstrate that the environmental management system meets or exceeds industry standards since this standard will be the accepted international measure of environmental management. A review of published environmental management systems and tools was conducted to ensure all aspects of environmental management are covered in the establishment or formalization of an environmental management system. The objective of this effort is to compare the ISO 14001 standard with other environmental management systems and tools

Soil fauna and its relation with environmental variables in soil management systems

Directory of Open Access Journals (Sweden)

Dilmar Baretta

Full Text Available The present study aims to generate knowledge about the soil fauna, its relation to other explanatory environmental variables, and, besides it, to select edaphic indicators that more contribute to separate the land use systems (LUS. Five different LUS were chosen: conventional tillage with crop rotation (CTCR; no-tillage with crop rotation (NTCR; conventional tillage with crop succession (CTCS; no-tillage with crop succession (NTCS and minimum tillage with crop succession (MTCS. The samples were made in the counties Chapecó, Xanxerê and Ouro Verde located in the state of Santa Catarina, Brazil, and were considered the true replicates of the LUS. In each site, nine points were sampled in a sampling grid of 3 x 3. At the same points, soil was sampled for the physical, chemical and biological attributes (environmental variables. Pitfall traps were used to evaluate the soil fauna. Data were analyzed using principal component analysis (PCA and canonical discriminant analysis (CDA. The soil fauna presented potential to be used as indictors of soil quality, since some groups proved to be sensible to changes of the environmental variables and to soil management and tillage. The soil management using crop rotation (NTCR and CTCR presented higher diversity, compared to the systems using crop succession (NTCS, MTCS and NTCS, evidencing the importance of the soil tillage, independent of the season (summer or winter. The variable that better contributed to explain these changes were the chemical variables (potassium, pH, calcium, organic matter, available phosphorus, potential acidity, and biological variables (Shannon diversity index, Collembola, Pielou equitability index and microbial biomass carbon, respectively.

Health and environmental risk-related impacts of actinide burning on high-level waste disposal

International Nuclear Information System (INIS)

Forsberg, C.W.

1992-05-01

The potential health and environmental risk-related impacts of actinide burning for high-level waste disposal were evaluated. Actinide burning, also called waste partitioning-transmutation, is an advanced method for radioactive waste management based on the idea of destroying the most toxic components in the waste. It consists of two steps: (1) selective removal of the most toxic radionuclides from high-level/spent fuel waste and (2) conversion of those radionuclides into less toxic radioactive materials and/or stable elements. Risk, as used in this report, is defined as the probability of a failure times its consequence. Actinide burning has two potential health and environmental impacts on waste management. Risks and the magnitude of high-consequence repository failure scenarios are decreased by inventory reduction of the long-term radioactivity in the repository. (What does not exist cannot create risk or uncertainty.) Risk may also be reduced by the changes in the waste characteristics, resulting from selection of waste forms after processing, that are superior to spent fuel and which lower the potential of transport of radionuclides from waste form to accessible environment. There are no negative health or environmental impacts to the repository from actinide burning; however, there may be such impacts elsewhere in the fuel cycle

Integrating international relations and environmental science course concepts through an interactive world politics simulation

Science.gov (United States)

Straub, K. H.; Kesgin, B.

2012-12-01

During the fall 2012 semester, students in two introductory courses at Susquehanna University - EENV:101 Environmental Science and POLI:131 World Affairs - will participate together in an online international relations simulation called Statecraft (www.statecraftsim.com). In this strategy game, students are divided into teams representing independent countries, and choose their government type (democracy, constitutional monarchy, communist totalitarian, or military dictatorship) and two country attributes (industrial, green, militaristic, pacifist, or scientific), which determine a set of rules by which that country must abide. Countries interact over issues such as resource distribution, war, pollution, immigration, and global climate change, and must also keep domestic political unrest to a minimum in order to succeed in the game. This simulation has typically been run in political science courses, as the goal is to allow students to experience the balancing act necessary to maintain control of global and domestic issues in a dynamic, diverse world. This semester, environmental science students will be integrated into the simulation, both as environmental advisers to each country and as independent actors representing groups such as Greenpeace, ExxonMobil, and UNEP. The goal in integrating the two courses in the simulation is for the students in each course to gain both 1) content knowledge of certain fundamental material in the other course, and 2) a more thorough, applied understanding of the integrated nature of the two subjects. Students will gain an appreciation for the multiple tradeoffs that decision-makers must face in the real world (economy, resources, pollution, health, defense, etc.). Environmental science students will link these concepts to the traditional course material through a "systems thinking" approach to sustainability. Political science students will face the challenges of global climate change and gain an understanding of the nature of

Environmental Impact and Relative Invasiveness of Free-Roaming Domestic Carnivores—a North American Survey of Governmental Agencies

Directory of Open Access Journals (Sweden)

Ana Lepe

2017-10-01

Full Text Available A survey of the United States and Canadian governmental agencies investigated the environmental impact and relative invasiveness of free-roaming domestic non-native carnivores—dogs, cats, and ferrets. Agencies represented wildlife, fish, game, natural or environmental resources, parks and recreation, veterinary and human health, animal control, and agriculture. Respondents were asked to document the number and frequency of sightings of unconfined animals, evidence for environmental harm, and the resulting “degree of concern” in their respective jurisdictions. Results confirmed the existence of feral (breeding cats and dogs, documenting high levels of concern regarding the impact of these animals on both continental and surrounding insular habitats. Except for occasional strays, no free-roaming or feral ferrets were reported; nor were there reports of ferrets impacting native wildlife, including ground-nesting birds, or sensitive species. This is the first study to report the relative impact of free-roaming domestic carnivores. Dogs and cats meet the current definition of “invasive” species, whereas ferrets do not. Differences in how each species impacts the North American environment highlights the complex interaction between non-native species and their environment. Public attitudes and perceptions regarding these species may be a factor in their control and agency management priorities.

Environmental Behavior's Dirty Secret: The Prevalence of Waste Management in Discussions of Environmental Concern and Action

Science.gov (United States)

Gould, Rachelle K.; Ardoin, Nicole M.; Biggar, Matt; Cravens, Amanda E.; Wojcik, Deb

2016-08-01

Humankind and the planet face many thorny environmentally related challenges that require a range of responses, including changing behaviors related to transportation, eating habits, purchasing, and myriad other aspects of life. Using data from a 1201-person survey and 14 Community Listening Sessions (CLSs), we explore people's perceptions of and actions taken to protect the environment. Our data indicate a striking prevalence of waste management-related actions. Survey respondents described actions and concerns related to trash, recycling, and composting as the most common environmental behaviors; similarly, participants in CLSs discussed waste-related topics, for which we did not prompt, as frequently as those topics for which we specifically prompted. Explanations for this prevalence emerging from the data include (1) the nature of waste-related behaviors (concrete, supported by infrastructure, simple, compatible with lifestyle); (2) norms and social dynamics (family interactions, feelings of belonging/participation, government policy); and (3) internal psychological processes (internalized norms and environmental concern). We also found that many waste-related discussions were relatively superficial, focusing on immediate waste-related issues (e.g., litter or recycling) rather than larger issues such as consumption. Our results may provide insight into future efforts to encourage pro-environmental behavior. Given that most pro-environmental behavior involves tasks more complex and lifestyle-changing than those related to simple aspects of waste management, we suggest focusing on the latter two intertwined categories that our data suggest are important: encouraging social dynamics and related development of norms concerning environmental behavior (category 2), and fostering internalized norms and environmental concern (category 3).

Guidelines for the Review of Environmental-Related Legislation Regarding the Realisation of the Right to Access to Sufficient Food

Directory of Open Access Journals (Sweden)

Inge Snyman

2015-12-01

Full Text Available The development of legislation for the progressive realisation of the right to access to sufficient food is labelled as an international and national objective. Section 27(2 of the Constitution of the Republic of South Africa, 1996 assigns a compulsory mandate to the South African government to take reasonable legislative and other measures, within its available resources, to achieve the progressive realisation of the right to access to sufficient food. The United Nations' Food and Agricultural Organization (FAO proposes a three-level strategy for the implementation of the right to food on a national legislative level, namely through: constitutional recognition, the implementation of a food framework law and the reviewing of relevant sectoral legislation. This contribution focuses on the last level of legislative provisioning, namely the reviewing of relevant sectoral legislation which influences, or possibly can, influence the realisation of the right to access to sufficient food. The right to access to sufficient food has multidimensional, interdisciplinary and cross-sectoral characteristics and consequently various sectors are involved in the realisation of the right to access to sufficient food. The FAO determines that the intended purpose will be to identify and review all sectoral legislation that might influence the availability, stability, access and adequacy of food, by means of a proposed reviewing process. The suggested reviewing process of the FAO is comprehensive and diverse; therefore the focus of this contribution is based on the reviewing of relevant environmental-related legislation only. The FAO does not make recommendations with regard to the specific aspects that need to be incorporated in environmental-related legislation to contribute to the progressive realisation of the right to access to sufficient food (in other words the aspects against which environmental-related legislation can be evaluated. Therefore this

Cognitive Function Related to Environmental Exposure to Manganese

Science.gov (United States)

Background: The towns of Marietta and East Liverpool (EL), Ohio, have been identified as having elevated manganese (Mn) in air due to industrial pollution. Objectives: To evaluate relationships between environmental Mn (Mn-air) exposure and distance from the source and cognitive...

Environmental history

DEFF Research Database (Denmark)

Pawson, Eric; Christensen, Andreas Aagaard

2017-01-01

Environmental history is an interdisciplinary pursuit that has developed as a form of conscience to counter an increasingly powerful, forward-looking liberal theory of the environment. It deals with the relations between environmental ideas and materialities, from the work of the geographers George...... risks”. These are exposed by environmental history’s focus on long-run analysis and its narrative form that identifies the stories that we tell ourselves about nature. How a better understanding of past environmental transformations helps to analyse society and agency, and what this can mean...... for solutions and policies, is the agenda for an engaged environmental history from now on....

Environmental futures research at the U.S. Environmental Protection Agency

Science.gov (United States)

Robert L. Olson

2012-01-01

Relatively little research on environmental futures has been carried out in the United States. An exception is the long-running futures research that the U.S. Environmental Protection Agency (EPA) has been conducting since the 1970s. This paper reviews past and current efforts toward developing a capacity for environmental foresight within the EPA, and discusses some...

Arsenic concentrations, related environmental factors, and the predicted probability of elevated arsenic in groundwater in Pennsylvania

Science.gov (United States)

Gross, Eliza L.; Low, Dennis J.

2013-01-01

Analytical results for arsenic in water samples from 5,023 wells obtained during 1969–2007 across Pennsylvania were compiled and related to other associated groundwater-quality and environmental factors and used to predict the probability of elevated arsenic concentrations, defined as greater than or equal to 4.0 micrograms per liter (µg/L), in groundwater. Arsenic concentrations of 4.0 µg/L or greater (elevated concentrations) were detected in 18 percent of samples across Pennsylvania; 8 percent of samples had concentrations that equaled or exceeded the U.S. Environmental Protection Agency’s drinking-water maximum contaminant level of 10.0 µg/L. The highest arsenic concentration was 490.0 µg/L.

Determination of Mercury in Fish: A Low-Cost Implementation of Cold-Vapor Atomic Absorbance for the Undergraduate Environmental Chemistry Laboratory

Science.gov (United States)

Niece, Brian K.; Hauri, James F.

2013-01-01

Mercury is a known neurotoxin that is particularly harmful to children and unborn fetuses. Consumption of contaminated fish is one major route of mercury exposure. This laboratory experiment gives students an opportunity to measure mercury concentrations in store-bought seafood and compare the results to suggested exposure limits. The U.S.…

The relative influence of demographic, individual, social, and environmental factors on physical activity among boys and girls

Directory of Open Access Journals (Sweden)

Barr-Anderson Daheia

2010-11-01

Full Text Available Abstract Background This study aimed to evaluate the associations of selected demographic, individual, social, and environmental factors with moderate-to-vigorous physical activity (MVPA in a sample of children and adolescents. Methods MVPA was assessed among youth (n = 294 10-17-years-old using the ActiGraph accelerometer. Youth completed measures of demographic and individual variables related to physical activity (PA, perceived social support by parents and peers, and perceived neighborhood characteristics. Parents completed the long-form of the International Physical Activity Questionnaire. The Physical Activity and Media Inventory was used to measure the home environment and Geographical Information Systems software was used to measure the physical neighborhood environment. Bivariate correlations and hierarchical multiple regression were conducted stratified by gender. Results Boys participated in significantly more MVPA than girls. In hierarchical analyses, peer support, home PA equipment, and temperature were significantly associated with MVPA among boys whereas distance to the school they attended was associated with MVPA among girls. The final models accounted for 25% and 15% of the variance in MVPA among boys and girls, respectively. Conclusions Important differences exist among the individual, social, and environmental factors related to MVPA between boys and girls. Boys' levels of activity appear to be influenced by factors closely linked to unstructured and social types of activities whereas girls' activities relate to internal and external barriers as well as their proximity to their schools. The prospective contribution of these important individual, social, and environmental factors to changes in MVPA among children and adolescents remains to be determined.

Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening

Science.gov (United States)

Hu, Xin; Legler, Patricia M.; Southall, Noel; Maloney, David J.; Simeonov, Anton; Jadhav, Ajit

2014-07-01

Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

Visitation to Natural Areas on Campus and Its Relation to Place Identity and Environmentally Responsible Behaviors

Science.gov (United States)

Lawrence, Eva K.

2012-01-01

This study examined college students' visits to natural areas on campus and how these visits relate to place identity and environmentally responsible behaviors. The majority (76.5%) of the 115 participants visited the natural areas, and 55.7% of these students visited for a course requirement. Students who lived on campus, were younger, and…

Immune recognition of botulinum neurotoxin B: antibody-binding regions on the heavy chain of the toxin.

Science.gov (United States)

Dolimbek, Behzod Z; Steward, Lance E; Aoki, K Roger; Atassi, M Zouhair

2008-02-01

The purpose of this work was to map the continuous regions recognized by human, horse and mouse anti-botulinum neurotoxin B (BoNT/B) antibodies (Abs). We synthesized a panel of sixty 19-residue peptides (peptide C31 was 24 residues) that overlapped consecutively by 5 residues and together encompassed the entire heavy chain of BoNT/B (H/B, residues 442-1291). Abs from the three host species recognized similar, but not identical, peptides. There were also peptides recognized by two or only by one host species. Where a peptide was recognized by Abs of more than one host species, these Abs were at different levels among the species. Human, horse and mouse Abs bound, although in different amounts, to regions within peptides 736-754, 778-796, 848-866, 932-950, 974-992, 1058-1076 and 1128-1146. Human and horse Abs bound to peptides 890-908 and 1170-1188. Human and mouse Abs recognized peptides 470-488/484-502 overlap, 638-656, 722-740, 862-880, 1030-1048, 1072-1090, 1240-1258 and 1268-1291. We concluded that the antigenic regions localized with the three antisera are quite similar, exhibiting in some cases a small shift to the left or to the right. This is consistent with what is known about protein immune recognition. In the three-dimensional structure, the regions recognized on H/B by anti-BoNT/B Abs occupied surface locations and analysis revealed no correlation between these surface locations and surface electrostatic potential, hydrophilicity, hydrophobicity, or temperature factor. A region that bound mouse Abs overlapped with a recently defined site on BoNT/B that binds to mouse and rat synaptotagmin II, thus providing a molecular explanation for the blocking (protecting) activity of these Abs. The regions thus localized afford candidates for incorporation into a synthetic vaccine design.

Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.

Directory of Open Access Journals (Sweden)

Luciana A F Gil

Full Text Available Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB, a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH3 developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH3 developed a protective immune response against both BoNT/C (5 IU/mL and BoNT/D (10 IU/mL, as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle.

Steam-treated wood pellets: Environmental and financial implications relative to fossil fuels and conventional pellets for electricity generation

International Nuclear Information System (INIS)

McKechnie, Jon; Saville, Brad; MacLean, Heather L.

2016-01-01

Highlights: • Steam-treated pellets can greatly reduce greenhouse gas emissions relative to coal. • Cost advantage is seen relative to conventional pellets. • Higher pellet cost is more than balanced by reduced retrofit capital requirements. • Low capacity factors further favour steam-treated pellets over conventional pellets. - Abstract: Steam-treated pellets can help to address technical barriers that limit the uptake of pellets as a fuel for electricity generation, but there is limited understanding of the cost and environmental impacts of their production and use. This study investigates life cycle environmental (greenhouse gas (GHG) and air pollutant emissions) and financial implications of electricity generation from steam-treated pellets, including fuel cycle activities (biomass supply, pellet production, and combustion) and retrofit infrastructure to enable 100% pellet firing at a generating station that previously used coal. Models are informed by operating experience of pellet manufacturers and generating stations utilising coal, steam-treated and conventional pellets. Results are compared with conventional pellets and fossil fuels in a case study of electricity generation in northwestern Ontario, Canada. Steam-treated pellet production has similar GHG impacts to conventional pellets as their higher biomass feedstock requirement is balanced by reduced process electricity consumption. GHG reductions of more than 90% relative to coal and ∼85% relative to natural gas (excluding retrofit infrastructure) could be obtained with both pellet options. Pellets can also reduce fuel cycle air pollutant emissions relative to coal by 30% (NOx), 97% (SOx), and 75% (PM 10 ). Lesser retrofit requirements for steam-treated pellets more than compensate for marginally higher pellet production costs, resulting in lower electricity production cost compared to conventional pellets ($0.14/kW h vs. $0.16/kW h). Impacts of retrofit infrastructure become increasingly

7 CFR 650.21 - Working relations with the U.S. Environmental Protection Agency (EPA) and related State...

Science.gov (United States)

2010-01-01

... recycling and disposal, environmental considerations in land use, Environmental Impact Statements (EIS's... and guidelines, develop agreements for undertaking specific activities or projects of national... projects of multistate significance and mutual advantage. (3) The state conservationist will: (i) Obtain...

Detection of marine neurotoxins and characterization of the presynaptic activity of iotrochotin from the sponge Iotrochota birotulata

International Nuclear Information System (INIS)

Martin, J.V.

1987-01-01

In order to detect novel presynaptic neurotoxins, a total of 766 extracts from marine organisms collected during expeditions of the research vessel Alpha Helix around the peninsula of Baja Mexico in 1974 and through the Caribbean in 1978 were tested for activity in a synaptosomal assay for the release of acetylcholine (ACh). To eliminate from consideration sample extracts which lysed the synaptosomal membrane, lactate dehydrogenase (LDH) activity was measured as a cytoplasmic marker. On the basis of the screening studies the extract of the sponge lotrochota birotulata was chosen for more detailed characterization. The active factor, iotrochotin (IOT), was sensitive to thermal inactivation, was partially activated by trypsin treatment and had a molecular weight of 12,000-13,000. The activity of IOT was found to be complete by one minute. The maximal release of radioactivity from synaptosomes preloaded with [ 3 H]choline was found to be dependent on the concentration of IOT irrespective of the time of further incubation. The concentration-response curve of IOT activity showed a sigmoid shape which did not fit the Hill equation. IOT caused release of both ACh and choline. Of the radioactivity released by IOT from synaptosomes preloaded with [ 3 H]choline, 50-60% was [ 3 H]ACh. IOT also released [ 3 H]GABA and [ 3 H]norepinephrine from synaptosomes preincubated with these labeled neurotransmitters. The activity of IOT was only minimally sensitive to reduction in Na + or Ca 2+ levels, and was not sensitive to tetrodotoxin. IOT did not dramatically change the fluorescence of synaptosomes incubated with a depolarization-indicating dye. However, depolarization of synaptosomes with high concentrations of K + was still detectable by this method in the presence of IOT

Smoking-Related Knowledge, Attitude, Social Pressure, and Environmental Constraints among New Undergraduates in Chongqing, China

Directory of Open Access Journals (Sweden)

Xianglong Xu

2015-01-01

Full Text Available Background: Smoking has resulted in numerous deaths in China. Data indicate that 21% of college students in China are smokers. Objective: This study aimed to examine the smoking-related behaviors of undergraduates, as influenced by knowledge, attitude, social pressure, and environmental constraints. Method: A convenience sampling of 412 fresh undergraduates from two universities in the University Town in Chongqing, China was recruited. Chi-square tests were used to compare the smoking-related variables between smokers and non-smokers. Moreover, logistic regression was used to examine the factors that associated with smoking status in undergraduates. Results: Smokers and non-smokers differ in terms of knowledge, attitudes toward smoking, participation in tobacco promotional activities, and sources of social pressure. Logistic regression model identified that sex, living cost, five smoking-related attitudes of “Smoking is pleasurable, Smoking relaxes me, Smoking makes me look strong, Smoking is a waste of money, Smoking can help me study better”, the social pressure “Smoking brings comfort during celebration”, and the environmental constraints “How did you get your cigarettes in the past 30 days?” are significantly associated with smoking. Conclusions: The findings provide a better understanding of the epidemic of smoking among fresh undergraduates in Chongqing, China. This study provides more detailed consideration of the implications for the WHO Framework Convention on Tobacco Control (FCTC policies, especially on restriction of retail sales outlets and tobacco promotion activities near universities in China.

Mechanisms of Resistance to Neurotoxins

National Research Council Canada - National Science Library

Schubert, David

2002-01-01

.... During all of these events, some groups of nerve cells are spared relative to others. It is therefore likely that biochemical mechanisms exist which lead to increased resistance to oxidative stress and other forms of cytotoxicity...

Pharmacokinetics of Naja sumatrana (equatorial spitting cobra venom and its major toxins in experimentally envenomed rabbits.

Directory of Open Access Journals (Sweden)

Michelle Khai Khun Yap

2014-06-01

Full Text Available The optimization of snakebite management and the use of antivenom depend greatly on the knowledge of the venom's composition as well as its pharmacokinetics. To date, however, pharmacokinetic reports on cobra venoms and their toxins are still relatively limited. In the present study, we investigated the pharmacokinetics of Naja sumatrana (Equatorial spitting cobra venom and its major toxins (phospholipase A2, neurotoxin and cardiotoxin, following intravenous and intramuscular administration into rabbits.The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h, terminal phase half-life (13.6 h and systemic bioavailability (41.9% of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively. Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5% compared to that of the phospholipase A2 (Fi.m.=68.6% or cardiotoxin (Fi.m.=45.6%. The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.Our results suggest that the venom neurotoxin is absorbed very rapidly and has the highest bioavailability following intramuscular injection, supporting its

Identification and Characterization of Botulinum Neurotoxin A Substrate Binding Pockets and Their Re-Engineering for Human SNAP-23.

Science.gov (United States)

Sikorra, Stefan; Litschko, Christa; Müller, Carina; Thiel, Nadine; Galli, Thierry; Eichner, Timo; Binz, Thomas

2016-01-29

Botulinum neurotoxins (BoNTs) are highly potent bacterial proteins that block neurotransmitter release at the neuromuscular junction by cleaving SNAREs (soluble N-ethyl maleimide sensitive factor attachment protein receptors). However, their serotype A (BoNT/A) that cleaves SNAP-25 (synaptosomal-associated protein of 25 kDa) has also been an established pharmaceutical for treatment of medical conditions that rely on hyperactivity of cholinergic nerve terminals for 25 years. The expansion of its use to a variety of further medical conditions associated with hypersecretion components is prevented partly because the involved SNARE isoforms are not cleaved. Therefore, we examined by mutational analyses the reason for the resistance of human SNAP-23, an isoform of SNAP-25. We show that replacement of 10 SNAP-23 residues with their SNAP-25 counterparts effects SNAP-25-like cleavability. Conversely, transfer of each of the replaced SNAP-23 residues to SNAP-25 drastically decreased the cleavability of SNAP-25. By means of the existing SNAP-25-toxin co-crystal structure, molecular dynamics simulations, and corroborative mutagenesis studies, the appropriate binding pockets for these residues in BoNT/A were characterized. Systematic mutagenesis of two major BoNT/A binding pockets was conducted in order to adapt these pockets to corresponding amino acids of human SNAP-23. Human SNAP-23 cleaving mutants were isolated using a newly established yeast-based screening system. This method may be useful for engineering novel BoNT/A pharmaceuticals for the treatment of diseases that rely on SNAP-23-mediated hypersecretion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Generation and Characterization of Six Recombinant Botulinum Neurotoxins as Reference Material to Serve in an International Proficiency Test

Directory of Open Access Journals (Sweden)

Jasmin Weisemann

2015-11-01

Full Text Available The detection and identification of botulinum neurotoxins (BoNT is complex due to the existence of seven serotypes, derived mosaic toxins and more than 40 subtypes. Expert laboratories currently use different technical approaches to detect, identify and quantify BoNT, but due to the lack of (certified reference materials, analytical results can hardly be compared. In this study, the six BoNT/A1–F1 prototypes were successfully produced by recombinant techniques, facilitating handling, as well as improving purity, yield, reproducibility and biosafety. All six BoNTs were quantitatively nicked into active di-chain toxins linked by a disulfide bridge. The materials were thoroughly characterized with respect to purity, identity, protein concentration, catalytic and biological activities. For BoNT/A1, B1 and E1, serotypes pathogenic to humans, the catalytic activity and the precise protein concentration were determined by Endopep-mass spectrometry and validated amino acid analysis, respectively. In addition, BoNT/A1, B1, E1 and F1 were successfully detected by immunological assays, unambiguously identified by mass spectrometric-based methods, and their specific activities were assigned by the mouse LD50 bioassay. The potencies of all six BoNT/A1–F1 were quantified by the ex vivo mouse phrenic nerve hemidiaphragm assay, allowing a direct comparison. In conclusion, highly pure recombinant BoNT reference materials were produced, thoroughly characterized and employed as spiking material in a worldwide BoNT proficiency test organized by the EQuATox consortium.

Environmental aspects of commercial radioactive waste management

International Nuclear Information System (INIS)

1979-05-01

Volume 2 contains chapters 6 through 10: environmental effects related to radioactive waste management associated with LWR fuel reprocessing - mixed-oxide fuel fabrication plant; environmental effects related to transporting radioactive wastes associated with LWR fuel reprocessing and fabrication; environmental effects related to radioactive waste management associated with LWR fuel reprocessing - retrievable waste storage facility; environmental effects related to geologic isolation of LWR fuel reprocessing wastes; and integrated systems for commercial radioactive waste management

[Examination of psychomotor development in relation to social-environmental factors in preterm children at 2 years old].

Science.gov (United States)

Kenyhercz, Flóra; Nagy, Beáta

2017-01-01

The development of children born prematurely is an important aspect in public health, because preterm birth rates are not decreasing with the development of medical sciences. Description of psychomotor development of preterm children related to potentially influencing environmental factors. Children born below 2.500 grams at the age of two (n = 75). Psychomotor development, quality of home environment, socio-demographic background were measured. Lower birth weight was associated with lower development quotients. Psychomotor development was also negatively affected by child deprivation, low levels of cognitive stimulation and maternal empathy, regardless of birth weight. Increased performance loss was found related to lower sociodemographic variables, such as low maternal education or ethnicity. Psychomotor development of 2-year-old premature children is affected by the examined social-environmental factors. We recommend the screening and developmental interventions for premature children as early as possible, thus preventing difficulties in mental and motor development in the future. Orv. Hetil., 2017, 158(1), 31-38.

(Environmental technology)

Energy Technology Data Exchange (ETDEWEB)

Boston, H.L.

1990-10-12

The traveler participated in a conference on environmental technology in Paris, sponsored by the US Embassy-Paris, US Environmental Protection Agency (EPA), the French Environmental Ministry, and others. The traveler sat on a panel for environmental aspects of energy technology and made a presentation on the potential contributions of Oak Ridge National Laboratory (ORNL) to a planned French-American Environmental Technologies Institute in Chattanooga, Tennessee, and Evry, France. This institute would provide opportunities for international cooperation on environmental issues and technology transfer related to environmental protection, monitoring, and restoration at US Department of Energy (DOE) facilities. The traveler also attended the Fourth International Conference on Environmental Contamination in Barcelona. Conference topics included environmental chemistry, land disposal of wastes, treatment of toxic wastes, micropollutants, trace organics, artificial radionuclides in the environment, and the use biomonitoring and biosystems for environmental assessment. The traveler presented a paper on The Fate of Radionuclides in Sewage Sludge Applied to Land.'' Those findings corresponded well with results from studies addressing the fate of fallout radionuclides from the Chernobyl nuclear accident. There was an exchange of new information on a number of topics of interest to DOE waste management and environmental restoration needs.

Human comfort and self-estimated performance in relation to indoor environmental parameters and building features

OpenAIRE

Frontczak, Monika Joanna; Wargocki, Pawel

2011-01-01

The main objective of the Ph.D. study was to examine occupants’ perception of comfort and self-estimated job performance in non-industrial buildings (homes and offices), in particular how building occupants understand comfort and which parameters, not necessarily related to indoor environments, influence the perception of comfort.To meet the objective, the following actions were taken: (1) a literature survey exploring which indoor environmental parameters (thermal, acoustic, visualenvironmen...

Environmental qualification - walkdowns: The documentation of configuration information for safety related components, equipment and systems

International Nuclear Information System (INIS)

Melmer, J.; Waters, M.

1995-01-01

Environmental Qualification walkdowns are conducted to collect field data to verify/validate/document configurations of safety related equipment and systems. This paper describes the process for conducting walkdowns and the justification for using an electronic format. The following are described: a) Background; b) Preparing, executing and processing walkdowns; c) Hardware/software; d) Impact of a paperless system on walkdown execution, maintenance and work planning; e) Other applications for the technology

Environmental and Life Style Factors in Relation to Male Reproductive Disorders

DEFF Research Database (Denmark)

Krysiak-Baltyn, Konrad

on the environmental aspects of TDS, generating further support for the hypothesis that environmental factors may play a critical role in the observed trends. This thesis is divided into four parts. In the first part I introduce male reproductive disorders and the current state of affairs. In the second part, I focus......During the past four decades, the incidence rates of testicular cancer and other male reproductive disorders have been increasing at a rapid rate, predominantly in developed and industrialized countries. This increase is considered too great to be explained by genetic factors alone, and thus...... environmental factors have strongly been suspected to play a major role. There is a large amount of clinical research which has tried to pinpoint the mechanism of action for this trend. Although the exact mechanism of action has not been elucidated, a number of genetic factors as well as environmental chemicals...

Regional monitoring of environmental physics climate related anomalies

Science.gov (United States)

El-Askary, Hesham

2004-11-01

Scientific communities have been working in creating and enhancing scientific research programs in which in situ and satellite data as well as remote sensing (RS) technologies are being applied to regional environmental issues. These issues include the effects of climate change on regional flooding, droughts and the impact of human activities as they relate to feedbacks on the global climate. More specifically, one needs to evaluate the potential impact of climatological variability on social, economic, and human activities. In addition, the study of their effects on agriculture, forests, local natural ecosystems and water climate-related resources, is most important. Finally, dust storms and other natural events such as droughts can have great local impacts. Approximately half of the dust in today's atmosphere may be the result of changes to the environment caused by human activities, including agriculture, overgrazing, and deforestation. Climate variability may lead to the occurrence of some severe environmental phenomena like dust storms, hurricanes, tornadoes, floods and droughts. Under normal conditions we can detect different dust effects associated with the movement of storms as well as different rain patterns that do not affect much of the surrounding environment either at regional or global scales. On the other hand, under abnormal climatological conditions, high anomalies of precipitation might occur due to the presence of hurricanes or other events, leading to severe flooding events. In this dissertation, we apply time series analysis techniques to remote sensing and in situ data to detect precipitation and dust storm anomalies and study their behavior on regional scales. The first application is the detection and monitoring of dust storms events over parts of the Middle East and Asia. Dust storms cause health and economic hazards. In this thesis dust storms development is examined based on using remote sensing. It utilizes a combination of optical

China's Environmental Crisis

Directory of Open Access Journals (Sweden)

Eva Sternfeld

2014-12-01

Full Text Available The following article discusses the environmental challenges of China‘s economic boom and its social consequences. Although the country has a relatively long history of institutionalized environmental policy, it is in the implementation at local level where it faces large implementation deficits. Environmental damage causes not only high economic costs, but also affects social stability.

Draft environmental statement related to the Union Carbide Corporation, Gas Hills Uranium Project (Natrona County, Wyoming)

International Nuclear Information System (INIS)

1979-01-01

The proposed action is the renewal of Source Material License SUA-648 issued for the operation of the Gas Hills Uranium Project in Wyoming, near Moneta. The project is an acid leach, ion-exchange, and solvent-extraction uranium ore processing mill at an increased capacity of 500,000 tons per year and the construction of two heap leach facilities in Natrona and Fremont Counties for initial processing of low-grade ore. After analysis of environmental impacts and adverse effects, it is the proposed position of NRC that the license be renewed subject to conditions relating to stabilization of the tailings, reclamation, environmental monitoring, evaluation of any future activity not evaluated by NRC, archeological survey, analysis of unexpected harmful effects, and decommissioning

Issues of Security and Informational Privacy in relation to an Environmental Scanning System for Fighting Organized Crime

DEFF Research Database (Denmark)

Gerdes, Anne; Larsen, Henrik Legind; Rouces, Jacobo

2013-01-01

This paper clarifies privacy challenges related to the EU project, ePOOLICE, which aims at developing an environmental scanning system for fighting organized crime by improving law enforcement agencies opportunities for strategic proactive planning in response to emerging organized crime threats...... privacy all through the system design process....

Bacterial biodiversity-ecosystem functioning relations are modified by environmental complexity.

Science.gov (United States)

Langenheder, Silke; Bulling, Mark T; Solan, Martin; Prosser, James I

2010-05-26

With the recognition that environmental change resulting from anthropogenic activities is causing a global decline in biodiversity, much attention has been devoted to understanding how changes in biodiversity may alter levels of ecosystem functioning. Although environmental complexity has long been recognised as a major driving force in evolutionary processes, it has only recently been incorporated into biodiversity-ecosystem functioning investigations. Environmental complexity is expected to strengthen the positive effect of species richness on ecosystem functioning, mainly because it leads to stronger complementarity effects, such as resource partitioning and facilitative interactions among species when the number of available resource increases. Here we implemented an experiment to test the combined effect of species richness and environmental complexity, more specifically, resource richness on ecosystem functioning over time. We show, using all possible combinations of species within a bacterial community consisting of six species, and all possible combinations of three substrates, that diversity-functioning (metabolic activity) relationships change over time from linear to saturated. This was probably caused by a combination of limited complementarity effects and negative interactions among competing species as the experiment progressed. Even though species richness and resource richness both enhanced ecosystem functioning, they did so independently from each other. Instead there were complex interactions between particular species and substrate combinations. Our study shows clearly that both species richness and environmental complexity increase ecosystem functioning. The finding that there was no direct interaction between these two factors, but that instead rather complex interactions between combinations of certain species and resources underlie positive biodiversity ecosystem functioning relationships, suggests that detailed knowledge of how individual

Bacterial biodiversity-ecosystem functioning relations are modified by environmental complexity.

Directory of Open Access Journals (Sweden)

Silke Langenheder

Full Text Available BACKGROUND: With the recognition that environmental change resulting from anthropogenic activities is causing a global decline in biodiversity, much attention has been devoted to understanding how changes in biodiversity may alter levels of ecosystem functioning. Although environmental complexity has long been recognised as a major driving force in evolutionary processes, it has only recently been incorporated into biodiversity-ecosystem functioning investigations. Environmental complexity is expected to strengthen the positive effect of species richness on ecosystem functioning, mainly because it leads to stronger complementarity effects, such as resource partitioning and facilitative interactions among species when the number of available resource increases. METHODOLOGY/PRINCIPAL FINDINGS: Here we implemented an experiment to test the combined effect of species richness and environmental complexity, more specifically, resource richness on ecosystem functioning over time. We show, using all possible combinations of species within a bacterial community consisting of six species, and all possible combinations of three substrates, that diversity-functioning (metabolic activity relationships change over time from linear to saturated. This was probably caused by a combination of limited complementarity effects and negative interactions among competing species as the experiment progressed. Even though species richness and resource richness both enhanced ecosystem functioning, they did so independently from each other. Instead there were complex interactions between particular species and substrate combinations. CONCLUSIONS/SIGNIFICANCE: Our study shows clearly that both species richness and environmental complexity increase ecosystem functioning. The finding that there was no direct interaction between these two factors, but that instead rather complex interactions between combinations of certain species and resources underlie positive biodiversity

A graphene oxide based fluorescence resonance energy transfer (FRET) biosensor for ultrasensitive detection of botulinum neurotoxin A (BoNT/A) enzymatic activity.

Science.gov (United States)

Shi, Jingyu; Guo, Jiubiao; Bai, Gongxun; Chan, Chunyu; Liu, Xuan; Ye, Weiwei; Hao, Jianhua; Chen, Sheng; Yang, Mo

2015-03-15

Botulinum neurotoxins (BoNTs) are among the most potent toxic bacterial proteins for humans, which make them potential agents for bioterrorism. Therefore, an ultrasensitive detection of BoNTs and their active states is in great need as field-deployable systems for anti-terrorism applications. We report the construction of a novel graphene oxide (GO)-peptide based fluorescence resonance energy transfer (FRET) biosensor for ultrasensitive detection of the BoNT serotype A light chain (BoNT-LcA) protease activity. A green fluorescence protein (GFP) modified SNAP-25 peptide substrate (SNAP-25-GFP) was optimally designed and synthesized with the centralized recognition/cleavage sites. This FRET platform was constructed by covalent immobilization of peptide substrate on GO with BSA passivation which have advantages of low non-specific adsorption and high stability in protein abundant solution. BoNT-LcA can specifically cleave SNAP-25-GFP substrate covalently immobilized on GO to release the fragment with GFP. Based on fluorescence signal recovery measurement, the target BoNT-LcA was detected sensitively and selectively with the linear detection range from 1fg/mL to 1pg/mL. The limit of detection (LOD) for BoNT-LcA is around 1fg/mL. Copyright © 2014 Elsevier B.V. All rights reserved.

Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding

Directory of Open Access Journals (Sweden)

Robert Gustafsson

2018-04-01

Full Text Available Botulinum neurotoxins (BoNTs are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G. Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C as their protein receptors. We here present a high resolution (2.0 Å co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain. The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction. Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.

Patterns of tree growth in relation to environmental variability in the ...

Indian Academy of Sciences (India)

Tree diameter growth is sensitive to environmental fluctuations and tropical dry forests experience high seasonal and inter-annual environmental variation. Tree growth rates in a large permanent plot at Mudumalai, southern India, were examined for the influences of rainfall and three intrinsic factors (size, species and ...

Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.

Science.gov (United States)

Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R; Stevens, Raymond C

2010-04-16

Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent. Copyright (c) 2010. Published by Elsevier Ltd.

[Environmental justice as an approach to tackle environmental health inequalities].

Science.gov (United States)

Bolte, Gabriele; Bunge, Christiane; Hornberg, Claudia; Köckler, Heike

2018-06-01

Current international studies show that environment-related diseases disproportionately affect vulnerable people. This is a case of environmental injustice. Environmental justice goes beyond the mere description of environment- and health-related social inequalities by comprising two dimensions of justice as a normative approach: distributional and procedural justice. Attempts to explain the link between social circumstances, the environment and health deal with both the socially unequal distribution of environmental hazards and environmental resources (exposure variation) and social differences in vulnerability to the health effects of environmental exposures (effect modification). Integrated monitoring approaches provide the basis for deriving interventions under various aspects of environmental justice. Parting from public health research and embedded in the Health in All Policies (HiAP) concept, environmental justice has now been taken up in a number of fields, including politics, administration and practice. There are strategic considerations and attempts to anchor it in politics at the federal, state and the communal level, both by government and non-government groups. Health-promoting urban development is a core field for intervention. The Soziale Stadt (Social City) programme for promoting urban planning and construction as well as place oriented sectoral planning make an important contribution by helping to focus on urban spaces with multiple health hazards and to implement target group-oriented participation processes. There continues to be a need to develop methods and systematically implemented evaluations of political strategies and corresponding interventions regarding their effects on inequalities in health and environmental justice.

75 FR 8754 - Notice of Environmental Assessment Related to the Issuance of a License Amendment to Masters...

Science.gov (United States)

2010-02-25

... NUCLEAR REGULATORY COMMISSION [Docket No. 030-34325; NRC-2010-0068] Notice of Environmental Assessment Related to the Issuance of a License Amendment to Masters Materials License 03-23853-01VA, for Unrestricted Release of a Department of Veterans Affairs Facility in Gainesville, FL AGENCY: Nuclear Regulatory Commission. ACTION: Issuance of...

Quality of Streams in Johnson County, Kansas, and Relations to Environmental Variables, 2003-07

Science.gov (United States)

Rasmussen, Teresa J.; Poulton, Barry C.; Graham, Jennifer L.

2009-01-01

The quality of streams and relations to environmental variables in Johnson County, northeastern Kansas, were evaluated using water, streambed sediment, land use, streamflow, habitat, algal periphyton (benthic algae), and benthic macroinvertebrate data. Water, streambed sediment, and macroinvertebrate samples were collected in March 2007 during base flow at 20 stream sites that represent 11 different watersheds in the county. In addition, algal periphyton samples were collected twice (spring and summer 2007) at one-half of the sites. Environmental data including water and streambed-sediment chemistry data (primarily nutrients, fecal-indicator bacteria, and organic wastewater compounds), land use, streamflow, and habitat data were used in statistical analyses to evaluate relations between biological conditions and variables that may affect them. This report includes an evaluation of water and streambed-sediment chemistry, assessment of habitat conditions, comparison of biological community attributes (such as composition, diversity, and abundance) among sampling sites, placement of sampling sites into impairment categories, evaluation of biological data relative to environmental variables, and evaluation of changes in biological communities and effects of urbanization. This evaluation is useful for understanding factors that affect stream quality, for improving water-quality management programs, and for documenting changing conditions over time. The information will become increasingly important for protecting streams in the future as urbanization continues. Results of this study indicate that the biological quality at nearly all biological sampling sites in Johnson County has some level of impairment. Periphyton taxa generally were indicative of somewhat degraded conditions with small to moderate amounts of organic enrichment. Camp Branch in the Blue River watershed was the only site that met State criteria for full support of aquatic life in 2007. Since 2003

Environmental law

International Nuclear Information System (INIS)

Anon.

1980-01-01

This pocketbook contains major federal regulations on environmental protection. They serve to protect and cultivate mankind's natural foundations of life, to preserve the environment. The environmental law is devided as follows: Constitutional law on the environment, common administrative law on the environment, special administrative law on the environment including conservation of nature and preservation of rural amenities, protection of waters, waste management, protection against nuisances, nuclear energy and radiation protection, energy conservation, protection against dangerous substances, private law relating to the environment, criminal law relating to the environment. (HSCH) [de

Environmental Measurements Laboratory 1994 annual report

Energy Technology Data Exchange (ETDEWEB)

Chieco, N.A. [ed.; Krey, P.W.; Beck, H.L.

1995-08-01

This report summarizes the activities of the Environmental Measurements Laboratory (EML) for the calendar year 1994 and it serves as an annual report to the Director of the Office of Energy Research (ER), the Associate Director and staff of the Office of Health and Environmental Research (OHER), the manager and staff of the Chicago Field Office, and the authors colleagues. Emphasized are the progress and accomplishments of the year, rather than future plans or expectations. The technical summaries are grouped according to the following seven general program areas: environmental radiation and radioactivity; radiation transport and dosimetry; environmental radon, thoron, and related aerosols; atmospheric and surface pollutant studies related to global climate change; atmospheric chemistry; metrology, consultation, and emergency response; environmental management. EML`s mission is to address important scientific questions concerning human health and environmental impacts. Through its multidisciplinary staff, EML conducts experimental and theoretical research on radioactive and other energy-related pollutants, and provides DOE and other federal agencies with the in-house capability to respond effectively and efficiently with regard to quality assurance activities, environmental issues and related national security issues.

Environmental Measurements Laboratory 1994 annual report

International Nuclear Information System (INIS)

Chieco, N.A.; Krey, P.W.; Beck, H.L.

1995-08-01

This report summarizes the activities of the Environmental Measurements Laboratory (EML) for the calendar year 1994 and it serves as an annual report to the Director of the Office of Energy Research (ER), the Associate Director and staff of the Office of Health and Environmental Research (OHER), the manager and staff of the Chicago Field Office, and the authors colleagues. Emphasized are the progress and accomplishments of the year, rather than future plans or expectations. The technical summaries are grouped according to the following seven general program areas: environmental radiation and radioactivity; radiation transport and dosimetry; environmental radon, thoron, and related aerosols; atmospheric and surface pollutant studies related to global climate change; atmospheric chemistry; metrology, consultation, and emergency response; environmental management. EML's mission is to address important scientific questions concerning human health and environmental impacts. Through its multidisciplinary staff, EML conducts experimental and theoretical research on radioactive and other energy-related pollutants, and provides DOE and other federal agencies with the in-house capability to respond effectively and efficiently with regard to quality assurance activities, environmental issues and related national security issues

Motivators and Barriers to Incorporating Climate Change-Related Health Risks in Environmental Health Impact Assessment

OpenAIRE

Turner, Lyle R.; Alderman, Katarzyna; Connell, Des; Tong, Shilu

2013-01-01

Climate change presents risks to health that must be addressed by both decision-makers and public health researchers. Within the application of Environmental Health Impact Assessment (EHIA), there have been few attempts to incorporate climate change-related health risks as an input to the framework. This study used a focus group design to examine the perceptions of government, industry and academic specialists about the suitability of assessing the health consequences of climate change within...

22 CFR 216.7 - Environmental impact statements.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Environmental impact statements. 216.7 Section... Environmental impact statements. (a) Applicability. An Environmental Impact Statement shall be prepared when... Environmental Impact Statement relating to paragraph (a)(2) of this section shall comply with the CEQ...

Environmental justice: a criminological perspective

Science.gov (United States)

Lynch, Michael J.; Stretesky, Paul B.; Long, Michael A.

2015-08-01

This article examines studies related to environmental justice in the criminological literature and from a criminological perspective. Criminologists have long been concerned with injustices in the criminal justice system related to the enforcement of criminal law. In the 1990s, following the emergence of green criminology, a handful of criminologists have drawn attention to environmental justice as an extension of more traditional criminological studies of justice and injustice. Relevant criminological studies of environmental justice are reviewed, and suggestions for future environmental justice research are offered.

DNA-Based Analyses of Molds in Singapore Public Buildings Results in a Proposed Singapore Environmental Relative Moldiness Index

Science.gov (United States)

Dust samples (n=75) were collected from shopping malls, hotels and libraries in Singapore and then analyzed using Mold Specific Quantitative Polymerase Chain Reaction(MSQPCR) for the 36 molds that make up the Environmental Relative Moldiness Index (ERMI). Most of these molds (23/...

Medical Isotopes Production Project: Molybdenum-99 and related isotopes - environmental impact statement. Volume II, comment response document

International Nuclear Information System (INIS)

1996-04-01

This Environmental Impact Statement (EIS) provides environmental and technical information concerning the U.S. Department of Energy's (DOE) proposal to establish a domestic source to produce molybdenum-99 (Mo-99) and related isotopes (iodine-131, xenon-133, and iodine-125). Mo-99, a radioactive isotope of the element molybdenum, decays to form metastable technetium-99 (Tc-99m), a radioactive isotope used thousands of times daily in medical diagnostic procedures in the U.S. Currently, all Mo-99 used in the U.S. is obtained from a single Canadian source. DOE is pursuing the Medical Isotopes Production Project in order to ensure that a reliable supply of Mo-99 is available to the U.S. medical community as soon as practicable. Under DOE's preferred alternative, the Chemistry and Metallurgy Research Facility at the Los Alamos National Laboratory (LANL) and the Annular Core Research Reactor and Hot Cell Facility at Sandia National Laboratories/New Mexico (SNL/NM) would be used for production of the medical isotopes. In addition, three other reasonable alternatives and a No Action alternative are analyzed in detail, The sites for these three reasonable alternatives are LANL, Oak Ridge National Laboratory (ORNL), and Idaho National Engineering Laboratory (INEL). The analyses in this EIS indicate no significant difference in the potential environmental impacts among the alternatives. Each of the alternatives would use essentially the same technology for the production of the medical isotopes. Minor differences in environmental impacts among alternatives relate to the extent of activity necessary to modify and restart (as necessary) existing reactors and hot cell facilities at each of the sites, the quantities of low-level radioactive waste generated, how such waste would be managed, and the length of time needed for initial and full production capacity. This document contains comments recieved from meetings held regarding the site selection for isotope production

Co-occurrence of the Cyanotoxins BMAA, DABA and Anatoxin-a in Nebraska Reservoirs, Fish, and Aquatic Plants

OpenAIRE

Al-Sammak, Maitham; Hoagland, Kyle; Cassada, David; Snow, Daniel

2014-01-01

Several groups of microorganisms are capable of producing toxins in aquatic environments. Cyanobacteria are prevalent blue green algae in freshwater systems, and many species produce cyanotoxins which include a variety of chemical irritants, hepatotoxins and neurotoxins. Production and occurrence of potent neurotoxic cyanotoxins β-N-methylamino-l-alanine (BMAA), 2,4-diaminobutyric acid dihydrochloride (DABA), and anatoxin-a are especially critical with environmental implications to public and...

Moderation of the Relation between Person-Environment Congruence and Academic Success: Environmental Constraint, Personal Flexibility and Method

Science.gov (United States)

Tracey, Terence J. G.; Allen, Jeff; Robbins, Steven B.

2012-01-01

The relation of interest-major congruence to indicators of college success was examined as it was moderated by environmental constraint, individual flexibility, and congruence definition in an initial sample of 88,813 undergraduates (38,787 men and 50,026 women) from 42 different colleges and universities in 16 states. College achievement (GPA…

Identification of fibroblast growth factor receptor 3 (FGFR3 as a protein receptor for botulinum neurotoxin serotype A (BoNT/A.

Directory of Open Access Journals (Sweden)

Birgitte P S Jacky

Full Text Available Botulinum neurotoxin serotype A (BoNT/A causes transient muscle paralysis by entering motor nerve terminals (MNTs where it cleaves the SNARE protein Synaptosomal-associated protein 25 (SNAP25206 to yield SNAP25197. Cleavage of SNAP25 results in blockage of synaptic vesicle fusion and inhibition of the release of acetylcholine. The specific uptake of BoNT/A into pre-synaptic nerve terminals is a tightly controlled multistep process, involving a combination of high and low affinity receptors. Interestingly, the C-terminal binding domain region of BoNT/A, HC/A, is homologous to fibroblast growth factors (FGFs, making it a possible ligand for Fibroblast Growth Factor Receptors (FGFRs. Here we present data supporting the identification of Fibroblast Growth Factor Receptor 3 (FGFR3 as a high affinity receptor for BoNT/A in neuronal cells. HC/A binds with high affinity to the two extra-cellular loops of FGFR3 and acts similar to an agonist ligand for FGFR3, resulting in phosphorylation of the receptor. Native ligands for FGFR3; FGF1, FGF2, and FGF9 compete for binding to FGFR3 and block BoNT/A cellular uptake. These findings show that FGFR3 plays a pivotal role in the specific uptake of BoNT/A across the cell membrane being part of a larger receptor complex involving ganglioside- and protein-protein interactions.

Dysport: pharmacological properties and factors that influence toxin action.

Science.gov (United States)

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.

TRP channels and traffic-related environmental pollution-induced pulmonary disease.

Science.gov (United States)

Akopian, Armen N; Fanick, E Robert; Brooks, Edward G

2016-05-01

Environmental pollutant exposures are major risk factors for adverse health outcomes, with increased morbidity and mortality in humans. Diesel exhaust (DE) is one of the major harmful components of traffic-related air pollution. Exposure to DE affects several physiological systems, including the airways, and pulmonary diseases are increased in highly populated urban areas. Hence, there are urgent needs to (1) create newer and lesser polluting fuels, (2) improve exhaust aftertreatments and reduce emissions, and (3) understand mechanisms of actions for toxic effects of both conventional and cleaner diesel fuels on the lungs. These steps could aid the development of diagnostics and interventions to prevent the negative impact of traffic-related air pollution on the pulmonary system. Exhaust from conventional, and to a lesser extent, clean fuels, contains particulate matter (PM) and more than 400 additional chemical constituents. The major toxic constituents are nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs). PM and PAHs could potentially act via transient receptor potential (TRP) channels. In this review, we will first discuss the associations between DE from conventional as well as clean fuel technologies and acute and chronic airway inflammation. We will then review possible activation and/or potentiation of TRP vanilloid type 1 (TRPV1) and ankyrin 1 (TRPA1) channels by PM and PAHs. Finally, we will discuss and summarize recent findings on the mechanisms whereby TRPs could control the link between DE and airway inflammation, which is a primary determinant leading to pulmonary disease.

Scope of environmental risk management

Energy Technology Data Exchange (ETDEWEB)

O' Riordan, T

1979-01-01

Environmental risk management embraces three techniques for project appraisal: cost/benefit analysis, environmental impact analysis and risk assessment. It also explicitly relates scientific investigations to political judgments, sometimes so closely that the two cannot be separated. Indeed it is now apparent that environmental risk management encompasses procedures both to review the relative merits and priorities of policies as well as to appraise the environmental risks of particular schemes. Until recently this relationship has not been fully appreciated, so much imagination and innovation is still required to develop the most-suitable mechanisms for review.

Present knowledge and perspectives on the role of copper in brake materials and related environmental issues: A critical assessment

International Nuclear Information System (INIS)

Straffelini, Giovanni; Ciudin, Rodica; Ciotti, Alessandro; Gialanella, Stefano

2015-01-01

This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed. - Highlights: • Copper in brake pad materials: role and concerns. • Environmental and health impact of copper. • Copper replacement in frictional brake materials. • International legislation and standards on the above issues. - Importance of copper in brake pad materials and concern as regards environmental and health impact of its emission as brake wear product.